Instruction: Extract chemical and disease entities from the following text.

Input: Effect of switching carbamazepine to oxcarbazepine on the plasma levels of neuroleptics. A case report. Carbamazepine was switched to its 10-keto analogue oxcarbazepine among six difficult-to-treat schizophrenic or organic psychotic patients using concomitantly haloperidol, chlorpromazine or clozapine. This change resulted within 2-4 weeks in the 50-200% increase in the plasma levels of these neuroleptics and the appearance of extrapyramidal symptoms. None of the patients showed any clinical deteriotation during the following 3-6 months. The results of this case report support the idea that in contrast with carbamazepine oxcarbazepine does not induce the hepatic microsomal enzyme systems regulating the inactivation of antipsychotic drugs.

Output: Chemical/Disease Entities: carbamazepine (Chemical), oxcarbazepine (Chemical), Carbamazepine (Chemical), oxcarbazepine (Chemical), schizophrenic (Disease), organic psychotic (Disease), haloperidol (Chemical), chlorpromazine (Chemical), clozapine (Chemical), extrapyramidal symptoms (Disease), carbamazepine (Chemical), oxcarbazepine (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Erythema multiforme and hypersensitivity myocarditis caused by ampicillin. OBJECTIVE: To report a case of erythema multiforme and hypersensitivity myocarditis caused by ampicillin. CASE SUMMARY: A 13-year-old boy was treated with ampicillin and gentamicin because of suspected septicemia. Medications were discontinued when erythema multiforme and congestive heart failure caused by myocarditis occurred. The patient was treated with methylprednisolone and gradually improved. Macrophage-migration inhibition (MIF) test with ampicillin was positive. DISCUSSION: After most infections causing erythema multiforme and myocarditis were ruled out, a drug-induced allergic reaction was suspected. Positive MIF test for ampicillin showed sensitization of the patient's lymphocytes to ampicillin. CONCLUSIONS: Hypersensitivity myocarditis is a rare and dangerous manifestation of allergy to penicillins.

Output: Chemical/Disease Entities: Erythema multiforme (Disease), hypersensitivity myocarditis (Disease), ampicillin (Chemical), erythema multiforme (Disease), hypersensitivity myocarditis (Disease), ampicillin (Chemical), ampicillin (Chemical), gentamicin (Chemical), septicemia (Disease), erythema multiforme (Disease), congestive heart failure (Disease), myocarditis (Disease), methylprednisolone (Chemical), ampicillin (Chemical), infections (Disease), erythema multiforme (Disease), myocarditis (Disease), drug-induced allergic reaction (Disease), ampicillin (Chemical), ampicillin (Chemical), Hypersensitivity myocarditis (Disease), allergy (Disease), penicillins (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Immediate allergic reactions to amoxicillin. A large group of patients with suspected allergic reactions to beta-lactam antibiotics was evaluated. A detailed clinical history, together with skin tests, RAST (radioallergosorbent test), and controlled challenge tests, was used to establish whether patients allergic to beta-lactam antibiotics had selective immediate allergic responses to amoxicillin (AX) or were cross-reacting with other penicillin derivatives. Skin tests were performed with benzylpenicilloyl-poly-L-lysine (BPO-PLL), benzylpenicilloate, benzylpenicillin (PG), ampicillin (AMP), and AX. RAST for BPO-PLL and AX-PLL was done. When both skin test and RAST for BPO were negative, single-blind, placebo-controlled challenge tests were done to ensure tolerance of PG or sensitivity to AX. A total of 177 patients were diagnosed as allergic to beta-lactam antibiotics. We selected the 54 (30.5%) cases of immediate AX allergy with good tolerance of PG. Anaphylaxis was seen in 37 patients (69%), the other 17 (31%) having urticaria and/or angioedema. All the patients were skin test negative to BPO; 49 of 51 (96%) were also negative to MDM, and 44 of 46 (96%) to PG. Skin tests with AX were positive in 34 (63%) patients. RAST was positive for AX in 22 patients (41%) and to BPO in just 5 (9%). None of the sera with negative RAST for AX were positive to BPO. Challenge tests with AX were performed in 23 subjects (43%) to establish the diagnosis of immediate allergic reaction to AX, and in 15 cases (28%) both skin test and RAST for AX were negative. PG was well tolerated by all 54 patients. We describe the largest group of AX-allergic patients who have tolerated PG reported so far. Diagnosis of these patients can be achieved only if specific AX-related reagents are employed. Further studies are necessary to determine the exact extent of this problem and to improve the efficacy of diagnostic methods.

Output: Chemical/Disease Entities: allergic reactions (Disease), amoxicillin (Chemical), allergic reactions (Disease), beta-lactam (Chemical), allergic (Disease), beta-lactam (Chemical), allergic (Disease), amoxicillin (Chemical), AX (Chemical), penicillin (Chemical), benzylpenicilloyl-poly-L-lysine (Chemical), BPO-PLL (Chemical), benzylpenicilloate (Chemical), benzylpenicillin (Chemical), PG (Chemical), ampicillin (Chemical), AMP (Chemical), AX (Chemical), BPO-PLL (Chemical), AX (Chemical), BPO (Chemical), PG (Chemical), AX (Chemical), allergic (Disease), beta-lactam (Chemical), AX (Chemical), allergy (Disease), PG (Chemical), Anaphylaxis (Disease), urticaria (Disease), angioedema (Disease), BPO (Chemical), MDM (Disease), PG (Chemical), AX (Chemical), AX (Chemical), BPO (Chemical), AX (Chemical), BPO (Chemical), AX (Chemical), allergic reaction (Disease), AX (Chemical), AX (Chemical), PG (Chemical), AX (Chemical), allergic (Disease), PG (Chemical), AX (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Persistent paralysis after prolonged use of atracurium in the absence of corticosteroids. Neuromuscular blocking agents (NMBAs) are often used for patients requiring prolonged mechanical ventilation. Reports of persistent paralysis after the discontinuance of these drugs have most often involved aminosteroid-based NMBAs such as vecuronium bromide, especially when used in conjunction with corticosteroids. Atracurium besylate, a short-acting benzylisoquinolinium NMBA that is eliminated independently of renal or hepatic function, has also been associated with persistent paralysis, but only when used with corticosteroids. We report a case of atracurium-related paralysis persisting for approximately 50 hours in a patient who was not treated with corticosteroids.

Output: Chemical/Disease Entities: paralysis (Disease), atracurium (Chemical), paralysis (Disease), vecuronium bromide (Chemical), Atracurium besylate (Chemical), benzylisoquinolinium (Chemical), paralysis (Disease), atracurium (Chemical), paralysis (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Habitual use of acetaminophen as a risk factor for chronic renal failure: a comparison with phenacetin. Six epidemiologic studies in the United States and Europe indicate that habitual use of phenacetin is associated with the development of chronic renal failure and end-stage renal disease (ESRD), with a relative risk in the range of 4 to 19. As a result of these and other studies, phenacetin has now been withdrawn from the market in most countries. However, three case control studies, one each in North Carolina, northern Maryland, and West Berlin, Germany, showed that habitual use of acetaminophen is also associated with chronic renal failure and ESRD, with a relative risk in the range of 2 to 4. These studies suggest that both phenacetin and acetaminophen may contribute to the burden of ESRD, with the risk of the latter being somewhat less than that of the former. This apparent difference in risk may not be due to differences in nephrotoxic potential of the drugs themselves. A lower relative risk would be expected for acetaminophen if the risk of both drugs in combination with other analgesics was higher than the risk of either agent alone. Thus, acetaminophen has been used both as a single agent and in combination with other analgesics, whereas phenacetin was available only in combinations. The possibility that habitual use of acetaminophen alone increases the risk of ESRD has not been clearly demonstrated, but cannot be dismissed.

Output: Chemical/Disease Entities: acetaminophen (Chemical), chronic renal failure (Disease), phenacetin (Chemical), phenacetin (Chemical), chronic renal failure (Disease), end-stage renal disease (Disease), ESRD (Disease), phenacetin (Chemical), acetaminophen (Chemical), chronic renal failure (Disease), ESRD (Disease), phenacetin (Chemical), acetaminophen (Chemical), ESRD (Disease), nephrotoxic (Disease), acetaminophen (Chemical), acetaminophen (Chemical), phenacetin (Chemical), acetaminophen (Chemical), ESRD (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Reduction of heparan sulphate-associated anionic sites in the glomerular basement membrane of rats with streptozotocin-induced diabetic nephropathy. Heparan sulphate-associated anionic sites in the glomerular basement membrane were studied in rats 8 months after induction of diabetes by streptozotocin and in age- adn sex-matched control rats, employing the cationic dye cuprolinic blue. Morphometric analysis at the ultrastructural level was performed using a computerized image processor. The heparan sulphate specificity of the cuprolinic blue staining was demonstrated by glycosaminoglycan-degrading enzymes, showing that pretreatment of the sections with heparitinase abolished all staining, whereas chondroitinase ABC had no effect. The majority of anionic sites (74% in diabetic and 81% in control rats) were found within the lamina rara externa of the glomerular basement membrane. A minority of anionic sites were scattered throughout the lamina densa and lamina rara interna, and were significantly smaller than those in the lamina rara externa of the glomerular basement membrane (p<0.001 and p<0.01 for diabetic and control rats, respectively). Diabetic rats progressively developed albuminuria reaching 40.3 (32.2-62.0) mg/24 h after 8 months in contrast to the control animals (0.8 (0.2-0.9) mg/24 h, p<0.002). At the same time, the number of heparan sulphate anionic sites and the total anionic site surface (number of anionic sites x mean anionic site surface) in the lamina rara externa of the glomerular basement membrane was reduced by 19% (p<0.021) and by 26% (p<0.02), respectively. Number and total anionic site surface in the remaining part of the glomerular basement membrane (lamina densa and lamina rara interna) were not significantly changed. We conclude that in streptozotocin-diabetic rats with an increased urinary albumin excretion, a reduced heparan sulphate charge barrier/density is found at the lamina rara externa of the glomerular basement membrane.

Output: Chemical/Disease Entities: heparan sulphate (Chemical), streptozotocin (Chemical), diabetic nephropathy (Disease), Heparan sulphate (Chemical), diabetes (Disease), streptozotocin (Chemical), cuprolinic blue (Chemical), heparan sulphate (Chemical), cuprolinic blue (Chemical), glycosaminoglycan (Chemical), diabetic (Disease), diabetic (Disease), Diabetic (Disease), albuminuria (Disease), heparan sulphate (Chemical), streptozotocin (Chemical), diabetic (Disease), heparan sulphate (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Effect of some anticancer drugs and combined chemotherapy on renal toxicity. The nephrotoxic action of anticancer drugs such as nitrogranulogen (NG), methotrexate (MTX), 5-fluorouracil (5-FU) and cyclophosphamide (CY) administered alone or in combination [MTX + 5-FU + CY (CMF)] was evaluated in experiments on Wistar rats. After drug administration, creatinine concentrations in the plasma and in the urine of the rats were determined, as well as creatinine clearance. Histopathologic evaluation of the kidneys was also performed. After MTX administration a significant increase (p = 0.0228) in the plasma creatinine concentration and a significant (p = 0.0001) decrease in creatinine clearance was noted compared to controls. After the administration of NG, 5-FU and CY neither a statistically significant increase in creatinine concentration nor an increase in creatinine clearance was observed compared to the group receiving no cytostatics. Following polytherapy according to the CMF regimen, a statistically significant decrease (p = 0.0343) in creatinine clearance was found, but creatinine concentration did not increase significantly compared to controls. CY caused hemorrhagic cystitis in 40% of rats, but it did not cause this complication when combined with 5-FU and MTX. Histologic changes were found in rat kidneys after administration of MTX, CY and NG, while no such change was observed after 5-FU and joint administration of MTX + 5-FU + CY compared to controls. Our studies indicate that nephrotoxicity of MTX + 5-FU + CY administered jointly is lower than in monotherapy.

