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)

The majority of women diagnosed with epithelial ovarian cancer will have persistent or recurrent disease after initial treatment. We evaluated response and toxicity in women with advanced stage disease given salvage paclitaxel as a low-dose, weekly infusion. We performed a retrospective review of 22 women with advanced stage epithelial ovarian (19 women) or primary peritoneal carcinoma (3 women) who had received low-dose, weekly paclitaxel salvage therapy. All women had refractory, persistent, or recurrent disease following first-line treatment with paclitaxel and platin chemotherapy. Response and toxicity were assessed. Measurable disease present on physical or radiologic exam and serum carbohydrate antigen-125 levels were used to assess disease response. Overall response rate to low-dose, weekly paclitaxel salvage therapy was 50% (27% complete, 23% partial). Median progression-free interval (PFI) in responders was 27 weeks (range, 14-68 weeks). Stabilization of disease occurred in an additional 27% of patients with a median PFI of 22 weeks (range, 15-89 weeks). No difference in response was detected between the 7 women with platin-sensitive disease and the 15 women with platin-resistant disease (P = 0.19). The median dose of paclitaxel was 80 mg/m2 (range, 60-80 mg/m2). During a total of 325 weeks of paclitaxel treatment (median per patient, 12 weeks; range, 6-49 weeks), 13 treatment delays occurred (hematologic indication, 9; nonhematologic indication, 4). No cases of grade 4 hematologic toxicity, sepsis, or worsening neuropathy were documented. Weekly paclitaxel infusion given as salvage therapy results in significant clinical response, even in women previously treated with paclitaxel. The regimen is well tolerated with no cases of grade 4 neutropenia or worsening neuropathy in our population.
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PMID:Weekly paclitaxel infusion as salvage therapy in ovarian cancer. 1462 24

Findings of diminished or absent pulses, pallor on elevation, redness of the foot on lowering of the leg, sluggish refilling of the toe capillaries, and thickened nails or absence of toe hair are consistent with impaired arterial perfusion to the foot. When ischemia is recognized as contributing to pedal ulceration and infection in the diabetic foot, quantitation of its severity may be difficult. Standard clinical evaluation of trophic changes is limited in an infected foot with its accompanying swelling, edema, and erythema. A palpable pedal pulse does not preclude the possibility of the presence of limb-threatening ischemia. Additional non-invasive vascular studies should be undertaken for these patients. Management of the diabetic foot is often a complex clinical problem. However, the principles of care are simple, including correction of systemic factors, such as blood glucose control, cardiovascular risk factor management, and smoking, as well as local factor correction, such as debridement, pressure relief, infection control, and revascularization when indicated. When a patient presents with evidence of infection, adequate drainage and antibiotic therapy are mandatory. The next step should be performed to differentiate the more common neuropathic ulcerations from the truly ischemic ulceration. Symptoms of rest pain or claudication are not often helpful because many of these patients are asymptomatic as a result of the presence of their neuropathy and inactivity. If an infected foot requires debridement or open partial forefoot amputation, observing the wound on a daily base is also important. Once infection is eradicated, there should be prompt signs of healing, including the development of wound granulation within several days. If wounds are not showing signs of prompt healing, arteriography is necessary. Early aggressive drainage, debridement, and local foot amputations combined with liberal use of revascularization results in cumulative limb salvage of 74% at 5 years in high-risk groups. Others report that pedal bypass to the ischemic infected foot is effective and safe as long as infection adequately controlled. These studies strongly suggest that early recognition and aggressive surgical drainage of pedal sepsis followed by surgical revascularization is critical to achieving maximal limb salvage in the high-risk population. Patients who have diabetes present a unique challenge in lower extremity revascularization because of the distal origination of many bypasses, distal distribution of the occlusive disease, and the frequently calcified arterial wall. An aggressive multidisciplinary approach to foot disease associated with diabetes involving the primary care provider, medical specialists, interventional radiology, and podiatric, plastic, and vascular surgeons will provide optimal medical and surgical care. Peripheral vascular disease is highly treatable if intervention is instituted in a timely and collegial fashion.
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PMID:Vascular evaluation and arterial reconstruction of the diabetic foot. 1463 33

