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Biomedical subjects

M B Brown

Publications and source records attributed to M B Brown.

At least 55 records · Page 3Linked to original sources
PubMed2000

Morbidity and mortality associated with a new mycoplasma species from captive American alligators (Alligator mississippiensis).

Nine of 74 American alligators (Alligator mississippiensis) from a captive Florida herd of 3-4-m-long, 200-350-kg, adult males greater than 30 yr of age died within a 10-day period during 1995. Nonspecific clinical signs included anorexia, lethargy, muscle weakness, paraparesis, bilateral white ocular discharge, and various degrees of periocular, facial, cervical, and limb edema. Pneumonia, pericarditis, and arthritis were found on postmortem evaluation of the spontaneously dead and euthanatized alligators. Rapidly growing mycoplasmas were identified by culture, and mycoplasma nucleotide sequences were identified by polymerase chain reaction testing of fresh lung and synovial fluid from an affected alligator. Culture of banked frozen lung from necropsy specimens and fresh lung and fresh synovial fluid from newly affected alligators confirmed the presence of a new mycoplasma species in seven of eight individuals. Oxytetracycline was administered, but related deaths continued for 6 mo until only 14 of the initial alligators remained. An enzyme-linked immunosorbent assay to detect antibody was developed, and the organism was transmitted experimentally to naive juvenile alligators, although the source of the organism, Mycoplasma sp. (ATCC 700619), has not been identified. The alligator isolate is a novel species in the mycoplasma family because its nucleotide sequence does not match those of over 75 characterized mycoplasma species. Such factors as population density, animal age, and mycoplasmal virulence likely contributed to the course of disease.

Alligators and Crocodiles↗
PubMed2000

Diagnosing written language disabilities using the Woodcock-Johnson Tests of Educational Achievement-Revised and the Wechsler Individual Achievement Test.

The writing portions of the Woodcock-Johnson Tests of Educational Achievement-Revised and the Wechsler Individual Achievement Test are often administered when establishing eligibility for special education services due to learning disabilities. The scores on these measures are typically regarded as equivalent although little is known about how scores on the two measures differ for the same students. Differences of only a few points, however, may affect eligibility for special education services. These tests were administered to 25 sixth grade students previously diagnosed with learning disabilities in written expression only. Students' Wechsler scores were consistently higher on the overall writing composite, while there was no difference in the mean scores on the language mechanics subtests. The WIAT Written Expression subtest mean, however, was significantly higher than the Woodcock-Johnson Writing Samples subtest mean. Use of the Wechsler test would be less likely to identify children for special education services in written expression when point discrepancy criteria are utilized for eligibility. Clinicians should be cognizant of the effect of the specific test chosen on eligibility outcome.

Achievement↗
PubMed2000

Pathology of upper respiratory tract disease of gopher tortoises in Florida.

Between August 1993 and September 1995, 24 gopher tortoises (Gopherus polyphemus) were received for pathological evaluations from various locations in Florida (USA). All tortoises were examined for clinical signs of upper respiratory tract disease (URTD) including nasal and ocular discharge, palpebral edema, and conjunctivitis. Of the 24 tortoises, 10 had current or previously observed clinical signs of URTD and 14 did not. A blood sample was drawn for detection of anti-mycoplasma antibodies by ELISA, and nasal lavage samples were collected for culture and detection of Mycoplasma agassizii gene sequences by polymerase chain reaction (PCR). Of the 14 clinically healthy tortoises, eight were sero-, culture- and PCR-negative, and six were seropositive for antibodies against M. agassizii. Of those six, five were culture- and/or PCR-positive for M. agassizii, and one was culture- and PCR-negative. Of the 10 ill tortoises, nine were seropositive by the ELISA and one was in the suspect range. Nine of the ill tortoises, including the suspect tortoise, were culture- and/or PCR-positive for M. agassizii, and one was culture- and PCR-negative. For histologic evaluation and discussion, the eight sero-, culture-, and PCR-negative tortoises were designated URTD-negative, and the other 16 were classified as URTD-positive. Histologic evaluation of the upper respiratory tract (URT) indicated the presence of mild to severe inflammatory, hyperplastic, or dysplastic changes in 14 URTD-positive tortoises. Seven of eight URTD-negative tortoises had normal appearing nasal cavities; one had mild inflammatory changes. Transmission electron microscopy revealed an organism consistent with Mycoplasma spp. on the nasal mucosal surface of tortoises with clinical signs and lesions of URTD. Additionally, gram-negative bacteria were isolated more frequently from the nasal cavities of URTD-positive tortoises than URTD-negative tortoises. Because clinical signs of URTD were never observed in six of the URTD-positive tortoises, we also conclude that subclinical URTD can occur in gopher tortoises.

