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The natural history of left ventricular spontaneous contrast. Spontaneous contrast in the left ventricle is an unusual entity. We retrospectively studied 16 patients who were found to have spontaneous contrast present on two-dimensional echocardiograms, specifically noting their clinical characteristics, the reproducibility of this phenomenon, the presence of thrombi and embolic events, and prognostic implications. Diagnoses included ischemic heart disease in nine patients, dilated cardiomyopathy in six patients, and hypertensive cardiomyopathy in one patient. The mean ejection fraction was 17.6%. There were six thromboembolic events in four patients. The spontaneous contrast was reproducible for periods of time up to 39 months. Patients who had improvement in their left ventricular dysfunction or who underwent aneurysmectomy had disappearance of the spontaneous contrast. Those patients who had spontaneous contrast reproduced on subsequent echocardiograms did not seem to have a worse prognosis than patients with similarly depressed ventricular function, but a larger study is necessary to verify this.
3
Clinical application of ras gene mutation for diagnosis of pancreatic adenocarcinoma. Most pancreatic adenocarcinomas are known to have ras gene (oncogene) mutations. The site of the mutations is localized in codon 12 of K-ras gene. Such high incidence and localization of the ras gene mutations have not been observed in any other human malignancies. Polymerase chain reaction and direct sequencing method enabled us to analyze DNA sequence around codon 12 of K-ras gene in small quantities of specimens obtained from needle biopsies and aspirate samples for pathological diagnosis. All the materials obtained from 12 patients with pancreatic adenocarcinoma showed the mutations, whereas those obtained from 6 patients with chronic pancreatitis showed no mutations. In several cases using the mutations of K-ras gene as a marker, this analysis supplemented conventional pathology and cytology in making the diagnosis of pancreatic adenocarcinoma. The analysis of ras-gene mutations was useful for the clinical diagnosis of pancreatic adenocarcinoma.
0
Synchronous Hodgkin's disease and myelofibrosis terminating with granulocytic sarcoma and acute megakaryocytic leukemia. Our patient had stage IIIAI Hodgkin's disease with synchronous myelofibrosis and myeloid metaplasia. A slowly progressive myeloproliferative disease developed over 9 1/2 years and terminated in a painful osteolytic bone disease, spinal extradural granulocytic sarcoma and acute megakaryocytic leukemia. It is likely that this was a result of the myeloproliferative disease rather than a late complication from combination chemotherapy. Our case demonstrates the importance of a curative approach to Hodgkin's disease even in the face of a coexistent disease with a long or unknown natural history.
0
Coronary angioplasty in young adults: initial results and late outcome. The initial and late outcome of coronary angioplasty was studied in 148 patients less than 40 years of age (mean 36.4 +/- 3). Angioplasty was performed on a single vessel in 70% of patients and on multiple vessels in 30%; it was performed on a totally occluded vessel in 20%. Angioplasty was successful in 90.5% of patients, unsuccessful but uncomplicated in 7.4% and complicated by myocardial infarction in 0.7%, emergency bypass surgery in 0.7% and death in 0.7%. At late (mean 3.7 +/- 3 years; range 0.5 to 11.5) follow-up study after successful angioplasty, 94% of patients were alive, 79% were free of angina and 85% had returned to work; late myocardial infarction occurred in 4%. Actuarial survival at 5 years was 95%, and 85% of patients were free from death, infarction or bypass surgery. A second angioplasty was performed in 29 patients (22%) (mean 6.1 +/- 8.4 months) and was successful in 27 (93%), with no deaths. Elective coronary bypass surgery was performed in 8.5% of patients, with perioperative infarction in 9% and no deaths. By univariate analysis, late death was more likely to occur in hypertensive patients (15% versus 2.5%; p less than 0.01) and diabetic patients (21.4% versus 3.6%; p less than 0.01). Cox proportional hazard regression analysis identified hypertension (p = 0.007) and diabetes (p = 0.04) as independent time-related predictors of subsequent death. Thus, early and late results after coronary angioplasty in young adults are favorable, but certain risk factors are important predictors of outcome. Late revascularization procedures (repeat angioplasty or surgery) for restenosis or disease progression are common.
4
Venous dysfunction of late pregnancy persists after delivery. Pregnancy is associated with DVT, pelvic thrombophlebitis, and lower extremity varicosities. Pelvic venous compression by the gravid uterus is blamed. A prospective controlled study using plethysmography was performed. Venous capacitance and outflow were measured at term, and at 1 week, 6 weeks and 3 months following delivery. Results show decreased venous capacitance and venous outflow at term pregnancy, no improvement 1 week after delivery, modest improvement at 6 weeks, and dramatic statistically significant improvement in both parameters by 3 months. The persistence of venous dysfunction for several weeks after delivery indicates that changes in venous function at term pregnancy are largely the result of factors other than pelvic venous compression by the gravid uterus.
3
Visual losses after myopic epikeratoplasty. The vision of seven patients who had undergone epikeratoplasty for myopia was evaluated by measuring their contrast sensitivity functions without and with the presence of a glare source. Compared with findings for a normal control population, these epikeratoplasty patients were found to have statistically significant contrast sensitivity losses. To evaluate the clinical relevance of these losses, the results were also compared with those for two other patient groups with abnormal corneal optics, seven radial keratotomy patients and seven keratoconus patients wearing rigid contact lenses. Contrast thresholds for the epikeratoplasty and keratoconus patients were similar and usually statistically indistinguishable, and their losses were far more profound than those of the radial keratotomy patients. The addition of glare did not alter this pattern of losses. The results document the extent of vision losses in these patients and suggest that increased intraocular light scattering is not a major contributor to the observed contrast sensitivity decrements.
2
Neutrophilic eccrine hidradenitis in two neutropenic patients. Neutrophilic eccrine hidradenitis is an uncommon, self-limited dermatosis with a variable clinical presentation. It seems to be due to chemotherapeutic drugs in most cases. Necrosis of the eccrine gland associated with a neutrophilic infiltrate is the histologic hallmark of this disease. We report two additional cases in neutropenic patients with acute myelogenous leukemia in which there was a striking lack of neutrophil infiltration. A new term, drug-associated eccrine hidradenitis, is suggested.
4
Controlled trials of antihypertensive drugs in pregnancy. It is taken for granted that severe hypertension in pregnancy should be treated, although the principle has not been formally tested by properly controlled trials. There is less certainty about treating mild to moderate hypertension (140/90 to 169/109 mm Hg). The risk of chronic hypertension in pregnancy depends on that of superimposed preeclampsia, which must be prevented by control of the blood pressure if antihypertensive treatment is to be beneficial. There is not a priori reason why lowering the blood pressure should have this effect. Most of the trials of treatment have been too small to provide conclusive answers. Usually treatment has been started too late to give a realistic expectation of influencing the evolution of superimposed preeclampsia. However, the largest trial of the early use of methyldopa in women with mild chronic hypertension, showed clearly that treatment does not prevent the superimposition of preeclampsia. beta-Adrenergic blocking agents, if used from the second start of the trimester, are associated with a major risk of severe growth retardation and are therefore contraindicated. Methyldopa has the best safety record, which includes long-term follow-up to assess the development of children exposed to methyldopa in utero. The ineffectiveness of antihypertensive drugs in preventing or ameliorating preeclampsia needs to be contrasted with the consistent evidence for the effectiveness of antiplatelet therapy. This is consistent with the increasing evidence that preeclampsia is not primarily, or even necessarily, a hypertensive disease.
3
Hepatic amino-nitrogen clearance to urea-nitrogen in control subjects and in patients with cirrhosis: a simplified method. The functional hepatic nitrogen clearance during amino acid infusion is a measure of liver cell mass. The clinical feasibility of the test has so far been limited by methodological problems. A simplified procedure was used to measure the urea-nitrogen synthesis rate and functional hepatic nitrogen clearance in nine subjects with normal liver function and in nine patients with cirrhosis. The method was based on only four consecutive 2-hr urine collections and five blood samples. Total body water was calculated from a nomogram based on age and anthropometric data, whereas the gut urea hydrolysis was assigned one fixed fraction of synthesis (0.17 in control subjects and 0.26 in patients with cirrhosis). Finally, a solution of a single amino acid, alanine, was infused as substrate for urea synthesis. Urea-nitrogen synthesis rate increased linearly with increasing alpha-amino-nitrogen concentration, and the slope of the regression (functional hepatic nitrogen clearance) was reduced in cirrhosis from 37.5 +/- 7.0 L/hr to 18.4 +/- 6.7 L/hr; p less than 0.005. The hepatic nitrogen clearance was linearly related to the clinical status (Child-Pugh score), to routine liver function tests and to galactose elimination capacity (r = 0.869), a well-established, quantitative, liver function measure. The simplified method makes the measurement of hepatic nitrogen clearance suitable for routine clinical use. The test might prove useful to study the alterations of nitrogen metabolism in cirrhosis, with special reference to hepatic encephalopathy.
1
Comparison of ulcer surgery at a Veterans Administration and University Hospital. We compared the patient populations and outcome of surgery for peptic ulcer disease in 81 patients at a Veterans Administration Hospital (OVAH) and 97 patients at an affiliated University Hospital (UNH). The surgeons and choice of operation were comparable at both facilities. Patients were similar with respect to severity of ulcer disease, percentage of elderly patients and distribution of comorbid conditions. There were significantly more female patients (45% vs 2%, P less than 0.05), patients less than 40 years old (22% vs 6%, P less than 0.05), and patients with gastric ulcers (27% vs 12%, P less than 0.05) at UNH. Alcoholism was more prevalent at OVAH (57% vs 22%, P less than 0.05). Postoperative morbidity and mortality rates were 27 per cent and 14 per cent at OVAH and 25 per cent and 16 per cent at UNH. These data suggest that quality of care for surgical therapy of ulcer disease at a VA Hospital is comparable to its tertiary care affiliate with a similar patient population.
1
Isolation and characterization of normal and neoplastic colonic epithelial cell populations. The aim of the present study was to characterize rat mucosal colonic cells harvested from the crypt continuum during differentiation and dimethylhydrazine-induced neoplasia. The collection of colonocytes was performed using a modified nonenzymatic isolation procedure based on Ca2+ chelation and gentle mechanical dissociation. Light and electron microscopy histomorphological examinations, [3H]thymidine incorporation studies, and activity gradients of alkaline phosphatase, thymidine kinase, and cytoskeleton-associated protein tyrosine kinase indicated that distinct cell populations were harvested from the various crypt regions in a temporal sequence mirroring their zonal and functional distribution in situ. After dimethylhydrazine administration, marked protein tyrosine kinase activity was noted in colonic cells harvested from upper crypt zones. The misplaced and sustained kinase activity preceded the actual polyp or tumor formation. This observation is consistent with the expansion of colonic proliferative compartments beyond allowable boundaries during the preneoplastic period. Companion studies in human colonic epithelial specimens corroborate the findings observed in normal and transformed murine colonocytes. It is believed that the characterization and manipulation of colonocytes using our in vitro model will provide important clues to the molecular events underlying the differentiation program and carcinogenic process in the colonic cell.
0
Syringomyelia secondary to compression of the cervical spinal cord by an extramedullary lymphoma. A case of syringomyelia secondary to an extramedullary cervical spinal cord compression by a non-Hodgkin's lymphoma is described. After radiotherapy, the syrinx was no longer seen. The pathogenesis of this type of syrinx is discussed, and the potential benefit of radiotherapy in these cases is suggested.
2
Photodynamic therapy of spontaneous cancers in felines, canines, and snakes with chloro-aluminum sulfonated phthalocyanine. This is the first report on the photodynamic treatment with a second-generation sensitizer, chloro-aluminum sulfonated phthalocyanine (CASPc) of spontaneously arising tumors and on the photodynamic therapy (PDT) of snake neoplasms. Each of 10 cats, 2 dogs, and 3 snakes presenting with a variety of tumor types (squamous cell carcinoma, mast cell malignant tumor, and mixed carcinoma/sarcoma) was given an intravenous injection of 1 mg of CASPc per kilogram body weight 48 hours prior to irradiation with 675-nm light. Some larger tumors (greater than 1.5 cm deep) were surgically debulked prior to PDT. No significant systemic toxicity or skin photosensitization was observed in any animal. The tumor responses were comparable to those seen with conventional cryotherapy, hyperthermia, or surgery. PDT with CASPc of these cases led to 67% (12 of 18) complete response, 22% (4 of 18) partial response, and 11% (2 of 18) no response (less than 50% reduction in tumor size). Four cases could not be evaluated. Since the overall tumor response to CASPc is very good, and the problem of skin photosensitivity is nonexistent, it is expected that using CASPc-PDT to eradicate human tumors would also yield comparable results. Further studies with long-term follow-up are necessary to optimize the use of CASPc-PDT in veterinary and human medicine.
