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Biomedical subjects

P Hayes

Publications and source records attributed to P Hayes.

At least 19 recordsLinked to original sources

A cDNA clone for a novel nuclear protein with DNA binding activity.

In an effort to identify trans-acting factors regulating specific genes, we cloned a novel human gene, DBP-5. The cDNA clone contains a predicted open reading frame coding for a potential 1,179 amino acid protein. The mRNA corresponding to DBP-5 is ubiquitously distributed, and the gene is phylogenetically conserved. Immunofluorescence analyses with several cell lines indicate that the protein is localized to the nucleus. Sequence analysis revealed unusual features of the predicted protein structure, including four completely conserved repeats. The phylogenetic conservation of DBP-5, the ubiquity of its expression, its nuclear localization, and its ability to bind DNA sequences, raise the possibility that DBP-5 may play a role in the organization of interphase chromatin and/or in transcriptional regulation.

Amino Acid Sequence

Sensitive detection of trypanosomes in tsetse flies by DNA amplification.

African trypanosome species were identified using the Polymerase Chain Reaction (PCR) by targeting repetitive DNA for amplification. Using oligonucleotide primers designed to anneal specifically to the satellite DNA monomer of each species/subgroup, we were able to accurately identify Trypanosoma simiae, three subgroups of T. congolense, T. brucei and T. vivax. The assay was sensitive and specific, detecting one trypanosome unequivocally and showing no reaction with non-target trypanosome DNA or a huge excess of host DNA. The assay was used to identify developmental stage trypanosomes in the tsetse fly. The use of radioisotopes was not necessary and mixed infections could be detected easily by incorporating more than one set of primers in a single reaction. The use of crude preparations of template made the process very rapid. The methodology should be suitable for large-scale epidemiological studies.

Animals

Physiologic effects of administration of interleukin 1 beta in cows.

The immunomodulating polypeptide interleukin 1 beta (IL-1 beta) has been shown to be homologous to osteoclast-activating factor and is capable of stimulating increased osteoclastic bone resorption. This effect prompted an investigation into the potential use of IL-1 beta for prevention of parturient paresis, a disease of dairy cows characterized by hypocalcemia and poor osteoclastic resorption of bone. Six nonpregnant cows were treated with a high dosage of IL-1 beta (166 ng/kg of body weight) every 8 hours for 4 days. The IL-1 beta treatment significantly (P < 0.05) increased urinary hydroxyproline excretion, an index of osteoclast activity, indicating that bone calcium resorption might be stimulated by IL-1 beta treatment of cows. However, IL-1 beta treatment also caused transient fever, inappetence, increased pulse and respiratory rate, and diuresis. The acute, but transient, effect of IL-1 beta treatment was to cause a decrease in plasma calcium and phosphorus concentrations. The pleiotropic effects of IL-1 beta administration negated the positive effects on osteoclastic bone resorption, and indicates that this cytokine may be of minimal benefit for prevention of parturient paresis.

Animals

Influence of menstrual cycle and gender on alprazolam pharmacokinetics.

The effects of menstrual cycle phases and gender on alprazolam pharmacokinetics were evaluated in normal volunteers. Alprazolam (1 mg) was administered to seven women during the late follicular and luteal phases of the menstrual cycle and to eight men on one occasion. No difference in alprazolam pharmacokinetic parameters was observed during the menstrual cycle phases. Mean alprazolam clearance (+/- SD) was 0.0037 +/- 0.0009 ml/hr during the follicular phase and 0.0036 +/- 0.001 ml/hr during the luteal phase (p greater than 0.05, difference not significant). With use of weight as a covariant, there was no difference in alprazolam pharmacokinetic parameters between women and men. Mean alprazolam clearance (+/- SD) was 0.0036 +/- 0.0009 ml/hr in women compared with 0.0041 +/- 0.0006 ml/hr in men (p greater than 0.05, difference not significant). Although alprazolam metabolism was similar on the 2 days tested, alterations may occur at other times during the menstrual cycle. Further investigation is needed to understand the effects of menstrual cycle phases and gender on drug metabolism.

Adult

Diving and hypothermia.

Hypothermia is not and should not be a prevalent feature of diving, yet many divers become extremely cold and uncomfortable during their work. It is not difficult to provide adequate insulation to protect the torso but if movement and dexterity are to be maintained, the extremities will inevitably suffer. Free swimming divers are limited by duration in cold (5 degrees C), shallow (10 m) water. Six hours is a typical maximum before both core cooling and extremity pain or dysfunction pose a threat. Habituation to cold may be observed in some divers. Surface supplied or bell supported divers, relying on supplementary hot water, need between 500 and 3500 Watts to preserve comfort over the range 10 to 300 m depth. Deep diving, using oxyhelium gas mixtures, can result in high respiratory convective losses in excess of 300 Watts. Heat exchangers are used to prevent damage to the tract. There have been a number of cases where hypothermia has been implicated in the cause of death in diving accidents, but generally the reason is not lack of physiological knowledge but equipment failure and inadequate contingency. Recent developments in diver protection have focused on electrically heated hand wear to preserve performance and prevent the risk of non freezing injury in a relatively inactive diver.

Acclimatization

Comparison of propranolol with injection sclerotherapy in prevention of rebleeding from oesophageal varices in cirrhotic patients.

Selected patients with variceal bleeding were randomly assigned to either weekly injection sclerotherapy (n = 56) or to oral propranolol (n = 52). During follow-up, 28 (54%) of the propranolol group and 25 (45%) of the sclerotherapy group had an episode of rebleeding. The long term risks of bleeding in the propranolol and sclerotherapy groups were 0.05 and 0.037 bleeds/patient-month, respectively, and the corresponding death rates during follow-up were 42 and 38%. There were no statistically significant differences between propranolol and the established therapy, but it was concluded that if propranolol is used in the prevention of rebleeding, it must be part of an overall approach that provides for the management of active variceal haemorrhage by other means if this condition continues.

