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Biomedical subjects

L Kaplan

Publications and source records attributed to L Kaplan.

At least 19 recordsLinked to original sources
PubMed1997

Insulin-like growth factor-I receptor overexpression mediates cellular radioresistance and local breast cancer recurrence after lumpectomy and radiation.

The insulin-like growth factor-I receptor (IGF-IR) plays a critical role in cell growth regulation and transformation. The radiosensitivity of NIH 3T3 fibroblasts overexpressing either wild-type or mutant IGF-IR was examined. High levels of wild-type IGF-IR conferred radioresistance, and mutational analysis revealed that this effect correlated with the transforming capacity but not the mitogenic activity of the receptor. The radioresistant phenotype was reversed when the cells were incubated with antisense oligonucleotides targeted to IGF-IR mRNA, demonstrating that IGF-IR directly influences radioresistance. The clinical significance of these findings was examined in an immunohistochemical analysis of primary breast tumors, revealing that high levels of IGF-IR in tumor samples were highly correlated with ipsilateral breast tumor recurrence (IBTR) following lumpectomy and radiation therapy (P = 0.001). Subgroup analysis revealed that, for early breast tumor relapses (within 4 years of initial breast tumor diagnosis), elevated levels of IGF-IR were strongly associated with IBTR (P = 0.004) but IGF-IR expression was not prognostic for IBTR from breast cancer patients with late relapses (P was not significant). These studies provide evidence for the influence of IGF-IR on cellular radioresistance and response to therapy and raise the possibility that the radiocurability of selected tumors may be improved by pharmaceutical strategies directed toward the IGF-IR.

3T3 Cells↗
PubMed1997

Aspects of spinal deformity in familial dysautonomia (Riley-Day syndrome).

Familial dysautonomia (FD) is a rare autosomal recessive disease occurring in Jews of Ashkenazi descent, with only some 500 recognized cases. The causative gene was identified on chromosome 9. FD is of considerable orthopedic interest, because of the prevalence of skeletal deformity. About 90% of surviving dysautonomic children will develop a spinal curvature, commonly a scoliosis. The scoliotic curve is usually kyphotic rather than lordotic, and appears during the first decade of life. Fifty-one of the 90 reported cases of familial dysautonomia in Israel involved patients who were seen at the scoliosis clinic for assessment and treatment of their spinal deformities. Most of the patients presented with a scoliotic deformity associated in 37 cases with an increased thoracic kyphosis. In our series orthotic treatment and physiotherapy were found to be minimally successful at best. Surgical treatment of the spine was performed in 13 of 51 patients in this series. A retrospective review of these patients' charts and radiographs was carried out. Six years of follow-up are reported. The primary indication for surgery was progression of the spinal curve. Only posterior spinal fusions were performed. Anterior transthoracic procedures were avoided in spite of the significance of the kyphotic deformity, because of the frequency of pulmonary complications. Harrington distraction and compression instrumentation was used. Three-millimeter compression rods were used in a distraction mode in thin, young children. "Harri-Luque" segmental sublaminar wiring technique and Wisconsin spinous process segmental wiring was used in some. In all cases, the spine fusion was supplemented by bank bone only, to avoid the additional trauma of graft removal. We believe that surgical intervention is advantageous, if done early in the evolution of spinal deformity. Greater technical difficulties and a higher complication rate were encountered in this series relative to the problems usually seen after spinal deformity surgery in children; this is all the more important in a disease in which general anesthesia is an additional major complicating factor. It is hoped that the improved physical condition now seen after early gastrostomy and fundoplication will aid in reducing this high complication rate. Only a small degree (about 25%) of correction was achieved in the majority of patients. Some of this apparent rigidity derived from the inability to apply sufficient instrumental corrective force because of the friable osteoporotic bone. After surgery, there was a marked decrease in the frequency of pneumonia and an improvement in the degree of ataxia, for reasons not understood, which led to an obvious improvement in the quality of life.