Output: Chemical/Disease Entities: renal toxicity (Disease), nephrotoxic (Disease), nitrogranulogen (Chemical), NG (Chemical), methotrexate (Chemical), MTX (Chemical), 5-fluorouracil (Chemical), 5-FU (Chemical), cyclophosphamide (Chemical), CY (Chemical), MTX (Chemical), 5-FU (Chemical), CY (Chemical), creatinine (Chemical), creatinine (Chemical), MTX (Chemical), creatinine (Chemical), creatinine (Chemical), NG (Chemical), 5-FU (Chemical), CY (Chemical), creatinine (Chemical), creatinine (Chemical), creatinine (Chemical), creatinine (Chemical), CY (Chemical), 5-FU (Chemical), MTX (Chemical), MTX (Chemical), CY (Chemical), NG (Chemical), 5-FU (Chemical), MTX (Chemical), 5-FU (Chemical), CY (Chemical), nephrotoxicity (Disease), MTX (Chemical), 5-FU (Chemical), CY (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Lithium-associated cognitive and functional deficits reduced by a switch to divalproex sodium: a case series. BACKGROUND: Lithium remains a first-line treatment for the acute and maintenance treatment of bipolar disorder. Although much has been written about the management of the more common adverse effects of lithium, such as polyuria and tremor, more subtle lithium side effects such as cognitive deficits, loss of creativity, and functional impairments remain understudied. This report summarizes our experience in switching bipolar patients from lithium to divalproex sodium to alleviate such cognitive and functional impairments. METHOD: Open, case series design. RESULTS: We report seven cases where substitution of lithium, either fully or partially, with divalproex sodium was extremely helpful in reducing the cognitive, motivational, or creative deficits attributed to lithium in our bipolar patients. CONCLUSION: In this preliminary report, divalproex sodium was a superior alternative to lithium in bipolar patients experiencing cognitive deficits, loss of creativity, and functional impairments.

Output: Chemical/Disease Entities: Lithium (Chemical), cognitive and functional deficits (Disease), divalproex sodium (Chemical), Lithium (Chemical), bipolar disorder (Disease), lithium (Chemical), polyuria (Disease), tremor (Disease), lithium (Chemical), cognitive deficits (Disease), loss of creativity (Disease), functional impairments (Disease), bipolar (Disease), lithium (Chemical), divalproex sodium (Chemical), cognitive and functional impairments (Disease), lithium (Chemical), divalproex sodium (Chemical), cognitive, motivational, or creative deficits (Disease), lithium (Chemical), bipolar (Disease), divalproex sodium (Chemical), lithium (Chemical), bipolar (Disease), cognitive deficits (Disease), loss of creativity (Disease), functional impairments (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Treatment of previously treated metastatic breast cancer by mitoxantrone and 48-hour continuous infusion of high-dose 5-FU and leucovorin (MFL): low palliative benefit and high treatment-related toxicity. For previously treated advanced breast cancer, there is no standard second-line therapy. Combination chemotherapy with mitoxantrone, high-dose 5-fluorouracil (5-FU) and leucovorin (MFL regimen) had been reported as an effective and well tolerated regimen. From October 1993 to November 1995, we treated 13 patients with previously chemotherapy-treated metastatic breast cancer by mitoxantrone, 12 mg/m2, on day 1 and continuous infusion of 5-FU, 3000 mg/m2, together with leucovorin, 300 mg/m2, for 48 h from day 1 to 2. Each course of chemotherapy was given every 4 weeks. Most of these patients had more than two metastatic sites, with lung metastasis predominant. Seven patients had been treated with anthracycline. Seven patients had previously received radiotherapy and seven had received hormone therapy. Median number of courses of MFL regimen given was six and the median cumulative dose of mitoxantrone was 68.35 mg/m2. One patient had complete response, seven had stable disease, none had partial response and five had progressive disease. The overall objective response rate was 7.6%. The median follow-up period was 14 months. Median survival was 16 months. Median progression-free survival was 5 months. A complete responder had relapse-free survival up to 17 months. Major toxicities were cardiotoxicity and leukopenia. Eight patients were dead in the last follow-up; two of them died of treatment-related toxicity. The MFL regimen achieves little palliative benefit and induces severe toxicity at a fairly high rate. Administration of this regimen to breast cancer patients who have been treated by chemotherapy and those with impaired heart function requires careful attention.

Output: Chemical/Disease Entities: breast cancer (Disease), mitoxantrone (Chemical), 5-FU (Chemical), leucovorin (Chemical), MFL (Chemical), toxicity (Disease), breast cancer (Disease), mitoxantrone (Chemical), 5-fluorouracil (Chemical), 5-FU (Chemical), leucovorin (Chemical), MFL regimen (Chemical), breast cancer (Disease), mitoxantrone (Chemical), 5-FU (Chemical), leucovorin (Chemical), anthracycline (Chemical), MFL regimen (Chemical), mitoxantrone (Chemical), toxicities (Disease), cardiotoxicity (Disease), leukopenia (Disease), toxicity (Disease), MFL regimen (Chemical), toxicity (Disease), breast cancer (Disease), impaired heart function (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Upregulation of the expression of vasopressin gene in the paraventricular and supraoptic nuclei of the lithium-induced diabetes insipidus rat. The expression of arginine vasopressin (AVP) gene in the paraventricular (PVN) and supraoptic nuclei (SON) was investigated in rats with lithium (Li)-induced polyuria, using in situ hybridization histochemistry and radioimmunoassay. The male Wistar rats consuming a diet that contained LiCl (60 mmol/kg) for 4 weeks developed marked polyuria. The Li-treated rats produced a large volume of hypotonic urine with low ionic concentrations. Plasma sodium concentrations were found to be slightly increased in the Li-treated rats compared with those in controls. Plasma concentration of AVP and transcripts of AVP gene in the PVN and SON were significantly increased in the Li-treated rats compared with controls. These results suggest that dehydration and/or the activation of visceral afferent inputs may contribute to the elevation of plasma AVP and the upregulation of AVP gene expression in the PVN and the SON of the Li-induced diabetes insipidus rat.

Output: Chemical/Disease Entities: vasopressin (Chemical), lithium (Chemical), diabetes insipidus (Disease), arginine vasopressin (Chemical), AVP (Chemical), lithium (Chemical), Li (Chemical), polyuria (Disease), LiCl (Chemical), polyuria (Disease), Li (Chemical), sodium (Chemical), Li (Chemical), AVP (Chemical), AVP (Chemical), Li (Chemical), dehydration (Disease), AVP (Chemical), AVP (Chemical), Li (Chemical), diabetes insipidus (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Suxamethonium-induced cardiac arrest and death following 5 days of immobilization. The present report describes a case of cardiac arrest and subsequent death as a result of hyperkalaemia following the use of suxamethonium in a 23-year-old Malawian woman. Five days after the onset of the symptoms of meningitis, the patient aspirated stomach contents and needed endotracheal intubation. Forty seconds after injection of suxamethonium, bradycardia and cardiac arrest occurred. Attempts to resuscitate the patient were not successful. The serum level of potassium was observed to be 8.4 mequiv L-1. Apart from the reduction in the patient's level of consciousness, there were no signs of motor neurone damage or of any of the other known predisposing conditions for hyperkalaemia following the administration of suxamethonium. It is postulated that her death was caused by hypersensitivity to suxamethonium, associated with her 5-day immobilization.

Output: Chemical/Disease Entities: Suxamethonium (Chemical), cardiac arrest (Disease), death (Disease), cardiac arrest (Disease), death (Disease), hyperkalaemia (Disease), suxamethonium (Chemical), meningitis (Disease), suxamethonium (Chemical), bradycardia (Disease), cardiac arrest (Disease), potassium (Chemical), hyperkalaemia (Disease), suxamethonium (Chemical), death (Disease), hypersensitivity (Disease), suxamethonium (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: An unusual toxic reaction to axillary block by mepivacaine with adrenaline. An increase in blood pressure, accompanied by atrial fibrillation, agitation, incomprehensible shouts and loss of consciousness, was observed in an elderly, ASA classification group II, cardiovascularly medicated male, 12 min after performance of axillary block with mepivacaine 850 mg containing adrenaline 0.225 mg, for correction of Dupuytren's contracture. After intravenous administration of labetalol, metoprolol and midazolam the patient's condition improved, and 15 min later he woke up. The block was successful and surgery was conducted as scheduled despite persisting atrial fibrillation. Postoperatively, the patient refused DC cardioversion and was treated medically. Both the temporal relationship of events and the response to treatment suggest that a rapid systemic absorption of mepivacaine with adrenaline and/or interaction of these drugs with the patient's cardiovascular medications were responsible for the perioperative complications.

Output: Chemical/Disease Entities: mepivacaine (Chemical), adrenaline (Chemical), increase in blood pressure (Disease), atrial fibrillation (Disease), agitation (Disease), incomprehensible shouts (Disease), loss of consciousness (Disease), mepivacaine (Chemical), adrenaline (Chemical), Dupuytren's contracture (Disease), labetalol (Chemical), metoprolol (Chemical), midazolam (Chemical), atrial fibrillation (Disease), mepivacaine (Chemical), adrenaline (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Clinical and histopathologic examination of renal allografts treated with tacrolimus (FK506) for at least one year. BACKGROUND: We clinically and pathologically analyzed renal allografts from 1 9 renal transplant patients treated with tacrolimus (FK506) for more than 1 year. METHODS: Twenty-six renal allograft biopsy specimens from 1 9 renal transplant patients who underwent transplantations between 1991 and 1993 were evaluated. Thirteen biopsies were performed from stable functioning renal allografts with informed consent (nonepisode biopsy) and the other 13 were from dysfunctional renal allografts with a clinical indication for biopsy (episode biopsy). RESULTS: The main pathologic diagnoses (some overlap) were acute rejection (AR; n = 4), chronic rejection (CR; n=5), AR+CR (n =4), recurrent IgA nephropathy (n =5), normal findings (n =2), minimal-type chronic FK506 nephropathy (n = 9), and mild-type FK506 nephropathy (n = 11). Of the nonepisode biopsies, 7 and 4 biopsies showed minimal-type and mild-type chronic FK506 nephropathy, respectively. Chronic FK506 nephropathy consisted of rough and foamy tubular vacuolization (5 biopsies), arteriolopathy (angiodegeneration of the arteriolar wall; 20 biopsies), focal segmental glomerulosclerosis (4 biopsies) and the striped form of interstitial fibrosis (11 biopsies). The serum creatinine levels of patients in the mild-type chronic FK506 nephropathy group, which included 7 episode biopsies, were statistically higher than those in the minimum-type chronic FK506-nephropathy group (P< 0.001). CONCLUSIONS: This study demonstrates that chronic FK506 nephropathy consists primarily of arteriolopathy manifesting as insudative hyalinosis of the arteriolar wall, and suggests that mild-type chronic FK506 nephropathy is a condition which may lead to deterioration of renal allograft function.

