Results of a randomized study of IM862 nasal solution in the treatment of AIDS-related Kaposi's sarcoma.
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PURPOSE: Although advances have been made in the treatment of AIDS-related Kaposi's sarcoma (AIDS-KS) with systemic chemotherapy, less toxic therapies are needed. IM862 is a naturally occurring peptide with antiangiogenic properties and was thus studied in patients with AIDS-KS. PATIENTS AND METHODS: IM862 was given as intranasal drops at a dose of 5 mg. Patients were randomized to two dosing schedules given in repeated cycles until disease progression or unacceptable toxicity: 5 days of therapy followed by 5 days off (n = 18) and every other day dosing (n = 26). RESULTS: Forty-two male patients and two female patients with a median age of 38 years (range, 22 to 53 years) were accrued. Twenty-one patients (47%) had more than 50 mucocutaneous lesions, 14 (32%) had lymphedema, and none had visceral involvement. Thirty-three patients (75%) had received prior systemic chemotherapy. Twenty-four patients (55%) had CD4(+) lymphocyte count +info)
Phase I and pharmacokinetic study of farnesyl protein transferase inhibitor R115777 in advanced cancer.
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PURPOSE: To determine the maximum-tolerated dose, toxicities, and pharmacokinetic profile of the farnesyl protein transferase inhibitor R115777 when administered orally bid for 5 days every 2 weeks. PATIENTS AND METHODS: Twenty-seven patients with a median age of 58 years received 85 cycles of R115777 using an intrapatient and interpatient dose escalation schema. Drug was administered orally at escalating doses as a solution (25 to 850 mg bid) or as pellet capsules (500 to 1300 mg bid). Pharmacokinetics were assessed after the first dose and the last dose administered during cycle 1. RESULTS: Dose-limiting toxicity of grade 3 neuropathy was observed in one patient and grade 2 fatigue (decrease in two performance status levels) was seen in four of six patients treated with 1,300 mg bid. The most frequent clinical grade 2 or 3 adverse events in any cycle included nausea, vomiting, headache, fatigue, anemia, and hypotension. Myelosuppression was mild and infrequent. Peak plasma concentrations of R115777 were achieved within 0.5 to 4 hours after oral drug administration. The elimination of R115777 from plasma was biphasic, with sequential half-lives of about 5 hours and 16 hours. There was little drug accumulation after bid dosing, and steady-state concentrations were achieved within 2 to 3 days. The pharmacokinetics were dose proportional in the 25 to 325 mg/dose range for the oral solution. Urinary excretion of unchanged R115777 was less than 0.1% of the oral dose. One patient with metastatic colon cancer treated at the 500-mg bid dose had a 46% decrease in carcinoembryonic antigen levels, improvement in cough, and radiographically stable disease for 5 months. CONCLUSION: R115777 is bioavailable after oral administration and has an acceptable toxicity profile. Based upon pharmacokinetic data, the recommended dose for phase II trials is 500 mg orally bid (total daily dose, 1, 000 mg) for 5 consecutive days followed by 9 days of rest. Studies of continuous dosing and studies of R115777 in combination with chemotherapy are ongoing. (+info)
The notion of "warning leaks" in subarachnoid haemorrhage: are such patients in fact admitted with a rebleed?
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OBJECTIVE: Often patients with subarachnoid haemorrhage (SAH) recall a recent episode of acute severe headache, usually interpreted as a "warning headache" or first SAH. An alternative explanation is recall bias. The clinical and radiological features of patients with SAH were studied in relation to previous headaches or later rebleeding. METHODS: Patients with either a previous headache episode or a subsequent rebleed were selected from the SAH database in Utrecht within 1 month of the index SAH. The clinical condition was graded on the World Federation of Neurological Surgeons (WFNS) scale. The CT was reviewed and the amounts of subarachnoid blood, hydrocephalus, and intraventricular, intracerebral, and subdural blood were rated. Proportions were compared by unpaired or paired t test. RESULTS: Forty four of 390 patients (11%) had had a severe headache before their index SAH (11 of these had a subsequent rebleed); 31 other patients had a rebleed in hospital but no preceding headache. Patients with and without preceding headache did not differ in level of consciousness (14 of 44 v 11 of 31 were comatose), nor in any of the radiological features. After rebleeding (42 patients), 37 of 42 patients were comatose (v 11 of 42 before), and CT showed higher proportions of intracerebral haemorrhage (17%), intraventricular haemorrhage, (27%), and hydrocephalus (12%) than baseline scans. Intraventricular haemorrhage was twice as frequent after rebleeding than at baseline. CONCLUSIONS: The clinical and radiological features of patients admitted with SAH after a preceding bout of headache did not differ from those without such an episode, and are clearly dissimilar from those after documented rebleeds. The findings challenge the existence of minor "warning headaches". (+info)
Posterior epidural space depth: safety of the loss of resistance and hanging drop techniques.
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We have compared skin to epidural space distance (SED) and tip to tip distance (TTD), a measure of posterior epidural space depth (PESD), in 40 patients with a 27-gauge Whitacre needle after identification of the epidural space using the hanging drop (HD) or loss of resistance (LOR) to air technique. After the LOR technique, TTD was found to be 2 mm greater than that after the HD technique, whereas SED was the same. We conclude that identification of the epidural space can be performed successfully with both techniques, but with a diminished risk of dural damage after LOR compared with the HD technique. (+info)
Cervical diskography: analysis of provoked responses at C2-C3, C3-C4, and C4-C5.
