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Biomedical subjects

J F Randolph

Publications and source records attributed to J F Randolph.

At least 19 recordsLinked to original sources

Comparison of low-technology and high-technology monitoring of clomiphene citrate ovulation induction.

OBJECTIVE: To determine whether newer monitoring techniques, including urinary detection of the LH surge and vaginal ultrasound, offer an advantage over basal body temperature (BBT) charts alone in achieving pregnancy using clomiphene citrate (CC). DESIGN: Randomized clinical trial. SETTING: Infertility patients in an academic research environment. PATIENT(S): Forty-five women undergoing ovulation induction with CC. INTERVENTION(S): The women were assigned randomly to receive either low- or high-technology ovulation monitoring for a total of 3 ovulatory cycles. Both groups were followed with BBT charts. The high-technology group also was monitored with urinary LH kits and vaginal ultrasound. MAIN OUTCOME MEASURE(S): Cycle fecundity rates for each technique were compared statistically with use of life-table analysis. RESULT(S): Forty-five patients were studied during a total of 134 cycles. The overall cycle fecundity rate was 8%, 10% (8 of 81 cycles) for the low-technology monitoring group and 6% (3 of 53 cycles) for the high-technology monitoring group. These rates were not statistically significant when evaluated by Fisher's exact test (P = .53) or when using life-table analysis and a log-rank test (P = .48). CONCLUSION(S): These data suggest that, for initial attempts at ovulation induction with CC in unselected patients, high-technology monitoring of ovulation offers no increase in fecundity over low-technology monitoring.

Adult

Naturally acquired leptospirosis in 36 dogs: serological and clinicopathological features.

Case records of 36 dogs with confirmed leptospirosis diagnosed at the New York State College of Veterinary Medicine from 1980 to 1995 were reviewed retrospectively, and clinical, serological and pathological findings were recorded to characterise the epidemiology of this disease in upstate New York. Titres were directed predominantly against serovars grippotyphosa and/or pomona in 31 of 34 dogs. Convalescent titres were measured for 53 per cent of dogs. The most common clinical presentation was acute renal failure. Increased liver enzyme activity was documented in 22 of 36 dogs. It is clear from this study that Leptospira pomona and grippotyphosa are important pathogens capable of causing severe renal and hepatic injury in dogs.

Animals

Bone mineral density and its change in pre-and perimenopausal white women: the Michigan Bone Health Study.

There is a need to better understand potential bone mineral density (BMD) loss during the menopausal transition since this period may include the initiation of interventions. The study purpose was to determine if there was BMD loss at the femoral neck, lumbar spine, or total body bone sites in a population-based study of women approaching or transitioning the midlife. The 583 enrollees were 25-45 years of age at the first of four annual measurements from 1992 through 1996. Bone mineral content and bone width were measured using dual-energy X-ray absorptiometry. Considering all enrollees collectively, there was a significant 3-year decline (1%) in BMD at the femoral neck over the 3-year period (p = 0.076). There was no significant annual change in the lumbar spine (p = 0.11), and a significant annual increase in the total body BMD (p = 0.0003). Within subgroups and cross-sectionally, BMD values of the femoral neck were 5% lower in women classified as perimenopausal compared with premenopausal enrollees; BMD was 3% and 1% lower at the lumbar spine and total body site, respectively. Longitudinally, among perimenopausal women, a double oophorectomy was associated with BMD loss in the spine (p = 0.0003), even though 75-85% of these women had a hormone replacement prescription at some time during the study period. In summary, the site with evidence of loss was the femoral neck, specifically among perimenopausal women. There was little evidence of substantial total body or lumbar spine BMD loss in premenopausal women with ovaries who maintained follicle-stimulating hormone levels < 20 mIU/l in the early follicular period. Double oophorectomy, even with hormone replacement, was associated with bone loss.

Absorptiometry, Photon

Urinary ovarian and gonadotropin hormone levels in premenopausal women with low bone mass.

