Effect of low dietary calcium on bone metabolism in the SENCAR mouse

The SENCAR (sensitive to carcinogenesis) mouse is a unique tool for investigating the interaction between a specific defect in intracellular signaling, dietary calcium, and metabolic bone disease. The SENCAR mouse was developed by selective breeding for enhanced sensitivity to two-stage carcinogenesis. Its major genetic defect, which renders it exquisitely sensitive to stimulation with diacylglycerol or phorbol esters, is in the regulatory domain of protein kinase C, one of the primary intracellular mediators of hormonal effects. At sexual maturity, SENCAR mice are large and have big bones, but our previous pharmacokinetic studies showed that they accumulate lesscalcium under normal conditions and lose more calcium under adverse conditions than do other, standard strains of mice. To histologically define the effect of low dietary calcium on bone metabolism, we performed histomorphometric analysis of tetracycline-labeled sections of femoral bone from male SENCAR mice maintained on calcium-sufficient and calcium-deficient diets during the critical period from 10 to 14 weeks of age. The bone volume, absolute osteoid volume, and mineral apposition rate were lower at 14 than at 10 weeks of age in SENCAR mice fed 0.02 or 0.6% calcium diets. Calcium deficiency increased the architectural disarray and the probability of observing focal discontinuities in the growth plate. Thus, characteristic features of impaired bone metabolism (low bone volume and apposition rate) develop early in SENCAR mice and are exacerbated by low dietary calcium. Detailed examinations of the histology and biochemistry of SENCAR mouse bone will provide insights into the mechanisms by which specific defects in the signal transduction of protein kinase C contribute to impaired bone metabolism.     

Methylmercury poisoning: Long-term clinical,radiological, toxicological,and pathological studies of an affected family

For 3 months in 1969 a family in the United States that included a pregnant mother consumed pork containing methylmercury. Children, aged 20, 13, and 8 years and a neonate, developed severe neurological signs. Twenty-two years later, the 2 oldest had cortical blindness or constricted visual fields, diminished hand proprioception, choreoathetosis, and atentional deficits. Magnetic resonance images showed tissue loss in the calcarine and parietal cortices and cerebellar folia. The youngest had quadriplegia, blindness, and severe mental retradation until their deaths. The brain of the 8-year-old who died at age 30 showed cortical atrophy, neuronal loss, and gliosis, most pronounced in the paracentral and parietooccipital regions. The total mercury level in formalin-fixed, left occipital cortex was 1,974 ng/gm as measured by atomic absorption. Regional brain mercury levels correlated with extent of brain damage. A control patient had 38.5 ng of mercury/gm in the occipital cortex. Systemic organs in the patient and a control subject had comparable mercury levels. In mercury-intoxicated rats, we found that only 5 to 10% of total brain mercury was lost by formalin fixation. Brain inorganic mercury in the patient ranged from 82 to 100%. Since inorganic mercury crosses the blood-brain barrier poorly, biotransformation of methyl to inorganic mercury may have occurred after methylmercury crossed the blood-brain barrier, accounting for its persistence in brain and causing part of the brain damage.     

Dacryocystitis following Kawasaki's disease

A 6 1/2-year-old white male child had developed bilateral dacryocystitis 1 year earlier, approximately 6 months after resolution of the acute phase of Kawasaki's disease. The patient had had no previous history of dacryostenosis or epiphora. After he failed to respond to appropriate antibiotic therapy, probing was partially successful on the right side, but complete obstruction persisted on the left side. At age 7 1/2 years, dacryocystorhinostomy was performed successfully on the left side. To our knowledge, dacryocystitis has not been reported previously following Kawasaki's disease. Other reported ocular complications of Kawasaki's disease, with the exception of a case of bilateral conjunctival scarring, have occurred in the acute phase of the disease.     

The Edgecombe County High Blood Pressure Control Program: the process of medical care and blood pressure control

As part of the Edgecombe County High Blood Pressure Control Program, a medical record review was conducted within a multispecialty private group practice in the county. The purposes of the review were to assess the relationship between the process of medical care and blood pressure control and to explore the variation in level and impact of medical care by race and sex. At the end of a three-year period, 41 percent of 628 hypertensive patients from the practice had uncontrolled diastolic blood pressure (DBP), as defined by Hypertension Detection and Follow-up Program criteria. The percentage of uncontrolled hypertensives ranged from 53 percent for black men to 34 percent for white women. Hypertensive patients whose physicians were more aggressive in their use of antihypertensive drug therapy were more likely to be controlled. The effect of the level of physician drug aggressiveness tended to be more pronounced for blacks than for whites. Differences by race in exposure to and efficacy of aggressive drug treatment may influence racial variation in blood pressure control.     

Anesthesia affects respiratory and sympathetic nerve activities differentially.

Phrenic and cervical sympathetic nerve responses to hypercapnia were examined before and after anesthesia in twelve midcollicularly decerebrated, vagotomized, glomectomized, paralyzed and ventilated cats. We measured responses of integrated phrenic and cervical sympathetic nerve activities to increases in end-tidal PCO2 (PETCO2) from apneic threshold to approximately 30 torr above threshold. All cats were studied first in the unanesthetized state. Six cats were then restudied after a quarter of a usual dose of chloralose/urethane (10 mg/kg and 62.5 mg/kg, respectively) and then after half the usual dose of chloralose/urethane (20 mg/kg and 125 mg/kg). The other six animals were restudied after quarter of a standard dose of pentobarbital (9 mg/kg), after half the standard dose (18 mg/kg) and then after the full (35 mg/kg) dose. Both anesthetic agents led to significant increases in apneic thresholds for both phrenic and sympathetic nerve activities. These agents also caused dose-dependent decreases in peak, tonic and respiratory-related sympathetic nerve activities. Peak (tidal) phrenic nerve activities, in comparison, were much less affected by the anesthetic agents. CO2 response curves showed that both of these anesthetic agents depressed, at any given level of PETCO2, respiratory-related sympathetic nerve responses more than the responses found in the phrenic nerve. We conclude that the relations between peak, tonic (i.e. between phasic bursts) and respiratory-related sympathetic nerve activities and phrenic nerve activity can be altered by anesthesia.