Peter Cohen

It now appears to be possible to continuously record changes in intracellular oxidation-reduction levels in terms of the fluorescence of reduced pyridine nucleotide in mitochondria of various tissues and organs in situ. Studies of kidney and brain cortex in the rat show that changes in fluorescence are not measurably affected by the presence of oxyhemoglobin. Nitrogen, sulfide, cyanide, and carbon monoxide cause increases in fluorescence to very nearly the same levels, and the increases are attributed to larger reduction of mitochondrial diphosphopyridine nucleotide. Amytal at a low blood concentration causes increased reduction in the kidney cortex, and at a high blood concentration, in the brain cortex. The qualitative response of the pyridine nucleotide to low oxygen concentrations shows the brain to be more sensitive than the kidney. The first measurable increase in pyridine nucleotide reduction observed on the brain occurs at a concentration of inspired oxygen of 8 percent. Breathing stops when the percentage increase of pyridine nucleotide reduction on the brain reaches about 90; at this point the percentage increase for the kidney is only about 30. This difference corresponds roughly to a tenfold difference in oxygen tension. Half-maximal increase in pyridine nucleotide reduction on the brain occurs at a concentration of inspired oxygen of about 4 percent and corresponds to an intracellular oxygen tension of about 0.2 mm (47).

BACKGROUND: Persons with parkinsonism have high rates of both associated and unrelated prevalent comorbid conditions. A better understanding of patterns of care and expenditures may aid in designing programs to enhance functioning, lengthen independent living, and manage costs. METHODS: The authors linked national survey data of 24,831 elderly to nearly 1.9 million Medicare claims. Persons with parkinsonism (n = 791) were identified from survey or Medicare encounters for paralysis agitans. Comorbid disease risk was measured using age-adjusted OR with 95% CI. Comorbidity cost ratios (ratio of average per person per year charges for parkinsonism alone vs with comorbid conditions) were developed to describe incremental costs of comorbidities. RESULTS: Patients with parkinsonism were older (78.5 +/- 7.6 vs 75.1 +/- 8.3 years, p < 0.0001) and had more injuries resulting in broken bones (35.6% vs 19.5%, p < 0.0001), including broken hips (15.9% vs 5.8%, p < 0.0001), during the 5-year study. Broken hips were more prevalent among men (OR 3.4, 95% CI 2.5 to 4.8) and women (OR 2.5, 95% CI 2.1 to 3.1) with than without parkinsonism. Among those with parkinsonism, comorbidity cost ratios demonstrated two- to threefold higher charges for dementia, broken bones, broken hip, and diabetes. CONCLUSIONS: Comorbidity associated with parkinsonism is an under-recognized contribution to higher resource use and expenditures. Further study of injuries, dementia, and diabetes is required to assess whether public health interventions could reduce excess morbidity and expenditures associated with parkinsonism.

We have characterized the temporal expression of the insulin-like growth factor (IGF) axis in the transgenic adenocarcinoma of mouse prostate (TRAMP) model as prostate cancer progression in this model closely mimics that observed in the human disease, and the model provides samples representing the earliest stages of prostate cancer that are clinically the most difficult to obtain. We report that prostate-specific IGF-I mRNA expression increased during prostate cancer progression in TRAMP mice and was elevated in the accompanying metastatic lesions, whereas prostatic IGF-I mRNA remained at nontransgenic levels in androgen-independent disease. Expression of IGF-II mRNA, however, was reduced in primary prostate cancer, metastatic lesions, and androgen-independent disease. Expression of type-1 IGF receptor (IGF1R) mRNA, encoding the cognate receptor for both IGF-I and IGF-II, as well as type-2 IGF receptor (IGF2R) mRNA was not found to be altered during primary prostate cancer progression in intact TRAMP mice but was dramatically reduced in metastatic lesions and in androgen-independent disease. Similar to reports from clinical disease, serum IGF-I levels were observed to increase precociously in TRAMP mice early in disease progression but remained at nontransgenic levels after castration. Elevated serum levels of IGF-binding protein 2 were observed to correlate with advanced prostate cancer in the TRAMP model. Together these observations implicate IGF-I as an important factor during the initiation and progression of primary prostate cancer and provide evidence that there is a strong selection against expression of IGF1R and IGF2R in metastatic and androgen-independent disease.

THE striking degree of malnutrition that may accompany chronic congestive heart failure has been termed cardiac cachexia. Hippocrates was perhaps the first to record this association between dropsy...