Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Five patients received overdoses of vincristine ranging from 3.5 to 32 mg. Neurotoxicity accounted for most of the complications observed. Peripheral neuropathies, cranial nerve palsies, paralytic ileus, atony of the bladder, hypertension, hypotension, seizures, inappropriate ADH secretion, and severe bone marrow depression were all encountered. Two patients died within 72 hours of the overdose. Another patient died of sepsis 22 days after the overdose. Two patients recovered and were discharged. The three patients who survived longer than a few days showed improvement in the vincristine-induced neuropathy, and the two long-term survivors had essentially complete recovery. It appears that if a patient can be supported through the critical period following an overdose, he can be expected to recover normal neurologic function.
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PMID:Overdosage with vincristine. 18 48

Clinical observations for 49 diabetic patients who required chronic hemodialysis or renal transplantation during a four year period are presented. Twenty-seven dialysis patients had a two year cumulative survival of 74% compared to 54% for 22 transplantation patients. The cumulative survival of live-related donor recipients (77%) was similar to that of the dialysis group and significantly better than that of cadaveric allograft recipients (36%). While the incidences of cardiomegaly and of motor neuropathy were high among live-related donor recipients, dialysis patients more often demonstrated peripheral vascular disease. Causes of death in hemodialysis patients included cardipulmonary arrest and patient decision to discontinue therapy; in the transplantation group included cardiopulmonary arrest, sepsis, and stroke. Living-related transplantation remains the preferred mode of therapy because of the potential for rehabilitation. In terms of patient survival, the risks of cadaver transplantation must be weighted against the discomforts of chronic dialysis.
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PMID:Chronic renal failure in diabetes: survival with hemodialysis vs. transplantation. 34 20

We report the first known case of daunorubicin administered directly into the human central nervous system. A 3 1/2-year-old female with pneumonia and otitis media was diagnosed with acute lymphoblastic leukemia and was admitted for antibiotics and chemotherapy. On the first day she inadvertently received a 17 mg intrathecal (IT) injection of daunorubicin. When the error was recognized about 1 hour later, her cerebrospinal fluid (CSF) was exchanged with sterile saline by barbotage, IT hydrocortisone was given, a subarachnoid catheter was inserted, and the CSF was allowed to drain for 36 hours. Only 5.6 mg (33%) of the dose was recovered from CSF, 2.7 mg as daunorubicin and 2.9 mg as the metabolite, daunorubicinol. Initially she was asymptomatic and induction therapy continued with vincristine, 1-asparaginase, prednisone, and IT methotrexate. One week after the daunorubicin injection she developed headache and irritability; CSF protein was 3.2 gm/dl. On the 12th day, she developed fungal sepsis and worsening pneumonia. On the 15th day, she became comatose with a flacid paraparesis, areflexia, and an ascending progressive bulbar palsy. A series of computerized tomography scans over 6 weeks showed increasing diffuse cerebral atrophy. Nerve conduction velocity studies were consistent with an axonal neuropathy. Despite her multiple concurrent medical problems, the timing and characteristics of neurologic damage suggest that IT daunorubicin caused progressive destruction of the nervous system.
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PMID:Inadvertent intrathecal injection of daunorubicin with fatal outcome. 157 39

We describe three patients who required mechanical ventilation for severe acute exacerbations of obstructive airways disease. When treatment with sedatives and muscle relaxants was withdrawn, they exhibited profound generalized weakness and consequently required prolonged ventilation despite resolution of the airway obstruction. Clinical features were variable, but none of the patients developed failure of other organs and infection was confined to the lungs. All had electrophysiologic evidence of a predominantly motor axonal syndrome. One patient in whom sensory action potentials were abnormal may represent an unusually severe case of critical illness neuropathy occurring in the absence of systemic sepsis and multiple organ failure. In the other two cases, this diagnosis is made less likely by the complete absence of sensory involvement and in these patients the lesion appeared to be either in the most distal portion of the motor neuron or at the neuromuscular junction. In all three patients, resolution was slow but eventually complete. The etiology of the condition is not clear, but it seems to be distinct from the acute myopathy previously described in asthmatics who had received mechanical ventilation. It is important to recognize this phenomenon to avoid erroneous conclusions about the likelihood of the patient recovering from ventilator dependence. A prolonged weaning period is to be expected in such cases.
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PMID:Prolonged neurogenic weakness in patients requiring mechanical ventilation for acute airflow limitation. 158 7

