Cash Transfers may Increase the No-show Rate for Surgical Patients in Low-resource Settings: A Randomized Controlled Trial.

BACKGROUND: Over two-thirds of the world's population cannot access surgery when needed. Interventions to address this gap have primarily focused on surgical training and ministry-level surgical planning. However, patients more commonly cite cost-rather than governance or surgeon availability-as their primary access barrier. We undertook a randomized, controlled trial (RCT) to evaluate the effect on compliance with scheduled surgical appointments of addressing this barrier through a cash transfer. METHODS: 453 patients who were deemed surgical candidates by a nursing screening team in Guinea, West Africa, were randomized into three study arms: control, conditional cash transfer, and labeled unconditional cash transfer. Patients in the conditional cash transfer group were given a cash transfer to cover their transportation costs once they had been discharged from care. Patients in the unconditional arm were given a cash transfer to cover their transportation costs before they left their homes to get care. Arrival to a scheduled surgical appointment was the primary outcome. The study was performed in conjunction with Mercy Ships. RESULTS: The overall no-show rate was five-fold lower in Guinea than previously published estimates, likely due to changes in the patient selection and retention process, leading to an underpowered study. In a post-hoc analysis, which included non-randomized patients, patients in the control group and the conditional cash transfer group demonstrated no effect from the cash transfer. Patients in the unconditional cash transfer group were significantly less likely to arrive for their scheduled appointment. Subgroup analysis suggested that actual receipt of the unconditional cash transfer, instead of a lapse in the transfer mechanism, was associated with failure to show. CONCLUSION: We find that cash transfers are feasible for surgical patients in a low-resource setting, but that unconditional transfers may have negative effects on compliance. Although demand-side barriers are large for surgical patients in low-resource settings, interventions to address them must be designed with care. CONTEXTE: Plus des deux tiers de la population mondiale n'ont pas accès à la chirurgie lorsqu'ils en ont besoin. Les interventions visant à combler cette lacune ont principalement sur la formation chirurgicale et la planification chirurgicale au niveau ministériel. Cependant, les patients citent plus souvent le coût - plutôt que la gouvernance ou la disponibilité des chirurgiens - comme étant leur principal obstacle à l'accès. Nous avons entrepris un essai contrôlé randomisé (ECR) pour évaluer l'effet sur le respect des rendez-vous chirurgicaux programmés en s'attaquant à cet barrière par un transfert d'argent. MÉTHODES: 453 patients considérés comme des candidats à la chirurgie par une équipe de dépistage infirmière en Guinée, Afrique de l'Ouest, ont été répartis de manière aléatoire dans trois bras d'étude : contrôle, transfert monétaire conditionnel et transfert monétaire non transfert monétaire inconditionnel. Les patients du groupe de transfert monétaire conditionnel ont reçu un transfert d'argent pour couvrir leurs frais de transport une fois qu'ils étaient sortis des soins. Les patients du groupe de transfert inconditionnel recevaient un transfert en espèces pour couvrir leurs frais de transport avant de quitter leur domicile pour recevoir des soins. L'arrivée à un rendez-vous chirurgical programmé était le résultat principal. L'étude a été réalisée en collaboration avec Mercy Ships. RÉSULTATS: Le taux global de non-présentation était cinq fois inférieur en Guinée que les estimations publiées précédemment, probablement en raison de changements dans le processus de sélection et de rétention des patients, ce qui a conduit à une étude insuffisamment puissante. Dans une analyse post-hoc, qui incluait des patients non randomisés, les patients dans le groupe de contrôle et dans le groupe de transfert conditionnel n'ont montré aucun effet du transfert d'argent. Les patients du groupe de transfert d'argent sans condition étaient significativement moins susceptibles d'arriver pour leur rendez-vous prévu. L'analyse des sous-groupes suggère que la réception effective du transfert monétaire inconditionnel plutôt d'un erreur en mécanisme de transfert, était associé à l'absence de rendez-vous. CONCLUSION: Nous constatons que les transferts d'argent sont possibles pour les patients chirurgicaux dans un environnement à faibles ressources, mais que les transferts inconditionnels peuvent avoir des effets négatifs sur l'observance. Bien que les obstacles liés à la demande sont importants pour les patients opérés dans des contextes à faibles ressources, les doivent être conçues avec soin. MOTS-CLÉS: Transferts monétaires, Chirurgie, Chirurgie globale, Guinée, Interventions financières, Utilisation chirurgicale, Essai contrôlé randomisé.

