Plasma catecholamines: Arterial-venous differences and the influence of body temperature

Using sensitive radio-enzymatic assays, levels of plasma total catecholamines and norepinephrine in rats change dramatically with changes in body temperature. The decrease in plasma catecholamines induced by warming the animal is reflected in an apparent arterio-venous difference when arterial blood is obtained at room temperature and tail sampling is aided by heat induced vasodilation. Combined blockade of extraneuronal and neuronal uptake reduces this arterio-venous difference. Blood samples obtained from the decapitated trunk of the rat contain similar levels of plasma catecholamines as those obtained from indwelling carotid catheters. Blood levels of dopamine-betahydroxylase were similar whether obtained by venous sampling during heat-induced vasodilation, decapitation or indwelling arterial cannula.     

Preterm birth without progesterone withdrawal in 15-hydroxyprostaglandin dehydrogenase hypomorphic mice

Parturition is a complex mammalian physiological process whose fundamental determinants have remained elusive. The increasing incidence of human preterm birth, a leading cause of infant mortality, highlights the importance of further understanding mechanisms regulating the timing of birth. Parturition is initiated in most nonprimate mammals, including mice, through a decrease in circulating progesterone caused by elevated prostaglandins. In humans, other higher primates, and guinea pigs, no consistent decrease in circulating progesterone occurs before the onset of labor. The divergence in endocrine control of labor initiation between most mammals compared with the great apes and guinea pigs gives rise to the question: how could a mechanism for the initiation of labor not requiring the withdrawal of progesterone evolve? Here, we genetically modulate prostaglandin signaling to determine the role of prostaglandin catabolism in the timing of birth. We find spontaneous preterm labor in the absence of progesterone withdrawal in 15-hydroxyprostaglandin dehydrogenase hypomorphic mice. The onset of labor in these hypomorphic mice is preceded by prematurely increased concentrations of prostaglandin E(2) and F(2alpha). Moreover, genetic crosses demonstrate a role for fetal genotype in birth timing. Together, these findings demonstrate a 15-hydroxyprostaglandin dehydrogenase-dependent shift in the physiology of murine parturition to one resembling the physiology of higher primates. Thus, endocrine control of labor has the capacity to plastically adapt to changes in genetically determined prostaglandin signals.     

Medical and Health Care in State Residential Institutions for Children and Youths: A Report of Survey Findings in Five Hospitals

A survey of five Northern California state residential institutions showed considerable variation in the type and amount of medical services provided for children and youths. There was no standard policy for relationships with regional centers, use of community hospitals, vision and hearing assessments, speech and rehabilitation therapy, or genetic and maternal health services. Some hospitals had no staff members certified to carry out cardiopulmonary resuscitation (CPR). Not all staff physicians and other health professionals working in state hospitals had specific training in the areas of genetics, seizure control and physical rehabilitation medicine. While all five state hospitals are involved in training personnel, there is a need to develop a statewide plan for the better sharing of knowledge and expertise of the state hospital personnel in the training of pediatricians and others.     

Plasma catecholamines and dopamine-beta-hydroxylase activity in spontaneously hypertensive rats.

Levels of plasma norepinephrine and total catecholamines in spontaneously hypertensive rats bred from a normotensive Kyoto strain of Wistar rats increase between their 8th to 12th week post utero concomitant with the development of hypertension, but levels of plasma norepinephrine are not significantly different between the spontaneously hypertensive strain, a normotensive Kyoto strain and a N.I.H. strain of Wistar rats at either 8 or 12 weeks of age. Plasma total catecholamine levels in the spontaneously hypertensive strain are significantly higher at 12 weeks of age than those in either control strain, while plasma levels of dopamine-β-hydroxylase show no consistant relationship between the three strains. It, therefore, appears unlikely that increased sympathetic neuronal activity is an etiological factor in this form of hypertension.     

Cirrhosis mortality and per capita consumption of distilled spirits,United States, 1949-94: trend analysis

ObjectiveTo describe, evaluate, and suggest interpretations for an observed aggregate level relation between trends in mortality from cirrhosis and per capita consumption of distilled spirits in the United States.DesignTrend analysis using data on US cirrhosis mortality and per capita alcohol consumption.ResultsThere is a consistent long term trend relation between mortality from cirrhosis and per capita consumption of distilled spirits in the United States from 1949 to 1994. Two instances of comparatively sharp drops in the consumption of spirits earlier in the 1940s generated mixed results in predicting changes in cirrhosis mortality.ConclusionsAn aggregate level relation between trends in long term cirrhosis mortality and the consumption of spirits falls considerably short of establishing a direct causal link between the two for individuals. Moreover, two sharp drops in the consumption of spirits generated only mixed results with respect to the short term trend in cirrhosis. Nevertheless, the observed relation between the consumption of spirits and cirrhosis mortality merits further investigation.

