Exposure to hazardous substances and male reproductive health: a research framework.

The discovery in the mid-1970s that occupational exposures to pesticides could diminish or destroy the fertility of workers sparked concern about the effects of hazardous substances on male reproductive health. More recently, there is evidence that sperm quantity and quality may have declined worldwide, that the incidence of testicular cancer has progressively increased in many countries, and that other disorders of the male reproductive tract such as hypospadias and cryptorchidism may have also increased. There is growing concern that occupational factors and environmental chemical exposures, including in utero and childhood exposures to compounds with estrogenic activity, may be correlated with these observed changes in male reproductive health and fertility. We review the evidence and methodologies that have contributed to our current understanding of environmental effects on male reproductive health and fertility and discuss the methodologic issues which confront investigators in this area. One of the greatest challenges confronting researchers in this area is assessing and comparing results from existing studies. We elaborate recommendations for future research. Researchers in the field of male reproductive health should continue working to prioritize hazardous substances; elucidate the magnitude of male reproductive health effects, particularly in the areas of testicular cancer, hypospadias, and cryptorchidism; develop biomarkers of exposure to reproductive toxins and of reproductive health effects for research and clinical use; foster collaborative interdisciplinary research; and recognize the importance of standardized laboratory methods and sample archiving.

Laparoscopic lymphadenectomy for gynecologic malignancies.

OBJECTIVE: The purpose of our study was to detail our 5-year experience with laparoscopic lymphadenectomy for gynecologic malignancies. METHODS: From 11/5/92 to 3/9/98, we performed laparoscopic lymphadenectomies on 94 patients with various gynecologic malignancies. Pelvic, paraaortic, and combinations of both pelvic and paraaortic lymphadenectomies were performed depending on the primary site of disease and indication for lymph node dissection. Data were prospectively collected on all patients. RESULTS: From 11/5/92 to 3/9/98 we performed 94 laparoscopic lymphadenectomies for gynecologic malignancies. The distribution included 64 patients with cervical cancer, 14 with ovarian cancer, 12 with endometrial cancer, 2 with fallopian tube cancer, 1 with a uterine malignant mixed mesodermal tumor, and 1 with a metastatic neuroendocrine tumor. Fifty-five patients had only pelvic lymph node dissections, 9 patients had paraaortic dissections only, and 30 had both pelvic and paraaortic dissections performed. Among 30 patients having laparoscopic lymphadenectomy only, the mean hospital stay was 3.6 days. Included in this group were 19 patients who received postoperative neoadjuvant chemotherapy for cervical cancer as inpatients prior to ambulatory radiation therapy. The mean length of stay for this group was 4.6 days versus 1.7 days for the 11 patients who did not receive postoperative chemotherapy (P = 0.0025). The mean number of pelvic nodes was 11.9 (range 0-57), with a mean of 4. 5 between 11/5/92 and 12/31/95 and a mean of 19.1 from 1/1/96 to 3/9/98. The mean number of paraaortic nodes obtained was 3.7 (range 0-14), with a mean of 3.4 from 11/5/92 to 12/31/95 and a mean of 4.1 from 1/1/96 to 3/9/98. A total of 3 patients required conversions to laparotomy. One was for a vascular injury to the vena cava, 1 for a large tumor extending to both sidewalls, and the third for removal of densely matted lymph nodes. CONCLUSIONS: Laparoscopic lymphadenectomy is a technically feasible procedure for patients with gynecologic malignancies requiring lymph node dissections, with an acceptable safety profile and nodal yield. The number of nodes obtained increased in direct proportion to operator experience. In addition, patients may benefit from a decrease in hospital stay compared to conventional lymphadenectomy via laparotomy.

Lead exposure among young urban women.

OBJECTIVE: Blood lead levels have declined among every age group in the United States, but urban minority residents remain at disproportionate risk for elevated lead levels. Our objective was to measure lead burden in young women of childbearing age in New York City. We also describe successful means of recruiting this population into a cohort study. MATERIAL AND METHODS: Healthy women aged 18-25 attending a New York City health care center in 1995-1998 were eligible for participation. Participants were recruited by health care providers, the study coordinator and the participants themselves. Venous blood samples were obtained for whole blood lead, ferritin and hematocrit measurements, and detailed questionnaires were administered. RESULTS: 239 women have been recruited to date. The population is predominately minority: 62% African-American, 33% Hispanic and 5% Caucasian/Asian. The average age of participants is 19.3 years. Recruitment of participants into the study is predominantly (55%) through "word of mouth" from previously enrolled participants. Few participants learned of the study through their health care providers. The mean blood lead level among study participants is 2.1 +/- 1.7 micrograms/dl, which is consistent with the most recent United States national survey. CONCLUSIONS: Blood lead levels are low in young, urban minority women of childbearing age in New York City. In this population, recruitment efforts were substantially enhanced with the help of enrolled participants and the health care community.