Myostatin deficiency partially rescues the bone phenotype of osteogenesis imperfecta model mice.

UNLABELLED: Mice with osteogenesis imperfecta (+/oim), a disorder of bone fragility, were bred to mice with muscle over growth to test whether increasing muscle mass genetically would improve bone quality and strength. The results demonstrate that femora from mice carrying both mutations have greater mechanical integrity than their +/oim littermates. INTRODUCTION: Osteogenesis imperfecta is a heritable connective tissue disorder due primarily to mutations in the type I collagen genes resulting in skeletal deformity and fragility. Currently, there is no cure, and therapeutic strategies encompass the use of antiresorptive pharmaceuticals and surgical bracing, with limited success and significant potential for adverse effects. Bone, a mechanosensing organ, can respond to high mechanical loads by increasing new bone formation and altering bone geometry to withstand increased forces. Skeletal muscle is a major source of physiological loading on bone, and bone strength is proportional to muscle mass. METHODS: To test the hypothesis that congenic increases in muscle mass in the osteogenesis imperfecta murine model mouse (oim) will improve their compromised bone quality and strength, heterozygous (+/oim) mice were bred to mice deficient in myostatin (+/mstn), a negative regulator of muscle growth. The resulting adult offspring were evaluated for hindlimb muscle mass, and bone microarchitecture, physiochemistry, and biomechanical integrity. RESULTS: +/oim mice deficient in myostatin (+/mstn +/oim) were generated and demonstrated that myostatin deficiency increased body weight, muscle mass, and biomechanical strength in +/mstn +/oim mice as compared to +/oim mice. Additionally, myostatin deficiency altered the physiochemical properties of the +/oim bone but did not alter bone remodeling. CONCLUSIONS: Myostatin deficiency partially improved the reduced femoral bone biomechanical strength of adult +/oim mice by increasing muscle mass with concomitant improvements in bone microarchitecture and physiochemical properties.

Conversion from tacrolimus to belatacept to prevent the progression of chronic kidney disease in pancreas transplantation: case report of two patients.

Belatacept is a novel immunosuppressive agent that may be used as an alternative to calcineurin inhibitors (CNI) in immunosuppression (IS) regimens. We report two cases of pancreas transplant that were switched from tacrolimus (TAC) to belatacept. Case 1: 38-year-old female with pancreas transplant alone maintained on TAC-based IS regimen whose serum creatinine (SCr) slowly deteriorated from 0.6 mg/dL at baseline to 2.2 mg/dL, 16 months posttransplant. A native kidney biopsy performed showed CNI toxicity. The patient was started on belatacept and TAC was eliminated. Case 2: 49-year-old female with simultaneous pancreas-kidney transplant, maintained on TAC-based regimen where the SCr worsened over an initial 3-month period from a baseline of 1.0 to 3.0 mg/dL. Belatacept was started and TAC was lowered. Due to persistent graft dysfunction and kidney transplant biopsy still showing changes consistent with CNI toxicity, the TAC was then discontinued. At >1 year postbelatacept and off TAC follow-up, kidney function as measured by SCr remains stable at 1.0±0.2 mg/dL in both recipients. Neither patient developed rejection following the switch, and pancreas allograft function remains stable in both recipients.

Obstructive sleep apnoea--an update.

