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Biomedical subjects

M Schwartz

Publications and source records attributed to M Schwartz.

At least 271 records · Page 15Linked to original sources
PubMed1996

Measuring effectiveness of eye movement desensitization and reprocessing (EMDR) in non-clinical anxiety: a multi-subject, yoked-control design.

Twenty-eight subjects from a university's subject pool were paired on sex, age, severity, and type of stressful or traumatic incident. One subject in each pair was selected to receive EMDR; the experimental partner spent the same amount of time receiving a visual (non-movement) placebo. Subjective units of discomfort (SUD) scores and physiological measurements were taken prior to and following treatment. Analysis of physiological measurements and self-reported levels of stress were performed within and between each group. While the EMDR group showed significant reductions of stress, EMDR was no better than a placebo. This suggests EMDR's specific intervention involving eye movement may not be a necessary component of the treatment protocol.

Adult↗
PubMed1996

Preclinical evaluation of brimonidine.

Preclinical studies of brimonidine show that it is a potent alpha 2-adrenoceptor agonist that is 1000-fold more selective for the alpha 2-vs. the alpha 1-adrenoceptor, and is 7-12-fold more alpha 2-selective than clonidine and 23- to 32-fold more alpha 2-selective than apraclonidine (p-aminoclonidine). Brimonidine decreased intraocular pressure (IOP) in various animal models but, unlike apraclonidine, brimonidine was not mydriatic. The site and pharmacology of the IOP response depends on the animal species. In rabbits, the IOP response to brimonidine is mediated by an ocular alpha 2-adrenoceptor while in monkeys, a central nervous system (CNS) 'imidazoline' receptor appears to be involved. Brimonidine decreased IOP by suppressing the rate of aqueous humor flow and enhancing uveoscleral outflow. Topical brimonidine resulted in posterior segment drug levels adequate to activate alpha 2-adrenoceptors, but was not vasoconstrictive in a model designed to assess the vasoactivity of the human retinal microvasculature. Brimonidine protected the rat optic nerve from secondary damage following mechanical injury to the optic nerve and was nontoxic in an array of experiments designed to evaluate ocular and organ toxicity. Taken together, the high alpha 2-adrenoceptor selectivity, ocular hypotensive efficacy, retinal bioavailability and neuroprotective properties make brimonidine an important addition to the field of antiglaucoma agents.

Adrenergic alpha-Agonists↗
PubMed1996

Acid phosphatase: defining a role in androgen-independent prostate cancer.

OBJECTIVES: In multivariable analysis, post-therapy change in prostate-specific antigen (PSA) was shown to be the most significant factor predictive of survival in patients with androgen-independent prostate cancer. To refine the model, we studied the patterns of change in acid phosphatase, alkaline phosphatase, and lactate dehydrogenase after treatment. METHODS: One hundred seven patients with androgen-independent prostate cancer treated on seven different protocols in Memorial Sloan-Kettering Cancer Center were evaluated. For tumor-specific (acid phosphatase and PSA) and nontumor-specific (alkaline phosphatase and lactate dehydrogenase) enzymes, a minimum 50% or 80% decrease from baseline documented on three separate occasions a minimum of 6 weeks apart was required to categorize a patient as having a decline. RESULTS: Nineteen patients (18%) had either a 50% decline in acid phosphatase or PSA, of whom 13 (68%) had a decline of both markers. Six (32%) patients showed discordance between the two parameters. Declines in PSA level typically preceded declines in acid phosphatase levels. The median survival of patients showing declines in both markers exceeded that of patients showing declines in PSA alone by 1 year. Although baseline measurements of alkaline phosphatase or lactate dehydrogenase did add additional prognostic information, post-therapy changes did not. CONCLUSIONS: Post-therapy declines in PSA and acid phosphatase represent reproducible endpoints for clinical trials in androgen-independent disease. The requirement of a repeated and parallel decline in both markers may improve the results observed by monitoring declines in PSA alone. Monitoring the two parameters may allow the development of models that can be used as surrogate endpoints for response and survival in a disease in which reproducible measurements of response are lacking.