We hypothesized that lower ovarian and gonadotropin hormone concentrations would be associated with lower levels of peak bone mineral density (BMD) in apparently normally menstruating women who did not exercise intensively and did not report anorexia or bulimia. This hypothesis was evaluated using a case-with-control study design (n = 65) which was nested within a population-based longitudinal study of peak bone mass (Michigan Bone Health Study) with annual assessment in women aged 25-45 years (n = 582). Cases were 31 premenopausal women with BMD of the lumbar spine, femoral neck, and total body less than the 10th percentile of the distribution, where controls were 34 premenopausal women with BMD between the 50th and 75th percentile. BMD was measured by dual-energy X-ray absorptiometry. In addition to their annual measurement, these 65 participants collected first-voided morning urine specimens daily through two consecutive menstrual cycles. The urine from alternating days of this collection was analyzed for estrone-3-glucuronide (E1G), pregnanediol glucuronide (PdG), testosterone, and follicle-stimulating hormone by radioimmunoassay and these values adjusted for daily creatinine excretion levels. Additionally, analyses of daily urine specimens for luteinizing hormone (uLH) was undertaken to better characterize the possible uLH surge. Cases had significantly lower amounts of E1G (p = 0.009) and PdG (p = 0.002) than did controls, whether amounts were characterized by a mean value, the highest value, or the area under the curve, and after statistically controlling for body size. Further, when B-splines were used to fit lines to the E1G and PdG data across the menstrual cycle, the 95% confidence intervals (CIs) about the line for the controls consistently excluded and excluded and exceeded the 95% confidence bands for the cases in the time frame associated with the luteal phase in ovulatory cycles. Likewise, 95% CIs for the LH surge in controls exceeded the fitted line for cases around the time associates with the LH surge. The cases and controls were not different according to dietary intake (energy, protein, calcium), family history of osteoporosis, reproductive characteristics (parity, age at menarche, age of first pregnancy), follicular phase serum hormone levels, calciotropic hormone levels, or by evidence of perimenopause. We conclude that these healthy, menstruating women with BMD at the lowest 10th percentile from a population-based study had significantly lower urinary sex steroid hormone levels during the luteal phase of menstrual cycles as compared with hormone levels in premenopausal women with BMD between the 50th and 75th percentile of the same population-based study, even after considering the role of body size. These data suggest that subclinical decreases in circulating gonadal steroids may impair the attainment and/or maintenance of bone mass in otherwise reproductively normal women.

Absorptiometry, Photon

Use of the urine cortisol-to-creatinine ratio for monitoring dogs with pituitary-dependent hyperadrenocorticism during induction treatment with mitotane (o,p'-DDD).

OBJECTIVE: To determine whether the urine cortisol-to-creatinine ratio (UCCR) could replace the ACTH stimulation test in monitoring effectiveness of mitotane induction treatment in dogs with pituitary-dependent hyperadrenocorticism (PDH). ANIMALS: 15 dogs with PDH. PROCEDURE: All 15 dogs were given an induction dose of mitotane (o,p'-DDD: 35 to 50 mg/kg of body weight/d) for 3 to 14 days. During the induction period, free-catch morning urine samples were collected for determination of UCCR, followed by ACTH stimulation testing, every other day. Treatment response was divided into 3 categories: well-controlled PDH (post-ACTH serum cortisol concentration > or = 28 nmol/L but < or = 138 nmol/L), deficient cortisol secretion (post-ACTH serum cortisol concentration < 28 nmol/L), and excess cortisol secretion (post-ACTH serum cortisol concentration > 138 nmol/L). RESULTS: The linear relation between UCCR and post-ACTH serum cortisol concentration was significant (P < 0.001); however, the prediction intervals surrounding the line were too broad to be clinically useful. The UCCR overlapped among the 3 categories of treatment response. Nevertheless, dogs with PDH receiving mitotane induction treatment and with UCCR > 79 x 10(-6) were always classified as having excess cortisol secretion. CONCLUSION AND CLINICAL RELEVANCE: The UCCR failed to predict post-ACTH cortisol concentration during mitotane induction treatment sufficiently close to be a clinically reliable indicator of treatment control. Seemingly, however, UCCR > 79 x 10(-6) obtained from a dog with PDH during mitotane induction would indicate inadequate adrenal cortex destruction and the need for continued mitotane induction; UCCR < or = 79 x 10(-6) would be inconclusive.

Adrenocortical Hyperfunction

Development of bone marrow toxicosis after albendazole administration in a dog and cat.

