Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0031117 (peripheral neuropathy)
 10,577 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neurological toxicity occurred in 8/219 patients treated with fludarabine (FAMP), 30 mg/m2 per day and cytosine arabinoside (Ara-C), 0.5 g/m2 per hour for 2-6 hours for 5 days, for new or relapsed acute leukemia or myelodysplasia. Two patients developed severe, progressive cerebral dysfunction that was ultimately fatal. This toxicity was similar to that seen with high-dose fludarabine therapy and was limited to patients with serum creatine > or = 2.0 mg/dl and age over 60 years, occurring in 2/9 such patients compared to 0/210 among the other patients (p < 0.005). Since FAMP is partially excreted by the kidney, toxicity in these two patients was likely due to receiving an effectively high dose of FAMP. Five patients developed peripheral neuropathy but there was no association with age, creatinine, dose of Ara-C, or number of courses. A patient, who also received intrathecal Ara-C, developed myelopathy. At this dose rate and duration of Ara-C peripheral neuropathy rarely arises, and cerebral toxicity is not seen. Neither toxicity was observed in 481 chronic lymphocytic leukemia patients treated with FAMP alone, by the same dose and schedule, suggesting that combination with Ara-C is important for the development of at least the peripheral neuropathy. The incidence of neurotoxicity with FAMP/Ara-C is low especially in comparison with high-dose Ara-C therapy (3 g/m2 over 2 hours). Cerebral toxicity can likely be decreased by dose reduction of FAMP in patients with increased creatinine and peripheral neuropathy decreased by detailed neurological examination before courses of FAMP/Ara-C.
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PMID:Neurotoxicity associated with fludarabine and cytosine arabinoside chemotherapy for acute leukemia and myelodysplasia. 844 43

Thirty-three patients with germ cell cancer (GCT) recurrent after two cisplatin-based regimens or cisplatin refractory (progression within 4 weeks of the last dose of cisplatin) were enrolled in a trial to establish the maximum tolerated doses (MTD) of carboplatin and etoposide given in combination with ABMT for two cycles. BM harvest of > or = 2 x 10(8) nucleated cells/kg preceded two cycles of therapy. Each agent was dose escalated, carboplatin from 1650 mg/m2 to 2100 mg/m2 and etoposide from 1200 mg/m2 to 2250 mg/m2 per cycle in successive cohorts. Twenty patients completed two cycles, 13 underwent only one due to: early death (4), toxicity (2), and progressive disease (6). There were four CR, three of whom achieved NED status with surgery, 14 PR, of whom eight have progressed. Four patients with stable disease and seven PD have died with a median survival of 6 months. There were six treatment-related deaths, four on course 1 and two on course 2. Causes of death on course 1 were: CNS hemorrhage (1), multiorgan failure (3); and on course 2: sepsis (1) and sudden death (1). Severe but reversible mucositis, transaminase and creatinine elevations were observed at the highest dose level. Three of five patients treated at this dose level had severe neurologic toxicity, manifested by both peripheral neuropathy and ototoxicity. The MTD in this patient population was carboplatin 2100 mg/m2 and etoposide 2250 mg/m2 on each of two cycles of therapy. Neurologic and mucosal toxicity were dose limiting.
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PMID:Dose escalation study of high-dose carboplatin and etoposide with autologous bone marrow support in patients with recurrent and refractory germ cell tumors. 853 6