0
Modified Kraske approach for disease of the mid-rectum. A modification of Dr. Paul Kraske's approach for removal of mid-rectal lesions has been used in 11 patients from 1977 to 1988 by the senior authors. Patients ranged in age from 56 to 89 yr, with an average of 67 yr. There were seven male and four female patients. Indications for surgery were as follows: villous adenoma (seven), carcinoid (one), recurrent dysplasia in a previous endoscopic polypectomy site (one), positive distal margin for neoplasm following low anterior sigmoid resection (one), and adenocarcinoma in one elderly poor-risk patient. All lesions were in the middle rectum (7-11 cm from the anal verge, average 9 cm). The postoperative stay ranged from 6 to 12 days with a mean of 8 days. The average follow-up for the 11 patients is 3 1/2 yr (1 month to 7 yr), with only one patient having a local recurrent lesion. There was no morbidity or mortality. We conclude that this modification of the Kraske approach offers a good alternative for excision of mid-rectal lesions in terms of technical ease, efficacy, safety, and patient tolerance. The modified Kraske approach is indicated in certain situations and should be a part of the surgeon's armamentarium.
1
Treatment of Kawasaki syndrome: a comparison of two dosage regimens of intravenously administered immune globulin. Because intravenously administered immune globulin (IVIG) is effective in reducing the incidence of coronary artery aneurysms in Kawasaki syndrome when given at a dose of 400 mg/kg daily for 4 days, we undertook a multicenter clinical trial comparing two dosage regimens of IVIG. Patients were randomly assigned to receive IVIG at either 400 mg/kg daily for 4 days (22 patients) or 1 gm/kg as a single dose (22 patients). All patients received aspirin therapy, and all were enrolled within 7 days of onset of fever. The presence of coronary artery aneurysms was evaluated by means of two-dimensional echocardiography before infusion; at days 4 to 6, 14 to 21, and 42 to 49 after infusion; and at 1 year. Coronary artery aneurysms were detected in 3 of the 44 patients, including one patient receiving 400 mg/kg and two patients receiving 1 gm/kg (p value not significant). No giant aneurysms were detected. No major side effects occurred with either dosage regimen. Patients receiving the 1 gm/kg dose had a faster resolution of fever and were discharged from the hospital approximately 1 day sooner than the 400 mg/kg group (p = 0.01). Although the relatively small sample size in this trial does not allow for a more definitive statement regarding the occurrence of coronary artery aneurysms, it appears that the 1 gm/kg dose is associated with a more rapid clinical improvement and a shorter hospital stay.
3
Lymphocytic hypophysitis with involvement of the cavernous sinus and hypothalamus. Two cases of lymphocytic hypophysitis are reported, in which hypothalamic involvement causing diabetes insipidus was a prominent clinical feature. In one case, a man had clinical and radiological evidence of the involvement of the cavernous sinus. This represents the second reported case of a man with lymphocytic hypophysitis. A transsphenoidal biopsy established the diagnosis in both cases. Neither the involvement of the cavernous sinus nor permanent diabetes insipidus has been reported previously. A review of the literature is provided.
4
Lymphokine-activated killer cell suppressor factor in malignant effusions. We examined the possibility that tumor-released products inhibit lymphokine-activated killer cell activation. Lymphokine-activated killer cells from human peripheral blood lymphocytes were activated with recombinant interleukin 2 for 4 days in the presence of malignant effusions or conditioned media from cultured cell lines (10% vol/vol). Eight of 10 malignant effusions/media suppressed the induction of lymphokine-activated killer cell cytotoxicity, as measured in a 4-hour sodium chromate release assay. Seven of 10 effusions/media inhibited lymphokine-activated killer cell proliferation. Suppression was both dose and time dependent. A representative suppressive effusion was fractionated by agarose gel chromatography, treated with detergents disruptive of ionic bonds and lipids, and refractionated using polyacrylamide gel chromatography. Seven suppressive fractions ranging in molecular weight from 1 x 10(5) to 3 x 10(5) d were isolated. It is speculated that this suppressor factor may represent a large multimeric structure with ionic-bonded individual suppressive components.
0
Human interleukin-3 mRNA accumulation is controlled at both the transcriptional and posttranscriptional level. Interleukin-3 (IL-3) is a hematopoietic growth factor that regulates the differentiation of multilineage and committed progenitor cells and the functions of some mature blood cells. The expression of human IL-3 appears to be restricted to stimulated T lymphocytes. We have investigated the kinetics and mechanisms involved in the induction of IL-3 expression in the human T lymphocytic tumor cell line Jurkat. We show that accumulation of IL-3 mRNA is controlled at both the transcriptional and posttranscriptional level. Transcription of the IL-3 gene in these cells appears to be constitutive but no IL-3 mRNA was detected in unstimulated cells, indicating that in resting cells IL-3 mRNA is highly unstable. Treatment with phytohemagglutinin (PHA) induced a small and transient increase in the IL-3 gene transcription rate and led to the production of detectable levels of IL-3 mRNA and protein. Optimal induction of IL-3 expression required a second stimulus. Costimulation of Jurkat cells with both phorbol myristate acetate and PHA caused both a transient increase in IL-3 gene transcription, which is dependent on new protein synthesis, and also a transient increase in mRNA stability.
0
The long-term prognosis of patients with out-of-hospital cardiac arrest but no inducible ventricular tachycardia. The long-term prognosis of patients successfully resuscitated from cardiac arrest who do not have acute precipitating factors and in whom ventricular arrhythmias cannot be induced during baseline electrophysiologic testing is controversial. The purpose of this investigation was to evaluate the long-term risk of recurrent sudden death and determine the clinical, angiographic, hemodynamic, and electrophysiologic predictors of recurrent cardiac arrest in such patients. Twenty-six (37%) of 71 consecutive patients with a single episode of aborted sudden death did not have inducible ventricular arrhythmias (less than 7 intraventricular responses) during baseline drug-free electrophysiologic study and they form the basis of this report. Their mean age was 54 +/- 13 (mean +/- SD) years and the left ventricular ejection fraction (LVEF) was 0.47 +/- 0.17. After a mean follow-up period of 16 months, 11 patients (42%) had a recurrent cardiac arrest (fatal in 10 patients). The actuarial incidence of recurrent cardiac arrest was 30 +/- 10% at 1 year and 55 +/- 13% at 3 years. Patients with LVEF less than or equal to 0.40 had a significantly higher occurrence of recurrent cardiac arrest than those with LVEF greater than 0.40 (p = 0.02; 1-year actuarial incidence of 57 +/- 17% versus 13 +/- 19%). Patients with recurrent sudden death had a significantly greater incidence of dilated cardiomyopathy (55% versus 7%; p = 0.02) and baseline frequent premature ventricular contractions (PVCs greater than 10/hr; 64% versus 17%, p = 0.036) or nonsustained ventricular tachycardia (36% versus 0%; p = 0.37) than patients without these characteristics.
3
Soluble interleukin-2 receptors in cerebrospinal fluid from individuals with various neurological disorders. Soluble interleukin-2 (IL-2R) levels in the cerebrospinal fluid (CSF) were studied in infectious, inflammatory, degenerative, and neoplastic disorders to evaluate their usefulness as a marker for the presence of activated T cells, thus indicating an inflammatory process. CSF from control subjects and patients with stationary, progressive, and treated multiple sclerosis (MS); aseptic meningitis; lymphoid and nonlymphoid central nervous system (CNS) tumors; Alzheimer's disease, as well as serum from MS patients and control subjects were studied for levels of soluble IL-2R. A significant increase in CSF IL-2R levels was observed in patients with MS, meningitis, and lymphoid CNS tumors; the MS group showed the highest values. CSF from individuals with Alzheimer's disease and from patients with nonlymphoid tumors did not show significantly elevated values. Serum IL-2R levels were significantly higher in MS patients than in control subjects, but there was no significant correlation between individual serum and CSF IL-2R levels. This study suggests the presence of activated T-lymphocytes in the CNS of patients with MS.
2
Factors associated with soft- and hard-tissue compromise of endosseous implants. This prospective analysis identifies factors associated with endosseous implant removal as well as factors associated with implant morbidity resulting in nonscheduled patient visits. Treatment of the latter conditions is discussed. The most important factors identified for implant success were surgery without compromise in technique, placing implants into sound bone, avoiding thin bone or implant dehiscence at the time of implant placement, avoiding premature implant exposure during the healing period, establishing a balanced restoration, and insuring appropriate follow-up hygiene care. In the posterior mandible, the presence of keratinized gingiva was strongly correlated with optimal soft- and hard-tissue health.
4
Beneficial effects of x-irradiation on recovery of lesioned mammalian central nervous tissue. We examined the potential of x-irradiation, at clinical dose levels, to manipulate the cellular constituents and thereby change the consequences of transection injury to adult mammalian central nervous tissue (rat olfactory bulb). Irradiation resulted in reduction or elimination of reactive astrocytes at the site of incision provided that it was delivered within a defined time window postinjury. Under conditions optimal for the elimination of gliosis (15-18 days postinjury), irradiation of severed olfactory bulbs averted some of the degenerative consequences of lesion. We observed that irradiation was accompanied by prevention of tissue degeneration around the site of lesion, structural healing with maintenance of the typical cell lamination, and rescue of some axotomized mitral cells (principal bulb neurons). Thus radiation resulted in partial preservation of normal tissue morphology. It is postulated that intrusive cell populations are generated in response to injury and reactive astrocytes are one such group. Our results suggest that selective elimination of these cells by irradiation enabled some of the regenerative processes that are necessary for full recovery to maintain their courses. The cellular targets of these cells, their modes of intervention in recovery, and the potential role of irradiation as a therapeutic modality for injured central nervous system are discussed.
2
Psychological stress and the fibrositis/fibromyalgia syndrome. The relationship of stress and social support to the fibrositis/fibromyalgia syndrome (FS) was investigated by administration of 4 questionnaire instruments to 28 patients with FS, 20 patients with rheumatoid arthritis (RA) and 28 pain-free normal controls. FS showed higher levels of stress as measured by daily "hassles" than did RA or controls. However, on a measure of major life stress, they reported lower levels. No differences were found between groups with regard to daily "uplifts" or social support. Correlations between those measures of stress and social support with their scores on the Arthritis Impact Measurement Scale showed that the Hassles Scale was significantly related to the AIMS Psychological component.
2
Long-term results of catheter ablation of idiopathic right ventricular tachycardia Ten consecutive patients with recurrent episodes of symptomatic, idiopathic, sustained monomorphic ventricular tachycardia (VT) originating in the right ventricle underwent an attempt at catheter ablation of the ventricular tachycardia. There were seven women and three men, with a mean age of 39 +/- 14 years (+/- SD). None of the patients had any evidence of structural heart disease. The VT had a left bundle branch block configuration and an inferior axis in each patient, and the mean cycle length was 313 +/- 75 msec. Based on the methods of induction of the VT and the response of the VT to verapamil, the VT mechanism was presumed to be reentry in six patients, triggered activity in three patients, and catecholamine-sensitive automaticity in one patient. Sites for ablation were guided by pace mapping, and an appropriate target site was identified in the right ventricular outflow tract in each patient. From one to three shocks of 100-360 J (mean total, 336 +/- 195 J) were delivered from a defibrillator between the tip of the ablation catheter (cathode) and a patch electrode on the anterior chest (anode). An electrophysiology test 7-9 days after ablation demonstrated that VT was still inducible in only one patient, who was treated with amiodarone. One other patient had a recurrence of VT 3 weeks after ablation and was treated with verapamil. Eight of 10 patients were not treated with antiarrhythmic medications and have had no episodes of symptomatic VT during 15-68 months of follow-up (mean follow-up, 33 +/- 18 months). There were no acute or long-term complications.
4
Early readmission of elderly patients with congestive heart failure. Repetitive hospitalizations are a major health problem in elderly patients with chronic disease, accounting for up to one fourth of all inpatient Medicare expenditures. Congestive heart failure, one of the most common indications for hospitalization in the elderly, is also associated with a high incidence of early rehospitalization, but variables identifying patients at increased risk and an analysis of potentially remediable factors contributing to readmission have not previously been reported. We prospectively evaluated 161 patients 70 years or older that had been hospitalized with documented congestive heart failure. Hospital mortality was 13% (n = 21). Among patients discharged alive, 66 (47%) were readmitted within 90 days. Recurrent heart failure was the most common cause for readmission, occurring in 38 patients (57%). Other cardiac disorders accounted for five readmissions (8%), and noncardiac illness led to readmission in 21 cases (32%). Factors predictive of an increased probability of readmission included a prior history of heart failure, four or more admissions within the preceding 8 years, and heart failure precipitated by an acute myocardial infarction or uncontrolled hypertension (all P less than .05). Using subjective criteria, 25 first readmissions (38%) were judged possibly preventable, and 10 (15%) were judged probably preventable. Factors contributing to preventable readmissions included noncompliance with medications (15%) or diet (18%), inadequate discharge planning (15%) or follow-up (20%), failed social support system (21%), and failure to seek medical attention promptly when symptoms recurred (20%). Thus, early rehospitalization in elderly patients with congestive heart failure may be preventable in up to 50% of cases, identification of high risk patients is possible shortly after admission, and further study of nonpharmacologic interventions designed to reduce readmission frequency is justified.