Classical familial amyloid polyneuropathy may have a course with progressive renal impairment. We studied 62 patients (24 males, 38 females) with FAP, transthyretin variant V30M, and end-stage renal disease (ESRD) treated with hemodialysis, all referred to a single center over a period of 11 years. Clinical course, morbidity and survival after dialysis were analyzed. Patient's mean age at first dialysis was 51.5 +/- 10.7 years, and mean duration of neuropathy was 10.2 +/- 3.8 years. The most frequent form of presentation of FAP nephropathy was nephrotic proteinuria with renal dysfunction. In the year prior to dialysis, renal function declined rapidly, and fluid overload was the main indication to initiate treatment. The presence of decubitus ulcers, significant disability, venous catheter for definitive vascular access for long-term treatment, and permanent bladder catheter, were related to death during the first year of dialysis. The mean duration of renal replacement therapy was 21 months, with a 54.5% one year, and 38.4% two year treatment survival. However, when the duration of neurological symptoms at first dialysis exceeded 10 years, survival was significantly lower. Infections, (41% were decubitus ulcers with sepsis) were the cause of early, as well as late mortality. Early creation of vascular access for hemodialysis, surveillance of skin wounds, and intervention on neurogenic bladder are essential to improve the prognosis of ESRD in FAP.
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PMID:End-stage renal disease and dialysis in hereditary amyloidosis TTR V30M: presentation, survival and prognostic factors. 1518 96

This Phase II trial was designed to evaluate the overall objective response rate, complete response rate, efficacy, and safety of weekly paclitaxel (Taxol) and carboplatin (Paraplatin) in the treatment of advanced urothelial carcinoma. Thirty-three patients with measurable, unresectable, stage III-IV carcinoma of the urothelium were enrolled. Paclitaxel (135 mg/m2) and carboplatin (AUC=2) were given by intravenous (IV) infusion weekly x 6 followed by two weeks rest. Patients were premedicated with oral dexamethasone, diphenhydramine, and cimetadine (or equivalent). Patient characteristics included an Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 (36%), one (36%), two (28%); median age 70 years (37-83); 29 (88%) male, four (12%) female; 16 (48%) patients had prior chemotherapy [eight postoperative (adjuvant), five neoadjuvant, three for metastatic disease] and eight (24%) had prior radiation therapy. Eight patients (24%) achieved objective responses, three complete responses (CR) and five partial responses (PR); one patient was not evaluable (patient died prior to first dose). The median duration of response was 13 months (range, 2-29). Nine patients (27%) had stable disease (SD) and 15 patients (45%) had progressive disease (PD). Median time to progression was 3.6 months (range, < 1-29) and median survival was 10.3 months (range, < 1-33). Grade 3 and 4 toxicities included: asthenia (46%), neutropenia (36%), leukopenia (15%), thromboembolism (12%), diarrhea (9%), nausea and vomiting (9%), hyperglycemia (7%), and neuropathy (6%). Two patients died of sepsis, one death was treatment-related. Weekly paclitaxel plus carboplatin shows promising activity; however in the current study, efficacy may have been limited by the toxicities associated with this dose-intensive regimen in an elderly, pretreated patient population with poor performance status. This regimen warrants further study, perhaps as a three out of four week regimen or at reduced doses.
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PMID:A phase II evaluation of weekly paclitaxel plus carboplatin in advanced urothelial cancer. 1549 58

ICU-acquired limb and respiratory muscle weakness is a common, serious ICU syndrome, increasing in frequency with prolonged ICU stay and sepsis. A systematic approach facilitates precise localization of the problem within central or peripheral nervous system. Most cases relate to critical illness polyneuropathy or myopathy or a combination of both (critical illness neuromyopathy). Within the latter entity, the relative contribution of neuropathy versus myopathy varies considerably among affected patients. Muscle enzyme testing, electromyography-nerve conduction and muscle biopsy are valuable investigative tests. Nerve biopsy is less commonly needed, but is useful when vascultis is suspected.
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PMID:A stronger approach to weakness in the intensive care unit. 1556 79