Output: Chemical/Disease Entities: tacrolimus (Chemical), FK506 (Chemical), tacrolimus (Chemical), FK506 (Chemical), IgA nephropathy (Disease), FK506 (Chemical), nephropathy (Disease), FK506 (Chemical), nephropathy (Disease), FK506 (Chemical), nephropathy (Disease), FK506 (Chemical), nephropathy (Disease), focal segmental glomerulosclerosis (Disease), interstitial fibrosis (Disease), creatinine (Chemical), FK506 (Chemical), nephropathy (Disease), FK506 (Chemical), nephropathy (Disease), FK506 (Chemical), nephropathy (Disease), FK506 (Chemical), nephropathy (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Memory facilitation and stimulation of endogenous nerve growth factor synthesis by the acetylcholine releaser PG-9. The effects of PG-9 (3alpha-tropyl 2-(p-bromophenyl)propionate), the acetylcholine releaser, on memory processes and nerve growth factor (NGF) synthesis were evaluated. In the mouse passive-avoidance test, PG-9 (10-30 mg/kg, i.p.), administered 20 min before the training session, prevented amnesia induced by both the non selective antimuscarinic drug scopolamine and the M1-selective antagonist S-(-)-ET-126. In the same experimental conditions, PG-9 (5-20 microg per mouse, i.c.v.) was also able to prevent antimuscarine-induced amnesia, demonstrating a central localization of the activity. At the highest effective doses, PG-9 did not produce any collateral symptoms as revealed by the Irwin test, and it did not modify spontaneous motility and inspection activity, as revealed by the hole-board test. PG-9 was also able to increase the amount of NGF secreted in vitro by astrocytes in a dose-dependent manner. The maximal NGF contents obtained by PG-9 were 17.6-fold of the control value. During culture, no morphological changes were found at effective concentrations of PG-9. The current work indicates the ability of PG-9 to induce beneficial effects on cognitive processes and stimulate activity of NGF synthesis in astroglial cells. Therefore, PG-9 could represent a potential useful drug able to improve the function of impaired cognitive processes.

Output: Chemical/Disease Entities: acetylcholine (Chemical), PG-9 (Chemical), PG-9 (Chemical), 3alpha-tropyl 2-(p-bromophenyl)propionate (Chemical), acetylcholine (Chemical), PG-9 (Chemical), amnesia (Disease), scopolamine (Chemical), S-(-)-ET-126 (Chemical), PG-9 (Chemical), amnesia (Disease), PG-9 (Chemical), PG-9 (Chemical), PG-9 (Chemical), PG-9 (Chemical), PG-9 (Chemical), PG-9 (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Angioedema due to ACE inhibitors: common and inadequately diagnosed. The estimated incidence of angioedema during angiotensin-converting enzyme (ACE) inhibitor treatment is between 1 and 7 per thousand patients. This potentially serious adverse effect is often preceded by minor manifestations that may serve as a warning.

Output: Chemical/Disease Entities: Angioedema (Disease), ACE inhibitors (Chemical), angioedema (Disease), angiotensin-converting enzyme (ACE) inhibitor (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Recurarization in the recovery room. A case of recurarization in the recovery room is reported. Accumulation of atracurium in the intravenous line led to recurarization after flushing the line in the recovery room. A respiratory arrest with severe desaturation and bradycardia occurred. Circumstances leading to this event and the mechanisms enabling a neuromuscular blockade to occur, following the administration of a small dose of relaxant, are discussed.

Output: Chemical/Disease Entities: atracurium (Chemical), respiratory arrest (Disease), desaturation (Disease), bradycardia (Disease), neuromuscular blockade (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Recurrent use of newer oral contraceptives and the risk of venous thromboembolism. The epidemiological studies that assessed the risk of venous thromboembolism (VTE) associated with newer oral contraceptives (OC) did not distinguish between patterns of OC use, namely first-time users, repeaters and switchers. Data from a Transnational case-control study were used to assess the risk of VTE for the latter patterns of use, while accounting for duration of use. Over the period 1993-1996, 551 cases of VTE were identified in Germany and the UK along with 2066 controls. Totals of 128 cases and 650 controls were analysed for repeat use and 135 cases and 622 controls for switching patterns. The adjusted rate ratio of VTE for repeat users of third generation OC was 0.6 (95% CI:0.3-1.2) relative to repeat users of second generation pills, whereas it was 1.3 (95% CI:0.7-2.4) for switchers from second to third generation pills relative to switchers from third to second generation pills. We conclude that second and third generation agents are associated with equivalent risks of VTE when the same agent is used repeatedly after interruption periods or when users are switched between the two generations of pills. These analyses suggest that the higher risk observed for the newer OC in other studies may be the result of inadequate comparisons of pill users with different patterns of pill use.

Output: Chemical/Disease Entities: oral contraceptives (Chemical), venous thromboembolism (Disease), venous thromboembolism (Disease), VTE (Disease), oral contraceptives (Chemical), OC (Chemical), OC (Chemical), VTE (Disease), VTE (Disease), VTE (Disease), OC (Chemical), VTE (Disease), OC (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Development of apomorphine-induced aggressive behavior: comparison of adult male and female Wistar rats. The development of apomorphine-induced (1.0 mg/kg s.c. once daily) aggressive behavior of adult male and female Wistar rats obtained from the same breeder was studied in two consecutive sets. In male animals, repeated apomorphine treatment induced a gradual development of aggressive behavior as evidenced by the increased intensity of aggressiveness and shortened latency before the first attack toward the opponent. In female rats, only a weak tendency toward aggressiveness was found. In conclusion, the present study demonstrates gender differences in the development of the apomorphine-induced aggressive behavior and indicates that the female rats do not fill the validation criteria for use in this method.

Output: Chemical/Disease Entities: apomorphine (Chemical), aggressive behavior (Disease), apomorphine (Chemical), aggressive behavior (Disease), apomorphine (Chemical), aggressive behavior (Disease), aggressiveness (Disease), aggressiveness (Disease), apomorphine (Chemical), aggressive behavior (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Serotonergic antidepressants and urinary incontinence. Many new serotonergic antidepressants have been introduced over the past decade. Although urinary incontinence is listed as one side effect of these drugs in their package inserts there is only one report in the literature. This concerns 2 male patients who experienced incontinence while taking venlafaxine. In the present paper the authors describe 2 female patients who developed incontinence secondary to the selective serotonin reuptake inhibitors paroxetine and sertraline, as well as a third who developed this side effect on venlafaxine. In 2 of the 3 cases the patients were also taking lithium carbonate and beta-blockers, both of which could have contributed to the incontinence. Animal studies suggest that incontinence secondary to serotonergic antidepressants could be mediated by the 5HT4 receptors found on the bladder. Further research is needed to delineate the frequency of this troubling side effect and how best to treat it.

Output: Chemical/Disease Entities: Serotonergic antidepressants (Chemical), urinary incontinence (Disease), serotonergic antidepressants (Chemical), urinary incontinence (Disease), incontinence (Disease), venlafaxine (Chemical), incontinence (Disease), serotonin (Chemical), paroxetine (Chemical), sertraline (Chemical), venlafaxine (Chemical), lithium carbonate (Chemical), incontinence (Disease), incontinence (Disease), serotonergic antidepressants (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Hypotension following the initiation of tizanidine in a patient treated with an angiotensin converting enzyme inhibitor for chronic hypertension. Centrally acting alpha-2 adrenergic agonists are one of several pharmacologic agents used in the treatment of spasticity related to disorders of the central nervous system. In addition to their effects on spasticity, certain adverse cardiorespiratory effects have been reported. Adults chronically treated with angiotensin converting enzyme inhibitors may have a limited ability to respond to hypotension when the sympathetic response is simultaneously blocked. The authors present a 10-year-old boy chronically treated with lisinopril, an angiotensin converting enzyme inhibitor, to control hypertension who developed hypotension following the addition of tizanidine, an alpha-2 agonist, for the treatment of spasticity. The possible interaction of tizanidine and other antihypertensive agents should be kept in mind when prescribing therapy to treat either hypertension or spasticity in such patients.

Output: Chemical/Disease Entities: Hypotension (Disease), tizanidine (Chemical), angiotensin (Chemical), hypertension (Disease), spasticity (Disease), disorders of the central nervous system (Disease), spasticity (Disease), angiotensin (Chemical), hypotension (Disease), lisinopril (Chemical), angiotensin (Chemical), hypertension (Disease), hypotension (Disease), tizanidine (Chemical), spasticity (Disease), tizanidine (Chemical), hypertension (Disease), spasticity (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Peritubular capillary basement membrane reduplication in allografts and native kidney disease: a clinicopathologic study of 278 consecutive renal specimens. BACKGROUND: An association has been found between transplant glomerulopathy (TG) and reduplication of peritubular capillary basement membranes (PTCR). Although such an association is of practical and theoretical importance, only one prospective study has tried to confirm it. METHODS: We examined 278 consecutive renal specimens (from 135 transplants and 143 native kidneys) for ultrastructural evidence of PTCR. In addition to renal allografts with TG, we also examined grafts with acute rejection, recurrent glomerulonephritis, chronic allograft nephropathy and stable grafts ("protocol biopsies"). Native kidney specimens included a wide range of glomerulopathies as well as cases of thrombotic microangiopathy, malignant hypertension, acute interstitial nephritis, and acute tubular necrosis. RESULTS: We found PTCR in 14 of 15 cases of TG, in 7 transplant biopsy specimens without TG, and in 13 of 143 native kidney biopsy specimens. These 13 included cases of malignant hypertension, thrombotic microangiopathy, lupus nephritis, Henoch-Schonlein nephritis, crescentic glomerulonephritis, and cocaine-related acute renal failure. Mild PTCR in allografts without TG did not predict renal failure or significant proteinuria after follow-up periods of between 3 months and 1 year. CONCLUSIONS: We conclude that in transplants, there is a strong association between well-developed PTCR and TG, while the significance of mild PTCR and its predictive value in the absence of TG is unclear. PTCR also occurs in certain native kidney diseases, though the association is not as strong as that for TG. We suggest that repeated endothelial injury, including immunologic injury, may be the cause of this lesion both in allografts and native kidneys.