We studied five patients who developed evidence of acute mainly motor peripheral polyneuropathy complicating a condition of prolonged sepsis associated with multi-organ failure. In the electrophysiological studies we observed normal motor and sensory nerve conduction velocities but there were drops in the amplitudes of the compound action potentials in the muscles and sensory peripheral nerves as well as high denervation activity on electromyography. Analytical studies of cerebrospinal fluid and blood did not show any findings of interest except for a deterioration in the nutritional parameters without specific deficiencies. The immunological and microbiological studies failed to determine factors related to the development of polyneuropathies. Nerve and muscle biopsies showed axonal neuropathy with some demyelination changes and reinnervation. Three patients survived the critical state and were re-examined presenting a moderate improvement in the neurological condition accompanied with signs of reinnervation in the electromyographic study. Given the absence of known factors implicated in the development of acute polyneuropathies in our patients, we suggest that the relevant disorders of the cellular metabolism observed in patients with prolonged sepsis aggravated by the defective nutritional condition, may be factors related to the development of these polyneuropathies.
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PMID:Peripheral polyneuropathy complicating conditions of sepsis and multi-organ failure. 164 5

Taxol is a unique mitotic inhibitor that has entered phase II investigation. Phase I studies demonstrated hypersensitivity reactions that were related to the cremophor vehicle and to the rate of drug infusion. As a result, the time span of intravenous (IV) infusion of taxol was routinely prolonged to 6 hours or beyond, and premedication with diphenhydramine, dexamethasone, and cimetidine was initiated. Early studies showed antitumor activity, especially against malignant melanoma and ovarian carcinoma. This phase I trial was performed giving taxol, as a 6-hour IV infusion every 21 days, without premedication. The purpose was to study the necessity of premedication and its impact on toxicity and pharmacokinetics. Thirty-one patients received 64 assessable courses of taxol. One patient had a hypersensitivity reaction, which was easily controlled using routine measures. Myelosuppression was dose-limiting, but sporadic, with two fatalities due to sepsis. Nonhematologic toxicity was of grade 1 and 2 except for one patient with grade 3 mucositis and two patients with grade 3 neuropathy. The neuropathy consisted of reversible painful paresthesias, requiring discontinuation of drug in two patients. Four partial responses were seen (three in patients with non-small-cell lung cancer, one in a patient with adenocarcinoma of unknown primary). Pharmacokinetic values were consistent with those previously reported. The occurrence of myelosuppression or neurotoxicity appeared to be associated with the area under the concentration x time curve (AUC) of taxol. The recommended phase II starting dose on this schedule is 225 mg/m2. Taxol merits broad investigation at the phase II level.
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PMID:A phase I trial of taxol given by a 6-hour intravenous infusion. 167 63

Three hundred ninety-seven insulin-dependent diabetic dialysis patients were screened by nursing staff for analgesic-seeking behavior. Thirty-eight patients were identified and classified as prescription abusers (n = 26) or illicit drug users (n = 12). The nine cocaine users, when compared with 14 insulin-dependent diabetics on dialysis matched by protocol, were found to be similar in terms of diabetic retinopathy and metabolic neuropathy. Although statistically not significant, cerebrovascular and cardiovascular complications were more common in the study group. Gastroenteropathy with malnutrition was more common the study group (P less than 0.025). Infection rate and severity were markedly worse in the cocaine group: bacterial cellulitis, sepsis, and abscess each increased greater than fourfold. All the visceral infections were in the cocaine-using group. Hepatitis viral antigen and antibody was increased 10-fold in the cocaine users. Recommendations for management of dialysis patients with analgesic-seeking behavior are formulated in light of these findings.
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PMID:Increased infection rate in diabetic dialysis patients exposed to cocaine. 188 27

Skeletal muscle wasting is commonly observed in critically-ill patients and has been attributed to catabolic fibre atrophy and to neuropathy. This study describes the occurrence of a necrotizing myopathy in 15 out of 31 critically-ill patients who had percutaneous biopsies taken from the tibialis anterior muscles. While most cases showed necrosis of isolated fibres, 5 of the 12 patients who had serial biopsies showed progressive necrosis of up to 95 per cent of the fibres. One other case showed infarction and one case had staphylococcal vasculitis. Atrophy of type 1 and/or type 2 fibres was documented by morphometry in 12 cases. Myoglobin-containing casts were demonstrated immunohistochemically in renal tubules on either biopsy or necropsy material in 5 out of 7 cases. The presence of muscle necrosis was a clinically unexpected finding which may contribute to weakness, complicate the interpretation of tissue biochemistry and energy balance studies, and potentiate renal failure. The necrosis is probably multifactorial in origin, with ischaemia and sepsis contributing factors.
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PMID:Necrotizing myopathy in critically-ill patients. 191 68