We report the case of a 34-year old man, who, after presenting with subacute traumatic subdural haematoma, was diagnosed as CTX. He presented a ten year history of progressive deterioration of cognitive functions, unsteadiness of gait and surgery for bilateral cataracts at age 21. Cholestanol level in serum was 120.7 mmol/liter, and cholestanol/cholesterol ratio 2.52%. Bile alcohols in urine were 23, 25-pentol: 2.2665 mg/mmol creatinine, 24, 25-pentol: 1.3226 mg/mmol creatinine, and 27-nor-24, 25-pentol: 0.7363 mg/mmol creatinine. Electrophysiological study was consistent with a mixed demyelinating and axonal neuropathy. The assessment of autonomic nervous system (ANS) showed a postganglionic cholinergic failure accompanying somatic peripheral neuropathy. Brain-stem auditory evoked potentials (BAEPs) demonstrated markedly low amplitude and poorly defined waves, and almost symmetrical peak V and I to V interpeak latency (IPL) slight delays. Two nodular, bilateral, symmetrical lesions, strongly suggestive of calcifications, in the cerebellar white matter on CT and MRI were noted. On T2-weighted images diffuse high signal lesions were found in the cerebellar white matter, and multiple, hyperintense cerebral foci of demyelination or gliosis. MRI study of the Achilles tendon showed neither enlargement of the tendon, nor areas of lipid deposits. After ten months of treatment with chenodeoxycholic acid (CDCA) (750 mg/d) the clinical course was unaffected and the neurophysiological measures, CT and MRI remained unchanged.
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PMID:Cerebrotendinous xanthomatosis diagnosed after traumatic subdural haematoma. 859 91

To determine the efficacy of pretreatment with amifostine in diminishing the hematologic and nonhematologic toxicities of cyclophosphamide and cisplatin in previously untreated patients with stage III/IV ovarian cancer, a multicenter randomized controlled trial of cyclophosphamide (1,000 mg/m(2)) and cisplatin (100 mg/m(2) with or without amifostine (910 mg/m(2)) was performed. Two hundred forty-two patients with stage III/IV epithelial ovarian cancer were enrolled. Following primary surgery, patients were stratified and randomized to either cyclophosphamide/cisplatin (CP; 120 patients) or amifostine plus CP (122 patients) every 3 weeks for six cycles. Patient characteristics were similar in both groups. Cytoprotective end points and tumor response were evaluated, including the need to delay or discontinue therapy because of toxicity and the incidence of febrile neutropenia with associated complications. Fourteen patients treated with CP discontinued protocol therapy because of hematologic or renal toxicity (eight hematologic and six renal). In contrast, only one patient treated with amifostine plus CP discontinued protocol therapy for hematologic or renal toxicity (P < .001). Forty-three percent of CP patients compared with 22% of amifostine plus CP patients had grade 4 neutropenia (P = .001); total days in hospital were reduced from 258 in the CP arm to 11 in the amifostine plus CP arm (P = .009, two-sided). Sixty-five percent of the CP patients and 41% of the amifostine plus CP patients (P = .004) had the next cycle of CP delayed because of an absolute neutrophil count below 1,500/microL at day 22. Platelet and red blood cell transfusion support were substantially reduced in the group that received amifostine. The serum creatinine failed to return to < or = to 1.5 mg/dL by day 22, requiring a delay in chemotherapy in 15% and 5%, respectively, of the CP and amifostine plus CP groups (P = .014). Over the six cycles, the incidence and severity of peripheral neuropathy were also significantly reduced in the amifostine-treated group (P = .029). Pathologic response rates and survival curves were equivalent. The significant reduction in the CP-induced acute and cumulative hematologic, renal, and neurologic toxicities by amifostine pretreatment with equivalent response and survival indicates selective cytoprotection. This selective effect has the potential to affect quality of life and medical economic considerations.
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PMID:Amifostine cytoprotection with chemotherapy for advanced ovarian carcinoma. 878 73