Animals↗
PubMed2000

Follicular phase hypothalamic-pituitary-gonadal axis function in women with fibromyalgia and chronic fatigue syndrome.

OBJECTIVE: Fibromyalgia (FM) and chronic fatigue syndrome (CFS) are clinically overlapping stress associated disorders. Neuroendocrine perturbations have been noted in both syndromes, and they are more common in women, suggesting abnormalities of gonadal steroid hormones. We tested the hypothesis that women with FM and CFS manifest abnormalities of the hypothalamic-pituitary-gonadal (HPG) hormonal axis. METHODS: We examined the secretory characteristics of estradiol, progesterone, follicle stimulating hormone (FSH), and luteinizing hormone (LH), including a detailed analysis of LH in premenopausal women with FM (n = 9) or CFS (n = 8) during the follicular phase of the menstrual cycle compared to matched healthy controls. Blood was collected from an indwelling intravenous catheter every 10 min. over a 12 h period. LH was assayed from every sample; pulses of LH were identified by a pulse-detection program. FSH and progesterone were assayed from a pool of hourly samples for the 12 h period and estradiol from samples pooled over four 3 h time periods. RESULTS: There were no significant differences in FSH, progesterone, or estradiol levels in patients versus controls. There were no significant differences in pulsatile secretion of LH. CONCLUSION: There is no indication of abnormal gonadotropin secretion or gonadal steroid levels in this small, but systematic, study of HPG axis function in patients with FM and CFS.

Adolescent↗
PubMed2000

Mycoplasma pulmonis genital disease: effect of rat strain on pregnancy outcome.

BACKGROUND AND PURPOSE: Mycoplasma pulmonis is a natural pathogen of the respiratory and genital tracts of rats. Differential susceptibility and severity of the respiratory form of the disease, known as murine respiratory mycoplasmosis (MRM), exist between rat strains. We now report that specific rat strains vary in susceptibility to genital tract infection and pregnancy outcome. METHODS: Specific-pathogen-free (SPF) female F344, LEW, Wistar (WIS) and Sprague Dawley (SD) rats were intravaginally inoculated with 3 x 10(7) colony-forming units (CFU) of M. pulmonis strain X1048 or sterile diluent, and allowed to breed at 10 days after inoculation. Pregnant dams and pups were necropsied within 24 hours of parturition. At necropsy, culture for M. pulmonis was performed on dam and pups, and adverse effects on pregnancy outcome were assessed by determination of the incidence of infertility, fetal resorption, stillbirths, changes in litter size, and pup birth weight. Blood from dams was collected prior to inoculation and at time of necropsy for measurement of IgM and IgG antibodies to M. pulmonis. RESULTS: At time of necropsy, WIS (50%) and SD (60%) dams had a higher frequency of M. pulmonis culture positivity in the genital tract than did LEW (22.2%) and F344 (17.6%) dams. Dams that were still infected with M. pulmonis at time of necropsy had various complications. The SD rats had the greatest degree of adverse effects on pregnancy outcome, which were: infertility, decreased litter size (P < or = 0.01), decreased pup birth weight (P < or = 0.01), increased frequency of resorptions, stillbirths (P < or = 0.05), and the highest rate of pup pulmonary infection (23.1%) (P < or = 0.001). Despite a 50% colonization rate, WIS dams were the least adversely affected. The WIS pups born from M. pulmonis. infected dams had slight decrease in birth weight, and only 6% had pulmonary infections. The LEW infected dams developed infertility and lower numbers of liveborn pups without evidence of vertical transmission. The F344 infected dams had lower numbers of liveborn pups that were smaller than their control counterparts, and none had pulmonary infections. None of the animals had detectable IgM and IgG antibodies to M. pulmonis before inoculation. At time of necropsy, all animals inoculated with M. pulmonis developed significantly (P < or = 0.001) higher amounts of M. pulmonis IgG and IgM antibodies, with SD rats developing the highest amounts (P < or = 0.005). CONCLUSIONS: Both F344 and LEW rats are more resistant to vaginal inoculation with M. pulmonis than are WIS and SD rats. However, only SD dams suffered severe adverse effects on pregnancy outcome. The SD dams also had the greatest IgM and IgG antibody response to M. pulmonis. Our studies clearly indicate differences among rat strains in their susceptibility to vaginal inoculation with M. pulmonis and in secondary complications associated with infection. This system may be a useful model for determining host-specific factors that influence the outcome of natural mycoplasmal infections of the genital tract.

