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Biomedical subjects

M Schwartz

Publications and source records attributed to M Schwartz.

At least 217 records · Page 12Linked to original sources

The deltaccr5 mutation conferring protection against HIV-1 in Caucasian populations has a single and recent origin in Northeastern Europe.

The chemokine receptor CCR5 is encoded by the CMKBR5 gene located on the p21.3 region of human chromosome 3, and constitutes the major co-receptor for the macrophage-tropic strains of HIV-1. A mutant allele of the CCR5 gene, Delta ccr5 , was shown to provide to homozygotes with a strong resistance against infection by HIV. The frequency of the Delta ccr5 allele was investigated in 18 European populations. A North to South gradient was found, with the highest allele frequencies in Finnish and Mordvinian populations (16%), and the lowest in Sardinia (4%). Highly polymorphic microsatellites (IRI3.1, D3S4579 and IRI3.2, D3S4580 ) located respectively 11 kb upstream and 68 kb downstream of the CCR5 gene deletion were used to determine the haplotype of the chromosomes carrying the Delta ccr5 variant. A strong linkage disequilibrium was found between Delta ccr5 and specific alleles of the IRI3.1 and IRI3.2 microsatellites: >95% of the Delta ccr5 chromosomes carried the IRI3.1-0 allele, while 88% carried the IRI3.2-0 allele. These alleles were found respectively in only 2 or 1.5% of the chromosomes carrying a wild-type CCR5 gene. From these data, it was inferred that most, if not all Delta ccr5 alleles originate from a single mutation event, and that this mutation event probably took place a few thousand years ago in Northeastern Europe. The high frequency of the Delta ccr5 allele in Caucasian populations cannot be explained easily by random genetic drift, suggesting that a selection advantage is or has been associated with homo- or heterozygous carriers of the Delta ccr5 allele.

Acquired Immunodeficiency Syndrome↗

Factor XIIIa as a nerve-associated transglutaminase.

Recent findings have led to changes in the traditional concept of nerve recovery, including the realization that injured nerves, like any other injured tissue, need the assistance of blood-derived cells and factors in order to heal. We show that factor XIIIa (FXIIIa, the potentially active a2subunit of factor XIII), an enzyme that participates in blood coagulation by stabilizing the fibrin clot, is also active in the nervous system where it may play a key role in the healing of injured tissue. We demonstrate that the plasma, macrophages and nerves of fish contain a 55 kDa form of transglutaminase that cross-reacts immunologically with the a-subunit of FXIII in mammals (80 kDa). The fish enzyme in the plasma, unlike its mammalian counterpart, is active, pointing to a difference in control of the coagulation pathway in the two species. Analysis of FXIIIa expression in mammalian neural tissues and their response to injury revealed high levels of the enzyme in media conditioned by peripheral nerves as compared with medium conditioned by nerves of the central nervous system. Furthermore, similarity was observed in the postinjury behavior of FXIIIa in regenerating nerve tissues (peripheral nervous system of mammals and the central nervous system of fish). We suggest that the postinjury level of factor XIIIa in the nervous system may be related to the tissue's regenerative capacity, and that FXIIIa may therefore be a link underlying a possible association between the processes of blood coagulation and nerve healing.

Animals↗

Xanthomatous hypophysitis.

Inflammatory lesions of the hypophysis include lymphocytic hypophysitis, pituitary abscess, and granulomatous inflammation, with or without specific infections (i.e., sarcoidosis, mycobacteria). These lesions are known to mimic pituitary neoplasms. We report the clinical and pathologic findings in three patients who underwent transsphenoidal resection for presumed pituitary adenoma. Two were women aged 30 years (one with a 5-month history of headache, the other with a 1-year history of menstrual irregularity) and one was a 12-year-old girl with headache, nausea, and diabetes insipidus. Preoperative endocrinologic studies showed increased prolactin in one patient and normal serum thyroid stimulating hormone and prolactin levels in another. By magnetic resonance imaging (MRI), the first case had a 1.2-cm mass with increased signal on T1 and isointensity on T2, ring enhancement after gadolinium, and lateral deviation of the pituitary stalk. The second patient had a 1.1-cm "cystic" mass seen during magnetic resonance imaging with adjacent bony changes seen during computed tomography. In the third, computed tomography showed a hypodense pituitary mass that enlarged during 1-month observation. At surgery, abnormal soft tissue surrounded liquefied material in the anterior pituitary in all cases. Histologic studies showed fragments of intact normal anterior pituitary with preserved vascular and reticulin network and regions of anterior pituitary infiltrated by foamy histiocytes. Other fragments resembled granulation tissue, and some consisted of acellular debris. Histiocytes were immunoreactive for the macrophage marker CD68 and negative for S-100 and CD1a. Ultrastructurally, the normal adenohypophysis was permeated by lipid-laden macrophages. There were no well-formed granulomas or giant cells, hemosiderin, acid-fast bacilli, or fungi. Serial sections and keratin immunostains failed to identify an epithelial cyst lining or keratin among the debris. We propose the term "xanthomatous hypophysitis" for this lesion.