3
Soluble interleukin-2 receptors in cerebrospinal fluid from individuals with various neurological disorders. Soluble interleukin-2 (IL-2R) levels in the cerebrospinal fluid (CSF) were studied in infectious, inflammatory, degenerative, and neoplastic disorders to evaluate their usefulness as a marker for the presence of activated T cells, thus indicating an inflammatory process. CSF from control subjects and patients with stationary, progressive, and treated multiple sclerosis (MS); aseptic meningitis; lymphoid and nonlymphoid central nervous system (CNS) tumors; Alzheimer's disease, as well as serum from MS patients and control subjects were studied for levels of soluble IL-2R. A significant increase in CSF IL-2R levels was observed in patients with MS, meningitis, and lymphoid CNS tumors; the MS group showed the highest values. CSF from individuals with Alzheimer's disease and from patients with nonlymphoid tumors did not show significantly elevated values. Serum IL-2R levels were significantly higher in MS patients than in control subjects, but there was no significant correlation between individual serum and CSF IL-2R levels. This study suggests the presence of activated T-lymphocytes in the CNS of patients with MS.
0
Arginine vasopressin gene expression in chronic cardiac failure in rats. Arginine vasopressin (AVP) is known to be increased in patients and experimental animals with chronic cardiac failure (CCF). The importance of an increase in biosynthesis of AVP in the hypothalamus has, however, not heretofore been investigated and is the purpose of the present study. CCF secondary to infarction of myocardial tissue was induced by ligation of the left anterior descending coronary artery and sham operated animals served as controls. Four weeks later hypothalamic AVP mRNA was determined by solution hybridization using sense and anti-sense strand RNA. The blood pressure was lower in CCF than sham animals (131.2 +/- 3.1 vs. 112.8 +/- 4.0 mm Hg, P less than 0.05) and the total heart, and right and left ventricle weights were significantly higher in CCF rats. Plasma AVP was higher in CCF (sham 6.78 +/- 0.30; CCF 11.46 +/- 0.64 pg/ml, P less than 0.001) and plasma atrial natriuretic peptide was also higher in CCF than sham animals (205 +/- 36 vs. 554 +/- 56 pg/ml, P less than 0.001). The AVP mRNA in hypothalamus was significantly higher in CCF than sham animals (55.5 +/- 3.7 vs. 95.9 +/- 4.0 pg/micrograms total RNA, P less than 0.001). There was no difference in beta-actin mRNA in the hypothalamus of sham and CCF rats, indicating that the AVP-mRNA increase was specific in CCF. These results therefore demonstrate that increased AVP biosynthesis in the hypothalamus, in addition to release of the hormone from the posterior pituitary, may occur in CCF.
3
The human hepatic asialoglycoprotein receptor is a target antigen for liver-infiltrating T cells in autoimmune chronic active hepatitis and primary biliary cirrhosis. Autoantibodies to the human hepatic asialoglycoprotein receptor have been found in nearly 50% of the sera of patients with autoimmune chronic active hepatitis and in 15% of patients with primary biliary cirrhosis. In this study we demonstrate that the human hepatic asialoglycoprotein receptor is also a target antigen for T cell-mediated immune responses. Peripheral blood lymphocytes of 37% (7 of 19) of patients with autoimmune chronic active hepatitis and 33% (2 of 6) of patients with primary biliary cirrhosis showed a proliferative response to highly purified human hepatic asialoglycoprotein receptor, whereas no proliferation was found with peripheral blood lymphocytes of patients with chronic viral hepatitis (0 of 13) and healthy blood donors (0 of 4). Moreover, we isolated T-cell clones from liver biopsy samples of two patients with autoimmune chronic active hepatitis and two patients with peripheral blood lymphocytes. Between 2.8% and 14.3% of these clones showed a specific proliferative response to purified human hepatic asialoglycoprotein receptor. The response was restricted to autologous antigen-presenting cells and could be blocked by monoclonal antibodies against human leukocyte antigen-DR molecules. The response of T cells to the human hepatic asialoglycoprotein receptor did not require the lectinlike activity of the asialoglycoprotein receptor. Thus the human hepatic asialoglycoprotein receptor could be identified as a major target antigen of humoral and cellular immune reactions in autoimmune-mediated liver diseases.
1
Protection from chemotherapy-induced alopecia in a rat model. Alopecia (hair loss) is among the most distressing side effects of cancer chemotherapy. Little progress has been made, however, in its prevention or treatment, partly because of the lack of suitable experimental model. In recent work on the treatment of myelogenous leukemia in the rat, the following observations were made: (i) treatment of 8-day-old rats with cytosine arabinoside consistently produced alopecia, and (ii) ImuVert, a biologic response modifier derived from the bacterium Serratia marcescens, uniformly produced complete protection against the alopecia. In subsequent experiments, both cyclophosphamide and doxorubicin also produced alopecia in this model, and the doxorubicin-induced alopecia was prevented by treatment with ImuVert. The potential relevance of these observations to chemotherapy-induced alopecia in the clinical setting should be examined.
0
Histopathology and immunohistochemistry of the caecum in children with the Trichuris dysentery syndrome. Caecal biopsy specimens from Jamaican children with the Trichuris dysentery syndrome (TDS) and age matched Jamaican controls were investigated by immunohistochemistry and by light microscopy. Biopsy specimens from all children (with TDS and controls) showed a mild to moderate increase in inflammatory cells. Except in the vicinity of the worm, where the epithelium was flattened, there was no other epithelial abnormality. Compared with controls, children with TDS had increased IgM lamina propria plasma cells and decreased intraepithelial T cells. There was also an increase in crypt epithelial cell proliferation. Lamina propria T cells (both activated and non-activated) were no more common in children with the Trichuris syndrome than controls. Epithelial cell HLA-DR and VLA-1 expression (which are increased in other colitides) were the same in both groups. Despite the presence of large worm burdens and chronic dysentery, therefore, only minor changes were seen in the caecal mucosa of children with TDS.
4
Modification of stroke susceptibility by genotype-dependent maternal influences. The influence of the prenatal and postnatal maternal environment on stroke susceptibility was evaluated by reciprocally crossing the spontaneously hypertensive (SHR) and the Dahl salt-sensitive (SS/Jr) inbred rat strains to produce reciprocal F1 hybrids that were nurtured, respectively, during prenatal and postnatal life by SHR or SS/Jr mothers. Following placement on a high-salt diet containing 8% NaCl at 35 days of age, F1 rats reared by SHR mothers had shorter survival times and were more likely to die with cerebral hemorrhage than F1s reared by SS/Jrs. Across reciprocal F1 female groups, enhanced susceptibility to stroke was associated with greater elevations of systolic blood pressure, but this association was not seen across reciprocal F1 male groups. There was also an association between blood pressure and stroke within each F1/gender subgroup: Rats eventually suffering strokes developed higher blood pressure after placement on the high-salt diet than rats that did not suffer stroke. Lower day 35 body weights (before exposure to the high-salt diet) were associated with greater likelihood of stroke both across the reciprocal F1 groups, and within three of the four F1/gender subgroups. The differences in stroke susceptibility between the reciprocal F1 groupings may be due to systematic differences in the prenatal and/or postnatal environments of SHR and SS/Jr mothers and may be mediated by variations in the nutritive capacity of the two inbred mothers.
4
Initial results with slightly modified Kock pouch. My initial experience with 20 patients undergoing Kock pouch continent urinary diversion is reviewed. The procedure has been slightly modified from that described by Kock and Skinner. All patients have been followed for at least four months (median, 33 months). There have been no early complications related to the pouch. The most significant problem, incontinence, has occurred in 2 patients (10%) at three and four months, respectively, after surgery. Only 1 of these patients required temporary use of an external appliance. Leakage was due, in both cases, to a patulous efferent nipple valve. Both were repaired by plication of the nipple, and no new efferent limbs were constructed. In 1 patient (5%) prolapse of the afferent limb associated with reflux and pyelonephritis developed one year post-surgery. Stones have developed in 3 patients (15%). All patients are currently continent and stone-free, and all are pleased with the result.
0
Genetic traits related to hypertension and electrolyte metabolism. The genetic and cultural heritability and intercorrelation of traits related to hypertension have been carried out in 98 Utah pedigrees (2,500 person) and 58 sibships with two or more hypertensive persons (131 hypertensive persons). Although none of these traits has been established as a marker for "sodium-sensitive hypertension," many of them are related at least indirectly to both electrolyte metabolism and risk of hypertension. Significant recessive monogenic effects and high total heritability (52-84%) were found for urinary kallikrein, high fat pattern index, intraerythrocytic sodium, Na-Li countertransport, and ouabain binding sites. Familial correlations more strongly attributable to shared environment than to genetic effects were found for Na,K-ATPase pump activity, intraerythrocytic magnesium, plasma digoxin-like factor, plasma renin activity, and plasma sodium concentration. All anthropometric variables tested showed highly significant genetic heritability with low and insignificant shared family environmental effects. Several of the genetically determined cellular cation tests also correlated with other genetic traits including plasma lipids, anthropometric measurements, and other cellular cation tests. Among hypertensive individuals with familial dyslipidemic hypertension, plasma insulin levels correlated with obesity and lipid abnormalities and with several cellular cation flux tests associated with hypertension.
3
Electrotonic influences on action potentials from isolated ventricular cells. This work combines a theoretical study of electrical interactions between two excitable heart cells, using a variable coupling resistance, with experimental studies on isolated rabbit ventricular cells coupled with a variable coupling resistance to a passive resistance and capacitance circuit. The theoretical results show that the response of an isolated cell to an increased frequency of stimulation is strongly altered by the presence of a coupling resistance to another cell. As the coupling resistance gradually is decreased, the stimulated cell becomes able to respond successfully to more rapid stimulation, and then, at levels of coupling resistance that allow conduction between the two cells, the coupled pair of cells exhibits arrhythmic interactions not predicted by the intrinsic properties of either cell. The experimental results show that the isolated rabbit ventricular cell is extremely sensitive to even a very small electrical load, with shortening of the action potential by 50% with electrical coupling to a model cell (of similar input resistance and capacitance to the ventricular cell) as high as 1,000 M omega, even though the action potential amplitude and current threshold are very insensitive to the electrical load.
4
Amelioration of cholinergic-induced pancreatitis with a selective cholecystokinin receptor antagonist. Acute edematous pancreatitis follows excessive cholinergic stimulation in patients exposed to anticholinesterase-containing insecticides. We describe the role of cholecystokinin and the benefits of cholecystokinin receptor blockade in this form of pancreatitis. A cholinergic mimetic (carbachol) was administered to rats weighing 300 to 350 g and produced a form of edematous pancreatitis that mimics that seen in humans. Animals received carbachol intraperitoneally, either alone (250 micrograms/kg of body weight) or with cholecystokinin-receptor antagonist devazepide (3 mg/kg of body weight) and were killed 4 hours later. Carbachol administration resulted in a 19% increase in pancreatic weight, a fourfold increase in serum amylase levels, and a 14-fold increase in serum lipase levels. Plasma cholecystokinin levels, however, were not altered. Devazepide administered prior to cholinergic hyperstimulation blocked pancreatic weight increase and reduced elevations in serum amylase levels twofold and lipase levels fourfold. Although cholecystokinin levels are not elevated in this model of pancreatitis, blockade of even low, background concentrations of this regulatory peptide is beneficial.
4
Infectious mononucleosis presenting as bilateral acute dacryocystitis. A case of infectious mononucleosis presenting as bilateral acute dacryocystitis in a 7-year-old girl is reported. Acute dacryocystitis is uncommon in this age group, and an underlying systemic illness should be suspected particularly when it is bilateral.
4
Dosage of haloperidol for schizophrenia. Eighty-seven newly admitted inpatients with schizophrenia were randomized to receive 10, 30, or 80 mg/d of oral haloperidol. They were treated under double-blind conditions for 6 weeks, less if their acute symptoms remitted sooner. Survival analysis showed no differences among the three treatments. Side effects were minimal in all three treatment groups, and there were no differences in side effects among the groups. These results suggest that dosages higher than 10 mg/d of haloperidol for most patients have no additional beneficial effect in the treatment of acute or exacerbated schizophrenia.
4
Ulcerative colitis disease activity as subjectively assessed by patient-completed questionnaires following orthotopic liver transplantation for sclerosing cholangitis. To assess whether or not liver transplantation and subsequent immunosuppression with cyclosporine and prednisone affect ulcerative colitis symptomatology, we surveyed by questionnaire all 23 surviving patients with pretransplant colonoscopy-documented ulcerative colitis who were transplanted for primary sclerosing cholangitis between June 1982 and September 1985. At follow-up [89.8 +/- 7.6 weeks (mean +/- SEM], all six patients who had had asymptomatic colonoscopy-documented ulcerative colitis reported continued ulcerative colitis quiescence. Among the 17 patients who had had symptomatic colonoscopy-documented ulcerative colitis at time of liver transplantation, 88.2% reported improvement in overall ulcerative colitis severity (P less than 0.001), with significant improvement in the frequency of bowel movements reported by 100%, in crampy abdominal pain by 87.5%, in bowel urgency by 75%, in the occurrence of pus or mucus in stool by 87.5%, in the incidence of ulcerative colitis flares by 81.8%, and in the number of days unable to function normally due to ulcerative colitis symptoms by 78.6% (all at least P less than 0.01). These data demonstrate that ulcerative colitis symptom severity significantly improves following liver transplantation with immunosuppression with cyclosporine and prednisone.
