Cattle immune responses to tetanus toxoid elicited by recombinant S. typhimurium vaccines or tetanus toxoid in alum or Freund's adjuvant

Cattle were immunised orally, nasally or subcutaneously with either S. typhimurium 4/74 aroA(-) aroD(-) or S. typhimurium 4/74 htrA-based live vaccines expressing Fragment C (TetC) of tetanus toxin from plasmid pTetnir15. Oral inoculation with S. typhimurium 4/74 aroA(-) aroD(-)- (pTetnir15) elicited mucosal anti-TetC IgA but no measurable systemic humoral responses to TetC. Subcutaneous inoculation with the same strain elicited both mucosal IgA and systemic anti-TetC IgG1 responses. Nasal inoculation did not elicit any detectable anti-TetC responses. Oral delivery of S. typhimurium htrA(-) proved fatal in inoculated animals. None of the animals inoculated with either mutant S. typhimurium developed detectable T cell proliferative responses to the guest antigen. Cattle were also inoculated with tetanus toxoid adsorbed in alum or emulsified in Freund's complete adjuvant. Animals inoculated subcutaneously with Ttox emulsified in FCA developed systemic IgG1 and IgG2 antibody, while animals inoculated with Ttox adsorbed in alum developed systemic IgG1 but little IgG2 to Ttox. Both of these groups of animals developed measurable TetC-specific proliferative T cell responses that were associated with the production of IFNgamma.     

Nutritionally relevant supplementation of vitamin B6 in lactating women: effect on plasma prolactin

Pharmacologic doses of vitamin B6 administered to lactating women have been reported to suppress plasma prolactin. As a result, some physicians have recommended restriction of vitamin B6 intake for lactating women. In the present investigation, 20 lactating women were given supplemental doses of vitamin B6, 0.5 to 4.0 mg/d, beginning 24 hours after delivery. Plasma prolactin, plasma pyridoxal phosphate, and breast milk total vitamin B6 concentrations were determined during the first 9 months postpartum. Women receiving the supplement of 4.0 mg compared with 0.5 mg of vitamin B6 per day had significantly higher plasma pyridoxal phosphate (P less than .01) and breast milk total vitamin B6 concentrations (P less than .05) beginning at 1 month postpartum and continuing through the duration of the study. Plasma prolactin concentrations were not significantly different between the two groups. The percentage of all women, regardless of treatment, in whom lactation persisted at 1 and 2 weeks and 1, 3, 6, and 9 months were 100%, 100%, 100%, 90%, 80%, and 65%, respectively. All women who ceased to lactate during the study reported doing so by choice. Nutritionally relevant doses of vitamin B6 elevated plasma pyridoxal phosphate and breast milk total vitamin B6 concentrations of lactating women without reducing plasma prolactin concentration or halting lactation.     

Statistical analysis of statural grwoth following kidney transplantation

Factors affecting the growth rates of 59 children and adolescents for the first 2 years following kidney transplantation were evaluated. The factors assessed were age at transplantation, renal function, prednisone dosage, donor source, and prior history of transplantation. The observed growth velocity was expressed as the percentage, of the growth velocity predicted by bone age. Normal growth (80%) was exhibited by 37% of the patients and 22% had accelerated growth (100%). The chronologic age at transplantation did not correlate significantly with growth when bone age was used as the reference for expected velocity. Males grew better than did females. There was a unique sex/race interaction with black males growing most rapidly. Better renal function, the ability to lower prednisone dosage, alternate day prednisone administration, and a decreasing diastolic blood pressure were positively correlated with better growth rates after transplantation. The donor source and prior history of transplantation did not significantly influence grwoth rate.Abbreviations ESRD end stage renal disease - BUN blood urea nitrogen     

Time course of early mesopic adaptation to luminance decrements and recovery of spatial resolution

The time course of recovery of spatial resolution following adaptation to a uniform field was measured for test probes presented at lower illuminance than the adapting field. Six observers were tested in a Maxwellian-view system using 20 degrees adapting fields of 1.6-2.6 log photopic trolands. Test stimuli were 7 degrees, 250 ms Gabor patches (1 and 6 cpd) of mean retinal illuminance 2-3 log units lower than the adapting field. During the 9 s after adapting field offset, contrast thresholds for orientation discrimination followed an exponential-decay function and showed longer recovery times for larger illuminance decrements and higher spatial frequency.     