Animals↗
PubMed1999

Effect of aldose reductase inhibition on nerve conduction and morphometry in diabetic neuropathy. Zenarestat Study Group.

OBJECTIVE: To determine whether the aldose reductase inhibitor (ARI) zenarestat improves nerve conduction velocity (NCV) and nerve morphology in diabetic peripheral polyneuropathy (DPN). METHODS: A 52-week, randomized, placebo-controlled, double-blinded, multiple-dose, clinical trial with the ARI zenarestat was conducted in patients with mild to moderate DPN. NCV was measured at baseline and study end. Contralateral sural nerve biopsies were obtained at 6 weeks and at the study's end for nerve sorbitol measurement and computer-assisted light morphometry to determine myelinated nerve fiber density (number of fibers/mm2 cross-sectional area) in serial bilateral sural nerve biopsies. RESULTS: Dose-dependent increments in sural nerve zenarestat level and sorbitol suppression were accompanied by significant improvement in NCV. In a secondary analysis, zenarestat doses producing >80% sorbitol suppression were associated with a significant increase in the density of small-diameter (<5 microm) sural nerve myelinated fibers. CONCLUSIONS: Aldose reductase pathway inhibition improves NCV slowing and small myelinated nerve fiber loss in DPN in humans, but >80% suppression of nerve sorbitol content is required. Thus, even low residual levels of aldose reductase activity may be neurotoxic in diabetes, and potent ARIs such as zenarestat may be required to stop or reverse progression of DPN.

Action Potentials↗
PubMed1999

Upper respiratory tract disease in the gopher tortoise is caused by Mycoplasma agassizii.

Upper respiratory tract disease (URTD) has been observed in a number of tortoise species, including the desert tortoise (Gopherus agassizii) and the gopher tortoise (Gopherus polyphemus). Clinical signs of URTD in gopher tortoises are similar to those in desert tortoises and include serous, mucoid, or purulent discharge from the nares, excessive tearing to purulent ocular discharge, conjunctivitis, and edema of the eyelids and ocular glands. The objectives of the present study were to determine if Mycoplasma agassizii was an etiologic agent of URTD in the gopher tortoise and to determine the clinical course of the experimental infection in a dose-response infection study. Tortoises were inoculated intranasally with 0.5 ml (0.25 ml/nostril) of either sterile SP4 broth (control group; n = 10) or 10(8) color-changing units (CCU) (total dose) of M. agassizii 723 (experimental infection group; n = 9). M. agassizii caused clinical signs compatible with those observed in tortoises with natural infections. Clinical signs of URTD were evident in seven of nine experimentally infected tortoises by 4 weeks postinfection (p.i.) and in eight of nine experimentally infected tortoises by 8 weeks p.i. In the dose-response experiments, tortoises were inoculated intranasally with a low (10(1) CCU; n = 6), medium (10(3) CCU; n = 6), or high (10(5) CCU; n = 5) dose of M. agassizii 723 or with sterile SP4 broth (n = 10). At all time points p.i. in both experiments, M. agassizii could be isolated from the nares of at least 50% of the tortoises. All of the experimentally infected tortoises seroconverted, and levels of antibody were statistically higher in infected animals than in control animals for all time points of >4 weeks p.i. (P < 0.0001). Control tortoises in both experiments did not show clinical signs, did not seroconvert, and did not have detectable M. agassizii by either culture or PCR at any point in the study. Histological lesions were compatible with those observed in tortoises with natural infections. The numbers of M. agassizii 723 did not influence the clinical expression of URTD or the antibody response, suggesting that the strain chosen for these studies was highly virulent. On the basis of the results of the transmission studies, we conclude that M. agassizii is an etiologic agent of URTD in the gopher tortoise.

