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Biomedical subjects

M Weiss

Publications and source records attributed to M Weiss.

At least 415 records · Page 23Linked to original sources
PubMed1993

Influence of pulmonary blood flow on gas exchange in piglets.

We previously reported that O2 diffusion was limited in piglets. To test the hypothesis of an inadequacy between diffusion and perfusion in piglets (< 4 wk) vs. older pigs (> 8 wk), we compared in these two age groups the effect of an increase (by opening an arteriovenous fistula) or a decrease (by inflating a balloon in the inferior vena cava) in cardiac output (Q) on gas exchange and on the O2 equilibration coefficient D/Q beta [ratio of the diffusion capacity of O2 (D) to the product of Q and the capacitance coefficient of blood (beta)]. In piglets but not in older pigs, a decrease in Q improved the alveolar-arterial Po2 difference (P < 0.05) and D/Q beta (P < 0.05), whereas an increase in Q had the opposite effect. Changes in the alveolar-arterial O2 difference and D/Q beta were linearly correlated with Q (r = 0.75, P < 0.01 and r = 0.88, P < 0.01, respectively). We suggest that the impaired O2 diffusion in piglets was due to inadequate diffusion-perfusion equilibrium of O2.

Aging↗
PubMed1993

neu(c-erbB-2/HER2) and the epidermal growth factor receptor (EGFR) in breast cancer.

One hundred and eighty thousand new cases of invasive breast cancer were diagnosed in 1992 within the United States. This disease affects approximately 1 out of 8 women in the US. Chemotherapy and/or hormonal therapy have shown some improved disease-free and/or overall survival rates. Unfortunately, this type of therapy is not directed specifically to the malignant cells, and systemic toxicities are observed. In order to develop site-specific treatment, the biology of the disease must be understood such that certain genes or their products which are involved in the pathogenesis of the disease can be targeted. Two structurally related tyrosine kinase growth factors, the epidermal growth factor receptor (EGFR) and c-erbB-2 (neu) have been identified in human breast cancer tissue and, in many instances, may function as oncogenes. The clinical data related to these two growth factor receptors as prognostic factors for the disease have been critically evaluated. Several problems with the critical studies were identified, and solutions were proposed to clarify the conflicting results reported in the studies which have attempted to examine whether c-erbB-2 (neu), in particular, is a prognostic indicator for breast cancer. In addition, data related to the structure of, ligands for and interaction between the proteins have been reviewed and presented with respect to their role in breast cancer development. A more thorough understanding of the genetic changes which contribute to the development of breast cancer will lead to more specific and less toxic treatment for this disease.

Breast Neoplasms↗
PubMed1993

Quantitation of thyroid hormone effect on skin perfusion by laser Doppler flowmetry.

Clinical observations have long suggested that skin perfusion (SP), among other factors, depends on thyroid status. However, quantitative data concerning this relationship are rather sparse. This study characterizes SP by means of laser Doppler flowmetry (LDF) in various thyroid dysfunctional states. The data reveal that mean capillary flow velocity, capillary pulse wave amplitude, and capillary flow oscillation amplitude, but not capillary flow oscillation frequency, are increased in hyperthyroid patients and decreased in hypothyroid patients. Regaining the euthyroid state is accompanied by normalization of LDF parameters only in hyperthyroid patients. It is concluded that LDF is useful in monitoring the thyroid effect on SP. However, it may not be used as a biological marker for the thyroid status of a given individual.

Adult↗
PubMed1993

Signal processing for hearing impairment.

Four noise reduction methods for use in sensory aids for hearing impairment were evaluated. These include a two-microphone adaptive noise canceller, short-term Wiener filtering, a transformed spectrum subtraction technique, and sinusoidal modelling. The largest improvements in speech recognition were obtained with the two-microphone adaptive noise canceller in a moderately reverberant room. Significant improvements were also obtained for short-term Wiener filtering for some hearing-impaired subjects. The transformed spectrum-subtraction technique failed to improve performance as the front-end of a hearing aid, but yielded improvements in performance as a preprocessor for the Nucleus Cochlear Implant. Sinusoidal modelling resulted in significant improvements in signal-to-noise ratio, but without a corresponding improvement in speech intelligibility.

Acoustic Stimulation↗
PubMed1993

[Carcinoid tumor of the lung. An unusual form of ocular metastasis].

