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Biomedical subjects

P Bennett

Publications and source records attributed to P Bennett.

At least 127 records · Page 7Linked to original sources

A two-year double-blind controlled study of the clinical effect of combined and sequential postmenopausal replacement therapy and steroid metabolism during treatment.

A total of 151 postmenopausal women were randomly allocated to 3 groups for treatment with hormone replacement therapy. One group received combined therapy (2 mg oestradiol (E2) and 1 mg norethisterone acetate (NETA) daily), the second group was placed on sequential therapy (2 mg E2 for 12 days, 2 mgE2 and 1 mg NETA for 10 days and 1 mg E2 for 6 days), while the third was given placebo. Treatment was administered over 24 cycles of 28 days. The two active treatments were equally effective in relieving climacteric symptoms. In the combined therapy group, 62% of the women experienced spotting and/or breakthrough bleeding during the first 3 cycles; thereafter this proportion decreased to between 3 and 18% in each of the following three-cycle periods. Sixty-four percent (64%) of these women had no more bleeding after the first 3 cycles. Endometrial atrophy was detected in 93% of the women in this group after 24 cycles of therapy. Bleeding irregularities occurred during the first 3 cycles in 27% of the patients treated with sequential therapy and in 21% of those receiving placebo. In the subsequent 3-cycle periods these figures fell to below 10% in the 2 groups. In all 3 groups weight remained stable but blood pressure increased equally in the actively treated groups and the placebo group. The levels of follicle-stimulating hormone (FSH), sex-hormone-binding globulin (SHBG) and the free fraction of E2 in serum were significantly lower in the combined therapy group than in the sequential therapy group. The higher level of free E2 in the latter group may have been caused by a decrease in metabolism associated with the increased SHBG concentration. It was concluded that combined treatment with E2 and NETA might provide an alternative to sequential treatment in postmenopausal women willing to tolerate the initial high risk of breakthrough bleeding/spotting in order to avoid subsequent regular bleeding. In the subgroup of women in whom bleeding irregularities continue, sequential treatment should be considered.

Double-Blind Method↗

Prediction of pulmonary function in wheelchair users.

As a result of the improved medical treatment of infectious diseases, these formerly leading causes of mortality in the United States have been supplanted in rank by chronic events as the major causes of death. The major causes include coronary artery disease, respiratory disease, and cancer. Static and dynamic pulmonary functions in the apparently healthy wheelchair user population were measured and then modelled using stepwise regression. One hundred and nine wheelchair users (97 males, 12 females) with paraplegia (n = 77) or quadriplegia (n = 32) gave informed consent and participated in this study. Subjects ranged from being Olympic caliber wheelchair marathon racers to those who live sedentary life styles. Subjects performed three slow vital capacity (SVC) tests, three forced vital capacity (FVC) tests, and three maximal voluntary ventilation (MVV) tests while seated in their standard wheelchair. The order of the pulmonary function tests was randomized. Subjects also completed two functional residual capacity (FRC) measurements. Analysis of variance revealed significant differences in several pulmonary functions based on gender (FEVC, p = 0.0001, FEV1, p = 0.0001, FEVC 25-75%, p = 0.005, PEF, p = 0.002, FIVC, p = 0.002, RV, p = 0.0001, MVV, p = 0.0001, SVC, p = 0.001). The women's unforced prediction equations using age, height, weight did yield some significant correlations with predictions based upon ambulatory subjects. The men's unforced adapted prediction equations did reveal significant correlations with the validation group for FEVC (r = 0.66, p = 0.007), FEV1 (r = 0.62, p = 0.015), PIF (r = 0.95, p = 0.015), MVV (r = 0.57, p = 0.067), SVC (r = 0.69, p = 0.019), and RV (r = 0.67, p = 0.009). Pulmonary function in male wheelchair users should be predicted using equations which incorporate years with disability and level of impairment. Additional study is required to make any recommendations regarding women wheelchair users. However, study of pulmonary function in women should be made a priority. Pulmonary function is affected by the extent of physical impairment, and tends to decline as years with disability increase.

Adolescent↗

Overexpression of esterase D in kidney from trisomy 13 fetuses.