Bone marrow toxicosis was detected in a dog and cat following albendazole administration. Both animals were admitted with pancytopenia. In the dog, pancytopenia was attributed to severe panmarrow hypoplasia, whereas the cat had hypoplasia of erythroid and megakaryocytic series, but with a left-shifted granulocytic hyperplasia. Results of cytologic examination of bone marrow from both animals were compatible with acute injury. Both animals had been treated with albendazole for giardiasis prior to the onset of clinical signs. Bone marrow toxicosis was attributed to albendazole administration for the following reasons: this was the only or most recent drug administered, other causes of bone marrow toxicosis were not found, and both animals recovered rapidly with supportive care that consisted of fluid and antibiotic administration. Albendazole induced toxicosis appeared to be dose related in the dog and idiosyncratic in the cat. On the basis of the findings in this report, there is a potential for the development of albendazole induced bone marrow toxicosis in dogs and cats; therefore, veterinarians should exercise caution when using this drug.

Albendazole

Intensive hormone monitoring in women with unexplained infertility: evidence for subtle abnormalities suggestive of diminished ovarian reserve.

OBJECTIVE: To determine hormone levels across the menstrual cycle in women with rigorously defined unexplained infertility. DESIGN: Prospective study. SETTING: National Center for Infertility Research at Michigan. PATIENT(S): Evaluation of 1,885 women with infertility identified 12 women who met the following rigorously defined criteria for unexplained infertility: [1] infertility of > or = 24 months' duration, with no male factor, anatomic or functional disorders of the reproductive tract, or immunologic infertility; [2] normal body mass index (BMI); (3) ovulatory cycles ranging from 26 to 32 days; [4] normal luteal phase determined by endometrial biopsy; and [5] normal baseline hormonal profile. Controls (n = 12) were healthy, parous women with normal ovulatory cycles and normal hormonal screens, and were matched for age and BMI with patients. MAIN OUTCOME MEASURE(S): Daily gonadotropin and steroid hormone levels across the menstrual cycle. RESULT(S): Basal FSH and LH levels in the early, middle and late follicular phases were increased significantly in the group with unexplained fertility compared with the normal controls. The mean (+/-SD) early follicular FSH levels were 7.0 +/- 0.57 mIU/mL in the unexplained-infertility group and 4.7 +/- 0.37 mIU/mL (conversion factor to SI units, 1.00) in the normal controls, respectively. There was no difference between groups over the periovulatory or luteal phase. Midluteal mean (+/-SD) P levels were lower in the unexplained-infertility group than in the normal controls (13.7 +/- 1.6 versus 24.0 +/- 3.2 ng/mL [conversion factor to SI units, 3.180]). Mean E2 concentrations were elevated in the group with unexplained infertility versus normal controls in the early through the late follicular phase but reached significance only in the midfollicular phase. Mean prolactin levels were elevated consistently across the menstrual cycle in the unexplained-infertility group compared with those in normal controls but reached significance only in the early and late follicular and midluteal phases of the cycle. Cortisol concentrations were similar between the two groups. CONCLUSION(S): These data indicate that there are subtle alterations in various hormones measured across the menstrual cycle in women with unexplained infertility compared with those in normal controls, suggesting a diminished ovarian reserve.

Adult

Expectant management versus elective curettage for the treatment of spontaneous abortion.

OBJECTIVE: To determine whether the amount of intrauterine tissue was prognostic of the risk of complications associated with the management of nonviable pregnancies diagnosed in the first trimester before cervical dilatation (termed here impending abortion) with either expectant observation or elective curettage. DESIGN: Historic cohort study. SETTING: University Infertility Service. PATIENT(S): All women with nonviable pregnancies followed by the Division of Reproductive Endocrinology during a 5-year period. The patients were divided into those with significant intrauterine tissue (gestational sac > 10 mm) and those with minimal intrauterine tissue. INTERVENTION(S): Women either underwent elective curettage or were followed expectantly. MAIN OUTCOME MEASURE(S): Complication rates. RESULT(S): In 89 women with minimal tissue, no complications occurred regardless of treatment mode. In 63 women with significant intrauterine tissue, expectant management resulted in more complications (9/24) than elective curettage (1/39). In the expectant group, complications included missed abortion, septic abortion, and incomplete abortion requiring emergency curettage, with one patient requiring a transfusion. In the curettage group one uterine perforation occurred. CONCLUSION(S): In women with impending abortions and minimal intrauterine tissue, expectant treatment is safe after ectopic pregnancy has been excluded. In patients with significant intrauterine tissue, the risk of complications may be decreased by elective uterine curettage compared with expectant management.