Carcinoid tumors are slowly and locally invasive growing neoplasms. Their main localization is in the ileum or in organs derived from the embryonic foregut, i.e. bronchus, stomach, pancreas and thyroid. The low rate of metastatic manifestation of about 10% indicates their potential malignancy. The endocrine effects vary. We describe the case of a 30-year-old female patient, who had had a carcinoid tumor of the bronchus with infiltration of a hilar lymph node, which had been resected two years previously. The postoperative course was marked by an increased level of urine 5-hydroxyindolacetic acid (5-HIAA). Finally, the patient complained a 4-month history of recurrent episodes of refractory conjunctival hyperemia, visual loss and visual field defects in both eyes. Examination revealed bilateral multiple choroidal masses associated with retinal detachment. As various authors have reported, carcinoid tumor metastases to the eye are extremely rare. Diagnostic approaches and therapeutic considerations are described. Ultrasonic examination of the choroidal lesion, applying standardized A-scan echography at tissue sensitivity, showed solid tissue masses and bilateral circumscribed exudative retinal detachment. The tumor was characterized by medium to high reflectivity and slight sound attenuation. The internal structure showed less irregularity than is usually seen in metastases.

Adult↗
PubMed1993

Frequency of bone marrow T cells responding to HLA-identical non-leukemic and leukemic stimulator cells.

Grafted immunocompetent cells are considered responsible for GVHD as well as for the elimination of residual leukemic cells ('graft-versus-leukemia reactivity', GVLR) in leukemic patients after allogeneic BMT. Clinical and experimental investigations have given contradictory answers to the question whether GVHD and GVLR are two manifestations of the same process or separate immunologic processes. We have addressed this question by analysing the primary in vitro response of BM-derived proliferating and cytotoxic T lymphocyte precursors (PTLp and CTLp) in HLA identical relative pairs (n = 17). PTLp frequency estimation reveals strong responses (> 1 in 5000) on non-leukemic as well as leukemic stimulation in a majority of cases. CTLp amount variably to 10-100% of the proliferating precursor cells. Preliminary specificity analyses show that on non-leukemic stimulation about 90% of colonies exhibit exclusive lysis of the non-leukemic target. At the same time, on leukemic stimulation, about 75% of cytolytic colonies are exclusively reactive against leukemic targets without crossreactivity against nonleukemic targets from the same patient. Our data show that primary in vitro responses in HLA identical sibling pairs may be as strong as those against allo MHC antigens. In addition CTL specifically lysing leukemic or non-leukemic targets may represent an in vitro model of the immunologic non-identity of GVHD and GVLR.

Bone Marrow↗
PubMed1993

[X-chromosomal recessively inherited lymphoproliferative syndrome. An analysis of EBV-induced immune deficiency].

In recent years an increasing number of reports have described Epstein-Barr virus (EBV)-induced lymphoproliferative disease, or portrayed EBV as a cofactor in lymphoproliferative diseases (e.g. Hodgkin's disease, Burkitt's lymphoma and nasopharyngeal carcinoma), in the presence of congenital or acquired immune defects. Improved molecular biological and immunological techniques now permit detailed investigation of EBV itself and of the immune system's reaction to EBV infection. Our analysis of X-chromosome-transmitted lymphoproliferative syndrome (XLP), an immune defect that occurs after EBV infection, depicts the whole spectrum of symptoms of EBV-associated diseases, explains various theories regarding pathogenesis, and discusses diagnostic and therapeutic measures.

Adolescent↗
PubMed1993

Severe toxicity limits intensification of induction therapy for acute lymphoblastic leukemia.

Fourteen adult patients with newly-diagnosed acute lymphoblastic, leukemia (ALL), and lymphoblastic lymphoma, were treated with a dose-intense induction regimen. This regimen was designed to increase the fraction of patients achieving an early complete remission, in an attempt to increase the fraction of patients who are long-term disease-free survivors. The induction regimen included vincristine, prednisone, intermediate-dose cytarabine (Ara-C), and idarubicin, all given during the first week of therapy. This combination led to significant hepatic, gastro-intestinal, infectious, and neurologic toxicity. There was unacceptable treatment-related mortality (29%). After the first eight patients, the study was modified, omitting the Ara-C from the induction phase. Gastrointestinal morbidity was less in the cohort treated without Ara-C; however, infectious morbidity persisted at unacceptable levels and this program was terminated as too toxic to administer. There were nine complete remissions, three early deaths, and two patients with resistant disease. There have been six relapses, three of which occurred in patients who, because of protracted grade III/IV toxicity, were no longer receiving chemotherapy. With a minimum follow-up of 20 months, only three patients are still alive. We conclude that this combination of vincristine, prednisone, Ara-C, and idarubicin, is too toxic to be used as induction therapy for adult patients with ALL and lymphoblastic lymphoma.

