Birth weight, infant weight gain, and cause-specific mortality: the Hertfordshire Cohort Study

Low birth weight, a marker of adverse intrauterine circumstances, is known to be associated with a range of disease outcomes in later life, including coronary heart disease, hypertension, type 2 diabetes, and osteoporosis. However, it may also decrease the risk of other common conditions, most notably neoplastic disease. The authors describe the associations between birth weight, infant weight gain, and a range of mortality outcomes in the Hertfordshire Cohort. This study included 37,615 men and women born in Hertfordshire, United Kingdom, in 1911-1939; 7,916 had died by the end of 1999. For men, lower birth weight was associated with increased risk of mortality from circulatory disease (hazard ratio per standard deviation decrease in birth weight = 1.08, 95% confidence interval: 1.04, 1.11) and from accidental falls but with decreased risk of mortality from cancer (hazard ratio per standard deviation decrease in birth weight = 0.94, 95% confidence interval: 0.90, 0.98). For women, lower birth weight was associated with a significantly (p < 0.05) increased risk of mortality from circulatory and musculoskeletal disease, pneumonia, injury, and diabetes. Overall, a one-standard-deviation increase in birth weight reduced all-cause mortality risk by age 75 years by 0.86% for both men and women.     

Support for Barker hypothesis upheld in rat model of maternal undernutrition during the preimplantation period: application of integrated 'random effects' statistical model

In response to a recent paper published in Reproductive BioMedicine Online by Walters and Edwards (2003), this study reports the application of a random effects regression analysis for evaluation of integrated data involving maternal and embryo/offspring components. Using this method, it is possible to confirm the conclusions of an earlier study that rat maternal undernutrition during the preimplantation period results in blastocyst cell number reduction and post-natal outcomes, including altered growth rates and elevated blood pressure.     

Contraceptive activity of a spermicidal aryl phosphate derivative of bromo-methoxy-zidovudine (compound WHI-07) in rabbits

OBJECTIVE: To determine the vaginal contraceptive activity of WHI-07 in the rabbit model. DESIGN: Prospective, controlled study. SETTING: Center for advanced preclinical sciences. ANIMAL(S): Subgroups of 15, 16, or 24 New Zealand White does and 24 bucks per experiment. INTERVENTION(S): Ex vivo (Experiment 1) and in vivo (Experiments 2 and 3) treatment of semen with WHI-07 or Nonoxynol-9 (N-9). In Experiment I, ovulated does in subgroups of 15 were artificially inseminated with semen mixed with WHI-07 or vehicle. In Experiment 2, ovulated does in subgroups of 24 were artificially inseminated within 2 min after intravaginal administration of 2% WHI-07 gel-microemulsion or 2% N-9 gel and allowed to complete term pregnancy. In Experiment 3, ovulated does in subgroups of 16 were artificially inseminated at 15, 30, or 60 minutes. MAIN OUTCOME MEASURE(S): The numbers of implanted embryos on postinsemination day 8 or the proportion of does that became pregnant and delivered newborn rabbits; the litter size, weight, growth, and viability of pups until lactation day 5. RESULT(S): Exposure of semen to WHI-07 at the time of artificial insemination completely inhibited pregnancy rates (WHI-07-pretreated, 0%, vs. control, 60%) and embryo implantation (WHI-07-pretreated, 0/175 vs. control, 68/170). Intravaginal administration of a 2% WHI-07 gel-microemulsion or 2% N-9 gel before artificial insemination significantly inhibited pregnancy rates (81% and 85% inhibition, respectively) when compared with control. Furthermore, the 2% WHI-07 gel-microemulsion provided >90% inhibition of fertility even when insemination was delayed until 60 minutes after intravaginal application. Rabbits that delivered litters despite intravaginal application of 2% WHI-07 gel-microemulsion had healthy offsprings with no perinatal or postnatal repercussions. CONCLUSION(S): WHI-07 is a potent contraceptive agent in vivo. Intravaginal use of WHI-07 gel-microemulsion has clinical potential as a safe prophylactic contraceptive, in addition to its microbicide activity to curb the sexual transmission of HIV.     

