Current physical health problems and their predictors among a community sample of crack-cocaine smokers in Ohio

The harmful effects of nonmedical cocaine use are well documented, but the overall health of people involved with crack is less well understood. This cross-sectional study describes the nature and extent of current health problems in a community sample of 430 crack smokers in Dayton, Ohio. Two-thirds of the sample reported one or more current physical health problems. The estimated annualized incidence of acute health problems was 152.6 conditions/100 persons/year. The estimated prevalence of chronic problems ranged from a low of 30.2 conditions/1000 persons for diabetes to a high of 223.2 conditions/1000 persons for anemias. Cardiovascular problems were common. Even though the results cannot prove a cause and effect relationship between crack use and health problems, they do suggest that crack users experienced higher than usual rates of problems, when compared with data from the National Health Interview Survey. The results of a cumulative logistic regression analysis suggest that men were significantly less likely, and older users more likely, to have health problems. Neither duration of crack use nor frequency of use of any drug predicted health problems. Incorporating assessments of physical problems as well as a mechanism for their treatment into the regimen of drug abuse treatment programs should be considered.     

Increased phosphorylation of skeletal muscle glycogen synthase at NH2-terminal sites during physiological hyperinsulinemia in type 2 diabetes

In type 2 diabetes, insulin activation of muscle glycogen synthase (GS) is impaired. This defect plays a major role for the development of insulin resistance and hyperglycemia. In animal muscle, insulin activates GS by reducing phosphorylation at both NH(2)- and COOH-terminal sites, but the mechanism involved in human muscle and the defect in type 2 diabetes remain unclear. We studied the effect of insulin at physiological concentrations on glucose metabolism, insulin signaling and phosphorylation of GS in skeletal muscle from type 2 diabetic and well-matched control subjects during euglycemic-hyperinsulinemic clamps. Analysis using phospho-specific antibodies revealed that insulin decreases phosphorylation of sites 3a + 3b in human muscle, and this was accompanied by activation of Akt and inhibition of glycogen synthase kinase-3alpha. In type 2 diabetic subjects these effects of insulin were fully intact. Despite that, insulin-mediated glucose disposal and storage were reduced and activation of GS was virtually absent in type 2 diabetic subjects. Insulin did not decrease phosphorylation of sites 2 + 2a in healthy human muscle, whereas in diabetic muscle insulin infusion in fact caused a marked increase in the phosphorylation of sites 2 + 2a. This phosphorylation abnormality likely caused the impaired GS activation and glucose storage, thereby contributing to skeletal muscle insulin resistance, and may therefore play a pathophysiological role in type 2 diabetes.     

Human small cell lung cancer NYH cells selected for resistance to the bisdioxopiperazine topoisomerase II catalytic inhibitor ICRF-187 demonstrate a functional R162Q mutation in the Walker A consensus ATP binding domain of the alpha isoform.

Bisdioxopiperazine drugs such as ICRF-187 are catalytic inhibitors of DNA topoisomerase II, with at least two effects on the enzyme: namely, locking it in a closed-clamp form and inhibiting its ATPase activity. This is in contrast to topoisomerase II poisons as etoposide and amsacrine (m-AMSA), which act by stabilizing enzyme-DNA-drug complexes at a stage in which the DNA gate strand is cleaved and the protein is covalently attached to DNA. Human small cell lung cancer NYH cells selected for resistance to ICRF-187 (NYH/187) showed a 25% increase in topoisomerase IIalpha level and no change in expression of the beta isoform. Sequencing of the entire topoisomerase IIalpha cDNA from NYH/187 cells demonstrated a homozygous G-->A point mutation at nucleotide 485, leading to a R162Q conversion in the Walker A consensus ATP binding site (residues 161-165 in the alpha isoform), this being the first drug-selected mutation described at this site. Western blotting after incubation with ICRF-187 showed no depletion of the alpha isoform in NYH/187 cells in contrast to wild-type (wt) cells, whereas equal depletion of the beta isoform was observed in the two sublines. Alkaline elution assay demonstrated a lack of inhibition of etoposide-induced DNA single-stranded breaks in NYH/187 cells, whereas this inhibition was readily apparent in NYH cells. Site-directed mutagenesis in human topoisomerase IIalpha introduced into a yeast Saccharomyces cerevisiae strain with a temperature-conditional yeast TOP2 mutant demonstrated that R162Q conferred resistance to the bisdioxopiperazines ICRF-187 and -193 but not to etoposide or m-AMSA. Both etoposide and m-AMSA induced more DNA cleavage with purified R162Q enzyme than with the wt. The R162Q enzyme has a 20-25% decreased catalytic capacity compared to the wt and was almost inactive at <0.25 mM ATP compared to the wt. Kinetoplast DNA decatenation by the R162Q enzyme at 1 mM ATP was not resistant to ICRF-187 compared to wt, whereas it was clearly less sensitive than wt to ICRF-187 at low ATP concentrations. This suggests that it is a shift in the equilibrium to an open-clamp state in the enzyme's catalytic cycle caused by a decreased ATP binding by the mutated enzyme that is responsible for bisdioxopiperazine resistance.     

