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Biomedical subjects

B Hamilton

Publications and source records attributed to B Hamilton.

At least 91 records · Page 5Linked to original sources

Estimation and characterization of the potential renal organ donor pool in Pennsylvania. Report of the Pennsylvania Statewide Donor Study.

The Pennsylvania Statewide Donor Study evaluated deaths under the age of 66 occurring in 149 participating hospitals in 1987. After elimination of 6146 patients from 11,983 based upon ICD-9 code criteria, an on-site medical record review was performed on 5603 patients. Each patient was assessed for organ donor suitability based upon brain death and medical suitability criteria--and, after a series of eliminations, 453 patients were found to have a moderate or higher potential as acceptable organ donors. An estimation of the organ donor rate was placed between 38.3 and 55.2 donors per million population per year, depending upon the stringency of organ donor criteria. Educational efforts targeted at physicians, patient's families and transplant surgeons will be necessary, however, to attain this maximal rate.

Adult↗

Meiotic chromosome behaviour reflects levels of sequence divergence in Sus scrofa domestica satellite DNA.

We present a general model for the evolution of chromosome-specific satellite DNA subfamilies. Sus scrofa domestica has a bimodal karyotype with two autosomal subsets of 12 meta-/submetacentric (Mc) and 6 acrocentric (Ac) chromosome types (Mc and Ac "subgenomes"). We show that the centromeric heterochromatin is characterised by two distinct satellite DNA families designed Mc1 and Ac2. Mc1 is a diverse satellite family of the Mc subgenome of which certain members with a 100 bp repeat unit are found to occur at the pericentromeric regions of each Mc autosome, while others are chromosome-specific, e.g. clone Mc pAv1.5, a higher order repeat variant, which hybridises specifically to chromosome 1. Ac2 is a homogeneous satellite occurring at the subterminal pericentromeric regions of all Ac autosomes. DNA sequence analyses showed that all clones investigated are built up from a 14 bp repeat unit which is highly conserved. In situ hybridisation to meiotic pachytene nuclei revealed a distinct spatial arrangement of the Ac2 centromeric satellite.

Animals↗

Multicenter comparison of once- and twice-daily isradipine to hydrochlorothiazide for the treatment of hypertension in elderly patients.

After 8 weeks of isradipine, a twice-a-day dihydropyridine calcium channel blocker, 49% of elderly patients showed a complete response (sitting diastolic blood pressure less than or equal to 85 mm Hg) and 36% showed a partial response (sitting diastolic blood pressure decrease greater than or equal to 10 mm Hg) for an 85% total response rate. Hydrochlorothiazide gave a complete response in 36% of the patients and a partial response in 33%, for a 69% total response rate (p less than 0.0046). Because elderly subjects have reduced clearance for many drugs, we determined how those who responded to twice-a-day administration would respond to once-a-day administration. After 4 weeks of isradipine administered once a day, 54% of the patients showed a complete or partial response, whereas 38% of the patients who were changed to placebo showed a response. In contrast, 82% of patients receiving hydrochlorothiazide once a day showed a response, whereas 60% of patients who were changed to placebo showed a response. These data indicate that the standard formulation of isradipine was not effective when administered once a day.

Aged↗

Nursing research.

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Clinical Competence↗

Functional outcome following spinal cord injury. A comparison of specialized spinal cord injury center vs general hospital short-term care.

The functional outcomes of 185 patients with spinal cord injuries undergoing rehabilitation who were initially treated in a specialized short-term care unit (center patients) were compared with those of 153 patients initially treated in general hospitals (noncenter patients). After stabilization, all patients were admitted to the Rehabilitation Institute of Chicago (Ill) and received the same rehabilitation program. The groups were comparable in terms of demographic, injury, and medical characteristics at the time of rehabilitation center admission, but the duration from injury to rehabilitation was more than twice as long for noncenter patients. While center patients were discharged from the rehabilitation center at equivalent functional skill levels, their daily rate of functional gains during the rehabilitation center stay was significantly greater than that of noncenter patients although the length of stay at the rehabilitation center was comparable for the two groups. These results support the practice of specialized short-term spinal cord injury care as a means of enhancing rehabilitation outcome.

Activities of Daily Living↗

Control of Saccharomyces cerevisiae catalase T gene (CTT1) expression by nutrient supply via the RAS-cyclic AMP pathway.

In Saccharomyces cerevisiae, lack of nutrients triggers a pleiotropic response characterized by accumulation of storage carbohydrates, early G1 arrest, and sporulation of a/alpha diploids. This response is thought to be mediated by RAS proteins, adenylate cyclase, and cyclic AMP (cAMP)-dependent protein kinases. This study shows that expression of the S. cerevisiae gene coding for a cytoplasmic catalase T (CTT1) is controlled by this pathway: it is regulated by the availability of nutrients. Lack of a nitrogen, sulfur, or phosphorus source causes a high-level expression of the gene. Studies with strains with mutations in the RAS-cAMP pathway and supplementation of a rca1 mutant with cAMP show that CTT1 expression is under negative control by a cAMP-dependent protein kinase and that nutrient control of CTT1 gene expression is mediated by this pathway. Strains containing a CTT1-Escherichia coli lacZ fusion gene have been used to isolate mutants with mutations in the pathway. Mutants characterized in this investigation fall into five complementation groups. Both cdc25 and ras2 alleles were identified among these mutants.

