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Biomedical subjects

M Weiss

Publications and source records attributed to M Weiss.

At least 325 records · Page 18Linked to original sources

Case study: obsessive difficult temperament and its response to serotonergic medication.

The syndrome of "obsessive difficult temperament" is described, and its response to serotonergic medication is reported. Diagnostic criteria are proposed for this temperamental pattern characterized by functional impairment due to obsessive rigidity, irritability, withdrawal, and poor self-regulation. The clinical characteristics, prior treatment, family history, and medication response are presented for a case series of eight children, five female and three male, presenting initially for assessment at ages 8 to 11 years, with obsessive difficult temperament which improved significantly as a result of serotonergic medication.

Child↗

An 18-year follow-up of primary hepatic carcinoid with carcinoid syndrome.

Primary hepatic carcinoid is extremely rare. Although one of the 18 previously reported cases was accompanied by clinical features of carcinoid syndrome, no patient manifested these features as the presenting complaint, as was true in our case. During the 18 years this patient has been followed, she has been treated with most of the major therapeutic methods, including systemic chemotherapy, hepatic artery chemoembolus injection, extended right hepatic lobectomy, and, eventually, more systemic chemotherapy and octreotide. She continues to be nearly asymptomatic and is still working. We present the results of extensive chemical and hormonal assays, briefly summarize the primary hepatic carcinoids reported previously, and review therapy of this disease.

Adult↗

A simple and rapid method for the determination of D-sorbitol in plasma using the Cobas Mira S.

The standard enzymatic assay for quantification of D-sorbitol in plasma was adapted to the automatic analyzer Cobas Mira S. In the assay, NAD (reagent) in the presence of sorbitoldehydrogenase (SDH; start reagent) converts D-sorbitol to fructose with formation of NADH, which was detected automatically as the difference between the first and last readings at 340 nm. The sample blank values for each specimen were subtracted to exclude both endogenous D-sorbitol and sugars, which also react as substrates for SDH. The method is simple, rapid (40 samples/h), precise down to endogenous concentrations (coefficient of variation < 5%; limit of determination: 0.38 mg/L) and linear up to 100 mg/L. Samples with higher D-sorbitol concentrations were estimated after dilution. The method was used to measure disposition curves of sorbitol in volunteers after a single intravenous dose of 0.8 g sorbitol.

Humans↗

Primary structure and effect of pH on the expression of the plasma membrane H(+)-ATPase from Dunaliella acidophila and Dunaliella salina.

The plasma membrane H(+)-ATPase gene was cloned and sequenced from the extremely acidophilic green alga Dunaliella acidophila and from the extremely halotolerant Dunaliella salina. A special feature of the Dunaliella H(+)-ATPase is an extended C-terminal domain. The deduced amino acid sequences of the two proteins are 75% identical but differ in their C terminus. A hydrophilic loop within this domain in D. salina, which presumably faces the cell exterior, has a high ratio of acidic over basic amino acids, typical of halophilic proteins. The amount of the ATPase protein in plasma membranes and the level of its mRNA transcript in D. acidophila are far higher than in D. salina, suggesting that D. acidophila overexpresses the enzyme. A pH shift from 9.0 to 7.0 induces in D. salina a large increase in the level of the H(+)-ATPase mRNA and in the amount of the H(+)-ATPase protein. This suggests that the expression of the H(+)-ATPase in D. salina is pH-regulated at the transcriptional level. The implications of these findings are discussed with respect to the adaptive pressures imposed on these algal species by their exceptional environmental conditions.

Amino Acid Sequence↗

Psychopathology in offspring of mothers with borderline personality disorder: a pilot study.

OBJECTIVE: Children of mothers with borderline personality disorder (BPD) were hypothesized to be at greater risk for psychopathology, particularly impulse spectrum disorders, than children of mothers with other personality disorders. METHOD: Twenty-one index children were compared with 23 children of mothers with a nonborderline personality disorder. Diagnoses were obtained using the Kiddie Schedule for Affective Disorders and Schizophrenia-Episodic Version (KSADS-E) and the Child Diagnostic Interview for BPD (CDIB), and functioning was rated with the Child Global Assessment Schedule (CGAS). Physical, sexual, and verbal abuse, as well as family violence and placements, were also assessed. RESULTS: The children of the borderline mothers, as compared with controls, had more psychiatric diagnoses, more impulse control disorders, a higher frequency of child BPD, and lower CGAS scores. There were no differences between the groups for trauma. CONCLUSION: The offspring of borderline mothers are at high risk for psychopathology.

