A comprehensive health care directive in a home for the aged.
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Biomedical subjects
Publications and source records attributed to M Diamond.
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Physicians have key roles both in treating disease and educating their patients about health and disease-related issues. To assess which factors correlate with Austrian physician's willingness to treat and educate patients about HIV-related risk behaviors and deal with AIDS issues, we conducted a survey of general practitioners, internists, and dermatologists in Graz, Austria. We report on some aspects of the knowledge, attitudes, and practices of these physicians. Factor analysis revealed two attitudinal components significantly associated with HIV-related practices of the respondents. We labeled these components Reluctance and Infection. "Reluctance" reflected discomfort with sex-related matters and was associated with less HIV counseling and less interest in HIV-related continuing medical education. "Infection" reflected a fear of contracting HIV disease and was positively associated with an increased assessment of different risk factors and a tendency to refer HIV-infected patients for all further treatment. Results suggest that physicians need further training in their ability to deal with HIV issues. Fortunately they seem willing to improve and take further training to do so. Patients, physicians, and the public would all benefit from acknowledging and dealing with the attitudes and needs of physicians toward HIV-related issues.
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Headache is a frequent presenting complaint in the emergency department. Once a diagnosis is established, and significant organic disease can be ruled out, relief of pain must be addressed. Referral for follow-up care and narcotic habituation is a recurrent problem for the emergency physician. This article discusses the differential diagnosis of headache, evaluation of the emergency room patient, and treatment of the patient with headache.
To examine the impact of opiate blockade on glucose counterregulation we performed two hypoglycemic insulin clamp studies with and without naloxone in healthy subjects and well-controlled insulin-dependent (IDDM) patients with defective glucose counterregulation. During both studies plasma glucose fell to 55-60 mg/dl and was then maintained at that level using a variable glucose infusion. In normal subjects, naloxone increased glucose production, thereby reducing the exogenous glucose dose needed to maintain the hypoglycemic plateau. Epinephrine and cortisol responses to hypoglycemia were increased during naloxone plus insulin compared with insulin alone; glucagon responses were unaffected. IDDM patients with suppressed hepatic and hormonal responses to insulin-induced hypoglycemia also demonstrated greater stimulation of glucose production as well as epinephrine, growth hormone, and cortisol release during the naloxone study. In the absence of hypoglycemia, naloxone did not significantly affect glucose production or glucoregulatory hormones. We conclude that opiate blockade augments glucoregulatory responses to insulin-induced hypoglycemia, even in IDDM patients with preexisting defects in glucose counterregulation. This effect is at least in part due to enhanced counterregulatory hormone release during hypoglycemia. Endogenous opiates may modulate hormonal responses during hypoglycemia; their blockade could provide a means of ameliorating defective counterregulation in IDDM patients.
To evaluate whether insulin resistance contributes to the increased risk of diabetes in patients with Turner's syndrome, we measured insulin sensitivity (using the euglycemic insulin clamp technique, 40 mU/m2.min) and whole body glucose and lipid oxidation (assessed by indirect calorimetry) in two groups of nondiabetic patients with Turner's syndrome and age-matched normal controls. Group 1 consisted of eight young patients (mean age, 10 +/- 0.8 yr) who had never received hormone therapy, and group 2 consisted of five patients (mean age, 17.6 +/- 1.4 yr) who had been or were on estrogen therapy. In group 2, [3-3H]glucose was also infused during the euglycemic clamp to assess hepatic sensitivity to insulin. During the euglycemic clamp, insulin-stimulated glucose metabolism was decreased in both groups of patients [group 1, 8.4 +/- 1.0 vs. 14.7 +/- 2 mM/m2.min in controls (P less than 0.05); group 2, 9 +/- 0.7 vs. 11.7 +/- 0.9 mM/m2.min in controls (P less than 0.05)]. The impairment of insulin-stimulated glucose metabolism in patients with Turner's syndrome was accounted for by reduced nonoxidative glucose disposal; glucose oxidation rose to a similar extent in Turner patients and normal controls. Insulin-induced suppression of hepatic glucose production (group 2) and plasma FFA and branched chain amino acid levels in Turner patients was also indistinguishable from that in normal controls. Our data suggest that in patients with Turner's syndrome, insulin resistance is a very early metabolic defect that may be restricted to nonoxidative pathways of intracellular glucose metabolism.