Animals↗
PubMed1999

Resistance exercise training increases mixed muscle protein synthesis rate in frail women and men >/=76 yr old.

Muscle atrophy (sarcopenia) in the elderly is associated with a reduced rate of muscle protein synthesis. The purpose of this study was to determine if weight-lifting exercise increases the rate of muscle protein synthesis in physically frail 76- to 92-yr-old women and men. Eight women and 4 men with mild to moderate physical frailty were enrolled in a 3-mo physical therapy program that was followed by 3 mo of supervised weight-lifting exercise. Supervised weight-lifting exercise was performed 3 days/wk at 65-100% of initial 1-repetition maximum on five upper and three lower body exercises. Compared with before resistance training, the in vivo incorporation rate of [(13)C]leucine into vastus lateralis muscle protein was increased after resistance training in women and men (P < 0.01), although it was unchanged in five 82 +/- 2-yr-old control subjects studied two times in 3 mo. Maximum voluntary knee extensor muscle torque production increased in the supervised resistance exercise group. These findings suggest that muscle contractile protein synthetic pathways in physically frail 76- to 92-yr-old women and men respond and adapt to the increased contractile activity associated with progressive resistance exercise training.

Aged↗
PubMed1999

Effect of selective screening for gestational diabetes.

OBJECTIVE: To estimate the percentage of pregnant women who would not be screened and the percentage of women with gestational diabetes mellitus (GDM) who would possibly remain undiagnosed if the American Diabetes Association's (ADA's) new selective screening recommendations are used rather than universal screening for GDM. RESEARCH DESIGN AND METHODS: Since 1987, the University of Michigan Health System has performed universal screening for GDM. In 1997, the ADA recommended that women having all four of the following characteristics need not be screened: age < 25 years, not members of an ethnic/racial group with a high prevalence of diabetes, normal body weight, and no family history of diabetes. We studied a random sample of the 25,118 deliveries at the University of Michigan between 1987 and 1997 to determine the prevalence of these four characteristics in our obstetric population. We also studied the prevalence of these four characteristics in 200 women who were diagnosed with GDM in the Endocrine Testing Unit and delivered at the University of Michigan between 1987 and 1997. RESULTS: Approximately 10-11% of women who delivered possessed all four low-risk characteristics and would not have been screened for GDM according to the new ADA recommendations. Only 4% of women (5 of 141) with GDM who delivered and for whom data on all four characteristics were reported possessed all four low-risk characteristics and would not have been screened. CONCLUSIONS: If the new ADA selective screening recommendations are used, few women with GDM will be missed (4%) but approximately 90% of pregnant women will still need to be screened for GDM.

Adult↗
PubMed1999

Seroepidemiology of upper respiratory tract disease in the desert tortoise in the western Mojave Desert of California.

Several factors have combined with an upper respiratory tract disease (URTD) to produce declines on some population numbers of desert tortoises (Gopherus agassizii) in the western USA. This study was designed to determine the seroepidemiology of URTD in a population of wild adult tortoises at the Desert Tortoise Research Natural Area (DTNA) study site in Kern County (California, USA). Prior to initiation of the study, there was a dramatic decline in the number of individuals in this population. At each individual time point, samples were obtained from 12 to 20 tortoises with radiotransmitters during winter, spring, summer, and fall from 1992 through 1995. During the course of the study, 35 animals were sampled at one or more times. Only 10 animals were available for consistent monitoring throughout the 4 yr period. Specific antibody (Ab) levels to Mycoplasma agassizii were determined for individual tortoises by an enzyme-linked immunosorbent assay (ELISA) test. Specific Ab levels were not influenced by the gender of the tortoise. Levels of Ab and distribution of ELISA+, ELISA- and suspect animals were not consistently affected by season within a single year or for a season among the study years. Significantly more tortoises presented with clinical signs in 1992 and 1995. The profile of ELISA+ animals with clinical signs shifted from 5% (1992) to 42% (1995). In 1992, 52% of tortoises lacked clinical signs and were ELISA-. In 1995, this category accounted for only 19% of tortoises. Based on the results of this study, we conclude that URTD was present in this population as evidenced by the presence of ELISA+ individual animals, and that the infectious agent is still present as evidenced by seroconversion of previously ELISA- animals during the course of the study. There is evidence to suggest that animals may remain ELISA+ without showing overt disease, a clinical pattern consistent with the chronic nature of most mycoplasmal infections. Further, there are trends suggesting that the clinical expression of disease may be cyclical. Continued monitoring of this population could provide valuable information concerning the spread of URTD in wild tortoise populations.