Abortion, Threatened

Midcycle increase of prolactin seen in normal women is absent in subjects with unexplained infertility.

OBJECTIVE: To compare the bioactive and immunoactive PRL in normal and unexplained infertility subjects. DESIGN: Prospective study. SETTING: Department of Obstetrics and Gynecology, Wayne State University and The University of Michigan. PATIENT(S): Twelve normal, fertile women compared with 12 patients with unexplained infertility. INTERVENTION(S): Serum samples were obtained across the menstrual cycle and for each subject, 5 pools were prepared by combining serum aliquots from the early follicular, late follicular, midcycle, and midluteal and late luteal phases of the cycle. MAIN OUTCOME MEASURE(S): Niobium lymphoma cell bioassay and an immunoradiometric assay were used to quantitate PRL. RESULT(S): A midcycle increase in PRL was seen in controls by both assays and these levels were greater compared with other cycle stages. Comparison of midcycle PRL between groups showed differences only between bioactive PRL (34.2 +/- 8.3 versus 19.2 +/- 3.4 ng/mL [conversion factor to SI unit, 1.00]). The ratios between bioactive and immunoactive PRL were comparable. Significant correlation between bioactive and immunoactive PRL was seen for both control (r = 0.616) and unexplained infertility (r = 0.660) groups. CONCLUSION(S): The midcycle elevations of bioactive and immunoactive PRL seen in normal women were absent in women with unexplained infertility. This alteration in PRL dynamics may be a part of subtle differences in the reproductive hormone profile of women with unexplained infertility compared with their fertile counterparts.

Adult

Luteal support with both estradiol and progesterone after clomiphene citrate stimulation for in vitro fertilization.

OBJECTIVE: To determine if pregnancy rates (PRs) for clomiphene citrate (CC)-stimulated IVF-ET can be increased by luteal support with E2 and P. DESIGN: Prospective randomized crossover clinical study. SETTING: Infertile women volunteers in an academic research environment. PATIENTS: Ninety-three infertile women underwent a total of 143 IVF-ET cycle using CC for ovulation induction. INTERVENTIONS: Each woman received either no luteal support (control group) or luteal support with both oral E2 (2 mg three times daily) starting on the day of retrieval and vaginal P suppositories (100 mg twice daily) starting on the day of ET. MAIN OUTCOME MEASURE: Clinical PR. RESULTS: In 79 of 143 (55%) of the cycles, at least one embryo was transferred. Compared with the control group (n = 35 cycles), the luteal support group (n = 44 cycles) had a significantly higher PR per retrieval (control: 2% versus luteal support: 16%) and were older (control: 33 +/- 4 versus luteal support: 35 +/- 4 years; mean +/- SEM). They did not differ in terms of E2 or P levels, endometrial thickness on the day of hCG, number of follicles > 16 mm in diameter, mature oocytes retrieved, or embryos transferred. CONCLUSIONS: Luteal support with both E2 and P significantly increase the clinical PRs for CC-stimulated IVF-ET.

Adult

Effects of oral ursodeoxycholic acid in healthy cats on clinicopathological parameters, serum bile acids and light microscopic and ultrastructural features of the liver.

A blind, placebo-controlled study evaluated the effects of ursodeoxycholic acid (UDCA) given orally, at a dose of 15 mg kg-1 per day for eight weeks, on the physical condition, haematological and serum biochemical profiles, urinalysis, total serum bile acids (TSBA) and hepatic histology of four healthy cats. There were no clinically important significant differences between the groups or within the treatment groups in clinicopathological parameters. TSBA concentrations or histology. A significant lower concentration/proportion of taurochenodeoxycholic acid was observed in the treated cats (P = 0.05). Only one treated cat accumulated measurable quantities of UDCA, and the compound appeared to be non-toxic. It did not increase the concentration of TSBA, and accumulated minimally in the serum. It should be investigated for therapeutic use in cats with hepatobiliary disease.

