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Biomedical subjects

L Kaplan

Publications and source records attributed to L Kaplan.

At least 55 records · Page 3Linked to original sources

Mitoguazone therapy in patients with refractory or relapsed AIDS-related lymphoma: results from a multicenter phase II trial.

PURPOSE: Patients with AIDS-related lymphoma usually have extensive lymphomatous disease, with relatively frequent involvement of the CNS. Approximately half may achieve complete remission after chemotherapy. Mitoguazone, an inhibitor of polyamine biosynthesis, has demonstrated efficacy in patients with de novo recurrent lymphoma. The drug is relatively nonmyelotoxic and may cross the blood-brain barrier. The current study was designed to assess the safety and potential efficacy of mitoguazone in patients with relapsed or refractory AIDS-lymphoma. PATIENTS AND METHODS: Thirty-five patients were accrued, all of whom had failed one (51%) or multiple (two to six) prior regimens. Mitoguazone (600 mg/m2) was given intravenously on days 1 and 8, and then every 2 weeks, until best response, progression, or toxicity. RESULTS: The median age was 39 years. High-grade lymphoma was diagnosed in 29 patients (83%). Extranodal disease was present in 30 patients (86%), with multiple extranodal sites (two to seven) in 18 (51%). The median CD4 cell count at study entry was 66/dL (range, zero to 549). Twenty-six patients were assessable for response. The objective response rate was 23% (95% confidence interval [CI], 6.9 to 39.3), with complete remission in three patients (11.5%), and partial remission (PR) in three patients (11.5%). Six patients experienced stable disease. Median survival from study entry was 2.6 months for the group as a whole; 21.5 months (range, 3.8 to 29.1) in complete responders, 5.6 months (range, 3.8 to 34.8) in partial responders. The most common toxicities occurred solely during drug infusion and included vasodilation (63%), paresthesia (86%), and somnolence (17%). Fourteen patients (40%) experienced nausea and 16 (46%) vomiting (grade 3 in one). Ten patients (29%) developed stomatitis, including grade 3 in two and grade 4 in one. Seven patients (20%) developed neutropenia, with grade 4 in one. Thrombocytopenia occurred in nine patients (26%). While on study, three patients developed sepsis, four had pneumonia, and two developed opportunistic infections. CONCLUSION: Mitoguazone is an effective agent in patients with multiply relapsed or refractory AIDS-related lymphoma, with acceptable toxicity. Further study in patients with newly diagnosed disease is warranted.

Adult↗

Professional associations and managed care. How four provider groups are helping their members.

Managed care is facilitating rapid change in the day-to-day practice of many addiction treatment and mental health professionals. It is only natural, therefore, that the associations representing the various disciplines in behavioral healthcare should seek to present short- and long-term plans, advice, and programs for their members. We have asked leaders from four prominent groups to present what their organizations are doing today to assist professionals in adapting to the new realities of the healthcare system. The comments below are by no means conclusive, and are representative of a few efforts and thoughts. It is our mission at Behavioral Healthcare Tomorrow to provide an independent platform for dialogue in the world of mental health and addiction treatment. It is our hope that the proposals and ideas published here stimulate even more planning amongst providers as managed care assertively enters public sector services.

Ethics, Medical↗

AIDS lymphoma.

Most AIDS-related non-Hodgkin's lymphomas can be categorized into one of three histologic subtypes: large-cell immunoblastic, small non-cleaved cell (Burkitt's or Burkitt's-like) and diffuse large cell. Rare histologies include Ki-1 anaplastic large cell lymphoma, angiotropic large cell lymphoma, mucosa-associated lymphoid tissue, primary pulmonary T-cell lymphoma, and Sézary syndrome. Although the role of Epstein-Barr virus remains uncertain, a new herpes virus, human herpes virus 8, has been identified in the rare subset of effusion-based lymphomas. Overexpression of the cytokines interleukin-6 and interleukin-10 may have a role in pathogenesis, and they may serve as potential therapeutic targets. In addition, chronic antigenic stimulation may correlate with elevated serum CD22 levels and may serve as a tool for early detection. Novel investigational therapies in clinical development include new chemotherapy-based regimens, immune modulators, antibody therapy, as well as cellular therapy.

Antineoplastic Agents↗

Neuropathy secondary to pigmented villonodular synovitis of the hip.

