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Biomedical subjects

M Weiss

Publications and source records attributed to M Weiss.

At least 253 records · Page 14Linked to original sources
PubMed1998

Renal reabsorption of inorganic phosphorus in pregnancy in relation to the calciotropic hormones.

OBJECTIVE: To measure renal reabsorption of inorganic phosphorus and the calciotropic hormones in early and late pregnancy. DESIGN: Prospective, cross-sectional study. SETTING: Endocrine Institute at Assaf Harofeh and E. Wolfson Medical Centers; the Department of Obstetrics and Gynaecology, Sheba Medical Centre and Tel Aviv University. POPULATION: Three groups of healthy women were studied: pregnant women at the end of the first trimester (n = 20), pregnant women at the end of the third, trimester (n = 22), and nonpregnant controls (n = 27). METHODS AND MAIN OUTCOME MEASURES: The renal tubular maximal phosphorus reabsorption per decilitre of glomerular filtrate (TmP/GFR) was measured in all women. Circulating levels of intact parathyroid hormone, calcitriol (1,25-dihydroxy vitamin D3) and insulin-like growth factor I were assayed in part of the women (8-11 of each group). RESULTS: TmP/GFR was elevated in the first trimester group (mean 0.263 mmol/L) compared with controls (95% CI 0.07-0.46, P = 0.003). Third trimester values did not differ from controls. Serum calcitriol in the first trimester group was higher (mean difference 17.68 pg/mL) compared with controls (95% CI 3.89-31.47, P = 0.006) and was higher still (mean difference 20.75 pg/mL) in the third trimester group (95% CI 1.01-40.49, P = 0.042). Serum parathyroid hormone in the first trimester group was lower than in controls or the third trimester group: mean differences were 4.40 pg/mL (95% CI-1.40 to 10.15, P = 0.078) and 8.18 pg/mL (95% CI 0.51-15.85, P = 0.019) respectively. Parathyroid hormone levels correlated negatively to calcitriol levels in the combined control and first trimester groups (r = -0.54, P = 0.022) and negatively to TmP/GFR values in the combined three groups (r = -0.68, P = 0.042). First trimester levels of insulin-like growth factor I were lower than those in controls or in the third trimester: mean differences were 10.24 nmol/L (95% CI 2.05-18.43, P = 0.007) and 13.57 nmol/L (95% CI 4.23-22.91, P = 0.003), respectively. CONCLUSIONS: The dominant change in mineral metabolism in pregnancy is a rise in calcitriol which most probably is responsible for the relative suppression of parathyroid hormone and thereby for the rise in TmP/GFR in early pregnancy. All the above support the transfer of minerals to the fetus without compromising maternal bone. The significance of circulating insulin-like growth factor I remains unclear.

Adult↗
PubMed1998

Relative dispersions of intra-albumin transit times across rat and elasmobranch perfused livers, and implications for intra- and inter-species scaling of hepatic clearance using microsomal data.

It is recognized that vascular dispersion in the liver is a determinant of high first-pass extraction of solutes by that organ. Such dispersion is also required for translation of in-vitro microsomal activity into in-vivo predictions of hepatic extraction for any solute. We therefore investigated the relative dispersion of albumin transit times (CV2) in the livers of adult and weanling rats and in elasmobranch livers. The mean and normalized variance of the hepatic transit time distribution of albumin was estimated using parametric non-linear regression (with a correction for catheter influence) after an impulse (bolus) input of labelled albumin into a single-pass liver perfusion. The mean+/-s.e. of CV2 for albumin determined in each of the liver groups were 0.85+/-0.20 (n = 12), 1.48+/-0.33 (n = 7) and 0.90+/-0.18 (n = 4) for the livers of adult and weanling rats and elasmobranch livers, respectively. These CV2 are comparable with that reported previously for the dog and suggest that the CV2 of the liver is of a similar order of magnitude irrespective of the age and morphological development of the species. It might, therefore, be justified, in the absence of other information, to predict the hepatic clearances and availabilities of highly extracted solutes by scaling within and between species livers using hepatic elimination models such as the dispersion model with a CV2 of approximately unity.

Albumins↗
PubMed1998

Consonant-vowel intensity ratios for maximizing consonant recognition by hearing-impaired listeners.