"The nursing care case". Costs of nursing treatment

A calculation of the costs for nursing a patient with apallic syndrome in a hospital for chronically ill patients totalled 624.26 DM per day. The calculation was based upon the documented expenditure of material and therapeutic personal and the basic costs of the hospital. The patient was chosen as an example for patients needing constant and expensive care.     

The multifidus muscle in patients with lumbar disc herniation. A histochemical and morphometric analysis of intraoperative biopsies

Structural changes in the multifidus muscle were analyzed in 41 patients operated on for herniated intervertebral disc. Twelve cadavers served as controls. The two main findings follow: Both in the patients and in the controls the Type 2 muscle fibers were markedly and selectively smaller than the Type 1 fibers, which were of normal size for striated muscles, and the internal structure of Type 1 fibers showed so-called core-targetoid and/or moth-eaten change. Group atrophy or fiber-type grouping (indicators of denervation and reinnervation) were observed only in a few patients. The selective small size of the Type 2 fibers may indicate atrophy due to relative inactivity of the multifidus muscle both in the patients and in the controls, ie, it does not need to be related to the herniated disc. Definite proof for denervation of the multifidus muscle was not observed, but neither the possibility be excluded. The cause of the core-targetoid and/or moth-eaten changes cannot yet be determined with certainty, because these changes are not specific for any single entity but may be due, for example, to denervation, ischemia, or altered use of the muscles because of pain. In any case, because the changes were significantly more common in the patients than in the controls, they signal for a pathologic condition, the character of which remains to be elucidated.     

The effect of physical work on the mucosal blood flow and gas exchange in the human maxillary sinus

The paranasal sinuses are lined with respiratory mucosa of principally the same structure as in the nasal mucosa but somewhat thinner. This mucosa has a rich blood flow and advanced system of blood vessels regulated mostly by the autonomous nervous system but also by other factors as acid/base balance and endocrine activity. The thickness of the nasal mucosa regulates the nasal breathing resistance and varies with among other factors, body activity. In this investigation we have studied the effect of physical work on the human maxillary sinus mucosa. The investigation shows that, as in the nose, the blood flow and the pulse amplitude are considerably reduced during physical work, in situations of heavy work falling to about half of the normal level, and probably result in the redistribution of blood from the respiratory mucosa. The gas exchange in the paranasal sinus is reduced only to a small extent, the reduction being too small to change the antral gas composition towards pathological conditions.     

Effects of family status on the geriatric hospital or geriatric nursing homes

The different personal status of patients at home and in the geriatric hospital are presented, especially that of the very old, including those over 100 years. The duration of stay in the hospital is affected by the family situation. Family conflicts and familial overprotection influenced the cave facilities. Gender-based considerations are discussed.     

Chemiluminescence, formation of thermostable E-rosettes and DNA synthesis of human mononuclear cells induced by various lectins

Various plant lectins differentiate in their ability to induce early (chemiluminescence and thermostable rosette formation) and later (DNA synthesis) activation events of human mononuclear cells. Both phytohaemagglutinin and concanavalin A induced a cell activation detectable by the three investigated parameters. Wheat germ agglutinin was characterized as an efficient stimulator in both assays of early events whereas the induction of DNA synthesis measured by [3H]-thymidine incorporation was low. In contrast, pokeweek mitogen did evoke only a weak chemiluminescence signal, but induced a small number of thermostable rosettes and a high [3H]-thymidine incorporation. The results obtained from experiments with mononuclear cells of twelve healthy donors did not show a firm correlation between the investigated three parameters of cell activation.