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Biomedical subjects

A M Powell

Publications and source records attributed to A M Powell.

At least 19 recordsLinked to original sources
PubMed1992

Benzodiazepine use in general practice--is it a problem?

AIMS: The aim of this study was to describe benzodiazepine use in a general practice. METHODS: A prevalence study in an Auckland general practice was undertaken to describe the benzodiazepines prescribed, patterns of use and compliance. An associated case control study compared benzodiazepine users and nonusers. RESULTS: The age standardised prevalence rate of benzodiazepine use in this Auckland general practice was 3.4% for patients over 20 years of age. The benzodiazepine users described were predominantly elderly (70% over 60 years of age) and female (62.5%). They had significantly more medical and psychiatric complaints than matched controls. Triazolam and diazepam accounted for 60.9% of the benzodiazepines prescribed. Over one-third of the patients using benzodiazepines were concurrently prescribed other psychotropic medications, primarily tricyclic antidepressants. CONCLUSION: This rate suggests an overall decline in benzodiazepine use since previous studies. Benzodiazepines continue to be prescribed predominantly in the elderly, a group at considerable risk from side effects. Doctors should continue to inform their patients about the side effects of benzodiazepines, the risks of dependence and difficulties of withdrawal.

Adult↗
PubMed1991

FSH injections and intrauterine insemination in protocols for superovulation of ewes.

In Exp. 1, five injections of crude FSH (20 mg total), starting 36 h before removal of progestin pessaries or injection of prostaglandin F2 alpha (PGF2 alpha), were found to be as effective for superovulation of ewes as seven injections starting 72 h before removal of pessaries. Seven injections caused superovulation (more than three ovulations) in 13 of 15 ewes with an average (all ewes) of 12 +/- 2.3 ovulations. Five injections caused superovulation in 17 of 19 ewes with an average of 11.5 +/- 1.6 ovulations after pessary-regulated estrus in 12 of 16 ewes with an average of 12.4 +/- 2.2 ovulations after PGF2 alpha injection. In Exp. 2, intrauterine artificial insemination (IUAI) of naturally mated ewes provided ovum fertilization rates of 75.3% with an embryo recovery rate of 39.4%, whereas mating alone (MATED) provided fertilization rates of 64.2% with an embryo recovery rate of 72.1%. However, subsequent replications of the MATED protocol (MATED2) resulted in a low fertilization rate (34.2%). In Exp. 3, surgical IUAI at 22 h after removal of pessaries resulted in a low rate of superovulation (5 of 12 ewes), presumably as the result of pentobarbital anesthesia. Conducting IUAI at 46 h after removal of pessaries resulted in a high rate of superovulation (14 of 16 ewes) but a low embryo recovery rate (30.7%). In two subsequent trials, IUAI at 40 h after removal of pessaries resulted in most ewes superovulating (33 of 35 in April/May and 16 of 17 in September) with acceptable embryo recovery (65.2% and 71.3%) and high fertilization rates (82.8% and 96.4%).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Effect of serum-free co-culture and synchrony of recipients on development of cultured sheep embryos to fetuses.

The percentage of sheep embryos that continued to develop after collection and immediate transfer on d 2 after estrus was similar when phosphate-buffered saline with 10% fetal calf serum (PBSFCS, 45%), physiological saline (50%), or tissue culture medium 199 supplemented with 10% fetal calf serum (M199FCS, 47%) was used to flush embryos from oviducts. Co-culture of sheep embryos for 3 d with oviductal cells tended (P = .1) to reduce the percentage of embryos that developed to fetuses after transfer compared with those embryos transferred immediately. Tissue culture medium 199 supplemented with .3% BSA (M199BSA) was an adequate substitute for M199FCS for culture of sheep oviductal cells if tissue culture wells were pretreated with fibronectin. Estradiol in concentrations from 10 to 1,000 pg/ml and progesterone at concentrations of 1 or 10 ng/ml in M199BSA failed to stimulate embryo development during 3 d of co-culture beyond that seen in co-culture with M199FCS or M199BSA without added steroid. Transfer of sheep embyros co-cultured for 3 d in M199BSA or M199FCS to recipients synchronized with donors resulted in about 19% of the embryos developing to fetuses, whereas transfer to recipients that were in estrus 24 h after donors resulted in 33% of embryos developing to fetuses. The significant (P less than .05) improvement for delayed recipients may reflect the relatively lesser developmental rate of co-cultured embryos compared with that of embryos in vivo. Embryo development into fetuses was similar after co-culture in M199FCS or M199BSA co-cultures; therefore, serum is not required for the co-culture of sheep embryos.

