Involvement of deprivation and environmental lead in neural tube defects: a matched case-control study

OBJECTIVE: To analyse the prevalence of neural tube defects in small geographical areas and seek to explain any spatial variations with reference to environmental lead and deprivation. SETTING: The Fylde of Lancashire in the north west of England. DESIGN: Cases were ascertained as part of a prospective survey of major congenital malformations in babies born in the Fylde to residents there between 1957 and 1981. A matched case-control analysis used infants with cardiovascular system, alimentary tract, and urinary system malformations as controls. Conditional logistic regression was used to assess the effects of more than 10 micrograms/l lead in drinking water and the Townsend deprivation score. RESULTS: The prevalence of neural tube defects in 1957-73 was higher in Blackpool, Fleetwood, and North Fylde, whereas the three control groups showed no significant spatial variation. In 1957-81 mothers living in electoral wards with either a higher proportion of houses with more than 10 micrograms/l lead in the water or a higher deprivation score had a greater risk of having a baby with a neural tube defect. For spina bifida and cranium bifidum alone, this was also true. For anencephaly, deprivation was less important although the effect of lead was still seen. In some neural tube defects, lead may act independently of other possible factors associated with deprivation. It seemed unlikely that lead levels changed significantly during the survey. The percentage of houses with 10 micrograms/l or more of lead in the water in 1984-5 was similar to that found in Great Britain 10 years previously. CONCLUSION: There is evidence to suggest that lead is one cause of neural tube defects, especially anencephaly. This could link the known preventive actions of hard water and folic acid. Calcium is a toxicological antagonist of lead. One cause of a deficiency of folic acid is impaired absorption secondary to zinc deficiency, which may be produced or exacerbated by lead.     

Evaluating chronic venous disease with a new venous severity scoring system

BACKGROUND: The Venous Clinical Severity Score (VCSS) has been proposed by the American Venous Forum as an objective means to clinically assess venous disease more completely than with the clinical CEAP classification. However, validation of the VCSS against an objective test is lacking. The purpose of this study was to test the VCSS against abnormalities found on venous ultrasound (US) scans. METHODS: As part of a screening project in a large kindred population with protein C deficiency, VCSS and venous US scanning were performed in 210 patients (420 limbs). A single examiner scored the VCSS (0-3) clinically for pain, varicose veins, edema, skin pigmentation, inflammation, induration, ulcer duration and size, and compressive therapy. Another experienced examiner, blinded to the subject's medical history, performed a US examination of the deep and superficial venous system, with a hand-carried US system. The relationship between US and VCSS scores was analyzed by calculating an odds ratio (OR) and its 95% confidence interval (CI). RESULTS: Of the 420 limbs screened, VCSS was 0 in 283 limbs, and VCSS was 1 or greater in the following categories: pain, 63 limbs; varicose veins, 70 limbs; edema, 51 limbs; skin pigmentation, 17 limbs; inflammation, 2 limbs; induration, 8 limbs; and compressive therapy, 9 limbs. The highest total score in any limb was 8. A clear association was seen with the VCSS and abnormalities found on US scans. When the score was dichotomized (0 = normal, 1 = any abnormality), it was a strong predictor of US scan abnormalities; limbs with VCSS greater than 0 had a 26-fold greater chance of US scan abnormalities than did limbs with VCSS = 0 (OR, 26.5; 95% CI, 11-64). With ultrasonography as the standard, sensitivity of VCSS compared with US scans was 89.3%, and specificity was 76.1%. Negative predictive value of VCSS = 0 was 97.9%, and positive predictive value for any positive score was 36.5% CONCLUSIONS: The results of this study are based on a large kindred population with a higher risk for venous disease than found in the general population. Though the VCSS was devised to quantify the severity of chronic venous disease, this study found it a useful screening tool. The VCSS showed good association with abnormalities on US scans, and when VCSS = 0 there is a high likelihood that the patient does not have venous disease. This simple test may prove valuable in clinical practice.     

Understanding gastrointestinal perfusion in critical care: so near, and yet so far

An association between abnormal gastrointestinal perfusion and critical illness has been suggested for a number of years. Much of the data to support this idea comes from studies using gastric tonometry. Although an attractive technology, the interpretation of tonometry data is complex. Furthermore, current understanding of the physiology of gastrointestinal perfusion in health and disease is incomplete. This review considers critically the striking clinical data and basic physiological investigations that support a key role for gastrointestinal hypoperfusion in initiating and/or perpetuating critical disease.     