The effect of adjusting the consonant-vowel (C-V) intensity ratio on consonant recognition in 18 subjects with sensorineural hearing impairment was investigated. C-V intensity ratios in a set of 48 vowel-consonant nonsense syllables were adjusted in steps of 3-6 dB depending on the subject's dynamic range of hearing. An increase in consonant intensity is referred to here as consonant enhancement (CE). The value of CE producing the highest consonant recognition score (CRmax) is defined as CEmax. Both CEmax and CRmax were determined for each subject for each of the 48 nonsense syllables. Consonant type was found to have a highly significant effect on CRmax, the gain in consonant recognition, and CEmax. The effect of vowel environment was also significant, but of much smaller magnitude. Audiogram configuration was found to have a small effect and was only significant for CRmax. The results of the study also showed that individualized adjustment of the C-V intensity ratio for each subject and consonant-vowel combination can produce substantial improvements in consonant recognition. These data can be used to estimate upper bounds of performance that, in principle, can be obtained by appropriate adjustment of the C-V intensity ratio.

Audiometry, Pure-Tone↗
PubMed1998

Dyskeratosis congenita: multisystemic disorder with special consideration of immunologic aspects. A review of the literature.

Dyskeratosis congenita (DC) is a rare, predominantly X-linked multisystemic disorder. It demonstrates a wide spectrum of clinical manifestations and typically presents with dermatologic symptoms during the first decade of life. This review of the literature points out the importance of hematologic and immunologic alterations in defining the course and prognosis of the disease process. Pancytopenia as well as the humoral and cellular disturbances in immunologic functions associated with this disease complex may lead to severe infections that represent the main cause of death. The pathogenesis of DC is still unclear and a curative therapy is presently lacking. Recent reports suggest that a beneficial effect may be observed in the administration of hematopoietic growth factors (G-CSF, GM-CSF) for patients with DC and neutropenia.

Adolescent↗
PubMed1998

Mutation screening of the BTK gene in 56 families with X-linked agammaglobulinemia (XLA): 47 unique mutations without correlation to clinical course.

OBJECTIVES: To determine the utility of single-stranded conformation polymorphism (SSCP) analysis for mutation screening in the BTK (Bruton's tyrosine kinase) gene, we investigated 56 X-linked agammaglobulinemia (XLA) families. To obtain genotype/ phenotype correlations, predicted protein aberrations were correlated with the clinical course of the disease. PATIENTS: This study included 56 patients with XLA, with or without a positive family history, who were diagnosed on the basis of their clinical features, low peripheral B-cell count, and low immunoglobulin levels. Ten patients with isolated hypogammaglobulinemia and 50 healthy males served as controls. METHODS: SSCP analysis was performed for the entire BTK gene, including the exon-intron boundaries and the promoter region. Structural implications of the missense mutations were investigated by molecular modeling, and the functional consequences of some mutations also were evaluated by in vitro kinase assays and Western blot analysis. RESULTS: We report the largest series of patients with XLA to date. All but 5 of the 56 index patients with XLA screened with SSCP analysis showed BTK gene abnormalities, and in 2 of the 5 SSCP-negative patients, no BTK protein was found by Western blot analysis. There were 51 mutations, including 37 novel ones, distributed across the entire gene. This report contains the first promoter mutation as well as 14 novel missense mutations with the first ones described for the Tec homology domain and the glycine-rich motif in the SH1 domain. Each index patient had a different mutation, except for four mutations, each in two unrelated individuals. This result supports the strong tendency for private mutations in this disease. No mutations were found in the controls. CONCLUSIONS: Our results demonstrate that molecular genetic testing by SSCP analysis provides an accurate tool for the definitive diagnosis of XLA and the discrimination of borderline cases, such as certain hypogammaglobulinemia or common variable immunodeficiency patients with overlapping clinical features. Genotype/ phenotype correlations are not currently possible, making prediction of the clinical course based on molecular genetic data infeasible.

Adolescent↗
PubMed1998

[Lyme borreliosis].