This study describes the efficacy and toxicity of a combination regimen consisting of cyclophosphamide, vincristine (oncovin) and carboplatin (COC) for advanced seminoma on an outpatient basis. Twenty-seven patients (mean age 43 years, range 28-63 years) were classified as stage IIC (n = 5), stage IID (n = 12), stage III (n = 9) or stage IV (n = 1). Six had been treated with prior radiotherapy; elevated beta-HCG and elevated LDH serum levels were observed in 15 and 25 patients respectively. Patients were treated with four cycles of 750 mg m-2 cyclophosphamide intravenously (i.v.), 1.4 mg m-2 vincristine i.v. (maximum 2 mg) and carboplatin adjusted to creatinine clearance. Cycles were given at 3 week intervals. The median dose of carboplatin administered was 400 mg m-2 (range 300-450 mg m-2). Six patients [22%; 95% confidence interval (CI), 6-38%] achieved a complete response (CR), 19 (70%; 95% CI, 51-88%) a partial response and two (8%; 95% CI, 0 18%) showed only a response in tumour markers but not a reduction of retroperitoneal mass (NR). Post-chemotherapeutic masses were not removed surgically or irradiated. After a median follow-up of 26 months (range 5-69 months), two patients have died, one from cardiac arrest 2 years after achieving CR, the other with relapsed seminoma 5 months after therapy. None of the other patients relapsed. Main toxicity was haematological, with 22 patients (81%) experiencing thrombocytopenia WHO grade III/IV and 27 (100%) leucocytopenia WHO grade III/IV, requiring dose reduction in five patients. Seven patients experienced granulocytopenic fever. Non-haematological toxicity was rare. Peripheral neuropathy grade I was observed in four patients and grade III in one. Haemorrhagic cystitis occurred once. In conclusion, despite considerable haematological toxicity, COC is feasible on an outpatient basis, even after prior radiotherapy, and is an effective regimen for advanced seminoma with only 1/27 treatment failures after a median follow-up of 26 months.
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PMID:Treatment of advanced seminoma with cyclophosphamide, vincristine and carboplatin on an outpatient basis. 882 63

Microscopic polyarteritis may involve medium-sized and small blood vessels as well as arterioles, venules and capillaries. We have compared the clinical and laboratory features in patients with microscopic polyarteritis and medium vessel involvement, with the features found in patients with polyarteritis nodosa affecting medium vessels alone. In a 9-year period, 21 patients presented to our hospital with a form of polyarteritis. Seven had microscopic polyarteritis demonstrated histologically (6/7, 86%) and associated with dysmorphic urinary red cells (7/7, 100%), as well as medium vessel vasculitis demonstrated histologically (7/7) or by angiography (1/7, 14%). Five patients had polyarteritis nodosa with medium vessel vasculitis demonstrated histologically (3/5, 60%) or by angiography (2/5, 40%); and no evidence of a glomerular vasculitis on biopsy (2/7, 29%) or in the urinary sediment (0/7, 0%). The remaining 9 patients had microscopic polyarteritis but medium vessel involvement was not excluded by angiography. All patients with microscopic polyarteritis and medium vessel involvement had glomerular hematuria (> 100,000 glomerular RBC/ml), proteinuria > 0.5 g/24 hours), and an elevated serum creatinine (0.166 to 0.811 mmol/l). Other symptoms included fever (6/7, 86%), night sweats (5/7, 71%), gastrointestinal bleeding (4/7, 57%), proximal myopathy (3/7, 43%) and peripheral neuropathy (3/7, 43%). One patient (1/7, 14%) had hypertension. Anemia (6/7, 86%), a raised ESR (6/7, 86%), thrombocytosis (6/7, 86%), hypoalbuminemia (6/7, 86%) and abnormal liver function tests (6/7, 86%) were common. Two patients (29%) had an eosinophilia. All 5 individuals who were tested for ANCA were positive (2cANCA, 2pANCA and one pattern not described). In contrast, in patients with polyarteritis nodosa and medium vessel involvement alone, an elevated ESR was common (4/5, 80%) but fever (1/5, 20%), night sweats (0/5, 0%), proximal myopathy (1/5, 20%) and peripheral neuropathy (1/5, 20%) were seen infrequently; hypertension (1/5, 20%) and eosinophilia (1/5, 20%) were also uncommon; and ANCA were not demonstrated (0/3, 0%). Medium-sized vessel involvement is common in patients with microscopic polyarteristis, and these patients are more likely to have renal involvement and systemic symptoms, and be ANCA-positive, than patients with polyarteritis nodosa alone. Gastrointestinal symptoms are often seen in both groups.
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PMID:Classical polyarteritis nodosa and microscopic polyarteritis with medium vessel involvement--a comparison of the clinical and laboratory features. 910 64