Acid Phosphatase↗
PubMed1996

Complete transection of rat optic nerve while sparing the meninges and the vasculature: an experimental model for optic nerve neuropathy and trauma.

In this study we present a method to achieve a complete transection of optic nerve axons in adult rat, while preserving the vasculature and retaining the continuity of the meninges. Under deep anesthesia, the optic nerve of adult rat is exposed. Using specially designed instruments built from disposable glass microsampling pipettes, a small opening is created in the meninges of the optic nerve, 2-3 mm behind the eye globe. A glass dissector is introduced through the opening and is used to cut all the axons through the whole width of the nerve. Complete transection of the optic nerve axons was achieved, while retaining the continuity of the meninges and avoiding damage to the nerve's vascular supply. Transection was confirmed by transillumination showing a complete gap in the continuity of the nerve axons, and by both morphological and electrophysiological criteria. Nerve transection performed by the conventional technique leads to neuroma formation and hampers regeneration. Crush injury may cause nerve ischemia, which is detrimental to axonal recovery. Both of these disadvantages are avoided by the method of transection presented here. The opening created in the 'meningeal tube' can be used to inject substances that may be of benefit in recovery, rescue and/or regeneration of the injured axons. The model is particularly suitable for in vivo studies on nerve regeneration, and especially for screening of putative therapeutic agents.

Animals↗
PubMed1996

HU-211, a nonpsychotropic cannabinoid, produces short- and long-term neuroprotection after optic nerve axotomy.

HU-211 is a novel synthetic analog of tetrahydrocannabinol that was recently shown in animal models to be nonpsychotropic. In this study we show that HU-211 can potentially be used as a neuroprotective compound in the CNS. Using a calibrated crush injury of adult rat optic nerve, we show that HU-211 can reduce injury-induced metabolic and electrophysiological deficits. Energy metabolism was monitored by measuring the intramitochondrial nicotine-amine adenine dinucleotide redox state hourly for 6 h after injury and treatment. Electrophysiological activity was assessed by compound action potential and visual evoked potential response. Beneficial effects were dose-dependent, being optimal at 7 mg/kg, administered intraperitoneally. The time window during which treatment was effective was found to be from the time of injury for at least 5 h, with treatment most effective at the time of injury. These results strongly suggest that HU-211, given immediately after CNS injury at the optimal dosage, may possess neuroprotective activities.

Action Potentials↗
PubMed1996

A ninth locus (RP18) for autosomal dominant retinitis pigmentosa maps in the pericentromeric region of chromosome 1.

We studied a large Danish family of seven generations in which autosomal dominant retinitis pigmentosa (adRP), a heterogeneous genetic form of retinal dystrophy, was segregating. After linkage had been excluded to all known adRP loci on chromosomes 3q, 6p, 7p, 7q, 8q, 17p, 17q and 19q, a genome screening was performed. Positive lod scores suggestive of linkage with values ranging between Z = 1.58-5.36 at theta = 0.04-0.20 were obtained for eight loci on proximal 1p and 1q. Close linkage without recombination and a maximum lod score of 7.22 at theta = 0.00 was found between the adRP locus (RP18) in this family and D1S498 which is on 1q very near the centromere. Analysis of multiply informative meioses suggests that in this family D1S534 and D1S305 flank RP18 in interval 1p13-q23. No linkage has been found to loci from this chromosomal region in six other medium sized adRP families in which the disease locus has been excluded from all known chromosomal regions harbouring an adRP gene or locus suggesting that there is (at least) one further adRP locus to be mapped in the future.

Base Sequence↗
PubMed1996

Transplantation of activated macrophages overcomes central nervous system regrowth failure.

