Fertility of workers chronically exposed to chemically contaminated sewer wastes.

Few studies have investigated the reproductive effects of exposure to chemical mixtures. The purpose of this study was to assess fertility in males exposed to mixed industrial and domestic wastes. A detailed reproductive history was obtained from the wives of 231 employees in order to evaluate fertility. Daily work records were used to define exposure status. To ascertain problems of infertility, the ratios of observed live births to expected live births (generated from U.S. birth probabilities) for exposed and nonexposed groups were calculated, and the ratios of these Standardized Fertility ratios (SRFs) were compared. Other analyses considered the couples' contraceptive history and preexposure versus postexposure experience. Though multiple statistical approaches were used to examine the data, the conclusion of this study was that exposure to chemical mixtures was not associated with a decrease in the couples' fertility.     

Ethanol consumption and free operant avoidance performance following exposure to dietary lead

Rats were exposed ad libitum to a diet containing either 500 ppm lead (Group Lead-Diet) or a control diet with no added lead (Group Control-Diet). On Day 60 both groups were presented with a 15% ethanol solution (nonchoice test) in the home cage for five days prior to placement on a choice test that presented animals with a 10% ethanol solution and tap water. Concurrently with the choice test in the home cage, animals were placed in operant chambers for one hr (pre-avoidance) prior to a 30 min free operant avoidance session (avoidance) and remained there for one hr (post-avoidance) after training. Throughout avoidance training, the choice test was conducted in the chamber as well as the home cage. In addition to evidence of greater ethanol consumption by Group Lead-Diet rats, the results showed that these animals lever pressed more frequently, but not more efficiently, than Group Control-Diet animals.     

Latex condom deterioration accelerated by environmental factors: I. Ozone

Commercial non-lubricated latex condoms were unpackaged and exposed in an environmental chamber to ozone levels (0.3 ppm) commonly present in urban smog conditions. Deterioration was observed by scanning electron microscopy after 18 hours exposure. Loss of mechanical strength was quantitated by measurement of the air pressures necessary to burst the condom and volumes at burst. After 24 hours exposure to ozone the latex surface was covered with craters and after 48 hours the pressure required to burst the condom was 44% that of control samples. Data suggest the need for study of the effectiveness of lubrication and packaging in protecting condoms from environmental factors which may accelerate deterioration.     

Effect of transplanted osteogenic sarcoma on urinary RNA catabolites

The usefulness of urinary RNA catabolites as markers for the early detection of a transplantable rat tumor and for the completeness of its resection was evaluated. The lack of correlation between tumor growth or size and the time of appearance of the elevated catabolites precludes their use for the early detection of cancer in this model. Complete removal of the tumor restored the elevated levels to normal but, if regrowth occurred, the elevated levels persisted, suggesting their possible use in monitoring the effectiveness of surgery. The data suggest that increased excretion of RNA catabolites is derived primarily from host tissue.     

Lethal enhancement of therapeutic doses of acetaminophen by alcohol

Summary A 47-year-old man undergoing supervised alcohol detoxification developed severe liver disease after receiving small doses of acetaminophen. Autopsy revealed extensive hepatic necrosis. Proposed mechanisms for alcohol potentiation of acetaminophen hepatotoxicity are described. We feel acetaminophen should not be routinely used for patients with active alcoholism unless its safety can be established.     

Long-term outcome of head injuries: a 23 year follow up study of children with head injuries.

The purpose of the 23 year follow up study was to determine the relationship between trauma variables including measures of head injury and very long-term sequelae. The study included 159 individuals with a mean age 31.40 years, of whom approximately 90% were admitted to hospital with a mild head injury during childhood (mean age 7.96). Extent of head injury was determined by unconsciousness, neurological status, skull fracture, EEG, post-traumatic seizures and a composite measure. The composite measure of neurological variables was the best predictor of long-term outcome. In addition, IQ recorded in the post-acute phase was a reliable predictor of long-term outcome. Of the sample, 32.7% reported physical complaints and 17.6% reported current psychological/psychiatric problems unrelated to the head injury. Subjective sequelae (physical, intellectual and emotional) specified as due to the head injury were reported by 31% of the sample, and the sequelae were found to be related to the extent of the head injury and initial IQ. There were no discernible relationships between attribute variables including premorbid status and age with subjective sequelae. There were, however, significant relationships between subjective sequelae and objective, psychosocial measures of adaptation including educational lag, unemployment, current psychological/psychiatric problems and relationships with family members. Finally, there appeared to be continuity of complaints elicited during the five year follow up of the original project and current sequelae. The severity of the head injury was identified as the primary contributory factor in the reconstitution process and in the prediction of long term outcomes.     

Cultural Meanings of Childbirth

In no known culture in the world is childbearing treated with indifference. Cultural beliefs about and values associated with childbearing touch all aspects of social life in any given culture. Such beliefs and values lend perspective to the meaning of childbirth to the childbearing woman. Having the opportunity to share the woman's perceptions of the meaning of childbearing may foster the self-actualization, promote maternal role attainment, and improve her relationship with her significant other and enrich the family perspective. Nursing interventions across the childbearing year should be culturally sensitive to promote positive outcomes for the woman and her family.     