Lyme borreliosis in childhood is a tick-borne disease that includes a variety of clinical symptoms in different organs. Most frequently dermatological manifestations such as erythema migrans and borrelial lymphocytoma are observed. Uni- or bilateral peripheral facial palsy and meningitis with lymphocytic pleocytosis represent typical symptoms of neuroborreliosis. Lyme arthritis occurs as an acute or chronic manifestation that should only be diagnosed after careful consideration of other causes of arthritis in childhood. After clinical and/or laboratory diagnosis of Lyme borreliosis, systemic antibiotic treatment should be initiated. Oral treatment with amoxicillin can be recommended for the treatment of erythema migrans and borrelial lymphocytoma. In contrast, the intravenous administration of 3rd generation cephalosporins is indicated for all generalized manifestations including facial palsy, meningitis, arthritis or involvement of other organ systems. Lyme borreliosis in childhood is characterized by a good prognosis. At the present time, many efforts are given to the development of vaccines using subunits of the different genospecies of Borrelia burgdorferi. First clinical trials with Lyme borreliosis vaccines have been started.

Animals↗
PubMed1998

Analysis of metabolite formation pharmacokinetics after intravenous and oral administration of the parent drug using inverse Laplace transformation.

Models describing the plasma concentration-time curves of generated metabolite after iv and oral drug administration are presented. Utilizing numerical inverse Laplace transformation, the method can readily be used for parameter estimation and model simulation in conjunction with appropriate curve-fitting software. The approach is not limited to compartment modeling and can be applied to any linear pharmacokinetic system exhibiting hepatic and renal elimination of the parent drug. The model is formulated for single and multiple dosing of the precursor, including bolus doses and/or infusions for iv administration and sustained-release dosage forms for oral administration.

Administration, Oral↗
PubMed1998

[Diagnosis of sentinel lymph node in malignant melanoma: preoperative lymphoscintigraphy and intraoperative gamma probe guidance].

AIM: The sentinel lymph node (SLN) has shown to reflect the histologic features of the remainder of the lymphatic basin in patients with melanoma and is of considerable prognostic relevance. Aim of the study was to localize the SLN pre and intraoperatively by means of lymphoscintigraphy and gamma probe guidance. METHODS: 38 patients with histologically proven malignant melanoma (tumor thickness > 0.75 mm) were preoperatively examined by injecting 40 MBq 99mTc-Nanocoll intradermally around the lesion. The first lymph node identified was marked on the skin. Immediately after scintigraphy patients were referred to the operation room and intraoperatively mapped using a handheld gamma probe. Activity of the SLN and of the adjacent nodes was measured ex vivo. After excision of the SLN, the lymphatic basin was re-checked for radioactivity and activity of the SLN and of the adjacent nodes was re-measured after removal. RESULTS: The hottest reading was found in all patients in vivo and ex vivo in the preoperatively marked lymph node. Morphologically (macroscopically, ultrasound, CT) all nodes were unsuspicious. Histologically, in 8 patients metastatic involvement of the lymph node was found which led to a wide exploration of the lymphatic basin with consecutive lymph node excision in 7 patients. CONCLUSION: The findings suggest that combined preoperative lymphoscintigraphy and intraoperative mapping with a gamma probe is a powerful approach for exact localization of the SLN. Diagnostic detection of the SLN may have considerable impact for patient management, since extended lymph node dissection may be confined to patients presenting with positive SLN.

Adult↗
PubMed1998

Adult human cardiomyocytes coexpress vimentin and Ki67 in heart transplant rejection and in dilated cardiomyopathy.

BACKGROUND: The aim of this study was to investigate whether adult human cardiomyocytes may reexpress vimentin and whether this is linked to cellular activation. METHODS: Myocardial samples of 81 heart transplant recipients (n=183) and patients with dilated cardiomyopathy (n=10) were investigated by immunohistochemistry with the use of the marker molecule vimentin, the muscle-specific protein desmin, and Ki67, a marker for cell activation. RESULTS: Vimentin protein expression in cardiomyocytes was found in 28 samples of transplant recipients and 5 myocardial samples of patients with dilated cardiomyopathy. Coexpression of vimentin and Ki67 was found in 52 of 340 vimentin-positive cardiomyocytes. CONCLUSIONS: We suggest that the vimentin/Ki67 coexpression indicates cell activation processes as the result of different growth stimuli.

Adult↗
PubMed1998

[Extramedullary plasmocytoma of the larynx. Analysis of four cases].

