Suicide prevention versus alcohol promotion.
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Alcoholism↗
Biomedical subjects
A Michael
Publications and source records attributed to A Michael.
Integrin-mediated interactions between primary/T-sv40 immortalized human glomerular epithelial cells and type IV collagen.
The use of human glomerular epithelial cells (HGEC) in research has been severely restricted by several obstacles, which have been circumvented by the generation of T-SV40 immortalized human visceral glomerular epithelial cells (Delarue et al, 1991). In this work, we compared the primary and immortalized HGEC for expression of integrin and some nonintegrin surface receptors. We also studied the adhesion of both types of HGEC to glomerular basement membrane (GBM), type IV collagen (tIV), and its major noncollagenous NC1 domain. The integrins mediating adhesion of HGEC to tIV were also examined. Expression of integrin and some nonintegrin cell surface receptors was analyzed by flow cytometry. Adhesion to GBM, tIV, and its major noncollagenous NC1 domain was studied by direct solid phase cell adhesion assays. Identification of integrins mediating adhesion of HGEC to tIV was achieved by inhibition of cell adhesion using monoclonal antibodies to integrin subunits. The primary and immortalized HGEC share phenotypic characteristics, and alpha3beta1 appeared to be the major integrin present on both HGEC types. The kinetics of binding to GBM, tIV, and its noncollagenous NCI domain were similar in both the primary and immortalized HGEC, although the latter displayed a somewhat weaker binding. Both the primary and immortalized HGEC displayed significantly better adhesion to NC1-alpha3 compared with NC1-alpha1, alpha3beta1 appears to be the major integrin mediating the adhesion of HGEC to tIV. Our studies suggest that alpha3beta1 is the major integrin present on HGEC. This has been confirmed by flow cytometric analysis. In addition, we demonstrated a functional role for this integrin in mediating attachment of HGEC to tIV. Our data also demonstrate a preference in binding of HGEC to alpha3 chains of NC1 compared with alpha1 chains of NC1. These findings were seen in both the primary and immortalized HGEC. The T-SV40 immortalized HGEC can therefore serve as a very useful tool to study glomerular visceral cell biology.
Animals↗
Financing gene therapy beyond phase II.
If all the gene therapy protocols now in development reach the market, not only will it be a miracle, it will also cost an estimated $37.5 billion. There are around 250 protocols currently in development, most of which are in their earliest phases. Each of them could cost between $100 million and $200 million to take to market. The money raised by gene therapy companies over the 18 months up to June 1996--550 million--would fund the development of only a small handful of protocols. Where, then, will companies get the money for clinical development?
Biotechnology↗
Morbid jealousy in alcoholism.
BACKGROUND: Morbid jealousy is an incompletely understood syndrome. The association between morbid jealousy and alcoholism is unclear. METHOD: Morbid jealousy was assessed in 207 male patients with alcohol dependence (DSM-III-R) using a semi-structured interview schedule administered both to patients and their spouses. RESULTS: Thirty-four per cent (71 out of 207) suffered from morbid jealousy. Morbid jealousy had different manifestations. Some patients expressed it only when intoxicated, others even when sober and in some the jealousy took the form of a delusional disorder. CONCLUSIONS: Alcoholism appears to have an aetiological role in the development of morbid jealousy. Detecting morbid jealousy when it is expressed only under the influence of alcohol has preventive implications.
Adult↗
Delusions of pregnancy.
We report five cases of delusions of pregnancy of whom three were women and four had chronic schizophrenia. We draw the attention of clinicians to this symptom which is not as rare as has previously been thought.
Adult↗
Periprosthetic bone mineral density after Mueller and Zweymueller total hip arthroplasties.
To assess the adaptive bone changes in adult human hips after insertion of cemented or uncemented acetabular and femoral components for total hip arthroplasty, a retrospective clinical study using dual energy xray densitometry was conducted. A consecutive homogeneous group of 52 female patients with an average age of 61 years was operated on for unilateral hip osteoarthritis. The types of prosthetic components used were the cemented Mueller and the uncemented Zweymueller socket and stem. Periprosthetic bone mineral density was measured in 7 different zones (Zones I to VII) in hips that were operated on and hips that were not, and the results were compared to quantify periprosthetic bone mineral changes over time. The Zweymueller socket induced bone resorption at the medial and caudal zone of the acetabulum, whereas implantation of the Mueller polyethylene socket was associated with a significant increase in bone mineral density only at the cranial zone of the acetabulum. The stem of the Mueller prosthesis induced bone mass reduction in the lesser trochanter area and in the distal lateral fixation cortex. The Zweymueller stem produced significant bone resorption in the area of the lesser trochanter, and in the medial and lateral distal cortex of the femur. The Mueller and Zweymueller stems induced bone mass increase in the greater trochanter area. These findings were unaffected by the age of the patients. Further improvement in densitometry technology may be of major clinical relevance for early detection of aseptic loosening in total hip arthroplasty.
