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Biomedical subjects

M Schneider

Publications and source records attributed to M Schneider.

At least 19 recordsLinked to original sources
PubMed1992

Correlation between dihydropyrimidine dehydrogenase activity in peripheral mononuclear cells and systemic clearance of fluorouracil in cancer patients.

Dihydropyrimidine dehydrogenase (DPD) is the initial key enzyme in the catabolism of 5-fluorouracil (5-FU). We measured DPD activity in lymphocytes from 57 consecutive head and neck cancer patients while simultaneously monitoring 5-FU pharmacokinetics during 5-day, continuous infusion (1000 mg/m2/day) 5-FU therapy (82 cycles in total). The mean value for DPD activity was 0.186 +/- 0.068 (SD) nmol/min/mg of protein (range, 0.058 to 0.357). The mean value for 5-FU clearance was 2522.6 +/- 684.2 ml/min/m2 (range, 1052 to 4029). A significant linear correlation was observed between DPD activity and 5-FU clearance (r = 0.716, P less than 0.0001). DPD activity was poorly correlated to plasma uracil concentrations (r = -0.260, P = 0.0215). Likewise, plasma uracil concentrations were poorly correlated to 5-FU clearance (r = -0.214, P = 0.0595). In patients evaluated for more than one cycle (n = 18), there was large intrapatient variability in both DPD activity and 5-FU clearance. No significant difference was noted between cycles for DPD activity or 5-FU clearance (Kruskal-Wallis test). Monitoring DPD activity in lymphocytes may be useful in identifying patients at risk for altered 5-FU disposition.

Adult↗
PubMed1992

Crystal and molecular structure of human annexin V after refinement. Implications for structure, membrane binding and ion channel formation of the annexin family of proteins.

Two crystal forms (P6(3) and R3) of human annexin V have been crystallographically refined at 2.3 A and 2.0 A resolution to R-values of 0.184 and 0.174, respectively, applying very tight stereochemical restraints with deviations from ideal geometry of 0.01 A and 2 degrees. The three independent molecules (2 in P6(3), 1 in R3) are similar, with deviations in C alpha positions of 0.6 A. The polypeptide chain of 320 amino acid residues is folded into a planar cyclic arrangement of four repeats. The repeats have similar structures of five alpha-helical segments wound into a right-handed compact superhelix. Three calcium ion sites in repeats I, II and IV and two lanthanum ion sites in repeat I have been found in the R3 crystals. They are located at the convex face of the molecule opposite the N terminus. Repeat III has a different conformation at this site and no calcium bound. The calcium sites are similar to the phospholipase A2 calcium-binding site, suggesting analogy also in phospholipid interaction. The center of the molecule is formed by a channel of polar charged residues, which also harbors a chain of ordered water molecules conserved in the different crystal forms. Comparison with amino acid sequences of other annexins shows a high degree of similarity between them. Long insertions are found only at the N termini. Most conserved are the residues forming the metal-binding sites and the polar channel. Annexins V and VII form voltage-gated calcium ion channels when bound to membranes in vitro. We suggest that annexins bind with their convex face to membranes, causing local disorder and permeability of the phospholipid bilayers. Annexins are Janus-faced proteins that face phospholipid and water and mediate calcium transport.

Amino Acid Sequence↗
PubMed1992

School-based adolescent health care. Review of a clinical service.

OBJECTIVE: To provide recommendations regarding the establishment and maintenance of school-based clinics, based on analysis of data from a clinic located in a New York City high school. DESIGN: Review of demographic, medical, and psychosocial data collected during student visits. SUBJECTS: During 2 1/2 years, 1283 students were seen. The students were 53% girls and 47% boys; 65% black and 25% Hispanic; and 65% grades 9-10 and 35% grades 11-12. RESULTS: There were 7920 visits. Visits were for acute or chronic medical problems (44%), physical examinations and immunizations (25%), gynecologic or sexuality-related issues (17%), and mental health concerns (14%). Psychosocial characteristics of the 378 students who enrolled during the 1989-1990 academic year indicated that only 27% lived with both natural parents, 55% were foreign-born, 37% had repeated a grade at least once, 44% were sexually active, 13% drank alcohol, and 14% had past or present suicidal ideation. CONCLUSIONS: These data demonstrate that a school-based clinic can be involved in the management of a wide range of health care needs for large numbers of at-risk youth. In addition, school-based clinics can serve as a major site for the teaching of medical students and residents, and as a valuable resource for clinical research.

Adolescent↗
PubMed1992

Effect of bone size, not density, on the stiffness of the proximal part of normal and osteoporotic human femora.

