Environmental organochlorines and semen quality: results of a pilot study

There have been numerous studies that suggest that sperm concentrations (sperm counts) are declining in men. However, other studies suggest that sperm counts are not declining or may be increasing in some areas. Although there is disagreement on whether there is a downward temporal trend in sperm counts, the studies provide evidence that sperm counts vary by geographic location. It has been hypothesized that the geographic variation in sperm concentrations may be due to environmental exposures, lifestyle factors, or some unknown causes. To determine whether contemporary ambient levels of polychlorinated biphenyls (PCBs) and p,p-DDE are associated with altered semen quantity and quality, we selected a study population without specific exposure to PCBs or p,p-DDE. The present study presents the results from a pilot study on the relationship between serum PCBs and p,p-DDE and semen quality in 29 subjects recruited from the Massachusetts General Hospital Andrology Laboratory. Of the 29 subjects, 3 had sperm concentrations < 20 million/mL, 7 had < 50% motile sperm, 9 had < 4% normal morphology, and 6 were below normal in more than one semen parameter. The 18 subjects with normal spermatozoa concentration, motility, and morphology were used as comparison subjects. The mean (SE) concentration of the sum of PCBs and p,p-DDE was 242 ng/g lipids (34.0) and 354 ng/g lipids (120), respectively, for men with below normal motility as compared to 202 ng/g lipids (16.6) and 240 ng/g lipids (31.1), respectively, for the comparison subjects. The data showed general trends that were suggestive of an association between PCBs and p,p-DDE and abnormal motility, as well as with sperm concentration and morphology. A full-scale study is currently in progress.     

The association of particulate air metal concentrations with heart rate variability

Numerous studies show an association between particulate air pollution and adverse health effects. Particulate matter is a complex mixture of elemental carbon, ammonium, sulfates, nitrates, organic components, and metals. The mechanisms of action of particulate matter less than or equal to 2.5 micro m in mean aerodynamic diameter (PM(2.5)), as well as the constituents responsible for the observed cardiopulmonary health effects, have not been identified. In this study we focused on the association between the metallic component of PM(2.5) and cardiac autonomic function based on standard heart rate variability (HRV) measures in an epidemiologic study of boilermakers. Thirty-nine male boilermakers were monitored throughout a work shift. Each subject wore an ambulatory electrocardiogram (Holter) monitor and a personal monitor to measure PM(2.5). We used mixed-effects models to regress heart rate and SDNN index (standard deviation of the normal-to-normal) on PM(2.5) and six metals (vanadium, nickel, chromium, lead, copper, and manganese). There were statistically significant mean increases in the SDNN index of 11.30 msec and 3.98 msec for every 1 micro g/m(3) increase in the lead and vanadium concentrations, respectively, after adjusting for mean heart rate, age, and smoking status. Small changes in mean heart rate were seen with all exposure metrics. The results of this study suggest an association between exposure to airborne metals and significant alterations in cardiac autonomic function. These results extend our understanding of the adverse health effects of the metals component of ambient PM(2.5).     

Novel polymorphisms in the somatostatin receptor 5 (SSTR5) gene associated with bipolar affective disorder

The somatostatin receptor 5 (SSTR5) gene is a candidate gene for bipolar affective disorder (BPAD) as well as for other neuropsychiatric disorders. The gene is positioned on chromosome 16p13.3, a region that has been implicated by a few linkage studies to potentially harbor a disease susceptibility gene for BPAD. Recent evidence shows that the dopamine D2 receptor (DRD2) and SSTR5 interact physically to form heterodimers with enhanced functional activity. Brain D2 dopamine receptors are one of the major targets of neuroleptic treatments in psychiatric disorders. In this study we systematically screened the promoter and coding region of the SSTR5 gene for genetic variation that could contribute to the development of neuropsychiatric disorders. Eleven novel single nucleotide polymorphisms (SNPs) were identified including four missense SNPs, Leu48Met, Ala52Val, Pro109Ser and Pro335Leu. We carried out an association study of BPAD using 80 Danish cases and 144 control subjects, and replication analysis using 55 British cases and 88 control subjects. For the Danish population, association was suggested between silent SNP G573A and BPAD (P = 0.008). For the British population we found association to BPAD with missense mutation Leu48Met (P = 0.003) and missense mutation Pro335Leu (P = 0.004). The statistical significance of the association was, however, greatly reduced after correcting for multiple testing. When combining genotypes from Leu48Met and Pro335Leu into haplotypes, association to BPAD was found in the British population (P = 0.0007). This haplotype association was not replicated in the Danish population. Our results may indicate that the SSTR5 gene is involved in the etiology of BPAD or may exist in linkage disequilibrium with a susceptibility gene close to SSTR5. However, given the marginal statistical significance and the potential for false-positive results in association studies with candidate genes, further studies are needed to clarify this hypothesis.     