Male reproduction and environmental and occupational exposures: a review of epidemiologic methods.

Concerns that chemical exposures in the environment have been detrimental to male sexual development and fertility have been heightened by reports of declining sperm counts over the past 50 years. Marked geographic variation has been found in semen quality and in the incidence of testicular cancer and certain urogenital defects. Debate continues over the existence, magnitude and significance of these trends, and how best to evaluate the hypothesis that in utero and childhood exposures to estrogenic compounds may be to blame. Epidemiologic methods for assessing the impact of hazardous substances on male reproductive health have been developed mainly in the area of occupational medicine, and this paper will review the currently recommended methods. These include questionnaires to determine reproductive history and sexual function; reproductive hormone profiles; and semen analyses such as sperm concentration, motility, and morphology. New research tools that show significant promise from the fields of clinical reproductive medicine and reproductive toxicology are discussed as possible additions to epidemiologic studies, including assays of sperm function and genetic integrity, and biomarkers of DNA damage. For population-based studies involving occupational groups or communities with environmental exposures, issues related to the cost, validity, precision and utility of these methods must be carefully considered.

Cardiovascular effects of the alpha2-adrenergic receptor agonist medetomidine in clinically normal cats anesthetized with isoflurane.

OBJECTIVE: To assess the cardiovascular effects of the alpha2-adrenergic receptor agonist medetomidine in healthy cats anesthetized with 2% isoflurane. ANIMALS: 11 clinically normal cats. PROCEDURE: Cats were anesthetized with isoflurane, and catheters were inserted for measurement of aortic, left ventricular, and right atrial pressures. For data collection, end-tidal isoflurane concentration was reduced to 2%, and end-tidal CO2 was maintained at 35 to 40 mm of Hg by use of positive-pressure ventilation. After measurement of baseline data, medetomidine (0.01 mg/kg of body weight, i.m.) was administered and data were collected continuously for 75 minutes. At the end of data collection, incisions were closed and cats were allowed to recover from anesthesia. RESULTS: Medetomidine significantly increased mean arterial pressure and systemic vascular resistance. The increase in mean arterial pressure was maximal at 17.8 +/- 7 minutes after medetomidine administration. Medetomidine also increased left ventricular peak systolic pressure, left ventricular end diastolic pressure, and right atrial pressure. Medetomidine significantly decreased heart rate and mean aortic flow. CONCLUSIONS: The low dosage of medetomidine (0.01 mg/kg, i.m.) promoted severe vasoconstriction in isoflurane-anesthetized cats, and resulted in sustained increases in left ventricular preload and afterload.

Use of videofluoroscopy in zoo dentistry: endodontic procedure in a tiger.

Videofluoroscopy was used as a radiographic technique to visualize a canine tooth during root canal therapy in a Siberian tiger. Videofluoroscopy was useful because the procedure was performed in a zoo setting with no access to an on-site darkroom. The fluoroscopic screen and videotape allowed for immediate viewing of the root canal system.

The risk of cancer in firefighters.

A substantial body of literature now exists on the carcinogenic hazards of firefighting. The authors discuss in detail the data on the carcinogens benzene, asbestos, PAHS, formaldehyde, and diesel exhaust, and they go on to examine the prevalent cancers in firefighters, including leukemia, non-Hodgkin's lymphoma, multiple myeloma, and cancer of the brain and bladder.

Teenage and current calcium intake are related to bone mineral density of the hip and forearm in women aged 30-39 years.