Adolescent↗

Cytarabine with high-dose mitoxantrone induces rapid complete remissions in adult acute lymphoblastic leukemia without the use of vincristine or prednisone.

PURPOSE: To evaluate the efficacy and safety of a new induction regimen for adult acute lymphoblastic leukemia (ALL) that does not contain vincristine or corticosteroids. PATIENTS AND METHODS: Thirty-seven adult patients with newly diagnosed 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 (CR) in an attempt to increase long-term disease-free survival. The induction regimen was cytarabine (Ara-C) 3 g/m2/d for 5 days and mitoxantrone 80 mg/m2 as a single dose on day 3. Granulocyte colony-stimulating factor (G-CSF) 200 micrograms/ m2/d beginning on day 7 was used to promote early myeloid recovery. RESULTS: There were 31 CRs (84%). Median time to CR was 34 days, median hospital stay was 28 days, and the median number of days with a neutrophil count less than 500/microL was 18. There were three patients with resistant disease who experienced treatment failure and three early deaths from sepsis. Four patients with Philadelphia chromosome-positive (Ph+) ALL achieved hematologic and cytogenetic CRs. CONCLUSION: This dose-intense induction regimen produced a high incidence of CRs with acceptable toxicity without the use of vincristine or corticosteroids. Comparisons with our prior vincristine/prednisone-based induction regimen (the L-20 protocol) suggest that patients treated on the current study were more likely to achieve a CR and that they achieved this remission earlier than patients treated with a traditional four-drug (vincristine, prednisone, doxorubicin, and cyclophosphamide) induction regimen.

Adolescent↗

Reduced myocardial 123I-metaiodobenzylguanidine uptake in newly diagnosed IDDM patients.

123I-labeled metaiodobenzylguanidine (123I-MIBG) scintigraphy is a novel technique for the assessment of cardiac sympathetic dysinnervation. To evaluate defects of the cardiac autonomic nervous system at the onset of IDDM, this technique together with conventional electrocardiogram (ECG)-based cardiac reflex tests and measurement of the QT interval was applied to 22 newly diagnosed metabolically stabilized IDDM patients without myocardial perfusion abnormalities (99mTc-labeled methoxyisobutylisonitrile scintigraphy) and 9 matched control subjects. Seventeen diabetic patients (77%), but none of the control subjects, were observed to have a reduced global myocardial uptake of 123I-MIBG. In contrast, only two diabetic patients (9%) demonstrated an ECG-based cardiac autonomic neuropathy (two or more of five age-related cardiac reflex tests abnormal) (P < 0.001). In newly diagnosed IDDM patients, the uptake of 123I-MIBG was reduced more in the posterior myocardial region compared with the lateral and apical region (P < 0.01, P = 0.03). The septal myocardial region exhibited a smaller uptake than the lateral myocardial region (P = 0.02). The maximum/minimum 30:15 ratio correlated with the global, anterior, lateral, and septal myocardial uptake of 123I-MIBG (P < 0.05, P < 0.05, P < 0.01, P < 0.05). A correlation between global and regional myocardial 123I-MIBG uptake and HbA1c or QT interval was not observed. Newly diagnosed metabolically stabilized IDDM patients without myocardial perfusion defects show evidence of cardiac sympathetic dysinnervation, as indicated by a reduction of 123I-MIBG uptake, at a significant higher proportion than ECG-based cardiac autonomic neuropathy. Furthermore, they present with regional differences of myocardial 123I-MIBG uptake.

3-Iodobenzylguanidine↗

Do etomidate and propofol influence oxygen radical production of neutrophils?

The effects of etomidate in an alcoholic vehicle and in a lipid-emulsion as well as those of propofol on N-formyl-methionyl-leucyl-phenylalanine (FMLP-) and zymosan-induced oxygen radical production of neutrophils were examined and compared with the effects of their respective vehicles. Furthermore free-radical scavenging capacities of these medications were investigated. The dose-response effects of etomidate, propofol and their respective vehicles on neutrophil function were tested by FMLP- and zymosan-induced chemiluminescence of neutrophils and, in addition, in a cell-free chemiluminescence system. Effects of commercial preparations of etomidate were generally not drug-specific but due to the vehicles and/or to unphysiologic osmolality values. Propofol impaired chemiluminescence of neutrophils in a drug-specific manner, even in the therapeutic concentration range. Free-radical scavenging contributed to this depression of chemiluminescence of neutrophils by propofol. Different composition of the lipid-emulsions of etomidate and propofol resulted in either a stimulation or suppression of chemiluminescence of neutrophils. Propofol but not etomidate impairs chemiluminescence of neutrophils drug-specifically. Besides a potential interaction with the neutrophils, free-radical scavenging accounts for this suppression.