Output: Chemical/Disease Entities: kidney disease (Disease), transplant glomerulopathy (Disease), TG (Disease), TG (Disease), glomerulonephritis (Disease), chronic allograft nephropathy (Disease), glomerulopathies (Disease), thrombotic microangiopathy (Disease), malignant hypertension (Disease), interstitial nephritis (Disease), acute tubular necrosis (Disease), TG (Disease), TG (Disease), malignant hypertension (Disease), thrombotic microangiopathy (Disease), lupus nephritis (Disease), Henoch-Schonlein nephritis (Disease), glomerulonephritis (Disease), cocaine (Chemical), acute renal failure (Disease), TG (Disease), renal failure (Disease), proteinuria (Disease), TG (Disease), TG (Disease), kidney diseases (Disease), TG (Disease), endothelial injury (Disease), immunologic injury (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Conformationally restricted analogs of BD1008 and an antisense oligodeoxynucleotide targeting sigma1 receptors produce anti-cocaine effects in mice. Cocaine's ability to interact with sigma receptors suggests that these proteins mediate some of its behavioral effects. Therefore, three novel sigma receptor ligands with antagonist activity were evaluated in Swiss Webster mice: BD1018 (3S-1-[2-(3,4-dichlorophenyl)ethyl]-1,4-diazabicyclo[4.3.0]nonane), BD1063 (1-[2-(3,4-dichlorophenyl)ethyl]-4-methylpiperazine), and LR132 (1R,2S-(+)-cis-N-[2-(3,4-dichlorophenyl)ethyl]-2-(1-pyrrolidinyl)cyclohexylamine). Competition binding assays demonstrated that all three compounds have high affinities for sigma1 receptors. The three compounds vary in their affinities for sigma2 receptors and exhibit negligible affinities for dopamine, opioid, GABA(A) and NMDA receptors. In behavioral studies, pre-treatment of mice with BD1018, BD1063, or LR132 significantly attenuated cocaine-induced convulsions and lethality. Moreover, post-treatment with LR132 prevented cocaine-induced lethality in a significant proportion of animals. In contrast to the protection provided by the putative antagonists, the well-characterized sigma receptor agonist di-o-tolylguanidine (DTG) and the novel sigma receptor agonist BD1031 (3R-1-[2-(3,4-dichlorophenyl)ethyl]-1,4-diazabicyclo[4.3.0]nonane) each worsened the behavioral toxicity of cocaine. At doses where alone, they produced no significant effects on locomotion, BD1018, BD1063 and LR132 significantly attenuated the locomotor stimulatory effects of cocaine. To further validate the hypothesis that the anti-cocaine effects of the novel ligands involved antagonism of sigma receptors, an antisense oligodeoxynucleotide against sigma1 receptors was also shown to significantly attenuate the convulsive and locomotor stimulatory effects of cocaine. Together, the data suggests that functional antagonism of sigma receptors is capable of attenuating a number of cocaine-induced behaviors.

Output: Chemical/Disease Entities: BD1008 (Chemical), oligodeoxynucleotide (Chemical), cocaine (Chemical), Cocaine (Chemical), BD1018 (Chemical), 3S-1-[2-(3,4-dichlorophenyl)ethyl]-1,4-diazabicyclo[4.3.0]nonane (Chemical), BD1063 (Chemical), 1-[2-(3,4-dichlorophenyl)ethyl]-4-methylpiperazine (Chemical), LR132 (Chemical), dopamine (Chemical), GABA (Chemical), NMDA (Chemical), BD1018 (Chemical), BD1063 (Chemical), LR132 (Chemical), cocaine (Chemical), convulsions (Disease), LR132 (Chemical), cocaine (Chemical), di-o-tolylguanidine (Chemical), DTG (Chemical), BD1031 (Chemical), 3R-1-[2-(3,4-dichlorophenyl)ethyl]-1,4-diazabicyclo[4.3.0]nonane (Chemical), toxicity (Disease), cocaine (Chemical), BD1018 (Chemical), BD1063 (Chemical), LR132 (Chemical), cocaine (Chemical), cocaine (Chemical), oligodeoxynucleotide (Chemical), convulsive (Disease), cocaine (Chemical), cocaine (Chemical)


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Input: Pharmacokinetic/pharmacodynamic assessment of the effects of E4031, cisapride, terfenadine and terodiline on monophasic action potential duration in dog. 1. Torsades de pointes (TDP) is a potentially fatal ventricular tachycardia associated with increases in QT interval and monophasic action potential duration (MAPD). TDP is a side-effect that has led to withdrawal of several drugs from the market (e.g. terfenadine and terodiline). 2. The potential of compounds to cause TDP was evaluated by monitoring their effects on MAPD in dog. Four compounds known to increase QT interval and cause TDP were investigated: terfenadine, terodiline, cisapride and E4031. On the basis that only free drug in the systemic circulation will elicit a pharmacological response target, free concentrations in plasma were selected to mimic the free drug exposures in man. Infusion regimens were designed that rapidly achieved and maintained target-free concentrations of these drugs in plasma and data on the relationship between free concentration and changes in MAPD were obtained for these compounds. 3. These data indicate that the free ED50 in plasma for terfenadine (1.9 nM), terodiline (76 nM), cisapride (11 nM) and E4031 (1.9 nM) closely correlate with the free concentration in man causing QT effects. For compounds that have shown TDP in the clinic (terfenadine, terodiline, cisapride) there is little differentiation between the dog ED50 and the efficacious free plasma concentrations in man (< 10-fold) reflecting their limited safety margins. These data underline the need to maximize the therapeutic ratio with respect to TDP in potential development candidates and the importance of using free drug concentrations in pharmacokinetic/pharmacodynamic studies.

Output: Chemical/Disease Entities: E4031 (Chemical), cisapride (Chemical), terfenadine (Chemical), terodiline (Chemical), Torsades de pointes (Disease), TDP (Disease), ventricular tachycardia (Disease), TDP (Disease), terfenadine (Chemical), terodiline (Chemical), TDP (Disease), TDP (Disease), terfenadine (Chemical), terodiline (Chemical), cisapride (Chemical), E4031 (Chemical), terfenadine (Chemical), terodiline (Chemical), cisapride (Chemical), E4031 (Chemical), TDP (Disease), terfenadine (Chemical), terodiline (Chemical), cisapride (Chemical), TDP (Disease)


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Input: Fatal myeloencephalopathy due to accidental intrathecal vincristin administration: a report of two cases. We report on two fatal cases of accidental intrathecal vincristine instillation in a 5-year old girl with recurrent acute lymphoblastic leucemia and a 57-year old man with lymphoblastic lymphoma. The girl died seven days, the man four weeks after intrathecal injection of vincristine. Clinically, the onset was characterized by the signs of opistothonus, sensory and motor dysfunction and ascending paralysis. Histological and immunohistochemical investigations (HE-LFB, CD-68, Neurofilament) revealed degeneration of myelin and axons as well as pseudocystic transformation in areas exposed to vincristine, accompanied by secondary changes with numerous prominent macrophages. The clinical course and histopathological results of the two cases are presented. A review of all reported cases in the literature is given. A better controlled regimen for administering vincristine and intrathecal chemotherapy is recommended.

Output: Chemical/Disease Entities: myeloencephalopathy (Disease), vincristin (Chemical), vincristine (Chemical), acute lymphoblastic leucemia (Disease), lymphoblastic lymphoma (Disease), vincristine (Chemical), paralysis (Disease), pseudocystic transformation (Disease), vincristine (Chemical), vincristine (Chemical)


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Input: Intravenous administration of prochlorperazine by 15-minute infusion versus 2-minute bolus does not affect the incidence of akathisia: a prospective, randomized, controlled trial. STUDY OBJECTIVE: We sought to compare the rate of akathisia after administration of intravenous prochlorperazine as a 2-minute bolus or 15-minute infusion. METHODS: We conducted a prospective, randomized, double-blind study in the emergency department of a central-city teaching hospital. Patients aged 18 years or older treated with prochlorperazine for headache, nausea, or vomiting were eligible for inclusion. Study participants were randomized to receive 10 mg of prochlorperazine administered intravenously by means of 2-minute push (bolus group) or 10 mg diluted in 50 mL of normal saline solution administered by means of intravenous infusion during a 15-minute period (infusion group). The main outcome was the number of study participants experiencing akathisia within 60 minutes of administration. Akathisia was defined as either a spontaneous report of restlessness or agitation or a change of 2 or more in the patient-reported akathisia rating scale and a change of at least 1 in the investigator-observed akathisia rating scale. The intensity of headache and nausea was measured with a 100-mm visual analog scale. RESULTS: One hundred patients were enrolled. One study participant was excluded after protocol violation. Seventy-three percent (73/99) of the study participants were treated for headache and 70% (70/99) for nausea. In the bolus group, 26.0% (13/50) had akathisia compared with 32.7% (16/49) in the infusion group (Delta=-6.7%; 95% confidence interval [CI] -24.6% to 11.2%). The difference between the bolus and infusion groups in the percentage of participants who saw a 50% reduction in their headache intensity within 30 minutes was 11.8% (95% CI -9.6% to 33.3%). The difference in the percentage of patients with a 50% reduction in their nausea was 12.6% (95% CI -4.6% to 29.8%). CONCLUSION: A 50% reduction in the incidence of akathisia when prochlorperazine was administered by means of 15-minute intravenous infusion versus a 2-minute intravenous push was not detected. The efficacy of prochlorperazine in the treatment of headache and nausea likewise did not appear to be affected by the rate of administration, although no formal statistical comparisons were made.

Output: Chemical/Disease Entities: prochlorperazine (Chemical), akathisia (Disease), akathisia (Disease), prochlorperazine (Chemical), prochlorperazine (Chemical), headache (Disease), nausea (Disease), vomiting (Disease), prochlorperazine (Chemical), akathisia (Disease), agitation (Disease), akathisia (Disease), akathisia (Disease), headache (Disease), nausea (Disease), headache (Disease), nausea (Disease), akathisia (Disease), headache (Disease), nausea (Disease), akathisia (Disease), prochlorperazine (Chemical), prochlorperazine (Chemical), headache (Disease), nausea (Disease)


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Input: Antithymocyte globulin in the treatment of D-penicillamine-induced aplastic anemia. A patient who received antithymocyte globulin therapy for aplastic anemia due to D-penicillamine therapy is described. Bone marrow recovery and peripheral blood recovery were complete 1 month and 3 months, respectively, after treatment, and blood transfusion or other therapies were not necessary in a follow-up period of more than 2 years. Use of antithymocyte globulin may be the optimal treatment of D-penicillamine-induced aplastic anemia.

Output: Chemical/Disease Entities: Antithymocyte globulin (Chemical), D-penicillamine (Chemical), aplastic anemia (Disease), antithymocyte globulin (Chemical), aplastic anemia (Disease), D-penicillamine (Chemical), antithymocyte globulin (Chemical), D-penicillamine (Chemical), aplastic anemia (Disease)


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Input: The relationship between hippocampal acetylcholine release and cholinergic convulsant sensitivity in withdrawal seizure-prone and withdrawal seizure-resistant selected mouse lines. BACKGROUND: The septo-hippocampal cholinergic pathway has been implicated in epileptogenesis, and genetic factors influence the response to cholinergic agents, but limited data are available on cholinergic involvement in alcohol withdrawal severity. Thus, the relationship between cholinergic activity and responsiveness and alcohol withdrawal was investigated in a genetic animal model of ethanol withdrawal severity. METHODS: Cholinergic convulsant sensitivity was examined in alcohol-na  ve Withdrawal Seizure-Prone (WSP) and-Resistant (WSR) mice. Animals were administered nicotine, carbachol, or neostigmine via timed tail vein infusion, and the latencies to onset of tremor and clonus were recorded and converted to threshold dose. We also used microdialysis to measure basal and potassium-stimulated acetylcholine (ACh) release in the CA1 region of the hippocampus. Potassium was applied by reverse dialysis twice, separated by 75 min. Hippocampal ACh also was measured during testing for handling-induced convulsions. RESULTS: Sensitivity to several convulsion endpoints induced by nicotine, carbachol, and neostigmine were significantly greater in WSR versus WSP mice. In microdialysis experiments, the lines did not differ in basal release of ACh, and 50 mM KCl increased ACh output in both lines of mice. However, the increase in release of ACh produced by the first application of KCl was 2-fold higher in WSP versus WSR mice. When hippocampal ACh was measured during testing for handling-induced convulsions, extracellular ACh was significantly elevated (192%) in WSP mice, but was nonsignificantly elevated (59%) in WSR mice. CONCLUSIONS: These results suggest that differences in cholinergic activity and postsynaptic sensitivity to cholinergic convulsants may be associated with ethanol withdrawal severity and implicate cholinergic mechanisms in alcohol withdrawal. Specifically, WSP mice may have lower sensitivity to cholinergic convulsants compared with WSR because of postsynaptic receptor desensitization brought on by higher activity of cholinergic neurons.