This study was undertaken to investigate the prevalence of diabetes complications and level of glycaemic and blood pressure control in Black African patients at the primary care level in the public sector Cape Town, South Africa. A stratified random sample of 300 patients attending the three largest ambulatory diabetes clinics in community health centres in Black African residential areas of Cape Town (100 patients from each) during the last 6 months of 1992 was selected. Each patient had a clinical examination, interview, and 1 year retrospective record review. Eighty-one per cent of the sampled patients were reviewed, 90% were non-insulin-dependent (NIDDM) and 10% were treated with insulin. The mean duration of diabetes was 8 (range 0-28) years. Acceptable glycaemic control was present in 49.4% (95% Confidence Intervals 45.6-53.5) of patients while 38.5% (CI 24.8-52.2) of hypertensive patients had acceptable blood pressure control. The prevalence of any grade of retinopathy was 55.4% (CI 48.90-62.9), proliferative and preproliferative retinopathy 15.6% (CI 8.5-22.8), cataracts 7.9% (CI 4.4-11.4), peripheral neuropathy 27.6% (CI 15.2-39.4), absent foot pulses 8.2% (CI 5.2-12.6), amputations 1.4% (CI 0.4-2.4), persistent proteinuria 5.3% (CI 2.5-8.1) and an elevated albumin-creatinine ratio 36.7% (CI 29.0-44.4). The complications were not documented in the clinic records of the preceding year with the exception of 1 patient with absent foot pulses and the 12 patients with proteinuria. The high prevalence of suboptimal glycaemic and blood pressure control as well as complications of diabetes, largely unrecorded in the preceding years' clinic notes, demonstrates the deficiency of and need for preventative diabetes care at the primary care level. The design, institution, and evaluation of effective intervention programmes are a priority to improve the quality of care provided and the health of diabetic patients.
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PMID:Audit of public sector primary diabetes care in Cape Town, South Africa: high prevalence of complications, uncontrolled hyperglycaemia, and hypertension. 945 36

Neuropathy in burn patients is frequently overlooked. This study aimed at looking for neuropathies among burn patients. It included 55 burn patients, whether symptomatic or asymptomatic, with variable depths of burn at different stages. Their ages ranged from 8 to 55 years with a mean age of 23.6 +/- 11.1 years. All patients were submitted to clinical examination, electromyographic and motor conduction velocities of burned and unburned limbs. Serum electrolyte, blood urea and creatinine were measured for all patients. Sixteen patients (29 per cent) had peripheral neuropathy. Only six had symptoms and signs of peripheral neuropathy. The most frequently diagnosed neuropathy in this study was mononeuritis multiplex in nine patients (56 per cent), then generalized distal axonal neuropathy in five patients (31 per cent) and entrapment neuropathy in two patients (13 per cent). In patients with mononeuritis, 29 nerves were affected, 24 nerves related to the site of the burn and five nerves were away from the site of the burn. All the entrapment neuropathy developed after wound healing. Age above 20 years, electric burns burns involving full thickness of the skin and a surface area of more than 20 per cent were associated with a significantly higher prevalence of neuropathy. Other parameters were not found to be significant in the development of neuropathy.
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PMID:Peripheral neuropathy in burn patients. 956 28