The basis of the histamine assay in human skin: II. Wheal formation.

1. Subepidermal injection of histamine solutions in isotonic saline in four subjects evoked whealing after a mean delay of 2.6 min, this estimate being derived by regression modelling. 2. Wheal growth was better modelled by the logarithm of time than by time, suggesting that wheal size depends upon assisted diffusion of histamine in the dermis. 3. Wheal growth was piecemeal, not continuous, consistent with the successive involvement of neighbouring vascular territories. 4. Wheal growth was completed by 9 min after injection.     

Guanyl nucleotide regulatory proteins in neoplastic and normal human thyroid tissue

Papillary and follicular thyroid neoplasms have been documented to have thyrotropin (TSH) receptors and an intact receptor-adenylate cyclase (AC) system. The AC response to TSH in most benign and malignant thyroid neoplasms is greater in the neoplasms than in the adjacent normal thyroid tissue. This increased AC response could be due to abnormal amounts of guanyl nucleotide regulatory (G) proteins, to an altered ratio of stimulating to inhibiting G proteins, or to the coupling of the G proteins—to either the receptor or to the catalytic unit of AC. To study why tumors have a greater AC response to TSH, we first extracted the G proteins from normal and neoplastic human thyroid tissue and placed them in membranes from cyclase minus S⁴⁹ mouse lymphoma cells that lack a stimulating guanyl nucleotide regulatory protein (Gs). These studies demonstrated that there were comparable amounts of guanyl nucleotide regulatory protein in normal and neoplastic thyroid tissue. We next investigated whether there was an alteration in the ratio of inhibiting (Gi) to stimulating (Gs) guanyl nucleotide regulating proteins in thyroid neoplasms. Pertussis toxin (PT) (10 g/ml) was used to study the activity of the inhibiting G protein since it stimulates AC activity by inhibiting the inhibitory regulatory protein by adenosine diphosphate ribosylating the alpha subunit of the Gi protein. Cholera toxin (CT) (10 ng/ml) was used because it selectively activates the stimulating G proteins. AC activity was determined by the conversion of [-³²P]ATP to cAMP in pmol/mg protein per 30 minutes. In 11 patients, PT-stimulated AC levels [8.55±1.7 SEM, (mean±standard deviation)] in normal tissues were higher than basal levels of AC (5.14±0.9,p< 0.01). However, there were no differences in basal and PT-stimulated levels in neoplastic tissues (6.43±1.0 and 6.87 ±1.8, respectively). This suggests that there is less Gi protein in the neoplasms since the AC response to PT was greater in normal tissues by 170%, but there was no significant stimulation in neoplastic tissues. In contrast, the AC response to CT (10 g/ml that directly activates the stimulatory guanyl nucleotide regulatory proteins was greater in neoplastic thyroid tissue (174.3±30.1) than in normal thyroid tissue (78.5±16.3) from the same patients (p<0.01).These experiments demonstrate that most thyroid neoplasms have less Gi and more Gs protein, which probably accounts for the greater AC response to TSH in thyroid neoplasms. The greater stimulation of Gs and the greater AC response in the neoplasms may be one reason for the more rapid growth of benign and malignant thyroid tumors.