Key messages

• US cirrhosis mortality peaked in 1973 but alcohol consumption did not peak until the early 1980s
• Both shifts in the distribution of US drinking patterns (which are not reflected in per capita consumption statistics) and the increase in the availability of treatment for alcoholism have been suggested as potential sources of the decline in cirrhosis
• The trend in the consumption of distilled spirits from 1949 to 1994 shows a close, aggregate level association with cirrhosis mortality
• This aggregate level relation suggests that research is needed into the link between the effects of specific alcoholic beverages and cirrhosis

     

Thyroid Storm—A Review of Cases at University of California,San Francisco

Retrospective study of the diagnosis and management of the 8 cases of thyroid storm in a series of 400 hyperthyroid patients led to conclusion that thyroid storm is a clinical diagnosis based on a life-endangering illness in a hyperthyroid patient whose hyperthyroidism has been severely exacerbated by a serious precipitating illness, and that storm is manifest by the symptoms of hyperpyrexia, tachycardia and striking alterations in consciousness. No laboratory tests were diagnostic of storm, and the underlying precipitating cause of thyroid storm was the major determinant of survival. Vigorous therapy must include blocking synthesis of thyroid hormones with antithyroid drugs, blocking release of preformed hormone with iodine, meticulous attention to hydration and supportive therapy, as well as correction of precipitating cause of storm. The blocking of the sympathetic nervous system with reserpine or guanethidine or with alpha and beta blocking drugs may be exceedingly hazardous and requires skillful management and constant monitoring in a critically ill patient.     

Effect of tyramine and guanethidine on dopamine-β-hydroxylase activity and norepinephrine concentrations in vesicular fraction of the heart and plasma of rats

Repeated administration of high doses of tyramine to rats results in a striking increase in plasma levels of norepinephrine (NE) and a marked depletion in tissue content of NE. The drug also may produces a moderate increase in plasma levels of dopamine-β-hydroxylase (DBH) and a decrease in DBH in synaptic vesicles of sympathetic nerves in the heart. The latter effects are prevented by a ganglionic blocking agent, indicating that they may be mediated by neuronal activation secondary to the stress attending the drug administration. Chronic administration of guanethidine, which is reported to destroy most sympathetic nerves produces more marked decrease in plasma NE levels and plasma DBH activity. The possible sources of this activity are discussed.     

Association of genetic variants at TOX3, 2q35 and 8q24 with the risk of familial and early-onset breast cancer in a South-American population

Recent Genome-Wide Association Studies have identified several single nucleotide polymorphisms (SNPs) associated with breast cancer (BC) among women of Asian, European, and African-American ancestry. Nevertheless, the contribution of these variants in the South American population is unknown. Furthermore, there is little information about the effect of these risk alleles in women with early BC diagnosis. In the present study, we evaluated the association between rs3803662 (TOX3, also known as TNRC9), rs13387042 (2q35), and rs13281615 (8q24) with BC risk in 344 Chilean BRCA1/2-negative BC cases and in 801 controls. Two SNPs, rs3803662 and rs13387042, were significantly associated with increased BC risk in familial BC and in non-familial early-onset BC. The risk of BC increased in a dose-dependent manner with the number of risk alleles (P-trend < 0.0001 and 0.0091, respectively). The odds ratios for BC in familial BC and in early-onset non-familial BC were 3.76 (95 %CI 1.02–13.84, P = 0.046) and 8.0 (95 %CI 2.20–29.04, P = 0.002), respectively, for the maximum versus minimum number of risk alleles. These results indicate an additive effect of the TOX3 rs3803662 and 2q35 rs13387042 alleles for BC risk. We also evaluated the interaction between rs3803662 and rs13387042 SNPs. We observed an additive interaction only in non-familial early-onset BC cases (AP = 0.72 (0.28–1.16), P = 0.001). No significant association was observed for rs13281615 (8q24) with BC risk in women from the Chilean population. The strongly increased risk associated with the combination of low-penetrance risk alleles supports the polygenic inheritance model of BC.