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.     

Role of frozen section and clinical parameters in distinguishing benign from malignant follicular neoplasms of the thyroid.

The determination of malignancy preoperatively or intraoperatively is difficult in patients with follicular neoplasms of the thyroid. This study reviews a series of 395 patients treated for follicular neoplasms at the Vancouver General Hospital and the British Columbia Cancer Agency between the years of 1955 and 1988, 198 of whom had frozen section at the time of surgery. Frozen section was 79% accurate in differentiating follicular adenomas from carcinomas, with a sensitivity of 52% and a specificity of 100%. The positive predictive value of a frozen section showing carcinoma was 100%, and the negative predictive value was 73%. An incorrect diagnosis of a benign lesion was made in 21% of patients in whom the final diagnosis by fixed section was carcinoma. These same statistics were calculated for patients aged greater than 50 years, tumor size greater than 3 cm, and patients with a history of previous neck irradiation, three clinical factors shown in a previous study to be strong prognostic indicators of malignancy. The results were compared with those found by frozen section. The implications of these results in terms of patient management are discussed.     

Platelet phospholipid synthesis in Alzheimer's disease

The rates of incorporation of [3H]choline and [3H]ethanolamine into membrane phospholipids of platelets from 22 drug-free Alzheimer's disease patients and 18 normal elderly controls were compared. No significant differences between groups were found. If alterations in lipid metabolism are involved in the pathophysiological processes underlying Alzheimer's disease, such alterations are not manifest in measures of radiolabeled base incorporation into platelet phospholipids.     

Acute myelocytic leukemia and prior allergies

The relationship between prior allergies and adult acute myelocytic leukemia was investigated in a population-based case-control study. Based on data from personal interviews of 98 cases and 133 controls, a history of any type of allergy was associated with a significantly decreased risk of acute myelocytic leukemia (OR = 0.35, 95% CI = 0.20-0.60). Risk declined with the total number of specific allergies reported (p less than 0.001), and was reduced in relation to a history of prior asthma, eczema and hives. The implications of these findings in relation to natural immune surveillance against developing neoplasms are discussed.     

The use of selegiline in Alzheimer's patients with behavior problems

BACKGROUND: Currently there is no regimen for managing the inappropriate behavior seen in Alzheimer's disease that does not cause significant patient sedation. Preliminary evidence suggests selegiline may be effective in behavioral modification without the adverse effects observed with other regimens. The purpose of this study was to document the efficacy of selegiline in Alzheimer's patients with behavior problems. METHOD: Eight Alzheimer's patients (6 women and 2 men) ranging in age from 50 to 82 years (mean +/- SD = 74.0 +/- 10.5) were enrolled in this single-blind study. Patients received selegiline 10 mg each day for 8 weeks. Prior to drug administration and at the end of Weeks 1, 2, 4, 6, and 8, patients were evaluated for behavior (BEHAVEAD), cognitive function (Mini-Mental State Examination), and caregiver stress (Caregiver Burden Scale). RESULTS: Of eight enrolled patients, five were available for analysis. No statistically significant differences were found between mean baseline and mean 8-week scores for any of the three tests. However, clinical significance was noted by improvement in cognition (orientation and recall), caregiver stress, and behavior. Behavior was noted to improve in the areas of paranoid and delusional ideation, hallucinations, activity disturbances, anxiety, and phobias. CONCLUSION: These data suggest that some Alzheimer's patients with behavior problems may benefit from selegiline therapy.     

A psychobiological perspective on the personality disorders

A preliminary but growing body of evidence supports the existence of genetic and biological substrates of personality, suggesting the utility of a psychobiological perspective on the personality disorders. The investigation of biological correlates of personality disorders can provide an empirical base to explore the relationship between biological predispositions and psychological function. The authors propose a psychobiological model based on dimensions of cognitive/perceptual organization, impulsivity/aggression, affective instability, and anxiety/inhibition. These dimensions span the DSM-III-R axis I and axis II disorders. The authors review phenomenological, genetic, and biological evidence in relation to each of these dimensions. Although such an approach remains heuristic, this model provides a promising vantage point from which to generate investigation of the development and treatment of the personality disorders.     

Effects of the phosphodiesterase inhibitor rolipram on the acoustic startle response in rats

Systemic administration of the phosphodiesterase inhibitor rolipram (0.05–10.0 mg/kg, IP) produced a rapid and dose-related increase in the amplitude of the acoustic startle response in rats. The (−) isomer was more potent than the (+) isomer in enhancing startle amplitude. Rolipram increased startle responses that were elicited by brief electrical stimulation of the ventral cochlear nucleus or nucleus reticularis pontis caudalis, two brainstem relay nuclei of the startle neural circuit. A low (5 μg) dose of rolipram produced an excitatory effect on startle following spinal (lumbar intrathecal) infusion but not following supraspinal (lateral ventricle) infusion. Rolipram (0.5 mg/kg, IP) excitation of startle was not blocked by drugs which differentially disrupt the release of monoamines (DSP4, reserpine + alpha-methylpara-tyrosine, reserpine + para-chloro-phenylalanine) or by drugs which differentially block monoamine receptors (haloperidol, prazosin, idazoxan, cinanserin, or cyproheptadine). The marked increase in startle seen following systemic rolipram injection is attributable, at least in part, on an action in the lumbar spinal cord that directly or indirectly facilitates neural transmission along the reticulospinal component of the startle reflex neural pathway. The startle reflex should be a useful behavioral test system for studying the mechanism of action of rolipram and related compounds purported to selectively inhibit calmodulin-independent forms of phosphodiesterase.     

Exercise training ameliorates progressive renal disease in rats with subtotal nephrectomy

To determine the effect of chronic exercise training on renal function in animals with moderate renal insufficiency, rats with 75% renal ablation were either exercise trained by swimming for two months or remained sedentary. Glomerular filtration rate was significantly higher in trained (1.89 +/- 0.07 ml/min) than in sedentary rats (1.52 +/- 0.11 ml/min). No change was observed in renal blood flow or the degree of hypertension. Proteinuria was reduced in trained (13.6 +/- 4.9 mg/24 hr) compared to sedentary animals (33.5 +/- 9.2 mg/24 hr). The degree of glomerulosclerosis was much less prominent in trained animals. Plasma, low-density lipoprotein cholesterol-levels and total triglycerides were reduced in trained compared to sedentary rats. This study suggests that chronic exercise training ameliorates the progression of renal disease and improves plasma lipids in rats with moderate renal insufficiency. The mechanism for this improvement in renal function appears to be independent of the influence of systemic blood pressure.