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M Weiss

Publications and source records attributed to M Weiss.

At least 109 records · Page 6Linked to original sources
PubMed2001

Structure-hepatic disposition relationships for cationic drugs in isolated perfused rat livers: transmembrane exchange and cytoplasmic binding process.

This work studied the structure-hepatic disposition relationships for cationic drugs of varying lipophilicity using a single-pass, in situ rat liver preparation. The lipophilicity among the cationic drugs studied in this work is in the following order: diltiazem > propranolol > labetalol > prazosin > antipyrine > atenolol. Parameters characterizing the hepatic distribution and elimination kinetics of the drugs were estimated using the multiple indicator dilution method. The kinetic model used to describe drug transport (the "two-phase stochastic model") integrated cytoplasmic binding kinetics and belongs to the class of barrier-limited and space-distributed liver models. Hepatic extraction ratio (E) (0.30--0.92) increased with lipophilicity. The intracellular binding rate constant (k(on)) and the equilibrium amount ratios characterizing the slowly and rapidly equilibrating binding sites (K(S) and K(R)) increase with the lipophilicity of drug (k(on): 0.05--0.35 s(-1); K(S): 0.61--16.67; K(R): 0.36--0.95), whereas the intracellular unbinding rate constant (k(off)) decreases with the lipophilicity of drug (0.081--0.021 s(-1)). The partition ratio of influx (k(in)) and efflux rate constant (k(out)), k(in)/k(out), increases with increasing pK(a) value of the drug [from 1.72 for antipyrine (pK(a) = 1.45) to 9.76 for propranolol (pK(a) = 9.45)], the differences in k(in/kout) for the different drugs mainly arising from ion trapping in the mitochondria and lysosomes. The value of intrinsic elimination clearance (CL(int)), permeation clearance (CL(pT)), and permeability-surface area product (PS) all increase with the lipophilicity of drug [CL(int) (ml x min(-1) x g(-1) of liver): 10.08--67.41; CL(pT) (ml x min(-1) x g(-1) of liver): 10.80--5.35; PS (ml x min(-1) x g(-1) of liver): 14.59--90.54]. It is concluded that cationic drug kinetics in the liver can be modeled using models that integrate the presence of cytoplasmic binding, a hepatocyte barrier, and a vascular transit density function.

Algorithms↗
PubMed2001

Androgen suppression and clinical improvement with dopamine agonists in hyperandrogenic-hyperprolactinemic women.

OBJECTIVE: To examine the effect of dopamine agonist (DA) treatment on clinical and biochemical features in hirsute, hyperprolactinemic (HPRL) women and the relationship between prolactin (PRL) and androgens. STUDY DESIGN: We evaluated 80 hirsute HPRL women (age, 27 +/- 1 years [mean +/- SE]) with neuroleptic treatment, prolactinoma and idiopathic HPRL (12, 13 and 55, respectively). DA, mainly bromocriptine, was administered for 11 +/- 1 months. Response indicators were Ferriman-Gallwey hirsutism (FGS) and Leeds acne (LAS) scores, circulating PRL, dehydroepiandrosterone sulfate (DHEAS), free and total testosterone, and androstenedione. RESULTS: Baseline PRL correlated positively with DHEAS (r = .23, P = .03) and free testosterone (r = .36, P < .001). In all women, FGS, LAS, PRL, free testosterone, DHEAS and androstenedione decreased by 40-85% during DA treatment (P < .001). The decline in free testosterone was higher when PRL was > or = 65 ng/mL than when PRL was < 65 (P = .03) and correlated positively with basal DHEAS (r = .40, P < .001). CONCLUSION: Our data suggest a modulation by PRL of adrenal androgen production. DA treatment reduces PRL and serum androgens. It results in a significant clinical improvement in acne and hirsutism. Therefore, DA is recommended as monotherapy for hyperandrogenic.

Adolescent↗
PubMed2000

The burden of hydrocele on men in Northern Ghana.