Obstructive sleep apnoea (OSA) is a common disorder characterized by the repetitive complete or partial collapse of the upper airway during sleep. It results in intermittent hypoxaemia and hypercapnia, cortical arousals and surges of sympathetic activity. The occurrence of OSA has also been linked to serious long-term adverse health consequences; such as hypertension, metabolic dysfunction, cardiovascular disease, neurocognitive deficits and motor vehicle accidents. There have been several advances in the field of particular clinical importance: (i) the development of portable monitoring as part of a simplified clinical algorithm for the diagnosis of OSA in selected patients; (ii) growing awareness of the cardio-metabolic health consequences of OSA and (iii) emerging evidence to support a range of non-continuous positive airway pressure (CPAP) treatment modalities, such as oral appliances.

Enhancement of recombinant hemoglobin production in Escherichia coli BL21(DE3) containing the Plesiomonas shigelloides heme transport system.

To produce recombinant hemoglobin in Escherichia coli, sufficient intracellular heme must be present, or the protein folds improperly and is degraded. In this study, coexpression of human hemoglobin genes and Plesiomonas shigelloides heme transport genes enhanced recombinant hemoglobin production in E. coli BL21(DE3) grown in medium containing heme.

A substitution at a non-glycine position in the triple-helical domain of pro alpha 2(I) collagen chains present in an individual with a variant of the Marfan syndrome.

A substitution for a highly conserved non-glycine residue in the triple-helical domain of the pro alpha 2(I) collagen molecule was found in an individual with a variant of the Marfan syndrome. A single base change resulted in substitution of arginine618 by glutamine at the Y position of a Gly-X-Y repeat, and is responsible for the decreased migration in SDS-polyacrylamide gels of some pro alpha 2(I) chains of type I collagen synthesized by dermal fibroblasts from this individual. Family studies suggest that this substitution was inherited from the individual's father who also produces abnormally migrating pro alpha 2(I) collagen chains and shares some of the abnormal skeletal features. This single base change creates a new Bsu36 I (Sau I, Mst II) restriction site detectable in genomic DNA by Southern blot analysis when probed with a COL1A2 fragment. The analysis of 52 control individuals (103 chromosomes) was negative for the new Bsu36 I site, suggesting that the substitution is not a common polymorphism.

Transgenic over-expression of plasminogen activator inhibitor-1 results in age-dependent and gender-specific increases in bone strength and mineralization.

The plasminogen activation system (PAS) and its principal inhibitor, plasminogen activator inhibitor-1 (PAI-1), are recognized modulators of matrix. In addition, the PAS has previously been implicated in the regulation of bone homeostasis. Our objective was to study the influence of active PAI-1 on geometric, biomechanical, and mineral characteristics of bone using transgenic mice that over-express a variant of human PAI-1 that exhibits enhanced functional stability. Femora were isolated from male and female, wildtype (WT) and transgenic (PAI-1.stab) mice at 16 and 32 weeks of age (n=10). Femora were imaged via DEXA for BMD and muCT for cortical mid-slice geometry. Torsional testing was employed for biomechanical properties. Mineral composition was analyzed via instrumental neutron activation analysis. Female femora were further analyzed for trabecular bone histomorphometry (n=11). Whole animal DEXA scans were performed on PAI-1.stab females and additional transgenic lines in which the functional domains of the PAI-1 protein were specifically disrupted. Thirty-two week female PAI-1.stab femora exhibited decreased mid-slice diameters and reduced polar moment of area compared to WT, while maintaining similar cortical bone width. Greater biomechanical strength and stiffness were demonstrated by 32 week PAI-1.stab female femora in addition to a 52% increase in BMD. PAI-1.stab trabecular bone architecture was comparable to WT. Osteoid area was decreased in PAI-1.stab mice while mineral apposition rate increased by 78% over WT. Transgenic mice expressing a reactive-site mutant form of PAI-1 showed an increase in BMD similar to PAI-1.stab, whereas transgenic mice expressing a PAI-1 with reduced affinity for vitronectin were comparable to WT. Over-expression of PAI-1 resulted in increased mineralization and biomechanical properties of mouse femora in an age-dependent and gender-specific manner. Changes in mineral preceded increases in strength/stiffness and deterred normal cross-sectional expansion of cortical bone in females. Trabecular bone was not altered in PAI-1.stab mice whereas MAR increased significantly, further supporting mineral changes as the underlying factor in strength differences. The primary influence of PAI-1 occurred during a period of basal bone remodeling, attributing a role for this system in remodeling as opposed to development. Comparison of transgenic lines indicates that PAI-1's influence on bone is dependent on its ability to bind vitronectin, and not on its proteolytic activity. The impact of PAI-1 on mouse femora supports a regulatory role of the plasminogen activation system in bone homeostasis, potentially elucidating novel targets for the treatment of bone disease.