Adult↗
PubMed1992

Adjunctive thrombolytic therapy for angioplasty in ischemic rest angina: results of a double-blind randomized pilot study.

OBJECTIVES: A multicenter pilot study was instituted to assess the role of intracoronary thrombolytic therapy during angioplasty for ischemic rest angina. BACKGROUND: Acute thrombotic coronary occlusion is increased during angioplasty for unstable angina, and intracoronary thrombolytic agents have been used to maintain patency. Prophylactic use of intracoronary thrombolytic agents has been advocated in certain high risk subgroups, although no studies have randomized therapy. METHODS: Ninety-three patients with either unstable angina and pain at rest (trial A, 66 patients) or postinfarction pain at rest (trial B, 27 patients) were randomized in double-blind fashion to administration of either intracoronary urokinase, 150,000 U, or saline solution placebo given immediately before angioplasty. Cineangiograms of the culprit lesion were recorded and analyzed in blinded fashion by a core laboratory for definite or possible (haziness) filling defects 15 min after angioplasty or after acute closure. RESULTS: Urokinase decreased filling defects at 15 min after angioplasty in comparison with placebo (14% vs. 29%, respectively, p = 0.08). Four patients in each treatment group developed acute vessel closure. However, although urokinase significantly reduced the incidence of filling defects in trial A (3% vs. 23%, p = 0.03), the drug had no effect at the selected dose in trial B (42% vs. 43%, respectively). Acute vessel closure occurred significantly more frequently in trial B than in trial A, and urokinase at the selected dose also had no effect. Ischemic events after angioplasty appeared to be related more to dissection than to thrombosis, although redilation, which was more frequent after placebo administration, may have reduced their incidence as well as that of acute closure. CONCLUSIONS: These data suggest a possible role for intracoronary urokinase during angioplasty for unstable angina. The lack of effect after infarction may represent a greater thrombus burden or degree of plaque disruption. A trial utilizing higher doses of urokinase in a larger patient group is in progress.

Angina, Unstable↗
PubMed1992

The "retinoic acid syndrome" in acute promyelocytic leukemia.

OBJECTIVE: To describe a novel complication of therapy with all-trans retinoic acid in patients with acute promyelocytic leukemia. DESIGN: Case series. SETTING: Comprehensive cancer center. PATIENTS: Consecutive patients with a morphologic diagnosis of acute promyelocytic leukemia who underwent remission induction treatment with all-trans retinoic acid, 45 mg/m2 body surface area per day. MEASUREMENTS AND RESULTS: Nine of 35 patients (26%; 95% CI, 9% to 52%) with acute promyelocytic leukemia who were treated with all-trans retinoic acid developed a syndrome consisting primarily of fever and respiratory distress. Additional prominent signs and symptoms included weight gain, lower-extremity edema, pleural or pericardial effusions, and episodic hypotension. The onset of this symptom complex occurred from 2 to 21 days after starting treatment. Three deaths occurred; post-mortem examinations in two patients showed pulmonary interstitial infiltration with maturing myeloid cells. Six other patients survived, each achieving complete remission (five patients with all-trans retinoic acid only; 1 patient with chemotherapy). In six of the nine cases, the onset of the syndrome was preceded by an increase in peripheral blood leukocytes to a level of at least 20 x 10(9) cells/L. Certain therapeutic interventions, including leukapheresis, temporary cessation of therapy with all-trans retinoic acid, and cytotoxic chemotherapy in moderate doses were not useful after respiratory distress was established. However, the administration of high-dose corticosteroid therapy (dexamethasone, 10 mg IV intravenously every 12 hours for 3 or more days) early in the course of the syndrome resulted in prompt symptomatic improvement and full recovery in three of four patients. CONCLUSIONS: The use of all-trans retinoic acid to induce hematologic remission in patients with acute promyelocytic leukemia is associated in some patients with the development of a potentially lethal syndrome that is not uniformly accompanied by peripheral blood leukocytosis. Early recognition of the symptom complex of fever and dyspnea, combined with prompt corticosteroid treatment, may decrease morbidity and mortality associated with this syndrome.

Adult↗
PubMed1992

Assessment of global and regional left ventricular performance at rest and during exercise after thrombolytic therapy for acute myocardial infarction: results of the Thrombolysis in Myocardial Infarction (TIMI) II Study.