The relation between diet and bone mineral density in premenopausal women was evaluated in a cross-sectional study of 139 women aged 30-39 years. The population consisted of volunteers recruited in Rockland County, New York, between September 1988 and August 1992. A food frequency questionnaire was used to determine nutrient intake for both the year prior to bone density measurement and for ages 13-17 years. Physical measurements included height, weight, grip strength, and percent body fat. Bone mineral density was measured in the lumbar spine, hip, and forearm. Multiple regression equations were used to relate nutrient intake to bone density while controlling for age, height, weight, and grip strength. There were no relations between lumbar spine or distal forearm bone density and any nutrient studied from either the current or teenage diet. Current dietary calcium intake was modestly related to hip bone density (beta = 0.077; p = 0.074). When fiber intake was added to the multiple regression model, the association between calcium and hip bone density was strengthened (beta = 0.101; p = 0.037); this would be expected, because fiber interferes with calcium absorption. In the teenage diet, phosphorus and calcium intake were related to hip bone density. A higher lifetime calcium intake was associated with a higher hip bone density compared with low lifetime calcium intake. An increase in teenage calcium intake from 800 to 1,200 mg per day is estimated to increase hip bone density by 6 percent.

Changes in creatine kinase expression induced by exercise in borderline hypertensive rat hearts.

Hypertrophy in hypertensive hearts is associated with increased risk of cardiac morbidity and mortality that is not characteristic of exercised hearts. This study was done to determine whether exercise training of normotensive and borderline hypertensive rats induces the increased myocardial expression of BB and MB isoforms of creatine kinase (CK) that characterizes hypertensive hypertrophy. Spontaneously hypertensive (SHR), borderline hypertensive (BHR), and normotensive Wistar-Kyoto (WKY) rats were subjected to either an 8% sodium chloride diet or swim training to produce myocardial hypertrophy. Both exercise and a high salt diet induced an increase in the combined expression of CK-MB and CK-BB in SHR after 2 months. However, since swimming also exacerbated hypertension in SHR, exercise induced effects on CK were not distinguishable from those of hypertension. In WKY, neither exercise nor a high salt diet induced significant changes in CK isozyme expression. In BHR fed a high sodium chloride diet, significant increases in mean arterial pressure and left ventricular weight to body weight were not associated with changes in CK expression. In contrast, following 10 months of swim training BHR exhibited mild hypertrophy, decreased resting heart rates, and an increase in the combined expression of CK-MB and CK-BB. Therefore, exercise associated with a cardiac training effect in BHR induced changes in CK isozyme expression similar to those in hypertensive hearts.

Ischemic dysfunction and impaired recovery in hypertensive hypertrophied hearts is associated with exaggerated intracellular sodium accumulation.

The primary objectives of this study were to determine if hypertrophied spontaneously hypertensive rat (SHR) hearts exhibited a greater increase in intracellular sodium (Na+i) compared with Wistar-Kyoto (WKY) control rats during low flow ischemia, and to determine whether Na+i accumulation in these hearts was associated with greater ischemic dysfunction and damage. In addition, intracellular pH and high energy phosphates were monitored to assess the relationships between changes in these variables and changes in Na+i. Interleaved 31P and 23Na spectra were acquired in perfused hearts from 8- to 10-month-old rats during low flow ischemia and reperfusion, while left ventricular pressures were monitored continuously. The majority of SHR (n = 13) exhibited an increase in Na+ similar to that for WKY and did not demonstrate exaggerated ischemic dysfunction or damage. However, a subgroup of SHR (n = 7) exhibited exaggerated Na+i accumulation during ischemia, compared with WKY, that was associated with contractile failure and a greater increase in left ventricular end diastolic pressure during ischemia, and slower recovery of developed pressure during reperfusion. Greater Na+i accumulation in this SHR subgroup preceded significantly greater depletion of high energy phosphates compared with WKY. In conclusion, increased Na+i accumulation was observed in all hypertrophied hearts with greater ischemic dysfunction compared with WKY. These results suggest that impaired Na+i handling may indeed contribute to the greater susceptibility of hypertrophied hearts to ischemic dysfunction and damage.

An epidemiologic study of sports and weight lifting as possible risk factors for herniated lumbar and cervical discs. The Northeast Collaborative Group on Low Back Pain.

The associations between participation in several specific sports, use of free weights, and use of weight lifting equipment and herniated lumbar or cervical intervertebral discs were examined in a case-control epidemiologic study. Specific sports considered were baseball or softball, golf, bowling, swimming, diving, jogging, aerobics, and racquet sports. Included in the final analysis were 287 patients with lumbar disc herniation and 63 patients with cervical disc herniation, each matched by sex, source of care, and decade of age to 1 control who was free of disc herniation and other conditions of the back or neck. Results indicated that most sports are not associated with an increased risk of herniation, and may be protective. Relative risk estimates for the association between individual sports and lumbar or cervical herniation were generally less than or close to 1.0. There was, however, a weak positive association between bowling and herniation at both the lumbar and cervical regions of the spine. Use of weight lifting equipment was not associated with herniated lumbar or cervical disc, but a possible association was indicated between use of free weights and risk of cervical herniation (relative risk, 1.87; 95% confidence interval, 0.74 to 4.74).