The social and economic impact of lymphatic filariasis was studied in Northern Ghana. Qualitative methods of gathering information revealed that even though the disease was a problem to both men and women, men with hydrocele suffered a greater psychosocial burden. Particular attention was paid to them, distinguishing men with small hydroceles and men with large ones. Out of frustration men with small hydroceles sought health care from a wider range of places than men with larger ones. The pain associated with adenolymphangitis (ADL) renders them inactive for up to 5 days. Complications of lymph scrotum and ridicule from community members were a problem. Unmarried men in particular found it difficult to find a spouse with their condition, and various degrees of sexual dysfunction were reported amongst married men. The clinical significance and the value of time and attention for counseling to mitigate the effects of the disease on damaged male identity and the need for gender studies to address male issues and the need for including psychosocial issues in the calculating of disability adjusted life years (DALY's) is also discussed.

Adolescent↗
PubMed2000

Protein sorting in the Golgi apparatus: a consequence of maturation and triggered sorting.

To explain how resident proteins distribute in peak-like patterns at various positions in the secretory pathway, Glick and co-workers postulated that resident proteins comprise different populations (termed kin populations) and that these compete with each other for entering retrograde transport carriers [Glick et al. (1997) FEBS Lett. 414, 177-181]. Using modelling and computer simulation, they could demonstrate that differences in competitiveness sufficed to generate overlapping but distinct peak-like steady state distributions of the different kin populations across the Golgi stack. In this study, we have tested the robustness of the competition model and find that over-expression or changes in the number of kin populations affect their overall steady state distributions. To increase the robustness of the system, we have introduced a milieu-induced trigger for recycling. This allows for a decrease in the coupling between kin populations permitting both over-expression as well as changes in the number of kin populations. We have also extended the model to include a Golgi to endoplasmic reticulum (ER) recycling pathway and find that only a small amount of resident proteins may recycle at any time without upsetting their observed distributions in the Golgi stack. The biological relevance of a trigger-induced sorting mechanism and ER recycling is discussed.

Binding, Competitive↗
PubMed2000

Basal plasma dehydroepiandrosterone sulfate level: a possible predictor for response to electroconvulsive therapy in depressed psychotic inpatients.

BACKGROUND: Dehydroepiandrosterone (DHEA) and its sulfate derivative DHEAS are neuroactive steroids. In the brain, they interact with gamma-aminobutyric acid (GABA(A)) receptors, which are involved in the regulation of anxiety and mood. The relevance of circulatory neurosteroids to psychiatric disorders and biological treatment is unknown. METHODS: Basal plasma levels of cortisol, DHEA, and DHEAS and the DHEAS-DHEA ratio were determined in 17 psychiatric inpatients before and after six electroconvulsive (ECT) therapy sessions, and all changes were statistically analyzed. For baseline values, 25 healthy individuals served as control subjects. Severity of depression and psychosis in the patients was measured with the Hamilton Depression Rating Scale (HDRS) and the Brief Psychiatric Rating Scale, respectively. RESULTS: Both basal and post-ECT levels of cortisol, DHEA, and DHEAS were significantly higher in the patients than in the control subjects. DHEAS levels in responding patients were higher at completion of treatment than at baseline. Patients defined as ECT nonresponders (change in HDRS < 30% from before treatments) exhibited elevated basal DHEAS levels compared with ECT responders. CONCLUSIONS: Markedly elevated basal DHEAS levels (mean + 2 SD of control value) are associated with resistance to ECT and may serve as a potential predictive marker of nonresponsiveness to ECT in depressed patients.

Adult↗
PubMed2000

New class of eigenstates in generic hamiltonian systems

In mixed systems, besides regular and chaotic states, there are states supported by the chaotic region mainly living in the vicinity of the hierarchy of regular islands. We show that the fraction of these hierarchical states scales as Planck's over 2pi(alpha) and we relate the exponent alpha = 1-1/gamma to the decay of the classical staying probability P(t) approximately t(-gamma). This is numerically confirmed for the kicked rotor by studying the influence of hierarchical states on eigenfunction and level statistics.