Human trisomy 13 (Patau syndrome) occurs in approximately 1 in 5,000 live births. It is compatible with life, but prolonged survival is rare. Anomalies often involve the urogenital, cardiac, craniofacial, and central nervous systems. It is possible that these abnormalities may be due to the overexpression of developmentally important genes on chromosome 13. The expression of esterase D (localized to chromosome 13q14.11) has been investigated in both muscle and kidney from trisomy 13 fetuses and has been compared with normal age- and sex-matched fetal tissues, by using northern analysis. More than a twofold increase in expression of esterase D was found in the kidney of two trisomy 13 fetuses, with normal levels in a third. Overexpression was not seen in the muscle tissues from these fetuses.

Abnormalities, Multiple↗

Caldesmon binds to smooth muscle myosin and myosin rod and crosslinks thick filaments to actin filaments.

It is well established that caldesmon binds to actin (Kb = 10(7) - 10(-8) M-1) and to tropomyosin (Kb = 10(6) M-1) and that it is a potent inhibitor of actomyosin ATPase. Caldesmon can also bind tightly to myosin. We investigated the binding of smooth muscle and nonmuscle caldesmon isoforms (CDh and CDl respectively) to myosin using proteins from sheep aorta. Both caldesmon isoforms bind to myosin with indistinguishable affinity. The affinity is about 10(6) M-1 in low salt buffer, but is weakened by increasing [KCl] reaching 10(5) M-1 in 100 mM KCl. The stoichiometry of binding is about three caldesmon per myosin molecule. Stoichiometry and affinity are not dependent on whether myosin is phosphorylated nor on the presence of Mg2+ and ATP, provided the ionic strength is maintained constant. The caldesmon binding site of smooth muscle myosin is located in the S-2 region, consequently both HMM and myosin rod bind to caldesmon. Over a range of conditions myosin and myosin rod binding to caldesmon were indistinguishable. Skeletal muscle myosin has no caldesmon binding site. Smooth muscle myosin rods form side-polar filaments in low salt buffer in which the backbone packing of LMM into the filament shaft is clearly visible in negatively-stained electron microscopic images. Sometimes the S-2 portions can be seen 'frayed' from the filament shaft. When caldesmon is bound the filament shaft appears to be about 20% thicker and the frayed effect is dramatically increased; long filamentous 'whiskers' are often seen curving out from the filament shaft. Similar structures are observed with smooth muscle and with non-muscle caldesmon. Myosin also binds to caldesmon when it is incorporated into the thin filament; however, this interaction is qualitatively different. Measurements of smooth muscle HMM binding to native thin filaments in the presence of 3 mM MgATP shows there is a high affinity binding (Kb = 10(6) M-1) which is independent of [Ca2+] and of the level of myosin phosphorylation. The stoichiometry is one HMM molecule per actin monomer which is equivalent to up to 14 HMM bound at high affinity per caldesmon. Negatively stained electron microscopic images of the HMM.ADP.Pi-thin filament complex have failed to show any attachment of HMM to the thin filaments. When rod filaments are added to actin plus caldesmon or to native thin filaments the rod filaments are strongly associated with the actin filament bundles. The majority of rod filaments are lined up parallel and in close proximity to actin filaments.(ABSTRACT TRUNCATED AT 400 WORDS)

Actin Cytoskeleton↗

Parents attitudinal and social influences on childhood vaccination.

The study examined beliefs and attitudes towards pertussis (and other) vaccinations in three groups of caregivers; those who had fully vaccinated a target child against pertussis (FV; n = 85), those whose child partially completed the course (PV; n = 70) and those who refused to have their child receive the pertussis vaccination (NV; n = 73). The NV group reported significantly more concern over long-term health problems as a result of pertussis vaccination, a lower risk of catching pertussis if not immunized and attached a lower importance to pertussis vaccination than either of the other two. They also rated their child as more likely to develop pertussis if immunized than those in the FV group. The NV group also reported a greater risk perception for some other vaccinations (e.g. mumps, rubella and measles) than the other groups. The implications for health education are discussed.

Adolescent↗

Characterization of the chromosomal aac(6')-Ic gene from Serratia marcescens.