In vitro fertilization and embryo transfer (IVF/ET): An established and successful therapy for endometriosis

The purpose of this report is to present a 6-year experience in the management of endometriosis with in vitro fertilization and embryo transfer (IVF/ET). We divided 136 patients who underwent 280 cycles into three groups: (1) previous history of endometriosis but normal pelvis at the time of oocyte retrieval, (2) stages I–II endometriosis (revised AFS classification), and (3) stages III–IV endometriosis. The stimulation protocols, estradiol (E₂) responses, and distribution of terminal E₂ patterns were similar in all groups. Group 3 had significantly fewer preovulatory and immature oocytes retrieved and fewer embryos transferred. The fertilization rate and the per cycle/per transfer pregnancy rates were similar in all groups. The miscarriage rate was higher in group 3, and the on-going pregnancy rate per cycle was lower, Luteal phase E₂ and progesterone levels were comparable in all groups. No differences were found when groups 2 and 3 were analyzed for the presence of one or two ovaries or the presencelabsence of ovarian endometriosis. The overall fertilization rate, the per cycle/per transfer pregnancy rates, and the miscarriage rate were similar to those of tubal factor patients. We underscore the excellent out-come of patients with minimal or mild endometriosis in IVF/ET. We conclude that patients with moderate or severe endometriosis have a compromised reproductive potential, probably because of a reduced oocyte recovery rate and poor embryo quality.     

Reproductive problems and birth defects in survivors of Wilms' tumor and their relatives

In a retrospective cohort study of 47 Wilms' tumor survivors and their 77 sibling controls, female survivors had a fourfold excess risk (risk ratio, 4.1; 95% confidence interval, 1.7-10.1) for any adverse livebirth outcome, including birth defects, compared with their sibling controls. Wives of male survivors had no apparent excess risk for problem pregnancies. The families had a number of severe reproductive problems and major birth defects, such as primary amenorrhea in two survivors, bicornuate uterus in two survivors and one control, and mental retardation in one male survivor and a male control. The son of a female survivor died after bilateral Wilms' tumors. Birth defects in the offspring of female survivors are compatible either with intrauterine constraint, possibly due to radiation-induced fibrosis or with the complex of malformations associated with Wilms' tumor. Female survivors of Wilms' tumor appear to be at increased risk for a variety of reproductive problems, from sterility to fetal loss, early delivery, and birth defects in offspring. Furthermore, relatives of survivors of Wilms' tumor may be at risk of having associated birth defects, with clinically significant consequences.     

Risk factors for prematurity and premature rupture of membranes: A prospective study of the vaginal flora in pregnancy

Prematurity remains a major cause of perinatal mortality in the United States. Some research has indicated that infectious agents play a role in either initiating preterm labor, causing premature rupture of the membranes, or preventing tocolysis. This study attempted to determine if the presence of various vaginal pathogens in early pregnancy was associated with the subsequent development of premature rupture of membranes or preterm labor. We found that among 233 evaluable patients those with Trichomonas vaninalis were significantly more likely to have premature rupture of the membranes (p < 0.03), and those with Bacteroides sp. were more likely to be delivered of their infants before 37 weeks (p < 0.03) and to have infants weighing less than 2500 gm (p < 0.05). Those with Ureaplasma urealyticum more frequently began preterm labor (p < 0.05). Preterm premature rupture of the membranes was found significantly more often among patients with Bacteroides sp. Stepwise multiple logistic regression analysis indicated that those associations were not related to the number of previous abortions, deliveries, or preterm deliveries or to maternal age. We conclude that microbiologic screening in early pregnancy may aid in the assessment of patient risk for preterm delivery.     