Journal Article↗
PubMed2000

Author reply

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Journal Article↗
PubMed2000

Effect of estrogen replacement therapy on speed of sound at multiple skeletal sites.

OBJECTIVES: To evaluate the effect of estrogen replacement therapy (ERT) on postmenopausal bone loss by multi-site ultrasound measurement. METHODS: A cross-sectional comparison of postmenopausal women, ERT users and non-users. The two study groups were enrolled for the reference database collection for the Sunlight Omnisense (Omnisense) and were matched by years since menopause. Speed of sound (SOS) was measured at the distal radius (RAD), mid-shaft tibia (TIB), fifth metatarsus (MTR) and proximal phalanx (PLX). RESULTS: 143 ERT users for 5.2+/-3.6 years were compared with 139 ERT non-users (age: 57.0+/-5.3 and 57.5+/-5.5, respectively). Both groups were 7.1+/-5.0 years since menopause. SOS, expressed in T-score units, was higher at the RAD in ERT users as compared to ERT non-users (-0.55+/-1.30 and -1.36+/-1.60, respectively, P<0.0001), and at the TIB (-0.73+/-1.34 and -1.28+/-1.45, respectively, P=0. 003). Same trend was observed at the MTR and PLX, but not statistically significant because of fewer observations. In early post menopause period, the ERT-non users RAD data shows an annual SOS decrease of 0.17 versus annual increase of 0.12 T-score units (P=0.037). Similar effect is observed at the TIB, though not statistically significant (non-users decrease of 0.20 vs. users increase of 0.08 T-score units/year, P=0.086). CONCLUSIONS: SOS measurements by Omnisense at multiple skeletal sites support the ERT protective effect on bone.

Aged↗
PubMed2000

Neuronal expression of Fos protein in the hypothalamus of rats with heart failure.

We sought to identify the areas that have altered neuronal activity within the hypothalamus of rats with heart failure (HF) by mapping neuronal staining of c-Fos protein (Fos) 6-8 weeks following coronary artery ligation (HF group; n=17) or sham surgery (sham-operated control group, n=15). Fos-like immunoreactivity was observed in the paraventricular nucleus (PVN), supraoptic nucleus (SON), median preoptic nucleus (MnPO), anterior hypothalamus (AH) and posterior hypothalamus (PH) using a standard ABC immunocytochemical protocol. The rats in the HF group displayed infarcts averaging 34+/-2% of the outer circumference and 41+/-1% of the inner circumference of the left ventricular wall. Sham-operated control rats had no observable damage to the myocardium. Rats with chronic heart failure (n=5) but no manipulation (no surgery) had a similar number of Fos-staining cells in PVN SON, MnPO, AH and PH compared to sham-operated rats. Acute surgery for isolation of vagus nerves and anesthesia for 90 min increased the number of Fos positive cells in PVN, SON and MnPO of both sham-operated rats and rats with HF. Furthermore, rats with heart failure (n=5) had significantly higher number of Fos-staining cells in PVN (four times), SON (4.5 times) and MnPO (1.5 times) compared to sham-operated rats after acute surgery for isolation of the vagus. The number of Fos-staining cells remained unaltered in AH and PH in both groups of rats. However, in a third series of experiments vagotomy reduced the number of Fos-staining cells in the PVN, SON or MnPO of rats with HF (n=5) to those observed in sham-operated vagotomized rats. This study shows that: (1) there is augmented neuronal activity as indicated by increased number of Fos staining neurons in the PVN, SON and MnPO due to acute surgical stress in rats with HF, and (2) vagal afferents are responsible for the increased neuronal activity in PVN, SON and MnPO of rats with HF during acute surgical stress. These data support the conclusion that vasopressin producing neurons and autonomic areas within the hypothalamus influenced by vagal afferents are activated during HF and are sensitive to 'acute surgical stress' and may contribute to the elevated levels of vasopressin and sympatho-excitation commonly observed in heart failure.