Administration, Oral

Evaluation of urinary cortisol:creatinine ratios for the diagnosis of hyperadrenocorticism associated with adrenal gland tumors in ferrets.

Assays were validated for the measurement of urinary concentrations of cortisol and creatinine in domestic ferrets (Mustela putorius furo). Urinary concentrations of cortisol and creatinine and the calculated urinary cortisol:creatinine ratio (UCCR) values were determined for 29 clinically normal female ferrets, 22 clinically normal male ferrets, and 12 ferrets with adrenal gland tumors. The UCCR values for the 51 clinically normal ferrets ranged from 0.04 x 10(-6) to 1.66 x 10(-6), with a median value of 0.22 x 10(-6). The UCCR values were significantly (P < or = 0.01) higher in the 12 ferrets with adrenal tumors, with a range of 0.5 x 10(-6) to 60.13 x 10(-6) and a median of 5.98 x 10(-6). We concluded that determination of UCCR values was useful in the diagnosis of hyperadrenocorticism associated with adrenal neoplasia in domestic ferrets.

Adenocarcinoma

Comparison of growth hormone and insulin-like growth factor-I regulation of estradiol and progesterone production in human luteinized granulosa cells.

Growth hormone (GH) appears to affect the timing of puberty in children. The effects of GH on puberty may be related to direct GH action on ovarian function or may be mediated by IGF-I. To determine the likelihood that GH has direct effects on ovarian function, we compared the ability of GH and IGF-I to increase luteinized granulosa cell steroidogenesis in the absence and presence of gonadotropins. Cells were obtained from women undergoing in vitro fertilization for tubal disorders or male factor infertility and were placed in static culture. GH alone failed to alter progesterone or estradiol accumulation in the medium of cultured luteinized granulosa cells. IGF-I produced no increase in progesterone accumulation but increased estradiol accumulation 5.6-fold compared with cells treated with vehicle. The combination of GH and FSH produced an 0.83-fold increase in estradiol accumulation, whereas the combination of IGF-I and FSH resulted in a 2.9-fold increase in estradiol accumulation above FSH alone. Thus the direct effects of GH on granulosa cell steroid synthesis are modest compared with those of IGF-I. If GH has an effect on ovarian development at puberty, it is likely to be mediated by a GH-induced increase in circulating IGF-I.

Cells, Cultured

Biochemical markers of bone turnover in lactating and nonlactating postpartum women.

We measured two bone-formation markers, osteocalcin and bone-specific alkaline phosphatase, and one bone-resorption marker, N-telopeptide, in a longitudinal study in order to describe levels of these markers in lactating and nonlactating women after parturition. This 18-month postpartum period included an initial 6 months in which a 5% short-term bone loss occurred at both spine and femoral neck among breast-feeding women. The second part of the 18-month period was characterized by bone recovery among women who had lost bone. These bone-change characteristics provided an opportunity to evaluate the performance of biochemical markers during both bone loss and recovery and to identify environmental exposures during lactation associated with bone turnover. The eligible population comprised 115 women whose bone-turnover markers were measured at 2 weeks (baseline) and at 2, 4, 6, 12, and 18 months after parturition. Participants reported reproductive characteristics, diet, physical activity, use of medications, and infant-feeding practices at each contact. Women were grouped according to lactation duration: 0-1 months, 2-5 months, and 6 months or more. Women who breast-fed for at least 6 months had significantly different levels of all three bone-turnover markers compared with the levels in bottle-feeding controls, which were indicative of substantially increased bone turnover. Factors that predicted the difference in biochemical markers from baseline to 6-month values by regression analysis were lactation of 2-6 months duration and lactation for 6 months or more. Dietary calcium intake, physical activity level, and body size did not explain the differences in the change from the baseline level to the 6-month level, a period of time that corresponded with bone loss in the lactating women. Factors that predicted the differences in bone-turnover markers between 6 and 18 months (the time of bone-mass recovery) were lactation status and number of months to resumption of menses. By the 18-month observation, there was no difference in the mean values for the measured bone-turnover markers among the three lactation groups. This suggests that menstrual activity, rather than diet or physical activity, is the primary factor in bone-mass recovery after the bone loss of lactation.

