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Biomedical subjects

A Mares

Publications and source records attributed to A Mares.

At least 19 recordsLinked to original sources

Hoptel equalizes length of stay for homeless and domiciled inpatients.

BACKGROUND: There is growing evidence that homeless individuals have longer inpatient lengths of stay with significantly higher medical costs than domiciled individuals. We compared adjusted mean lengths of stay among domiciled patients and homeless patients discharged to a hospital hotel (hoptel). Because the hoptel allowed homeless patients to be discharged when medically indicated, we hypothesized no significant differences in lengths of stay between the 2 groups after adjustment for severity of illness. METHODS: Demographic, diagnosis, and length of stay data were obtained for all patients discharged from all inpatient wards at a large, urban Veterans Affairs Medical Center during the first 32 months of hoptel operation (1996 through 1998). Adjusted mean lengths of stay for domiciled patients and homeless patients discharged to the hoptel were compared. ANCOVA was used to adjust for demographic characteristics (age, income, race/ethnicity), diagnosis-related group (DRG), principal diagnosis, and substance abuse comorbidity. Three types of hospitalizations were analyzed on the basis of major DRG categories: general medical, psychiatric, and all hospitalizations. RESULTS: No significant differences were found in adjusted mean lengths of stay between domiciled patients and homeless patients discharged to the hoptel. Homeless hoptel patients stayed an average 0.7, 0.3, and 0.4 days longer than domiciled patients for all, general medical, and psychiatric hospitalizations (P = 0.504, 0.627, and 0.839), respectively. CONCLUSIONS: These data suggest that hoptels may help equalize inpatient lengths of stay among domiciled and homeless patients discharged to a hoptel. Public health care systems seeking innovative ways of reducing inpatient lengths of stay among homeless patients ought to consider establishing hoptels.

Aftercare↗

Reducing psychiatric hospitalization among mentally ill veterans living in board-and-care homes.

OBJECTIVE: The effectiveness of a community-based case management program at the Veterans Affairs West Los Angeles Healthcare Center in reducing hospital readmission of mentally ill veterans living in privately operated board-and-care homes was evaluated. METHODS: A retrospective cohort design was used. The sample consisted of 321 patients identified by hospital records as living in one of 24 board-and-care homes in the Los Angeles area that were approved by the community residential care program. A total of 214 subjects who received monthly home visits from case managers (program group) were compared with 107 subjects who did not receive monthly home visits (comparison group). The median number of psychiatric bed-days used was calculated for the two years before and after follow-up. The number of days from the start of follow-up to the first psychiatric hospitalization was also calculated. RESULTS: Among subjects in the program group, the median number of psychiatric bed-days used decreased significantly, from 59 days to 50 days. No significant change in the median number was observed for comparison subjects. Comparison subjects were rehospitalized 1.7 times more often than program subjects. Overall, program subjects under age 62 (younger subjects) were rehospitalized 2.5 times more often than older subjects. In the program group, those who had received home visits for more than two years were hospitalized three times more often than those who had received visits for less than two years, and younger subjects were rehospitalized 1.8 times more often than older subjects. CONCLUSIONS: The findings suggest that home visits conducted by case managers in a community residential care program helped reduce psychiatric hospitalization among veteran patients living in privately operated board-and-care homes.

Female↗

[Is there justification for limited percutaneous surgical drainage in severe neonatal necrotizing enterocolitis in low birth weight premature infants?].

The usual treatment of complicated neonatal necrotizing enterocolitis (NEC) is resection of the necrotic bowel, lavage of the peritoneal cavity and diversion enterostomy. Low-birth-weight premature neonates with this condition are in special danger if general anesthesia and full exploratory surgery is contemplated. A relatively simple alternate procedure is percutaneous insertion under local anesthesia of a soft abdominal drain, most often in the right lower quadrant. The procedure is done in the neonatal intensive care unit without moving the whole set-up to the operating room. 4 such cases have been treated within the past year. 3 were discharged home as they did not require additional surgical treatment, not having developed intestinal stenosis or obstruction. 1 recovered from the acute episode, but succumbed to a severe intraventricular hemorrhage and respiratory failure 7 days after the procedure. Our limited but most gratifying experience, in addition to similar experience of others, encourages us to recommend this simple surgical approach in the very sick low-birth-weight premature with fulminant NEC.