1
Spinal cord arteriovenous malformation with an associated lymphatic anomaly. Case report. Spinal cord arteriovenous malformations (AVM's), like other vascular anomalies of the central nervous system, can be associated with similar vascular lesions of the skin and viscera. A 7-year-old girl, who presented with rapidly progressing paraplegia, was found to have a spinal cord AVM, cutaneous angioma, and a chylous malformation of the lymphatic system. She had previously undergone treatment for a posterior thoracic cutaneous angioma. At surgery, upon incision of the paravertebral muscle fascia, viscous pale fluid was encountered emanating from a foramen in the thoracic lamina. The spinal AVM was resected in spite of concern that the abnormality represented spinal osteomyelitis. Postoperatively, there was full return of function in the lower extremities, along with recurrent episodes of chylothorax, which slowly came under control with dietary manipulation. A review of the anatomy of the thoracic duct and nontraumatic causes of chylothorax is presented, and the association of cutaneous and central angiomas is discussed. Finally, the treatment of chylothorax is delineated.
3
Spinal hemangioblastoma, syrinx, and hydrocephalus in a two-year-old child. A two-year-old child presented with an acute inability to bear weight. Radiological investigation revealed a large cervicothoracolumbar syrinx of no known cause. During investigation, acute communicating hydrocephalus developed, which required a shunt. At surgery, a small thoracic spinal cord hemangioblastoma was discovered and excised. Complete recovery with collapse of the syrinx followed. The clinical features of this rare childhood tumor and its associated effects are discussed.
2
Circumflex artery ventricular fistula and pseudoaneurysm after mitral reoperation. Prosthetic mitral valve reoperation complicated by atrioventricular groove pseudoaneurysm and circumflex ventricular fistula is presented. Ligation of the circumflex artery during mitral valve replacement is implicated after review of a previous cardiac angiogram.
4
Late deaths after treatment for childhood cancer. An investigation of 749 deaths occurring among 4082 patients surviving at least five years after the diagnosis of childhood cancer in Britain before 1971 has been undertaken. Of the 738 with sufficient information the numbers of deaths attributable to the following causes were: recurrent tumour, 550 (74%), a second primary tumour, 61 (8%), a medical condition related to treatment of the tumour, 49 (7%), an traumatic death unrelated to the tumour or its treatment, 34 (5%), finally, any other cause unrelated to the tumour or its treatment, 44 (6%). Less than 10% of five year survivors of non-Hodgkin lymphomas, neuroblastoma, retinoblastoma, Wilms' tumour, or a soft tissue sarcoma died of recurrent tumour during the next 15 years, while more than 25% of five year survivors of Hodgkin's disease, ependymoma, medulloblastoma, and Ewing's tumour died of recurrent tumour during the corresponding period. Almost 50% of five year survivors of acute lymphoblastic leukaemia died of recurrent disease during the corresponding 15 years, a large proportion of deaths being due to central nervous system relapse in an era before central nervous system prophylaxis was routinely given. Comparison of the mortality observed with that expected from mortality rates in the general population indicated three times the expected number of deaths from non-neoplastic causes. Five times the expected number of deaths from cardiovascular causes were observed, these were predominantly myocardial infarction and cerebrovascular accidents. There was no evidence of an excess in the number of suicides observed, but there were three times the expected number of deaths from accidents observed after central nervous system tumours.
3
Maternal outcome after open fetal surgery. A review of the first 17 human cases. A few fetal diseases may benefit from surgical treatment before birth, but hysterotomy and subsequent delivery by cesarean section pose a risk to the otherwise unaffected mother. To assess maternal risk of mortality, morbidity, and reproductive potential after fetal surgery, we reviewed our experience with 17 highly selected women who underwent fetal surgery. Fifteen of these procedures were performed for one of two congenital anomalies: severe bilateral hydronephrosis and congenital diaphragmatic hernia. There were no deaths or serious maternal injuries. In the 14 women who continued pregnancy after hysterotomy, uterine irritability and preterm labor were frequent complications, requiring early confinement in most cases. There has been no detectable effect on future fertility, as indicated by eight subsequent normal pregnancies. We conclude that hysterotomy for fetal surgery can be accomplished without unduly endangering the mother's life or her future reproductive potential. However, morbidity related to premature labor remains a serious problem, and our ability to control uterine contractions after hysterotomy remains the limiting factor in human fetal surgery.
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Intestinal cryptosporidiosis: pathophysiologic alterations and specific cellular and humoral immune responses in rnu/+ and rnu/rnu (athymic) rats. In order to develop an experimental model of symptomatic cryptosporidiosis in an immunosuppressed mammal, we investigated the pathophysiology of infection with Cryptosporidium and the humoral and cellular host responses in rnu/rnu (athymic) rats and their heterozygous (rnu/+) littermates by challenging suckling rats with greater than or equal to 2.5 x 10(6) Cryptosporidium oocytes oro-gastrically. Normal and immunodeficient animals were followed for onset and duration of infection (fecal oocysts), physiologic consequences (diarrhea, impaired weight gain, brush-border enzyme activities), and immunologic response (both B- and T-lymphocyte-mediated). Homozygosity for the rnu gene was associated with protracted cryptosporidial infections; shedding for up to 52 days occurred, and delay in weight gain was noted in rnu/rnu-infected compared with rnu/rnu-uninfected rats (p less than 0.05). In contrast, cryptosporidial challenge of rnu/+ rats resulted in self-resolving infections, occasionally with transient diarrhea lasting four days or less occurring 10-15 days after oro-gastric challenge. The latter animals mounted a cell-mediated immune response to Cryptosporidium: three months after challenge, five of five rnu/+ rats demonstrated positive skin test responses to a subcutaneous 3.5 micrograms dose of cryptosporidial antigen. Further, sera from 6 rnu/+ rats taken two to three months after oro-gastric oocyst challenge exhibited specific anticryptosporidial immunoglobulin binding (A405 = 0.96), compared to that of seven uninfected rnu/+ controls (A405 = 0.09, P less than 0.02). Macromolecules of 150, 105, and 88 kD in the Cryptosporidium antigen preparation were bound by serum immunoglobulin from previously infected, recovered rnu/+ rats. Two brush-border enzymes (lactase and alkaline phosphatase) were markedly reduced in the ileum 8-10 days after oro-gastric challenge in rats with diarrhea and oocyst shedding. We find the rnu/rnu (athymic, nude) rat provides a useful model for study of prolonged cryptosporidial infection with impaired weight loss, brush-border enzyme alteration and intermittent diarrhea. These studies further suggest that a T-lymphocyte population is involved in recovery from Cryptosporidium infection and that this recovery is associated with both cellular and humoral immune responses to specific cryptosporidial antigenic macromolecules. This model should open further avenues for the study of the pathogenesis and protective immunity in cryptosporidial infection.
1
DMPO and reperfusion injury: arrhythmia, heart function, electron spin resonance, and nuclear magnetic resonance studies in isolated working guinea pig hearts. With the use of isolated working guinea pig hearts with normothermic global ischemia, it was shown that 5,5-dimethyl-pirroline-N-oxide (DMPO), an organic spin trap agent designed specifically to form stable adducts with oxygen free radicals in electron spin resonance studies, can dramatically reduce the vulnerability of the heart to reperfusion-induced arrhythmias. Studied in concentrations ranging from 10 to 500 mumol/L, DMPO exerted a dose-dependent protective effect. Thus, after 30 minutes of global ischemia, the incidence of ventricular fibrillation (total) and tachycardia was reduced from control values of 100% and 100% to 100% and 100%, 91% and 100%, 25% (p less than 0.001) and 50% (p less than 0.05), and 25% (p less than 0.001) and 41% (p less than 0.05), respectively, with DMPO concentrations of 10, 30, 100, and 500 mumol/L. Maximum signals of DMPO-OH adduct, with the use of electron spin resonance studies, were observed after 3 minutes of reperfusion in fibrillated hearts but were not detected in nonfibrillated hearts. Results of nuclear magnetic resonance studies of myocardial adenosine triphosphate, creatine phosphate, pH, and inorganic phosphate showed that these parameters were not significantly changed by treatment with DMPO, and consequently myocardial heart function was not improved, although there was a dissociation between myocardial adenosine triphosphate content and left ventricular developed pressure during reperfusion. The data presented here indicate that oxygen free radicals play an important role in the development of reperfusion-induced arrhythmias but trapping these cytotoxic free radicals does not improve the recovery of postischemic heart function and high-energy phosphate contents in isolated working guinea pig hearts.
4
Tissue-expanded radial forearm free flap in neck burn contracture. Neck contracture after burn injury can result in severe functional as well as aesthetic deformities. Contracture can recur even after wide and complete release and full-thickness skin grafting. Recurrence is partly due to the inherent difficulties in both early postoperative immobilization and the required long-term splinting. When adjacent tissues are also burned, adequate local tissue for reconstruction may not be available; therefore, free-tissue transfer may be necessary. The large surface area that is required after adequate release may be provided by tissue expansion before free-tissue transfer. In the case presented the use of tissue-expanded radial forearm free flap for the reconstruction of a recurrent neck contracture is described.
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Normalization of plasma arginine vasopressin concentrations when children with meningitis are given maintenance plus replacement fluid therapy We hypothesized that plasma arginine vasopressin (AVP) concentrations in children with meningitis are appropriate for the children's degree of hypovolemia, even though the concentrations were higher than expected for the serum osmolality. A randomized study was conducted to compare the effect on plasma AVP concentrations of giving maintenance fluid requirements plus replacement of any deficit versus restricting fluids to two thirds of maintenance requirements for 24 hours. Plasma AVP concentrations and serum osmolality were measured before fluid therapy was begun and again after 24 hours. Nineteen children, 2 months to 17 years of age, were studied; 13 had bacterial meningitis (12 with Haemophilus influenzae type b). Ten children (seven with bacterial meningitis) received a mean of 1.42 times the calculated maintenance fluid requirements, and nine (six with bacterial meningitis) were restricted to a mean of 0.65 times maintenance. Children in the maintenance group also received significantly more sodium (mean = 6.3 mEq/kg/24 hr) than children in the fluid-restricted group (mean = 2.0 mEq/kg/24 hr). The two groups were comparable for plasma AVP concentration and serum osmolality before fluid therapy was begun. The plasma AVP concentration was significantly lower after 24 hours of maintenance plus replacement fluids than after fluid restriction (p = 0.005), and the change in AVP concentration correlated with the amount of sodium given (p less than 0.02). This study supports the hypothesis that serum AVP concentrations are elevated in patients with meningitis because of hypovolemia and become normal when sufficient sodium is given to facilitate reabsorption of water by the proximal tubule of the kidney. Patients with meningitis can be given maintenance plus replacement fluids but should be monitored for the development of the syndrome of inappropriate secretion of antidiuretic hormone.
2
Repeat hepatic resection for primary and metastatic carcinoma of the liver. During the last 15 years, 19 patients underwent repeated hepatic resections for malignant lesions of the liver. The first hepatic resection had been performed four to 40 months earlier for treatment of hepatocellular carcinoma (nine patients) or hepatic metastases (ten patients), eight of which were of colorectal origin. Repeat resection was an extensive hepatectomy in six, a segmentectomy in six and a local excision in seven. In one patient, three wedge resections and, finally, hepatic transplantation were subsequently performed after an initial extended right lobectomy. The operative mortality rate was 5.2 per cent. The three year actuarial survival rate was 64 per cent after the second resection.
4
The ras oncogenes in human lung cancer. The three well-characterized genes of the ras gene family H-ras, K-ras, and N-ras, code for closely related 21-kD proteins that have a role in the transduction of growth signals. The ras proteins acquire transforming potential when a point mutation in the gene leads to replacement of an amino acid in one of the critical positions 12, 13, or 61. Overexpression of the normal protein, usually associated with gene amplification, can have similar effects. The detection of mutationally activated ras genes has been facilitated by the development of oligonucleotide hybridization assays that allow the identification of each possible mutation at the critical sites. Employment of the polymerase chain reaction has greatly increased the sensitivity of these assays. Studies of human lung cancer have shown that adenocarcinoma is the only subtype associated with ras mutations. These occur in about 30% of primary tumors. In almost all cases, the mutation is present in codon 12 of the K-ras gene. No mutations have been observed to date in tumors of nonsmokers, suggesting that the mutation may result from exposure to carcinogenic ingredients of tobacco smoke. Amplifications of ras genes were shown to be very uncommon in clinically early stages of lung cancer. Analysis of the clinical data of patients who were operated on for adenocarcinoma of the lung shows that K-ras mutations are not associated with particular histologic characteristics of the tumors or with specific presenting features. Patients with K-ras mutations, however, had significantly worse survival than did those without an activation.