Animals↗
PubMed2000

[Clinical value of scintigraphy for gastrointestinal bleeding. Experiences in a large community hospital].

BACKGROUND AND OBJECTIVE: In the majority of cases of gastrointestinal bleeding the site and cause can be determined by gastroscope. If this is unsuccessful, radiological and nuclear-medical tests are available. This study was undertaken to determine the value of scintigraphy in diagnosing of the site of gastrointestinal bleeding. PATIENTS AND METHODS: The data on 155 patients who, between 1984 and 1988, had undergone 161 scintigraphies (with 99mTc-labelled erythrocytes, 5 with 99mTc-Sn colloid) were retrospectively analysed. The results were compared with other diagnostic tests that had been performed, with the definitive diagnosis and, where applicable, the findings at surgery. RESULTS: 78 scintigrams (47%) provided positive results. The site of bleeding had been demonstrated ca. 20 hours after the diagnostic studies had begun. In 47 of the cases the diagnosis was confirmed by additional tests. The intestine was the most common site of bleeding. Localization of the source of bleeding by scintigraphy and other diagnostic tests succeeded in 34 cases, with a 82% concordance between the tests. No bleeding was demonstrated in 88 scintigrams (53%), including all those done with Sn-colloid. In 13 cases the final diagnosis suggested that there had been no previous bleeding and in 43 cases the source of bleeding could not be determined. In 32 scintigraphically negative cases the source of bleeding was demonstrated by other tests. But only 2 of the 13 angiograms and none of the 33 double-contrast studies of the small intestine gave positive results. Among the total number of cases in which bleeding was demonstrated, scintigraphy had a sensitivity of 71%. CONCLUSION: Because of the long duration of observation, scintigraphy with 99mTc-labelled erythrocytes proved superior to other diagnostic tests in the demonstration of the bleeding. By localizing the source of bleeding in a definite part of the gastrointestinal tract, scintigraphy points the way to choosing other diagnostic methods or treatment. If the initial endoscopy has failed, scintigraphy, a method of low invasiveness, should be included when further tests are planned.

Angiography↗
PubMed2000

Commentary: using the convection-dispersion model and transit time density functions in the analysis of organ distribution kinetics.

The convection-dispersion model and its extended form have been used to describe solute disposition in organs and to predict hepatic availabilities. A range of empirical transit-time density functions has also been used for a similar purpose. The use of the dispersion model with mixed boundary conditions and transit-time density functions has been queried recently by Hisaka and Sugiyama in this journal. We suggest that, consistent with soil science and chemical engineering literature, the mixed boundary conditions are appropriate providing concentrations are defined in terms of flux to ensure continuity at the boundaries and mass balance. It is suggested that the use of the inverse Gaussian or other functions as empirical transit-time densities is independent of any boundary condition consideration. The mixed boundary condition solutions of the convection-dispersion model are the easiest to use when linear kinetics applies. In contrast, the closed conditions are easier to apply in a numerical analysis of nonlinear disposition of solutes in organs. We therefore argue that the use of hepatic elimination models should be based on pragmatic considerations, giving emphasis to using the simplest or easiest solution that will give a sufficiently accurate prediction of hepatic pharmacokinetics for a particular application.

Algorithms↗
PubMed2000

Difficult airway management: comparison of the Bullard laryngoscope with the video-optical intubation stylet.