Obstructive sleep apnea and hypertension: epidemiology, mechanisms and treatment effects.

Obstructive sleep apnea (OSA) is a highly prevalent disorder of breathing during sleep. A growing body of evidence suggests that OSA is independently associated with an increased risk of cardiovascular disease, although the extent of this risk and underlying mechanisms remain to be elucidated. However, there is clearer evidence from epidemiological and pathophysiological research of a causal link between OSA and hypertension. The acute hemodynamic and autonomic perturbations that accompany obstructive apneas during sleep, with associated repeated arousals and intermittent hypoxemia, appear to result in sustained hypertension. In addition to the metabolic and humoral effects from obesity, OSA appears to predispose individuals to autonomic imbalance characterized by sympathetic overactivity and altered baroreflex mechanisms as well as alterations to vascular function. Treatment of OSA restores normal sleep architecture and generally mitigates the acute hemodynamic effects of OSA. Treatment of symptomatic OSA, particular at the severe end of the spectrum, appears to be associated with improvements in blood pressure, both during sleep and wakefulness, and there may also be additional gains in subjects who are hypertensive and/or resistant to antihypertensive medications. The severe group appears to be particularly at risk for developing fatal and non-fatal cardiovascular events and treatment with continuous positive airway pressure appears to markedly reduce that risk. Future treatment studies will need to be extended for greater than the current average of 1-2 months in order to more fully evaluate any time dependent improvements in blood pressure, and consequent cardiovascular risk.

17 Beta-estradiol and progesterone inhibit transcription of the genes encoding the subunits of ovine follicle-stimulating hormone.

FSH, the primary trophic hormone for gamete development in mammals, is composed of two protein subunits, alpha and beta. It is known that 17 beta-estradiol (E2) and progesterone (P4) can decrease the secretion and synthesis of FSH in ovine pituitary cultures. Data presented here indicate that E2 and P4 decrease the steady state levels of FSH beta mRNA concomitantly with FSH secretion in ovine pituitary cultures. By 24 h, E2 decreased the steady state levels of FSH beta mRNA and FSH secretion by 68% +/- 5%. P4 also decreased both concomitantly, but by 58% +/- 7% after 24 h. E2 and P4 also decrease steady state levels of alpha mRNA, but at a lower rate. Finally, it is shown that E2 and P4 decrease transcription of the FSH beta by greater than 85% in 2 h; alpha mRNA transcription is decreased by 70% in 12 h. These effects are not altered even when cycloheximide is present to block protein synthesis by 95%. These data further define the mechanisms whereby E2 and P4 inhibit ovine FSH secretion/synthesis directly at the pituitary level. They also provide the first example of negative transcriptional regulation by P4 and the second of two examples now established for E2.

Diabetes mellitus and nontraumatic lower extremity amputation in black and white Americans: the National Health and Nutrition Examination Survey Epidemiologic Follow-up Study, 1971-1992.