Animals↗
PubMed1998

Importance of the gonadotropin-releasing hormone (GnRH) surge for induction of the preovulatory luteinizing hormone surge of the ewe: dose-response relationship and excess of GnRH.

The preovulatory LH surge in the ewe is stimulated by a large sustained surge of GnRH. We have previously demonstrated that the duration of this GnRH signal exceeds that necessary to initiate and sustain the LH surge. The objective of the present study was to determine whether a similar excess exists for amplitude of the GnRH surge. Experiments were performed using an animal model in which GnRH secretion was blocked by progesterone, which in itself does not block the pituitary response to GnRH. To assess the amplitude of the GnRH surge needed to induce the LH surge, we introduced artificial GnRH surges of normal contour and duration but varying amplitudes. Twelve ewes were run through 3 successive artificial follicular phases (total of 36). Six of these artificial follicular phases were positive controls, in which progesterone was removed, the estradiol stimulus was provided, and vehicle was infused. In these control cycles, animals generated endogenous LH surges. In the remaining artificial follicular phases, progesterone was not withdrawn, the estradiol stimulus was provided, and either vehicle (negative control) or GnRH solutions of varying concentrations (experimental) were infused. The circulating GnRH concentrations achieved by infusion were monitored. No LH surges were observed in negative controls, whereas LH surges were induced in experimental cycles provided a sufficient dose of GnRH was infused. A highly significant dose-response relationship was observed between the amplitude of the GnRH surge and both the amplitude of the LH surge and the area under the curve describing the LH response, but no such relationship existed between the amplitude of the GnRH surge and the duration of the LH response. In numerous cases, LH surges similar to those in the positive control animals resulted from infusion of amounts of GnRH estimated to be considerably less than those delivered to the pituitary during the endogenously generated GnRH/LH surge. These findings indicate that, in the ewe, increased GnRH secretion drives the preovulatory LH surge in a dose-dependent fashion, and they provide evidence that the amplitude of the GnRH surge may exceed that needed to generate the LH surge.

Animals↗
PubMed1998

In pubertal girls, naloxone fails to reverse the suppression of luteinizing hormone secretion by estradiol.

Estradiol (E2) negative feedback on LH secretion was examined in 10 pubertal girls, testing the hypothesis that E2 suppresses LH pulse frequency and amplitude through opioid pathways. At 1000 h, a 32-h saline infusion was given, followed 1 week later by an E2 infusion at 13.8 nmol/m2 x h. During both infusions, four iv boluses of saline were given hourly beginning at 1200 h, and four naloxone iv boluses (0.1 mg/kg each) were given hourly beginning at 1200 h on the following day. Blood was obtained every 15 min for LH determination and every 60 min for E2 determination from 1200 h to the end of the infusion. E2 infusion increased the mean serum E2 concentration from 44+/-17 to 112+/-26 pmol/L (P < 0.01). The mean LH concentration between 2200-1200 h decreased from 3.19+/-0.89 to 1.99+/-0.65 IU/L (P = 0.014), and LH pulse amplitude decreased from 3.4+/-0.6 to 2.6+/-0.5 IU/L (P = 0.0076). Although there were 1.2 fewer pulses during E2 infusion compared to saline infusion, differences did not reach significance (P = 0.1; 95% confidence interval for the difference, -3.5, 1.1). Pituitary responsiveness to GnRH, assessed at the end of the infusion by administering 250 ng/kg GnRH iv, did not change during E2 infusion. The effect of naloxone blockade of opioid activity on LH secretion was determined by assessing the area under the curve (AUC) from 1200-1600 h. During saline infusion, the LH AUC was 1122+/-375 IU/L during saline boluses and 1575+/-403 IU/L during naloxone boluses (P = 0.39). When E2 was infused, the LH AUCs during saline and naloxone boluses were 865+/-249 and 866+/-250 IU/L, respectively. Thus, in pubertal girls: 1) E2 decreases the LH concentration and LH pulse amplitude; 2) the main site of negative feedback effect of E2 appears to be at the level of the hypothalamus; 3) an increase in LH secretion after naloxone administration could not be demonstrated in these girls and may depend on the maturity of the hypothalamic-pituitary-gonadal axis; and 4) opioid receptor blockade does not reverse the E2 inhibition of LH secretion even in the most mature girls. Thus, E2 suppression of LH secretion in pubertal girls appears to be mediated by a decrease in hypothalamic GnRH secretion that is independent of opioid pathways.