Adult↗
Synthesis and pharmacological evaluation of hexahydrofluorenamines as noncompetitive antagonists at the N-methyl-D-aspartate receptor.
The noncompetitive (PCP) site of the N-methyl-D-aspartate (NMDA) receptor complex has been implicated in a number of pathologies, including the etiology of ischemic stroke. Recent testing has shown that cis-1,2,3,4,9,9a-hexahydro-N-methyl-4aH-fluoren-4a-amine (1), a rigid analog of PCP, is a potent antagonist at this site (IC50 = 30 nM for displacement of [3H]TCP). On the basis of this finding, a number of derivatives encompassing variations in stereochemistry, amine substitution and position, aromatic and aliphatic ring substitution, and heteroatom ring substitution have been prepared to explore the structure-activity relationships around this ring system. All compounds were evaluated for their PCP receptor affinity; potent compounds were also tested in vitro (cultured neurons) and in vivo (prevention of NMDA-induced lethality in mice). The present hexahydrofluorenamines demonstrated a wide range of potencies, with optimal affinity concentrated in analogs containing a heteroatom (sulfur) in the B ring (IC50 of 11 nM versus [3H]TCP for 16b), methyl substitution on the amine, and R stereochemistry at the 4a position. No significant improvement in affinity was seen with aromatic ring substitution. Aliphatic ring substitution, large amine substituents, and alterations in the position of amine substitution on the ring system resulted in a loss of potency. To explore the effect of simultaneous hydrogen bonding with a putative receptor atom from two directions, the 2-hydroxymethyl derivatives were prepared. This substitution resulted in a loss in receptor binding affinity. Molecular modeling, X-ray, and NMR studies have been used to determine an optimal conformation of the hexahydrofluoreneamines at the receptor site.
Animals↗
Fertility prognosis for infertile couples.
OBJECTIVE: To develop a fertility prognosis model for infertile couples. DESIGN: Prospective follow-up study. PARTICIPANTS: In the period November 30, 1977 to June 1, 1985, 321 consecutive couples were investigated for infertility at Hvidovre University Hospital. Investigation of the female included detection of ovarian, cervical, and anatomic disorders, whereas in the male semen analysis and sperm penetration test (P-test) were performed. Altogether, 108 couples (34%) conceived, whereas 213 (66%) were observed for an average of 2.3 years without having achieved pregnancy. MAIN OUTCOME MEASURE: The Cox regression model was used to predict the time required to conceive based on informations provided by fertility investigations. RESULTS: Three of 16 prognostic variables (the period of infertility, the female infertility factor, and the P-test) possess significant prognostic information. The period of infertility and the P-test are best scored as continuous variables, whereas the female infertility factor are best categorized in four classes, i.e., normal, ovulation or cervical disorder, anatomic disorder, or a combination of disorders. CONCLUSIONS: The three prognostic variables are combined to form a prognostic index that predicts the fecundability of the individual infertile couple.
Adult↗
Antigenuria in healthy Papua New Guinean children with nasal Haemophilus influenzae type b carriage.
In 100 healthy children under the age of 3 years living in the vicinity of Goroka, Papua New Guinea, the nares were cultured for Haemophilus influenzae type b (Hib), and a urine sample was obtained for measurement of Hib polysaccharide (PS) by ELISA. Hib carriage was detected in nine children and Hib PS was detected in the urine of 11. Hib PS was found in seven of nine Hib nasal carriers compared with four of 91 healthy children without Hib in their nares (p < 0.001). The range of urine antigen concentrations in the two groups was similar (0.6 to 2.7 ng/ml). The relative risk of antigenuria in the carriers, compared with the children with negative nares cultures, was 58 (95% confidence interval, 10.5-324). These data extend previous observations from Hib carriers studied in the United States and show that Hib carriage in children from a developing country is associated with antigenuria. Further studies are needed to determine whether carriers and patients can be differentiated by differences in the magnitude of the concentration of Hib PS excreted in urine.
Antigens, Bacterial↗
Interhemispheric electroencephalographic coherence as a biological marker in alcoholism.
Electroencephalographic coherence scores in 21 teetotaler first-degree relatives of alcoholics, 27 subjects with alcohol dependence and 21 healthy subjects without a family history of alcohol abuse were compared. The relatives had significantly higher coherence scores in the frontal and parietal leads than the alcoholics and in the frontal and centroparietal leads than in the healthy subjects. This might represent a trait marker of resilience in subjects at high risk for the development of alcoholism.
Adult↗
Do social and demographic factors influence the nature and localisation of somatic complaints?