BACKGROUND: The comparative long-term risk of non-traumatic lower extremity amputation (LEA) in black and white Americans, 2 groups with strikingly different rates of diabetes mellitus, is not known. OBJECTIVE: To examine the 20-year incidence of LEA in relation to race and diabetes mellitus. METHODS: The 14 407 subjects in the National Health and Nutrition Examination Survey Epidemiologic Follow-up Study were observed prospectively between 1971 and 1992. Prevalent diabetes mellitus was ascertained at the baseline examination, and incident diabetes mellitus, during follow-up. Lower extremity amputation was ascertained from hospital discharge records. Cox regression analysis was used to estimate associations between race, diabetes mellitus, and risk of first LEA. RESULTS: During the study period, 158 LEAs occurred among 108 subjects. While black subjects constituted 15.2% of the cohort, they represented 27.8% of the subjects with amputation (P = .002). The 20-year age-adjusted rate ratio of first LEAs for black subjects-white subjects was 2.14. Regression analyses confirmed the importance of diabetes mellitus as a key LEA risk factor. The association between prevalent diabetes mellitus and LEA risk was substantially higher (relative risk [RR], 7.19; 95% confidence interval [CI], 4.61-11.22) than that for incident diabetes mellitus (RR, 3.15 [CI, 1.84-5.37]), highlighting the importance of diabetes mellitus duration on LEA risk. While preliminary analyses adjusted for age and diabetes indicated a significant association between race and LEA risk (RR, 1.93 [95% CI, 1.26-2.96]), the effect of race diminished (RR, 1.49 [95% CI, 0.95-2.34]) following adjustment for education, hypertension, and smoking. CONCLUSIONS: Although black subjects experienced higher age- and diabetes mellitus-adjusted rates of amputation than their white counterparts, a combination of social and environmental factors may account for the apparent ethnic difference. More research into nonbiological factors associated with LEA may reduce the occurrence of these procedures in both black and white individuals.

Effects of ascorbic acid on proliferation and collagen synthesis in relation to the donor age of human dermal fibroblasts.

Several events are associated with cellular aging: alterations in the extracellular matrix, loss of the cell's proliferative capacity, and decreased responsiveness to growth factors. In skin, a major component of the extracellular matrix is collagen; an important regulator of collagen synthesis is ascorbic acid, which may also have growth factor-like properties. To investigate the relationship of the extracellular matrix and proliferative capacity to aging, we examined the effects of ascorbic acid on cell proliferation and collagen expression in dermal fibroblasts from donors of two age classes, newborn (3-8 d old) and elderly (78-93 years old). In the absence of ascorbic acid (control) proliferative capacities were inversely related to age; newborn cell lines proliferated faster and reached greater densities than elderly cell lines. However, in the presence of ascorbic acid both newborn and elderly cells proliferated at a faster rate and reached higher densities than controls. To determine whether there are age-related differences in extracellular matrix production and ascorbic acid responsiveness we examined and found that collagen biosynthesis (collagenase-digestible protein) was inversely related to age, but the stimulation by ascorbic acid appeared age independent. The increase in collagen synthesis was reflected by coordinate increases in steady-state pro alpha 1(I) and pro alpha 1(III) collagen mRNAs, suggesting a pretranslational mechanism. Ascorbic acid appears capable of overcoming the reduced proliferative capacity of elderly dermal fibroblasts, as well as increasing collagen synthesis in elderly cells by similar degrees as in newborn cells even though basal levels of collagen synthesis are age dependent.

Construction of a full-length murine pro alpha 2(I) collagen cDNA by the polymerase chain reaction.

Construction of large collagen cDNA has been hindered by the relatively large size and high G-C content of processed mRNA. We describe here the development of a rapid and efficient method for obtaining large full-length collagen cDNA. A full-length (4.3 kb) murine pro alpha 2(I) collagen cDNA was constructed by synthesis of a first-strand cDNA library with use of poly-A RNA (MC3T3-E1) and the oligo-dT17-adapter primer described by Frohman et al (Proc Natl Acad Sci USA 85:8998, 1988). Pro alpha 2(I) collagen cDNA were specifically amplified by the polymerase chain reaction (PCR) with a pro alpha 2(I) specific primer as the 5' primer (20mer; corresponding to nucleotide positions 42-61 in the first exon of the murine pro alpha 2(I) collagen gene, COL1A2), and with the adapter sequence 5' to the dT17 as the 3' primer. The PCR conditions were optimized to allow amplification of the expected 4.0-5.0-kb product; a major 4.3-kb product was visualized by ethidium bromide, identified by in situ gel hybridization, and cloned. DNA sequencing determined that it contained the correct 5' sequence and the 3' end had a 68 basepair (bp) 3' untranslated region. The entire sequence that codes the amino-terminal propeptide domain has been determined and compared to the human sequence. The homology between human and mouse is less in the amino terminal propeptide than in the triple helical domain; exon 5 of murine COL1A2 codes for an additional six amino acids not found in human COL1A2.