Association of co-occurring psychosocial health problems and increased vulnerability to HIV/AIDS among urban men who have sex with men

OBJECTIVES: We measured the extent to which a set of psychosocial health problems have an additive effect on increasing HIV risk among men who have sex with men (MSM). METHODS: We conducted a cross-sectional household probability telephone sample of MSM in Chicago, Los Angeles, New York, and San Francisco. RESULTS: Psychosocial health problems are highly intercorrelated among urban MSM. Greater numbers of health problems are significantly and positively associated with high-risk sexual behavior and HIV infection. CONCLUSIONS: AIDS prevention among MSM has overwhelmingly focused on sexual risk alone. Other health problems among MSM not only are important in their own right, but also may interact to increase HIV risk. HIV prevention might become more effective by addressing the broader health concerns of MSM while also focusing on sexual risks.     

Self-perpetuating effects of birth size on blood pressure levels in elderly people

It has been suggested that essential hypertension is determined by 2 separate mechanisms: a growth-promoting process in childhood and a self-perpetuating mechanism in adult life. We report a clinical study of 500 people taken from a cohort of 7086 men and women who were born in Helsinki from 1924 to 1933, and whose body size at birth was recorded. As expected, blood pressure levels were inversely related to birthweight and birth length. These associations, however, were confined to the 213 people who had previously been diagnosed as having hypertension. In them, a 1-kg increase in birthweight was associated with a 6.4-mm Hg (95% confidence interval, 1.0 to 11.9) decrease in systolic blood pressure recorded at the clinic, and with a 9.3-mm Hg (95% confidence interval, 2.1 to 16.5) decrease recorded by ambulatory measurement. We conclude that pathological processes initiated in utero become self-perpetuating in adult life and lead to hypertension. Among elderly people with established hypertension, these processes have a strong effect on blood pressure levels, because they are processes that do not respond well to treatment.     

Spatiotemporal variation of metabolism in a plant circadian rhythm: the biological clock as an assembly of coupled individual oscillators

The complex dynamic properties of biological timing in organisms remain a central enigma in biology despite the increasingly precise genetic characterization of oscillating units and their components. Although attempts to obtain the time constants from oscillations of gene activity and biochemical units have led to substantial progress, we are still far from a full molecular understanding of endogenous rhythmicity and the physiological manifestations of biological clocks. Applications of nonlinear dynamics have revolutionized thinking in physics and in biomedical and life sciences research, and spatiotemporal considerations are now advancing our understanding of development and rhythmicity. Here we show that the well known circadian rhythm of a metabolic cycle in a higher plant, namely the crassulacean acid metabolism mode of photosynthesis, is expressed as dynamic patterns of independently initiated variations in photosynthetic efficiency (phi(PSII)) over a single leaf. Noninvasive highly sensitive chlorophyll fluorescence imaging reveals randomly initiated patches of varying phi(PSII) that are propagated within minutes to hours in wave fronts, forming dynamically expanding and contracting clusters and clearly dephased regions of phi(PSII). Thus, this biological clock is a spatiotemporal product of many weakly coupled individual oscillators, defined by the metabolic constraints of crassulacean acid metabolism. The oscillators operate independently in space and time as a consequence of the dynamics of metabolic pools and limitations of CO(2) diffusion between tightly packed cells.     

