In vivo effect of human growth hormone on hepatic adenylate cyclase activity.

Significant increases in basal, and glucagon and fluoride stimulated adenylate cyclase activity were observed in liver plasma membranes of hypophysectomized rats compared to normal adult and weanling rats. The fluoride stimulated adenylate cyclase activity was 2-3 fold greater in the membranes from hypophysectomized animals while the glucagon stimulated activity was 5-7 fold greater, and the basal activity was approximately double that of membranes from normal adult animals. Administration of growth hormone to hypophysectomized rats by an intramuscular or intravenous route decreased adenylate cyclase activity to levels equivalent to those in normal adult rats. Estradiol and thyroxine replacement did not alter the adenylate cyclase activity of the membranes from hypophysectomized animals. The fluoride or epinephrine stimulated adenylate cyclase activity of rat diaphragm homogenates was not affected by hypophysectomy.

In vitro and in vivo evaluation of dihydropyrimidinone C-5 amides as potent and selective alpha(1A) receptor antagonists for the treatment of benign prostatic hyperplasia.

alpha(1) Adrenergic receptors mediate both vascular and lower urinary tract tone, and alpha(1) receptor antagonists such as terazosin (1b) are used to treat both hypertension and benign prostatic hyperplasia (BPH). Recently, three different subtypes of this receptor have been identified, with the alpha(1A) receptor being most prevalent in lower urinary tract tissue. This paper explores 4-aryldihydropyrimidinones attached to an aminopropyl-4-arylpiperidine via a C-5 amide as selective alpha(1A) receptor subtype antagonists. In receptor binding assays, these types of compounds generally display K(i) values for the alpha(1a) receptor subtype <1 nM while being greater than 100-fold selective versus the alpha(1b) and alpha(1d) receptor subtypes. Many of these compounds were also evaluated in vivo and found to be more potent than terazosin in both a rat model of prostate tone and a dog model of intra-urethral pressure without significantly affecting blood pressure. While many of the compounds tested displayed poor pharmacokinetics, compound 48 was found to have adequate bioavailability (>20%) and half-life (>6 h) in both rats and dogs. Due to its selectivity for the alpha(1a) over the alpha(1b) and alpha(1d) receptors as well as its favorable pharmacokinetic profile, 48 has the potential to relieve the symptoms of BPH without eliciting effects on the cardiovascular system.

Subcutaneous tissue cages for examination of slow release of materials from long-term implants.

A subcutaneous tissue cage implant system was examined for its utility in evaluating the subcutaneous response to slow release of potentially irritating materials from implanted devices. The degree of the inflammatory response was measured by the total number of polymorphonuclear leucocytes per microliter in the tissue exudate. Bolus injection of kappa carrageenan resulted in a 100-fold increase in polymorphonuclear leucocytes within 2 d with a return to basal levels within the next 3 d. Slow infusion of the same solution over 7 d also resulted in a statistically significant increase in polymorphonuclear leucocytes response 4 d following expected termination of infusion, which did not return to basal levels before study termination 3 d later. The peak response obtained from slow infusion of carrageenan did not differ significantly from that observed following bolus injection of the same solution.

Grieving characteristics after spontaneous abortion: a management approach.

Twenty-two women who experienced a spontaneous abortion were treated during a 15-month period. All patients were seen for counseling sessions immediately after the spontaneous abortion. The initial counseling was followed by patient contacts and by a second counseling session four to six weeks later. All 22 women demonstrated intense emotional reactions to their pregnancy loss, characterized by the seven stages of grief. Guilt was the state that appeared to be the most difficult for the women and their spouses to resolve without help. Counseling sessions are considered an essential part of the total obstetric care for patients who experience a pregnancy loss.

Learning from the community about barriers to health care.

One of the major challenges facing obstetrician-gynecologists, especially those serving populations that are diverse in culture and circumstances, is to identify and address the barriers that keep women from seeking timely preventive and prenatal health care. The Department of Obstetrics and Gynecology at Rochester General Hospital held a community focus groups to learn more about women's attitudes toward health care. In addition to economic issues, such as lack of insurance and an inability to pay, the organizers found that many of the factors that prevent or discourage women from seeking health care involve issues of communication and understanding. Many women wanted what they perceived to be additional services. In reality, many of the things desired involved changes in doctor-patient interactions rather than the addition of any new service, and could be addressed with relative ease and minimal cost. Providing staff members with training in cultural sensitivity and encouraging them to develop a real awareness of patient circumstances are first steps that can lead to better communication between provider and patient and to the development of mutual trust. Other factors, such as the fear of incarceration or of losing one's children if health care is sought, present more serious challenges. Providers of care to high-risk, impoverished populations need to develop strong links to mental health, substance abuse, and family preservation services that allow them to intervene with troubled women and their families with services that are alternatives to incarceration and punitive actions.