We treated 25 newly diagnosed patients with advanced epithelial ovarian cancer with an intensive induction chemotherapy regimen using high-dose cisplatin in combination with cyclophosphamide and doxorubicin. All patients had either stage IIIC or stage IV disease. Two intensive induction courses of chemotherapy were administered at 28-day intervals, which consisted of cisplatin 40 mg/m2 daily for 5 days, cyclophosphamide 500 mg/m2 day 1, and doxorubicin 40 mg/m2 day 1. Four courses of chemotherapy using cisplatin 60 mg/m2, doxorubicin 40 mg/m2, and cyclophosphamide 500 mg/m2 followed the high-dose induction therapy. Two of the first six patients died during high-dose induction therapy (one died of neutropenia and sepsis, one of intercurrent intracerebral hemorrhage). Doxorubicin was subsequently omitted from the induction therapy due to unacceptable myelosuppression; no deaths occurred in the remaining 19 patients, and myelosuppression was manageable. Peripheral neuropathy was the most severe side effect with this regimen. This complication was unpredictable, developed during the third or fourth month of treatment, and was disabling in five patients. Other toxicity included prolonged nausea and vomiting (eight patients), ototoxicity (five patients), and nephrotoxicity (two patients), but these did not compromise therapy. All 23 assessable patients had objective response to therapy. Four of 12 patients who underwent second-look laparotomy had pathologic complete response, while four additional patients had only microscopic residual disease. The median survival for the entire group was 25 months. Four patients remain continuously disease-free 23 to 48 months following completion of therapy. Although this regimen was tolerated by most patients, the unpredictable occurrence of disabling neuropathy may limit its usefulness.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:High-dose cisplatin combination chemotherapy in the treatment of advanced epithelial ovarian carcinoma. 211 72

205 patients with germ cell tumors were entered into the GPO Cooperative Study MAKEI 83/86 and classified as follows: 97 teratomas, 66 yolk sac tumors, 22 dysgerminomas, 17 embryonal carcinomas and three choriocarcinomas; 20% of all tumors were classified as mixed histology. Predominant primary sites were the ovaries (91 pts), the saccrococcygeal region (74 pts), the mediastinum (12 pts), the peritoneal cavity (10 pts) and other sites (18 pts). The treatment of teratomas was primarily surgery. Localised dysgerminomas received radiotherapy following surgery, in advanced stages (III, IV) four courses of chemotherapy vinblastine 3 mg/m2/day (days 1 + 2), bleomycin 15 mg/m2/day (days 1-3) and cisplatinum 20 mg/m2/day (days 4-8) (VBC) were applied. The other fully malignant tumors received four courses of VBC chemotherapy, in extragonadal primary tumors and advanced stages of all sites additional four courses of VP16 100 mg/m2/day (days 1-3), ifosfamide 1500 mg/m2/day (days 1-5) and cisplatin 20 mg/m2/day (days 1-5) (VPIC) were administered. To avoid mutilating surgery in advanced disease, four courses of VBC chemotherapy were administered prior to resection. The relapse-free survival according to Kaplan-Meier for protocol patients with teratomas is 0.97 +/- 0.01, for dysgerminomas 0.73 +/- 0.09 and for other fully malignant histologic entities 0.81 +/- 0.02 with a median period of observation of 31 months. The toxicity mainly consisted of myelosuppression during VPIC chemotherapy in 39 of 62 pts resulting in twelve incidents of sepsis with lethal outcome in two pts. Impaired renal function was reported in 14 pts, the incidence of neuropathy, ototoxicity and pulmonary toxicity was negligible. For the follow-up study a reduction in chemotherapy seems justified in patients with favourable prognosis. The substitution of VP16 for vinblastine may result in reduced toxicity.
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PMID:[Non-testicular germ cell tumors: analysis of the therapy study MAKEI 83/86 anc changes in the protocol for the follow-up study]. 247 83


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