The primary objective of these trials was to determine the 1-year survival of advanced non-small cell lung cancer (ANSCLC) patients (> or =70 years with PS 0-2 or > or =18 years with PS 2) receiving sequential paclitaxel and carboplatin (P --> C) or concurrent P + C. The secondary objectives were assessment of toxicities and quality of life. A total of 121 patients with NSCLC were treated. P--> C patients received paclitaxel (80 mg/m(2)) weekly x 3, followed by 1 week of rest; these 4-week cycles were repeated until relapse. At relapse, patients received carboplatin (AUC = 5, IV) on Day 1 of each 3-week cycle until evidence of further progression or lack of improvement. P + C patients received paclitaxel (80 mg/m(2)) and carboplatin (AUC = 2), weekly x 3, followed by 1 week of rest, until relapse. Patients in both studies were premedicated prior to paclitaxel administration. Sequential P + C resulted in a median survival of 8.2 months (range: <1-18.8) and P + C patients had a median survival of 9.2 months (range: <1-22.0). In both groups (P--> C) and P + C), the 1-year survival was 31%. For patients treated sequentially, treatment-related AEs (TRAE, > or =Grade 3) included fatigue (7%), neuropathy (5%), and leukopenia and diarrhea (3%, each). Grade 4 AEs were limited to neutropenia, febrile neutropenia, and sepsis (1 episode each). For patients receiving concurrent P + C, TRAE included neutropenia and leukopenia (15%, each) and shortness of breath and bilateral bone pain (10%, each). Leukopenia (n = 2) and neutropenia (n = 1) were the only Grade 4 events reported. The analysis of quality of life (QOL) questionnaires indicated that there were no obvious differences between treatment groups during the study. These drugs and treatment schema were well-tolerated when administered in the community setting and resulted in survival rates that were similar to what is reported in the literature with combination therapy administered to "high risk" patients. Finding the optimal chemotherapy regimen, that can be tolerated, remains a challenge in elderly patients.
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PMID:Sequential versus concurrent paclitaxel and carboplatin for the treatment of advanced non-small cell lung cancer in elderly patients and patients with poor performance status: results of two Phase II, multicenter trials. 1560 61

The tropical diabetic hand syndrome (TDHS) is a complication affecting patients with diabetes mellitus in the tropics. The syndrome encompasses a localized cellulitis with variable swelling and ulceration of the hands, to progressive, fulminant hand sepsis, and gangrene affecting the entire limb. TDHS is less well recognized than foot infections and not generally classified as a specific diabetes complication. Hand infection was first described in Nigeria in 1984. Since then, the majority of cases have been reported in the African continent and more recently in India. There is often a history of antecedent minor hand trauma (e.g. scratches or insect bites). Presentation to hospital is often delayed due to the patients' unawareness of the potential risks, lack of concern because the initiating trauma might have been trivial, or decision to seek initial help from traditional healers. The first analytic study was done in Dar es Salaam, Tanzania, to characterize the epidemiology, clinical characteristics and risk factors of TDHS. Independent risk factors for TDHS include poorly controlled diabetes, neuropathy, insulin treatment or malnutrition. Clinicians should be aware of these complications and be prepared to immediately admit TDHS patients to hospital for aggressive surgical intervention (i.e. debridement, pus drainage or amputation) and high-dose, intravenous, broad-spectrum antibacterial therapy that includes anti-anaerobic activity. Without prompt, aggressive treatment TDHS can lead to permanent disability, limb amputation (13% of TDHS patients require major upper limb amputation), or death. Prevention strategies include patient and staff education that focuses on proper hand care, nutrition, and the importance of seeking medical attention immediately following hand trauma regardless of the severity of the injury, or at the earliest onset of hand-related symptoms, such as redness or swelling. Prevention of permanent disability and death due to TDHS will require improved management of glycemic levels in resource-limited countries, and surgical intervention during less severe stages of the condition.
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PMID:Tropical diabetic hand syndrome. Epidemiology, pathogenesis, and management. 1567 87