Fetus papyraceus causing dystocia: inability to detect blighted twin antenatally.

A case is reported of fetus papyraceus diagnosed intrapartum. There was no clinical evidence in early and midpregnancy to suggest such a diagnosis. Ultrasound examination performed 1 week prior to delivery was nondiagnostic, but an x-ray taken intrapartum revealed dystocia caused by fetus papyraceus, thus necessitating cesarean section. It is suggested that the clinician consider x-ray as well as ultrasound in the diagnosis of fetus papyraceus. In addition to the obstetric morbidity, there is considerable neonatal morbidity which further increases the importance of antenatal diagnosis of fetus papyraceus.

The effect of cocaine abuse on birth weight and gestational age.

A retrospective study of 343 women who lacked prenatal care was conducted to ascertain the effect of recent cocaine abuse on birth weight and gestational age. All pregnant women admitted in labor to a large urban teaching hospital between January 1 and December 31, 1986 who had not received prenatal care were included. The charts of these women were evaluated to obtain information about medical and obstetric complications of pregnancy, labor and delivery, and birth weight and gestational age of the infant. Information about drug use was obtained by urine toxicology at the time of admission. Results of ordinary least-squares multiple regression analyses indicated cocaine abuse to be a significant predictor of low birth weight and early gestational age. No correlation was found between cocaine abuse and abruptio placentae or maternal hypertension.

Use of everted intestinal rings for in vitro examination of oral absorption potential.

The ability to predict in vivo oral absorption potential based on ex vivo screening in an everted intestinal ring model was examined. In vitro drug accumulation in cross sectional rings of everted rat jejunum was determined with 12 compounds whose in vivo absorptions (as distinct from bioavailabilities) are well characterized. The compounds examined ranged from well- to poorly-absorbed and included compounds absorbed by active and passive mechanisms. The effects of drug concentration, pH, cosolvents, and tissue origin site on drug accumulation were determined. Light microscopic observation indicated that the mucosal tissue remained intact up to 3 h after the intestine was excised. Accumulations of two nonabsorbable markers were also determined as measures of tissue integrity. A strong correlation (slope = 23 pmol/mg of tissue weight per percent oral absorption, r2 = 0.9430 by linear regression analysis) of in vitro uptake into everted rings from a 10 mM drug solution versus the known in vivo bioavailability for each compound was observed. These results indicated that under appropriate conditions, in vitro uptake of drug by the everted intestinal ring model closely paralleled known in vivo bioavailability and was relatively independent of pH, cosolvent, and tissue origin.

Involvement of active sodium transport in the rectal absorption of gentamicin sulfate in the presence and absence of absorption-promoting adjuvants.

The involvement of active sodium transport in the rectal absorption of gentamicin sulfate was examined in rats, employing aqueous microenemas of known total ionic strength (mu) in the presence or absence of absorption-promoting adjuvants. Rectal gentamicin bio-availability, which is negligible (1 +/- 1.2%) at an ionic strength of 0.15 without adjuvants, is significantly (p less than 0.01) increased by including adjuvants in the formulation (sodium salicylate, 12 +/- 4.0%; sodium-5-bromosalicylate, 59 +/- 15.1%; disodium ethylene (dinitrilo)tetraacetate, 24 +/- 9.3%). Pretreating the rectal mucosa cells with ouabain, a specific inhibitor of active sodium transport, significantly (p less than 0.01) reduced gentamicin absorption in response to all three adjuvants. In contrast to previous findings with sodium chloride, high ionic strength choline chloride (mu = 1.056) did not promote gentamicin absorption. The data indicate that active sodium transport is an integral component of rectal absorption of water-soluble compounds and may be involved in the mechanism of action of absorption-promoting adjuvants.

Influence of ionic strength on rectal absorption of gentamicin sulfate in the presence and absence of sodium salicylate.