The continuing HIV epidemic among men who have sex with men

OBJECTIVES: This study characterized the AIDS epidemic among urban men who have sex with men (MSM). METHODS: A probability sample of MSM was obtained in 1997 (n = 2881; 18 years and older) from New York, Los Angeles, Chicago, and San Francisco, and HIV status was determined through self-report and biological measures. RESULTS: HIV prevalence was 17% (95% confidence interval = 15%, 19%) overall, with extremely high levels in African Americans (29%), MSM who used injection drugs (40%), "ultraheavy" noninjection drug users (32%), and less educated men (< high school, 37%). City-level HIV differences were non-significant once these other factors were controlled for. In comparing the present findings with historical data based on public records and modeling, HIV prevalence appears to have declined as a result of high mortality (69%) and stable, but high, incidence rates (1%-2%). CONCLUSIONS: Although the findings suggest that HIV prevalence has declined significantly from the mid-1980s, current levels among urban MSM in the United States approximate those of sub-Saharan countries (e.g., 14%-25%) and are extremely high in many population subsegments. Despite years of progress, the AIDS epidemic continues unabated among subsegments of the MSM community.     

A Randomized, Clinical Trial Comparing Butylcyanoacrylate with Octylcyanoacrylate in the Management of Selected Pediatric Facial Lacerations

OBJECTIVE: To compare two tissue adhesives, butylcyanoacrylate and octylcyanoacrylate, in the treatment of small (<4 cm) superficial linear traumatic facial lacerations in children. METHODS: This was a randomized, clinical trial with parallel design. 94 children <18 years of age seen in the ED of a tertiary care pediatric hospital with a facial laceration suitable for tissue adhesive closure underwent laceration closure using either butylcyanoacrylate or octylcyanoacrylate. The primary outcome was the cosmetic result at three months rated from photographs by a plastic surgeon on a visual analog scale (VAS). Secondary outcomes included the time to perform the procedure, the perceived difficulty of the procedure, the pain perceived by the patient, and a wound evaluation score at ten to 14 days and three months. RESULTS: Ninety-four patients were randomized with 47 in each group. The two groups were similar for baseline demographic and clinical characteristics. There was no difference in the three-month cosmesis VAS (median, 70.0 mm for n-butyl-2-cyanoacrylate vs 67.5 mm for octylcyanocrylate, p = 0.84). There was no difference between the groups for time to complete the procedure (p = 0.88), parent/patient-perceived pain of the procedure (p = 0.37), or physician-perceived difficulty of the procedure (p = 0.33). Similarly, there was no difference between the groups for the percentage of early (p = 0.58) or late (p = 0.71) optimal wound evaluation scores. CONCLUSIONS: In the closure of small linear pediatric facial lacerations, octylcyanoacrylate is similar to butylcyanoacrylate in ease of use and early and late cosmetic outcomes. The superior physical properties of octylcyanoacrylate appear to add little benefit to the management of these selected lacerations. Physician preference and differing costs may dictate use for these small selected lacerations.     

Can total prorenin in human plasma be determined by current activation methods?

A proper evaluation of the physiological significance of plasma prorenin depends on its accurate determination. However, current activation methods do not necessarily measure total prorenin, or a known proportion of it, even when carried out to apparent completion. Thus, extending cold activation of human plasma at -4 degrees C generally revealed progressive increments of prorenin, mainly during the first 15 days, but the total and the time required to achieve it varied considerably among individuals. Similarly, the titration curves of individual plasmas varied with increments of added trypsin and achieved totals that were not necessarily greater than those obtained by cold activation. This indicates the inappropriateness of attributing greater effectiveness to one method over the other. When the two methods were paired in sequence, a synergism was apparent in that prorenin estimates increased consistently; in one case more than 10-fold. Thus, total prorenin by any single method generally fell short of the total achieved by double methods. However, this too may still not represent the unknown true total prorenin. The sequence of activation steps was important, providing clues as to the mechanism of the observed synergism. Trypsin-before-cold activation proved to be more effective than trypsin-after-cold activation, with no further advantage being gained from triple treatments involving cold before and after trypsin, or trypsin before and after cold. The inferiority of trypsin-after-cold activation was apparently due to sensitization of the plasma to the destructive effects of trypsin, shifting its titration curve to the left.(ABSTRACT TRUNCATED AT 250 WORDS)