The association between APOE and dementia does not seem to be mediated by vascular factors

OBJECTIVE: The effect of APOE on dementia may be mediated through dyslipidemia and atherogenesis through its effect on cholesterol metabolism. The authors investigated this possibility among aged survivors from the UK Medical Research Council Trial of the Treatment of Hypertension in Older Adults. DESIGN: A total of 370 of 657 survivors from an initial cohort of 1,088 recruited into the trial between 1983 and 1985 were traced in 1994 and agreed to be screened for dementia. Blood samples were analyzed for APOE genotype and serum fibrinogen. Cholesterol level, smoking behavior, blood pressure, body mass index, and EKG recordings had been measured at recruitment 10 to 12 years earlier. Odds ratios (ORs) for the association between APOE epsilon4/* and both AD and dementia were estimated and adjusted incrementally for the effect of age and premorbid intelligence, cholesterol, other risk factors for vascular disease, and EKG evidence of cardiovascular disease. RESULTS: The authors diagnosed 24 cases of National Institute of Neurological and Communicative Disorders and Stroke AD from 41 cases of dementia. The crude OR for the association between APOE epsilon4/* and AD was 3.40 (95% CI 1.30 to 8.91). APOE genotype was associated with serum cholesterol level, and there was a nonsignificant trend for an association with smoking behavior. After adjusting for these and all other vascular risk factors and vascular disease variables listed earlier, the OR for the association between APOE epsilon4/* and AD increased to 4.81 (1.60 to 14.4). CONCLUSION: Presence of APOE epsilon4/* seems to increase the risk for dementia and AD independently of its effect on dyslipidemia and atherogenesis.     

Thromboembolic disease: variability of interobserver agreement in the interpretation of CT venography with CT pulmonary angiography

OBJECTIVE: The objective of this study was to determine interobserver agreement in the diagnosis of acute deep venous thrombosis on CT venography performed in addition to CT pulmonary angiography. SUBJECTS AND METHODS: One hundred forty-six CT venograms of 144 patients (mean age, 61.74 years) clinically suspected of having pulmonary embolism were analyzed prospectively and independently by two experienced thoracic and body imaging radiologists and later by consensus of the two radiologists. The CT venography protocol consisted of 5-mm-thick axial images at 20-mm intervals from the popliteal fossa to the renal veins. Images were acquired 3-4 min after the start of 100-150 mL of undiluted contrast medium administration at 4 mL/sec. Thirteen venous segments were analyzed in each patient. There were 1586 analyzable venous segments. RESULTS: Interobserver agreement, with the patient as the unit of analysis, was moderately good (kappa, 0.59; 95% confidence interval [CI], 0.39-0.78). Kappa values were similar for CT venography studies performed with 150 mL of contrast medium and 4-min delay (kappa, 0.62; 95% CI, 0.30-0.88) and with 3-min delay and 100 mL of contrast medium (kappa, 0.56; 95% CI, 0.32-0.80). Interobserver disagreement occurred in 17 (12%) of 146 CT venography studies. Findings of 11 CT venography studies were interpreted as negative, and six were interpreted as positive after consensus interpretation. CONCLUSION: Interobserver agreement for deep venous thrombosis with CT venography is moderately good.     

Correction of taste abnormality of malignancy with intravenous hyperalimentation.