Output: Chemical/Disease Entities: acetylcholine (Chemical), seizure (Disease), seizure (Disease), alcohol (Chemical), alcohol (Chemical), ethanol (Chemical), alcohol (Chemical), Seizure (Disease), nicotine (Chemical), carbachol (Chemical), neostigmine (Chemical), tremor (Disease), potassium (Chemical), acetylcholine (Chemical), ACh (Chemical), Potassium (Chemical), ACh (Chemical), convulsions (Disease), convulsion (Disease), nicotine (Chemical), carbachol (Chemical), neostigmine (Chemical), ACh (Chemical), KCl (Chemical), ACh (Chemical), ACh (Chemical), KCl (Chemical), ACh (Chemical), convulsions (Disease), ACh (Chemical), convulsants (Disease), ethanol (Chemical), alcohol (Chemical), convulsants (Disease)


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Input: Prenatal dexamethasone programs hypertension and renal injury in the rat. Dexamethasone is frequently administered to the developing fetus to accelerate pulmonary development. The purpose of the present study was to determine if prenatal dexamethasone programmed a progressive increase in blood pressure and renal injury in rats. Pregnant rats were given either vehicle or 2 daily intraperitoneal injections of dexamethasone (0.2 mg/kg body weight) on gestational days 11 and 12, 13 and 14, 15 and 16, 17 and 18, or 19 and 20. Offspring of rats administered dexamethasone on days 15 and 16 gestation had a 20% reduction in glomerular number compared with control at 6 to 9 months of age (22 527+/-509 versus 28 050+/-561, P<0.05), which was comparable to the percent reduction in glomeruli measured at 3 weeks of age. Six- to 9-month old rats receiving prenatal dexamethasone on days 17 and 18 of gestation had a 17% reduction in glomeruli (23 380+/-587) compared with control rats (P<0.05). Male rats that received prenatal dexamethasone on days 15 and 16, 17 and 18, and 13 and 14 of gestation had elevated blood pressures at 6 months of age; the latter group did not have a reduction in glomerular number. Adult rats given dexamethasone on days 15 and 16 of gestation had more glomeruli with glomerulosclerosis than control rats. This study shows that prenatal dexamethasone in rats results in a reduction in glomerular number, glomerulosclerosis, and hypertension when administered at specific points during gestation. Hypertension was observed in animals that had a reduction in glomeruli as well as in a group that did not have a reduction in glomerular number, suggesting that a reduction in glomerular number is not the sole cause for the development of hypertension.

Output: Chemical/Disease Entities: dexamethasone (Chemical), hypertension (Disease), renal injury (Disease), dexamethasone (Chemical), increase in blood pressure (Disease), renal injury (Disease), dexamethasone (Chemical), dexamethasone (Chemical), reduction in glomerular number (Disease), dexamethasone (Chemical), dexamethasone (Chemical), elevated blood pressures (Disease), reduction in glomerular number (Disease), dexamethasone (Chemical), glomerulosclerosis (Disease), dexamethasone (Chemical), reduction in glomerular number (Disease), glomerulosclerosis (Disease), hypertension (Disease), Hypertension (Disease), reduction in glomerular number (Disease), reduction in glomerular number (Disease), hypertension (Disease)


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Input: The risk of venous thromboembolism in women prescribed cyproterone acetate in combination with ethinyl estradiol: a nested cohort analysis and case-control study. BACKGROUND: Cyproterone acetate combined with ethinyl estradiol (CPA/EE) is licensed in the UK for the treatment of women with acne and hirsutism and is also a treatment option for polycystic ovary syndrome (PCOS). Previous studies have demonstrated an increased risk of venous thromboembolism (VTE) associated with CPA/EE compared with conventional combined oral contraceptives (COCs). We believe the results of those studies may have been affected by residual confounding. METHODS: Using the General Practice Research Database we conducted a cohort analysis and case-control study nested within a population of women aged between 15 and 39 years with acne, hirsutism or PCOS to estimate the risk of VTE associated with CPA/EE. RESULTS: The age-adjusted incidence rate ratio for CPA/EE versus conventional COCs was 2.20 [95% confidence interval (CI) 1.35-3.58]. Using as the reference group women who were not using oral contraception, had no recent pregnancy or menopausal symptoms, the case-control analysis gave an adjusted odds ratio (OR(adj)) of 7.44 (95% CI 3.67-15.08) for CPA/EE use compared with an OR(adj) of 2.58 (95% CI 1.60-4.18) for use of conventional COCs. CONCLUSIONS: We have demonstrated an increased risk of VTE associated with the use of CPA/EE in women with acne, hirsutism or PCOS although residual confounding by indication cannot be excluded.

Output: Chemical/Disease Entities: venous thromboembolism (Disease), cyproterone acetate (Chemical), ethinyl estradiol (Chemical), Cyproterone acetate (Chemical), ethinyl estradiol (Chemical), CPA (Chemical), EE (Chemical), acne (Disease), hirsutism (Disease), polycystic ovary syndrome (Disease), PCOS (Disease), venous thromboembolism (Disease), VTE (Disease), CPA (Chemical), EE (Chemical), oral contraceptives (Chemical), acne (Disease), hirsutism (Disease), PCOS (Disease), VTE (Disease), CPA (Chemical), EE (Chemical), CPA (Chemical), EE (Chemical), CPA (Chemical), EE (Chemical), VTE (Disease), CPA (Chemical), EE (Chemical), acne (Disease), hirsutism (Disease), PCOS (Disease)


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Input: Pseudoacromegaly induced by the long-term use of minoxidil. Acromegaly is an endocrine disorder caused by chronic excessive growth hormone secretion from the anterior pituitary gland. Significant disfiguring changes occur as a result of bone, cartilage, and soft tissue hypertrophy, including the thickening of the skin, coarsening of facial features, and cutis verticis gyrata. Pseudoacromegaly, on the other hand, is the presence of similar acromegaloid features in the absence of elevated growth hormone or insulin-like growth factor levels. We present a patient with pseudoacromegaly that resulted from the long-term use of minoxidil at an unusually high dose. This is the first case report of pseudoacromegaly as a side effect of minoxidil use.

Output: Chemical/Disease Entities: Pseudoacromegaly (Disease), minoxidil (Chemical), Acromegaly (Disease), endocrine disorder (Disease), hypertrophy (Disease), cutis verticis gyrata (Disease), Pseudoacromegaly (Disease), pseudoacromegaly (Disease), minoxidil (Chemical), pseudoacromegaly (Disease), minoxidil (Chemical)


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Input: Combined androgen blockade-induced anemia in prostate cancer patients without bone involvement. BACKGROUND: To determine the onset and extent of combined androgen blockade (CAB)-induced anemia in prostate cancer patients without bone involvement. PATIENTS AND METHODS: Forty-two patients with biopsy-proven prostatic adenocarcinoma [26 with stage C (T3N0M0) and 16 with stage D1 (T3N1M0)] were included in this study. All patients received CAB [leuprolide acetate (LHRH-A) 3.75 mg, intramuscularly, every 28 days plus 250 mg flutamide, tid, per Os] and were evaluated for anemia by physical examination and laboratory tests at baseline and 4 subsequent intervals (1, 2, 3 and 6 months post-CAB). Hb, PSA and Testosterone measurements were recorded. Patients with stage D2-3 disease, abnormal hemoglobin level or renal and liver function tests that were higher than the upper limits were excluded from the study. The duration of the study was six months. RESULTS: The mean hemoglobin (Hb) levels were significantly declined in all patients from baseline of 14.2 g/dl to 14.0 g/dl, 13.5 g/dl, 13.2 g/dl and 12.7 g/dl at 1, 2, 3 and 6 months post-CAB, respectively. Severe and clinically evident anemia of Hb < 11 g/dl with clinical symptoms was detected in 6 patients (14.3%). This CAB-induced anemia was normochromic and normocytic. At six months post-CAB, patients with severe anemia had a Hb mean value of 10.2 +/- 0.1 g/dl (X +/- SE), whereas the other patients had mild anemia with Hb mean value of 13.2 +/- 0.17 (X +/- SE). The development of severe anemia at 6 months post-CAB was predictable by the reduction of Hb baseline value of more than 2.5 g/dl after 3 months of CAB (p = 0.01). The development of severe CAB-induced anemia in prostate cancer patients did not correlate with T baseline values (T < 3 ng/ml versus T > or = 3 ng/ml), with age (< 76 yrs versus > or = 76 yrs), and clinical stage (stage C versus stage D1). Severe and clinically evident anemia was easily corrected by subcutaneous injections (3 times/week for 1 month) of recombinant erythropoietin (rHuEPO-beta). CONCLUSION: Our data suggest that rHuEPO-beta correctable CAB-induced anemia occurs in 14.3% of prostate cancer patients after 6 months of therapy.

Output: Chemical/Disease Entities: anemia (Disease), prostate cancer (Disease), anemia (Disease), prostate cancer (Disease), prostatic adenocarcinoma (Disease), leuprolide acetate (Chemical), LHRH-A (Chemical), flutamide (Chemical), anemia (Disease), Testosterone (Chemical), anemia (Disease), anemia (Disease), anemia (Disease), anemia (Disease), anemia (Disease), anemia (Disease), prostate cancer (Disease), anemia (Disease), anemia (Disease), prostate cancer (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Reversible dilated cardiomyopathy related to amphotericin B therapy. We describe a patient who developed dilated cardiomyopathy and clinical congestive heart failure after 2 months of therapy with amphotericin B (AmB) for disseminated coccidioidomycosis. His echocardiographic abnormalities and heart failure resolved after posaconazole was substituted for AmB. It is important to recognize the rare and potentially reversible toxicity of AmB.

Output: Chemical/Disease Entities: dilated cardiomyopathy (Disease), amphotericin B (Chemical), dilated cardiomyopathy (Disease), heart failure (Disease), amphotericin B (Chemical), AmB (Chemical), coccidioidomycosis (Disease), heart failure (Disease), posaconazole (Chemical), AmB (Chemical), toxicity (Disease), AmB (Chemical)


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Input: Risks of the consumption of beverages containing quinine. Although the United States Food and Drug Administration banned its use for nocturnal leg cramps due to lack of safety and efficacy, quinine is widely available in beverages including tonic water and bitter lemon. Numerous anecdotal reports suggest that products containing quinine may produce neurological complications, including confusion, altered mental status, seizures, and coma, particularly in older women. Psychologists need to inquire about consumption of quinine-containing beverages as part of an evaluation process.