Esophageal and Gastric Varices

The effect of mode of delivery on the risk of intraventricular hemorrhage in nondiscordant twin gestations under 1500 g.

The effect of birth order, presentation, and mode of delivery on neonatal outcome in nondiscordant twin gestations under 1500 g was investigated. All neonates had echoencephalograms performed by the fourth day of life to diagnose the presence and severity of intraventricular hemorrhage. One hundred fifty-six sets of twins were included in the study, of which 59 were in a vertex/vertex presentation, 59 in vertex/nonvertex presentation, and 38 with twin A in a nonvertex presentation. Second twins were characterized by a higher incidence of respiratory distress syndrome (RDS): 66 versus 54% (P less than .05), and severe grades of intraventricular hemorrhage: 30 versus 19% (P less than .01). For vertex/vertex twins, cesarean delivery did not result in improved outcome. Rather, the incidence of RDS was significantly increased in neonates from this group delivered by cesarean birth: 67 versus 46% (P less than .01). Among twins in which at least one of the fetuses was in a nonvertex presentation, those born via cesarean delivery demonstrated a lower incidence of both severe grades of intraventricular hemorrhage and mortality. However, after multivariate analysis to correct for differences in birth weight between the groups, no advantage for cesarean delivery could be demonstrated. Therefore, differences in birth weight, rather than in mode of delivery, accounted for the differences in the neonatal outcome of nonvertex-presenting twins.

Birth Order

Epidemic listeriosis associated with Mexican-style cheese.

In Los Angeles County, California, 142 cases of human listeriosis were reported from January 1 through August 15, 1985. Ninety-three cases (65.5 percent) occurred in pregnant women or their offspring, and 49 (34.5 percent) in nonpregnant adults. There were 48 deaths: 20 fetuses, 10 neonates, and 18 nonpregnant adults. Of the nonpregnant adults, 98 percent (48 of 49) had a known predisposing condition. Eighty-seven percent (81 of 93) of the maternal/neonatal cases were Hispanic. Of the Listeria monocytogenes isolates available for study, 82 percent (86 of 105) were serotype 4b, of which 63 of 86 (73 percent) were the same phage type. A case-control study implicated Mexican-style soft cheese (odds ratio, 5.5; 95 percent confidence interval, 1.2 to 24.8) as the vehicle of infection; a second case-control study showed an association with one brand (Brand A) of Mexican-style soft cheese (odds ratio, 8.5; 95 percent confidence interval, 2.4 to 26.2). Laboratory study confirmed the presence of L. monocytogenes serogroup 4b of the epidemic phage type in Brand A Mexican-style cheese. In mid-June, all Brand A cheese was recalled and the factory was closed. An investigation of the cheese plant suggested that the cheese was commonly contaminated with unpasteurized milk. We conclude that the epidemic of listeriosis was caused by ingestion of Brand A cheese contaminated by one phage type of L. monocytogenes serotype 4b.

Adult

Experimental analysis of effects of pin pretensioning on external fixator rigidity.

The effects of same-fragment pin pretensioning on the rigidity of a simple fixator system were investigated. An external fixator device constructed to apply same-fragment pin pretensioning of a defined amount was applied to a bone model made of pedilen cylinders. System rigidity was tested for varying degrees of pin pretensioning in axial compression and AP bending. Pin pretensioning, bringing transfixing pins together, tended to weaken the system in both modalities tested. Tensioning by bringing the pins apart increased the rigidity of the system in AP bending and axial compression.

Biomechanical Phenomena

Transjugular liver biopsy--an Australian experience.

During the four year period 1983-87 transjugular liver biopsy was performed on 67 patients (M43, F24) aged 17-79 yr (mean 45.6 yr). Standard percutaneous biopsy was contraindicated by coagulation disorders (95%) often with ascites (17%). Biopsies were taken using a specially modified Ross trans-septal needle passed into hepatic veins under fluoroscopic guidance. Hepatic tissue samples were obtained from the initial biopsy in 62 (93%) patients. In 30 consecutive transjugular biopsies a mean area of 38.2 mm2 per section (0.9-100 mm2) was available for histology compared with an area of 15.9 mm2 (9.3-48.8 mm2) in 50 consecutive percutaneous biopsies. Improved techniques of sample washing, sieving and fixation optimised separation of hepatic tissue from blood clot and fibrin. Four patients experienced significant complications but no deaths occurred. Individual diagnoses were changed in 17 patients as a result of biopsy findings. This study confirms the efficacy and relative safety of the transjugular approach in obtaining liver biopsies from patients with contraindications to standard percutaneous techniques.

Adolescent

A major histocompatibility complex class III allotype (C4B 2) associated with primary biliary cirrhosis (PBC).

Primary Biliary Cirrhosis (PBC) is a female associated disease of unknown aetiology, although there is evidence of immunological abnormalities. There is no known cure; liver damage is progressive and eventually fatal, although transplantation can prevent patient death. Data presented here show, for the first time, a strong association in Caucasoids between PBC and the major histocompatibility complex (MHC). 45% of patients studied, compared with only 17% in a control group, expressed an MHC Class III allotype C4B 2 (pc = 0.014). Polymorphisms of MHC Class I, Class II, and other Class III gene products which flank the C4 genes were not found to be associated with the disease. Although we cannot rule out the involvement of other loci linked to the C4B 2 complement gene, the data provide strong evidence that this genetic area is implicated in the pathogenesis of this disease.

Complement C3