Abdomen↗

Effector protease receptor 1 mediates the mitogenic activity of factor Xa for vascular smooth muscle cells in vitro and in vivo.

The binding of 125I-factor Xa to human aortic smooth muscle cell (SMC) monolayers was studied. At 4 degreesC, 125I-factor Xa bound to a single class of binding sites with a dissociation constant value of 3.6+/-0.7 nM and a binding site density of 11,720+/-1,240 sites/cell (n = 9). 125I-factor Xa binding was not affected by factor X, thrombin, or by DX9065, a direct inhibitor of factor Xa, but was inhibited by factor Xa (IC50 = 5.4+/-0.2 nM; n = 9) and by antibodies specific for the effector cell protease receptor 1 (EPR-1), a well-known receptor of factor Xa on various cell types. A factor X peptide duplicating the inter-EGF sequence Leu83-Leu88-(Gly) blocked the binding of 125I-factor Xa to these cells in a dose-dependent manner (IC50 = 110+/-21 nM). Factor Xa increased phosphoinositide turnover in SMCs and when added to SMCs in culture was a potent mitogen. These effects were inhibited by DX9065 and by antibodies directed against EPR-1 and PDGF. Increased expression of EPR-1 was identified immunohistochemically on SMCs growing in culture and in SMCs from the rabbit carotid artery after vascular injury. When applied locally to air-injured rabbit carotid arteries, antibodies directed against EPR-1 (100 mug/ artery) strongly reduced myointimal proliferation 14 d after vascular injury (65-71% inhibition, P < 0.01). DX9065 (10 mg/kg, subcutaneous) inhibited myointimal proliferation significantly (43% inhibition, P < 0.05). These findings indicate that SMCs express functional high affinity receptors for factor Xa related to EPR-1, which may be of importance in the regulation of homeostasis of the vascular wall and after vascular injury.

Animals↗

Two-dimensional echocardiography and Doppler ultrasound in managing obstetric patients.

OBJECTIVE: To test the usefulness of ultrasound-derived measurements of intracardiac filling pressures and cardiac performance in the noninvasive management of obstetric patients with an indication for hemodynamic monitoring. METHODS: We included patients with oliguria unresponsive to crystalloid boluses, with hypertension unresponsive to hydralazine, and at high risk for pulmonary edema who were determined to be candidates for invasive monitoring. They were first studied with two-dimensional echocardiography and Doppler ultrasound using a technique previously validated at our institution. Cardiac dimensions, filling pressures, and function were assessed at the bedside. Subsequently, management decisions were made based on these findings. RESULTS: Fourteen patients were studied. Two received a pulmonary artery catheter after noninvasive evaluation indicated a need for continuous monitoring. The 12 patients managed without the need for a pulmonary artery catheter included women with intractable hypertension (one patient), pulmonary edema (two patients), complex cardiac lesions (two patients), oliguria (five patients), intractable hypertension and oliguria (one patient), and unexplained dyspnea with peripheral arterial oxygen desaturation (one patient). Although some patients received as much as 8 L of crystalloid, none developed pulmonary edema or left ventricular failure. In all 12 cases, the ultrasound monitoring allowed successful noninvasive management of the patient. CONCLUSION: This pilot study suggests that two-dimensional echocardiography and Doppler examination may be an effective alternative to invasive monitoring in the management of selected pregnant patients.

Adult↗

Ovarian fibroma in a prepubertal girl.

Ovarian fibroma rarely occurs in prepubertal girls. However, we found such an asymptomatic, large, uncalcified pelvic mass in an otherwise healthy 12-year-old girl. The plain films (radiographs), US and CT findings are presented.