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BACKGROUND AND PURPOSE: Previous authors have described the locations of provoked responses to cervical diskography from C3-C4 to C6-C7, but we have found no description of the findings at C2-C3. This study was undertaken to analyze the sensations provoked during cervical diskography at C2-C3 and to compare the results with those provoked at C3-C4 and C4-C5. METHODS: The locations of diskographically provoked responses from 40 consecutive patients who had undergone C2-C3, C3-C4, and C4-C5 diskography were analyzed. Only intensely painful (> or = 7/10) and concordant responses were considered. Disk morphology on MR images and diskograms was also compared with the provoked responses. RESULTS: Eighteen subjects described either unilateral (n = 10) or bilateral (usually asymmetric) (n = 8) concordant pain at the craniovertebral junction in response to C2-C3 diskography. Nine subjects described either unilateral (n = 5) or bilateral (n = 4) neck pain during injection. Cephalalgia or head pain was provoked in 19 subjects, seven bilaterally. Four subjects described either unilateral (n = 3) or bilateral (n = 1) trapezius muscle and/or shoulder pain. Preliminary MR studies were not helpful, as most C2-C3 disks either appeared normal or exhibited nonspecific signs of degeneration. All disks exhibited either fissuring or extradiskal leakage of contrast material at diskography, regardless of the response provoked. CONCLUSION: Diskography at C2-C3 and C3-C4 frequently produces pain sensations in the head, craniovertebral junction, and neck. There is no correlation between C2-C3 disk morphology and the diskographically provoked response. (+info)
Audit of topical glyceryl trinitrate for treatment of fissure-in-ano.
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PURPOSE: To clarify the clinical role of topical glyceryl trinitrate (GTN) in the management of anal fissures. PATIENTS AND METHODS: Fifty-six consecutive patients with fissure-in-ano attending a colorectal clinic from April 1997 to May 1998 included 16 acute and 40 chronic anal fissures. Patients were instructed to apply 0.2% 0.5 g of GTN to the painful area of the anus. Patients were followed-up in the clinic at 4, 8 and 12 weeks, and by telephone interviews at a median follow up of 10 months. RESULTS: Ten of 16 acute fissures (63%) were healed by 4 weeks and 13 (81%) by 8 weeks. Thirteen of 40 chronic fissures (33%) were healed by 8 weeks and 20 (50%) by 12 weeks. Seventeen patients (30%) underwent lateral sphincterotomy and all healed. There were five recurrences within 3 months of treatment with GTN. Thirty-four (61%) suffered from headaches, eight being severe headaches. None of the patients developed incontinence with GTN or lateral sphincterotomy. CONCLUSIONS: Treatment of fissure-in-ano using GTN ointment was effective in up to 50% of patients with chronic anal fissure, and has the benefit of being repeatable if the fissure recurs. Patients should be aware that treatment is likely to take some months to be effective and is associated with significant side effects in up to 15% of patients. (+info)
Diagnosis and management of subdural haematoma complicating bone marrow transplantation.
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Subdural haematoma (SDH) is a known complication of bone marrow transplantation (BMT). A retrospective review of 657 consecutive patients undergoing allogeneic or autologous bone marrow/stem cell transplantation at the Royal Brisbane Hospital between January 1991 and December 1998 is reported. Seventeen cases of subdural haematoma/hygroma were identified (2.6%). Eleven of these (65%) were bilateral. Four required surgical drainage, with two developing re-accumulation of SDH. All cases presented with a headache and eight of these had associated neurological complications. Diagnosis was made predominately by CT scan: however in 25% of cases definitive diagnosis could only be made in MRI studies. An association with intrathecal methorexate-containing conditioning therapy, post lumbar puncture headache, prolonged thrombocytopenia and coagulopathy was noted. In our experience, conservative management with platelet support and correction of coagulopathy achieved resolution of subdural haematoma in most cases, with surgical intervention being reserved for neurological deterioration. Bone Marrow Transplantation (2000) 25, 549-552. (+info)
Craniomandibular status and function in patients with habitual snoring and obstructive sleep apnoea after nocturnal treatment with a mandibular advancement splint: a 2-year follow-up.
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The aim of the investigation was to evaluate the status and function of the temporomandibular joint (TMJ) and masticatory system in patients with habitual snoring and obstructive apnoea after 2 years nocturnal treatment with a mandibular advancement splint. Thirty-two patients participated in the study, ranging from 43.0 to 79.8 years of age (mean 54.4 years, SD 8.78) at the start of treatment. All patients had been referred from the ENT department for treatment with a mandibular advancement splint. The acrylic splint advanced the mandible 50-70 per cent of maximal protrusion, opened 5 mm vertically, and was used 6-8 hours per night and 5-7 nights per week. Overjet, overbite, and molar relationship were measured on dental casts. The patients were asked to answer a questionnaire concerning symptoms of craniomandibular dysfunction (CMD). They were also clinically examined in a standardized manner, including registration of range of mandibular movements, TMJ sounds, pain on movement, and palpatory tenderness of the TMJ and the masticatory muscles. None of the patients showed more than five symptoms of dysfunction either at the start of or after 2 years of treatment. A decrease in the frequency of headache was found for nine of those 18 patients that reported headache (P = 0.004). A minor, but significant decrease in overjet and overbite was found and the molar relationship was also changed. It was concluded that 2 years' treatment with a mandibular advancement splint had no adverse effects on the craniomandibular status and function, but the observed occlusal changes requires further evaluation. (+info)