Animals↗
PubMed1991

Evaluation and therapy of breakthrough bleeding in women using a triphasic oral contraceptive.

This study was designed to investigate the incidence and pattern of breakthrough bleeding (BTB) in 1,259 women who were prescribed for the first time a triphasic oral contraceptive (OC, 7-7-7) and to evaluate a hypothesis of management for BTB persisting after three cycles. The new users were compared with a control group of 696 women who had used various OCs for at least 6 months. The incidence of BTB in the control group was 16.8% and in the new users was 24.9%, 17.5%, and 15.3% in the first 3 months, respectively. Breakthrough bleeding occurred late in the 7-7-7 package in 58% and early or midway through the package in 17% and 25%, respectively. We hypothesized that late-package BTB would improve if the patient was switched to a monophasic pill similar to the relatively estrogenic formulation of the beginning of the package and vice versa for early or midpackage BTB. Seventy women with BTB at 3 months were randomly given 0.5/35 or 1/35 for a further 3 months. Breakthrough bleeding was more likely (P less than 0.05) to improve in women switched to 1/35 compared with 0.5/35 regardless of where in the package BTB occurred.

Adolescent↗
PubMed1990

Neuropeptide content in pancreas and pituitary of obese and diabetes mutant mice: strain and sex differences.

The nature of the primary genetic defects in ob/ob and db/db mice are unknown. Both the obese (ob) and diabetes (db) mutations produce similar, multicomponent obese-hyperinsulinemic syndromes when maintained in the same strain of mouse. In an attempt to find differences between these mutations in neuroendocrine function affecting the islets of Langerhans or the pituitary, tissue content of four neuropeptides that are known to be capable of influencing the rate of insulin secretion was examined in obese (ob/ob) and diabetes (db/db) mice. In the first study, C57BL/6Job/ob and control males were studied at 3, 4, and 11 weeks of age. In the second study, db/db mice of both sexes and two inbred strains (C57BL/6J and C57BL/KsJ), which differ markedly in the severity of expression of the diabetes phenotype, were studied at 3 weeks of age, before the development of hyperglycemia and secondary consequences thereof. Immunoreactive peptides were measured in acetic acid extracts of pancreas and pituitary. No differences between male ob/ob and db/db mice of the C57BL/6J strain were found. Marked sex differences in lean control mice were found at 3 weeks of age in pancreatic Met-enkephalin-LI and galanin-LI (with two- to threefold higher content in males). Low pancreatic content (50% to 70% lower than in control mice) of galanin-LI, Met-enkephalin-LI and Leu-enkephalin-LI was associated with hyperinsulinemia in male B6 ob/ob and db/db mice at 3 weeks of age, though not in B6 db/db females and not in BKs db/db mice of either sex.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Multiple alterations in insulin responses to glucose in islets from 48-h glucose-infused nondiabetic rats.

To examine the biochemical mechanisms by which hyperglycemia produces insulin secretory abnormalities, we studied isolated islets from control rats and rats infused for 48 h with a 50% glucose solution. To preserve the effects of in vivo hyperglycemia during in vitro handling for islet isolation, our standard isolation procedure utilized buffers containing 16.8 mM glucose. Islets from infused rats released similar amounts of insulin in low or high glucose during first incubations at 37 degrees C (92.4 +/- 7.0 ng.10 islets-1.45 min-1 at 2.8 mM, 84.4 +/- 4.1 ng.10 islets-1.45 min-1 at 16.8 mM) in contrast with control (uninfused) islets (18.6 +/- 2.8 ng.10 islets-1.45 min-1 at 2.8 mM and 109.8 +/- 8.0 ng.10 islets-1.45 min-1 at 16.8 mM glucose) (P less than 0.01). Secretion by islets of glucose-infused rats was lower during 60-min second incubations at 28 mM glucose than in first incubations of the same islets in low glucose (P less than 0.01). This phenomenon is comparable to the paradoxical hypersecretion observed during the first 10-15 min of exposure of glucose-infused pancreas to low-glucose perfusions. Paradoxical secretion in low glucose waned rapidly, so that during second incubations at 37 degrees C, little immunoreactive insulin release occurred at 2.8 mM glucose, despite the persistence of two additional lesions. The glucose-insulin dose-response curves in second incubations showed a leftward shift for glucose-infused islets, with two- to threefold higher secretion at 5.6-8.4 mM glucose than control islets. This is termed sensitization to glucose.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Developmental patterns for pancreatic opioids in the rat.