Child↗

Simvastatin inhibits myointimal hyperplasia following carotid artery injury in cholesterol-fed rabbits.

The effect of simvastatin, a potent inhibitor of 3-hydroxy 3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) was evaluated in an experimental model of myointimal hyperplasia in cholesterol-fed rabbits. Myointimal hyperplasia was induced by an air-drying injury of the left carotid artery followed by a 2%-cholesterol diet for 14 days. A 2-week oral treatment with simvastatin (6 mg/kg/day, p.o.) significantly lowered the circulating levels of cholesterol and triglycerides (41% and 49% inhibition respectively) as well as the low density lipoprotein (LDL)-cholesterol and high density lipoprotein (HDL)-cholesterol levels. Simvastatin also strongly affected the uptake of cholesterol in the arteries occurring as a consequence of vascular injury (44% inhibition, P < 0.001). Morphometric analysis revealed that both the intima and the media areas increased substantially 2 weeks after the lesion and showed a considerable smooth muscle cell accumulation in the neointima together with the presence of numerous foam cells. A 16-day oral treatment with simvastatin strongly reduced smooth muscle cells hyperplasia occurring in both the media and the intima following deendothelialization (19% and 60% inhibition respectively) suggesting that simvastatin may be a useful inhibitor of restenosis which occurs following vascular injury.

Animals↗

Synthesis of a novel biotin-estradiol conjugate and its use for the development of a direct, broad range enzyme immunoassay for plasma estradiol.

The synthesis and purification by high pressure liquid chromatography of a novel biotinoyl-diaminodioxaoctane-estradiol conjugate is described. The conjugate was used for the development of an enzyme immunoassay (EIA) for the direct determination of estradiol in human plasma. This assay was characterized by a low limit of detection (77 pM) and a broad working range. Estradiol concentrations ranging from 77 to 24300 pM, i.e. from the lower levels observed in the follicular phase of the normal menstrual cycle to the very high levels attained during hyperstimulation for in vitro fertilization, could be determined directly in undiluted plasma samples. Intra-assay variation ranged from 3.6 to 10.9% and interassay variation from 6.1 to 12%. The results obtained by the present EIA correlate well with target values obtained by isotope-dilution gas chromatography-mass spectrometry (r = 0.96) and with results obtained by a direct RIA (r = 0.97). The EIA requires no special apparatus, is simple, fast and robust, and could be applied in any clinical laboratory.

Animals↗

A direct non-competitive idiometric enzyme immunoassay for serum oestradiol.

We report a novel non-competitive enzyme immunoassay for oestradiol based on the use of two types of anti-idiotypic antibody that recognize different epitopes within the hypervariable region of the primary anti-oestradiol idiotypic antibody (Ab1). The first anti-idiotype, the betatype, competes with the analyte for an epitope of the primary antibody at the binding site. On the other hand, the second anti-idiotype, the alphatype, binds to the Ab1 in the presence of analyte but does not bind to the betatype/Ab1 complex because of steric hindrance. In the present format the biotinylated alphatype was captured onto anti-biotin IgG which was adsorbed on the surface of microtitre wells. Reaction mixtures containing the Ab1 complexed sequentially with an enzyme labelled second antibody reagent, with oestradiol standards or serum samples and with the betatype anti-idiotypic antibody were then allowed to react with the immobilized alphatype anti-idiotypic antibody. The enzyme activity of the bound fraction measured at 405 nm increased with increasing oestradiol concentrations over the range 0.06-2.5 ng/ml. The detection limit of the assay was 28 pg/ml. The intra-assay variation ranged from 3.5 to 12.4%, and inter-assay variation from 6 to 13.4%. The results obtained by the colorimetric idiometric immunoassay correlated well with those obtained by a direct radioimmunoassay (n = 85, r = 0.97). This non-competitive immunoassay, termed idiometric assay, for haptens permits the development of sensitive immunoassays with a wide working range, and a variety of end-point determinations depending on the label used (e.g., enzyme, chemiluminescent or fluorogenic compound).