Macrophages have long been known to play a key role in the healing processes of tissues that regenerate after injury; however, the nature of their involvement in healing of the injured central nervous system (CNS) is still a subject of controversy. Here we show that the absence of regrowth in transected rat optic nerve (which, like all other CNS nerves in mammals, cannot regenerate after injury) can be overcome by local transplantation of macrophages preincubated ex vivo with segments of a nerve (e.g., sciatic nerve) that can regenerate after injury. The observed effect of the transplanted macrophages was found to be an outcome of their stimulated activity, as indicated by phagocytosis. Thus, macrophage phagocytic activity was stimulated by their preincubation with sciatic nerve segments but inhibited by their preincubation with optic nerve segments. We conclude that the inability of nerves of the mammalian CNS to regenerate is related to the failure of their macrophages recruited after injury to acquire growth-supportive activity. We attribute this failure to the presence of a CNS resident macrophage inhibitory activity, which may be the biochemical basis underlying the immune privilege of the CNS. The transplantation of suitably activated macrophages into injured nerves may overcome multiple malfunctioning aspects of the CNS response to trauma, and thus may be developed into a novel, practical, and multipotent therapy for CNS injuries.

Animals↗
PubMed1996

Liposomal prostaglandin E1 in acute respiratory distress syndrome: a placebo-controlled, randomized, double-blind, multicenter clinical trial.

OBJECTIVE: To evaluate the safety and efficacy of liposomal prostaglandin E1 (TLC C-53) in the treatment of patients with the acute respiratory distress syndrome (ARDS). DESIGN: Randomized, prospective, multicenter, double-blind, placebo-controlled, phase II clinical trial. SETTING: Eight community and university-affiliated hospitals in the United States. PATIENTS: Twenty-five patients with ARDS. INTERVENTIONS: Patients were prospectively randomized in an unbalanced ratio within each site to receive either TLC C-53 (n = 17) or placebo (n = 8). Study drug was infused intravenously over 60 mins every 6 hrs for a 7-day period, starting at a dose of 0.15 micrograms/kg/hr. The dose was increased every 12 hrs until the maximal dose (3.6 micrograms/kg/hr) was attained, intolerance to further increases developed, or invasive monitoring was discontinued. Patients received standard, aggressive, medical/surgical care throughout the trial. MEASUREMENTS AND MAIN RESULTS: Outcome measurements were Pao2/FI0(2), dynamic pulmonary compliance, ventilator dependence on day 8, and 28-day all-cause mortality rate. At baseline, the distribution of variables describing Lung Injury Scores, Acute Physiology and Chronic Health Evaluation II scores, Pao2/FI0(2), pulmonary compliance, and time from onset of ARDS to first dose of study drug was similar between patients in the TLC C-53 and placebo treatment groups. On day 8, all eight patients given placebo required mechanical ventilation, while eight of 17 patients given TLC C-53 were healthy enough to be removed from the ventilator (p = .03). Improvement in PaO2/FIO2 during the initial 8-day study period was greater in patients receiving TLC C-53. This trend achieved statistical significance on day 3, when the increase in PaO2/FIO2 from baseline was 82.5 +/- 14.6 in the TLC C-53 group compared with 28.3 +/- 22.1 in the placebo group (p = .05). By day 8, lung compliance also increased from baseline significantly more in TLC C-53 patients than in placebo patients (5.7 +/- 1.7 vs -1.5 +/- 1.8 mL/cm H2O; p = .01). The 28-day mortality rate was 6% (1/17 patients) in the TLC C-53 group and 25% (2/8 patients) in the placebo group (p = .23). Drug-related adverse events were reported in 82% of the patients receiving TLC C-53 compared with 38% of the placebo group, with half of the adverse events in the TLC C-53 group being localized infusion site irritation. TLC C-53 was hemodynamically well tolerated, with transient hypotension occurring in three patients. CONCLUSIONS: In patients with ARDS, TLC C-53 was associated with improved oxygenation, increased lung compliance, and decreased ventilator dependency.

Adult↗
PubMed1996

Drainage of CSF through lymphatic pathways and arachnoid villi in sheep: measurement of 125I-albumin clearance.