Developmental patterns for rat pancreatic opioid peptides and islet hormones were studied from gestational day 20 through adulthood. Fetal tissue was obtained as well as pancreas at birth (day 0), and postnatal days 3, 7, 14, and 21, and 7 weeks. The hormones measured included insulin, glucagon, and somatostatin. The opioids measured were beta-endorphin, Met- and Leu-enkephalins, and the high molecular weight enkephalin precursors. Pancreata were pooled as necessary and extracted (acid alcohol, or hot acetic acid), and opioids were further purified on reversed-phase C-18 (Sep-pak) cartridges. In all instances measurements were made by radioimmunoassays. Precursor peptides were first digested (with trypsin and carboxypeptidase B) prior to immunoassay. All opioids and hormones except the precursors for enkephalins showed a well-defined surge in pancreatic concentration during the first postnatal week. In contrast, the precursors had the highest concentration in the fetus, and by the seventh day of life had decreased by greater than 50%. This progressive decrease may represent maturation of the enkephalin convertase and trypsin-like enzymes in the islets. The opioid and hormonal surges that we have described are similar to the surge in islet concentration of thyroid-releasing hormone (TRH) previously described in neonatal rat islets. It is suggested that these postnatal alterations in opioid and hormone concentration relate to a specific function in the development of the endocrine pancreas.

Animals↗
PubMed1989

Thyrotropin and prolactin responses to thyrotropin-releasing hormone in premenstrual syndrome.

Recent reports of altered TSH responsiveness to its releasing hormone (TRH) in women with premenstrual syndrome (PMS) suggested that subclinical hypothyroidism may be responsible for the mood changes, such as depression, that occur in these women. In this study we measured basal and TRH-stimulated serum TSH and PRL levels in 15 women with PMS and in 19 age-matched normal women. The mean baseline serum TSH concentrations were similar in the 2 groups in both the follicular [normal, 1.3 +/- 0.2 (+/- SE); PMS, 0.9 +/- 0.2 mU/L] and luteal (normal, 1.1 +/- 0.2; PMS, 1.1 +/- 0.2 mU/L) phases of the cycle. The mean baseline serum PRL levels also were similar in the 2 groups in the follicular (normal, 16 +/- 2; PMS, 13 +/- 2 micrograms/L) and luteal (normal, 13 +/- 2; PMS, 14 +/- 2 micrograms/L) phases of the cycle. After TRH administration, peak serum PRL and TSH levels were reached at 15 and 30 min, respectively, and the response curves were virtually identical in the 2 groups in both phases of the cycle. One normal woman had elevated basal and TRH-stimulated TSH concentrations compatible with subclinical hypothyroidism, but had normal noncyclic scores on her prospective rating scales. Our findings suggest that PMS is not associated with thyroid dysfunction or abnormal PRL secretion and that thyroid hormone replacement therapy is not indicated in this condition.

Adult↗
PubMed1988

Reversible impairment of glucose-induced insulin secretion in SHR/N-cp rats. Genetic model of type II diabetes.

The SHR/N-cp rat is a new genetically obese model for non-insulin-dependent diabetes mellitus. Expression of the diabetes is enhanced by a high-sucrose (54%) diet. After 4 wk on the diet, the cp/cp rats weigh significantly more than their +/? controls, have postprandial hyperglycemia (greater than 400 mg/dl), and are hyperinsulinemic, with immunoreactive insulin (IRI) levels 10- to 20-fold greater than controls. Total pancreatic IRI tends to be increased 1.6-fold in the cp/cp rats (although not significantly). There is no increase in pancreatic proinsulin content as a percent of total IRI. Studies of in vitro pancreatic function were carried out with the isolated nonrecirculating perfused pancreas method. The cp/cp rats (n = 10) showed impaired or absent IRI responses to 16.5 mM glucose, whereas +/? rats (n = 9) responded with classic biphasic curves. Comparison of insulin secreted in 20 min revealed a greater than 53% decrease in IRI secretion in cp/cp rats (P less than .05). A paradoxical hypersecretion of IRI at glucose concentrations of 0-2.7 mM was noted in cp/cp but not lean rats, i.e., 1.8 +/- 0.2 mU/min IRI in cp/cp rats vs. 0.04 +/- 0.007 mU/min in +/? rats. Perfusion of pancreases for 45 min with buffers containing no glucose resulted in restoration of a normal biphasic IRI response to 16.5 mM glucose in the cp/cp rats, whereas response in the lean rats was markedly reduced. Brisk IRI responses to 10 mM arginine in buffers with no glucose also occurred in cp/cp but not +/? rats. Glucagon secretion was relatively suppressed in the cp/cp rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Co-culture of ovine ova with oviductal cells in medium 199.

