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Biomedical subjects

P Goldstein

Publications and source records attributed to P Goldstein.

At least 19 recordsLinked to original sources

Effects of dimethyl sulfone (DMSO2) on early gametogenesis in Caenorhabditis elegans: ultrastructural aberrations and loss of synaptonemal complexes from pachytene nuclei.

The free-living nematode Caenorhabditis elegans has been used extensively for studies in developmental and reproductive genetics. Recently, toxicologic studies have been initiated using specific sex chromosome mutations. In the present study, high incidence of male (him) mutants, him-5 and him-8, were treated with dimethyl sulfone (DMSO2), the primary metabolite of dimethyl sulfoxide (DMSO). In addition to differential effects on X-chromosome nondisjunction, loss of viability and fertility were observed. Much lower concentrations of DMSO2 were required to elicit the same aberrational effects characteristic of DMSO (1); thus, the toxicity of the former was significantly more potent. The observed decrease in life span was associated with senescent morphology of meiotic prophase nuclei, such that nuclei from young and old specimens could not be differentiated. Aging in oocytes at pachytene is characterized by nucleo-cytoplasmic aberrations, increased density of the nucleoplasm and cytoplasm, and decrease in numbers of mitochondria. Increasing concentrations of DMSO2 resulted in a corresponding decrease in fertility and increased production of abnormal gametes. At DMSO2 concentrations higher than 1.0%, synaptonemal complexes (SC) were absent from pachytene nuclei; thus, effective pairing and segregation of homologous chromosomes was prohibited. Since the SC is essential for regulating pairing and subsequent separation of bivalents, the lack of an SC explains the loss of fertility, due to the production of unbalanced gametes, observed in DMSO2-treated specimens.

Animals

[Hydatid cyst of the kidney in the child].

Three pediatric cases of hydatic cyst of the kidney are reported. This is a very rare condition in children. Usually, the presentation is a cystic space-occupying lesion of the kidney. Several diagnostic methods are available but it is stressed that ultrasonography may be sufficient. Surgical treatment is still necessary.

Child

Ventriculoamniotic shunt for treatment of hydrocephalus in one of twins: medical, ethical and legal considerations.

One of a pair of preterm twin fetuses was identified as having progressive hydrocephalus. After an extensive evaluation of the parents and both fetuses, a ventriculoamniotic shunt was placed. The affected twin, despite multiple additional neonatal procedures, has done well as matched against her normal twin sister. Both children are well 4 years after the surgery. The case presented a remarkable complexity of medical, ethical and legal issues which are presented.

Adult

[Alcohol and psychotropic drugs in fatal traffic accidents (the Nord-Pas-de-Calais region, France)].

UNLABELLED: Consumption of alcohol and tranquilizers reaches a very high level in France. Studies about simultaneous alcohol and psychotropic drugs involvement in motor related fatalities have never been described in this country. A retrospective study was done on 482 fatalities broken down by drivers and pedestrians within one year (1987) in Région Nord-Pas de Calais (France). METHOD: 132 cases met the criteria for complete study. Blood samples obtained at the time of death were analysed for alcohol (BAC) by gas-chromatography and assayed for barbiturates (BA), benzodiazepines (BE) and tricyclic antidepressants (TA) by Emit. RESULTS: Out of 132 fatalities there were 86% men (mean age 38.5 years) and 14% women (mean age 46 years). 57% belonged to the working population. Of the fatalities, 38% occurred from Friday 8 p.m. to Sunday 12 p.m. We distinguished 3 categories: pedestrians (18.2%), 2-wheel vehicles (19%) and 4-wheel vehicles (62.8%). Alcohol involvement is given in Table 2. [table: see text] Notice that 53% were above the legal limit (0.8 g/l) and 34.8% had no alcohol. Psychotropic drugs were detected in 10.6% of the cases (Table 3). [table: see text] BZ were found in 50% of men and 100% of women. drugs and alcohol were present simultaneously in 8.3% of the individuals. Results are in % of total in Table 4: [table: see text] Positive BAC and positive drugs are not related. No significant difference was found in the distribution of alcohol between positive or negative drugs findings. Our results are consistent with those described by North-American authors, but largely superior to those from French or other studies done only on injured persons.