Oim mice exhibit altered femur and incisor mineral composition and decreased bone mineral density.

To investigate the role of the pro alpha 2(I) collagen chains of type I collagen in mineralization we used the oim (osteogenesis imperfecta model) mouse as our model system. The oim/oim mouse (homozygous for a null mutation in its COL1A2 gene of type I collagen) fails to synthesize functional pro alpha 2(I) collagen chains, synthesizing only homotrimers of pro alpha 1(I) collagen chains. To evaluate the role of pro alpha 2(I) collagen in type I collagen structure/function in mineralized tissues, we examined age-matched oim/oim, heterozygous (oim/+), and wild-type (+/+) mouse femurs and incisors for mineral composition (calcium, phosphorus, magnesium, fluoride, sodium, potassium, and chloride) by neutron activation analyses (NAA), and bone mineral content (BMC) and bone mineral density (BMD) by dual-energy X-ray absorptiometry (DEXA) in a longitudinal study (7 weeks to 16 months of age). NAA demonstrated that oim/oim femurs had significant differences in magnesium, fluoride, and sodium content as compared with +/+ mouse femurs, and oim/oim teeth had significant differences in magnesium content as compared to +/+ teeth. The ratio of calcium to phosphate was also significantly reduced in the oim/oim mouse femurs (1.58 +/- 0.01) compared with +/+ femurs (1.63 +/- 0.01). DEXA demonstrated that oim/oim mice had significantly reduced BMC and BMD as compared to oim/+ and +/+ mice. Serum and urine calcium, magnesium, and phosphorus levels, and Ca(47) absorption across the gut were equivalent in oim/oim and +/+ mice, with no evidence of hypercalciuria. These studies suggest that the known decreased biomechanical properties of oim/oim bone reflect both altered mineral composition as well as the decreased BMD, which further suggests that the presence of alpha2(I) chains plays an important role in mineralization.

Mutations in the COL1A2 gene of type I collagen that result in nonlethal forms of osteogenesis imperfecta.

Although virtually all mutations that result in osteogenesis imperfecta (OI) affect the genes that encode the chains of type I procollagen, the effects of mutations in the COL1A2 gene have received less attention than those in the COL1A1 gene. We have characterized mutations in 4 families that give rise to different OI phenotypes. In three families substitutions of glycine residues by cysteine in the triple helical domain (a single example at position 259 and 2 families in which substitution of glycine at 646 by cysteine) have been identified, and in the fourth a G for A transition at position +4 in intron 33 led to use of an alternative splice site and inclusion of 6 amino acids (val-gly-arg-ile-leu-phe) between residues 585 and 586 of the normal triple helix. The relation between position of substitution of glycine by cysteine in the COL1A2 gene does not follow the pattern developed in the COL1A1 gene. To determine how COL1A2 mutations produce OI phenotypes, we have produced a full-length mouse cDNA into which we plan to place mutations and examine their effects in stably transfected osteogenic cells and in transgenic animals.

Serum albumin in older persons: relationship with age and health status.