The rectal absorption of gentamicin sulfate in rats, both in the presence and absence of sodium salicylate, was facilitated by the use of high ionic strength aqueous formulations. The relative order of effectiveness in promoting gentamicin absorption was sodium dihydrogen phosphate congruent to sodium chloride much greater than potassium chloride, indicating a preferential effect of sodium ions. The increased gentamicin bioavailability in response to sodium salicylate adjuvant activity appeared to be independent of and additive to the increased gentamicin absorption due to high ionic strength conditions. The inability of sorbitol to increase gentamicin bioavailability above control levels indicated that elevated osmotic pressure was not a major determinant of rectal gentamicin absorption.

The use of phenothiazines to enhance the rectal absorption of water-soluble compounds.

The ability of phenothiazines to enhance the rectal absorption of sodium cefoxitin and gentamicin sulphate from aqueous formulations was examined in rats. In the absence of absorption-promoting adjuvants, sodium cefoxitin and gentamicin sulphate bioavailabilities from the rectal compartment were less than 5% of the corresponding intravenous administration. In aqueous microenemas containing 20 mg ml-1 phenothiazine, sodium cefoxitin bioavailability increased to 16-62%, while gentamicin sulphate bioavailability increased to 74-146%. The absorption-promoting potential of chlorpromazine and perphenazine was concentration-dependent, with significant increases in gentamicin sulphate absorption occurring with 1 mg ml-1 chlorpromazine or 2.5 mg ml-1 perphenazine. Maximal gentamicin sulphate bioavailability and serum concentrations were achieved with 10 mg ml-1 chlorpromazine or 20 mg ml-1 perphenazine. The findings indicate that the phenothiazines, which are well absorbed rectally, also significantly enhance the rectal absorption of water-soluble, poorly absorbed compounds.

The effect of medroxyprogesterone acetate on blood pressure.

Twenty-four women (21 normotensive and 3 hypertensive) aged 16-35 years received 150-mg injections of medroxyprogesterone acetate (MPA) for contraception. Their blood pressure (BP) was measured under basal conditions by the same nurse before treatment and at 1-, 2- and 3-month intervals. Their mean BP fell from 124.1/79.4 to 119.8/74.6 mm Hg at one month (p less than 0.05 for diastolic pressure) to 117.0/74.9 mm Hg at two months and to 115.6/73.2 mm Hg at three months. When the normotensive patients were analyzed separately, their BP fell, but not significantly. Only one patient had a rise of 20 mm Hg systolic, but she remained normotensive. We conclude that medroxyprogesterone acetate does not raise BP.

Epidemiology of uterine leiomyomas. With an etiologic hypothesis.

OBJECTIVE: The few previous epidemiologic studies of uterine myomas have relied on clinical evaluation to select controls, but we previously showed that myomas may be present in more than 75% of such uteri. STUDY DESIGN: We therefore attempted to evaluate risk factors using age-matched controls whose uteri were serially sectioned to exclude the presence of myomas. RESULTS: The small study size precluded a meaningful evaluation of most parameters but tended to confirm the negative association of myomas with cigarette smoking (P = .07). CONCLUSION: Using monoclonal smooth muscle proliferation in human atherosclerotic plaques as a model, we suggest that excessive injury to and repair of the endometrial lining of the uterus may promote monoclonal expansion of smooth muscle cell populations in the uterine wall (i.e., myomas). This theory is largely compatible with the estrogen hypothesis, but fundamental principles of tumorigenesis and previous epidemiologic data on myomas suggest that nutritional factors should be scrutinized as possible initiators (DNA-damaging substances) in the pathogenesis of uterine myomas.

Peripheral pulmonary artery stenosis in pregnancy. A report of two cases.

Peripheral pulmonary artery stenosis is a rare congenital anomaly often associated with the maternal rubella syndrome. Two patients with the disorder underwent four successful pregnancies.

Analyzing strategies for developing a prenatal health care outreach program to reduce social and cultural barriers.

Beginning in March, 1994, a multi-cultural, interdisciplinary team of health care providers at Rochester General Hospital in Rochester, New York, planned and implemented a prenatal outreach program in partnership with the Rochester YWCA. The purpose of the project is to increase access to obstetric and gynecological services for low-income African-Americans, Hispanic, and white women. The processes involved in developing an outreach intervention program, Opening Doors, are described and the conflicts that surfaced during the initial stages of program development are analyzed. The problems which occurred can be attributed to role boundary conflict and differences in philosophy regarding ethnicity and health behavior. Through interviews with the anthropologist on the management team and some changes in the overall structure of the program administration, resolution of the conflicts became possible.