Animals↗

Sudden cardiac death in hypertrophic cardiomyopathy. Variability in phenotypic expression of beta-myosin heavy chain mutations.

BACKGROUND: Recent identification of mutations in the beta-myosin heavy chain gene (MYH7), a major responsible gene for HCM, has provided the opportunity to characterize genotype-phenotype correlation in HCM families. In this study we analysed the phenotypic expression of two beta-myosin heavy chain (beta MHC) mutations in three unrelated HCM families. METHODS: Living individuals from three unrelated HCM families (Families 1, 2, and 3) were screened by history, physical examination, electrocardiography, and two-dimensional echocardiography. Blood was collected from all individuals for DNA extraction. Polymerase chain reaction (PCR), restriction endonuclease digestion and chemical cleavage were utilized for detection of mutations. All mutations were confirmed by sequence analysis. RESULTS: Identification of mutations: A missense mutation in exon 13 of the beta MHC gene (Arg403 Gln) was detected in HCM patients from Families 1 and 2. PCR amplification of the exon 13 DNA, followed by Ddel digestion of the PCR product and gel electrophoresis, showed two fragments of 84 and 70 bp in normal individuals and four fragments of 84, 70, 52 and 32 bp in HCM patients. Sequence analysis showed substitution of an adenine for guanine at coding position 1208. In Family 3, a missense mutation in exon 16 of the beta MHC gene (Val606 Met) was detected in HCM patients. Chemical cleavage of the PCR products showed an uncleaved product of 337 bp in the normal individuals, while in the affected individuals, in addition to the uncleaved product, a 90 bp cleaved product was also detected, indicating the presence of a mismatch in one allele. Sequence analysis showed substitution of an adenine for guanine in coding position 1817. CLINICAL CHARACTERISTICS: Seven members of Family 1 had HCM, of whom five are alive. One patient died from sudden cardiac death (SCD) and another from recurrent cerebral emboli. In Family 2, 15 individuals had HCM of whom nine have died, seven from SCD. The mean age at the time of SCD was 33 years. The third family is comprised of 11 affected individuals and one obligate carrier, of whom one patient died at age 17 from progressive heart failure. Two additional individuals in this family have also succumbed to SCD to age 60. A variety of clinical and echocardiographic manifestations of HCM were present in each family. Logrank test of Kaplan-Meier survival curves indicates that Arg403 Gln mutation was associated with a poor prognosis in HCM families as compared to Val606 Met (P = 0.034). CONCLUSIONS: beta MHC mutations despite showing variable clinical and echocardiographic manifestations of HCM are predictors of survival in HCM families.

Adolescent↗

Influence of pH, salt and nitrite on the heme-dependent catalase activity of lactic acid bacteria.

A screening of commercial starter cultures used for the production of dry sausage showed a maximum heme-dependent catalase activity in the range of 60 mumol/l hematin for Lactobacillus sake, Lactobacillus plantarum, Lactobacillus pentosus and Pediococcus acidilactici. Pseudocatalase activity was not detected. In standard dry sausage production, 2-3% (w/w) nitrite salt (0.6% sodium nitrite per 100 g NaCl) is normally added, which corresponds to 4-6% salt in the water phase. In vitro experiments with L. sake and L. plantarum have shown that such a high concentration of salt caused a significant reduction of catalase activity and bacterial growth. In the case of P. acidilactici, the catalase activity remained constant at a salt concentration up to 6% (w/w); at 7% (w/w) the activity decreased sharply. The pH also affected the catalase activity, which remained constant up to pH 5.1 and decreased dramatically at lower values. The effect of nitrite has also been investigated. L. pentosus and P. acidilactici were not affected by the addition of 160 ppm nitrite (NO2-); L. plantarum, on the other hand, showed a significantly reduced catalase activity. In practice, optimum fermentation characteristics combined with an optimum catalase activity which are not inhibited by salt concentrations higher than 6% (w/v) and a residual nitrite content of about 160 ppm (w/v), are of the utmost importance in screening and selection of lactic acid bacteria for starter cultures.