Adolescent↗
PubMed1998

Pathology of diseases in wild desert tortoises from California.

Twenty-four ill or dead desert tortoises (Gopherus agassizii) were received between March 1992 and July 1995 for necropsies from the Mojave and Colorado deserts of California (USA). Diseases observed in these animals included cutaneous dyskeratosis (n = 7); shell necrosis (n = 2); respiratory diseases (n = 7); urolithiasis (n = 3); and trauma (n = 5). In tortoises with cutaneous dyskeratosis the horn layer of shell was disrupted by multiple crevices and fissures and, in the most severe lesions, dermal bone showed osteoclastic resorption, remodeling, and osteopenia. In tortoises with shell necrosis, multiple foci of necrotic cell debris and heterophilic inflammation within the epidermal horn layer were subtended by necrotic dermal bone colonized by bacteria and fungi. Of the seven tortoises with respiratory disease, five were diagnosed with mycoplasmosis. The diagnosis of mycoplasmosis was based on the presence of chronic proliferative rhinitis and positive serologic tests and/or isolation of Mycoplasma sp. Chronic fungal pneumonia was diagnosed in one tortoise with respiratory disease. In the three tortoises with urolithiasis, two were discovered dead, and the live tortoise had renal and articular gout. Traumatic injuries consisted of one tortoise entombed within its burrow, one tortoise burned in a brush fire, two tortoises struck by moving vehicles, and one tortoise attacked by a predator. While the primary cause of illness could be attributed to one or two major disease processes, lesions were often found in multiple organ systems, and a variety of etiologies were responsible for morbidity and mortality.

Animal Diseases↗
PubMed1998

Pathogenicity of Mycoplasma volis in mice and rats.

A new species of Mycoplasma, M. volis, was isolated from the respiratory tract of clinically normal field-trapped prairie voles (Microtus ochrogaster) that were to be housed in close proximity to other rodents. To determine the pathogenic potential of the new mycoplasmal isolate, three groups of rodents (Sprague Dawley rats, BALB/c mice, and severe combined immunodeficient [SCID] mice) were intranasally inoculated with 2 x 10(8) color-changing units (CCU) of M. volis and were observed for 4 to 6 weeks. Experimental animals did not manifest clinical signs of disease; however, one experimental SCID mouse was euthanized 5 days after inoculation because of a severe circling disorder. Lung lesions in experimental SD rats ranged from mild to severe bronchial-associated lymphoid tissue (BALT) hyperplasia. Lung lesions in BALB/c and SCID mice ranged from no lesions to mild pneumonia. We were able to isolate M. volis from some control mice, none of which had lung lesions. All mice were seronegative for Sendai virus, mouse hepatitis virus, and M. pulmonis. All immunocompetent experimental animals (BALB/c mice and Sprague Dawley rats) were seropositive for M. volis. All immunocompetent control animals and SCID mice were seronegative for M. volis. Our data suggest that M. volis is capable of causing microscopic lesions and seroconversion in rats and mice, and therefore these rodents should not be housed in close proximity to voles.

Animals↗
PubMed1998

Disaggregating the effects of race on breast cancer survival.

BACKGROUND AND OBJECTIVES: This study examines differences in breast cancer survival between African-American and white women to determine whether there is a racial difference in survival after accounting for established influences on outcome, such as stage of cancer, health status, health behavior, utilization patterns, access to care, quality of care, and the doctor-patient relationship. METHODS: This study is a retrospective review of clinical records. The sample consists of 246 patients of three staff model HMOs who had mastectomies at stage II or above. Data on patient demographics, stage of cancer, health status, and health behavior and utilization, including preventive care, were extracted from patient records. Multivariate logistic regression was used to predict the determinants of advanced stage of cancer. Cox survival analysis was used to predict the determinants of survival. RESULTS: Missed appointments and stage of cancer were the key determinants of survival. The effect of race on survival was marginal after adjusting for these factors. Race, patients who missed appointments, and patients who delayed in reporting breast cancer symptoms were determinants of advanced stage. African-Americans were overrepresented among patients who missed appointments. CONCLUSIONS: Missed appointments was a determinant of both advanced stage and shorter survival. This measure is an important component of how race affects survival. Compliance with appointment keeping and alleviating reasons for noncompliance must be considered as factors in breast cancer survival.