0
Spontaneous reactivation in chronic hepatitis B: patterns and natural history. We identified spontaneous reactivation of hepatitis B virus (HBV) retrospectively by utilizing serum alanine aminotransferase and HBV DNA in 19 men (79% homosexual), with an estimated annual incidence of 7.3%. In 11 patients, spontaneous reactivation occurred as a single episode and in eight patients, reactivation was recurrent, with two to five episodes each. The mean serum alanine aminotransferase level was elevated over 10-fold at the peak of reactivation. Serum anti-HBc IgM was detected during 73% of the reactivation episodes. Actuarial analysis revealed that reactivation was long lasting with 45% and nearly 20% of episodes continued after 6 and 24 months, respectively. The course of 24 chronic HBV carriers with a negative serum HBV DNA test and normal alanine aminotransferase levels at initial appearance was unremarkable. We could not identify clinical features predictive of reactivation or its resolution. Severe reactivation hepatitis occurred in three patients (10%), with two deaths (6%). None of the patients lost HBsAg. Spontaneous reactivation in chronic hepatitis B can appear variably, persist long term, recur, and be fatal. Therefore, accurate classification of chronic HBV infection requires prolonged observation, and spontaneous reactivation should be considered a variable in therapeutic trials for chronic hepatitis B.
4
Co-trimoxazole for childhood febrile illness in malaria-endemic regions. The efficacy of co-trimoxazole for the treatment of Plasmodium falciparum parasitaemia in children younger than 5 years of age was evaluated in Malawi. 46 children with P falciparum parasitaemia, 37% of whom also met clinical criteria for a diagnosis of acute lower respiratory tract infection, were treated with 20 mg/kg co-trimoxazole twice daily for five days. Parasitaemia (mean clearance time 2.7 days) and symptoms were rapidly abolished and improvement was maintained during follow-up for 14 days. Co-trimoxazole may be an effective single treatment for febrile illness in young children in areas where malaria is endemic, resources are few, and diagnosis must rely on clinical findings alone.
4
The efficacy of central venous and pulmonary artery catheters and therapy based upon them in reducing mortality and morbidity. The purpose of this study was to (1) evaluate the relative cost effectiveness of the central venous pressure and flow-directed pulmonary artery catheters used to maintain normal hemodynamic values as therapeutic goals in the control groups vs supranormal values empirically observed in critically ill postoperative survivors in the protocol groups, and (2) to evaluate tissue perfusion and oxygenation in relationship to organ failure and mortality. In two prospective clinical trials there were no significant differences in outcome between the central venous pressure and pulmonary artery control groups that used normal values as therapeutic goals. However, there were marked and significant reductions in morbidity and mortality of the protocol groups using the supranormal cardiac index, oxygen delivery, and oxygen consumption values as goals. The cumulative oxygen debt was less and organ failures were fewer and less severe in the protocol groups than in the control groups.
4
Diagnosis of nasopharyngeal carcinoma by means of recombinant Epstein-Barr virus proteins. The immune response of patients with nasopharyngeal carcinoma to Epstein-Barr virus (EBV) antigens is diagnostic of the tumour. Existing tests use EBV antigens produced in EBV-infected lymphoblastoid cells, but the virus replicates poorly in these cells. Serum samples from 18 patients diagnosed as having nasopharyngeal carcinoma were screened by western blot analysis, enzyme-linked immunosorbent assay (ELISA), and immunofluorescence tests for antibodies to the EBV-coded alkaline deoxyribonuclease (DNase), thymidine kinase, and membrane antigen (gp340/220) produced in recombinant baculovirus or bovine papillomavirus systems. Each protein was a useful diagnostic marker for nasopharyngeal carcinoma, although in the gp340/220 ELISAs there was substantial overlap for both IgG and IgA antibodies between serum samples from nasopharyngeal carcinoma patients and those from healthy donors seropositive for EBV. The EBV thymidine kinase was the most sensitive predictor of nasopharyngeal carcinoma; all such samples showed both IgG and IgA antibody responses to this protein and all gave clearly distinct titres from those of the EBV-seropositive donors in the IgA test. Each of the recombinant systems described is suitable for use in large-scale screening programmes for the early diagnosis of nasopharyngeal carcinoma.
0
Primary hepatic malignancy: the role of liver transplantation. Between January 1982 and April 1989, 134 patients with a suspected liver neoplasm were referred to the liver unit, Queen Elizabeth Hospital, Birmingham. In 105 (78 per cent), a primary hepatic neoplasm was histologically confirmed, and 47 patients (45 per cent) proved to have primary hepatocellular carcinoma. Twenty-nine orthotopic liver transplants were performed in 28 of these patients (27 per cent). Twenty patients (71 per cent) survived 30 days or longer (median 11.5 months; range 2-87 months), of whom nine are currently alive. We retrospectively analysed our data to determine the influence of preoperative evaluation, histological type and staging on outcome. Computed tomography proved to be superior to intraoperative assessment (86 versus 58 per cent) in diagnosing tumour positive nodes. Patients with tumour negative lymphadenopathy had a better prognosis. Postoperative stage I/II had a median survival of 16 months (range 3-87 months) compared with 7.5 months (range 2-20 months) for stage III. Non-cirrhotic patients with hepatocellular carcinoma had the best prognosis; cholangiocellular carcinoma and cirrhotic patients with hepatocelluar carcinoma had the worst outcome with no survivors beyond 1 year. Because of the advanced stage of disease at the time of presentation, the value of liver transplantation in primary liver cancer is limited. For those presenting with advanced disease confined to the liver (stage I/II) in whom conventional hepatic resection is not possible, significant benefit can be achieved in selected cases.
1
Pulmonary complications of combination therapy with cyclophosphamide and prednisone. Oral cyclophosphamide and prednisone are standard treatment for some neoplasms and necrotizing systemic vasculitis and are advocated with increasing frequency for idiopathic interstitial lung disease. During a 15-month period, we observed four cases of acute respiratory failure from Pneumocystis carinii pneumonia (PCP) in patients treated with oral cyclophosphamide and prednisone. One patient each had polyarteritis nodosa, Wegener's granulomatosis, bronchiolitis obliterans with organizing pneumonia, and chronic lymphocytic leukemia with red blood cell aplasia. Hypoalbuminemia (serum albumin level less than 3.0 g/dl) and daily therapy were associated with increased risk for development of PCP (p less than 0.05). None of the patients had leukopenia (less than 3,500/cu mm) or neutropenia (less than 1,000/cumm) at diagnosis. All were negative for the human immunodeficiency virus. Patients receiving oral cyclophosphamide and prednisone may be at higher or increasing risk for PCP. A high index of suspicion and aggressive evaluation for opportunistic infection are needed in these patients; consideration for trimethoprim-sulfamethoxazole prophylaxis and development of more quantitative measures of immunosuppression are needed.
0
Dietary deficiency of antioxidants exacerbates ischemic injury in the rat kidney. We examined the effects of dietary deficiency of vitamin E and selenium on the ischemia-reperfusion model of renal injury in the rat. Deficient diets imposed for six weeks on three-week-old weanling rats led to no significant differences in body weights, serum creatinine, GFR, RBF, TmPAH or urinary total protein excretory rates prior to ischemia. Twenty-four hours after one hour of ischemia, animals on the deficient diet demonstrated more markedly impaired GFR, RBF, TmPAH and urine to plasma creatinine concentrations and an increased renal failure index. Tubular damage was more severe injury in the deficient animals. Lipid peroxidation, 15 minutes after the release of the ischemic clamp, was increased in the deficient animals. We confirmed the effects of our dietary manipulation in impairing the oxidant scavenging system in the deficient animals since glutathione peroxidase activity was reduced to less than 5% in the basal state, and this striking reduction persisted following ischemia. Plasma vitamin E concentrations were also markedly depressed in the deficient diets. This dietary deficiency also worsened the course of acute renal injury and was accompanied by 50% mortality compared to 0% mortality in the control animals. Thus, dietary deficiency of vitamin E and selenium led to greater structural and functional renal impairment and increased lipid peroxidation following ischemia. These data provide support for the role of reactive oxygen species in mediating ischemia-reperfusion injury.
4
Fucosylated oligosaccharides of human milk protect suckling mice from heat-stabile enterotoxin of Escherichia coli. Human milk protects suckling mice from the diarrheagenic effects of heat-stabile enterotoxin of Escherichia coli (ST). To identify the human milk fraction responsible for this protection, pooled skimmed, deproteinated milk was passed through charcoal, whereupon lactose was separated from the oligosaccharides. The oligosaccharides contained ST-protective activity; the lactose did not. The neutral, but not the acidic, fraction exhibited protective activity against ST (22% vs. 57% mortality, respectively; P less than .001). The fucosylated, but not the nonfucosylated, subfractions of the neutral fraction contained the factor protective against ST (35% vs. 50% mortality, respectively; P less than .05). An oligosaccharide isolation scheme based on different principles produced confirmatory results. The commercially available neutral fucosylated oligosaccharides of human milk did not significantly protect the mice from the effects of ST. Thus, the protective factor against ST seems to be a minor neutral fucosyloligosaccharide of human milk.
1
Laryngeal framework reconstruction with miniplates. Defects of the laryngeal framework after trauma, cancer, and thyroplasty have been reconstructed with mini-reconstruction plates. Six patients had miniplates used to repair the thyroid cartilage defect after type I thyroplasty to prevent lateralization of the Silastic implant; three patients had miniplates used after hemilaryngectomy to bridge the thyroid cartilage remnants, resulting in better deglutition after hemilaryngectomy; and three patients had miniplates used to repair laryngeal fractures. The plates were tolerated well by the patients; there were no major complications. Rigid fixation using miniplates for laryngeal reconstruction has unique advantages over the use of wires. It offers the advantages of rigid and immediate stabilization with the ability to bridge large defects. It can be an alternative to existing techniques of laryngeal reconstruction.
4
Tumor of the atrioventricular nodal region. A clinical and immunohistochemical study. Autopsy specimens of 17 tumors of the atrioventricular nodal region were studied. Sudden death occurred in 14 children and adults; seven of these patients had a history of atrioventricular block or syncope. Three tumors were incidental findings in infants with other congenital anomalies; diaphragmatic agenesis, pulmonary hypoplasia, and Meckel's diverticulum in one patient; mitral atresia in one; and congenital hydrocephalus, ventricular septal defect, patent ductus arteriosus, coarctation of the aorta, and patent omphalovitelline duct in the third. Immunohistochemical stains demonstrated strong positivity for carcinoembryonic antigen in 13 of 13 cases, B72.3 antigen in 5 of 7 cases, and cytokeratin in 11 of 11 cases. Twenty control cases of mesothelioma and mesothelial hyperplasia were all negative for B72.3; one showed focal carcinoembryonic antigen staining. Ultrastructural analysis of one case demonstrated short rudimentary microvilli not characteristic of mesothelial cells. We conclude that so-called mesotheliomas of the atrioventricular nodal region are not of mesothelial origin, because of strong carcinoembryonic antigen positivity and occasional positivity with B72.3, as these antibodies react with glycoproteins found in endodermally derived tissue and generally not with mesothelial tissue. Conduction system tumors are most likely congenital rests of endodermal origin, can be associated with other congenital anomalies, and often cause symptoms of heart block and sudden death.
0
Segmented turboFLASH: method for breath-hold MR imaging of the liver with flexible contrast. A method called segmented turboFLASH imaging allows high-resolution, multisection, short-inversion-time (TI) inversion-recovery (STIR), T1- or T2-weighted magnetic resonance (MR) studies of the liver to be completed within a breath-hold interval. The method was applied in a phantom and in 19 patients with hepatic lesions. Sequence comparisons were performed among segmented turboFLASH, single-shot turboFLASH, T1-weighted gradient-echo with ultrashort echo time, and T2-weighted spin-echo (SE) techniques. Signal from fat and liver could be nulled with the segmented turboFLASH method, with TIs of 10 and 300 msec, respectively; signal from these tissues could not be eliminated with the single-shot approach. Signal-difference-to-noise ratios and contrast for the best segmented sequences were comparable with those of the best T2-weighted SE and T1-weighted gradient-echo techniques. It is concluded that it is feasible to obtain breath-hold images with arbitrary tissue contrast by means of segmented turboFLASH imaging. The method may prove helpful for the detection and characterization of hepatic lesions and will likely have applications to other anatomic regions such as the chest and pelvis.
3
Receptor imaging: application to MR imaging of liver cancer. A new contrast agent for magnetic resonance (MR) imaging, directed to asialoglycoprotein (ASG) receptors on hepatocytes, was used for detection of liver cancer in rats. Ultrasmall superparamagnetic (mean size, 12 nm) particles of iron oxide (USPIOs) were targeted to ASG receptors by coating particles with arabinogalactan (AG). Liver T2 relaxation times decreased more effectively after a single intravenous administration of AG-USPIO than after an equal dose of a conventional superparamagnetic liver MR contrast agent (AMI-25; mean size, 72 nm). Receptor affinity studies demonstrated that receptor-mediated attachment and subsequent cellular endocytosis do not occur in primary malignant (hepatocellular carcinoma) or metastatic (adenocarcinoma) tumors, because the surface ASG receptors are lost during malignant dedifferentiation. In vitro relaxation and in vivo MR imaging experiments of liver tumors show that targeting USPIO to hepatocytes rather than to the mononuclear phagocytic system allows a considerable dose reduction, increases tumor-liver contrast, and potentially allows distinction of ASG-positive (benign hepatocellular) and ASG-negative (malignant hepatocellular) tumors.