We analyzed data from 4115 persons aged 71 years and older who had blood drawn at a home visit in three communities to examine the cross-sectional distribution of serum albumin and correlates of hypoalbuminemia. Mean albumin was lower among older persons, from 41.6 g/l in men aged 71-74 years to 38.5 g/l in men 90 years or older, and from 41.1 g/l to 38.9 g/l in women of the same ages, respectively. Hypoalbuminemia (albumin less than 35 g/l) was observed in 3.1% of subjects. Hypoalbuminemia and lower serum albumin were independently associated with anemia, recent diagnosis of cancer, two or more limitations in activities of daily living, residence in a nursing home, heavy cigarette smoking (greater than 1 pack/day), and older age. A 10-year age increment was associated with 0.8 g/l lower serum albumin and odds ratio of 1.56 (95% CI 1.14, 2.13) for hypoalbuminemia after adjusting for demographic factors and health status. Characteristics associated with serum albumin may confound the reported relationship between serum albumin and mortality.

Anemia and hemoglobin levels in older persons: relationship with age, gender, and health status.

OBJECTIVE: To determine the relationship of hemoglobin levels and anemia with age and health status in older adults. DESIGN: Survey. SETTING: Community. PARTICIPANTS AND METHODS: Hematologic tests were obtained from 3,946 adults aged greater than or equal to 71 years in three communities (East Boston, MA; Iowa and Washington counties, IA; and New Haven, CT). RESULTS: Hemoglobin level was inversely associated with age, although this was more pronounced in men than in women. The proportion anemic was equal for men and women aged 71-74 years (8.6%) and increased differentially with age, reaching 41% and 21% for men and women aged greater than or equal to 90 years, respectively. Hemoglobin and anemia were independently associated with age, race, body-mass index, smoking, cancer, hospitalization, renal insufficiency, and hypoalbuminemia. The adjusted relative odds of anemia for a 5-year increase in age was 1.5 (95% confidence interval [CI] 1.3-1.8) for men and 1.2 (95% CI 1.1-1.4) for women. CONCLUSIONS: Age is significantly associated with both hemoglobin levels and anemia, with a stronger effect in men compared with women, even after simultaneously adjusting for demographic characteristics and health status. The decline of hemoglobin and concomitant increased anemia with age is not necessarily a result of "normal aging" so the detection of anemia in an older person should prompt appropriate clinical attention.

The gene encoding ovine follicle-stimulating hormone beta: isolation, characterization, and comparison to a related ovine genomic sequence.

Follicle-stimulating hormone (FSH), the primary stimulus for egg and sperm maturation in mammals, is an alpha/beta heterodimer. Each subunit is encoded by a single-copy gene in the human, bovine, and rat genomes. Transcription of both subunits is inhibited by estradiol and progesterone in ovine pituitary cultures. We report the sequence of one ovine FSH-beta gene (-1,527 to +3,664) that is expressed in vivo and the identification of a novel, second ovine FSH-beta-like sequence. Digestion of ovine genomic DNA with Bgl II yielded two fragments of 10 kb and 15 kb that hybridized to a bovine FSH-beta cDNA. The 10-kb fragment contained 6 kb of 5'-flanking region and all but about 200 bp of the 3' terminus of the ovine FSH-beta gene. This FSH-beta gene encodes a protein that differs from the published ovine protein sequence only at the carboxy terminus (Arg-109Glu-110[STOP codon] instead of Glu-109Arg-110[Glx-111]) and at positions 49 (Ala instead of Thr) and 88 (Arg instead of Ser). This gene is organized similarly to the human, bovine, porcine, and rat FSH-beta genes, and its coding sequence is nearly identical (99.5%) to a reported ovine FSH-beta cDNA. Expression of the FSH-beta gene on the 10-kb fragment in vivo was determined by analysis of wether mRNA using the polymerase chain reaction. A 95-bp sequence of the 15-kb fragment was 87% homologous to the corresponding coding region of the 10-kb fragment. This comparison suggested that the 15-kb fragment contains either an FSH-beta-like sequence or a pseudogene. Several potential steroid response elements were found by sequence analysis of the 5'-flanking region of the FSH-beta gene on the 10-kb fragment. A mechanism by which these elements may act is suggested.

Hyperoxic reperfusion exacerbates postischemic renal dysfunction.