A site of DNA polymorphism linked to the myelin basic protein gene, identified as restriction fragment length polymorphism, was analyzed in a population-based study comparing patients with clinically definite multiple sclerosis (MS) and population-matched control subjects. A 0.9-kilobase (kb) genomic DNA fragment (EcoG) encompassing the first exon of the human myelin basic protein gene, located on the long arm of chromosome 18, identified ten alleles arising from a region of DNA, 1.5 kb 5' to the myelin basic protein gene first exon coding region. Produced by RsaI digests and ranging in length from 2.05 to 2.15 kb, these alleles vary in size by up to 100 base pairs due to insertion or deletion, or both, from a 1-kb length of repetitive DNA. Allele frequencies among 65 patients with MS were compared with those of 63 control subjects. Chi square for these data was significant (p less than 0.001), largely due to a preponderance in the patients with MS of alleles in the 2.14- to 2.15-kb range. Comparison of the numbers of patients with MS and control subjects bearing specific alleles showed that 45% of the patients carried at least one allele of 2.14 to 2.15 kb as opposed to 19% of control subjects (p less than 0.005). These data, while preliminary, suggest that patients with MS differ from population-matched control subjects with respect to DNA polymorphism linked to the myelin basic protein gene. Although no pathogenic relationship between this polymorphism and MS can be presupposed, this finding raises the possibility that the myelin basic protein gene or some other myelin basic protein-linked locus may be a factor in susceptibility to MS.
Eight cases of autoerotic asphyxia deaths on Oahu are reviewed. Distinguishing features typically separate these deaths from intentional suicides or homicides. The sexual nature of these incidents is a salient feature of the death. The etiology of the practice is unknown but worth investigation.
This first statewide study, using random phone interviews, found a community standard for the acceptance of sexually explicit material. Research shows respondents are conservative in voting for the death penalty and against the legalization of those drugs presently illegal, even marijuana. In other regards, Hawaiians think abortion should be only for the women to decide and that adults should not be denied access to explicit material that shows other adults in consensual sexual acts. The majority of those interviewed had themselves seen erotically explicit materials, often obtaining it themselves. Only a minority found the material offensive. A review of studies on sexually explicit material elsewhere in the country shows these findings to be consistent with all other communities investigated; none would restrict adults from access to sexually explicit material.
The relationship between the endocrine system and immune monokines, such as interleukin-1 (IL-1), is of increasing interest. IL-1, a protein secreted by peripheral monocytes and tissue macrophages, mediates a wide variety of immune responses, and its production appears to be inversely related to the level of gonadal steroids. In this report, we have investigated the relationship between estradiol and progesterone concentrations and the level of IL-1 beta mRNA in cultured human peripheral monocytes and pelvic macrophages. Human peripheral monocytes, isolated during the luteal phase of the menstrual cycle, were activated with lipopolysaccharide (10 micrograms/mL). Cellular RNA was isolated and analyzed by Northern analysis using an 800-basepair IL-1 beta cDNA probe. Hybridization with 32P-labeled probe showed maximal levels of IL-1 beta mRNA occurring between 3 and 7 h of culture. Cultures of lipopolysaccharide-activated human peripheral monocytes incubated for 3-6 h with increasing amounts of progesterone or estradiol (0-10(-5) M) in the presence of either 5% fetal calf serum or 0.1% BSA demonstrated an inverse relationship between IL-1 beta mRNA levels and steroid concentration. In both cases, IL-1 beta mRNA levels decreased by 80-90% as the progesterone concentration increased to 10(-5) M and by 70-90% as the estradiol concentration increased similarly. A similar 80% decrease in IL-1 beta mRNA was observed with peritoneal macrophages incubated with increasing amounts of progesterone. This reciprocal relationship between IL-1 beta mRNA and gonadal steroids may have important ramifications in reproductive biology for both embryonic implantation and fetal survival as well as for clinically relevant changes in bone mass.