Output: Chemical/Disease Entities: quinine (Chemical), nocturnal leg cramps (Disease), quinine (Chemical), quinine (Chemical), neurological complications (Disease), confusion (Disease), seizures (Disease), coma (Disease), quinine (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Organophosphate-induced convulsions and prevention of neuropathological damages. Such organophosphorus (OP) compounds as diisopropylfluorophosphate (DFP), sarin and soman are potent inhibitors of acetylcholinesterases (AChEs) and butyrylcholinesterases (BChEs). The acute toxicity of OPs is the result of their irreversible binding with AChEs in the central nervous system (CNS), which elevates acetylcholine (ACh) levels. The protective action of subcutaneously (SC) administered antidotes or their combinations in DFP (2.0 mg/kg BW) intoxication was studied in 9-10-weeks-old Han-Wistar male rats. The rats received AChE reactivator pralidoxime-2-chloride (2PAM) (30.0 mg/kg BW), anticonvulsant diazepam (2.0 mg/kg BW), A(1)-adenosine receptor agonist N(6)-cyclopentyl adenosine (CPA) (2.0 mg/kg BW), NMDA-receptor antagonist dizocilpine maleate (+-MK801 hydrogen maleate) (2.0 mg/kg BW) or their combinations with cholinolytic drug atropine sulfate (50.0 mg/kg BW) immediately or 30 min after the single SC injection of DFP. The control rats received atropine sulfate, but also saline and olive oil instead of other antidotes and DFP, respectively. All rats were terminated either 24 h or 3 weeks after the DFP injection. The rats treated with DFP-atropine showed severe typical OP-induced toxicity signs. When CPA, diazepam or 2PAM was given immediately after DFP-atropine, these treatments prevented, delayed or shortened the occurrence of serious signs of poisoning. Atropine-MK801 did not offer any additional protection against DFP toxicity. In conclusion, CPA, diazepam and 2PAM in combination with atropine prevented the occurrence of serious signs of poisoning and thus reduced the toxicity of DFP in rat.

Output: Chemical/Disease Entities: Organophosphate (Chemical), convulsions (Disease), neuropathological damages (Disease), organophosphorus (Chemical), OP (Chemical), diisopropylfluorophosphate (Chemical), DFP (Chemical), sarin (Chemical), soman (Chemical), toxicity (Disease), OPs (Chemical), acetylcholine (Chemical), ACh (Chemical), DFP (Chemical), pralidoxime-2-chloride (Chemical), 2PAM (Chemical), diazepam (Chemical), adenosine (Chemical), N(6)-cyclopentyl adenosine (Chemical), CPA (Chemical), NMDA (Chemical), dizocilpine maleate (Chemical), atropine sulfate (Chemical), DFP (Chemical), atropine sulfate (Chemical), DFP (Chemical), DFP (Chemical), DFP (Chemical), atropine (Chemical), OP (Chemical), toxicity (Disease), CPA (Chemical), diazepam (Chemical), 2PAM (Chemical), DFP (Chemical), atropine (Chemical), poisoning (Disease), Atropine (Chemical), MK801 (Chemical), DFP (Chemical), toxicity (Disease), CPA (Chemical), diazepam (Chemical), 2PAM (Chemical), atropine (Chemical), poisoning (Disease), toxicity (Disease), DFP (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Differential modulation by estrogen of alpha2-adrenergic and I1-imidazoline receptor-mediated hypotension in female rats. We have recently shown that estrogen negatively modulates the hypotensive effect of clonidine (mixed alpha2-/I1-receptor agonist) in female rats and implicates the cardiovascular autonomic control in this interaction. The present study investigated whether this effect of estrogen involves interaction with alpha2- and/or I1-receptors. Changes evoked by a single intraperitoneal injection of rilmenidine (600 microg/kg) or alpha-methyldopa (100 mg/kg), selective I1- and alpha2-receptor agonists, respectively, in blood pressure, hemodynamic variability, and locomotor activity were assessed in radiotelemetered sham-operated and ovariectomized (Ovx) Sprague-Dawley female rats with or without 12-wk estrogen replacement. Three time domain indexes of hemodynamic variability were employed: the standard deviation of mean arterial pressure as a measure of blood pressure variability and the standard deviation of beat-to-beat intervals (SDRR) and the root mean square of successive differences in R-wave-to-R-wave intervals as measures of heart rate variability. In sham-operated rats, rilmenidine or alpha-methyldopa elicited similar hypotension that lasted at least 5 h and was associated with reductions in standard deviation of mean arterial pressure. SDRR was reduced only by alpha-methyldopa. Ovx significantly enhanced the hypotensive response to alpha-methyldopa, in contrast to no effect on rilmenidine hypotension. The enhanced alpha-methyldopa hypotension in Ovx rats was paralleled with further reduction in SDRR and a reduced locomotor activity. Estrogen replacement (17beta-estradiol subcutaneous pellet, 14.2 microg/day, 12 wk) of Ovx rats restored the hemodynamic and locomotor effects of alpha-methyldopa to sham-operated levels. These findings suggest that estrogen downregulates alpha2- but not I1-receptor-mediated hypotension and highlight a role for the cardiac autonomic control in alpha-methyldopa-estrogen interaction.

Output: Chemical/Disease Entities: estrogen (Chemical), imidazoline (Chemical), hypotension (Disease), estrogen (Chemical), hypotensive (Disease), clonidine (Chemical), estrogen (Chemical), rilmenidine (Chemical), alpha-methyldopa (Chemical), estrogen (Chemical), rilmenidine (Chemical), alpha-methyldopa (Chemical), hypotension (Disease), alpha-methyldopa (Chemical), hypotensive (Disease), alpha-methyldopa (Chemical), rilmenidine (Chemical), hypotension (Disease), alpha-methyldopa (Chemical), hypotension (Disease), a reduced locomotor activity (Disease), 17beta-estradiol (Chemical), alpha-methyldopa (Chemical), estrogen (Chemical), hypotension (Disease), alpha-methyldopa (Chemical), estrogen (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Cardioprotective effect of tincture of Crataegus on isoproterenol-induced myocardial infarction in rats. Tincture of Crataegus (TCR), an alcoholic extract of the berries of hawthorn (Crataegus oxycantha), is used in herbal and homeopathic medicine. The present study was done to investigate the protective effect of TCR on experimentally induced myocardial infarction in rats. Pretreatment of TCR, at a dose of 0.5 mL/100 g bodyweight per day, orally for 30 days, prevented the increase in lipid peroxidation and activity of marker enzymes observed in isoproterenol-induced rats (85 mg kg(-1) s. c. for 2 days at an interval of 24 h). TCR prevented the isoproterenol-induced decrease in antioxidant enzymes in the heart and increased the rate of ADP-stimulated oxygen uptake and respiratory coupling ratio. TCR protected against pathological changes induced by isoproterenol in rat heart. The results show that pretreatment with TCR may be useful in preventing the damage induced by isoproterenol in rat heart.

Output: Chemical/Disease Entities: tincture of Crataegus (Chemical), isoproterenol (Chemical), myocardial infarction (Disease), Tincture of Crataegus (Chemical), TCR (Chemical), alcoholic extract of the berries of hawthorn (Chemical), Crataegus oxycantha (Chemical), TCR (Chemical), myocardial infarction (Disease), TCR (Chemical), isoproterenol (Chemical), TCR (Chemical), isoproterenol (Chemical), ADP (Chemical), oxygen (Chemical), TCR (Chemical), isoproterenol (Chemical), TCR (Chemical), isoproterenol (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Safety and adverse effects associated with raloxifene: multiple outcomes of raloxifene evaluation. OBJECTIVE: To examine the effect of raloxifene on major adverse events that occur with postmenopausal estrogen therapy or tamoxifen. METHODS: The Multiple Outcomes of Raloxifene Evaluation, a multicenter, randomized, double-blind trial, enrolled 7,705 postmenopausal women with osteoporosis. Women were randomly assigned to raloxifene 60 mg/d or 120 mg/d or placebo. Outcomes included venous thromboembolism, cataracts, gallbladder disease, and endometrial hyperplasia or cancer. RESULTS: During a mean follow-up of 3.3 years, raloxifene was associated with an increased risk for venous thromboembolism (relative risk [RR] 2.1; 95% confidence interval [CI] 1.2-3.8). The excess event rate was 1.8 per 1,000 woman-years (95% CI -0.5-4.1), and the number needed to treat to cause 1 event was 170 (95% CI 100-582) over 3.3 years. Risk in the raloxifene group was higher than in the placebo group for the first 2 years, but decreased to about the same rate as in the placebo group thereafter. Raloxifene did not increase risk for cataracts (RR 0.9; 95% CI 0.8-1.1), gallbladder disease (RR 1.0; 95% CI 0.7-1.3), endometrial hyperplasia (RR 1.3; 95% CI 0.4-5.1), or endometrial cancer (RR 0.9; 95% CI 0.3-2.7). CONCLUSION: Raloxifene was associated with an increased risk for venous thromboembolism, but there was no increased risk for cataracts, gallbladder disease, endometrial hyperplasia, or endometrial cancer. LEVEL OF EVIDENCE: I

Output: Chemical/Disease Entities: raloxifene (Chemical), raloxifene (Chemical), raloxifene (Chemical), estrogen (Chemical), tamoxifen (Chemical), Raloxifene (Chemical), osteoporosis (Disease), raloxifene (Chemical), venous thromboembolism (Disease), cataracts (Disease), gallbladder disease (Disease), raloxifene (Chemical), venous thromboembolism (Disease), raloxifene (Chemical), Raloxifene (Chemical), cataracts (Disease), gallbladder disease (Disease), endometrial hyperplasia (Disease), endometrial cancer (Disease), Raloxifene (Chemical), venous thromboembolism (Disease), cataracts (Disease), gallbladder disease (Disease), endometrial hyperplasia (Disease), endometrial cancer (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Ceftriaxone-associated biliary pseudolithiasis in paediatric surgical patients. It is well known that ceftriaxone leads to pseudolithiasis in some patients. Clinical and experimental studies also suggest that situations causing gallbladder dysfunction, such as fasting, may have a role for the development of pseudolithiasis. In this study, we prospectively evaluated the incidence and clinical importance of pseudolithiasis in paediatric surgical patients receiving ceftriaxone treatment, who often had to fast in the post-operative period. Fifty children who were given ceftriaxone were evaluated by serial abdominal sonograms. Of those, 13 (26%) developed biliary pathology. Comparison of the patients with or without pseudolithiasis revealed no significant difference with respect to age, sex, duration of the treatment and starvation variables. After cessation of the treatment, pseudolithiasis resolved spontaneously within a short period. The incidence of pseudolithiasis is not affected by fasting.