Etomidate↗

Late-onset keratoconjunctivitis sicca syndrome after bone marrow transplantation: incidence and risk factors. European Group or Blood and Marrow Transplantation (EBMT) Working Party on Late Effects.

The incidence, time course and risk factors associated with late-onset keratoconjunctivitis sicca syndrome after bone marrow transplantation (BMT) was evaluated in a multicenter retrospective cohort study conducted by the European Group for Blood and Marrow Transplantation (EBMT) Working Party on Late Effects. Data were requested from participating European centers on all patients transplanted up to December 1980 and on all patients treated during the year of 1984. Twenty-eight centers reported data on 258 patients and 248 could be evaluated for keratoconjunctivitis. Forty-eight of the 248 (19%) patients developed a keratoconjunctivitis sicca syndrome between 3 and 127 months (13.8 months) after BMT. The actuarial probability of developing dry eyes was 21 +/- 3% at 15 years. Thirty-three of the 48 (69%) patients with sicca syndrome had graft-versus-host disease (GVHD) compared to 60 of 200 (30%) patients without keratoconjunctivitis (P < 0.0001). The probability of developing keratoconjunctivitis sicca syndrome at 15 years was 38 +/- 6% for patients with and 10 +/- 3% (P < 0.0001) for those without chronic GVHD. Factors associated with an increased risk for late-onset of keratoconjunctivitis are chronic GVHD (relative risk 3.5; CI, 1.9-6.9), female patients (5.6; CI, 1.6-18.8), age older than 20 years (3.1; CI, 1.6-5.6), single dose irradiation for preparation to BMT (3.8; CI, 1.3-11.3) and methotrexate for prevention of GVHD (3.6, CI, 1.05-12.8). Late-onset kerato- conjunctivitis is a frequent ocular complication of BMT. With adequate treatment, severe corneal defects can be avoided. It occurs more frequently in patients with chronic GVHD, but, independent of chronic GVHD, more frequently in older patients and in females as it is observed in de novo Sjögren's syndrome. These data support the current concept that chronic GVHD is a reaction of both, allo- and autoimmunity.

Adolescent↗

Is inhibition of oxygen radical production of neutrophils by sympathomimetics mediated via beta-2 adrenoceptors?

Despite their beneficial effects on cardiovascular derangements in patients with severe sepsis, high doses of sympathomimetics might contribute to an impaired neutrophil function. This study was conducted to examine whether various sympathomimetics [(-)-epinephrine (EPI), dopamine (DA) and dobutamine (DOB)] differ in their potency to suppress the formation of oxygen radicals by neutrophils and whether this potency correlates with their affinity to or intrinsic activity for beta-2 adrenoceptors (beta-2 AR). Oxygen radical production of human neutrophils was induced by N-formyl-methionyl-leucyl-phenyl-alanine and detected by chemiluminescence measurements. Dose-response curves for the inhibition of chemiluminescence by sympathomimetics were measured in the absence and presence of 0.1 microM CGP 20,712 A (1-[2(3-carbamoyl-4-hydroxy phenoxy)-ethylamino]-3-[4-(1-methyl-4-trifluoromethyl-2-imidazolyl) phenoxy]-2-propanol methanesulfonate) and 0.1 microM ICI 118,551 (erythro-(+/-)-1-(7-methylindan-4-yloxy)-3 isopropylaminobutan-2-ol hydrochloride) to selectively antagonize beta-1 AR and beta-2 AR, respectively. Inhibition of chemiluminescence of neutrophils by EPI was approximately 100-fold more potent than that by DA and DOB. Only the inhibition curve by EPI exhibited two components, one at nanomolar and one at micromolar concentrations. The nanomolar component was sensitive against beta-2 AR blockade, whereas the micromolar one was insensitive against both beta AR antagonists. Dose-response curves for DA and DOB exhibited a simple hyperbolic shape at micromolar concentrations and were insensitive against both beta AR antagonists. Maximum inhibition by DA and DOB was equipotent to that by EPI. However, the EC50 for DA was much lower than its dissociation constants, KD, assayed in membrane preparations by radioligand binding, whereas the EC50 of DOB matched KD. This difference could not be explained by a different efficiency of signal transduction, which was determined in receptor-coupled adenylate cyclase activity and which only showed a slightly higher efficiency of DA (51%) than of DOB (34%). Therefore, sympathomimetics were also investigated in a cell-free system, in which chemiluminescence was generated by horseradish peroxidase with hydrogen peroxide as substrate. Surprisingly, all of the sympathomimetics suppressed chemiluminescence with micromolar concentrations. We conclude that sympathomimetics with high affinity and high intrinsic activity (EPI) inhibit neutrophil function via occupation of beta-2 AR, whereas sympathomimetics with low affinity (DA) or low intrinsic activity (DOB) may act by direct scavenging of oxygen radicals.