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Transvaginal follicle aspiration guided by transvaginal ultrasound for ova recovery is rapidly gaining popularity in many centers practicing in vitro fertilization and embryo transfer (IVF-ET). Cycle outcome following this new method has not been directly compared to the traditional, laparoscopic recovery technique. To this end, the authors evaluated multiple parameters in 66 laparoscopic (group A), and 44 transvaginal ova recovery procedures (group B) in patients undergoing IVF-ET. No statistically significant differences could be demonstrated between the groups in all but the rate of ova fertilization. The rate of fertilization was higher in the ova recovered by transvaginal follicle aspiration (59.6 versus 69.2%; P less than 0.01). No difference could be demonstrated between the groups in the other parameters examined, which included the number of ova recovered (5.7 +/- 0.4 versus 6.0 +/- 0.7), ova maturity (87 versus 84% intermediate ova), rate of polyspermic fertilization (3.9 versus 5%), rate of cleavage (88 versus 91%), cleavage stage at transfer (3.7 +/- 0.8 versus 3.5 +/- 0.4 cells per embryo), number of embryos transferred per patient (2.7 +/- 0.1 versus 3.3 +/- 0.2), and pregnancy rates. The potential detrimental effects of general anesthesia and CO2 pneumoperitoneum present during laparoscopy but not ultrasound guided recovery on ova quality may underlie the observed difference in fertilization between the groups.
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A Mr = 110,000 glycoprotein, GP 110, was partially purified using wheat germ agglutinin-Sepharose affinity chromatography from a bile canalicular-enriched membrane fraction denoted N2u of rat liver. This fraction was subjected to preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis and the Mr = 110,000 polypeptide was excised and used as an immunogen in rabbits. The antisera were found to specifically recognize a Mr = 110,000 polypeptide, named GP 110, in the N2u membrane fraction. In isolated hepatocytes, GP 110 was readily accessible to cell surface iodination catalyzed by lactoperoxidase at 4 degrees C and was judged by immunoprecipitation studies to contain about 2% of total radioactivity incorporated into externally oriented proteins of the cell. Immunoprecipitated GP 110 was shown by two-dimensional polyacrylamide gel electrophoresis to migrate with an approximate pI of 4.9. Indirect immunofluorescence on frozen liver sections demonstrated that GP 110 was primarily localized in the bile canaliculus. In corroborative studies employing subcellular fractionation, it was found that GP 110 was enriched nearly 19-fold in P2, a plasma membrane fraction primarily derived from the sinusoidal domain, and 44-fold in N2u. In contrast, only low levels of GP 110 were present in endoplasmic reticulum, mitochondrial, cytosolic, and nuclear-enriched fractions of liver. The physiological function of GP 110 is as yet unknown; antisera to it did not immunoprecipitate other known bile canalicular proteins of similar molecular weights. GP 110 was found to be extensively glycosylated relative to other known membrane proteins; approximately 33% of the apparent molecular weight appear to be carbohydrate. In agreement, limited removal of N-linked carbohydrate chains indicated that there are approximately eight chains/GP 110 polypeptide. Neuraminidase treatment of GP 110 resulted in a desialylated Mr = 85,000 polypeptide suggesting that the majority of carbohydrate chains on GP 110 are of the complex type.