Adolescent↗
PubMed1997

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1995

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1993

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↗
PubMed1993

A non-lymphoma idiotype is indicative and predictive for B cell malignancies in AIDS.

The 1F7 idiotype previously defined (J Immunol 147:933;1991 and Eur J Immunol 22:1749;1992) is expressed on antibodies reactive to different proteins of HIV (gp41, p24, gp120). Since serum levels of 1F7 (IgM or IgG) are significantly higher in patients with HIV lymphoma as opposed to HIV-infected individuals, normal controls and non-HIV lymphoma patients, we hypothesized the B-cell neoplasms were the source of the idiotype. However, immunohistochemistry on cryostat sections revealed no 1F7 idiotype signal on neoplastic B-cells nor tumor infiltrative T-cells (n = 8). Interestingly, reactive lymphocytosis adjacent to tumor masses and reactive follicular hyperplastic controls (n = 5) exhibited significant 1F7 reactivity. The reactivity appeared in paracortical and perifollicular lymphoid regions, predominantly regions of B, T and antigen presenting cells in lymph nodes or tonsils. A survey of electrophoretically defined paraproteins with anti-HIV specificities derived from HIV-infected patients showed no Western blot reactivity with the 1F7 anti-idiotypic antibody. Therefore, the idiotype does not appear to be a direct product of B-cell neoplasia or abnormal B-cell proliferation, but is produced by B cell clones responding to HIV infection. This high level of serum 1F7 reactivity could be an important clue in the pathogenesis of HIV lymphomas and confers a highly predictive serological test for HIV lymphoma.

Animals↗
PubMed1993

Clinical aspects of HIV-related lymphoma.

The number of cases HIV-associated non-Hodgkin's lymphoma continues to increase as the AIDS epidemic grows. Approximately 3% of AIDS-defining illnesses are non-Hodgkin's lymphoma. The number of non-Hodgkin's lymphoma cases may actually be higher because many cases go unreported. There is also evidence that increasing numbers of patients who are surviving longer on antiretroviral therapy are developing non-Hodgkin's lymphoma. A majority of HIV-related lymphomas are large cell, either high-grade immunoblastic or aggressive intermediate grade, diffuse cleaved, or small noncleaved (Burkitt's-like). HIV-related non-Hodgkin's lymphomas behave aggressively. They are predominantly extranodal and often show unusual patterns of organ involvement. They are typically stage III or IV at the time of diagnosis. Current treatment strategies involve the use of combination chemotherapy regimens with or without antiretroviral therapy. Current studies are evaluating the efficacy of low-dose chemotherapy regimens versus standard-dose regimens with granulocyte-macrophage colony-stimulating factor support. New strategies for treating AIDS-associated non-Hodgkin's lymphoma will incorporate our current knowledge of AIDS-related lymphoma pathogenesis. Factors that reflect a patient's state of immunodeficiency seem to be the most important prognostic features determining clinical outcome after treatment. Patients with good prognostic features may benefit the most from aggressive treatment regimens. AIDS-related primary central nervous system lymphomas continue to comprise approximately 15% of AIDS-related non-Hodgkin's lymphoma cases. Treatment is limited. Although whole-brain radiation therapy can result in an improved neurologic status, the median survival remains 3 to 4 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain Neoplasms↗
PubMed1993

Marriage, spousal caregiving, and a husband's move to a nursing home. A changing role for the wife?

1. Gerontological nurses, when working with elderly couples experiencing role transitions upon nursing home placement, must attend to the needs of the healthier spouse, as well as the institutionalized patient. 2. Letting the community-dwelling wife set the tone for what her continued role will be allows her to define her marriage in a way that serves her needs at this transitory time. 3. If a woman defines herself as a wife, the nurse or nurse clinician's task may be to aid her in redefining the role's tasks, responsibilities, and limitations imposed by the nursing home setting. 4. If a woman does not perceive herself as a wife, nurses must help her accept these feelings as natural, and support her need to establish an identity as an individual and not as part of a couple.

Aged↗