Adenylyl Cyclases↗

Endogenous inhibition of red blood cell Na,K-ATPase in essential and pregnancy-induced hypertension.

Digoxin-like inhibitors of Na,K-ATPase have been implicated in the pathophysiology of essential (EH) and pregnancy-induced hypertension (PIH). A technique that enhances dissociation of digoxin from red blood cells (RBC) was used to displace endogenous digoxin-like substances from RBCs. RBC membranes were preincubated in Na and ATP (Release) or Na,K,Mg and ATP (Retention) prior to measuring ATPase activity. Groups studied were: 39 men with EH and 34 controls plus 10 women with PIH and 17 normotensive controls. All displayed similar increases in Na,K-ATPase activity (24.0 +/- 7.9%) following Release. Plasma digoxin immunoreactivity (DI) was measured in pregnant women, m = 0.25 +/- 0.07 ng/ml. No DI was detected in nonpregnant women, but RBCs from these women demonstrated the same increase in Na,K-ATPase activity after Release. The 24% increase in activity achieved by Na and ATP preincubation can be reversed by adding K and Mg to the Release suspension. However, after RBC-bound digoxin is displaced by Release preincubation, addition of K and Mg cannot promote renewed binding and pump inhibition. Thus, the observed endogenous inhibition is not due to displacement of a digoxin-like substance but probably is related to alteration of the enzyme-membrane interaction. Furthermore, even though pregnant women demonstrate DI, an inhibitory substance with digoxin-like binding could not be recognized using this technique.

Adult↗

Efficacy and safety of isradipine in hypertension.

Of the calcium channel blocking drugs, only verapamil is approved in the United States for treatment of hypertension. Isradipine is a 1,4-dihydropyridine calcium blocker that may be given on a twice-daily basis. It causes peripheral vasodilation with minimal cardiodepressant activity. We undertook a double-blind, parallel group randomized, multicenter study of 203 hypertensive subjects to examine the efficacy and safety of isradipine in treatment of hypertension. Subjects were given 0, 2.5, 5, 7.5, or 10 mg isradipine twice daily for up to 5 weeks. There was a significant dose-response relationship between isradipine dose and decrease in systolic blood pressure (SBP) and diastolic blood pressure (DBP). Isradipine 15 mg/day reduced supine pressure by 16/15 mm Hg in patients with starting DBP less than 105 mm Hg and by 38/22 mm Hg in those with starting DBP greater than or equal to 105 mm Hg. There was no significant orthostatic fall in blood pressure at any dose. Heart rate (HR) increased on an average by only a maximum of four beats/min. The drug was slightly more effective in the elderly in the standing position than in the young in the standing position. Adverse effects were mild, and only six patients were discontinued from the study because of adverse effects. Isradipine appears to be a safe, effective drug in monotherapy of hypertension at a wide range of patient ages.

Adolescent↗

Relationship between cellular RecA protein concentration and untargeted mutagenesis in Escherichia coli.

We measured the production of untargeted mutations in the cI and cII genes of untreated lambda phage undergoing a lytic cycle in UV-irradiated bacterial hosts. As previously shown, treatment with 4 micrograms/ml of rifampicin during post-irradiation incubation inhibited amplification of the RecA protein in these cells. In addition, we observed a decreased mutation rate compared to the untreated, irradiated bacteria. Treatment with 4 micrograms/ml or 8 micrograms/ml rifampicin did not prevent the UV induction of the umuDC operon, as judged by assay of beta-galactosidase activity in a umuC-lacZ fusion strain. In contrast, the UV-induction of beta-galactosidase in the sulA-lacZ fusion strain was decreased by 4 micrograms/ml rifampicin. The inhibition of untargeted mutagenesis by this drug treatment was also observed in a strain constitutive for SOS functions (lexA (Def)) as well as in a RecA-overproducing plasmid strain, suggesting the requirement of other factor(s) in wild-type recA+ cells. An htpR165-carrying strain, that blocks induction of heat-shock proteins, exhibited normal UV-promoted mutagenesis. A correlation was observed between the cellular concentration of RecA protein, increased spontaneously by a temperature shift in a lexA(Ts) strain, and the extent of UV-promoted untargeted mutagenesis. These results suggest a mechanistic role of RecA protein in this process.

Bacterial Proteins↗

Munchausen syndrome by proxy.