Accidents, Traffic

Initial experience with SPECT imaging of the brain using I-123 p-iodoamphetamine in focal epilepsy.

Nineteen patients with complex partial seizures refractory to medical treatment were examined with routine electroencephalography (EEG), video EEG monitoring, computed tomography or magnetic resonance imaging, neuropsychological tests and interictal single photon emission computed tomography (SPECT) with I-123 iodoamphetamine (INT). In 18 patients, SPECT identified areas of focal reduction in tracer uptake that correlated with the epileptogenic focus identified on the EEG. In addition, SPECT disclosed other areas of neurologic dysfunction as elicited on neuropsychological tests. Thus, IMP SPECT is a useful tool for localizing epileptogenic foci and their associated dynamic deficits.

Adolescent

A meta-analysis of randomized control trials of progestational agents in pregnancy.

The continued use of progestational agents in attempts to achieve a normal outcome of pregnancy in women with a 'high-risk' pregnancy (previous miscarriage, stillbirth or present preterm labour) prompted this meta-analysis of randomized control trials of such therapy. Of 20 trials of a progestogen 15 had combinable data. Combined comparisons, using odds ratios with confidence intervals, were made of the rates of livebirths at term or preterm and the sum of term and preterm deliveries, miscarriages, stillbirths and neonatal deaths. All but one comparison failed to show a significant benefit. Only the preterm delivery versus the term delivery comparison approached statistical significance. There were average deficiencies of quality apparent in the studies, and a test for heterogeneity among the studies was positive, but these caveats do not diminish the conclusion that progestogens should not be used outside of randomized trials at present. If trials are done, they should include only women with demonstrated hormonal abnormalities who are carrying a live fetus as shown by ultrasonography.

Abortion, Spontaneous

Quality assurance and utilization review in a health insuring organization. The HealthPASS example.

HealthPASS is a Philadelphia-based health insurance organization (HIO), owned and operated by the Penn Health Corporation, a subsidiary of Maxicare, the large for-profit health maintenance organization (HMO) company based in California. In a contractual agreement with the Pennsylvania Department of Public Welfare (DPW), Maxicare contracts primary care physician services on a capitated basis, and other services on a fee basis, to about 96,000 Medicaid enrollees in certain zip codes in Philadelphia. Although HealthPASS does not provide care directly, it contracts with providers for these medical services. HealthPASS serves a primarily poor, minority, and inner city population with high rates of drug abuse, alcoholism, and mental illness. Currently, the enrollees are served by a network of providers including more than 40 participating hospitals and over 500 primary care providers (PCPs) in the community. HealthPASS is unique as previous HIOs in Kentucky and Arizona both failed. This paper describes the quality assurance and utilization review (QA-UR) system implemented by HealthPASS with specific examples of case discussions and a detailed look at the structure and function of the internal review process. Before outlining the QA-UR system, a brief history is provided of the recent controversial trend toward managed care for Medicaid recipients, as there have been marked failures in this arena nationally. The HealthPASS system is described--what it is, how it is staffed, who it serves, and the health services it offers.(ABSTRACT TRUNCATED AT 250 WORDS)

Health Maintenance Organizations

Resistance to lethal levels of diethylstilboestrol in the nematode Caenorhabditis elegans.

Concentrations of diethylstilboestrol (DES) exceeding 100 microM are normally fatal to all living tissues due to inhibition of cell division and other cell processes. However, in Caenorhabditis elegans, with increasing levels of DES, there was an observed decrease in fertility and fecundity (99%), although a small percentage of the population (1%) survived concentrations as high as 400 microM DES. Uptake studies, using tritiated-DES liquid scintillation and ELISA analysis, revealed that uptake exhibited saturation at 100 microM and levels exceeding 100 microM resulted in no further biological response. Thus, ultrastructural morphology and viability of the organism was unchanged after the DES saturation point.