We investigated lymphatic drainage pathways of the central nervous system in conscious sheep and quantified the clearance of a cerebrospinal fluid (CSF) tracer into lymph and blood. In the first group of studies, 125I-HSA was injected into the lateral ventricles of the brain or into lumbar CSF and after 6 h, various lymph nodes and tissues were excised and counted for radioactivity. Multiple lymphatic drainage pathways of cranial CSF existed in the head and neck region defined by elevated 125I-HSA in the retropharyngeal/cervical, thymic, pre-auricular and submandibular nodes. Implicated in spinal CSF drainage were mainly the lumbar and intercostal nodes. In a second group of experiments, multiple cervical vessels and the thoracic duct were cannulated and lymph diverted from the animals. Transport of tracer through arachnoid villi was taken from recoveries in venous blood. Following intraventricular administration, the 6 h recoveries of 125I-HSA in the lymph (sum of cervical and thoracic duct) and blood were 8.2% +/- 3.0 and 12.5% +/- 4.5 respectively and at 22 h, 25.1% +/- 6.9 and 20.8% +/- 4.1 respectively. When 125I-HSA was injected into lumbar CSF, the 6 h recoveries of tracer in thoracic duct and blood were 11.6% +/- 2.7 and 16.3% +/- 3.7 respectively. Total lymph and blood recoveries were not significantly different in any experiment. We conclude that the clearance of 125I-HSA from the CSF is almost equally distributed between lymphatic and arachnoid villi pathways.

Animals↗
PubMed1996

Variable clinical expression in a family with OI type IV due to deletion of three base pairs in COL1A1.

We have studied a family with autosomal dominant osteogenesis imperfecta (OI) type IV. Electrophoresis of collagen produced by cultured fibroblasts revealed a slower migrating population of collagen I. Cyanogen bromide peptide mapping localised the structural defect to the area of the alpha 1(1)CB3 peptide. Subsequent sequencing revealed a deletion of nucleotides 1964-1966 in exon 27 of COL1A1. By means of restriction enzyme analysis, the deletion could be detected in all affected family members. This in-frame deletion resulted in the removal of alanine-438 and Glu437Asp substitution in the pro alpha 1(I) collagen chain. Clinical variation was considerable among affected family members. The most consistent clinical features were reduced height and extraosseous manifestations of OI.

Cells, Cultured↗
PubMed1996

Psychological and social impact of carrier screening for cystic fibrosis among pregnant woman--a pilot study.

The aim of the current study was to assess the psychological and social impact of delta F508 carrier screening for cystic fibrosis among pregnant women. The impact of carrier screening was assessed in terms of anxiety, perception of health, reproductive decisions, retention of results, and sharing of information with relatives by two self-administered questionnaires sent to 160 women with a positive and 200 women with a negative test result. While no attempt was made to make women accept or decline testing, 22-28% of those tested found it difficult to reject the test when offered. Women with a positive test result became more anxious than did women with a negative result. However, their perception of future health did not change. Most carriers shared the information about their result with relatives and friends. Carriers had the best retention of pretest information and test result, although a third of the carriers believed that they could not have a child with cystic fibrosis when the partner's test for delta F508 and five other mutations were negative. Most women with a negative test result did not remember their result correctly a year after testing. Few women with a positive result changed their reproductive plans because of the result of the test.

Attitude to Health↗
PubMed1996

Prenatal diagnosis of choroideremia.

With the mapping of the locus CHM for choroideremia and the subsequent cloning of the gene, reliable carrier and prenatal diagnosis has become a possibility. We discuss our experience with prenatal diagnosis of choroideremia, an X-linked choroidoretinal dystrophy leading to blindness in otherwise healthy males. In the period 1987-1995, five prenatal diagnoses have been performed by either indirect linkage analysis or by detection of the disease-causing mutation, reflecting the impact of molecular biology in clinical genetic practice.

Adult↗
PubMed1996

Hepatocellular carcinoma in long-term oral contraceptive use.