Pigmented villonodular synovitis is a benign proliferative process of unknown origin that may cause extensive bone and joint destruction. Patients with this condition typically present with symptoms of mild discomfort and associated stiffness of the involved joint; however, the spectrum of presentations is broad. Although pigmented villonodular synovitis begins in, and usually is confined within, a synovium-lined joint, it may extend beyond the joint capsule and present as a soft tissue mass. Three cases of a previously unrecognized presentation of pigmented villonodular synovitis of the hip joint are presented. The authors believe these to be the first reported cases in the English language literature of pigmented villonodular synovitis of the hip seen with femoral or sciatic neuropathy.

Adult↗

Pharmacokinetics of extended relief vs regular release Tylenol in simulated human overdose.

BACKGROUND: The purpose of this trial was to compare the pharmacokinetics of the two available acetaminophen dosage forms in simulated human overdose. METHODS: Ten healthy volunteers received acetaminophen, 75 mg/kg orally, either as the regular release or extended relief formulation in a random, crossover fashion. Blood samples were analyzed using a TDx assay and a best fit correlation of data points was determined by PCNONLIN. RESULTS: The area under the curves for extended relief acetaminophen and regular release acetaminophen were 426 mg h/L and 432 mg h/L, respectively (p = 0.768). The mean half times for extended relief acetaminophen and regular release acetaminophen were 4.02 h and 2.56 h, respectively (p < 0.001). The mean maximum serum acetaminophen concentrations were 62.6 mg/L (414.4 mmol/L:) and 94.3 mg/L (624.3 mmol/L) for extended relief acetaminophen and regular release acetaminophen, respectively (p < 0.001) and the mean time to maximum serum acetaminophen concentrations were 0.87 h and 0.75 h for extended relief acetaminophen and regular release acetaminophen, respectively (p = 0.508). CONCLUSIONS: Although the formulations appear to have equal bioavailability, their half-lives and peak concentrations were significantly different. Further study is required to determine whether these differences affect the assessment and management of poisoned patients.

Acetaminophen↗

Preliminary typology of couplehood for community-dwelling wives: "I" versus "we".

A qualitative analysis of women whose husbands reside in nursing homes was conducted to understand the concept of couplehood. Couplehood is defined here as the extent to which one person perceives herself as married to another person (feeling like an "I" or like part of a "We"). An "I"--"We" continuum was presented to each woman, and noticeable patterns emerged. Some women identified themselves as perceiving no couplehood with their institutionalized husbands ("Unmarried Marrieds"). A second group of women perceived a high degree of couplehood ("'Til Death Do Us Parts"), while a third group perceived low couplehood ("Husbandless Wives"). Differences seem to exist in terms of the degree to which couplehood is perceived (no, low, high). Implications of such a typology are offered for researchers, clinicians, and community-dwelling wives.

Adaptation, Psychological↗

Comparison of high resolution chromosome banding and fluorescence in situ hybridization (FISH) for the laboratory evaluation of Prader-Willi syndrome and Angelman syndrome.

The development of probes containing segments of DNA from chromosome region 15q11-q13 provides the opportunity to confirm the diagnosis of Prader-Willi syndrome (PWS) and Angelman syndrome (AS) by fluorescence in situ hybridization (FISH). We have evaluated FISH studies and high resolution chromosome banding studies in 14 patients referred to confirm or rule out PWS and five patients referred to confirm or rule out AS. In four patients (three from the PWS category and 1 from the AS group) chromosome analysis suggested that a deletion was present but FISH failed to confirm the finding. In one AS group patient, FISH identified a deletion not detectable by high resolution banding. Review of the clinical findings in the discrepant cases suggested that the FISH results were correct and high resolution findings were erroneous. Studies with a chromosome 15 alpha satellite probe (D15Z) on both normal and abnormal individuals suggested that incorrect interpretation of chromosome banding may occasionally be attributable to alpha satellite polymorphism but other variation of 15q11-q13 chromosome bands also contributes to misinterpretation. We conclude that patients who have been reported to have a cytogenetic deletion of 15q11-q13 and who have clinical findings inconsistent with PWS and AS should be re-evaluated by molecular genetic techniques.