Animals

BioGraf 3D: an algorithm for optimization and graphical representation of nuclear structure spatial distributions.

BioGraf 3D is a computer algorithm for rapid three dimensional visualization and analysis of digitized three dimensional biological data to aid in the subsequent generation of models of nuclei or cells. This graphically oriented program permits unlimited three dimensional perspective viewpoints of data in onscreen single frame, zoom or stereo forms. Analysis of data is enhanced by an optimization problem solution which determines viewpoint coordinates whereby maximum clustering of preselected structures is achieved. Mathematical representation of the transformations and optimization is presented in detail. Biograf 3D is written in the C programming language for IBM and compatible personal computers. In this study BioGraf 3D is utilized to examine the infrastructure of the nucleus and the spatial distribution of meiotic chromosomes in the hermaphroditic nematode Caenorhabditis elegans.

Algorithms

Electron microscopic autoradiographic analysis: evidence of RNA transcription along pachytene chromosomes of rad-4, him-4 and wild-type Caenorhabditis elegans.

Decondensed chromatin regions have been described along the pachytene chromosomes of Caenorhabditis elegans (Goldstein, 1985). Regions of similar appearance, but not in pachytene chromosomes, have been shown to be transcriptionally active in other organisms (Angelier et al., 1979; Nagl, 1985). Incorporation of tritiated-uridine and electron microscopy autoradiography were utilized, in the present study, to determine if RNA transcription occurred along meiotic chromosomes of C. elegans. This study presents new evidence that RNA transcription occurs in highly defined regions along pachytene bivalents.

Animals

Regional individual allergen based miniscreen to predict IgE-mediated airborne allergy.

A small panel of local individual regional allergens (miniscreen) tested in vitro by FAST was developed to evaluate the utility of screening for IgE-mediated airborne allergy. Using this miniscreen in a population of 125 subjects referred for evaluation of possible allergic respiratory disorders would have increased the accuracy of referral from 74.4% to 95.6%. The miniscreen correctly classified 119 of the 125 subjects. The miniscreen appears to be a potentially useful tool for the allergy specialist in the present medical climate.

Adolescent

Effects of dimethyl sulphoxide on early gametogenesis in Caenorhabditis elegans: ultrastructural aberrations and loss of synaptonemal complexes from pachytene nuclei.

In Caenorhabditis elegans, loss of viability and fertility was observed after treatment with dimethyl sulphoxide (DMSO). The decrease in life span is associated with senescent morphology of meiotic prophase nuclei, such that nuclei from young and old specimens cannot be differentiated. Aging in oocytes at the pachytene stage of meiotic prophase is characterized by nucleo-cytoplasmic aberrations, increased density of the nucleoplasm and cytoplasm and decrease in numbers of mitochondria (Goldstein and Curis, 1987). Increasing concentrations of DMSO result in decrease in fertility and increased production of abnormal gametes. At DMSO concentrations higher than 5.0%, synaptonemal comlexes (SC) are absent from the nuclei, thus, effective pairing and segregation of homologous chromosomes is not possible. The absence of SCs may be the result of: (1) a premeiotic colchicine-like effect which influences pairing of chromosomes; (2) changes in the structure of the DNA due to DMSO binding that results in changes in expression of the DNA; and (3) changes in temporal DNA synthesis in response to DMSO. Since the SC is essential for regulating pairing and subsequent separation of bivalents, the lack of an SC explains the loss of fertility, due to the production of unbalanced gametes, observed in DMSO treated specimens.

Animals

Age-related changes in the meiotic chromosomes of the nematode Caenorhabditis elegans.