Catalase↗

A missense mutation in the beta myosin heavy chain gene is a predictor of premature sudden death in patients with hypertrophic cardiomyopathy.

BACKGROUND: Familial hypertrophic cardiomyopathy (FHCM) is an autosomal dominant disease with protean clinical manifestations, ranging from asymptomatic to that of severe heart failure or sudden death. There is no known parameter in individuals with hypertrophic cardiomyopathy (HCM) that predicts a specific clinical event. This is particularly troublesome for premature sudden death that frequently occurs in young athletes without prior symptoms. Recent identification of mutations in the beta myosin heavy chain (beta MHC) gene that co-segregate with the inheritance of the disease provides an opportunity to determine whether certain mutations are more likely to induce a particular clinical event. In this study we analyzed the genotype and phenotype of individuals from two unrelated families with HCM in which the affected individuals have the same missense mutation in exon 13 (G1208A) of the coding sequence for beta MHC. METHODS: Individuals from two unrelated families with the diagnosis of FHCM were screened by history, physical examination, electrocardiography, and two dimensional echocardiography. After extraction of DNA from the blood of these individuals, the exon 13 of the beta MHC gene was amplified by polymerase chain reaction (PCR), and the PCR product was digested with Ddel restriction endonuclease. The digestion products were separated by gel electrophoresis and identified by ethidium bromide staining. RESULTS: We studied 54 individuals from the two families, 21 were affected with HCM of which eleven died prematurely, eight from sudden cardiac death. While most of the nine affected individuals studied had septal hypertrophy, three had concentric hypertrophy and six, left ventricular outflow tract obstruction. Onset of symptoms was in the second decade of life. Electrophoretic separation of the digested DNA (exon 13) from unaffected individuals provided two fragments of 84 and 70 bp in size, as expected. In contrast, DNA from individuals affected with HCM showed four fragments of 84 bp, 70 bp, 52 bp and 32 bp indicating they inherited the mutation. In only one 10 year old male was the mutation present without evidence of HCM which gives an overall penetrance of 86%. CONCLUSIONS: The missense mutation in exon 13 of the beta MHC gene in individuals with FHCM is associated with high penetrance, highly variable expressivity, severe disease, early in onset and a high incidence of premature sudden death. Based on these results we recommend individuals from families with HCM be screened for this missense mutation and if positive, be counselled to avoid combative sports, as it is these activities that often precipitate sudden death.

Adult↗

[Hirschprung's disease in the Negev].

We treated 65 children with proven Hirschprung's disease between 1970-1992. After definitive surgery, 35 were over 10 years of age and 13 were over 18. The male:female ratio was 4:1. All but 3 were born full-term. 44% were of Bedouin origin, with a higher prevalence in 3 families of 2 tribes. 38 (58%) were diagnosed in the neonatal period: by barium enema and rectal muscle biopsy in 42 (65%), and by barium enema alone in 23 (35%). In the latter the diagnosis was verified by intra-operative biopsy. Severe constipation, intestinal obstruction or enterocolitis were the presenting features. 19 associated anomalies were found in 12 children, but none was life-threatening; 5 (8%) had cardiac anomalies; none had Down's syndrome. The rectosigmoid colon was the most common aganglionic segment involved (only 1 had total colonic aganglionosis). 7 of the 8 with short segment involvement responded well to posterior rectal myectomy. 55 patients had an abdominoperineal pull-through: 48 by Swenson's procedure and 5 by the Soave and 2 by the Duhamel modifications. In 43 a protective colostomy was performed at the end of the procedure. 53 had complete diversion colostomy at the time of initial diagnosis (neonatal and early infancy). There was no intra- or immediate post-operative death. 1 patient died 2 months after operation of complications following enterocolitis and total parenteral nutrition. 2 died a few hours after admission of severe sepsis due to enterocolitis before operation was possible. There were early postoperative complications in 11% of the 151 operations, mostly minor wound infections.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Hypertrophic cardiomyopathy mutation is expressed in messenger RNA of skeletal as well as cardiac muscle.