Four cases of solitary extramedullary plasmocytoma of the larynx (3 men, 1 women) treated with radiotherapy are presented. Laboratory and X-ray examinations showed no evidence of systemic plasmacytoma. One patient was treated with conventional X-ray therapy and 3 patients with telegammatherapy Co-60. All patients survived 10 years with no evidence of disease.

Adult↗
PubMed1997

Detection of proviral DNA of bovine immunodeficiency virus in bovine tissues by polymerase chain reaction (PCR) and PCR in situ hybridization.

In this study, experiments were designed to investigate the distribution of bovine immunodeficiency virus (BIV) proviral DNA in the tissues and cells of infected calves by solution-phase polymerase chain reaction (SP-PCR) and PCR in situ hybridization (PCR-ISH). Total DNA samples extracted from tissues of 10 BIV-infected and 5 uninfected calves were amplified by SP-PCR with the primers directed to the BIV conserved pol gene segment. The identity of the SP-PCR product was confirmed by Southern hybridization with a BIV pol gene cDNA probe. SP-PCR results demonstrated that BIV proviral DNA was present predominantly in neural tissues and some lymphoid tissues in BIV-infected calves. It also was detected frequently in other tissues including lung, heart, esophagus, and pancreas. Further investigation on cell location of BIV proviral DNA was performed by in situ amplification of DNA on formalin-fixed tissue sections. The amplified DNA was subjected to in situ hybridization with an internal biotinylated probe and detected with streptavidin-gold followed by silver enhancement. Specific BIV proviral DNA signals were observed in neurons, microglial cells, lymphocytes, septal macrophages, smooth muscle cells, and endothelial cells. On the basis of these results, we conclude that BIV replicates in a variety of bovine tissues in vivo and has a broad cell tropism.

Animals↗
PubMed1997

Vaccine tolerance in steroid substituted patients with congenital adrenal hyperplasia.

The tolerance and side effects of vaccinations were determined in patients with congenital adrenal hyperplasia (CAH) who receive physiological corticosteroid substitution. In a retrospective approach, questionnaires about the frequencies of vaccinations and observed side effects were sent to CAH patients, and medical records were reviewed. We received 82 questionnaires from 63 patients with CAH and salt-losing and 19 patients without salt-losing. Patients age ranged from 2-40 years. No statistical differences were found for vaccination frequencies between patients with or without salt-losing. CAH patients had received complete vaccinations against diphtheria, tetanus and poliomyelitis in 79%, 85% and 78%, respectively, whereas pertussis vaccination was complete in only 23%. Live vaccination against measles, mumps and rubella was performed in 63%, 50% and 38%. Side effects of vaccination were indicated in 5 out of 82 questionnaires who all belonged to CAH patients with salt-losing. Transient side effects were an anaphylactic reaction, probably to tetanus immunoglobulin, in 1 case, and fever and convulsions after diphtheria, pertussis and tetanus (DPT) vaccine in 2 cases. In 2 further patients putative complications were noted. Encephalitis with permanent disabilities was observed after the third DPT vaccination, but a causative relation could not be established. In another boy, encephalopathy noticed after measles vaccination was induced by previous toxicosis. Although encephalopathy was described in 2 patients after vaccinations, no vaccination damage could be proven in our retrospective study. As expected, an increased vaccination risk in CAH patients was not demonstrated.

Adolescent↗
PubMed1997

Preferential expression of novel MUC1 tumor antigen isoforms in human epithelial tumors and their tumor-potentiating function.