The DNA sequence of the chromosomal aac(6')-Ic gene from Serratia marcescens, which had been previously cloned (H. M. Champion, P. M. Bennett, D. A. Lewis, and D. S. Reeves, J. Antimicrob. Chemother. 22:587-596, 1988) was determined. High-pressure liquid chromatographic analysis of extracts prepared from Escherichia coli carrying the chromosomal aac(6')-Ic gene on a plasmid confirmed the presence of 6'-N-acetyltransferase activity in this strain, which was suggested by the aminoglycoside resistance profile. DNA sequence analysis of the cloned 2,057-bp PstI fragment revealed several regions of homology to previously characterized sequences from GenBank, including the rpoD and tRNA-2 genes of E. coli. Subcloning experiments confirmed the coding sequence of the aac(6')-Ic gene to be at positions 1554 to 1992. The predicted amino acid sequence of the AAC(6')-Ic protein suggested that it was the third member of a family of AAC(6') proteins which included a coding region identified between the aadB and aadA genes of Tn4000 and an AAC(6') protein encoded by pUO490, which was isolated from Enterobacter cloacae. Primer extension analysis suggested that the -35 region of the aac(6')-Ic promoter overlapped a large palindromic sequence which may be involved in the regulation of the aac(6')-Ic gene. Hybridization experiments utilizing a restriction fragment from the aac(6')-Ic gene showed that all S. marcescens organisms carried this gene whether or not the AAC(6')-I resistance profile was expressed. Organisms other than Serratia spp. did not hybridize to this probe.

Base Sequence↗

The contribution of body composition, substrates, and hormones to the variability in energy expenditure and substrate utilization in premenopausal women.

Twenty-four-hour energy expenditure and substrate use were measured by indirect calorimetry in respiration chambers on a fixed physical program and related to body composition and plasma concentrations of various substrates and thermogenic hormones. Fifty premenopausal women with a wide range of body weight were examined in the follicular menstrual phase under weight stable conditions. Most of the variance in the sleeping energy expenditure (82%) was accounted for by two covariates, lean body mass (75%, P less than 0.0001), and fat mass (7%, P less than 0.0001). An additional 6% of the variance in sleeping energy expenditure was accounted for by plasma androstenedione concentration (4%, P = 0.0005) and by free T3 index (2%, P = 0.03). Thus physiological variation among individuals in plasma androstenedione concentration may result in a difference in energy expenditure of 908 kJ/day and the corresponding variation in free T3 index may result in a difference between individuals of 594 kJ/day. Fifty four percent of the variation in carbohydrate oxidation rates was accounted for by 24-h energy balance, and by plasma concentrations of insulin, nonesterified fatty acids, and estradiol. Waist circumference, plasma nonesterified fatty acids, and estradiol concentrations explained 49% of the variance in 24-h lipid oxidation. An obese subgroup of women (n = 27) had significantly higher 24-h energy expenditure, lipid, and carbohydrate oxidation rates than an age-matched normal weight group (n = 16), but the entire group difference in energy expenditure was explained by differences in body composition. We conclude that physiological variations in plasma androstenedione and T3 concentrations contribute to the interindividual variance in energy expenditure of women, and their role is not different in obese women. A positive energy balance and increased insulin action may be mediators of the higher carbohydrate oxidation in obesity, whereas an increased substrate availability seems to bring about the increased lipid oxidation.

Adolescent↗

The pituitary-gonadal axis in women with benign or malignant ovarian tumors.

The serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), human chorionic gonadotropin (hCG), estradiol, progesterone, androstenedione, testosterone (total and free) and dehydroepiandrosterone sulphate (DHEAS) were investigated prior to surgery in 24 postmenopausal women with benign and 28 postmenopausal women with malignant epithelial ovarian tumors. The serum concentrations of hormones were compared with those of 28 healthy, postmenopausal, age-matched controls. Significantly lower serum FSH levels were demonstrated in women with malignant tumors. No significant differences were found between the groups regarding the serum LH levels. The hCG levels were low in all groups. Regarding progesterone and estradiol levels, low postmenopausal steroid levels were found in all groups examined and no significant differences were demonstrated within the groups. No significant correlations between the levels of estradiol and FSH or progesterone and LH were demonstrated. To exclude a central depression of gonadotropin release mediated by the dopaminergic system we examined the thyroid stimulating hormone (TSH) and prolactin. No differences were found between the groups regarding TSH and prolactin levels. A possible relationship between other hormones/factors produced by the tumor and exerting a negative feedback, either centrally or directly, on the gonadotropin release remains to be investigated. A change in biological activity in the gonadotropins might explain the present findings.

Aged↗

Serum sex hormones and endurance performance after a lacto-ovo vegetarian and a mixed diet.