0
Persistent lower respiratory tract inflammation associated with interstitial lung disease in patients with tropical pulmonary eosinophilia following conventional treatment with diethylcarbamazine. Tropical pulmonary eosinophilia (TPE) presents as an acute syndrome with dyspnea, fluffy infiltrates, and rounded opacities on the chest radiograph, reduced lung function, marked eosinophilia in the blood and lower respiratory tract, and high titers of specific IgE and IgG antifilarial antibodies. The standard therapy for TPE is a 3-wk course of diethylcarbamazine (DEC) following which there is almost always a marked improvement in all parameters. However, clinical observations suggest that the disease can persist despite DEC therapy and lead to chronic dyspnea with restrictive lung impairment. To evaluate the concept that DEC therapy is not completely "curative" for TPE, but rather leaves most individuals with a mild, chronic form of TPE defined by persistent inflammation of the lower respiratory tract, we evaluated 23 individuals an average of 12 +/- 2 months following a standard 3-wk course of diethylcarbamazine for acute TPE. In the majority there were mild, persistent symptoms referrable to the lung, chest X-ray abnormalities, blood eosinophilia, and elevated serum IgE and filarial specific IgG. On the average, lung function was consistent with the presence of chronic, mild interstitial lung disease. When the inflammatory cells from the lower respiratory tract were examined, there was a persistent eosinophilic alveolitis (TPE/post-DEC 1769 +/- 376 eosinophils/microliters epithelial lining fluid; normal subjects 256 +/- 38, p less than 0.02). Evaluation of the lower respiratory tract inflammatory cells recovered from the TPE/post-DEC-treated individuals demonstrated spontaneous release of exaggerated amounts of O2-. and H2O2 compared to normal subjects (p less than 0.05, both comparisons).
4
Mediastinitis following coronary artery bypass surgery: a 3-year review. Twenty cases of mediastinitis after coronary artery bypass graft operations in 1985-1987 were reviewed to determine risk factors. Two distinct clusters with a methicillin-resistant Staphylococcus aureus (MRSA) strain occurred in 1986. One resident was exposed to six cases but to only 5 of 24 controls (P less than .008). Cultures of his nares in January and November 1986 revealed the same MRSA strain as that of the cases. An attempt to eradicate the resident's nasal carriage of MRSA in January 1986 failed; eradication of his carrier state was achieved only after treatment with mupirocin. In a case-control study examining patients exposed to the resident, a prolonged duration of surgery (P less than .05) and a preoperative albumin level of less than 3.0 g/dl (P less than .009) were associated with mediastinitis with this MRSA. For the other 14 mediastinitis patients, who were not exposed to the resident, a preoperative albumin level of less than 3.0 g/dl was also a risk factor (8/14 cases vs. 8/43 controls, P less than .009). Thus, this study suggests that it is important to follow MRSA disseminators and to recognize that preoperative serum albumin levels are a risk factor for mediastinitis.
4
Granulocyte-macrophage colony-stimulating factor synergizes with interleukin-6 in supporting the proliferation of human myeloma cells. The role of granulocyte-macrophage colony-stimulating factor (GM-CSF) in the growth of multiple myeloma (MM) was investigated in 21 patients with MM. In 17 patients with proliferating myeloma cells in vivo, recombinant GM-CSF significantly increased the endogenous-IL-6-mediated spontaneous myeloma cell proliferation occurring in 5-day cultures of tumor cells in vitro (P less than .01). Furthermore, GM-CSF was detected in 5-day culture supernatants of myeloma bone marrow cells. This endogenous GM-CSF was produced by the myeloma bone marrow microenvironment but not by myeloma cells and contributed to the spontaneous myeloma-cell proliferation observed in 5-day cultures. In fact, this proliferation was partially blocked (67%) by anti-GM-CSF monoclonal antibodies. The stimulatory effect of rGM-CSF was mediated through IL-6 because it was abrogated by anti-IL-6 monoclonal antibodies. rGM-CSF did not reproducibly increase the endogenous IL-6 production in short-term cultures of bone marrow cells of MM patients. Using an IL-6-dependent myeloma cell line (XG-1 cell line), rGM-CSF was shown to act directly on myeloma cells stimulating by twofold their IL-6 responsiveness. rGM-CSF did not induce any IL-6 production in XG-1 cells, nor was it able to sustain their growth alone. Although no detectable GM-CSF levels were found in the peripheral or bone marrow blood of MM patients, it is possible that GM-CSF, produced locally by the tumoral environment, enhances the IL-6 responsiveness of myeloma cells in vivo in a way similar to that reported here in vitro.
0
Angiographic assessment of the culprit coronary artery lesion before acute myocardial infarction. Serial angiographic studies of patients with myocardial infarction and unstable angina suggest that the culprit plaque underlying a thrombus need not have produced severe luminal obstruction before onset of the event. An atherosclerotic coronary artery lesion can, therefore, have 2 important characteristics. First, it may be obstructive. Second, it may be "vulnerable" in that it has the potential to become thrombogenic if exposed to the appropriate triggering stimulus. A lesion need not be obstructive to become thrombogenic, nor do all obstructive lesions have thrombogenic potential. The cause of an infarction may thus be rupture of a nonobstructive plaque leading to occlusive thrombus formation. Because it may be difficult to predict the site of a subsequent occlusion from a coronary angiogram, coronary bypass surgery or angioplasty directed only at discernible stenotic lesions may not be effective for preventing subsequent myocardial infarctions. Appropriate therapy may need to be directed at the entire coronary tree. Such therapy might include cholesterol lowering, beta blockade and aspirin.
4
Tourette syndrome and other tic disorders. Diagnosis, pathophysiology, and treatment. In this report, we discuss the definition, characteristics, pathophysiology, and treatment of tic disorders with a major emphasis on Tourette syndrome. Although the diagnosis of a tic disorder depends on the presence of motor and/or phonic tic(s), patients with these problems also have a variety of co-morbid features including obsessive-compulsive symptoms, attention-deficit hyperactivity disorder, behavioral difficulties, and learning disabilities. Conservative estimates for Tourette syndrome suggest a prevalence rate of 0.1-1.0 per 1000. This syndrome is inherited in a sex-influenced autosomal dominant pattern with either chronic multiple tic disorder or obsessive-compulsive disorder as alternative phenotypes of the putative gene. Current evidence continues to support a pathophysiologic mechanism involving synaptic neurotransmission, with the dopaminergic system as a primary candidate. Therapeutically, it is essential to clarify whether a patient's problems are related to tics or associated behavioral difficulties. Pharmacotherapy for motor and phonic tics is strictly symptomatic and should be reserved for those with functionally disabling symptoms. A comprehensive individualized treatment program is often required in the care of individuals with tic disorders.
2
Local failure and related complications after definitive treatment of carcinoma of the prostate by irradiation or surgery. The authors review their institution's experience with the failure of definitive treatment to achieve local tumor control and with the distant dissemination and local morbidity associated with such failure. The causes of local failure are various: incomplete resection, implantation of spilled cells, and, possibly, selective implantation of circulating tumor cells in traumatized tissues after surgery and totally or partially resistant cells, new tumors, or radiologic misses after radiation. Treatment of local failure may be prophylactic or therapeutic and differs depending on the stage of the disease. Failure to control the tumor locally in the presence of distant metastases does not alter the length of survival, but it can profoundly affect the quality of survival.
4
Molecular phenotype of a pediatric small round cell tumor. Molecular probes were used to characterize an unusual small round cell abdominal tumor arising from the fallopian tube of a 15-year-old girl. DNA and RNA extracted from the tumor and adjacent normal tissue was subjected to Southern and Northern blot analysis using a variety of different probes. N-myc oncogene RNA was greatly expressed in the tumor, but was not expressed in normal tissue or amplified in chromosomal DNA. Insulin-like growth factor II RNA was similarly overexpressed in the neoplasm, but not in normal tissue. While histopathologic studies could not distinguish between a neuroectodermal neoplasm and Wilms' tumor, electron microscopy and the pattern of gene expression was most consistent with Wilms' tumor.
0
Point mutation, allelic loss and increased methylation of c-Ha-ras gene in human hepatocellular carcinoma. Somatic alterations of the c-Ha-ras gene were examined in 21 Japanese patients with hepatocellular carcinoma. Restriction endonuclease analysis by double digestion with MspI and HpaII revealed that DNAs from two of 21 hepatocellular carcinoma tissues were affected by nucleotide substitution at the twelfth amino acid coding sequence of the c-Ha-ras gene. DNAs from cirrhotic noncancerous liver tissue, but not leukocytes, of one of these patients possessed the mutation, whereas DNAs from noncirrhotic liver tissue and leukocytes of the other patient did not. In one of the nine patients harboring heterozygosity for c-Ha-ras-related BamHI-fragments, the loss of one allele was demonstrated as a somatic change not only in DNA from the tumor tissue but also in DNA from the cirrhotic nontumorous tissue. In two of the 19 patients comparatively examined for digestion patterns of c-Ha-ras locus with HpaII and MspI, extensive methylation was observed as a somatic modification in both DNAs from the tumor and the cirrhotic nontumorous tissues. These results thus indicate that the genetic lesions affecting the c-Ha-ras gene do occur in human hepatocellular carcinoma and probably serve as one of the multiple steps in the process of hepatic carcinogenesis.
0
Total pelvic exenteration with simultaneous bowel and urinary reconstruction. The technique of total pelvic exenteration with simultaneous bowel and urinary reconstruction is described as a surgical option for the management of pelvic sarcoma in adults and for highly selected patients with other types of advanced pelvic malignancy. The surgical technique is presented in detail as performed in a 43-year-old man who presented with extensive primitive pelvic sarcoma. We believe that this approach may provide the benefits of an exenterative operation without the undesirable psychosocial sequelae of a permanent colostomy and external urinary diversion.
0
Cardiac involvement in AIDS. Cardiac involvement in AIDS may occur at any stage of HIV disease and may manifest as congestive cardiomyopathy, potentially lethal arrhythmia, or pericardial effusion and tamponade. The heart may be affected by nearly all of the opportunistic infections and many of the malignancies associated with the syndrome. Although often clinically unobtrusive, cardiac lesions may be important in the pathogenesis of significant clinical symptoms and play an often unrecognized role in the prognosis and natural history of AIDS.
3
Diabetes insipidus associated with craniopharyngioma in pregnancy. A case is presented of a pregnancy complicated by a suprasellar mass diagnosed at 27 weeks' gestation. This patient developed diabetes insipidus, which was successfully treated with 1-desamino-8-D-arginine vasopressin. Thyrotropin-releasing hormone and ACTH stimulation tests were also abnormal, requiring the institution of thyroid and cortisol replacement therapy. The patient was delivered at 34 weeks' gestation secondary to worsening visual field testing. A craniotomy was performed in the postpartum period with removal of a craniopharyngioma. With successful medical treatment and careful observation, surgical intervention may be postponed until postpartum or until a gestational age with lower neonatal morbidity and mortality is reached.
0
Risks factors for cerebral infarction in good-grade patients after aneurysmal subarachnoid hemorrhage and surgery: a prospective study. A prospective series of 265 patients with aneurysmal subarachnoid hemorrhage (SAH) of Grades I to III (Hunt and Hess classification) upon admission were evaluated as to neurological outcome and computerized tomography (CT) findings 1 to 3 years (mean 1.4 years) after the SAH and surgery. A total of 73 patients underwent acute surgery (within 72 hours after the bleed: Days 0 to 3), 86 were operated on subacutely (between Days 4 and 7), and 91 had late surgery (on Day 8 or later). Fifteen patients died before surgery was undertaken and another 20 patients died during the follow-up period. A total of 104 patients received nimodipine and the rest of the patients received either placebo (109 patients) or no medication (52 patients). A logistical regression analysis revealed the following prognostic factors for cerebral infarction, in order of importance: the amount of blood on the primary CT scan; postoperative angiographic vasospasm; the timing of the operation; and a history of hypertension. The use of nimodipine was associated with a significant reduction of cerebral infarcts visualized by CT scanning in patients who received intermediate or late surgery. In patients who underwent acute surgery no significant difference between the incidence of cerebral infarcts was observed.
3
Pruritic papular eruption of the acquired immunodeficiency syndrome: a clinicopathologic study. The pruritic papular eruption of the acquired immunodeficiency syndrome is characterized by generalized, pruritic, skin-colored papules and nodules. Chronic lesions are excoriated and hyperpigmented. The eruption and pruritus typically wax and wane and are resistant to oral antihistamine and topical steroid therapy. The characteristic histologic features are (1) superficial and mid dermal perivascular and perifollicular mononuclear cell infiltrate with numerous eosinophils and (2) follicular damage of varying degrees. When compared with control subjects, these patients did not demonstrate any significant difference in laboratory or demographic data.