Adult↗

Dynamic cleft maxillary orthopedics and periosteoplasty: benefit or detriment?

In 1990, Drs Millard and Latham published their initial experience with dynamic maxillary appliances (DMAs) and periosteoplasty for children with cleft lip and palate. The technique provided for alveolar alignment and consolidation, with elimination of oronasal fistulas. Opponents to this approach speculated about impairments to facial growth. To date no longitudinal studies have been published. Over the last 10 years, 35 unilateral and 10 bilateral complete clefts have been treated with this technique. All patients have been followed and documented clinically, orthodontically, and radiographically. Cephalometric analyses were performed on children after the age of 6 years. The children have excellent facial aesthetics with well-balanced lips and noses. Radiographs demonstrate bone within the repaired alveolar clefts. Articulated impressions show anterior and lateral crossbites in the unilateral patients that improve over time and appear to be correctable orthodontically. The bilateral patients have satisfactory occlusions and arch forms. Cephalometric analyses confirmed no evidence of skeletal crossbites or midfacial growth retardation. This is a work in progress that will continue as the children grow. Although definite and final conclusions would be premature, it can be stated that to date all patients are following consistent and favorable growth patterns. Our team is confident in proceeding with this technique.

Alveoloplasty↗

Higher incidence of diabetes in liver transplant recipients with hepatitis C.

We assessed the clinical and biochemical parameters associated with the development of posttransplantation diabetes (PTDM) in 52 liver transplant recipients followed up for 1 year. Diabetes was present before transplantation in 9.6% (5 of 52) of patients, and PTDM occurred in 23% (11 of 47) of the remaining liver transplant recipients. Of the 13 patients who had hepatitis C as the cause of their liver failure (HC-LD), 8 (62%) developed PTDM; of the 34 patients with other causes of liver failure, 3 (9%) developed PTDM (p < 0.001). Posttransplantation diabetes was also associated with the development of early posttransplantation hyperglycemia, a higher number of liver rejection episodes, and lower serum albumin levels at 6 months. The association of PTDM with HC-LD remained significant in a logistic regression model after adjustment for potential confounding variables. We conclude that PTDM is common in liver transplant recipients. Associated clinical parameters predictive of PTDM include a diagnosis of HC-LD before transplantation, the development of early hyperglycemia after transplantation, multiple episodes of posttransplantation liver rejection and low serum albumin levels at 6 months. The fact that HC-LD remained an independent risk factor for the development of PTDM may suggest a direct or immune-mediated pancreatic effect of the virus.

Adolescent↗

Clinico-tremorgraphic features of neuroleptic-induced tremor.

Instrumental tremorgrams have been used to improve the diagnostic accuracy of various movement disorders, including tardive akathisia. The aim of the present work was to evaluate their place in the diagnosis of neuroleptic-induced tremor and to determine whether they can help to differentiate this disorder from other neuroleptic-induced movement disorders and from other types of tremor. Fourteen psychiatric patients treated with various neuroleptic medications were diagnosed as having neuroleptic-induced tremor on the basis of clinical criteria. They underwent accelerometric recordings following diagnosis. All patients demonstrated upper-limb tremor; four also had involvement of the lower limbs, jaw or tongue. Most demonstrated both resting and postural tremor, the latter being the more prominent. The tremor was mainly rhythmic, regular and sinusoidal. It did not significantly interfere with activities of daily living in the majority of patients, but four did exhibit some degree of impairment. Repeated accelerometric recordings showed constant and regular waveforms and frequencies (between 4 and 7 Hz) in each patient. We conclude that the presence of repeated constant waveforms and frequencies on accelerometric tracings may serve as confirmation of the diagnosis of neuroleptic-induced tremor. In light of the findings of this and other studies, we suggest that tremorgrams may be helpful in differentiating neuroleptic-induced tremor from other neuroleptic-induced movement disorders (e.g., tardive dyskinesia and tardive akathisia) and from psychogenic tremor. Although these techniques may also assist in the differentiation of neuroleptic-induced tremor from some tremor disorders (e.g., asterixis or ataxic tremor), their overall potential to distinguish it from other types of organic tremor is more limited.

Adult↗

Care tracker: a new approach to nursing care in ambulatory settings.