---

Resumen Se ha podido documentar la presencia de receptores de tirotropina (TSH) y de un sistema receptor de TSH-adenilato ciclasa (AC) en los neoplasmas papilares y foliculares de la glándula tiroides. La respuesta de la AC a la TSH en la mayoría de los neoplasmas benignos y malignos de la tiroides es mayor en el tejido neoplásico que en el tejido tiroideo normal adyacente. Esta respuesta aumentada de la AC puede ser debida a cantidades anormales de las proteínas regulatorias guanil nucleótidas (G), a una alteración en la relación entre las proteínas G estimulantes e inhibitorias o a una ligazón de las proteínas G bien al receptor o a la unidad catalítica de la AC. Con el fin de estudiar por qué los tumores poseen una mayor capacidad de respuesta de la AC a la TSH, primera hicimos la extracción de las proteínas G de tejidos tiroideos humanos normales y neoplásicos y los colocamos en membranas de ciclasa menos células del linfoma S⁴⁹ del ratón que carecen de G. Estos estudios demonstraron que existían cantidades comparables de G en los tejidos tiroideos normal y neoplásico. A continuación investigamos si existía una altercación en la relación entre las proteínas regulatorias guanil nucleótidas inhibidoras (Gi) y estimulantes (Ge) en los neoplasmas tiroideos. Se utilizó toxina de pertusis (PT) (10 g/ml) para determinar la actividad de la Gi, puesto que ésta estimula la actividad de AC mediante la inhibición de la proteína regulatoria inhibidora por la ribosilación por ADP de la subunidad alpha de la proteína Gi. Se utilizó toxina del cólera (CT) (10 ng/ml) por cuanto ésta activa en forma selectiva las proteínas G estimulantes. La actividad de AC fue determinada por la tasa de conversion de [-³²P]ATP a cAMP en pmpl/mg de proteína por 30 minutos. En 11 patientes los niveles de AC estimulada por PT (8.55±1.7) en los tejidos normales fueron superiores a los niveles basales de AC (5.14±0.9,p<0.01). Sin embargo, no se observó diferencia entre los niveles basales y los niveles estimulados por PT en los tejidos neoplásicos (6.43±1.0 y 6.87±1.8, respectivamente). Esto sugiere que existe menos proteína Gi en los neoplasmas puesto que la respuesta de AC a la PT fue mayor en un 170% en los tejidos normales y no se presentó estimulación significativa en los tejidos neoplásicos. En contraste, la respuesta de AC a la CT (10 g/ml) que directamente activa las proteínas regulatorias guanil nucleotidas, fue mayor en el tejido neoplásico tiroideo (174.3±30.1) que en el tejido tiroideo normal (78.5±16.3) extraídos del mismo paciente (p<0.01).Estos experimentos demuestran que la mayoría de los neoplasmas tiroideos poseen menos proteína Gi y más proteína Ge, lo cual probablemente explica el mayor grado de respuesta de la AC a la TSH en los neoplasmas tiroideos. El mayor estímulo de Ge y el mayor grado de respuesta de la AC en los neoplasmas puede representar la razón del crecimiento más rápido de los tumores benignos y malignos de la tiroides.

---

Résumé Les tumeurs papillaire et folliculaire de la thyroïde ont des récepteurs à la thyrotropine (TSH) et à l'adénylate cyclase (AC). Pour la plupart d'entre elles, la réponse AC à la TSH est plus importante dans les tumeurs bénignes et malignes de la thyroïde que dans le tissu avoisinant normal. Cette augmentation d'activité peut être due: à des quantités anormalement importantes de protéines régulatrices de la guanyl-nucléotide (G), à un rapport anormal de protéines G de stimulation/ protéines d'inhibition, ou à un couplage de protéines G soit au récepteur soit à l'unité de catalyse de l'AC. Pour étudier les raisons pour lesquelles ces tumeurs ont une réponse AC augmentée vis-à-vis de la TSH, nous avons extrait les protéines G des tissus thyroïdes normal et tunoral de l'homme et nous les avons placés sur des membranes d'adénylate-cyclase des cellules lymphomateuses de souris S⁴⁹ n'ayant pas de protéines de stimulation de la guanyl-nucléotide (Gs). Ces études ont montré qu'il y avait des quantités comparables de protéines régulatrices de la guanyl-nucléotide dans les tissus thyroïdiens normal et tumoral. Nous avons ensuite mesuré le rapport des protéines régulatrices de la guanyl-nucléotide d'inhibtion (Gi) et de stimulation (Gs) dans les tumeurs thyroïdiennes. La toxine pertussis (TP) (10 g/ml) a été utilisée pour étudier l'activité de la protéine G d'inhibition puisqu'elle stimule l'activité AC en inhibant la protéine d'inhibition par ribosylation ADP de la sous-unité de la protéine Gi. La toxine choléra (TC) (10 ng/ml) active sélectivement les protéines G de stimulation. L'activité AC a été déterminée par la conversion de l'[-³²P]ATP en cAMP dosée en pmol/mg de protéine/30 minutes. Chez 11 patients, les taux d'AC stimulés par la TP étaient plus élevés (8.55±1.7, moyenne±écart type) que les taux d'AC de base dans les tissus normaux (p<0.01). Cependant, aucune différence significative n'a été trouvée entre les taux d'AC de base et après stimulation par la TP dans les tissus néoplasiques (6.43±1.0 vs. 6.87±1.8, respectivement). Cela suggère qu'il y a moins de protéine Gi dans le tissu néoplasique puisque la réponse AC à la TP était supérieure par rapport aux tissus normaux de 170%, mais sans stimulation significative dans les tissus néoplasiques. En revanche, la réponse AC à la TC était supérieure dans les tissus néoplasiques (174.3±30.1) par rapport aux tissus normaux (78.5±16.3,p<0.01) chez ces mêmes patients.Ces expériences démontrent que, par rapport au tissu thyroïdien normal, la plupart des néoplasmes thyroïdiens contiennent moins de Gi et plus de Gs, ce qui explique probablement la réponse AC à la TSH plus importante dans les néoplasmes. La plus grande stimulation des Gs et la réponse AC plus importante dans les tissus néoplasiques pourraient expliquer la croissance plus rapide des tumeurs thyroïdiennes bénigne ou maligne.

---

---

Presented at the International Association of Endocrine Surgeons in Sydney, Australia, September, 1987.

---

Supported in part by the Medical Research Service of the Veterans Administration Medical Center, San Francisco, California, U.S.A.