Adenylyl Cyclases↗

Systematic screening for pharmacokinetic interactions during drug development.

The possible involvement of a new chemical entity in pharmacokinetic drug interactions is an important safety issue. Not all relevant drug combinations for evaluation of the interactive potential of a new drug can be examined. Therefore, experiments should be selected to provide information which is valid not only for the interaction investigated, but which can be extrapolated to other comedications. In this respect the typical approaches currently used, including interaction studies with high risk drugs and compounds frequently given as comedication, or studies involving standard inhibitors and standard substrates are unsatisfactory. A better approach is to characterize drugs according to their effects on the underlying pharmacokinetic processes. Indeed, recent progress in understanding drug interaction mechanisms and in the development and refinement of in vitro test systems enables in many cases experiments to be designed which predict the occurrence of drug interactions. This paper illustrates systematic investigational procedures based on mechanism of interaction. Interaction mechanisms involving drug absorption, distribution, metabolism, and/or excretion are briefly summarized. Detailed proposals are derived which allow identification of the possible role of a new drug in interaction mechanisms for which valid test systems are available. Emphasis is placed on the rational selection of experiments with optimal cost-effectiveness. In vitro methods are integrated in the schemes wherever possible. In addition, it is proposed that pharmacoepidemiological screening, starting in phase II of drug development, be used to identify those relevant drug interactions missed by the mechanism-based approach. As exemplified by several recently discovered interactions it should be possible, by implementation of the proposed procedure, to avoid most serious unexpected adverse effects due to pharmacokinetic drug interactions.

Animals↗

[Lymphoscintigraphy for non-invasive long term follow-up of functional outcome in patients with autologous lymph vessel transplantation].

AIM: Autologous lymph vessel transplantation significantly improves the lymphdrainage in patients with primary and secondary lymphedema. The aim of the present study was to answer the question, whether scintigraphic long-term follow up and semiquantitative evaluation of lymphatic flow could prove the persisting success of this sophisticated microsurgical technique. METHODS: In this study visual and semiquantitative lymphoscintigraphy was used to prove the function of lymphatic vessel grafts in 20 patients (17 females, 3 males) comparing a preoperative baseline study with postoperative follow up investigations for a period of 7 years. The reason for microsurgical lymph vessel transplantation was in 4 patients a primary and in 16 patients a secondary lymphedema. In 12 cases the transplantation site was at the upper extremity, in 8 cases at the lower limb. RESULTS: In 17/20 patients lymphatic function significantly improved after autologous lymph vessel transplantation compared to the preoperative findings, as verified by visual improvement of lymph drainage and decrease of a numeric transportindex. In 5 cases the vessel graft could be directly visualized. In these patients with scintigraphic visualization of the vessel graft the transportindex decreases to a significantly greater extent compared to the preoperative baseline study. Only 3 patients did not benefit from microsurgical treatment CONCLUSION: Lymphoscintigraphy combined with semiquantitative estimation of lymphatic transport kinetics has shown to be an easy, reliable and readily available technique to assess lymphatic function before and after autologous lymph vessel transplantation. Thus, the method is not only helpful in planning microsurgical treatment but also in monitoring the postoperative improvement of lymph drainage. Patients with scintigraphic visualization of the vessel graft showed a significant better postoperative outcome than those without. The scintigraphic visualization of the vessel graft therefore seems to indicate a favourable prognosis regarding to lymph drainage.

Adult↗

[Bovine virus diarrhea/mucosal disease in cattle--clinical findings in 103 calves and cattle].