The shift from inpatient to ambulatory settings and the increasingly large and diverse numbers of ambulatory clients require reengineering and cost-effective approaches to managing ambulatory care. With data on 921 encounters in 12 ambulatory clinics, we developed CARE TRACKER, an instrument to describe nursing encounters by type, intervention, staff, time, and cost. Distinguishing nursing from medical interventions is an appreciable improvement over the traditional practice of bundling nursing as part of overhead costs. If managers can track the care delivered, they can better calculate staffing requirements, staff mix, inservice needs, and the costs of their existing and projected services.

Ambulatory Care↗

Central infusion of melanocortin agonist MTII in rats: assessment of c-Fos expression and taste aversion.

Like leptin (OB protein), central infusion of the nonspecific melanocortin agonist MTII reduces food intake for relatively long periods of time (i.e., 12 h; W. Fan, B. A. Boston, R. A. Kesterson, V. J. Hruby, and R. D. Cone, Nature; 385: 165-168, 1997). To test the hypothesis that MTII may influence ingestive behavior via mechanisms similar to those that mediate the effects of leptin, we infused a single dose of MTII into the third ventricle (i3vt) of Long-Evans rats and examined three dependent measures that have been studied following i3vt infusion of leptin: 1) effects on long-term food intake and body weight (48 h), 2) patterns of c-Fos expression in the brain, and 3) conditioned taste aversion learning. Similar to leptin, MTII reduced 48-h food intake (1.0 nmol dose), reduced body weight at 24 and 48 h (0.1 and 1.0 nmol doses, respectively), and induced c-Fos expression in the paraventricular nucleus of the hypothalamus and the central nucleus of the amygdala. In contrast to leptin, MTII was found to produce conditioned taste aversions. These results are consistent with the hypothesis that MTII may influence regulatory behavior via mechanisms similar to those that mediate the effects of leptin.

Administration, Oral↗

High association of anticardiolipin antibodies with psychosis.

BACKGROUND: Lupus anticoagulant (LA) and anticardiolipin antibodies (aCL) are autoantibodies that can be detected in plasma or serum of patients with autoimmune-related diseases. The presence of these autoantibodies has been associated with recurrent arterial and/or venous thromboembolism as well as with recurrent fetal loss and thrombocytopenia. In recent years, other medical conditions such as dementia, chorea, psychosis, migraine, and peripheral neuropathy have been associated with these autoantibodies. An adverse response to neuroleptic treatment was reported to be associated with the presence of autoantibodies, but these patients rarely developed clinical vascular manifestations. METHOD: We conducted a study of 34 unmedicated patients admitted to the hospital with acute psychosis in whom aCL and LA were examined before and after neuroleptic treatment to determine the presence of antibodies relative to the treatment condition. RESULTS: 32% (11/34) of the unmedicated psychotic patients had antiphospholipid antibodies: we detected elevated titers of IgG-aCL isotype in 24% (8/34) of unmedicated patients (p < .02 compared with 20 normal controls, none of whom tested positive), and 9% (3/34) had LA. Twenty-two patients were followed up after medication; 31.8% (7/22) of these patients showed moderate titers of IgG-aCL (p < .28), and 18.2% (4/22) were LA positive. Altogether, antiphospholipid antibodies were detected in 40.9% (9/22) of the medicated patients. CONCLUSION: This study shows the increased incidence of LA and aCL antibodies in neuroleptic-treated psychotic patients and the possible association between psychosis and antiphospholipid antibodies.

Acute Disease↗

The effects of focal and diffuse brain damage on strategy application: evidence from focal lesions, traumatic brain injury and normal aging.

A new test of strategy application was designed to be relatively free of the constraints that limit the standard neuropsychological assessment of supervisory abilities. The validity of the test was assessed in 3 samples of participants with varying degrees of supervisory deficits and frontal systems dysfunction: focal frontal lesions, traumatic brain injury (TBI), and normal aging. Inefficient strategy application varied systematically across the 3 groups and was not due to extraneous factors such as forgetting the test instructions. Previous case studies have emphasized strategy application deficits in the face of normal neuropsychological test performance. In this study, it was shown that strategically impaired participants from a consecutive series can include those both with and without deficient neuropsychological test performance. When neuropsychological impairment was present, it was greatest on executive functioning tasks. Among participants with nonstrategic performance, there was evidence for a dissociation of knowledge from action. This finding was not specific to focal frontal lesions. A number of supervisory processes contributing to strategy application were identified. Exploratory analyses indicated differential effects of lesion location on these processes, especially inferior medial frontal and right hemisphere lesions. Overall, the results supported the use of unstructured tasks in the assessment of supervisory abilities.

Adolescent↗

The prevention and management of the broken curet.