Munchausen syndrome by proxy is a form of child abuse in which a disorder of the child is fabricated by a parent. Although often considered rare, it may have been overlooked frequently in the past. The reported cases of children with Munchausen syndrome by proxy range in age from infancy to 8 years. Their "illnesses" consist of fabricated histories, inflicted physical findings, altered laboratory specimens, and induced disorders. The perpetrator usually is the child's mother, who may have Munchausen syndrome. Consequences of the syndrome may include painful tests, frequent hospitalizations, potentially harmful treatment, and death. The diagnosis can be made when medical and social histories are characteristic of the syndrome and clinical findings are absent, suggestive of induced illness, or resolve upon separation of the child and parent. Suspicion of the syndrome should be discussed with the family once the safety of the child is insured, and the case should be reported under the child abuse reporting law of the state. Social, family, and medical histories must be obtained and verified, and court intervention should be considered. Four patients who illustrate typical features of the syndrome are described.

Child↗

Use of a "pneumatic" tube in anatomic pathology.

In anticipation of the temporary relocation of Surgical Pathology some distance from the operating rooms, a "pneumatic" tube system was installed to transport fresh tissue from surgery to pathology at the Hospital of the University of Pennsylvania. The point-to-point 4-inch internal diameter system is actually of the blower or "pea-shooter" type. Side-opening carriers were preferred, and electronic sensors were installed for monitoring and safety. At the pathology end of the system, a complete panel of electrical controls exist that are capable of initiating the blower at either end, enabling full control. For possible future retrieval of stuck carriers, several points of mechanical entry were desired and constructed. The transit time over 886 feet varies with the weight of the specimen but averages 25-35 seconds. Thus far, after 32 months and 12,652 transits, no specimens have been lost or damaged. During the first few months, two specimens became stuck for reasons relating to human error but were easily retrieved. This system, in conjunction with operating room telephone intercoms, has become fully accepted and trusted by surgeons and pathologists.

Biopsy↗

High school students' long-term retention of sex education information.

Ninth grade students in a rural South Carolina school were pretested about sexuality information, completed a 12-unit reproductive health course in eight months, and were posttested. A control group received the same pretest and posttest. Both groups were retested after the 10th and 11th grades and mean scores were calculated and compared. The difference between the experimental group's pretest and posttest mean scores was 8.49 (p less than .001); the difference between the control group's pretest and posttest mean scores was 1.0 (p = .003). The experimental group's mean score remained at least 5.2 points higher (p less than .001) than the control group's score on the same test one and two years after the course. Comparison of the mean gain between the pretest and posttest scores, and between the pretest and fourth test scores, confirmed the results obtained by mean test scores. The test scores indicated that the knowledge of the experimental students increased significantly and was sustained for two years. Their scores remained significantly higher than those of the control group on the posttest, and on tests one and two years later.

Adolescent↗

Clinical trial of the efficacy and safety of ticarcillin and clavulanic acid.

Forty-three hospitalized patients were treated with a new antibiotic combination containing ticarcillin plus the beta-lactamase inhibitor, clavulanic acid, in a fixed combination for intravenous use. A variety of infections were treated, including pneumonia, bacteremia, urinary tract infection, and osteomyelitis. Of 50 episodes of infection in 43 patients, 44 clinical cures were obtained, with 5 patients improving and 1 patient failing to respond to treatment. In vitro susceptibility testing of 101 clinical isolates was notable for the rarity of resistance to the combination antibiotic. Of specific interest, all 14 isolates of Staphylococcus aureus were susceptible to ticarcillin plus clavulanic acid, whereas only 2 of the 14 isolates were susceptible to ticarcillin alone. Adverse reactions to the study drug were minimal; eosinophilia, unaccompanied by other allergic phenomena, and oral candidiasis were most frequent. Overall, the combination of ticarcillin with the beta-lactamase inhibitor, clavulanic acid, appears to be a safe and effective drug for the treatment of infections caused by susceptible organisms.

Aged↗

Lethal graft-versus-host disease: modification with allogeneic cultured donor cells.

The use of the bone marrow culture technique was studied as a means to prepare donor marrow for bone marrow transplantation to avoid lethal graft-versus-host disease (GVHD). Preliminary experiments demonstrated the rapid loss of theta-positive cells in such cultures, so that theta-positive cells were not detected after 6 days. Initial experiments in C3H/HeJ (H-2k, Hbbd) recipients prepared with 900 rad demonstrated improved survival when 3-day cultured C57BL/6 (H-2b, Hbbs) donor cells were used in place of hind limb marrow for transplantation. However, hemoglobin typing of recipient animals revealed only short-term donor engraftment, with competitive repopulation of recipient marrow occurring. Subsequent experiments were done in 1,200-rad prepared recipients, with long-term donor engraftment demonstrated. The majority of 1,200-rad prepared animals receiving cultured allogeneic cells died of GVHD, but animals receiving 28-day cultured cells had an improved 90-day survival and a delay in GVHD development over animals receiving hind limb marrow or marrow from shorter times in culture. In addition, animals receiving anti-theta-treated, 3-day nonadherent cells had an improved survival (44%) over animals receiving anti-theta-treated hind limb marrow (20%). These experiments demonstrate modest benefit for the use of cultured cells in bone marrow transplantation across major H-2 histocompatibility complex differences.

Animals↗