Three experiments were conducted to test the suitability of medium 199 supplemented with 10% fetal calf serum (M199FCS) as a medium for co-culture of one-cell sheep ova with sheep oviductal cells. In Exp. 1, ova were co-cultured for 5 d in 5 ml of M199FCS or in Ham's F10 medium supplemented with 10% fetal calf serum (F10FCS). Co-culture did not increase the number of cleavages at the end of 5 d of culture, but M199FCS supported more cleavages than did F10FCS (P = .016). In Exp. 2, ova were cultured for 1 to 3 d in M199FCS alone or on oviductal, uterine or kidney cell monolayers from ewes 2 d postestrus and transferred to recipients from which they were recovered at 8 d postestrus. Co-culture with oviductal cells improved (P less than .001) the cleavage index of recovered embryos compared with culture in medium alone or co-culture with other cell types. In Exp. 3, monolayers of oviductal cells from ewes 2 d postestrus and from luteal-phase ewes were cultured as in Exp. 2. No difference was observed between the two sources of oviductal cells for their ability to support in vitro development of one-cell sheep eggs for 1 or 2 d. These studies suggest that M199FCS may be a good medium to use in an oviductal cell co-culture system for one-cell sheep ova. Results further suggest that specific secretions of oviductal cells may be important for early embryo development in vivo.

Animals↗
PubMed1986

Premenstrual syndrome: documentation by a linear analog scale compared with two descriptive scales.

We examined the use of a six-item linear analog scoring system comprised of three somatic and three mood-related items for the documentation of premenstrual syndrome. One hundred forty women with suspected premenstrual syndrome completed the linear analog scale, as well as the validated 36-item Self-Rating Scale for Premenstrual Tension Syndrome and the 35-item Prospective Record of the Impact and Severity of Menstrual Symptomatology calendar. Ninety patients and 20 normal control subjects completed two cycles of records. With use of clinical criteria and self-rating scale scores as the "gold standard," 73 patients were diagnosed as having premenstrual syndrome. Linear analog scale scores were highly correlated with both self-rating scale scores (r = 0.72, day 9; r = .66, day 27; p = 0.001) and prospective record scores (r = 0.74, day 9; r = 0.60, day 27; p = 0.001). Our results suggest that the linear analog scale may be a useful clinical tool in the study of premenstrual syndrome. Because of its simplicity, the linear analog scale may increase patient compliance. Because of its sensitivity to detect changes in symptom severity throughout the menstrual cycle, it may prove useful in evaluating the effects of therapy for premenstrual syndrome.

Adult↗
PubMed1985

Menstrual-PGF2 alpha, PGE2 and TXA2 in normal and dysmenorrheic women and their temporal relationship to dysmenorrhea.

Although it has been demonstrated that primary dysmenorrhea is associated with elevated levels of PGF2 alpha in the menstrual fluid, little is actually known of the menstrual-PG profiles of either dysmenorrheic or normal women. In this study, menstrual fluid from normal and dysmenorrheic women was collected from tampons and extracted for PG-like substances. The PGF2 alpha, PGE2 and TXA2 content was analyzed by RIA. This study demonstrates that dysmenorrheics have significantly higher levels/concentrations of menstrual-PGF2 alpha and PGE2 than do normal women, and that there is no difference in the menstrual-PGF2 alpha : PGE2 ratio between the two groups. Also, there is no significant difference in the amount/concentration of menstrual-thromboxane between dysmenorrheic and normal women. Of the parameters considered, the levels/-concentrations of menstrual-PGF2 alpha, PGE2 and TXA2, dysmenorrheic pain correlates best with the rate of menstrual-PGF2 alpha release.

Adolescent↗
PubMed1984

Differential effects of ibuprofen and naproxen sodium on menstrual prostaglandin release and on prostaglandin production in the rat uterine homogenate.

In two independent studies, ibuprofen and naproxen sodium were found to be equi-effective in alleviating dysmenorrheic symptoms. However, the effects of these drugs on menstrual PG release were found to be dissimilar. Ibuprofen primarily inhibited menstrual PGF2 alpha release with little effect on PGE2 release, whereas, naproxen sodium inhibited both PGF2 alpha and PGE2 release equally. To verify these results, we determined the inhibitory potency, IC50, of ibuprofen and naproxen sodium on PGF2 alpha and PGE2 synthesis in the rat uterine homogenate system. The preferential PGF2 alpha inhibitory activity of ibuprofen was confirmed. These findings suggest that ibuprofen may, in addition to inhibiting fatty acid cyclooxygenase, also inhibit PGF2 alpha reductase, or some other PG metabolic pathways which affect PGF2 alpha and PGE2 synthesis differently. The significance of this differential PG synthesis inhibitory effect in dysmenorrheic therapy is discussed.