Identification of non-amplifying CYP21 genes when using PCR-based diagnosis of 21-hydroxylase deficiency in congenital adrenal hyperplasia (CAH) affected pedigrees

Steroid 21-hydroxylase deficiency is among the most common inborn errors of metabolism in man. Characterization of mutations in the 21- hydroxylase gene (CYP21) has permitted genetic diagnosis, facilitated by the polymerase chain reaction (PCR). The most common mutation is conversion of an A or C at nt656 to a G in the second intron causing aberrant splicing of mRNA. Homozygosity for nt656G is associated with profoundly deficient adrenal cortisol and aldosterone synthesis, secondary hypersecretion of adrenal androgens, and a severe form of congenital adrenal hyperplasia (CAH) characterized by ambiguous genitalia and/or sodium wasting in newborns. During the course of genetic analysis of CYP21 mutations in CAH families, we and others have noticed a number of relatives genotyped as nt656G homozygotes, yet showing no clinical signs of disease. A number of lines of evidence have led us to propose that the putative asymptomatic nt656G/G individuals are incorrectly typed due to dropout of one haplotype during PCR amplification of CYP21. For prenatal diagnosis, we recommend that microsatellite typing be used as a supplement to CYP21 genotyping in order to resolve ambiguities at nt656.      

Effect of menstrual cycle phase on dopamine D2 receptor availability in female cynomolgus monkeys

Sex differences have been reported in a variety of affective and neurodegenerative disorders that involve dysfunctional dopamine (DA) neurotransmission. In addition, there is evidence for differences in sensitivity to the abuse-related effects of psychostimulants across the menstrual cycle which may result from effects of ovarian hormones on DA function. The goal of the present study was to extend previous work examining menstrual cycle-related changes in DA D2 receptor availability in humans to drug-naive female cynomolgus monkeys (n=7) using the selective D2-like receptor ligand [(18)F]fluoroclebopride (FCP) and a high-resolution microPET P4 scanner. Menstrual cycle phase was characterized by daily vaginal swabs and measurements of serum progesterone levels. PET studies were conducted once during the luteal phase and once during the follicular phase. Regions of interest in the caudate nucleus, putamen, and cerebellum were defined on coregistered MRIs. Distribution volumes were calculated for FCP in each structure and the distribution volume ratio (DVR) for both brain regions relative to the cerebellum was used as a measure of D2 receptor availability. FCP DVRs were significantly higher in the luteal phase compared to the follicular phase in both the caudate nucleus (11.7% difference, p=0.02) and putamen (11.6% difference, p=0.03). These findings extend earlier work in humans and suggest that changes in DA receptor availability may be involved in the variation in symptoms of various neuropsychiatric disorders across the menstrual cycle, including differences in sensitivity to the abuse-related effects of stimulants.     

Myelinated and nonmyelinated nerves: comparison of proton MR properties

The magnetic resonance (MR) relaxation rates of protons were compared in the myelinated and nonmyelinated nerves of the garfish. The long, large olfactory nerve of the garfish, as an easily accessible source of nonmyelinated axons, is uniquely suited for such a comparison. The T1 and T2 measurements revealed distinct and consistent differences between nonmyelinated olfactory nerves and myelinated optic and oculomotor nerves. Comparisons between water content, lipid content, and relaxation rates indicated that the differences in MR properties represent complex differences in the distribution and physical environment of the constituent lipid and water protons.     

FM sonography in diffuse liver disease: prospective assessment and blinded analysis

FM sonography - a signal-processing technique that uses frequency and phase information as well as amplitude data - shows promise in evaluation of patients with diffuse liver disease. In a prospective blinded review of 37 patients with biopsy-proved liver disease and 42 healthy volunteers, FM sonography was clearly superior to traditional amplitude-based (AM) sonography in distinguishing healthy from diseased subjects. Statistically significant differences were seen in accuracy (FM, 98.7%; AM, 84.8%), sensitivity (FM, 97.3%; AM, 70.3%), and negative predictive value (FM, 97.7%; AM, 78.8%). Our data also suggest that current FM sonographic techniques cannot differentiate among histologic findings associated with different hepatic parenchymal abnormalities. It is unclear, therefore, whether FM imaging can reduce the numbers of patients who require biopsy for diagnosis or the frequency of biopsy procedures in patients with known disease.