An epidemiologic study of non-occupational lifting as a risk factor for herniated lumbar intervertebral disc. The Northeast Collaborative Group on Low Back Pain.

An epidemiologic case-control study of herniated lumbar intervertebral disc was conducted in Springfield, Massachusetts, New Brunswick, New Jersey, and New York, New York, to evaluate the role of several possible risk factors in the etiology of this disorder. Patients with signs and symptoms of herniated lumbar disc (N = 287) were matched to control subjects without back pain by age, sex, source of care, and geographic area. Of the total case-subject group, 177 were confirmed by surgery, computed tomographic scan, myelogram, or magnetic resonance imaging. This article focuses on non-occupational lifting, an activity not previously reported on. Frequent lifting of objects or children weighing 25 or more pounds with knees straight and back bent was associated with increased risk of herniated lumbar disc. This association was particularly strong among confirmed case subjects (relative risk = 3.95). Positive associations among confirmed case subjects were also seen for frequent lifting with arms extended (relative risk = 1.87) and twisting while lifting (relative risk = 1.90). No associations were found for frequent stretching or carrying. If confirmed in other investigations, these data suggest that instruction in lifting techniques should be extended into the home.

Root canal obturation using Thermafil endodontic obturators in dog teeth.

The technique of using Thermafil endodontic obturators to fill root canals in dog teeth is discussed in detail. Stainless steel carriers coated with gutta-percha were heated and inserted in instrumented canals of dog teeth. The ease of the technique is discussed and obturation efficacy is evaluated. No perfect apical seal was achieved.

Evaluation of the calcium channel-blocking agents diltiazem and verapamil for treatment of feline hypertrophic cardiomyopathy.

To determine the efficacy of and clinical response to several pharmacologic agents for treatment of idiopathic hypertrophic cardiomyopathy in cats, 17 symptomatic cats were randomized to treatment with either propranolol, diltiazem, or verapamil. Clinical, laboratory, radiographic, electrocardiographic, and echocardiographic data were obtained before treatment and after 3 and 6 months of chronic oral therapy. Too few of the cats receiving propranolol or verapamil survived long enough to obtain long-term data needed to make statistical comparisons between groups. However, all 12 cats ultimately treated with diltiazem became asymptomatic, and no adverse effects from this drug were noted in any of these cats. Treatment with diltiazem was associated with a significant reduction of pulmonary congestion assessed radiographically (P less than 0.01), and improved ventricular filling based on echocardiographic measurements of left atrial size (P less than 0.05), left ventricular internal diastolic dimension (P less than 0.05), and relaxation time index (P less than 0.001). There was also a drug-related improvement in jugular venous oxygen tension (P less than 0.001) and blood lactate concentration (P less than 0.01) suggesting improved peripheral perfusion in the cats receiving diltiazem. The results indicate that diltiazem provides an effective and apparently safe treatment for the management of feline hypertrophic cardiomyopathy.

Evidence for or against the efficacy of calcium channel blockers for management of hypertrophic cardiomyopathy in cats.

The positive lusitropic and direct coronary vasodilating properties of the calcium channel blocking agents are beneficial therapeutic effects not provided by the beta-adrenergic blocking agents for the management of feline HCM. Data from cats studied at the University of Tennessee suggest that diltiazem more consistently alleviates clinical signs and more effectively prolongs survival in cats with HCM than either propranolol or verapamil. Orally administered diltiazem appears to have sustained beneficial effects on left ventricular filling and cardiac performance based on its ability to reduce resting heart rate, decrease blood lactate concentration, increase venous oxygen tension, improve echocardiographic parameters, and resolve radiographic abnormalities. Long-term diltiazem administration may also reverse myocardial hypertrophy in some patients. There appear to be few if any side effects of this drug. Diltiazem, therefore, provides a safe and effective approach for the management of feline HCM.

Familial predisposition for herniation of a lumbar disc in patients who are less than twenty-one years old.