Proximal femur fractures in the elderly lead to a high rate of hospitalization. In studying the operative treatment of such fractures, it is first necessary to understand the relationship between the morphologic properties of this part of the femur (related to both geometry and density) and its mechanical properties. Numerous investigations showed that femoral strength correlates with bone mass; however, the dimension of the bones was not taken into account. We measured the relationship between the stiffness of the proximal femur under physiologic load and its geometry and density. Conventional x-rays and quantitative computed tomography (QCT) were carried out on pairs of human cadaver femora. Eight pairs were instrumented with strain gauges. Bones were subjected to an eccentric load that simulates moderate weight bearing (single-leg stance), and the strain parallel to the bone axis was plotted as a function of the load applied. An apparent bone stiffness was calculated as the ratio between the strain gradient within the section and the load applied. Strong correlation was found between x-ray densitometry and QCT. The bone stiffness also correlates strongly with the geometry (area) and slightly with bone mass; however, an unexpectedly low correlation was found between stiffness and density. We chose stiffness as a mechanical parameter (not strength) because it describes the "normal" bone behavior under load. Our results clearly demonstrate that the cross-sectional size of the bones must be taken into account when establishing the relationship between the mechanical characteristics of the bone and its morphology. In accordance with previous predictions, our results support that bone loss due to osteoporosis is compensated for by an increase in bone diameter.

Absorptiometry, Photon↗
PubMed1992

Mutational analysis of the 'conserved region' of maize streak virus suggests its involvement in replication.

Maize streak virus as well as other geminiviruses contain a potential hairpin structure with the conserved sequence TAATATTAC in the loop. We assessed the possible involvement of this structure in replication and symptom induction of the virus. A series of insertion and deletion mutants were analyzed by agroinfection. Deletion of the hairpin or insertions in the conserved sequence abolished symptom development. Viral DNA could not be detected in the infected tissue. However, a mutant with a point mutation in the 'conserved' sequence, isolated after inoculation of maize plants with an insertion mutant, was able to replicate and to induce symptoms.

Agrobacterium tumefaciens↗
PubMed1992

Effect of tumor burden and route of administration on the immunotherapeutic properties of polyinosinic-polycytidylic acid stabilized with poly-L-lysine in carboxymethyl cellulose [Poly(I,C)-LC].

We examined the immunomodulatory and therapeutic activities of poly(I,C)-LC. Mice received a subcutaneous (s.c.) injection of sufficient numbers of MBL-2 lymphoma cells to produce in 1 week either a high or low tumor burden. A week after tumor cell injection, poly(I,C)-LC treatment was initiated; the agent was administered intraperitoneally (i.p.) at 5 mg/kg twice a week or at 2.5 or 0.5 mg/kg every day or as an intravenous (i.v.) injection at 0.5, 0.05, or 0.005 mg/kg three times a week. Poly(I,C)-LC treatment significantly increased antitumor effector cell functions in a variety of organs (including spleen, lungs, and peritoneum), as shown by increased killing of MBL-2 cells in vitro and increased tumor cell killing by natural killer cells and macrophages. Furthermore, prolongation of survival correlated with peritoneal macrophage tumoricidal activity when poly(I,C)-LC was given i.p. and with pulmonary effector cell function (including natural killer, cytolytic T-lymphocyte and macrophage tumoricidal activity) when the agent was administered i.v.

Animals↗
PubMed1992

Selective amplification and partial sequencing of cDNAs encoding G protein alpha subunits from cochlear tissues.

An approach utilizing the polymerase chain reaction (PCR) was devised to clone members of a family of cDNAs encoding the alpha subunit of G proteins in the cochlea. RNA was extracted from the whole cochlea of the mouse and from the organ of Corti or the lateral wall of the cochlea microdissected from the guinea pig cochlea. The RNA was reverse-transcribed to cDNA which was selectively amplified by PCR using degenerate primers corresponding to two conserved regions of the G protein coding sequence. PCR products were cloned into a plasmid for sequencing. The following seven cDNA clones of particular interest were obtained: three clones putatively coding for part of the alpha-subunit of a stimulatory G protein (Gs), one clone putatively coding for part of the alpha-subunit of an inhibitory G protein (Gi) and three clones putatively coding for part of the alpha-subunit of a transducin (Gi)-like protein. Possible functions in the cochlea of putative G proteins with alpha-subunits partly encoded by these cDNA clones are briefly discussed and future studies are suggested.

Amino Acid Sequence↗
PubMed1992

No effect of dose, hepatic function, or nutritional status on 5-FU clearance following continuous (5-day), 5-FU infusion.