With repeated sharpening or improper technique, a curet tip may break inside a periodontal pocket. This creates a problem for the clinician because the tip usually cannot be seen or felt. This article offers suggestions that can prevent such breakage. The include instrument selection and application, appropriate use of force, and proper sharpening. The article also describes a pair of magnetic instruments that can remove a loose fragment when curet fracture occurs and explains how the instruments are used.

Dental Instruments↗

Peripheral nerve-stimulated macrophages simulate a peripheral nerve-like regenerative response in rat transected optic nerve.

We have previously demonstrated that the failure of the mammalian central nervous system (CNS) to regenerate following axonal injury is related to its immunosuppressive nature, which restricts the ability of both recruited blood-borne monocytes and CNS-resident microglia to support a process of repair. In this study we show that transected optic nerve transplanted with macrophages stimulated by spontaneously regenerating nerve tissue, e.g., segments of peripheral nerve (sciatic nerve), exhibit axonal regrowth at least as far as the optic chiasma. Axonal regrowth was confirmed by double retrograde labeling of the injured optic axons, visualized in their cell bodies. Transplanted macrophages exposed to segments of CNS (optic) nerve were significantly less effective in inducing regrowth. Immunocytochemical analysis showed that the induced regrowth was correlated with a wide distribution of macrophages within the transplanted-transected nerves. It was also correlated with an enhanced clearance of myelin, known to be inhibitory for regrowth and poorly eliminated after injury in the CNS. These results suggest that healing of the injured mammalian CNS, like healing of any other injured tissue, requires the partnership of the immune system, which is normally restricted, but that the restriction can be circumvented by transplantation of peripheral nerve-stimulated macrophages.

Animals↗

Validation of capillary electrophoresis for analysis of the X-Y homologous amelogenin gene.

Capillary electrophoresis (CE) is a versatile technology with tremendous potential applications in forensic science. A refinement of the traditional slab-gel, separation occurs in a liquid polymer contained within a capillary. The capillary electrophoresis unit is computer-driven, semi-automating the loading and analysis of samples. As with any new technology, a full performance assessment is required before it may be implemented with confidence. This paper focuses on validation of CE technology for analysis of a portion of the X-Y homologous amelogenin gene used in gender determination. Typical Y/X ratios of peak heights for male samples were determined. Instrument linearity, sample resolution and reproducibility were examined. Samples subjected to contamination, extreme environmental conditions or extracted from a variety of substrates were also tested by CE. All samples typed correctly. Genetic material from a number of common non-primate animals was amplified with amelogenin primers. Some species yielded no product. Products derived from the animal samples that did amplify produced peaks on CE analysis readily distinguishable from those of human origin.

Amelogenin↗

Chronic postnatal hypoxia increases the numbers of cortical neurons.

Premature infants have been shown to undergo prolonged periods of sublethal hypoxia. There is considerable evidence to link these hypoxic events with neurodevelopmental disorders. As an animal model for this clinical problem, rats were raised from the third day of life in a chamber where the O2 level was 9.5%. After 30 days of hypoxia the rats were sacrificed and their brains processed for determination of the number of cortical neurons. This work was performed to test the hypothesis that chronic hypoxia would result in increased cortical cell death. The hypoxic rats had lower body and brain weights as well as decreased cortical volumes. However, hypoxic rats had increased neuronal density and significantly more cortical neurons than controls (P < 0.05). The results of this study suggest that chronic sublethal hypoxia may lead to reduction in the amount of programmed cell death in the developing neocortex.

Animals↗

Friction properties at the bone-metal interface: comparison of four different porous metal surfaces.

Detailed friction load-displacement response of four distinct metallic surfaces [one beaded porous metal (CTR) and three cast Co-Cr alloy ingrowth mesh surfaces, nonplanar mesh (INX), cast mesh 1 (CM1), and cast mesh 2 (CM2)] on poly-urethane and cancellous bone specimens of six tibiae were measured under different normal stresses (0.1, 0.15, or 0.025 MPa). Bone cubes were obtained from different proximal regions of resurfaced cadaveric tibiae. Both monotonic and cyclic fatigue loadings of up to 4000 cycles at 1 Hz were considered. Comparison of measured results indicated that the friction coefficient was not affected by the magnitude of normal stress and the bone excision site (medial, lateral, anterior, posterior, and central). The CM2 surface showed significantly greater resistance with friction coefficients of more than 0.9 for the bone and 0.8 for the polyurethane. The INX surface yielded the second largest resistance followed by CM1 and CTR surfaces. NO significant difference was found between these latter two surfaces. Fatigue tests of up to 4000 loading-unloading cycles showed about 10% reduction in friction coefficient for CTR and INX surfaces, while negligible reduction was found for CM1 and CM2 surfaces.

Bone Substitutes↗