Hepatocellular carcinoma (HCC) is one of the most common malignancies in certain parts of the world, particularly in Africa and Asia, but it is less commonly encountered in the United States. It is closely associated with chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, and almost always develops in a cirrhotic liver. In non-cirrhotic livers, HCC is found in about 20% of asymptomatic carriers of HBV and rarely in patients taking androgenic-anabolic or oral contraceptive (OC) steroids. We report four patients, who developed HCC after prolonged use of OC steroids. Whether OC steroids act as mutagen or co-carcinogen in hepatocarcinogenesis is not clear. To exclude latent HCV and HBV infections which may occur in the absence of their serological markers, we employed polymerase chain reaction for the detection of HBV and HCV sequences in the tumor and non-tumorous liver tissue. Viral sequences of HBV and HCV were undetectable in all four cases. These findings suggest OC use as the only known risk factor in these cases and, therefore, strengthen its possible role in hepatocarcinogenesis.

Adult↗
PubMed1996

p53 plays a regulatory role in differentiation and apoptosis of central nervous system-associated cells.

This study demonstrated the involvement of the tumor suppressor protein p53 in differentiation and programmed cell death of neurons and oligodendrocytes, two cell types that leave the mitotic cycle early in development and undergo massive-scale cell death as the nervous system matures. We found that primary cultures of rat oligodendrocytes and neurons, as well as of the neuronal PC12 pheochromocytoma cell line, constitutively express the p53 protein. At critical points in the maturation of these cells in vitro, the subcellular localization of p53 changes: during differentiation it appears mainly in the nucleus, whereas in mature differentiated cells it is present mainly in the cytoplasm. These subcellular changes were correlated with changes in levels of immunoprecipitated p53. Infection of cells with a recombinant retrovirus encoding a C-terminal p53 miniprotein (p53 DD), previously shown to act as a dominant negative inhibitor of endogenous wild-type p53 activity, inhibited the differentiation of oligodendrocytes and of PC12 cells and protected neurons from spontaneous apoptotic death. These findings suggest that p53, upon receiving appropriate signals, is recruited into the nucleus, where it plays a regulatory role in directing primary neurons', oligodendrocytes, and PC12 cells toward either differentiation or apoptosis in vitro.

Animals↗
PubMed1996

Gly802Asp substitution in the pro alpha 2(I) collagen chain in a family with recurrent osteogenesis imperfecta due to paternal mosaicism.

A proband with osteogenesis imperfecta (OI) type III/IV was born to clinically normal parents, who subsequently had two pregnancies terminated because of OI in the fetuses. Cultured fibroblasts from the proband, one fetus and the father produced abnormal collagen I. Cyanogen bromide mapping localised the defect to the region of the alpha 1(I)CB7 peptide. Sequencing revealed a G to A transition at nucleotide 2814 in COL1A2 in the proband, the fetus, and the father, which resulted in a Gly802Asp substitution in the pro alpha 2(I) collagen chain. About 25% of the paternal alleles from fibroblasts and leucocytes and 40% of paternal alleles from spermatocytes carried the mutation consistent with somatic and germinal mosaicism. For genetic counselling, parental mosaicism must be considered in all sporadic cases of OI.

Aspartic Acid↗
PubMed1996

Psychological impact of carrier screening for cystic fibrosis among pregnant women.

The aim of the present study was to assess the impact of being identified carrier of cystic fibrosis. The impact was assessed in terms of retention of the result, sharing of the information about the result with relatives, non-relatives and GPs, changes in reproductive plans, and regrets about having been tested Three unsupervised questionnaires were sent to 160 women identified as carriers between 1990 and 1992 in June 1992, October 1993, and November 1994. Carriers freely shared the information about their result with relatives, friends, and GPs. The inconclusiveness of the test gave rise to some confusion. This may reflect inadequacies in the information and counselling given to carriers, but psychological factors are also believed to be responsible. Thus, false reassurance may be a problem in a carrier screening with a test that detect only a proportion of carriers. Few carriers considered changing their reproductive plans due to the result of the test. A few women identified as carrier regretted having had the test.

Cystic Fibrosis↗