4
Mycosis fungoides-like lesions associated with phenytoin and carbamazepine therapy. We report the cases of four patients who were taking the anticonvulsant drugs phenytoin or carbamazepine and in whom skin lesions developed that showed histologic features suggestive of mycosis fungoides. Two patients had a solitary lesion on the trunk, whereas the other two patients had multiple plaques. In all four patients systemic signs were absent.
0
Ehlers-Danlos syndrome type IV: diagnosis and therapy of associated bowel perforation. Ehlers-Danlos syndrome type IV is a heritable disease of type III collagen metabolism. This diagnosis is suspected in a patient with a combination of clinical manifestations and family history, but it is confirmed only by culture of the patient's skin fibroblasts and demonstration of a defect in type III collagen metabolism. The disease may rarely present with spontaneous colonic perforation, a complication traditionally treated by primary closure of the perforated segment and creation of an end colostomy. Attempts at bowel reanastomosis have often resulted in repeated colon perforations. We present the first patient with Ehlers-Danlos type IV syndrome to develop a colon perforation proximal to an end colostomy, and discuss the surgical strategy to prevent recurrences of this and other postoperative complications associated with the syndrome.
1
Circadian rhythm of heart rate variability after acute myocardial infarction and its influence on the prognostic value of heart rate variability. This study examined heart rate (HR) variability in patients surviving acute myocardial infarction (AMI) to find the optimum time and duration of recording of the ambulatory electrocardiogram for the prediction of the risk of sudden cardiac death, or serious arrhythmic events, or both. Twenty patients (group I) who initially survived an AMI but later experienced serious events (death or symptomatic sustained ventricular tachycardia) during a 6-month follow-up were compared with 20 patients (group II) who remained free of complications for greater than 6 months after discharge. Groups I and II were matched with regard to age, gender, infarct site, ejection fraction, and beta-blocker treatment. HR variability was assessed in the 24-hour electrocardiograms recorded during the first 2 weeks after an AMI and in various portions of the complete 24-hour recording, with both the beginning and the length of the analyzed portion varied by 20 minutes (a total of 5,113 possibilities). The maximum reduction of HR variability in group I patients was systematically found when assessing HR variability in recordings starting approximately at 6 A.M. and lasting for approximately 8 hours. In the low-risk patient, the diurnal rhythm of HR variability is more marked than in the high-risk patient and the long-term components of HR variability due to the diurnal variation must be included in the measurement of HR variability when using it as a long-term predictor of risk from arrhythmic events after an AMI.
3
Plasma norepinephrine and dihydroxyphenylglycol in essential hypertension. The aim of the present study was to examine whether essential hypertension is associated with altered plasma concentrations of dihydroxyphenylglycol, the principal presynaptic metabolite of norepinephrine. Forearm venous plasma dihydroxyphenylglycol and norepinephrine were determined at rest and during graded orthostasis in 47 normotensive control subjects and 58 outpatients with essential hypertension. There was no group difference in age. At supine rest as well as during sitting and standing, hypertensive subjects had plasma norepinephrine concentrations similar to those in normotensive control subjects, but plasma dihydroxyphenylglycol concentrations were higher than those in normotensive control subjects. Both groups showed a linear relation between plasma dihydroxyphenylglycol (ordinate) and plasma norepinephrine (abscissa). The resulting regression line was steeper (p less than 0.02) and its ordinate intercept higher (p less than 0.01) in hypertensive than in control subjects. Eleven normotensive and 14 hypertensive subjects were also tested 3 hours after desipramine (1.5 mg/kg orally) was administered to inhibit neuronal norepinephrine reuptake. The drug did not alter plasma norepinephrine, but did reduce plasma dihydroxyphenylglycol and did abolish plasma dihydroxyphenylglycol responses to upright posture in both groups of subjects. The mean plasma dihydroxyphenylglycol concentration observed in the presence of desipramine again was higher in the hypertensive than in the control group (p less than 0.01) and closely agreed, in both groups, with the dihydroxyphenylglycol concentration given by the ordinate intercept of the dihydroxyphenylglycol versus norepinephrine regression line in the absence of desipramine.
3
Relationship of clinical features with psychological status in primary fibromyalgia. Clinical features and psychological status determined by the Minnesota Multiphasic Personality Inventory (MMPI) in 103 patients with primary fibromyalgia syndrome (PFS) were analyzed by univariate and multivariate techniques to determine if clinical features were related to psychological status or were intrinsic to PFS per se. The central features of PFS, e.g., number of pain sites, number of tender points, fatigue, and poor sleep, were independent of psychological status. However, discriminant analysis identified 4 variables--patient-reported depression, anxiety, stress, and pain severity--which together predicted 3 MMPI subgroups with an accuracy of 55% (P less than 0.001); the only musculoskeletal feature--pain severity--alone provided an accuracy of only 34% (P greater than 0.05). These data suggest a new concept, that the central features of fibromyalgia are independent of the psychological status and are more likely related to the PFS itself. However, pain severity may be influenced by psychological factors.
2
Aerobic and anaerobic microbiologic factors and recovery of beta-lactamase producing bacteria from obstetric and gynecologic infection. Specimens obtained from 736 patients with obstetric and gynecologic infections were studied for aerobic and anaerobic bacteria. Bacterial growth was present in 714 specimens. These included 53 specimens of infected fallopian tubes, 470 of infected endometrium, 94 of infected amniotic fluid, 57 of aspirates of cul-de-sacs in instances of pelvic inflammatory disease, 14 labial and vaginal abscesses and 26 of Bartholyn's cyst abscess. A total of 2,052 isolates (2.9 per specimen), 1,139 anaerobes (1.6 per specimen) and 913 aerobic or facultative (1.3 per specimen) were recovered. The most commonly isolated anaerobic bacteria was Bacteroides species (566 isolates), which included Bacteroides bivius (151), Bacteroides fragilis group (130), Bacteroides melaninogenicus group (110) and Bacteroides ureolyticus (47). Others included an anaerobic gram-positive cocci (391), Clostridium species (48) and Fusobacterium species (36). The most frequently recovered aerobic and facultative bacteria were Lactobacillus species (169), Escherichia coli (85), Neisseria gonorrhoeae (62), Staphylococcus aureus (59) and Group B streptococcus (55). Three hundred and sixty-five (18 per cent) of the isolates recovered from 276 (39 per cent) patients were beta-lactamase producing organisms (BLPO); 222 (61 per cent) anaerobes and 143 (39 per cent) aerobes or facultatives. The most common BLPO were B. fragilis group, B. bivius, B. melaninogenicus, B. disiens, Enterobacteriaceae and S. aureus. These data illustrate the polymicrobial nature and important role of BLPO in obstetric and gynecologic infection.
4
Multilevel transneuronal degeneration after brain damage. Behavioral events and effects of anticonvulsant gamma-aminobutyric acid-related drugs. Recent morphologic and behavioral studies of the effects of gamma-aminobutyric acid agents on transsynaptic degeneration after cortical and striatal damage are reviewed and discussed. Following unilateral lesions of the anteromedial cortex, mild atrophy appears in the ipsilateral striatum and substantia nigra pars reticulata. Long-term diazepam administration greatly enhances this degeneration, extends the degeneration into the thalamus, and severely disrupts recovery from somatosensory asymmetries. Following unilateral excitotoxic lesions of the striatum, progressive degeneration of neurons occurs in the substantia nigra pars reticulata and efferent targets in the thalamus. This degeneration can be prevented by chronic infusion of muscimol, a gamma-aminobutyric acid agonist. Unexpectedly, this treatment did not facilitate recovery from somatosensory asymmetries. Recovery in muscimol-treated animals was impaired relative to saline-treated controls. Thus, gamma-aminobutyric acid agonists either may enhance or prevent neural atrophy secondary to brain damage, but the behavioral outcome appears to depend importantly on the excitatory and inhibitory characteristics of the affected networks.
2
Chordoma: a 20-year clinicopathologic review of the experience at Groote Schuur Hospital, Cape Town. Eighteen chordomas (11 females and 7 males) were seen over a 20-year period; 61% of the tumors occurred in the sphenoid region. The youngest patient was 3 years old and had a family history of chordoma. Histologically, the tumors were divided into classical (epithelial) and chondroid variants, which in this series, had no effect on outcome. Follow-up on 12 patients ranged from 3 to 170 months, and they were treated with various combinations of surgery and radiotherapy. One patient was administered the neutron beam and died after 94 months. The mean survival of this series is 73.4 months, with a survival rate of 50% (6 out of 12 patients alive). Surgical resection offers the best chance of survival, but chordomas have a propensity to metastasize, hence have a poor prognosis.
4
Le Fort I osteotomy approach to the skull base. Horizontal osteotomy allows the surgeon to safely down-fracture the maxilla for wide exposure of the central skull base. This surgical approach is easily extended posteriorly in the midline to include the clivus and the arch of C1, providing 8 cm of horizontal anterior exposure and 5 cm of posterior. Wide operative exposure and a low rate of complications afford superior functional and cosmetic preservation in removing tumors of the central cranial base.
0
Acute central nervous system symptoms caused by ibuprofen in connective tissue disease. We describe 2 cases of acute encephalopathy in patients with connective tissue disease caused by small doses of ibuprofen. In addition to aseptic meningitis, both patients had altered mental status and focal neurologic signs, ophthalmoplegia in one and hemiparesis in the other. The spectrum of neurologic manifestations of ibuprofen hypersensitivity is reviewed.
2
Successful surgical treatment of subaortic stenosis caused by an accessory mitral valve. A 22-month-old boy with subaortic stenosis was found to have relatively mature mitral valve tissue beneath the aortic valve, associated with a hypertrophic and prominent interventricular septum. This tissue caused obstruction of the left ventricular outflow tract and resulted in a pressure gradient of 70 mmHg between the aorta and the left ventricle. Surgical treatment was successfully performed to excise the tissue and part of the hypertrophic ventricular septum. Results of microscopic examination of the resected specimen are shown and discussed.
3
Characterization of astrocytomas, meningiomas, and pituitary adenomas by phosphorus magnetic resonance spectroscopy. Phosphorus magnetic resonance (MR) spectroscopy allows noninvasive measurement of phosphate-containing compounds and pH within brain cells. The authors obtained localized phosphorus MR spectra from 10 normal brains, four low-grade astrocytomas, six glioblastomas, four meningiomas, and three pituitary adenomas and found differences in the spectra of each tumor type. Compared to normal brain, the spectra from low-grade astrocytomas showed a significant reduction of the phosphodiester (PDE) peak. Glioblastomas were characterized by a significant reduction of the PDE peak, elevation of the phosphomonoester (PME) peak, and a relatively alkaline intracellular pH. The spectra from meningiomas and pituitary adenomas were markedly different from the glial tumors. Meningiomas showed significant reductions in phosphocreatine, PDE, and inorganic phosphate, as well as a relatively alkaline pH. Pituitary adenomas resembled meningiomas, but had a much higher PME peak. Although the number of tumors studied was small, there appears to be a characteristic spectrum associated with these different tumor types. The present findings can be useful in the preoperative identification of these tumors and in furthering understanding of their growth and metabolism in vivo.
0
Properties of strains of Escherichia coli O26:H11 in relation to their enteropathogenic or enterohemorrhagic classification. Thirty-seven strains of Escherichia coli O26:H11 from infants and calves with diarrhea were examined for properties associated with enteropathogenic (EPEC) or enterohemorrhagic E. coli (EHEC). Strains were heterogeneous with respect to Vero cytotoxin (VT) production and hybridization with the EHEC plasmid-specific (CVD419) probe; 26 strains produced VT1; 1 produced VT2. Twenty-four of 27 VT+ strains and 5 of 10 VT- strains hybridized with the CVD419 probe and produced enterohemolysin; these properties are characteristic of EHEC. The strains did not hybridize with the EPEC adherence factor probe, a property characteristic of some EPEC. Nevertheless, 36 strains adhered to HEp-2 cells in a localized manner and were positive by the fluorescence actin staining (FAS) test that is considered to correlate with the ability to cause attaching and effacing lesions in vivo. EPEC and EHEC cause these lesions. Although the FAS test appeared to be the most general pathogenicity test for the O26:H11 strains, it could not be used to assign strains specifically to EPEC or EHEC groups.
4
Selective evaluation and management of coronary artery disease in patients undergoing repair of abdominal aortic aneurysms. A 16-year experience. Reduction of cardiac mortality associated with abdominal aortic aneurysm (AAA) repair remains an important goal. Five hundred consecutive urgent or elective operations for infrarenal nonruptured AAA were reviewed. Patients were divided into three groups based on preoperative cardiac status: group I (n = 260, 52%), no clinical or electrocardiographic (ECG) evidence of coronary artery disease (CAD); group II (n = 212, 42.2%), clinical or ECG evidence of CAD considered stable after further evaluation with studies such as dipyridamole-thallium scanning, echocardiography, or coronary arteriography; group III (n = 28, 5.6%), clinical or ECG evidence of CAD considered unstable after further evaluation. Group I had no further cardiac evaluation and groups I and II underwent AAA repair without invasive treatment of CAD. Group III underwent repair of cardiac disease before (n = 21) or coincident with (n = 7) AAA repair. In all instances, perioperative fluid volume management was based on left ventricular performance curves constructed before operation. The 30-day operative mortality rate for AAA repair in all 500 patients was 1.6% (n = 8). There was one (0.4%) cardiac-related operative death in group I, which was significantly less than the five (2.4%) in group II (p less than 0.02). Total mortality for the two groups were also significantly different, with one group I death (0.4%) and seven group II deaths (3.3%), (p less than 0.02). These data support the conclusions that (1) the leading cause of perioperative mortality in AAA repair is myocardial infarction, (2) correction of severe or unstable CAD before or coincident with AAA repair is effective in preventing operative mortality, (3) patients with known CAD should be investigated more thoroughly to identify those likely to develop perioperative myocardial ischemia so that their CAD can be corrected before AAA repair, and (4) patients with no clinical or ECG evidence of CAD rarely die of perioperative myocardial infarction, and thus selective evaluation of CAD based on clinical grounds in AAA patients is justified.