Adult

Adrenocortical function in neonatal and weanling beagle pups.

Adrenocortical function was assessed in 27 Beagle pups at 2, 4, 6, 8, 10, and 12 weeks of age by determination of plasma sodium, potassium, and chloride concentrations; serum aldosterone and cortisol concentrations; and plasma ACTH concentrations. Serum cortisol concentration was measured before and 1 and 2 hours after IM administration of 2.2 IU of ACTH/kg of body weight. Serum progesterone concentration also was determined for all pups at 2, 4, and 6 weeks of age. Mean baseline cortisol concentration was lower for pups 8 weeks old or younger than for mature dogs. Nevertheless, mean serum ACTH-stimulated cortisol concentration in dogs of all age groups increased into the adult reference range after administration of ACTH. For pups 4 weeks old or younger, increase in cortisol concentration was maximal at 2 hours after ACTH administration. However, in pups between 6 and 12 weeks of age, the increase in cortisol concentration was maximal 1 hour after ACTH administration in about a third of the pups, whereas the remaining pups had peak values at 2 hours. Mean plasma sodium, potassium, and chloride concentrations for each age group were within the reference ranges established for mature dogs, with the exception of lower mean plasma sodium and chloride concentrations in pups 4 weeks old or younger. Mean serum aldosterone concentration in pups of each age group was substantially higher than the range of aldosterone concentrations for clinically normal mature dogs. Median progesterone concentration was uniformly less than 0.2 ng/ml for all pups 6 weeks old or younger.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex

Morphologic assessment of endometrium overlying submucosal leiomyomas.

The effect of submucosal leiomyomas on endometrial structure in women with symptomatic clinical findings was studied retrospectively. The endometrial histology from 13 hysterectomies for uterine leiomyomas was examined using three 2-mm sections of endometrium (one overlying a submucosal leiomyoma and two without underlying leiomyomas). Endometrial thickness, gland number and appearance, vessel number and diameter, and stromal inflammation were assessed. The thickness of the myometrium between the leiomyoma and the overlying 2-mm section of endometrium analyzed was also evaluated. The control group consisted of seven nonmyomatous uteri removed for benign disease. Analysis of the endometrium with underlying submucosal leiomyomas identified two groups using endometrial gland number as the criterion for this division. Five cases (group A) were found to have no endometrial glands, while the remaining eight (group B) had an average gland number of 74.5 per 2-mm section of endometrium. The mean gland number for the control group was 82.6, showing no significant difference from group B. Group A had an average endometrial area (2-mm thickness) of 0.38 mm2, and group B had an average area of 4.47 mm2, for a significant difference (t = -3.76, P = .007). Comparison of the two groups with the control group (mean area, 4.71 mm2) showed a significant difference in endometrial area only with group A (t = -7.64, P < .0005). A significant difference (t = -2.93, P = .019) was observed in the analysis of the thickness of the myometrium between the leiomyoma and overlying endometrium between groups A (mean thickness, 0.53 mm) and B (mean thickness, 1.70 mm).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Open laparoscopy without special instruments or sutures. Comparison with a closed technique.

An important advantage of open laparoscopy over closed techniques is the avoidance of placing a sharp trocar blindly into the peritoneal cavity. Although an open technique theoretically minimizes the risk of major retroperitoneal vessel injury and bowel injury, most laparoscopies are performed using a closed technique. In an effort to simplify open laparoscopy, a technique was developed that can be done without special equipment or sutures and nearly as quickly as a closed technique. To compare the effectiveness of this open laparoscopic technique to a closed technique, a prospective, observational, cohort study was carried out on 66 women undergoing laparoscopy for either infertility or pelvic pain. The open technique was performed on 35 consecutive patients and compared to a closed technique performed on 31 patients on a different service during the same period. Evaluation included total duration of the procedure, length of the incision, incidence of CO2 leakage and complications. The open technique took slightly longer, and the incision was slightly longer. CO2 leakage occurred in 5 of 35 of the open cases but in none of the 31 closed cases. Leakage was controlled effectively in every case by application of a towel clip to the skin incision. No complications occurred with either technique. This study suggested that an open technique that requires no special equipment or sutures may be a useful alternative approach for laparoscopy when insertion of a sharp trocar is undesirable.

Adult