Adult↗
PubMed1997

Grapefruit juice increases felodipine oral availability in humans by decreasing intestinal CYP3A protein expression.

The increase in oral availability of felodipine and other commonly used medications when taken with grapefruit juice has been assumed to be due to inhibition of CYP3A4, a cytochrome P450 that is present in liver and intestine. To evaluate the effect of repeated grapefruit juice ingestion on CYP3A4 expression, 10 healthy men were given 8 oz of grapefruit juice three times a day for 6 d. Before and after receiving grapefruit juice, small bowel and colon mucosal biopsies were obtained endoscopically, oral felodipine kinetics were determined, and liver CYP3A4 activity was measured with the [14C N-methyl] erythromycin breath test in each subject. Grapefruit juice did not alter liver CYP3A4 activity, colon levels of CYP3A5, or small bowel concentrations of P-glycoprotein, villin, CYP1A1, and CYP2D6. In contrast, the concentration of CYP3A4 in small bowel epithelia (enterocytes) fell 62% (P = 0.0006) with no corresponding change in CYP3A4 mRNA levels. In addition, enterocyte concentrations of CYP3A4 measured before grapefruit juice consumption correlated with the increase in Cmax when felodipine was taken with either the 1st or the 16th glass of grapefruit juice relative to water (r = 0. 67, P = 0.043, and r = 0.71, P = 0.022, respectively). We conclude that a mechanism for the effect of grapefruit juice on oral felodipine kinetics is its selective downregulation of CYP3A4 in the small intestine.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Nonclassical secretory dynamics of LH revealed by hypothalamo-hypophyseal portal sampling of sheep.

Continuous withdrawal of hypophyseal portal blood from unrestrained sheep has permitted detailed assessments of the pulsatile secretion of gonadotrophin-releasing hormone (GnRH). To determine if this blood can also be used to characterize the sensory dynamics of pituitary hormones, patterns of luteinizing hormone (LH) in the hypophyseal portal blood of ovariectomized ewes was compared with previous patterns of GnRH and peripheral LH. Hypophyseal portal blood and jugular vein blood were collected every 5 min from six ovariectomized ewes over 6-12 h. Hypophyseal portal blood contained GnRH-associated, sharply defined LH pulses that were much larger than in the periphery. Pulses of secreted LH (hypophyseal portal LH less peripheral LH) showed much faster rates of rise and fall than peripheral and followed pulses of GnRH by an average of 1.26 min. In contrast to pulses in jugular blood, secreted LH pulses often reached a relatively unchanging interpulse nadir-plateau and thereby approached closely algorithm-estimated, extrapolated baselines. The interpulse baseline concentrations of secreted LH (99.6 ng/mL) in hypophyseal portal blood were 31-fold higher than those for jugular LH (3.23 ng/mL). These elevated concentrations also exceeded mean jugular peak concentrations (11.1 ng/mL) and, thus, primarily must represent newly secreted LH. The non-Gaussian profiles of this secreted LH were substantially more complex than the inputs predicted from jugular LH measurements by deconvolution. Furthermore, regardless of the analytical approach, estimations of the mass of secreted LH in each pulse did not correlate well with inputs predicted by deconvolution or Kushler-Brown pulsefit analysis of corresponding pulses in jugular blood (r2 ranging 0.40-0.48). Among alternative explanations is the possibility of heterogeneity in concentrations of GnRH in the portal vessels and variable distribution within the hypophysis. In summary, assay of hypophyseal portal blood obtained directly from the pituitary provides a method for direct assessment of secretory responses to hypothalamic peptides, and thereby serves as an unmatched method for studying the dynamics of LH secretion in vivo. With this approach, LH is revealed to be secreted as complex, non-Gaussian pulses that are far more sharply defined that those in the periphery, include non-GnRH-dependent, secretory components that cannot be predicted by deconvolution and are followed by periods of relatively constant, basal secretion.

Algorithms↗