BACKGROUND: Hyperoxic reperfusion from global ischemia worsens functional outcome because of oxygen radical-mediated injury. This study tested the hypothesis that hyperoxic reperfusion would exacerbate postischemic renal dysfunction. METHODS: Twenty-nine healthy, uninephrectomized, male mongrel rabbits (Oryctolagus cuniculus) in 3 groups were subjected to 30 minutes of complete normothermic renal ischemia followed by reperfusion under hyperoxic or normoxic conditions. The groups were: hyperoxically reperfused (n = 8), normoxically reperfused (n = 8), hyperoxic sham (no ischemia, n = 5), and allopurinol-pretreated (50 mg/kg, intravenously), hyperoxically reperfused animals (n = 8). Plasma concentrations of creatinine, urea nitrogen and electrolytes were measured at 0, 24, 48, and 72 hours after ischemia and served as functional outcome markers. Histopathologic analysis of kidneys for injury was performed by an expert who was blinded to the procedures. RESULTS: Plasma creatinine in hyperoxically reperfused rabbits was significantly elevated above normoxic (P =.02) and sham (P =.003) animals by 48 hours and remained elevated to 72 hours. Plasma urea nitrogen in hyperoxically reperfused rabbits was significantly elevated above the normoxic group (P = .01), the sham group (P = .02), and the allopurinol group (P = .04) by 72 hours. These coincided with a significantly elevated histopathologic injury score in hyperoxically reperfused rabbits compared with sham (P = .019), normoxic (P = .035), and allopurinol-pretreated hyperoxically reperfused animals (P = .037). CONCLUSIONS: Hyperoxic reperfusion exacerbates renal dysfunction after 30 minutes of complete normothermic ischemia. This dysfunction may be mediated by oxygen radical-related injury.

Fluoride intake from beverage consumption in a sample of North Carolina children.

Since the 1940's, the prevalence of dental fluorosis has increased in the US, concomitant with a reduction in dental decay. These changes have been attributed in part to the widespread use of systemic and topical fluorides. Various sources of increased systemic fluoride exposure have been investigated. However, little is known regarding fluoride intake from beverages in a sample of children of ages susceptible to dental fluorosis. The purpose of this study was to estimate the amount of fluoride ingested from beverages by a sample of North Carolina (NC) children of ages 2-10 years. Data on beverage consumption were collected by means of a diary format. A questionnaire was included so that demographic information and self-assessment on the accuracy of the diaries could be obtained. Beverages reported in the diaries were purchased, and their fluoride content was assayed. Daily total fluid intake ranged from 970 to 1240 mL, and daily beverage consumption ranged from 585 to 756 mL. The estimated mean daily fluoride intakes from beverages for children 2-3, 4-6, and 7-10 years of age were 0.36, 0.54, and 0.60 mg, respectively.

Physical disability and social interaction: factors associated with low social contact and home confinement in disabled older women (The Women's Health and Aging Study).

OBJECTIVES: This study examines the association of disability and social interaction, measured as in-person contact with non-household members and home confinement, and identifies sociodemographic, socioeconomic, and health-related factors that modify this relationship. METHODS: Participants were 1,002 moderately to severely disabled community-dwelling women aged 65 and older from the Women's Health and Aging Study, identified by screening an age-stratified random sample of Medicare beneficiaries in Baltimore, Maryland. Logistic regression models were used to estimate the odds of low social interaction associated with disability and each independent modifier. RESULTS: In a typical week, 23% did not visit with anyone residing outside their households and 17% did not leave their homes. In addition to and independent of disability level, older age, not completing high school, having a driver in the home, hearing difficulties and incontinence were associated with low social contact; older age and African American race were related to home confinement. African American women living alone are especially vulnerable to home confinement. DISCUSSION: Physical disability is not necessarily socially disabling, as many of the most severely disabled in our study had at least daily social interaction. Improvements in social interaction appear possible through more effective management of certain health conditions and attention to potential sociocultural barriers.