One hundred and eighty seven patients (155 males, 32 females) with histologically proven and previously untreated head and neck cancer were entered in the study. A total of 222 cycles of therapy were analyzed (cisplatin 100 mg m-2 on day 1 and 5-day continuous intravenous infusion of 5-FU 550-1069 mg m-2 day-1, mean 875.5 mg m-2 day-1). Significant interpatient variability for various 5-FU pharmacokinetic parameters was observed including an almost ten-fold range in 5-FU clearance (5-FU Cl, ml min-1 m-2 = 791-7769, mean 2820.7). Log 5-FU Cl was not modified by 5-FU dose (r = -0.1034, P = 0.124, n = 222). Poor linear correlations between log 5-FU Cl and hepatic function tests were observed (respective r and P values for 222 cycles, log AST:0.0526, 0.4365; Log ALT: -0.1167, 0.0842; Log A1K. Phos.:0.154, 0.0214; Log GGT: 0.0652, 0.3436; Log LDH: -0.0984, 0.1563; Log bilirubin: 0.1278, 0.0601). The log 5-FU Cl was also poorly correlated with the serum concentration of various nutritional proteins (respective r and P values for 222 cycles, Albumin: 0.0110, 0.8714; prealbumin: -0.1067, 0.1129; transferrin: 0.0439, 0.5226). Laboratory data including indices of hepatic function and nutritional status cannot account for the interpatient variability in 5-FU disposition.

Blood Proteins↗
PubMed1992

Polymeric microballoons as ultrasound contrast agents. Physical and ultrasonic properties compared with sonicated albumin.

Air-filled polymeric microballoons were prepared with number-mean diameters of approximately 3 microns, volume-mean diameters of approximately 5 microns, and narrow particle-size distributions (standard deviation [SD] = 1.2 microns in number and SD = 2.0 microns in volume). More than 99% of the particles were below 8 microns. These particles were found to be highly echogenic for ultrasound, showing backscatter coefficients at 7.5 MHz, similar to the ones obtained with sonicated albumin microspheres. However, at 2.25 MHz, microballoons were less echogenic than albumin microspheres. These results are consistent with ultrasound attenuation measurements, which showed a maximum at 8 to 9 MHz for the microballoons compared with a reported value of 3.5 to 4.5 MHz for albumin microbubbles. Polymeric microballoons were found to be stable in plasma or under applied pressure as evidenced by unchanged particle concentration and echogenicity. Albumin microspheres were particularly unstable to applied pressure (150 mm Hg) and showed a rapid decrease in both particle counts and echogenicity.

Air↗
PubMed1992

Laryngospasm during transtracheal high frequency jet ventilation.

A 74-year-old woman developed severe cardiovascular depression during percutaneous transtracheal high frequency jet ventilation for laser surgery of the epiglottis. This was found to be caused by acute airway obstruction secondary to severe laryngospasm. We recommend profound neuromuscular blockade during percutaneous transtracheal jet ventilation, in order to prevent this complication.

Aged↗
PubMed1992

Vitiligo-like depigmentation and morpheas after specific intralymphatic immunotherapy for malignant melanoma.

We report the case of a patient with stage 2 malignant melanoma (MM), who received a specific immunotherapy consisting of intralymphatic injections of irradiated MM cells. She developed subsequently vitiligo-like leukoderma and several plaques of localized scleroderma. Simultaneously an increase in the patient's cytotoxic activity against MM cells was detected in vitro. The responsibility of immune phenomena and specific immunotherapy for the appearance of depigmentation and morpheas is discussed.

Aged↗
PubMed1992

Influence of sex and age on fluorouracil clearance.

PURPOSE: Currently, fluorouracil (5-FU) is one of the major drugs used in cancer chemotherapy. Several investigators, including ourselves, have demonstrated a link between abnormalities in 5-FU clearance (Cl) and the risk of developing more or less 5-FU-related toxicities. Age and sex are among the host factors that have been implicated in the pharmacokinetic variability of drugs. Presently, no data are available on the possible influence of sex and age on 5-FU Cl. PATIENTS AND METHODS: Three hundred eighty patients (mean age, 61.7 years; range, 25 to 91; 301 men and 79 women) with squamous cell carcinoma (sre) of the head and neck were treated in our institution between 1987 and 1991. 5-FU Cl was determined for a total of 1,092 chemotherapy cycles. Each cycle consisted of cisplatin and 5-day continuous intravenous infusion 5-FU (daily doses ranging between 365 and 1,224 mg/m2). RESULTS: 5-FU Cl values (L/h/m2) showed a wide dispersion for both men (median, 179; range, 29 to 739) and women (median, 155; range, 56 to 466). 5-FU Cl values were lower significantly for women compared with men (P = .0005). When adjusted for age and dose, the influence of sex on log Cl remained significant (P = .013). There was no evidence that age modified 5-FU Cl when adjusted for sex and dose. Interestingly, for both men and women, the oldest patients (greater than 70 years) maintained their ability to clear 5-FU with daily doses that ranged from 500 to 1,000 mg/m2. CONCLUSIONS: These data indicate that the capacities to clear 5-FU are lower in women compared with men and are not influenced by age. It would be of interest to know whether this sex-related difference in 5-FU Cl may be clinically relevant by considering both toxicity and tumor response to 5-FU treatment.