Animals↗
PubMed1983

Effects of naproxen sodium on menstrual prostaglandins and primary dysmenorrhea.

Prostaglandins E2 and F2 alpha in the menstrual fluid from 12 patients with primary dysmenorrhea were measured by radioimmunoassay (RIA). Each patient was studied for 3 cycles, using vaginal tampons issued for this study. All tampons were collected individually for prostaglandin extraction and RIA. Severity of dysmenorrhea and clinical response to treatment were evaluated by a scoring method and by the patients' self-assessment. Each patient in this double-blind cross-over study had a control cycle and 2 treatment cycles with naproxen sodium tablets (275 mg) or placebo in random order. The treatment regimen was 2 tablets at the first sign of menses followed by one tablet 4 times daily for 3 days. Nine patients obtained good to excellent relief from naproxen sodium, but no relief from the placebo. Two patients had moderate to good response to both naproxen and placebo, and one patient showed no response. Naproxen therapy but not placebo therapy sharply reduced menstrual prostaglandin F2 alpha and prostaglandin E2 release. There was a positive correlation between menstrual prostaglandin levels and the severity of dysmenorrhea. Symptomatically, naproxen sodium was most effective in alleviating severe menstrual cramps but had little effect on mild cramps. It was also effective in ameliorating many but not all of the subjective symptoms such as dizziness, nausea, and vomiting. Relief of dysmenorrhea was apparent within one hour after the initial dose, attained maximum level in 2 hours, and was maintained throughout therapy.

Adult↗
PubMed1982

Antioxytocic and antiprostaglandin-releasing effects of oxytocin antagonists in pregnant rats and pregnant human myometrial strips.

There is now increasing evidence that both oxytocin (OT) and prostaglandin (PG) play a role in term as well as preterm labor. OT stimulates myometrial contractions and uterine PG release. Specific OT antagonists, therefore, may be of value in the treatment of preterm labor. Recently, we have synthesized two highly potent OT antagonists, [1-penicillamine, 4-threonine]OT ([Pen1, Thr4]OT) and [1-penicillamine, 2-phenylalanine, 4-threonine]OT ([Pen1, Phe2, Thr4]OT). We have determined their antioxytocic activity in 21- to 22-day-pregnant rats and on isolated human myometrial strips obtained from term pregnant patients at caesarean section for childbirth. We also studied their effects on PG synthesis and OT-stimulated PG synthesis on uterine slices from pregnant rats. We found that the two OT antagonists were effective inhibitors of the OT responses in pregnant rats and on pregnant human myometrial strips. The two OT antagonists had no agonistic activity on PG release at a dose range that was antioxytocic. When administered together with OT, the PG-releasing action of OT was inhibited. Thus, [Pen1, Thr4]OT and [Pen1, Phe2, Thr4]OT are effective inhibitors of both the uterotonic and PG-releasing actions of OT. The potentials of OT antagonists as tocolytic agents for the treatment of preterm labor should be explored.

Animals↗
PubMed1980

Synthesis, pharmacological, conformational, and dynamic studies of the potent hormone antagonists [1-penicillamine, 4-threonine]-oxytocin and [1-penicillamine, 2-phenylalanine, 4-threonine]-oxytocin. Conformational and dynamic considerations in the design of antagonists.

The solid phase synthesis of [1-penicillamine, 4-threonine]-oxytocin and [1-penicillamine, 2-phenylalanine, 4-threonine]-oxytocin is reported. The two compounds have no in vitro milk ejecting activity and no in vivo or in vitro oxytocic activity, but both are potent antagonists in these three assay systems. In the in vitro oxytocic assay, [1-penicillamine, 4-threonine]- and [1-penicillamine, 2-phenylalanine, 4-threonine]-oxytocin have pA2 values of 7.55 +/- 0.04 and 7.67 +/- 0.02, respectively, and both inhibit the uterine contractile response to oxytocin in nonpregnant and pregnant rats. [1-Penicillamine, 2-phenylalanine, 4-threonine]-oxytocin has a weak antipressor activity and at high doses, consistently caused a weak and transient fall in blood pressure in the rat. Carbon-13 nuclear magnetic resonance chemical shift parameters and spin-lattice relaxation times (T1) indicate that these two new oxytocin antagonists have very similar conformation and dynamic properties to oxytocin inhibitors which have previously been examined. These results are discussed in terms of conformational and dynamic models of oxytocin antagonism at the uterus. It is suggested that conformational restrictions at the 2- and 4-positions of penicillamine-1 analogues of oxytocin are important to antagonist activity and potency.

Amino Acid Sequence↗