Antiserum was raised in rabbits against a bile canalicular glycoprotein of Mr = 110,000 purified to homogeneity from of rat liver. The antisera specifically immunoprecipitated a Mr = 110,000 polypeptide from hepatocytes metabolically labeled with [35S]methionine. When hepatocytes in primary culture were incubated with tunicamycin before labeling with [35S]methionine in the presence of tunicamycin, the major polypeptide immunoprecipitated by the specific antiserum from Triton X-100 extracts of cells had a molecular weight of 59,000. Enzymatic removal of N-linked carbohydrates from the Mr = 110,000 glycoprotein by N-glycanase digestion also yielded a polypeptide with minimum Mr = 59,000. In pulse-chase experiments using [35S]methionine, the Mr = 110,000 protein detected by the specific antisera first appears as Mr = 85,000 and 75,000 intermediate species which are endoglycosidase H sensitive. The Mr = 85,000 intermediate form is lost first with time followed by the Mr = 75,000 form giving rise to the Mr = 110,000 form that is endoglycosidase H resistant. Neuraminidase digestion of the Mr = 110,000 form generated an Mr 85,000 form but with a different carbohydrate structure than the intermediate Mr 85,000 form detected in the pulse-chase experiments. The time required to accomplish the processing of the Mr = 85,000 and 75,000 forms is relatively slow. Finally, the terminal sugars are added and the mature Mr = 110,000 glycoprotein is rapidly transported to the cell surface. A minimum time of 90 min is required for the Mr = 110,000 bile canalicular glycoprotein to be synthesized, processed, and reach the cell surface which is long relative to the time required (10 min) for another domain-specific protein, the receptor for asialoglycoproteins, to reach the sinusoidal surface. The Mr = 110,000 bile canalicular glycoprotein turns over in the bile canalicular domain with a half-life of 43 h while the asialoglycoprotein receptor turns over in the sinusoidal domain with a half-life of 23 h.
A region of DNA 5' to the human myelin basic protein (MBP) gene, located on the long arm of chromosome 18, is a site of restriction-fragment-length polymorphism (RFLP) showing 37% heterozygosity in 40 subjects studied. Southern transfer analysis using a 0.9-kb genomic fragment encompassing the first exon of the human MBP gene reveals this polymorphism with at least nine restriction enzymes, indicating that insertion, deletion, or both is the basis for the DNA length variation. Double restriction-enzyme digest analysis suggests that this polymorphism is within the region 0.5-2.0 kb upstream of the coding region of the first exon of the human MBP gene. Eleven different allelic RFLPs were identified, differing in size by as many as 450 bp. The distribution of insertion/deletion-size variants from this region is bimodal, with most restriction fragments varying in size over a 0.1-kb range. Pedigree analysis of polymorphism at this site in one three-generation family shows Mendelian assortment of parental haplotypes. The form and frequency of polymorphism generated by this site is similar to that reported for human DNA regions comprised of homologous short tandem repeats.
The dbl oncogene was initially isolated following transfection of NIH3T3 cells with DNA of a human diffuse B cell lymphoma. Its transcribed sequences were shown to be distributed over a 30-kb span within a molecularly cloned 45-kb segment of human DNA which contained the transforming gene. By restriction mapping, its transcribed region corresponded to that of its normal allele, except at the 5' end where a rearrangement involved transcribed dbl oncogene sequences from another locus. An independent isolate of a dbl-related transforming gene was obtained following transfection of NIH3T3 cells with DNA of a human nodular poorly differentiated lymphoma (NPDL). Physical mapping indicated that this transforming gene, designated NPDL-dbl, shared considerable homology with the dbl oncogene, but differed at both 5' and 3' termini. Its point of divergence from the normal allele at the 5' end was at least 10 kb upstream from that of the dbl oncogene. The oncogenes each expressed truncated transcripts compared to the 5.3-kb normal transcript. The dbl and NPDL-dbl oncogene translational products of 66 and 76 kDa, respectively, were consistent with their corresponding major 2.8- and 3.5-kb transcripts. It was not possible to detect evidence of the 5' structural rearrangements associated with these oncogenes in either of the original tumors. Thus, if these rearrangements were critical to their activation, they occurred in the process of gene transfer or in vivo in only a minority of tumor cells.