Demographic characteristics of specific somatic complaints were studied systematically in 60 consecutive patients whose main complaints were bodily symptoms without organic pathology, to determine if the social and demographic factors in any way influenced the nature or localisation of specific common somatic complaints. The Scale for Assessment of Somatic Symptoms was used to systematically acquire details of individual complaints. The commonest somatic complaints identified were weakness of body or mind (72%), headache (67%), fatiguability (37%) and burning sensations (35%). Subjects with less education reported weakness of body and mind, and multiple sites of pain more often, but lethargy and fatiguability less often than those with higher education. Rural subjects reported burning sensations and pain in their extremities more frequently. A sensation of 'gas' was more often reported by younger subjects, and pain in the extremities by male subjects. The factors which determine the choice of somatic complaints remain elusive and the exact reasons for these demographic relationships are unclear at present.
Adolescent↗
Endometrial ablation and air embolism.
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Adult↗
Safety and efficacy of long-term cyclosporine-ketoconazole administration and preliminary results of a randomized trial.
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Azathioprine↗
Cyclosporine-ketoconazole interaction. Long-term follow-up and preliminary results of a randomized trial.
Forty-three renal transplant recipients receiving cyclosporine were started on 200 mg/day of oral ketoconazole 10 days to 75 months posttransplant. The cyclosporine dose was reduced by 70% when ketoconazole was started. The mean cyclosporine dose was 5.6 mg/kg/day preketoconazole, and 0.9, 0.8, and 0.7 mg/kg/day at one, two, and three years after addition of ketoconazole (cyclosporine dose reduction 84%, 86%, and 88% at one, two, and three years, respectively). Two patients died after two years of combination therapy, six patients returned to dialysis, and ketoconazole was discontinued in four. Renal function in patients on ketoconazole remained stable (serum creatinine 1.8, 1.7, 1.7, and 1.8 mg/dl preketoconazole and at one, two, and three years, respectively). In a second study, 52 patients were randomized to standard doses of cyclosporine (n = 28), or reduced doses of cyclosporine with ketoconazole (n = 24); seven of the patients were not started on ketoconazole. In 28 patients on standard-dose cyclosporine, there were two deaths and one graft loss. In 17 patients receiving ketoconazole there were two deaths and no graft losses. Renal function and the frequency of rejection episodes was similar in the two groups. In the ketoconazole group, the cyclosporine dose was < 20% of that in the patients on standard doses. In both studies addition of ketoconazole to cyclosporine-treated patients resulted in significant inhibition of cyclosporine metabolism and decrease in dosage in patients followed for up to four years. This drug interaction provides a significant reduction in cost of immunosuppressive therapy in organ transplant recipient.
Adult↗
Stereoselective epoxidation of phenyl allyl ether by alkene-utilizing bacteria.
Eighteen newly isolated ethene- and propene-utilizing bacteria were screened for the ability to produce phenyl glycidyl ether, a common precursor for the synthesis of beta blockers, from phenyl allyl ether. These organisms included Aerococcus, Alcaligenes, Micrococcus and Staphylococcus spp. and a variety of Gram-negative, Gram-positive and Gram-variable mesophilic rods/coccobacilli not yet identified. The majority of ethene- and propene-grown cultures (14 strains) accumulated phenyl glycidyl ether (0.4-1.7 mM) as the sole oxidation product. The bioconversions with the three most promising ethene-utilizers (M26, M90C, M93A) were scaled-up to yield essentially optically pure (enantiomeric excess = 93%) S-(+)-phenyl glycidyl ether. This is currently under investigation for commercial production of optically pure beta blockers.
Alkenes↗
Stability of negative symptoms of schizophrenia.
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Adult↗
Reduction in the incidence of acute bronchitis by an oral Haemophilus influenzae vaccine in patients with chronic bronchitis in the highlands of Papua New Guinea.
Following the administration of a standardized questionnaire, 62 adult patients with chronic bronchitis were enrolled into a double-blind controlled trial of an oral killed Haemophilus influenzae vaccine in the highlands of Papua New Guinea. A 3-day course of vaccine or placebo was given monthly for 3 consecutive months. Participants were monitored weekly over 12 months for acute exacerbations; early morning sputum specimens were collected monthly and during acute exacerbations. Density of colonization by H. influenzae and H. parainfluenzae was determined by standard quantitative and semiquantitative techniques, and the latter method (quadrant score) was used to determine the density of growth of pneumococci. A total of 30 patients received vaccine and 32 placebo. The incidence rate of acute bronchitis in the vaccine group (0.011 episodes/person-weeks) was significantly lower than that in the placebo group (0.021 episodes/person-weeks), but there was no difference between the two groups in the incidence rates of more severe disease. Vaccine efficacy was maximal at times of peak incidence of disease. There was no evidence of a decline in vaccine efficacy for acute bronchitis over the 12-month follow-up period. The number of viable H. influenzae in the sputum declined in both vaccine and placebo groups over the 12-month follow-up period. The average concentration of H. influenzae in the vaccine group fell below that in the placebo group within 1 to 2 months after first immunization and remained so for 12 months, although the difference between the two groups narrowed during the follow-up period.(ABSTRACT TRUNCATED AT 250 WORDS)
Acute Disease↗