Serum sex hormones and endurance performance after a lacto-ovo vegetarian and a mixed diet. Med. Sci. Sports Exerc., Vol. 24, No. 11, pp. 1290-1297, 1992. The effect of a lacto-ovo vegetarian (V) and a mixed, meat-rich (M) diet on the level of serum sex hormones, gonadotropins, and endurance performance of eight male endurance athletes was investigated in a 2 x 6 wk cross-over study. The energy contribution from carbohydrate, fat, and protein was 58%, 27%, and 15% on the V diet and 58%, 28%, and 14 E% on the M diet. For total fasting serum testosterone (T) there was a significant interaction between diet and time (P < 0.01). Thus, the V diet resulted in a lower total T level (13.7, 9.8-32.4 nmol.l-1) (median and range) compared with the M diet (17.4, 11.8-33.5 nmol.l-1). During exercise after 6 wk on the diets total T was also significantly lower on the V than on the M diet (P < 0.05). Serum free testosterone, however, did not differ significantly during the 6 wk dietary intervention periods and neither did serum concentrations of sex hormone binding globulin, dihydrotestosterone, dehydroepiandrosterone sulphate, 4-androstenedione, estrone, estradiol, estrone sulphate, or gonadotropins. Endurance performance time was higher for six and lower for two after the mixed diet compared with the vegetarian diet. This was not significant, however. In conclusion, 6 wk on a lacto-ovo vegetarian diet caused a minor decrease in total testosterone and no significant changes in physical performance in male endurance athletes compared with 6 wk on a mixed, meatrich diet.

Diet↗

Testis cancer. Ichthyosis constitutes a significant risk factor.

Testis cancer and ichthyosis are both relatively rare diseases. Hence the finding of six individuals with both these conditions in a small population with testicular cancer is highly conspicuous and indicates some kind of connection among such persons. Despite the identical clinical appearances of their ichthyoses, three of the ichthyotic subjects had no measurable activity of the enzyme, steroid sulfatase (STS) in leucocytes, a distinct characteristic of recessive X-linked ichthyosis (RXLI). However, the remaining three subjects had normal STS activity, a strong indicator of autosomal dominant ichthyosis (ADI). The STS activity in patients with testicular cancer who do not have ichthyosis (N = 30) was also within the normal range. The patients with testicular cancer with no skin disease had elevated serum levels of 4-androstenedione (4-AD), follicle stimulating hormone (FSH), and luteinizing hormone (LH) but had reduced levels of estrone and estrone sulfate. The other serum parameters measured did not significantly differ from normal levels. In essence, the hormone levels obtained for the patients with ichthyotic testicular cancer followed the same pattern, although their dehydroepiandrosterone sulfate (DHEAS) and estrone sulfate levels tended to be slightly higher than normal. However, no conspicuous aberrations in any of the parameters examined were observed, and why men with ichthyosis are at high risk for testicular cancer remains an unresolved issue.

Adult↗

Treating Type A behaviours and mild hypertension in middle-aged men.

Unmedicated mildly hypertensive Type A men were randomly allocated to one of three conditions: stress management intervention training (N = 15), Type A management (N = 15), and delayed Type A management intervention. Significantly greater reductions in blood pressure at rest and during the Type A structured interview were found following the active interventions than during the minimal treatment control period of the delayed intervention. Type A management was more successful in changing a number of Type A behaviours, including anger, hostility and global Type A behaviour. Changes on measures of anger-in, -out, hostility, and SI ratings of Type A behaviour were associated with changes in systolic and diastolic blood pressure reactivity during interview.

Adult↗

Menopausal age and sex hormones in postmenopausal women with alcoholic and non-alcoholic liver disease.

In order to evaluate age at menopause and serum sex hormone profiles in postmenopausal women with stable chronic liver disease, six non-cirrhotic alcoholics, 13 with alcoholic cirrhosis, eight with non-alcoholic cirrhosis, and 46 healthy controls were studied. In all three groups, patients were significantly (p less than 0.05) younger at the time of natural menopause than controls. Compared to controls, non-cirrhotic alcoholic women had significantly (p less than 0.05) reduced levels of DHAS, significantly (p less than 0.05) more alcoholic cirrhotic women had detectable oestradiol concentrations, elevated concentrations of oestrone and sex hormone binding globulin (SHBG) and reduced levels of 5 alpha-dihydrotestosterone (DHT), while women with non-alcoholic cirrhosis had significantly elevated concentrations of SHBG and reduced levels of oestrone sulphate, DHT, androstenedione and dehydroepiandrosterone sulphate (DHAS) (p less than 0.05). The observed changes may be a consequence of liver disease since similar changes were observed in patients with alcoholic and non-alcoholic liver disease, but an additional effect of alcohol cannot be excluded.

Aged↗