PURPOSE: To evaluate, whether the video-optical intubation stylet (VOIS) was more successful for difficult tracheal intubation than the Bullard laryngoscope (BL). METHODS: An intubation mannequin head was modified so that, using a Macintosh blade size 3, only the epiglottis was visible at direct laryngoscopy, representing a grade III laryngoscopic view. Forty anesthesiologists attempted tracheal intubation using each technique. Tracheal intubation with the Bullard laryngoscope was performed using the attached non-malleable intubating stylet preloaded with an endotracheal tube. The video-optical intubation stylet inserted into an endotracheal tube was used with direct laryngoscopy. During conventional laryngoscopy, the video-view from the stylet tip allowed the tracheal tube to be guided behind the epiglottis into the trachea. Ten attempts with each technique were performed by each anesthesiologist in randomized order. Intubation time, and failed intubation (> 60 sec/esophageal intubation) were recorded. The operators assessed the degree of difficulty of each method using a Likert-scale. RESULTS: Mean intubation time (19.2+/-4.5 sec for the BL and 18.8+/-4.6 sec for the VOIS) was almost the identical. The video-optical intubation stylet was associated with fewer failed intubations (8 vs. 41; P<0.005) and had a lower degree of difficulty (1.7+/-0.65 for the VOIS and 2.6+/-0.74 for the BL; P<0.0001). No correlation was found between the anesthesiologist's experience and mean intubation time, estimated degree of difficulty or number of unsuccessful intubation. CONCLUSION: The video-optical intubation stylet was a more effective and simpler intubation device to facilitate difficult tracheal intubation than the Bullard laryngoscope.

Epiglottis↗
PubMed2000

Video-intuboscopic monitoring of tracheal intubation in pediatric patients.

PURPOSE: To evaluate the efficacy of video-intuboscopic monitoring during orotracheal intubation in a pediatric anesthesia teaching unit. METHODS: In 100 pediatric patients direct laryngoscopy performed by residents or nurse anesthetists was monitored on a video display using a flexible, ultralight video-endoscopic system (O.D. 2.8 mm/length 1.8 m) within the endotracheal tube (ETT). Best direct laryngoscopic view was assessed by the intubator. The instructor observed the intubation procedure on the video display and noted number of intubation attempts, best laryngoscopic monitor view, tube passage through the larynx and final tube position. If required he gave instructions or corrections. After removal of the laryngoscope, tracheal tube position was adjusted using the monitor view. Difficulties attributed to the fibreoptic endoscope during intubation and removal from the ETT were recorded. RESULTS: The trachea was successfully intubated at the first attempt in all patients. The supervisor detected one esophageal and 12 endobronchial intubations that were immediately corrected before starting ventilation. Final visualized endotracheal tube adjustment above the carina was possible in all patients except in one with copious tracheal secretions. Compared with direct laryngoscopy the video display provided an improved view of the vocal cords during intubation. In six patients direct laryngoscopy was difficult but the tracheas were intubated using the monitor view. No difficulties with the equipment were encountered except that the black coated endoscope compromised recognition of the black ETT depth-markings in small tubes. CONCLUSIONS: Video-intuboscopic monitoring is a useful monitor of tracheal intubation. "The improved view of the cords may provide assistance during difficult laryngoscopy.

Adolescent↗
PubMed2000

Syringe size and flow rate affect drug delivery from syringe pumps.

PURPOSE: To evaluate the effect of syringe size and infusion rate on drug delivery after vertical displacement of syringe pumps. METHODS: Four syringes (10 ml, 20 ml, 30 ml, 50 ml) were studied at three infusion speeds (2 ml x hr(-1), 1 ml x hr(-1) and 0.5 ml x hr(-1)). Fluid delivery was measured gravimetrically using an electronic balance. Aspiration volume (amount of fluid retracted into the syringe-infusion line assembly) and zero-drug delivery time (time between the lowering of the syringe pump and reattainment of the initial weight) were determined after lowering the syringe pump 130 cm or 50 cm. Then, infusion bolus was measured after elevating the pump to its initial position. Syringe compliance was calculated from the occlusion release bolus at an occlusion pressure of 300 mmHg. RESULTS: Zero-drug delivery time, aspiration volume and infusion bolus increased with syringe size (P < 0.0001). At 0.5 ml x hr(-1), a zero-drug delivery time of 29.7 +/- 0.6 min was recorded for the 50 ml syringe and 5.5 +/- 0.15 min for the 10 ml syringe. As infusion rates increased, zero-drug delivery times decreased following a 1/x ratio. Zero-drug delivery time highly correlated with calculated syringe compliance (Pearson's r = 0.97, P < 0.001), which was closely related to syringe plunger area (R2 = 0.93, P < 0.001). CONCLUSIONS: Vertical displacement of syringe pumps causes flow irregularities which correlate directly with syringe size and indirectly with infusion rate. Extreme vertical maneuvering of syringe pumps should be avoided. Infusion rates > or = 1 ml x hr(-1) and low-compliant, small syringes are recommended when highly concentrated drugs are administered.