Adult↗
PubMed1992

Pharmacokinetics and pharmacodynamics of medroxyprogesterone acetate in advanced breast cancer patients.

PURPOSE: Medroxyprogesterone acetate (MPA) is one of the major drugs used in endocrine therapy for advanced breast cancer. However, its optimal dose still has not been clearly established. Response to treatment and drug-related side effects were analyzed as a function of plasma MPA concentrations during prolonged MPA treatment. PATIENTS AND METHODS: MPA plasma concentrations were measured (high-performance liquid chromatography [HPLC] assay) at steady state (Css min) in 129 patients (mean age, 63 years; range, 34 to 87) treated by MPA (86% were treated orally exclusively with daily doses ranging from 400 to 2,000 mg). RESULTS: A wide interpatient variability was noted in MPA Css min for the 70 patients who received 1,000 mg/d orally (median, 51 ng/mL; range, 10 to 269 ng/mL). Intrapatient analysis of the evolution of MPA Css min during prolonged treatment showed relative stability of MPA concentrations (mean CV, 20.6%). A weak but significant correlation was demonstrated between oral doses and MPA Css min (P = .016). Thirty-five percent of patients (45 of 129) developed MPA-related side effects that were associated with the highest plasma MPA concentrations; medians were 81 and 32 ng/mL for toxic and nontoxic treatments, respectively (P less than .001). Objective response was assessable in 55 patients who were treated by MPA exclusively. Plasma MPA concentrations were significantly different (P = .025) between patients with progressive disease (PD) (median, 46 ng/mL) and those with complete response (CR), partial response (PR), or stable disease (SD) (median 65 ng/mL). Comparison of CR plus PR versus SD versus PD showed only a tendency toward significant differences in MPA Css min (P = .07). Analysis of toxicity and response as a function of the oral dose did not show any significant relationship. These data suggested an optimal therapeutic window for MPA Css min located within 50 to 70 ng/mL. CONCLUSION: This study demonstrates that plasma MPA concentration, as opposed to the administered dose, is a determining factor for toxicity and response therapy [corrected].

Adult↗
PubMed1992

[Dihydropyrimidine dehydrogenase activity in lymphocytes: predictive factor for 5-fluorouracil clearance].

We previously have shown that pharmacokinetic monitoring of 5-fluorouracil (5-FU) could significantly improve the 5-FU therapeutic index when given in continuous venous infusion (Br J Cancer 59, 287-290, 1989). However, the more rational approach would be to find individual biological factors which could predict 5-FU clearance. Dihydropyrimidine dehydrogenase (DPD) is the initial enzyme in the catabolism of 5-FU. DPD activity was measured in 57 head and neck cancer patients receiving CDDP (100 mg/m2, day 1) plus 5-FU (1 g/m2/day x 5, day 2-day 6). DPD activity was measured in lymphocytes using a radioenzymatic assay (2.5 mM MgCl2, 250 microM NADPH, 20 microM 14C-5-FU) with separation of 14C-5-FU from 14C-5-FUH2 by HPLC coupled with a radiodetector. The average DPD activity measured in lymphocytes was 0.186 +/- 0.068 nmol/min/mg protein (range 0.058-0.357) and the average 5-FU clearance (Cl) was 2,523 +/- 684 ml/min/m2 (range 1,052-4,029). A significant linear correlation was demonstrated between DPD activity and 5-FU clearance (Cl = 1,099 + 7,580 DPD, r2 = 0.613, P < 0.0001). In patients evaluated for more than one cycle (n = 18), variations in 5-FU clearance were associated with corresponding variations in DPD activity. The individual determination of DPD activity measured in lymphocytes could be useful for identifying patients at risk for altered 5-FU pharmacokinetics and could be used to adjust the optimal 5-FU dose for each patient before starting the treatment.

Adult↗
PubMed1992

The nature and management of communication disorders in a rural area: the role of the community speech and hearing therapy workers.

Six hospitals where Community Speech and Hearing Therapy Workers (CWs) are working in Gazankula were visited. Firstly, data were collected from records, reports and case files over an 18 month period to determine the nature and prevalence of the communication disorders seen by the CWs. Secondly, the CWs were interviewed about their work situation, organisation of their time and intervention strategies used with communicatively disordered people in order to evaluate the efficacy of their work. Methodological issues requiring consideration when undertaking this type of research are discussed. The results are discussed in terms of the implications for course modifications as well as policy decisions within the profession of Speech and Hearing Therapy.

Communication Disorders↗