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Biomedical subjects

R Francis

Publications and source records attributed to R Francis.

At least 55 records · Page 3Linked to original sources

Corticotropin releasing factor stimulates growth hormone secretion in neonatal rats.

Corticotropin releasing factor (CRF) both stimulates ACTH secretion from the pituitary and inhibits secretion of growth hormone (GH) in adult rats through actions in the CNS. The purpose of the present study was to evaluate these pituitary and central actions of CRF in neonatal rats, in which the hypothalamo- pituitary adrenal (HPA) axis is relatively hypo-functional. The results of this study show that central or peripheral administration of CRF evokes a marked dose-related rise in serum corticosterone in 6-day old rats. The same doses of CRF stimulate, rather than inhibit GH secretion. These results suggest that CRF has unique central actions early in ontogeny.

Animals↗

Muscle cell attachment in Caenorhabditis elegans.

In the nematode Caenorhabditis elegans, the body wall muscles exert their force on the cuticle to generate locomotion. Interposed between the muscle cells and the cuticle are a basement membrane and a thin hypodermal cell. The latter contains bundles of filaments attached to dense plaques in the hypodermal cell membranes, which together we have called a fibrous organelle. In an effort to define the chain of molecules that anchor the muscle cells to the cuticle we have isolated five mAbs using preparations enriched in these components. Two antibodies define a 200-kD muscle antigen likely to be part of the basement membrane at the muscle/hypodermal interface. Three other antibodies probably identify elements of the fibrous organelles in the adjacent hypodermis. The mAb IFA, which reacts with mammalian intermediate filaments, also recognizes these structures. We suggest that the components recognized by these antibodies are likely to be involved in the transmission of tension from the muscle cell to the cuticle.

Animals↗

Storage of thawed cryoprecipitated AHF is better at room temperature than at 1 degree C to 6 degrees C for factor VIII content.

Before November 1989, both the American Association of Blood Banks and the Food and Drug Administration required that thawed cryoprecipitated antihemophilic factor (AHF) should be used immediately or be stored at room temperature and administered within 6 hours. However, in November 1989, the American Association of Blood Banks changed the requirement for storage of thawed cryoprecipitated AHF from room temperature to 1 degree C to 6 degrees C, while the Food and Drug Administration still required thawed cryoprecipitated AHF to be stored at room temperature. The present study was designed to measure and compare the factor VIII activity in 10 bags of thawed cryoprecipitated AHF that were split into aliquots and stored at room temperature and at 1 degree C to 6 degrees C. At 6 and 24 hours after thawing, the mean factor VIII activities (% of normal) of the room temperature-stored cryoprecipitated AHF were 741% and 680% vs 650% and 608% for the 1 degree C- to 6 degrees C-stored cryoprecipitated AHF (P less than .05 at 6 hours and P = .11 at 24 hours). The storage of thawed cryoprecipitated AHF at 1 degree C to 6 degrees C also resulted in precipitation of both factor VIII and fibrinogen. These data show that it is better to store thawed cryoprecipitated AHF at room temperature vs 1 degree C to 6 degrees C for factor VIII activity. These data also suggest that adequate levels of factor VIII are maintained in thawed cryoprecipitated AHF that has been stored at room temperature for up to 24 hours.

Chemical Precipitation↗

Altered coagulation in cerebral ischemia. Platelet, thrombin, and plasmin activity.

We investigated hemostatic function in patients with cerebral ischemia by evaluating platelet activation, fibrin generation, and fibrinolysis. Plasma beta-thromboglobulin, an index of platelet activation, was significantly increased both acutely (14.9 +/- 9.2 ng/mL; n = 85) and approximately 2 months later (17.3 +/- 10.1 ng/mL; n = 57). Thrombin activity was measured using assays for fibrinopeptide A and fibrin D-dimer. Increased fibrinopeptide A was found in 9 (11.5%) of 78 patients acutely and 6 (10.7%) of 56 at follow-up; fibrin D-dimer levels were significantly increased acutely (166 +/- 188 ng/mL; n = 66) but not at follow-up. Fibrinolytic activity was measured using assays for fibrinopeptide B-beta 1-42 and plasminogen activator inhibitor 1. Fibrinopeptide B-beta 1-42 was significantly reduced acutely (6.3 +/- 2.2 pmol/mL; n = 35) and at follow-up (4.8 +/- 1.5 pmol/mL; n = 21). Plasminogen activator inhibitor 1 was normal acutely (20.1 +/- 12.0 ng/mL; n = 73) but increased at follow-up (27.8 +/- 20.1 ng/mL; n = 45). These results demonstrate that patients with cerebral ischemia have abnormal hemostatic function that is not explained by the acute phase reaction, and that components of the prethrombotic state are present in some of these patients.

Adult↗

The effects of fluoride on bone and implant histomorphometry in growing rats.