The effects of tetanus toxin on the orbicularis oculi muscle

PURPOSE: Tetanus toxin can cause localized neuromuscular weakness, but it also can produce systemic tetany. The action of tetanus toxin on the orbicularis muscle has not been studied in animals immunized to prevent systemic tetany. Our objective was to determine whether tetanus toxin could be used to treat orbicularis oculi muscle spasms. METHODS: We analyzed the clinical, electrophysiologic, and histopathologic effects of tetanus toxin injected into the orbicularis oculi muscle of rabbits with passive immunity to tetanus toxin. In six rabbits, the orbicularis oculi function in both eyes was assessed clinically, and the baseline orbicularis oculi muscle action potential was measured physiologically with electromyography (EMG). The rabbits then were immunized against tetanus toxin with tetanus immunoglobulin for immediate and definitive immunity. Tetanus toxin was injected into the left orbicularis oculi muscles, leaving the right eyes as controls. Ten days later, the rabbits were again assessed by clinical examination and with EMGs on both the injected side and the noninjected side. The animals were killed at 14 days, and the orbicularis muscle was removed from both sides. The injected and control tissues were examined microscopically for signs of neuromuscular denervation. RESULTS: All six rabbits showed weakness in eye closure on the side injected with tetanus toxin. In addition, four rabbits developed complete ear ptosis on the tetanus toxin injected side because of spread of the toxin to adjacent ear muscles. EMGs showed both a denervation of the orbicularis oculi muscle and a poor blink potential on the side injected with tetanus toxin. Histopathologic studies of the orbicularis oculi muscle injected with tetanus toxin showed angulation of both slow and fast types of muscle fibers compatible with neuromuscular denervation. CONCLUSIONS: Tetanus toxin can cause localized orbicularis oculi weakness, as documented clinically, physiologically, and microscopically, without producing systemic tetany in immunized rabbits. Tetanus toxin may have a potential application in the treatment of blepharospasm and hemifacial spasm.     

Haptoglobin phenotype is an independent risk factor for cardiovascular disease in individuals with diabetes: The Strong Heart Study

OBJECTIVES: The goal of this study was to determine if the haptoglobin phenotype was predictive of cardiovascular disease (CVD) in diabetic mellitus (DM). BACKGROUND: Cardiovascular disease is the most frequent, severe, and costly complication of type 2 DM. There are clear geographic and ethnic differences in the risk of CVD among diabetic patients that cannot be fully explained by differences in conventional CVD risk factors. We have demonstrated that a functional allelic polymorphism in the haptoglobin gene acts as a major determinant of susceptibility for the development of diabetic microvascular complications. METHODS: We sought to determine if this paradigm concerning the haptoglobin gene could be extended to CVD in DM. We tested this hypothesis in a case-control sample from the Strong Heart study, a population-based longitudinal study of CVD in American Indians. Haptoglobin phenotype was determined by polyacrylamide gel electrophoresis in 206 CVD cases and 206 matched controls age 45 to 74 years. Median follow-up was six years. RESULTS: In multivariate analyses controlling for conventional CVD risk factors, haptoglobin phenotype was a highly statistically significant, independent predictor of CVD in DM. The odds ratio of having CVD in DM with the haptoglobin 2-2 phenotype was 5.0 times greater than in DM with the haptoglobin 1-1 phenotype (p = 0.002). An intermediate risk of CVD was associated with the haptoglobin 2-1 phenotype. CONCLUSIONS: This study suggests that determination of haptoglobin phenotype may contribute to the algorithm used in CVD risk stratification, and in evaluation of new therapies to prevent CVD in the diabetic patient.     

Myocardial and microcirculatory kinetics of BR14, a novel third-generation intravenous ultrasound contrast agent

OBJECTIVES: This study sought to investigate the myocardial and microvascular kinetics of BR14, a novel third-generation ultrasound contrast agent. BACKGROUND: BR14 produces persistent myocardial opacification after the administration of a single intravenous bolus when the left ventricular cavity contrast has considerably diminished. The mechanism of this finding is unknown. METHODS: Nine open-chest dogs with non-critical stenosis of a single coronary artery were given intravenous bolus injections of BR14 during coronary hyperemia. Time versus acoustic intensity (AI) plots were generated from the normal and stenosed beds and myocardial blood flow (MBF) was measured with radiolabeled microspheres. Intravital microscopy was performed on an exteriorized cremaster muscle in 11 wild-type mice to study the microvascular kinetics of the agent. RESULTS: At peak contrast enhancement, the ratio between AI in the stenosed and normal bed was 0.44+/-0.23, which was similar to the radiolabeled microsphere-derived MBF ratio between the two beds (0.45 +/-0.20). At 400 s after injection, the AI ratio between the two beds approximated unity (0.99+/-0.07) despite no changes in MBF, indicating redistribution of the agent. The myocardial kinetics of BR14 was best characterized by a modified lagged normal density function. Only about 3% of administered microbubbles were estimated to be retained in the myocardium. Intravital microscopy showed that most of these bubbles were retained only transiently (2 to 3 s) within capillaries. CONCLUSIONS: BR14 demonstrates redistribution because of transient retention within capillaries. Therefore, similar to (201)Tl, it could potentially be used to detect both coronary stenosis and myocardial viability after a single injection during stress.