BACKGROUND: The beta-myosin heavy chain (beta-MHC) gene has been identified as a major locus for familial hypertrophic cardiomyopathy (FHCM). We recently showed that one of the common mutations associated with FHCM is expressed in the cardiac muscle messenger RNA (mRNA) of an affected individual. Since beta-MHC is a major sarcomeric protein of cardiac and skeletal muscle, studies were performed to determine whether the mutation is also expressed in skeletal muscle. METHODS AND RESULTS: Biopsies were obtained of skeletal muscle (biceps brachii) from a proband with FHCM known to have the missense mutation in exon 13 of the beta-MHC gene. RNA was extracted from skeletal muscle and lymphocytes by the RNAzol method. First-strand complementary DNA was synthesized by reverse transcription using an antisense primer to exon 16. Polymerase chain reaction (PCR) was performed using primers to exons 12 and 14 to amplify the segment encompassing exon 13. The PCR products were digested with Ddel restriction endonuclease. Undigested PCR product in the control and the proband was 321 base-pairs (bp). Ddel digestion of the PCR product from normal skeletal and lymphocytes showed two DNA fragments of 181 and 140 bp as expected, whereas digestion of the PCR product from the proband's skeletal muscle and lymphocytes showed four DNA fragments of 181, 149, 140, and 32 bp due to the mutation in exon 13. This indicates that the mutation in affected individuals is also expressed in the mRNA of skeletal muscle and lymphocytes. CONCLUSIONS: To our knowledge, this is the first documentation of a beta-MHC gene mutation expressed in skeletal muscle. This finding is provocative. Does it impair skeletal muscle function? If so, how? If not, why not? Is the impairment, or lack of it, a clue to the molecular defect of cardiac muscle? Furthermore, skeletal muscle provides a readily accessible source of mRNA for expression studies and for purification of the beta-MHC protein, which is probably essential to future investigation designed to unravel the molecular basis of this disorder.

Adult↗

The natural history of community-acquired hepatitis C in the United States. The Sentinel Counties Chronic non-A, non-B Hepatitis Study Team.

BACKGROUND: Chronic liver disease develops in more than half of patients with post-transfusion hepatitis C, but little is known about the natural history of community-acquired hepatitis C. METHODS: In 1985 and 1986 we identified adults with acute non-A, non-B hepatitis in four counties in the United States and followed them prospectively. We used three markers to detect hepatitis C virus (HCV) infection in stored samples of serum: antibody to HCV (anti-HCV) detected by second-generation serologic assays; HCV RNA detected by polymerase-chain-reaction assay; and antibody to HCV antigen (anti-HCVAg) detected by fluorescent-antibody-blocking assay. RESULTS: Of 130 patients with non-A, non-B hepatitis, 106 (82 percent) had HCV infection, 93 were positive for anti-HCV, and 13 were positive only for HCV RNA or anti-HCVAg. Chronic hepatitis developed in 60 (62 percent) of 97 HCV-infected patients followed for 9 to 48 months, with no relation to the risk factors for infection. Ten of the 30 patients who had liver biopsies had chronic active hepatitis. In samples collected 42 to 48 months after the onset of hepatitis, HCV RNA was detected in 12 of 13 tested patients with chronic hepatitis and in all 15 tested patients with hepatitis that had resolved. Anti-HCV persisted in all but two of the initially positive patients, for a rate of antibody loss of 0.6 per 100 person-years. CONCLUSIONS: Patients with community-acquired hepatitis C have a high rate of chronic hepatitis. HCV may be a major cause of chronic liver disease in the United States, and in most patients HCV infection seems to persist for at least several years, even in the absence of active liver disease.

Adolescent↗