4
Continuous electrocardiographic monitoring in hypertensive crises in pregnancy. Twenty-four patients first seen with hypertensive crises during pregnancy were studied by continuous electrocardiographic monitoring for a period of 24 hours to detect the presence of serious ventricular arrhythmias. Three patients were excluded from analysis because of low serum potassium levels. Thirteen of the remaining 21 patients had ventricular tachycardia on subsequent analysis of the electrocardiogram. These arrhythmias subsided after induction of anesthesia when blood pressure control was optimal. This finding may be implicated in the pathogenesis of pulmonary edema and sudden death in these patients.
4
Indium-labeled anti-colorectal carcinoma monoclonal antibody accumulation in non-tumored tissue in patients with colorectal carcinoma. Indium-111- (111In) labeled murine monoclonal antibodies ZCE 025 (against carcinoembryonic antigen) and CYT-103 MAb B72.3 (against tumor-associated glycoprotein - 72) have been used to image patients with colorectal cancers with encouraging results. The objectives of this study were to assess the frequency and causes of 111In MAb localization in tumor-free, benign tissues. Thus, scans of 75 patients who have undergone exploratory surgery following radioimmunoscintigraphy with 111In-ZCE 025 (n = 37) or 111In-CYT-103 (n = 38) were reviewed in conjunction with operative and histopathology reports. Localization in non-tumored tissues was seen in 10.8% and 13.1%, respectively, of patients receiving ZCE 025 and CYT-103. The most common sites involved were: degenerative joint disease, abdominal aneurysms, postoperative bowel adhesions, and local inflammatory changes secondary to surgery or external irradiation. Review of patients' medical history and results of concurrent diagnostic modalities is likely to lessen the false-positive rate of 111In-labeled MAb scan interpretation.
0
Sensitivity of effect variables in rheumatoid arthritis: a meta-analysis of 130 placebo controlled NSAID trials [published erratum appears in J Clin Epidemiol 1991;44(6):613] In a meta-analysis of placebo controlled NSAID trials, the sensitivity of the effect variables was calculated as the correlation coefficient and as the difference between drug and placebo, divided by the placebo group standard deviation. The patient's global evaluation was the most sensitive variable overall. Pain was more sensitive than Ritchie's index. Several variables may be omitted from clinical trials, especially if two active drugs are being compared. For example, the best maximum estimate for the difference in ESR between NSAIDs and placebo was 1.0 mm/hr (95% confidence interval -1.5 to 3.4 mm/hr), and for joint size 0.44% (-1.0 to 1.9%), corresponding to a quarter of a millimeter for each of the 10 joints usually measured. It is suggested to record only the patient's global evaluation, pain, and morning stiffness.
2
Tumor angiogenesis and metastasis--correlation in invasive breast carcinoma. BACKGROUND. Experimental evidence suggests that the growth of a tumor beyond a certain size requires angiogenesis, which may also permit metastasis. To investigate how tumor angiogenesis correlates with metastases in breast carcinoma, we counted microvessels (capillaries and venules) and graded the density of microvessels within the initial invasive carcinomas of 49 patients (30 with metastases and 19 without). METHODS. Using light microscopy, we highlighted the vessels by staining their endothelial cells immunocytochemically for factor VIII. The microvessels were carefully counted (per 200x field), and their density was graded (1 to 4+), in the most active areas of neovascularization, without knowledge of the outcome in the patient, the presence or absence of metastases, or any other pertinent variable. RESULTS. Both microvessel counts and density grades correlated with metastatic disease. The mean (+/- SD) count and grade in the patients with metastases were 101 +/- 49.3 and 2.95 +/- 1.00 vessels, respectively. The corresponding values in the patients without metastases were significantly lower--45 +/- 21.1 and 1.38 +/- 0.82 (P = 0.003 and P less than or equal to 0.001, respectively). For each 10-microvessel increase in the count per 200x field, there was a 1.59-fold increase in the risk of metastasis (95 percent confidence interval, 1.19 to 2.12; P = 0.003). The microvessel count and density grade also correlated with distant metastases. For each 10-microvessel increase in the vessel count per 200x field, there was a 1.17-fold increase in the risk of distant metastasis (95 percent confidence interval, 1.02 to 1.34; P = 0.029). CONCLUSIONS. The number of microvessels per 200x field in the areas of most intensive neovascularization in an invasive breast carcinoma may be an independent predictor of metastatic disease either in axillary lymph nodes or at distant sites (or both). Assessment of tumor angiogenesis may therefore prove valuable in selecting patients with early breast carcinoma for aggressive therapy.
0
Sexually transmitted causes of gastrointestinal symptoms in homosexual men. The possible etiologic agents that may cause gastrointestinal complaints in homosexually active men are multiple, and their diagnosis is complex. This article presents a logical approach to the work-up and diagnosis of gastrointestinal complaints in homosexually active men and to discuss their treatment and disease intervention.
1
Stools containing altered blood-plasma urea: creatinine ratio as a simple test for the source of bleeding. The plasma urea:creatinine ratio (U:C ratio) is known to be elevated in cases of upper gastrointestinal bleeding. Almost all patients with haematemesis have upper gastrointestinal (or generalized) bleeding so that in this study we characterized the diagnostic power of the U:C ratio in patients with stools containing altered blood without haematemesis in the hope that this simple laboratory test (used in conjunction, perhaps, with clinical data) might reduce the number of patients subjected to an unrewarding gastroscopy or colonoscopy. Of 76 cases seen in a provincial and a metropolitan hospital, 42 and 34 patients had upper and lower gastrointestinal bleeding, respectively. Fifty-four per cent of those with upper gastrointestinal bleeding and none of those with lower gastrointestinal bleeding had U:C ratios above 110 on admission. However, a discriminating level of 90 is considered to be more suitable, judged by the quadratic uncertainty score. At this level the odds for upper gastrointestinal bleeding were 15:1.
1
Postoperative complications after Molteno implant surgery. We performed Molteno implant surgery in one eye each of 41 patients with uncontrolled glaucoma. Intraocular pressure was controlled (intraocular pressure less than or equal to 18 mm Hg) in 32 eyes (78%). The mean preoperative intraocular pressure was 40 +/- 13.2 mm Hg, whereas the mean postoperative intraocular pressure was 16 +/- 6.6 mm Hg. Patients were followed up for an average of 16 months after the operation. Visual acuity was unchanged in 23 eyes (56%), improved in nine eyes (22%), and poorer in nine eyes (22%). The major complications included shallow anterior chamber and hypotony in six eyes (14.6%), vitreous hemorrhage in two eyes (4.9%), retinal detachment in one eye (2.4%), and malignant glaucoma in two eyes (4.9%). Less grave complications included hyphema in four eyes (9.8%), peripheral choroidal effusion in 15 eyes (36.6%), obstruction of the tube in six eyes (14.6%), recession of the tube into the angle in two eyes (4.9%), erosion of the tube in one eye (2.4%), and Tenon's cyst formation in three eyes (7.3%).
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The effect of ambulation on recovery from postoperative ileus. To determine whether ambulation hastens recovery from ileus following laparotomy, 34 patients were studied, 10 of whom followed an ambulatory regimen beginning on postoperative day 1 (group A). The other 24 patients (group C) did not become ambulatory until postoperative day 4. All patients underwent placement of seromuscular bipolar recording electrodes on the Roux limb, if present, stomach, jejunum, and colon at laparotomy. Group A was recorded before and after ambulation so comparisons could be made to determine if ambulation had an acute effect on myoelectric activity. Group A preambulation and group C recordings were compared to judge whether there was an over-all effect of ambulation on myoelectric recovery. No effect on slow wave frequency or percentage of slow waves with associated spike potentials was noted acutely or overall in the stomach, colon, or jejunum in continuity with the duodenal pacemaker. Transient increases in phase II spike activity in patients having a Roux limb and their jejunum distal to the enteroenterostomy were noted on postoperative days 1 to 2, but these differences resolved by postoperative days 3 or 4. The data suggest that ambulation as a means to help resolve postoperative ileus and its accompanying cramps and bloating may be more perceived than real.
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Vascular and nonvascular expression of INCAM-110. A target for mononuclear leukocyte adhesion in normal and inflamed human tissues. Inducible cell adhesion molecule 110 (INCAM-110), is a 110-kd adhesion receptor for lymphocytes and monocytes identified on cytokine-activated endothelium. Using immunoperoxidase techniques, little or no INCAM-110 was detected on endothelium in normal human tissues. In contrast, INCAM-110 was expressed in postcapillary venules in a variety of active inflammatory processes. In acute appendicitis, INCAM-110 was found coincident with strong expression of endothelial leukocyte adhesion molecule 1 (ELAM-1), a cytokine-inducible molecule that functions in neutrophil adhesion. However, in certain chronic inflammatory processes (eg, sarcoidosis), INCAM-110 was observed without simultaneous ELAM-1 expression. Anti-INCAM-110 antibody E1/6 also marked several extravascular cell types, including lymphoid dendritic cells, some tissue macrophages, synovial lining cells, and reactive mesothelial cells. These data suggest a role for endothelial INCAM-110 in the pathophysiology of both acute and chronic inflammatory reactions. Furthermore INCAM-110 may function as an adhesion molecule for mononuclear leukocytes in a variety of extravascular sites.
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DNA ploidy in the primary tumor from patients with nonseminomatous testicular germ cell tumors clinical stage I. The DNA stemline ploidy was assessed in paraffin-embedded, formalin-fixed primary tumor tissue from 68 patients with nonseminomatous germ cell cancer (NSCGT) clinical Stage I (CS I). Forty-three patients had a single aneuploid (greater than 1C) DNA stemline, whereas 24 patients had multiple aneuploid stemlines. In one tumor there was no evidence of an abnormal DNA stemline. Most DNA stemlines had DNA indices around the 3c value. In 13 patients there was a good correlation between the DNA stemline values observed in the primary tumor and in the retroperitoneal lymph node metastases. No correlation was found between the DNA index and the histologic subclassification or the metastatic behavior. The size of the S-phase fraction did not appear to be predictive of subclinical metastases. In CS I patients with NSCGT determination of DNA stemline values does not yield information of predictive or prognostic significance but may contribute to the understanding of the pathogenesis of NSCGT.
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Progression of peripheral occlusive arterial disease in diabetes mellitus. What factors are predictive? The clinical, biochemical, and vascular laboratory measurements potentially associated with the development and/or progression of peripheral occlusive arterial disease (POAD) were assessed during a 4-year period in 110 normal control subjects, 112 patients with POAD without diabetes mellitus, 240 patients with diabetes mellitus without POAD, and 100 patients with diabetes mellitus and POAD. Age, history of hypertension or coronary heart disease, history of cigarette smoking, presence of POAD, systolic blood pressure, and beta-thromboglobulin level were associated with progression of POAD. A multivariate logistic regression model indicated that the presence of diabetes mellitus or POAD or both at baseline, decreased postexercise ankle-brachial index, increased arm systolic blood pressure, and current smoking were independently associated with progression of POAD. This study suggests that cessation of smoking and control of hypertension are essential treatment modifications to decrease the risk of progression of peripheral vascular disease in diabetic patients.
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Fingernail deformities secondary to ganglions of the distal interphalangeal joint (mucous cysts). Twenty-six nail deformities secondary to ganglions of the distal interphalangeal joint were retrospectively reviewed to assess the important aspects of their management. The patients' ages ranged from 41 to 79 years. The long and index fingers were most commonly involved. A depression or groove was present in 23 of 26 digits reviewed. Two had gross disruption of the nail. Fifty-eight percent of the cysts had spontaneously drained or had been drained by the patient or a physician preoperatively. Degenerative arthritic changes were seen in 87 percent of those with x-rays or a radiology report available. Most underwent surgical removal of the cyst and debridement of associated osteophytes of the distal interphalangeal joint. The cyst was located above the germinal matrix in all but two digits. Osteophytes were found in all 20 digits in which the joint was explored. No recurrences were seen in those available for postoperative follow-up (22 of 25). Normal nail growth was found in 14 of 22, although follow-up was short in one. All eight postoperative nail deformities were quite mild and of little concern to the patient. There was no correlation between preoperative cyst drainage and aesthetic postoperative nail growth. Nail removal at the time of surgery appeared to be unnecessary unless the nail was grossly disrupted.
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