Comparison of pachytene karyotypes from old and young wild-type hermaphrodites and males and the mutant him-5 were made following three-dimensional reconstruction of serial ultrathin sections. Age-related changes included: (1) differential condensation of chromatin with increased variance in length of chromosomes; and (2) increased variation in nuclear and nucleolar volume along with increased density of the nucleoplasm. Synaptonemal complex (SC) fine structure was not altered in the nuclei from older specimens. Attachment of only one end of the SC to the nuclear envelope (NE), common to all nematodes, was present at all ages in the wild-type hermaphrodite and male, however, clustering of the SC ends was present in nuclei from older him-5 hermaphrodites. Condensed chromatin along the SC formed a continuous mass except in those small regions where the chromatin had a granular appearance and was decondensed. Such regions, termed "Disjunction Regulator Regions" (DRR), have been implicated in the regulation of X-chromosome segregation (Goldstein, P., The synaptonemal complexes of Caenorhabditis elegans: Pachytene karyotype analysis of the Dp 1 mutant and disjunction regulator regions. Chromosoma, 93 (1985) 177-182). In the present study, it was observed that the number of DRRs in the nucleus change with aging. In the wild-type hermaphrodite and male, the rate of X-chromosome non-disjunction increases with age which correlates with a decrease in the number of DRRs to the point where they are absent in older males. In him-5, the DRRs increase in number with advanced age, which correlates with an observed decrease in the rate of X-chromosome non-disjunction.

Animals

Multiple synaptonemal complexes (polycomplexes): origin, structure and function.

Multiple synaptonemal complexes (polycomplexes) (PC) are similar in structure to synaptonemal complexes (SC) and are also highly conserved through evolution. They have been described in over 70 organisms throughout all life forms. The appearance of PCs are restricted to meiotic and germ-line derived tissues and are most commonly present after SC formation. However, in a number of animals and plants, both extra- and intranuclear PCs are present during premeiotic and pre-pachytene stages. The structure and biochemical composition of PCs is similar to SCs that the basic unit is tripartite, consisting of two lateral elements and a central region (in which transverse elements are located), and the dimensions of such structures are equivalent. Stacking of SC subunits, while still maintaining equivalent SC dimensions, creates a problem since the lateral elements (LE) would then be twice as thick in the PC as compared to the SC. Recently, it has been shown that the LE of the SC is actually multistranded, thus the LE of each subunit of the PC is half as thick as its counterpart in the SC.

Animals

Halothane and enflurane metabolite elimination during anaesthesia in man.

Ten patients received 0.75% halothane and 12 received 1.5% enflurane for 1 h in a 50:50 nitrous oxide/oxygen mixture. Plasma and end-tidal concentrations were measured by gas-liquid chromatography (GLC) using the head-space method. Fluoride ion assay was performed with a specific electrode by HPLC, trifluoroacetate and oxalate ion levels were determined after extraction, by GLC. Comparison of the evolution of the non-metabolized forms showed that enflurane was more rapidly eliminated: by the third hour after starting, enflurane plasma concentrations were 3.6 micrograms ml-1 compared with 6.3 micrograms ml-1 for halothane. Fluoride plasma levels were nearly constant in the halothane group, but a significant increase up to 14.9 microM was observed in the enflurane group. The ratio of 10:1 in peak urinary concentrations was linked to the molecular structure and the metabolic pathways.

Adult

'Metamorphosis': computer-assisted rotational analysis and interspatial distribution of nuclear structures from serial ultrathin sections.

'Metamorphosis' is a group of computer programs designed to permit rapid three-dimensional analysis and generation of models of nuclei cells from digitized data. Infinite exterior views are possible using the rotation program and the user has the added ability to enter the object and peer out. This permits analysis of structural associations from any perspective. Since many chromosome associations cannot be abstracted without a computer, using rotation and cluster analysis reveals obscure relationships. This concept becomes important when proposing theories involving interactions between two or more objects. The program is written in BASICA and designed for use on IBM-compatible personal computers equipped with a digitizer. Three-dimensional transformations are accomplished via matrix manipulation which permits rapid generation of new images.

Animals