Output: Chemical/Disease Entities: Ceftriaxone (Chemical), biliary pseudolithiasis (Disease), ceftriaxone (Chemical), pseudolithiasis (Disease), gallbladder dysfunction (Disease), pseudolithiasis (Disease), pseudolithiasis (Disease), ceftriaxone (Chemical), ceftriaxone (Chemical), pseudolithiasis (Disease), pseudolithiasis (Disease), pseudolithiasis (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Evaluation of the anticocaine monoclonal antibody GNC92H2 as an immunotherapy for cocaine overdose. The illicit use of cocaine continues in epidemic proportions and treatment for cocaine overdose remains elusive. Current protein-based technology offers a new therapeutic venue by which antibodies bind the drug in the blood stream, inactivating its toxic effects. The therapeutic potential of the anticocaine antibody GNC92H2 was examined using a model of cocaine overdose. Swiss albino mice prepared with intrajugular catheters were tested in photocell cages after administration of 93 mg/kg (LD50) of cocaine and GNC92H2 infusions ranging from 30 to 190 mg/kg. GNC92H2 was delivered 30 min before, concomitantly or 3 min after cocaine treatment. Significant blockade of cocaine toxicity was observed with the higher dose of GNC92H2 (190 mg/kg), where premorbid behaviors were reduced up to 40%, seizures up to 77% and death by 72%. Importantly, GNC92H2 prevented death even post-cocaine injection. The results support the important potential of GNC92H2 as a therapeutic tool against cocaine overdose.

Output: Chemical/Disease Entities: GNC92H2 (Chemical), cocaine overdose (Disease), cocaine (Chemical), cocaine overdose (Disease), GNC92H2 (Chemical), cocaine overdose (Disease), cocaine (Chemical), GNC92H2 (Chemical), GNC92H2 (Chemical), cocaine (Chemical), cocaine (Chemical), toxicity (Disease), GNC92H2 (Chemical), seizures (Disease), death (Disease), GNC92H2 (Chemical), death (Disease), cocaine (Chemical), GNC92H2 (Chemical), cocaine overdose (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: The effects of short-term raloxifene therapy on fibrinolysis markers: TAFI, tPA, and PAI-1. BACKGROUND: Markers of fibrinolysis, thrombin-activatable fibrinolysis inhibitor (TAFI), tissue-type plasminogen activator (tPA), and plasminogen activator inhibitor-1 (PAI-1) levels were studied for the evaluation of short-term effects of raloxifene administration in postmenopausal women. METHODS: Thirty-nine postmenopausal women with osteopenia or osteoporosis were included in this prospective, controlled clinical study. Twenty-five women were given raloxifene hydrochloride (60 mg/day) plus calcium (500 mg/day). Age-matched controls (n = 14) were given only calcium. Plasma TAFI, tPA, and PAI-1 antigen levels were measured at baseline and after 3 months of treatment by commercially available ELISA kits. Variations of individuals were assessed by Wilcoxon's test. Relationship between those markers and demographic characteristics were investigated. RESULTS: Three months of raloxifene treatment was associated with a significant decrease in the plasma TAFI antigen concentrations (16% change, P < 0.01), and a significant increase in tPA antigen concentrations (25% change, P < 0.05). A significant correlation was found between baseline TAFI antigen concentrations and the duration of amenorrhea (P < 0.05; r = 0.33). CONCLUSION: We suggest that the increased risk of venous thromboembolism due to raloxifene treatment may be related to increased tPA levels, but not TAFI levels.

Output: Chemical/Disease Entities: raloxifene (Chemical), raloxifene (Chemical), osteopenia (Disease), osteoporosis (Disease), raloxifene hydrochloride (Chemical), calcium (Chemical), calcium (Chemical), raloxifene (Chemical), amenorrhea (Disease), venous thromboembolism (Disease), raloxifene (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Ketoconazole induced torsades de pointes without concomitant use of QT interval-prolonging drug. Ketoconazole is not known to be proarrhythmic without concomitant use of QT interval-prolonging drugs. We report a woman with coronary artery disease who developed a markedly prolonged QT interval and torsades de pointes (TdP) after taking ketoconazole for treatment of fungal infection. Her QT interval returned to normal upon withdrawal of ketoconazole. Genetic study did not find any mutation in her genes that encode cardiac IKr channel proteins. We postulate that by virtue of its direct blocking action on IKr, ketoconazole alone may prolong QT interval and induce TdP. This calls for attention when ketoconazole is administered to patients with risk factors for acquired long QT syndrome.

Output: Chemical/Disease Entities: Ketoconazole (Chemical), torsades de pointes (Disease), Ketoconazole (Chemical), coronary artery disease (Disease), prolonged QT interval (Disease), torsades de pointes (Disease), TdP (Disease), ketoconazole (Chemical), fungal infection (Disease), ketoconazole (Chemical), ketoconazole (Chemical), TdP (Disease), ketoconazole (Chemical), long QT syndrome (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Pharmacological evidence for the potential of Daucus carota in the management of cognitive dysfunctions. The present study was aimed at investigating the effects of Daucus carota seeds on cognitive functions, total serum cholesterol levels and brain cholinesterase activity in mice. The ethanolic extract of Daucus carota seeds (DCE) was administered orally in three doses (100, 200, 400 mg/kg) for seven successive days to different groups of young and aged mice. Elevated plus maze and passive avoidance apparatus served as the exteroceptive behavioral models for testing memory. Diazepam-, scopolamine- and ageing-induced amnesia served as the interoceptive behavioral models. DCE (200, 400 mg/kg, p.o.) showed significant improvement in memory scores of young and aged mice. The extent of memory improvement evoked by DCE was 23% at the dose of 200 mg/kg and 35% at the dose of 400 mg/kg in young mice using elevated plus maze. Similarly, significant improvements in memory scores were observed using passive avoidance apparatus and aged mice. Furthermore, DCE reversed the amnesia induced by scopolamine (0.4 mg/kg, i.p.) and diazepam (1 mg/kg, i.p.). Daucus carota extract (200, 400 mg/kg, p.o.) reduced significantly the brain acetylcholinesterase activity and cholesterol levels in young and aged mice. The extent of inhibition of brain cholinesterase activity evoked by DCE at the dose of 400 mg/kg was 22% in young and 19% in aged mice. There was a remarkable reduction in total cholesterol level as well, to the extent of 23% in young and 21% in aged animals with this dose of DCE. Therefore, DCE may prove to be a useful remedy for the management of cognitive dysfunctions on account of its multifarious beneficial effects such as, memory improving property, cholesterol lowering property and anticholinesterase activity.

Output: Chemical/Disease Entities: cognitive dysfunctions (Disease), cholesterol (Chemical), extract of Daucus carota seeds (Chemical), DCE (Chemical), Diazepam (Chemical), scopolamine (Chemical), amnesia (Disease), DCE (Chemical), DCE (Chemical), DCE (Chemical), amnesia (Disease), scopolamine (Chemical), diazepam (Chemical), Daucus carota extract (Chemical), cholesterol (Chemical), DCE (Chemical), cholesterol (Chemical), DCE (Chemical), DCE (Chemical), cognitive dysfunctions (Disease), cholesterol (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Cauda equina syndrome after epidural steroid injection: a case report. OBJECTIVE: Conventional treatment methods of lumbusacral radiculopathy are physical therapy, epidural steroid injections, oral medications, and spinal manipulative therapy. Cauda equina syndrome is a rare complication of epidural anesthesia. The following case is a report of cauda equina syndrome possibly caused by epidural injection of triamcinolone and bupivacaine. CLINICAL FEATURES: A 50-year-old woman with low back and right leg pain was scheduled for epidural steroid injection. INTERVENTION AND OUTCOME: An 18-gauge Touhy needle was inserted until loss of resistance occurred at the L4-5 level. Spread of the contrast medium within the epidural space was determined by radiographic imaging. After verifying the epidural space, bupivacaine and triamcinolone diacetate were injected. After the injection, there was a reduction in radicular symptoms. Three hours later, she complained of perineal numbness and lower extremity weakness. The neurologic evaluation revealed loss of sensation in the saddle area and medial aspect of her right leg. There was a decrease in the perception of pinprick test. Deep-tendon reflexes were decreased especially in the right leg. She was unable to urinate. The patient's symptoms improved slightly over the next few hours. She had a gradual return of motor function and ability of feeling Foley catheter. All of the symptoms were completely resolved over the next 8 hours. CONCLUSION: Complications associated with epidural steroid injections are rare. Clinical examination and continued vigilance for neurologic deterioration after epidural steroid injections is important.

Output: Chemical/Disease Entities: Cauda equina syndrome (Disease), steroid (Chemical), radiculopathy (Disease), steroid (Chemical), Cauda equina syndrome (Disease), cauda equina syndrome (Disease), triamcinolone (Chemical), bupivacaine (Chemical), steroid (Chemical), bupivacaine (Chemical), triamcinolone diacetate (Chemical), numbness (Disease), lower extremity weakness (Disease), loss of sensation (Disease), steroid (Chemical), neurologic deterioration (Disease), steroid (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: High-dose testosterone is associated with atherosclerosis in postmenopausal women. OBJECTIVES: To study the long-term effects of androgen treatment on atherosclerosis in postmenopausal women. METHODS: In a population-based study in 513 naturally postmenopausal women aged 54-67 years, we studied the association between self-reported intramuscularly administered high-dose estrogen-testosterone therapy (estradiol- and testosterone esters) and aortic atherosclerosis. Aortic atherosclerosis was diagnosed by radiographic detection of calcified deposits in the abdominal aorta, which have been shown to reflect intima atherosclerosis. Hormone therapy users were compared with never users. RESULTS: Intramuscular hormone therapy use for 1 year or longer was reported by 25 women. In almost half of these women severe atherosclerosis of the aorta was present (n=11), while in women without hormone use severe atherosclerosis of the aorta was present in less than 20% (OR 3.1; 95% CI, 1.1-8.5, adjusted for age, years since menopause, smoking, and body mass index). The association remained after additional adjustment for diabetes, cholesterol level, systolic blood pressure, or alcohol use. No association was found for hormone use less than 1 year. CONCLUSION: Our results suggest that high-dose testosterone therapy may adversely affect atherosclerosis in postmenopausal women and indicate that androgen replacement in these women may not be harmless.

Output: Chemical/Disease Entities: testosterone (Chemical), atherosclerosis (Disease), atherosclerosis (Disease), estrogen (Chemical), testosterone (Chemical), estradiol- and testosterone esters (Chemical), atherosclerosis (Disease), atherosclerosis (Disease), atherosclerosis (Disease), atherosclerosis (Disease), atherosclerosis (Disease), diabetes (Disease), cholesterol (Chemical), alcohol (Chemical), testosterone (Chemical), atherosclerosis (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Sirolimus-associated proteinuria and renal dysfunction. Sirolimus is a novel immunosuppressant with potent antiproliferative actions through its ability to inhibit the raptor-containing mammalian target of rapamycin protein kinase. Sirolimus represents a major therapeutic advance in the prevention of acute renal allograft rejection and chronic allograft nephropathy. Its role in the therapy of glomerulonephritis, autoimmunity, cystic renal diseases and renal cancer is under investigation. Because sirolimus does not share the vasomotor renal adverse effects exhibited by calcineurin inhibitors, it has been designated a 'non-nephrotoxic drug'. However, clinical reports suggest that, under some circumstances, sirolimus is associated with proteinuria and acute renal dysfunction. A common risk factor appears to be presence of pre-existing chronic renal damage. The mechanisms of sirolimus-associated proteinuria are multifactorial and may be due to an increase in glomerular capillary pressure following calcineurin inhibitor withdrawal. It has also been suggested that sirolimus directly causes increased glomerular permeability/injury, but evidence for this mechanism is currently inconclusive. The acute renal dysfunction associated with sirolimus (such as in delayed graft function) may be due to suppression of compensatory renal cell proliferation and survival/repair processes. Although these adverse effects occur in some patients, their occurrence could be minimised by knowledge of the molecular effects of sirolimus on the kidney, the use of sirolimus in appropriate patient populations, close monitoring of proteinuria and renal function, use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers if proteinuria occurs and withdrawal if needed. Further long-term analysis of renal allograft studies using sirolimus as de novo immunosuppression along with clinical and laboratory studies will refine these issues in the future.

