Dopamine differentially regulates dynorphin, substance P, and enkephalin expression in striatal neurons: in situ hybridization histochemical analysis.

Dopamine regulation of the levels of dynorphin, enkephalin, and substance P messenger RNAs in rat striatal neurons was analyzed with in situ hybridization histochemistry (ISHH). Relative levels of peptide mRNA expression in the patch and matrix compartments of the dorsolateral striatum were compared among control rats, rats treated for 10 d with apomorphine, rats with unilateral 6-hydroxydopamine (6-OHDA) lesions of the nigrostriatal dopaminergic system, and rats with nigrostriatal dopaminergic lesions followed 2 weeks later by 10 d of apomorphine treatment. Image analysis of ISHH labeling demonstrated that the number of neurons expressing each peptide mRNA remained constant, whereas the relative level of peptide mRNA per neuron changed significantly, depending on the experimental treatment. Dynorphin mRNA expression increased following chronic apomorphine treatment: striatal patch neurons increased to an average of 100% above control values, whereas striatal matrix neurons showed only a 25% increase. Dynorphin mRNA expression decreased following 6-OHDA lesions: patch neurons showed an average 75% reduction in expression, whereas matrix neurons showed no significant change. In animals with 6-OHDA lesions followed by apomorphine treatment, both patch and matrix neurons showed an average increase in dynorphin expression of 300% above control levels. Changes in dynorphin mRNA levels with these treatments were matched by qualitative changes in dynorphin immunoreactivity both in the striatum and in striatonigral terminals in the substantia nigra. Neither substance P nor enkephalin mRNA levels showed a significant difference between the striatal patch and matrix compartments in any experimental condition (in the dorsolateral striatum). Substance P mRNA expression was increased an average of 50% after 10 d of apomorphine treatment and showed an average decrease of 75% following 6-OHDA lesions of the mesostriatal system. There was no significant change in the expression of substance P mRNA in striatal neurons compared to control values in rats with combined 6-OHDA lesion and apomorphine treatment. Enkephalin mRNA expression was not significantly altered by chronic apomorphine treatment but showed an average increase per cell of some 130% above control levels following 6-OHDA-induced lesions of the mesostriatal system. In animals with a 6-OHDA lesion and apomorphine treatment, enkephalin mRNA was also elevated but not significantly above the levels produced by the lesions alone. These data show that the expression of dynorphin, enkephalin, and substance P is differentially regulated by the mesostriatal dopaminergic system and, further, suggests that the mechanisms by which this regulation occurs may be different for the 3 peptide families.     

Double-blind, placebo-controlled comparison of clonazepam and alprazolam for panic disorder

To test the reported antipanic efficacy of clonazepam, the authors randomized 72 subjects with panic disorder to 6 weeks of treatment with either alprazolam, clonazepam, or placebo. Endpoint analysis demonstrated a significant beneficial effect of both active treatments, but not placebo treatment, on the frequency of panic attacks, overall phobia ratings, and the extent of disability. Comparison of the two active treatments revealed no significant differences and no consistent tendency for one agent to be favored over another, although power to detect small differences was limited. Sedation and ataxia were the most common side effects reported, but these effects were mild and transient and did not interfere with treatment outcome. The results of this double-blind, placebo-controlled trial are consistent with previous reports of clonazepam's antipanic efficacy.     

Medical and financial implications of discontinuing a statewide free insulin program involving 3,720 people

In 1981 a statewide program supplying free insulin to 3,720 patients of state health clinics was discontinued. We attempted to assess whether this action had an adverse effect medically and financially on those concerned. A computer randomized sample of 351 patients (9%) was studied by personal interview and questionnaire. Information obtained focused on certain events that occurred 18 months before and after the program ceased. Measurements used to determine medical impact were number of hospitalizations, emergency room and physician visits, changes in weight and glucose levels, and episodes of ketoacidosis. Financial impact was measured by cost of hospitalization and physician visits. Our results revealed no significant changes in any of the medical parameters studied except for fasting serum glucose levels above 300 mg/dl, which occurred less frequently after the free insulin program was discontinued. There were fewer hospitalizations, more visits to physicians, and no change in number of emergency room visits after discontinuance of the free program. The overall cost saving was estimated to be +883,558 for the 18-month study period, in addition to the +550,000 the plan had been costing the state.     

Concurrent review of the duration of antimicrobial prophylaxis in surgery.

The administration of prophylactic antibiotics in surgery is appropriate for many patients. Data have shown extending the duration of prophylaxis beyond 48 hours does not lower the rate of postoperative-infection. The purpose of this project was to concurrently assess the duration of prophylactic antibiotic use. A total of 95 patients were monitored over 3 weeks. Eighty patients (84.2%) received antimicrobial therapy. In 23 of these patients (28.75%) the duration of antibiotic administration was longer than 2 days without clinical or microbiological evidence of infection. In 5 other patients only postoperative antibiotics were prescribed. The cost difference between the actual duration of antibiotic administration and 2 days of the same regimen was +1,364.58. Extrapolating for one year, it can be estimated that antibiotic costs could be reduced about +23,600. Pharmacists can focus on the duration of antibiotic prophylaxis as a cost containment measure.     

Uptake of iodine-123 MIBG by pheochromocytomas, paragangliomas, and neuroblastomas: a histopathological comparison

The percentage uptake of [123I]metaiodobenzylguanidine (MIBG) by tumors of the paraganglion system is compared with the number of neurosecretory granules (assessed by both light and electron microscopy) in the subsequently resected tumors in six patients. Iodine-123 MIBG was injected intravenously; the tumor uptake of [123I]MIBG varied between 0.001% and 0.14% of the injected dose per gram of tumor tissue at 22 hr. The number of neurosecretory granules in tissue sections was scored on a scale of I-III. A direct proportional correlation was found between the percentage uptake of [123I]MIBG by the tumor and the number of neurosecretory granules in the tissue sections but not with plasma or urinary catecholamines. This technique for imaging reflects the storage status of the tumor better than plasma and urinary catecholamine measurements.     

A HIGH FREQUENCY OF INHERITED DEFICIENCY OF COMPLEMENT COMPONENT C4 IN DARWIN ABORIGINES

Abstract A high frequency of serum complement component C4A deficiency may explain the higher prevalence and greater severity of systemic lupus erythematosus reported in Australian Aborigines. Inherited deficiencies of serum complement components C4A, C4B, and C2 were examined in two Australian Aboriginal populations from Darwin and Alice Springs and compared with the prevalence of complement deficiencies in white Australian blood donors. The frequency of C4A deficiency alleles was 29% in Darwin Aborigines compared with 12% in Alice Springs and 17% in Canberra blood donors. Partial C4B deficiency was also higher in Darwin Aborigines than in the other populations. Inherited deficiency of serum complement component C2 was not observed.