The purpose of this study was to evaluate the efficacy and toxicity of paclitaxel and cisplatin combination chemotherapy as salvage treatment in patients with non-seminomatous germ cell tumour. Sixteen patients with histologically proven germ cell tumour, measurable disease and/or elevated serum tumour markers were eligible for the protocol. All patients had previously not achieved a complete remission (CR) to platinum-based induction chemotherapy and cytoreductive surgery. The treatment consisted of paclitaxel 175-225 mg/m2 as a 3-hour infusion, followed by cisplatin 100 mg/m2, repeated every 3 weeks for up to four cycles. Seven patients achieved a marker-positive partial remission (PR) by the end of the cisplatin-based induction chemotherapy; the remainder had disease progression at the start of the paclitaxel plus cisplatin treatment. One (6%) CR and 3 (19%) PRs were achieved, with an overall response rate of 25% (90% confidence interval 7-43). The duration of the CR is currently 9+ months; two PRs lasted 2 months. One patient with a PR has been lost to follow-up. During a median follow-up of 8 months (range 1-11), 12 patients died from the disease progression. The median survival for the whole group was 7 months. Toxicity was moderate, with neutropenia grade 3 occurring in 29% of patients, thrombocytopenia grade 1-3 in 29%, creatinine > 130 mmol/l in 36%, peripheral neuropathy grade 1-2 in 50%, and nausea and vomiting in 43%. Paclitaxel plus cisplatin showed modest activity, with an overall response rate of 31% in patients with poor prognosis who had not achieved a CR on induction chemotherapy.
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PMID:Paclitaxel and cisplatin as salvage treatment in patients with non-seminomatous germ cell tumour who failed to achieve a complete remission on induction chemotherapy. 984 29

Improved survival in testicular cancer has been accompanied by concern about long-term side effects of chemotherapy or radiotherapy. Secondary malignant neoplasia represents one of the worst possible long-term complications, leading to death in patients cured of their primary malignancy. Patients with testicular germ cell tumors appear to have a 2-fold increased risk of developing any second cancer 25-30 years after the diagnosis, resulting in a cumulative incidence of 16-23% at that time. The risk for secondary solid tumors can be mainly attributed to radiotherapy. There is strong evidence of an increasing risk for secondary solid tumors with time since treatment. Tumor-specific analysis of the risk for second cancers revealed statistically significant excesses for stomach, pancreas, bladder, rectum, prostate, and kidney cancer, as well as for cancer of the thyroid, melanoma, sarcomas, and non-Hodgkin's lymphoma. No significantly elevated risk for secondary solid tumors was observed after treatment with chemotherapy alone. The risk of secondary leukemia was associated with both radiotherapy and in particular with chemotherapy. In recent clinical surveys of patients with testicular cancer, estimates of the risk of leukemia after chemotherapy have ranged from 10- to 300-fold. An elevated risk was observed within the first two decades after diagnosis, later the risk was as expected in the normal population. Etoposide seems to be leukemogenic, especially at cumulative doses higher than 2 g/m2, although the effects of dose and schedule as well as the effects of other cytotoxic agents and radiotherapy remain to be finally clarified. Based on currently available data in patients with testicular cancer, it can be concluded that a significant elevated risk for the development of secondary leukemia exits after chemotherapy. However this risk does by far not outweigh the therapeutic benefit of etoposid-based therapy in patients with germ cell tumors. Secondary Raynaud's phenomenon is the main late vascular toxicity affecting about one third of patients after curative chemotherapy for testicular cancer. Hypertension will occur in one fifths of the patients. The incidence of vascular toxicity appears to be lower following PEB-therapy compared to PVB-therapy and major vascular events seem to be rare. Other frequent symptomatic toxicities are ototoxicity and peripheral neuropathy. A major risk factor for the development of toxicity is the cumulative dose of cisplatin given. Alterations of gonadotropin levels and Leydig cell insufficiency persist in more than half of young patients cured from testicular cancer by cisplatin-based combination chemotherapy. Approximately one fourth of patients have low serum magnesium or phosphat levels, or elevated creatinine levels. These toxicities seldomly result in clinical symptoms. We conclude that 3-4 courses with bleomycin, cisplatin and etoposide in testicular cancer patients will only rarely lead to symptomatic impairment of organ functions and a decrease of quality of life. Germ cell cancers have served as a valuable model for the development of new treatment strategies contributing largely to defining the role of cisplatinum, etoposide and recently ifosfamide in medical oncology. However, germ cell cancer may also be a useful model for investigating the long term side effects of the oncological therapies. Thus, germ cell cancer is not only a "model for a curable neoplasm" (L.H. Einhorn) but can also be seen as a "model for the study of late sequelae of modern oncological therapies".
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PMID:[Late toxicity after chemotherapy of malignant testicular tumors]. 988 93


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