The foot complications of diabetic patients are one of the commonest and most devastating of medical problems that occurs in the Caribbean. The scale of the problem is reflected in the fact that, on average, 75% of the beds in the general surgical wards of the Queen Elizabeth Hospital in Barbados are occupied by patients with this problem. Of the patients admitted, a third lose a limb by amputation and another third of the patients lose toes or part of their feet and remain in hospital an average of two months as doctors struggle to prevent them losing their limbs. Half of the patients are in their 70s when they are admitted to hospital but 4 per cent are as young as thirty to forty years. It is clear to the surgeons who struggle to save the limbs of these patients that preventive care and early and aggressive intervention, when problems occur, are the best way to avoid prolonged hospitalization and loss of limb. The events that precipitate the problems often appear trivial to most people. a little nick cutting a nail or a callus, a crack under the toe, an ingrowing nail, stepping on a rock in the yard or, even more devastating, on a dirty or rusty nail. The diabetic's foot is more susceptible to injury, sepsis and gangrene because of an altered inflammatory response and an increased incidence of occlusive vascular disease and neuropathy. Injuries normally considered minor can threaten the limb in diabetics by rapid progression of necrosis along tissue planes. Prevention is of primary importance and patients need to be educated and to remind themselves over and over again to clean their feet daily, paying particular attention to the interdigital areas: looking at them to make sure that there is no swelling or cuts or change in colour. Looking is important since diabetics, especially those with neuropathy, cannot rely-on pain as a symptom of injury. Patients have to be trained to recognise and respond to the signs of injury and infection without relying on the signal of pain that they and the health care workers usually rely upon to assess the seriousness of most conditions. Diabetics should wear something on their feet at all times, in and out of the house. What is worn should have a good firm sole to prevent penetration. If a sandal is worn, it should be strapped on so that it does not slip off easily. If something goes wrong, or is noticed to be wrong with the feet, professional help should be sought the same day. Treatment and observation are needed on a daily basis. In order to try and save a limb, patients may need to have a series of minor operations and for those who are seen by surgeons early enough, four out of every five persons will have their limbs preserved. However, after the limb is saved, it is in greater danger for further problems and patients may require special shoes to prevent recurrence. The area of rehabilitation and prevention needs a great deal of improvement in the Caribbean for specialist orthotic advice and skills are scarce. Team work is essential for, by working together, patients, doctors, nurses, chiropodists and orthotic technicians can improve outcomes for the diabetic patient.
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PMID:The Caribbean experience with the diabetic foot management of the diabetic foot. 1597 11

The aim of the present study was to investigate the electrophysiology of the phrenic nerve and the diaphragm muscle during sepsis. In total, 26 rats underwent either sham laparotomy or caecal ligation and puncture (CLP). Electrophysiology was evaluated via a phrenic nerve conduction study and needle electromyography of the diaphragm, prior to CLP, 6 and 24 h post-CLP and on day 7. The histopathology of the diaphragm muscle and phrenic nerve was also examined on day 7. In the sepsis group, the phrenic nerve conduction study showed decreased amplitude of compound action potential (CMAP), and prolongation in the duration and the latency of CMAP. The diaphragmatic needle electromyography showed decreased amplitude and frequency of the motor unit action potential (MUP), and prolongation in the duration of MUP, at all time points, compared with the pre-CLP values. The electrophysiological abnormalities were consistent with axonal and demyelinating phrenic nerve neuropathy. Electrophysiological abnormalities were present at 6 h with worsening at 24 h and on day 7. Histopathological examination showed normal muscular fibres and focally slight myelin degenerations of the phrenic nerve fibres. In conclusion, sepsis induced phrenic nerve neuropathy as early as the 6th h in rats.
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PMID:Sepsis induces early phrenic nerve neuropathy in rats. 1620 2

This phase I study investigated the maximum tolerated dose and pharmacokinetics of a 3-weekly administration of BMS-188797, a paclitaxel derivate, at three dose levels (DLs) (80, 110 and 150 mg m(-2) DL), combined with cisplatin (standard dose 75 mg m(-2)). In 16 patients with advanced malignancies treated, one patient experienced dose-limiting febrile neutropenia, sepsis and severe colitis at the 150 mg m(-2) DL; at the 110 mg m(-2) DL one episode of dose-limiting grade 3 diarrhoea/nausea occurred. Grade 3/4 haematological toxicities were leucopenia/neutropenia; grade 3 nonhaematological toxicities were neuropathy, nausea, diarrhoea and stomatits. Objective response was seen in four patients, with three complete remissions in ovarian and cervical cancer patients. Pharmacokinetics of BMS-188797 appeared linear through the 110 mg m(-2), but not through the 150 mg m(-2) DL. The mean+/-SD values for clearance, distribution volume at steady state and terminal half-life during cycle 1 were 317+/-60 ml min(-1) m(-2), 258+/-96 l m(-2) and 30.8+/-7.7 h, respectively. The maximum tolerated and recommended phase II dose for BMS-188797 was 110 mg m(-2) (1-h infusion, every 3 weeks) combined with cisplatin 75 mg m(-2).
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PMID:A phase I and pharmacokinetic study of novel taxane BMS-188797 and cisplatin in patients with advanced solid tumours. 1633 10


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