One hundred and three calves and heifers persistently infected with BVD virus were examined. The most important clinical findings in order of frequency were weight loss, erosions of the oral mucosa, diarrhea, anorexia and fever. In addition, nasal discharge, lymph node enlargement, erosions of the nose, muzzle and interdigital cleft and bronchopneumonia occurred in less than half of the patients. Furthermore, crustaceous dermatitis was observed in three patients and petechial hemorrhage of the oral mucosa occurred in two other cases with severe thrombocytopenia. Haemoconcentration, leukocytosis, hyperfibrinogenemia and azotemia were the most important haematological findings. To confirm the clinical diagnosis, the serum antibody titre of 69 patients was compared with that of a clinically healthy control animal from the same herd. There was no positive antibody titre in 65 of the 69 patients, whereas 67 of the control animals had positive titres. In 34 patients, EDTA blood samples were collected for virus detection. In 20 of these, skin biopsy samples were also obtained for virus demonstration. Virus has been demonstrated in the blood of 32 of the 34 cases and in all 20 skin biopsy specimens.

Animals↗

Utility of follow-up tests for detecting recurrent disease in patients with malignant melanomas.

OBJECTIVE: To determine the effectiveness of follow-up tests for signaling recurrences in patients with intermediate- and high-risk malignant melanomas treated with curative intention. DESIGN: Retrospective analysis of prospectively collected data. SETTING: North Central Cancer Treatment Group. PATIENTS: A total of 261 patients with resected local (> or = 1.69 mm) and regional nodal malignant melanomas who were enrolled in a single prospective adjuvant trial were studied. All patients were scheduled to be followed up monthly for 2 months, then every 2 months for the first year, every 4 months the second year, every 6 months the next 3 years, and annually thereafter, with each visit consisting of a history, physical examination, complete blood cell count, blood chemistry panel, and a chest x-ray. RESULTS: Of the 145 evaluable patients who developed recurrent melanomas, 99 patients (68%) developed symptoms that signaled the diagnosis of recurrent disease. Physical examination of asymptomatic patients led to the diagnosis of recurrent disease in 37 patients (26%). The other nine patients (6%) with recurrent disease had abnormal chest x-rays. Laboratory results were never a sole indicator of recurrent disease. CONCLUSION: The majority of recurrences following resection of primary melanomas are discovered by history and/or physical examination despite the frequent use of other follow-up tests. The present data indicate that routine blood analyses and chest x-rays have limited value in the postoperative follow-up of patients with resected intermediate- and high-risk melanomas.

Clinical Laboratory Techniques↗

Interaction of the beta-carboline harmaline with a GABA-benzodiazepine mechanism: an electrophysiological investigation on rat hippocampal slices.

An interaction of harmaline (HA), a beta-carboline, with benzodiazepine (Bzd) receptors, has been reported. HA perfusion induced a similar, although less potent, depressing effect as clonazepam (CLO) on the amplitude of the population spikes (PS) evoked by Schaffer collateral stimulation in the CA1 area of rat hippocampal slices. The suppressant effect of both CLO and HA on PS amplitude was reversed by simultaneous perfusion of the GABA antagonist picrotoxin. These results suggest that HA acts as a weak or partial agonist at Bzd receptors.

Action Potentials↗

Specificity of the PTB domain of Shc for beta turn-forming pentapeptide motifs amino-terminal to phosphotyrosine.

Shc phosphorylation in cells following growth factor, insulin, cytokine, and lymphocyte receptor activation leads to its association with Grb2 and activation of Ras. In addition to being a cytoplasmic substrate of tyrosine kinases, Shc contains an SH2 domain and a non-SH2 phosphotyrosine binding (PTB) domain. Here we show that the Shc PTB domain, but not the SH2 domain, binds with high affinity (ID50 approximately equal to 1 microM) to phosphopeptides corresponding to the sequence surrounding Tyr250 of the polyoma virus middle T (mT) antigen (LLSNPTpYSVMRSK). Truncation studies show that five residues amino-terminal to tyrosine are required for high affinity binding, whereas all residues carboxyl-terminal to tyrosine can be deleted without loss of affinity. Substitution studies show that tyrosine phosphorylation is required and residues at -5, -3, -2, and -1 positions relative to pTyr are important for this interaction. 1H NMR studies demonstrate that the phosphorylated mT antigen-derived sequence forms a stable beta turn in solution, and correlations between structure and function indicate that the beta turn is important for PTB domain recognition. These results show that PTB domains are functionally distinct from SH2 domains. Whereas SH2 domain binding specificity derives from peptide sequences carboxyl-terminal to phosphotyrosine, the Shc PTB domain gains specificity by interacting with beta turn-forming sequences amino-terminal to phosphotyrosine.

Amino Acid Sequence↗