The parents of sixty-three patients who were less than twenty-one years old and who had operatively confirmed herniation of a lumbar disc were interviewed regarding a history of sever back pain, sciatica, and herniated disc, to determine whether aggregation of herniation of a lumbar disc occurs in families of patients in this young age-group. The parents of sixty-three additional patients who had a non-spinal orthopaedic diagnosis (control group) were matched for age and sex with the study group and were given the same interview. Of the patients who had herniation of a lumbar disc and were less than twenty-one years old, 32 per cent had a positive family history for that lesion compared with 7 per cent of the control group. The relative risk of development of herniation of a lumbar disc before the age of twenty-one years is estimated to be approximately five times greater in patients who have a positive family history. The results indicate a familial basis for herniation of a lumbar disc in patients who are less than twenty-one years old.

Use of relaxation half-time as an index of ventricular relaxation in clinically normal cats and cats with hypertrophic cardiomyopathy.

Relaxation half-time (t1/2) was evaluated as a measure of isovolumic ventricular relaxation in clinically normal cats and cats with hypertrophic cardiomyopathy. Relaxation half-time was determined directly from the left ventricular pressure tracing as the time required for the left ventricular pressure at the beginning of isovolumic relaxation to decrease by half. The value of t1/2 was unaffected by moderate changes in heart rate, inotropic state, and afterload in clinically normal cats. However, t1/2 increased significantly (P = 0.003) with increased preload. The value of t1/2 was significantly higher (P = 0.0003) in a group of cats with hypertrophic cardiomyopathy, compared with that of a group of clinically normal cats. Although t1/2 must be interpreted in the context of changes in loading conditions, the index is useful as a measure of relaxation in clinically normal cats and cats with hypertrophic cardiomyopathy.

Low back pain/prolapsed lumbar intervertebral disc.

Low back pain is common throughout the adult years in both men and women; first episodes most frequently occur among people in their 20s and 30s. Prolapsed lumbar disc most often affects individuals in the age range 25-45 years; prolapses occur infrequently in persons below 20 years or over 65 years. Major risk factors for low back pain in general and for prolapsed disc specifically include frequent lifting of objects weighing 25 pounds or more, especially if the objects are lifted with the arms extended and with the knees straight and if the lifting is done while the body is twisted; exposure to whole-body vibration, including driving motor vehicles; cigarette smoking; and, for prolapsed lumbar disc, narrow lumbar vertebral canals. Possible risk factors for which the evidence is weak or inconsistent include frequent stretching, reaching, pulling, and pushing on the job; sedentary occupations; jobs in which workers stay in one position for long periods of time; recent employment in a physically demanding job; jobs requiring frequent twisting without lifting; tallness; heredity; extent of forward flexibility in the lumbar area; lack of physical fitness; pregnancies; psychological symptoms; and frequent participation in bowling. The methods suggested to date with the greatest potential for prevention include modification of jobs so as to reduce exposure to known occupational risk factors, and careful selection of workers by such means as strength testing for the particular job for which they are to be employed.

Captopril provides sustained hemodynamic benefits in dogs with experimentally induced mitral regurgitation.

Mitral regurgitation was created surgically in 10 dogs. After measurement of baseline hemodynamic parameters on day 2, treatment with captopril (2 mg/kg orally 3 times daily) was begun in five dogs. Five control dogs received no therapy during the study. The hemodynamic parameters were measured again at weeks 6 and 22. In the treated dogs, the forward ejection fraction (FEF) increased slightly and the total peripheral resistance index (TPRI) decreased. In the controls, the FEF decreased and the TPRI increased. Changes in FEF and TPRI were significantly different between the two groups. The change in FEF correlated significantly with the change in TPRI in both groups. Although the most dramatic changes were observed at week 6, the differences persisted throughout the study. Captopril administration resulted in sustained hemodynamic improvement and may, therefore, delay the onset of congestive heart failure in dogs with mitral regurgitation.

Problems with dental equipment and materials.

The proper selection of dental equipment and materials is of absolute importance in the successful practice of veterinary dentistry. Improper equipment can make a difficult procedure more time consuming or impossible to perform. Materials must be selected that can withstand the oral environment and biting forces of the animal. The purpose of this chapter is not to recommend specific products, but rather to increase the reader's basic understanding of the application and limitations of dental equipment and materials. With better comprehension of the properties of the materials, the veterinary dentist should be able to intelligently select products that will fit the specific needs of his or her veterinary dental practice.