The effects of fluoride at concentrations of 2.0 and 4.5 mM in drinking water on growth rate, vitamin D, water and mineral metabolism, bone histomorphometry, and osteoinduction of demineralized allogenic bone matrix (DABM) were compared in the rat. Whereas fluoride did not influence fluid intake or growth rate at the lower concentration, it increased fluid intake and inhibited growth rate at the higher concentration. Fluoride produced dose-related increases in serum fluoride and alkaline phosphatase but did not alter serum 25-hydroxyvitamin D or 1,25-dihydroxyvitamin D. Serum calcium and phosphate were reduced by fluoride at concentrations of 2.0 mM but not 4.5 mM. Cancellous bone fractional area was increased by fluoride at 2.0 mM and was reduced by fluoride at 4.5 mM. Fluoride had no effect on cancellous bone surface length or the percentage surface lined by osteoblasts and osteoclasts. Fluoride increased medullary area and decreased the endosteal bone formation rate. Fluoride increased periosteal bone formation and apposition rates at concentrations of 2.0 mM but not 4.5 mM. Fluoride inhibited mineralization in DABM implants, and at the higher concentration, fluoride increased the formation of new bone matrix. These results indicate that in the rat, fluoride increases cortical and trabecular bone at therapeutic doses and reduces trabecular bone at toxic doses. The serum concentration of fluoride at therapeutic doses in the rat is similar to that in patients with osteoporosis who are on treatment with fluoride. In the rat, there is a narrow range between toxic and therapeutic doses.

Alkaline Phosphatase↗

Variation in hypertension prevalence in elderly blacks in the United States: the effect of mortality trends.

Few controlled studies on the clinical course of hypertension in the elderly have been done, and similar studies are lacking specifically regarding the aging black population. Such studies are indeed difficult considering the complexity of determining the true incidence and prevalence of the disease, the presence of confounding variables such as genetic and environmental influences, and physiologic effects of aging. However, United States vital statistics data on race- and age-specific mortality and morbidity from cardiovascular and cerebrovascular disease are available. The literature has established that hypertension is the principal risk factor and has a direct relationship to the evolution of cardio- and cerebrovascular events. Therefore, examination of these data together with hypertension morbidity could contribute to our knowledge of the prevalence of hypertension in the elderly black population.

Aged↗

Evidence that smoking alters prostacyclin formation and platelet aggregation in women who use oral contraceptives.

Smoking markedly intensifies the risk of cardiovascular disease in women who use oral contraceptives. The mechanism of this effect is not known, but evidence in vitro and in male smokers suggests that nicotine and cigarette smoke can alter prostaglandin formation and platelet function. However, these effects had not been studied with regard to women. We evaluated the effects of smoking on prostacyclin formation and platelet aggregation in 38 women who were matched according to age and weight. These included 24 women who used oral contraceptives (15 smokers, 9 nonsmokers) and 7 smokers who did not use oral contraceptives. In addition, a control group comprised seven healthy, nonsmoking women who did not take oral contraceptives. Prostacyclin formation, reflected by the excretion rate of its stable metabolite 6-keto-prostaglandin F1 alpha, was measured by means of radioimmunoassay in 4-hour urine specimens obtained during a smoking-free period and after participants had inhaled smoke from four high-nicotine cigarettes. In addition, ex vivo platelet aggregation in response to adenosine diphosphate and the stable thromboxane/endoperoxide analog U 46619 was evaluated before and after the inhalation of cigarette smoke. Oral contraceptive users who smoked greater than or equal to 5 years had a lower basal 6-keto-prostaglandin F1 alpha level than nonsmokers or those with a smoking history of less than 5 years (84 +/- 11 versus 159 +/- 28 versus 171 +/- 18 ng/gm of creatinine, p less than 0.01). Inhalation of smoke from four high-nicotine cigarettes did not alter 6-keto-prostaglandin F1 alpha in the smokers who did not use oral contraceptives. However, excretion of 6-keto-prostaglandin F1 alpha was further reduced in the smokers who used oral contraceptives (133 +/- 20 to 86 +/- 9 ng/gm of creatinine, p less than 0.05). Platelet aggregation did not change after inhalation of cigarette smoke in the women who did not take oral contraceptives, but aggregation increased in participants who used oral contraceptives. These results suggest that prostacyclin inhibition may be an important mechanism for the increased cardiovascular risk in women smokers who take oral contraceptives.

6-Ketoprostaglandin F1 alpha↗

Infusion of synthetic human C-peptide does not affect plasma glucose, serum insulin, or plasma glucagon in healthy subjects.

We studied six healthy male subjects to determine whether a four-hour infusion of synthetic human C-peptide sufficient to achieve mean (+/- SD) peripheral plasma concentrations of 1.3 +/- 0.7 pmol/mL affected plasma glucose, serum insulin, or plasma glucagon. Subjects were studied in a fasting state and following an oral glucose load during four-hour 0.9% NaCl (control) and C-peptide (mean dose: 70 nmol) infusions. No differences were observed between saline and C-peptide infusions for mean values of fasting plasma glucose (94 +/- 6 v 87 +/- 5 mg/dL), serum insulin (3 +/- 1 v 2 +/- 1 microU/mL), or plasma glucagon (124 +/- 65 v 112 +/- 70 pg/dL). Following oral glucose ingestion no differences were detected between saline and C-peptide infusions for mean peak values of plasma glucose (168 +/- 18 v 168 +/- 31) and serum insulin (59 +/- 6 v 57 +/- 21) or mean nadir values of plasma glucagon (80 +/- 73 v 75 +/- 70). There was a slight delay in the insulin rise following oral glucose on the C-peptide infusion day, but differences between mean values for individual sampling times were not statistically significantly different.