The human MUC1 gene expresses at least 2 type 1 membrane proteins: MUC1/REP, a polymorphic high m.w. MUC1 glycoprotein often highly expressed in breast cancer tissues and containing a variable number of tandem 20 amino acid repeat units, and the MUC1/Y protein, which lacks this repeat array and, therefore, is not polymorphic. Despite their documented importance in signal transduction processes, the relative expression of the 2 isoforms in epithelial tumors is unknown. Using antibody reagents which recognize different MUC1 domains, the expression of these isoforms in malignant epithelial cells has been evaluated. A comparison of the amounts of the 2 isoforms revealed preferential expression of the novel MUC1/Y protein in breast cancer tissue samples. Furthermore, although the MUC1/REP protein is almost undetectable in HeLa cervical adenocarcinoma epithelial cells, the MUC1/Y isoform is extensively expressed in these cells. The presence of the MUC1/Y sequence as well as that of an additional tandem-repeat-array-lacking isoform, designated MUC1/X, were demonstrated by reverse transcriptase PCR amplification of RNA extracted from HeLa and ovarian carcinoma cells. It has been shown previously that the MUC1 cytoplasmic domain interacts with the SH2 domain containing GRB2 protein, which transduces signals to ras, a protein which in its activated form can lead to cell transformation. We present here data demonstrating that MUC1/Y isoform expression increases the tumorigenic potential of DA3 mouse mammary epithelial cells; in contrast, potentiation of tumorigenicity is not observed with MUC1/REP expression. Our studies thus demonstrate that expression of the MUC1 gene in epithelial tumors can give rise to substantial levels of MUC1 proteins devoid of the tandem repeat array, which are generated by alternative splicing mechanisms.

Amino Acid Sequence↗
PubMed1997

Health and functional status of long-term survivors of bone marrow transplantation. EBMT Working Party on Late Effects and EULEP Study Group on Late Effects. European Group for Blood and Marrow Transplantation.

BACKGROUND: Although many patients now survive the short-term complications of bone marrow transplantation for life-threatening hematologic disease, information on the health and activity of long-term survivors is sparse. OBJECTIVE: To evaluate the morbidity and mortality of patients surviving more than 5 years after allogeneic bone marrow transplantation. DESIGN: Retrospective, multicenter study. PATIENTS: 798 recipients of bone marrow transplants (477 adults, 321 children) from 43 European centers. Patients had received transplants before December 1985 and had survived at least 5 years. Patients had received allogeneic or syngeneic bone marrow for leukemia, lymphoma, inborn diseases of the hematopoietic and immune systems, and severe aplastic anemia. MEASUREMENTS: Survival, clinical performance according to Karnofsky score (in increments of 10%), and social reintegration were assessed as outcomes. Patient age and sex, primary disease and status at transplantation, histocompatibility of the donor, conditioning regimen, type of prophylaxis of graft-versus-host disease, and acute and chronic graft-versus-host disease were evaluated as variables. RESULTS: For the 55 5-year survivors, actuarial mortality was 8% at 10 years and 14% at 15 years. The leading causes of death were disease recurrence (21 patients), chronic graft-versus-host disease with complicating infections and lung disease (11 patients), secondary cancer (8 patients), and the acquired immunodeficiency syndrome (AIDS) (5 patients). When patients with recurrent disease were excluded, late death was associated with chronic graft-versus-host disease (P < 0.001), occurrence of secondary cancer (P < 0.001), male sex of the patient (P = 0.05), and female sex of the donor (P = 0.002). Clinical performance was normal (Karnofsky score, 100%) or minimally reduced (Karnofsky score, 90%) in 93% of patients; 89% of patients resumed full-time work or school. Reduced performance status and incomplete resumption of social activity were associated with chronic graft-versus-host disease, recurrent leukemia, AIDS, secondary cancer, organ dysfunction, and neurologic or psychological problems. Other risk factors for incomplete resumption of social activity were female sex (P = 0.002) and older age at transplantation (P = 0.001). CONCLUSIONS: More than 5 years after bone marrow transplantation, most patients were in good health (93%) and had returned to full-time work or school (89%). Recurrence of the primary disease, secondary cancer, and chronic graft-versus-host disease and its sequelae remain problems for some patients.

Adult↗
PubMed1997

A note on the interpretation of tracer dispersion in the liver.

The transit time distribution of intravascular markers and highly diffusible solutes is determined by the mixing process within the network of interconnected sinusoids. Based on the role of the relative dispersion or coefficient of variation (CV2) of transit times as a measure of distribution dynamics (macromixing) various intrahepatic mixing processes are discussed, which are implied by current models of hepatic elimination. The opposite extremes of perfect micromixing and complete segregation are reflected by the dispersion model and the distributed parallel tube model, respectively. Assuming various capillary structures-including that of a fractal network-the dispersion models differ with regard to the predicted scaling behaviour of CV2. The observed flow independence of CV2 suggests that molecular diffusion and Taylor dispersion can be neglected but does not allow discrimination between mixing models.

Animals↗