Output: Chemical/Disease Entities: Sirolimus (Chemical), proteinuria (Disease), renal dysfunction (Disease), Sirolimus (Chemical), rapamycin (Chemical), Sirolimus (Chemical), nephropathy (Disease), glomerulonephritis (Disease), autoimmunity (Disease), cystic renal diseases (Disease), renal cancer (Disease), sirolimus (Chemical), nephrotoxic (Disease), sirolimus (Chemical), proteinuria (Disease), acute renal dysfunction (Disease), chronic renal damage (Disease), sirolimus (Chemical), proteinuria (Disease), sirolimus (Chemical), acute renal dysfunction (Disease), sirolimus (Chemical), sirolimus (Chemical), sirolimus (Chemical), proteinuria (Disease), angiotensin (Chemical), angiotensin II (Chemical), proteinuria (Disease), sirolimus (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Progressive myopathy with up-regulation of MHC-I associated with statin therapy. Statins can cause a necrotizing myopathy and hyperCKaemia which is reversible on cessation of the drug. What is less well known is a phenomenon whereby statins may induce a myopathy, which persists or may progress after stopping the drug. We investigated the muscle pathology in 8 such cases. All had myofibre necrosis but only 3 had an inflammatory infiltrate. In all cases there was diffuse or multifocal up-regulation of MHC-I expression even in non-necrotic fibres. Progressive improvement occurred in 7 cases after commencement of prednisolone and methotrexate, and in one case spontaneously. These observations suggest that statins may initiate an immune-mediated myopathy that persists after withdrawal of the drug and responds to immunosuppressive therapy. The mechanism of this myopathy is uncertain but may involve the induction by statins of an endoplasmic reticulum stress response with associated up-regulation of MHC-I expression and antigen presentation by muscle fibres.

Output: Chemical/Disease Entities: myopathy (Disease), statin (Chemical), Statins (Chemical), myopathy (Disease), hyperCKaemia (Disease), statins (Chemical), myopathy (Disease), necrosis (Disease), necrotic (Disease), prednisolone (Chemical), methotrexate (Chemical), statins (Chemical), myopathy (Disease), myopathy (Disease), statins (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Direct inhibition of cardiac hyperpolarization-activated cyclic nucleotide-gated pacemaker channels by clonidine. BACKGROUND: Inhibition of cardiac sympathetic tone represents an important strategy for treatment of cardiovascular disease, including arrhythmia, coronary heart disease, and chronic heart failure. Activation of presynaptic alpha2-adrenoceptors is the most widely accepted mechanism of action of the antisympathetic drug clonidine; however, other target proteins have been postulated to contribute to the in vivo actions of clonidine. METHODS AND RESULTS: To test whether clonidine elicits pharmacological effects independent of alpha2-adrenoceptors, we have generated mice with a targeted deletion of all 3 alpha2-adrenoceptor subtypes (alpha2ABC-/-). Alpha2ABC-/- mice were completely unresponsive to the analgesic and hypnotic effects of clonidine; however, clonidine significantly lowered heart rate in alpha2ABC-/- mice by up to 150 bpm. Clonidine-induced bradycardia in conscious alpha2ABC-/- mice was 32.3% (10 microg/kg) and 26.6% (100 microg/kg) of the effect in wild-type mice. A similar bradycardic effect of clonidine was observed in isolated spontaneously beating right atria from alpha2ABC-knockout and wild-type mice. Clonidine inhibited the native pacemaker current (I(f)) in isolated sinoatrial node pacemaker cells and the I(f)-generating hyperpolarization-activated cyclic nucleotide-gated (HCN) 2 and HCN4 channels in transfected HEK293 cells. As a consequence of blocking I(f), clonidine reduced the slope of the diastolic depolarization and the frequency of pacemaker potentials in sinoatrial node cells from wild-type and alpha2ABC-knockout mice. CONCLUSIONS: Direct inhibition of cardiac HCN pacemaker channels contributes to the bradycardic effects of clonidine gene-targeted mice in vivo, and thus, clonidine-like drugs represent novel structures for future HCN channel inhibitors.

Output: Chemical/Disease Entities: cyclic nucleotide (Chemical), clonidine (Chemical), cardiovascular disease (Disease), arrhythmia (Disease), coronary heart disease (Disease), heart failure (Disease), clonidine (Chemical), clonidine (Chemical), clonidine (Chemical), clonidine (Chemical), clonidine (Chemical), Clonidine (Chemical), bradycardia (Disease), clonidine (Chemical), Clonidine (Chemical), cyclic nucleotide (Chemical), clonidine (Chemical), clonidine (Chemical), clonidine (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Influence of smoking on developing cochlea. Does smoking during pregnancy affect the amplitudes of transient evoked otoacoustic emissions in newborns? OBJECTIVE: Maternal tobacco smoking has negative effects on fetal growth. The influence of smoking during pregnancy on the developing cochlea has not been estimated, although smoking has been positively associated with hearing loss in adults. The objective of this study was to determine the effects of maternal smoking on transient evoked otoacoustic emissions (TEOAEs) of healthy neonates. METHODS: This study was undertaken as part of neonatal screening for hearing impairment and involved both ears of 200 newborns. Newborns whose mothers reported smoking during pregnancy (n=200 ears) were compared to a control group of newborns (n=200 ears), whose mothers were non-smokers. Exposure to tobacco was characterized as low (<5 cigarettes per day, n=88 ears), moderate (5< or =cigarettes per day<10, n=76) or high (> or =10 cigarettes per day, n=36). RESULTS: In exposed neonates, TEOAEs mean response (across frequency) and mean amplitude at 4000Hz was significantly lower than in non-exposed neonates. Comparisons between exposed newborns' subgroups revealed no significant differences. However, by comparing each subgroup to control group, we found statistically significant decreases of TEOAEs amplitudes at 4000Hz for all three groups. Mean TEOAEs responses of highly exposed newborns were also significantly lower in comparison to our control group. CONCLUSION: In utero, exposure to tobacco smoking seems to have a small impact on outer hair cells. These effects seem to be equally true for all exposed newborns, regardless of the degree of exposure. Further studies are needed in order to establish a potential negative effect of maternal smoking on the neonate's hearing acuity.

Output: Chemical/Disease Entities: smoking (Chemical), smoking (Chemical), smoking (Chemical), smoking (Chemical), smoking (Chemical), hearing loss (Disease), smoking (Chemical), hearing impairment (Disease), smoking (Chemical), decreases of TEOAEs amplitudes (Disease), smoking (Chemical), smoking (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Neuroinflammation and behavioral abnormalities after neonatal terbutaline treatment in rats: implications for autism. Autism is a neurodevelopmental disorder presenting before 3 years of age with deficits in communication and social skills and repetitive behaviors. In addition to genetic influences, recent studies suggest that prenatal drug or chemical exposures are risk factors for autism. Terbutaline, a beta2-adrenoceptor agonist used to arrest preterm labor, has been associated with increased concordance for autism in dizygotic twins. We studied the effects of terbutaline on microglial activation in different brain regions and behavioral outcomes in developing rats. Newborn rats were given terbutaline (10 mg/kg) daily on postnatal days (PN) 2 to 5 or PN 11 to 14 and examined 24 h after the last dose and at PN 30. Immunohistochemical studies showed that administration of terbutaline on PN 2 to 5 produced a robust increase in microglial activation on PN 30 in the cerebral cortex, as well as in cerebellar and cerebrocortical white matter. None of these effects occurred in animals given terbutaline on PN 11 to 14. In behavioral tests, animals treated with terbutaline on PN 2 to 5 showed consistent patterns of hyper-reactivity to novelty and aversive stimuli when assessed in a novel open field, as well as in the acoustic startle response test. Our findings indicate that beta2-adrenoceptor overstimulation during an early critical period results in microglial activation associated with innate neuroinflammatory pathways and behavioral abnormalities, similar to those described in autism. This study provides a useful animal model for understanding the neuropathological processes underlying autism spectrum disorders.

Output: Chemical/Disease Entities: Neuroinflammation (Disease), behavioral abnormalities (Disease), terbutaline (Chemical), autism (Disease), Autism (Disease), neurodevelopmental disorder (Disease), deficits in communication and social skills (Disease), repetitive behaviors (Disease), autism (Disease), Terbutaline (Chemical), preterm labor (Disease), autism (Disease), terbutaline (Chemical), terbutaline (Chemical), terbutaline (Chemical), terbutaline (Chemical), terbutaline (Chemical), behavioral abnormalities (Disease), autism (Disease), autism spectrum disorders (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Acute myocarditis associated with clozapine. OBJECTIVE: A case of acute myocarditis associated with the commencement of clozapine is described, highlighting the onset, course and possible contributing factors. There is an urgent need to raise awareness about this potentially fatal complication of clozapine use. RESULTS: A 20-year-old male with schizophrenia developed a sudden onset of myocarditis after commencement of clozapine. The patient recovered with intensive medical support. The symptoms occurred around 2 weeks after starting clozapine in an inpatient setting. Possible contributing factors may have been concomitant antidepressant use and unaccustomed physical activity. CONCLUSIONS: Myocarditis is an increasingly recognized complication associated with the use of clozapine. It can be fatal if not recognized and treated early. Considering that clozapine remains the gold standard in treatment of resistant psychosis, there is an urgent need to raise awareness among medical and paramedical staff involved in the care of these patients. There are also implications for recommendations and regulations regarding the use of clozapine.

Output: Chemical/Disease Entities: myocarditis (Disease), clozapine (Chemical), myocarditis (Disease), clozapine (Chemical), clozapine (Chemical), schizophrenia (Disease), myocarditis (Disease), clozapine (Chemical), clozapine (Chemical), antidepressant (Chemical), Myocarditis (Disease), clozapine (Chemical), clozapine (Chemical), psychosis (Disease), clozapine (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Encephalopathy induced by levetiracetam added to valproate. BACKGROUND: We report on the manifestation of a levetiracetam (LEV)-induced encephalopathy. FINDINGS: A 28-year-old man suffering from idiopathic epilepsy with generalized seizures was treated with LEV (3000 mg) added to valproate (VPA) (2000 mg). Frequency of generalized tonic-clonic seizures increased from one per 6 months to two per month. Neuropsychological testing showed impaired word fluency, psychomotor speed and working memory. The interictal electroencephalogram (EEG) showed a generalized slowing to 5 per second theta rhythms with bilateral generalized high-amplitude discharges. OUTCOME: Following discontinuation of LEV, EEG and neuropsychological findings improved and seizure frequency decreased.

Output: Chemical/Disease Entities: Encephalopathy (Disease), levetiracetam (Chemical), valproate (Chemical), levetiracetam (Chemical), LEV (Chemical), encephalopathy (Disease), idiopathic epilepsy (Disease), seizures (Disease), LEV (Chemical), valproate (Chemical), VPA (Chemical), tonic-clonic seizures (Disease), impaired word fluency, psychomotor speed and working memory (Disease), LEV (Chemical), seizure (Disease)