Humans↗
PubMed2000

[Tropisetron for prevention of nausea and vomiting in children undergoing tonsillectomy and/or adenoidectomy].

BACKGROUND: Postoperative nausea and vomiting (PONV) after tonsillectomy is a common problem in children. Tropisetron is a new 5HT3 receptor antagonist and is successfully used in paediatric patients receiving cancer therapy. The aim of the study was to assess efficacy and safety of a single intravenous dose of tropisetron for prevention of PONV in paediatric patients at risk for postoperative vomiting. METHODS: In a randomised, double-blind, placebo-controlled trial, we studied 98 children aged 2-12 years undergoing tonsillectomy or adenotonsillectomy. Patients received placebo or tropisetron 0.1 mg (= 0.1 ml)/kg body weight immediately after induction of anesthesia. A standard general anesthetic technique (Sevoflurane/N2O/O2 without neuromuscular blockers or opioids) was used. Perioperative vital signs, grade of sedation and episodes of postoperative nausea and vomiting were recorded. RESULTS: No vomiting episodes occurred in 65.3% of the tropisetron treated patients compared to 34.7% of the placebo group (p = 0.0024). Only 10.2% of the tropisetron treated patients vomited more than 3 times compared to 22.4% of the control patients (p = 0.0004). The need for antiemetic rescue medication was significantly lower in the study group (10.4%) compared to 28.6% (p = 0.025). No significant adverse effects of the study medication were shown. CONCLUSION: A single intravenous prophylactic dose of tropisetron effectively reduces the incidence of PONV during the first 24 postoperative hours after tonsillectomy and/or adenoidectomy. Because of the low incidence of adverse effects, the prophylactic use of tropisetron seems to be safe and justified in paediatric surgical patients at high risk for postoperative vomiting.

Adenoidectomy↗
PubMed2000

[The effect of air within the infusion syringe on drug delivery of syringe pump infusion systems] .

Application of highly concentrated short-acting vasoactive drugs in the critically ill patient requires precisely working syringe pump systems for continuous intravenous drug delivery. We performed a bench study to investigate the consequences of small amounts of air entrapped within a 50-ml infusion syringe. In particular we studied the effect of entrapped air on drug delivery after moderate vertical displacement of the pump by 50 cm (e.g. in preparation for transport) and the effect on the time required to trigger the pressure alarm after occlusion of the infusion line. At a flow rate of 1 ml/h, lowering the syringe pump prolonged the zero-drug delivery time from (mean +/- SD) 4.1 +/- 0.8 min (without air) to 6.2 +/- 0.9 (with 1 ml air) and to 13.1 +/- 0.9 min (with 2 ml of air, p < 0.001 for all comparisons). Entrapping of 2 ml of air within the syringe resulted in a 2.6-fold prolongation of the occlusion alarm time after accidental occlusion of the infusion line and a 3-fold increase of the resulting infusion bolus after occlusion. Enclosed air within infusion syringes considerably affects the syringe compliance. It increases the susceptibility of constant drug delivery to vertical displacement of syringe pumps and impairs the occlusion alarm function. Therefore, any air in syringe of infusion pump systems should be carefully removed. To avoid infusion boluses of short-acting vasoactive drugs after accidental occlusions, the occluded infusion line should be released to ambient pressure first.

Air↗