Angelman Syndrome↗

High affinity nerve growth factor binding displays a faster rate of association than p140trk binding. Implications for multi-subunit polypeptide receptors.

Nerve growth factor (NGF) binds to two cell surface receptors, p140trk and p75NGFR, which are both expressed in responsive sensory, sympathetic, and basal forebrain cholinergic neurons. While p140trk belongs to the family of receptor tyrosine kinases, p75NGFR is a member of the TNF/Fas/CD40/CD30 family of receptors. Current views of neurotrophin receptor function have tended to interpret p140trk as the high affinity NGF-binding site. To assess if the binding of NGF to p140trk was distinguishable from binding to high affinity sites on neuronal cells, PC12 cell sublines were generated which expressed p140trk alone, or coexpressed both p140trk and p75NGFR. Kinetic analysis of 125I-NGF binding indicates that it has an unusually slow rate of association with p140trk (k + 1 = 8 x 10(5) M-1 s-1). When both p140trk and p75NGFR receptors are coexpressed, the rate of association of NGF is increased 25-fold to produce a higher affinity binding site. An increase in the rate of internalization was also observed. Since high affinity binding and internalization are believed to be prerequisite for the biological activities of NGF, these results suggest that the biological effects by NGF are derived from a novel kinetic binding site that requires the expression of both receptors. The implications of these results with respect to multisubunit polypeptide receptors are discussed.

Animals↗

A shooting incident in an elementary school: effects of worker stress on public safety, mental health, and medical personnel.

The effects of impact of event and five categories of worker stress were studied with 140 police, fire, medical, and mental health personnel who were involved in emergency service work following a shooting in an elementary school. A questionnaire distributed 6 months after the incident was utilized. Public safety personnel reported a recollection of significantly fewer intrusive thoughts than medical and mental health professionals immediately following the incident. Groups did not differ in intrusive or avoidance scores on the Impact of Event Scale 6 months after the event and all groups showed a significant decrease in both scores over time. Stepwise linear regression showed that a self-reported qualitatively heavy work load predicted intrusiveness and avoidance of thoughts both immediately after and at the 6-month anniversary of the incident. Additionally, time pressure and quantitatively heavy work load also predicted avoidance score at the time of the incident. Results are discussed in terms of control models of anxiety and as foci for debriefing with affected personnel.

Adjustment Disorders↗

Lipoprotein glomerulopathy: first report in a Chinese male.

Only seven patients with lipoprotein glomerulopathy have been reported, all in Japanese subjects. We describe the first Chinese patient with lipoprotein glomerulopathy, a 28-year-old man followed for 8 years. As in all patients described thus far, our patient has hyperlipoproteinemia phenotypically similar to the familial type III hyperlipoproteinemia, a high serum level of apolipoprotein E (apo E) (but with the heterozygous E 2/3 isoform instead of the E 2/2 isoform), and the absence of the typical clinical features associated with type III hyperlipoproteinemia. The common clinical presentation is the nephrotic syndrome. The characteristic pathologic features are concentrically layered vacuolated lipid "thrombi" in distended glomerular capillary lumens that contain beta/pre-beta lipoprotein. Immunofluorescence studies demonstrate lipoprotein "thrombi" staining for apo E and apo B, but not apo A-I, apo A-II, or apo J. Immunoglobulins, complement, and fibrin are absent or present in trace amounts. The long-term follow-up demonstrates progressive deterioration of renal function despite lipolytic therapy. The apparent predilection of lipoprotein glomerulopathy in Orientals, particularly Japanese subjects, is poorly understood, but appears to be related to genetic factors. The cause of the hyperlipoproteinemia and lipoprotein "thrombi" containing apo E and apo B is unknown, but is possibly related to defective receptor-binding mechanisms.

Adult↗

Maffucci's syndrome: two case reports with a literature review.

Sixty-three cases of Maffucci's syndrome in the English literature plus two additional cases of our own are reviewed. This syndrome is nonhereditary and is characterized by multiple enchondromas and hemangiomas. It occurs in all races with no sex predominance. The enchondromas and hemangiomas can occur anywhere but are most common in the hands. Long bone involvement is common and leads to progressive skeletal deformity and pathologic fractures. The incidence of malignancies in patients with this syndrome is high. Chondrosarcomas are especially common and occur in 30% of the patients.

Adult↗