Adult↗

Residual prejudice in the helping profession.

The author briefly discusses negative attitudes and prejudices held by some helping professionals, and the consequences for the patients in their care. She stresses the need for mental health workers to maintain respect for their clients from the outset, and to support them in their struggle for growth and self-esteem, rather than becoming detached from them, patronizing them, or blaming them for their illness. Respect requires humility in the face of another's misfortune, and a strong affirmation of our common humanity.

Attitude of Health Personnel↗

The effect of estrogen dose on postmenopausal bone loss.

In order to establish whether the favorable effect of estrogen therapy on postmenopausal bone loss was dose related, we measured sequential changes in the cortical diameters of the metacarpals by radiographic morphometry in 120 normal postmenopausal women who were being treated with ethinyl estradiol in doses ranging from 5 to 50 micrograms daily. There was a net loss of bone at doses below 15 micrograms per day and a net gain at doses of 25 micrograms per day and above. At doses between 15 and 25 micrograms daily, bone was neither gained nor lost. The loss of bone with the low doses was due to expansion of the medullary cavity that was unaccompanied by any change in total bone width. There was no change in bone volume with the intermediate doses because endosteal resorption of bone was offset by periosteal apposition. The net gain of bone with the higher doses occurred because endosteal resorption was totally inhibited but periosteal bone apposition continued. Thus, in postmenopausal women the reduction in the rate of cortical bone loss in response to estrogen therapy depends on the dose administered.

Adult↗

Postoperative intervertebral disc space infection.

Intervertebral disc space infection is an uncommon, but serious, complication of disc surgery. By a retrospective chart review, we identified 27 patients at our institution who had a postoperative disc space infection; 14 were diagnosed and treated within the last 5 years. The characteristic symptoms were severe spinal pain and limited spinal mobility beginning 7 to 30 days postoperatively. The key physical findings were paravertebral muscle spasm and marked mechanical signs. The key laboratory findings were an elevated erythrocyte sedimentation rate and a mildly elevated white blood cell count. The diagnosis was based on the clinical presentation and early radiographic changes in the vertebral bodies adjacent to the involved disc, especially irregularities of the cortical margins seen best by tomography. Definitive bacteriological diagnosis by Craig needle biopsy was attempted in 14 patients; 7 had positive cultures and all yielded a Staphylococcus species. The usual treatment consisted of the administration of antistaphylococcal antibiotics and immobilization of the spine with a spica cast, a plastic body jacket, or complete bedrest. The final radiographic findings showed bony fusion or bridging in 19 patients, and 25 patients had a pain-free recovery after 1 to 9 months. There was 1 recurrent infection, and 3 patients eventually required an anterior discectomy and fusion. Based on a review of our own cases and those reported in the literature, we stress the importance of spinal tomography in establishing the diagnosis of postoperative disc space infection at a relatively early stage in a patient who is suspected of having this condition on the basis of typical symptoms and signs combined with an elevated sedimentation rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effects of prenatal cocaine exposure on haloperidol-induced increases in prolactin release and dopamine turnover in weanling, periadolescent, and adult offspring.

Offspring of dams given 40 mg/kg cocaine SC on gestational days (GD) 8-20 (E8-20) (C40), dams given 0.9% saline SC on E8-20 that were pair fed and watered to C40 dams (PF), and untreated control dams given ad lib access to food and water (LC) were challenged with haloperidol (0.0, 0.05, 0.10, or 0.50 mg/kg) at either 21, 35, or 60 days postnatally (P21, 35, 60). One hour postinjection, animals were sacrificed, trunk blood collected for assay of prolactin, and the striatum (ST) and nucleus accumbens (NAc) removed. The ratio of the dopamine metabolites 3,4-dihydroxyphenylacetic acid and homovanillic acid to dopamine (DA) as well as the ratio of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) to serotonin (5-HT) were determined in these brain regions as an index of DA and 5-HT turnover, respectively. Assessment of 5-HIAA/5-HT ratios did not indicate any reliable dose or prenatal treatment effects. Reminiscent of previous findings obtained in C40 offspring at P11 (35), P21 C40 offspring exhibited a slightly reduced sensitivity to haloperidol relative to LC controls both in terms of DA ratios in the NAc as well as plasma prolactin levels. These findings were also evident in PF controls suggesting that they may be the result of prenatal undernutrition. Furthermore, this reduced sensitivity was not evident at the older test ages. At P60, planned comparisons revealed haloperidol-induced increases in prolactin levels in C40 males but not PF or LC males; these findings could potentially reflect feminization in males following prenatal cocaine exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