A complete remission of widely metastatic bladder carcinoma was obtained with chemotherapy in a 41-year-old man. Severe persistent anorexia led to a 33% weight loss. The anorexia correlated with an elevated sucrose recognition threshold. Following 16 days of intravenous hyperalimentation, taste sensation returned to normal, anorectic symptoms cleared, and weight gain and positive nitrogen balance resulted. There was no stimulation of tumor growth. Restoration of nutritional deficits with intravenous hyperalimentation can improve taste function and appetite so that adequate oral alimentation can be tolerated.     

"Is there life on dialysis?": time and aging in a clinically sustained existence

Increasingly, in the United States, lives are being extended at ever-older ages through the implementation of routine medical procedures such as renal dialysis. This paper discusses the lives and experiences of a number of individuals 70 years of age and older at two dialysis units in California. It considers what kind of life it is that is being sustained and prolonged in these units, the meanings of the time gained through (and lost to) dialysis for older people, and the relationship of "normal" life outside the units to an exceptional state on the inside that some patients see as not-quite-life. Highlighting the unique dimensions of gerontological time on chronic life support, the article offers a phenomenology of the end of life as that end is drawn out, deferred by technological means, and effaced by the ethos and experiential course of dialysis treatment.     

Gore-Tex Grafts for Replacement of the Superior Vena Cava

In an effort to evaluate polytetrafluoro-ethylene (Gore-Tex) as a replacement for large veins, tubular grafts of the material were substituted for the precava in 33 mongrel dogs weighing 15 to 30 kg. Thirteen dogs had grafts 10 cm long by 12 mm wide with a 15- to 30-u pore size; 15 dogs had grafts of the same length and width from 90-μ. pore size material; and 5 dogs had grafts 5 cm long by 12 mm wide, of 90-μ pore size Gore-Tex. The effect of Gore-Tex tubes with and without spiral support and the differences in anatomical positions of the grafts were evaluated in terms of patency. Dogs were killed if a venogram showed occlusion of the graft. Twelve dogs survived 90 days; the longest survivor was killed at eleven months. At postmortem examination, the graft was patent but extremely narrow at the atrial end. Modification in the fabrication of Gore-Tex may eliminate factors contributing to graft failure; experiments longer than 90 days are necessary to evaluate Gore-Tex as a large vein replacement material. The 90-μ pore size material used in this experiment was unsuitable as a canine venous substitute.     

Evidence of oxidative stress in full-term healthy infants

We hypothesized that early infancy would be a time of oxidative stress due to the difficulty of adapting to ambient oxygen. Therefore, we measured levels of products of lipid peroxidation (F2-isoprostanes), antioxidant enzyme activity (catalase (CAT) and superoxide dismutase (SOD)), and ability to resist oxidative stress (ferric reducing ability of plasma (FRAP)) in full-term infants (38-42 wk) fed human milk from birth. Seventy-seven infants were followed at 1, 3.5, 6, and 12 mo of age. F2-isoprostanes in plasma declined significantly (p < 0.05) from 1 to 6 mo (160 +/- 43; 90 +/- 33; 41 +/- 27 pg/mL (mean +/- SD)). FRAP values (775 +/- 196, 723 +/- 133, 697 +/- 126, 669 +/- 145 microM) 1, 3.5, 6, and 12, respectively) declined (p = 0.06) from 1 to 3.5 mo and from 3.5 to 6 mo of age. RBC-SOD (2.7 +/- 2, 3.2 +/- 2.8, 2.1 +/- 1.8, 2.5 +/- 1.8 U, 1, 3.5, 6, 12 mo, respectively) declined from 3.5 to 6 mo. RBC-CAT (76 +/- 23, 94 +/- 28, 81 +/- 22, 85 +/- 31 U, 1, 3.5, 6, 12 mo, respectively) also declined between 3.5 and 6 mo, after a significant increase between 1 and 3.5 mo. These data suggest that the human infant is under oxidative stress early in infancy and further study may be warranted to assess the potential benefits of antioxidant supplementation for either the mother or the infant.