SummaryA diet deficient in the amino acid methionine has previously been shown to extend lifespan in several stocks of inbred rats. We report here that a methionine-deficient (Meth-R) diet also increases maximal lifespan in (BALB/ cJ × × × × C57BL/6 J)F1 mice. Compared with controls, Meth-R mice have significantly lower levels of serum IGF-I, insulin, glucose and thyroid hormone. Meth-R mice also have higher levels of liver mRNA for MIF (macrophage migration inhibition factor), known to be higher in several other mouse models of extended longevity. Meth-R mice are significantly slower to develop lens turbidity and to show age-related changes in T-cell subsets. They are also dramatically more resistant to oxidative liver cell injury induced by injection of toxic doses of acetaminophen. The spectrum of terminal illnesses in the Meth-R group is similar to that seen in control mice. Studies of the cellular and molecular biology of methionine-deprived mice may, in parallel to studies of calorie-restricted mice, provide insights into the way in which nutritional factors modulate longevity and late-life illnesses.

A prospective observational study of the performance of patients enrolled in an individually customized program of habituation and balance rehabilitation physical therapy was conducted from January 1988 to January 1990. Patients ranged in age from 20 to 89 years, with a wide variety of diagnoses. Two global outcome measures--posttherapy symptom response score and pretherapy and posttherapy disability score--were developed and used to judge overall patient performance. In addition, two specific indicators--one for balance performance (dynamic posturography) and one for sensitivity to rapid head movements (motion sensitivity quotient)--were used to measure performance in these two areas. Results indicate statistically significant changes before versus after therapy for both specific measures, and 80% to 85% of the patients showed a reduction in symptoms and disability score following therapy. Analysis of variance and multiple regression analysis indicate that nature of symptoms, pretherapy disability level, history of head injury, and results on dynamic posturography were the variables most predictive of therapy outcome, while age and duration of symptoms made no difference. Other variables, such as medications and site of lesion, were found to affect the length of therapy but not the outcome.

Snell dwarf mice have multiple hormonal deficits, but the way in which these deficits postpone aging are still uncertain. In this study, Snell dwarf mice received 11 weeks of growth hormone and thyroxine injections that increased their weight by approximately 45%, although they remained much smaller than controls. The hormone treatment also restored fertility to male dwarf mice. Despite these effects on growth and maturation, the hormone treatments did not diminish life span or lower the resistance of dwarf mice to cataracts and kidney disease. Administration of thyroxine in food throughout adult life did diminish longevity of Snell dwarf mice, although these mice remain longer lived than control animals. These results show that a 45% increase in body size does not impair longevity or disease resistance for dwarf mice of either sex, and that the exceptional longevity of Snell dwarf mice does not, at least for males, depend on prepubertal immaturity.

The association between the APOE-epsilon4 allele and a reduced risk of AMD was established in a large cohort with sufficient statistical power. How distinct APOE alleles affect AMD susceptibility warrants further investigation.

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Patients with bilateral peripheral vestibular dysfunction present a substantial diagnostic and therapeutic challenge to the otologist. Caloric irrigations that suggest bilateral weakness may mislead the clinician when considerable peripheral function remains. Rotary chair testing at several frequencies is helpful in confirming the degree of residual function and may identify patients who have a better prognosis in rehabilitation. Forty-nine patients with bilateral vestibular paresis were evaluated. The diagnosis was based on caloric responses of less than 5 degrees/sec in both ears and reduced gain on rotary chair trials. Oscillopsia occurred in the minority of patients (35%) and was rare unless severe paresis was present. Episodic vertigo occurred in 43%. All patients had abnormal posturography results, with vestibular dysfunction and severe dysfunction patterns predominating. The treatment outcomes of 22 patients who underwent vestibular rehabilitation are discussed. Prevention of bilateral vestibular paresis remains a high priority.

Simple clinical measures of static and dynamic equilibrium can reliably distinguish vestibular disorder patients from normal subjects. Dynamic posturography continues to play an important role in the functional evaluation and management of vestibular disorder patients.

Chronic vestibular dysfunction is often a frustrating problem for both patient and physician. A program of customized vestibular habituation therapy is introduced and its efficacy in a group of 65 patients is evaluated. Preliminary findings suggest that 59% of patients will have a dramatic improvement, after which their vestibular symptoms no longer cause any restriction in their lifestyles. An additional 23% of patients note considerable improvement, but have persistent symptoms that continue to restrict their activities. Vestibular habituation therapy is a rational, multidisciplinary approach to the treatment of chronic vestibular dysfunction that is a significant alternative to traditional pharmacologic management. Failure of vestibular compensation after involvement in a disciplined program of habituation therapy constitutes a much stronger indication for vestibular surgery in patients with unilateral peripheral lesions.