Global and regional left ventricular performances were evaluated with equilibrium radionuclide angiocardiography in patients in the Thrombolysis in Myocardial Infarction (TIMI) II trial at the time of hospital discharge. Studies at rest were available in 1,162 (69%) of the invasive and 1,150 (69%) of the conservative strategy patients, and exercise studies in 1,133 (67%) of the invasive and 1,145 (69%) of the conservative patients. Repeat studies were performed at the time of 6-week follow-up. Global and regional ejection fraction at rest were both comparable in patients assigned to each of the treatment strategies. However, at the time of hospital discharge patients in the invasive strategy had normal exercise responses more frequently (29.7 vs 25.8% p = 0.01), greater peak exercise LV ejection fraction (54.8 +/- 13.8% vs 53.1 +/- 14.1%, p = 0.004), greater exercise--rest change in LV ejection fraction (3.7 +/- 6.7% vs 2.7 +/- 7.2%, p less than 0.001) and greater peak exercise infarct zone regional ejection fraction (53.2 +/- 31.1% vs 50.3 +/- 33.0%, p less than 0.001) than patients assigned to the conservative strategy. At 6-week follow-up these differences between treatment strategies were no longer evident. When data were restricted to those collected at comparable work loads, similar differences in hospital discharge exercise performance between invasive vs conservative strategy patients were observed. Thus, there is a small transient difference in exercise global and regional LV performance associated with an invasive as opposed to conservative strategy after thrombolytic therapy. These differences are noted at the time of hospital discharge but not at 6 weeks, and are unlikely to confer clinical benefit.

Chi-Square Distribution↗
PubMed1992

The use of FK506 and RS61443 for reversal of small-bowel rejection.

Successful clinical small-bowel transplantation is still difficult to achieve. Two features render the small intestine unique among vascularised solid organ grafts. First, the bowel contains a large amount of lymphoid tissue within the Peyer's patches, mesenteric lymph nodes, and intraepithelial lymphocytes, which are thought to mediate graft-versus-host disease and provide a major stimulus for the recipient's immune system. Unfortunately, mere surgical reduction of these tissues, by using segmental allografts, does not furnish any immunological advantage. Second, the small bowel lacks specific serum markers such as blood urea nitrogen (BUN) in the kidney or bilirubin in liver transplantation. Clinical signs such as fever, pain, or tenderness of the abdomen may indicate an already advanced destruction of the graft. Therefore, very potent immunosuppressive regimens are necessary to avoid small-bowel allograft rejection or even to reverse an ongoing rejection process. Cyclosporin was shown in small and large animal models to control rejection reactions sufficiently. However, there are two even more promising immunosuppressive agents currently under investigation. FK506, a macrolide lactone isolated from Streptomyces tsukubaensis, leads to long-term survival of small-bowel allografts in a rodent model and has already been used in a few clinical small-bowel transplantations. RS61443, a mycophenolic acid morpholinoethylester, selectively inhibits T- and B-cell proliferation. We have investigated the use of FK506 and RS61443 for the reversal of small-bowel allograft rejection in a small animal model.

Animals↗
PubMed1992

Tumoral calcinosis of the ischium.

The authors report on a case of tumoral calcinosis of the ischium in a 63-year-old female. By means of this particular case a general review of the literature on pathogenesis, histological characteristics, the possible way of treatment and the prognosis of tumoral calcinosis is presented.

Bone Diseases↗
PubMed1992

Dynamics of drug distribution. I. Role of the second and third curve moments.

Conventionally, the dynamics of distribution in the body is evaluated by the so-called distribution half-life (e.g., t1/2, alpha); but then the mean time of the distribution process is underestimated due to the influence of elimination. By contrast, information about the dynamics of distribution contained in drug disposition curves can be extracted by the second and third curve moments, parameters that are related to the variance (VDRT) and skewness (SDRT) of residence time distributions; whereas the equilibrium state characterized by the volume of distribution (Vss), is determined by the mean residence time (MDRT) or the first curve moment. The approach represents a general noncompartmental analysis that is independent of a detailed structural model or a particular disposition function. Two parameters are introduced to characterize the dynamics of drug distribution: (i) the degree of departure of the system from "well-mixed" behavior of instantaneous distribution equilibrium (related to VDRT) and (ii) the mean time until equilibration is achieved (mean equilibration time, MEQT), which additionally depends on SDRT. Both parameters are quantitative measures of the dynamics of distribution and display explicit physical significance in terms of distribution within the corresponding noneliminating system. It is further shown that the so-called "distribution phase" in biexponential disposition curves is related to a monoexponential mixing curve of its corresponding noneliminating system with an equilibration or mixing half-time, t1/2,M = t1/2,alpha (V beta/Vss*), where Vss* denotes the distribution volume of the noneliminating system. The results are applied to mixing and disposition curves measured for acetaminophen in liver-ligated and intact rats, respectively.

Acetaminophen↗