The effects of three nebulized osmotic agents in the dry larynx.

PURPOSE: This investigation examined the effects of nebulized hypertonic saline, isotonic saline (IS), and sterile (hypotonic) water on phonation threshold pressure (PTP) and self-perceived phonatory effort (PPE) following a surface laryngeal dehydration challenge. METHOD: In a double-blind, randomized experimental trial, 60 vocally healthy women (n = 15 per group) underwent a laryngeal desiccation challenge involving oral breathing for 15 min using medical-grade dry air (RH<1%). Three of the four groups then received nebulized isotonic saline (0.9% NaCl), hypertonic saline (7% NaCl), or sterile (hypotonic) water, respectively; the 4th group served as a nontreatment control. PTP and PPE were estimated for high-pitched productions at baseline, immediately postdesiccation, and at 5, 20, 35, and 50 min postnebulization. RESULTS: PTP increased significantly for all groups following the desiccation challenge. PTP values were, on average, 0.5 cm H(2)O greater immediately postdesiccation versus baseline. In contrast, PTP values did not change significantly following the administration of nebulized treatments, although a temporary trend toward a reduction in PTP was observed for the IS group. Unexpectedly, PPE ratings decreased significantly after the desiccation challenge. In general, PPE ratings were poorly correlated with PTP measures. CONCLUSION: A laryngeal desiccation challenge (i.e., temporary exposure to extremely low relative humidity while breathing transorally) significantly increased PTP. Although interesting trends emerged, none of the nebulized treatments significantly enhanced recovery from the negative effects of desiccation on PTP. In light of very low correlations between PTP and PPE, serious questions are raised regarding presumed associations between these measures.     

Fructose metabolism in the adult mouse optic nerve, a central white matter tract.

Our recent report that fructose supported the metabolism of some, but not all axons, in the adult mouse optic nerve prompted us to investigate in detail fructose metabolism in this tissue, a typical central white matter tract, as these data imply efficient fructose metabolism in the central nervous system (CNS). In artificial cerebrospinal fluid containing 10 mmol/L glucose or 20 mmol/L fructose, the stimulus-evoked compound action potential (CAP) recorded from the optic nerve consisted of three stable peaks. Replacing 10 mmol/L glucose with 10 mmol/L fructose, however, caused delayed loss of the 1st CAP peak (the 2nd and 3rd CAP peaks were unaffected). Glycogen-derived metabolic substrate(s) temporarily sustained the 1st CAP peak in 10 mmol/L fructose, as depletion of tissue glycogen by a prior period of aglycaemia or high-frequency CAP discharge rendered fructose incapable of supporting the 1st CAP peak. Enzyme assays showed the presence of both hexokinase and fructokinase (both of which can phosphorylate fructose) in the optic nerve. In contrast, only hexokinase was expressed in cerebral cortex. Hexokinase in optic nerve had low affinity and low capacity with fructose as substrate, whereas fructokinase displayed high affinity and high capacity for fructose. These findings suggest an explanation for the curious fact that the fast conducting axons comprising the 1st peak of the CAP are not supported in 10 mmol/L fructose medium; these axons probably do not express fructokinase, a requirement for efficient fructose metabolism.     

Premalignant conditions and markers of elevated risk in the breast and their management

Most epithelial hyperplasias of the human breast indicate an increased likelihood of carcinoma development, and the majority are best understood as markers or indicators of higher risk. Prospective studies of women with hyperplasia biopsied in the premammographic era indicate that about 70 per cent of women had mild or no hyperplastic epithelial alterations and experienced no increase in the risk of subsequent carcinoma. About 25 per cent of women had well-developed hyperplastic changes associated with a risk 1.5 to 2.0 times that of the general population controlled for age and length of follow-up. Somewhat fewer than 5 per cent of women had specific patterns of atypical hyperplasia that approached the patterns of carcinoma in situ. The women with atypical hyperplasia had a risk of cancer four to five times that of the general population, or about half the risk associated with microscopic carcinoma in situ. Only ductal carcinoma in situ should be considered without question to be an intrinsically precancerous lesion because of its regular association with recurrence at the site of its initial diagnosis. No follow-up studies of comparable type involving women with mammographically detected lesions are as yet available. However, it is clear that the incidence of atypical hyperplasia is higher in mammographically directed biopsies. The principal therapeutic implication of these premalignant lesions is a need for intensified breast cancer surveillance and screening for these patients.     

1 alpha,25-dihydroxyvitamin D3-induced increments in hepatocyte cytosolic calcium and lysophosphatidylinositol: inhibition by pertussis toxin and 1 beta,25-dihydroxyvitamin D3

1 alpha,25-Dihydroxyvitamin D3 rapidly increases cytosolic calcium and alters membrane phospholipid metabolism in hepatocytes. To define the causal relationship between these events, we examined the effects of 1 alpha,25-dihydroxyvitamin D3 on 32P-labeled lysophosphatidylinositol levels and cytosolic calcium as affected by pertussis toxin and 1 beta,25-dihydroxyvitamin D3, the biologically inactive analog. 32P-labeled lysophosphatidylinositol was determined by two-dimensional thin-layer chromatography. Cytosolic calcium was measured in cells loaded with quin-2AM. Within 5 min, 1 alpha,25-dihydroxyvitamin D3 increased hepatocyte cytosolic calcium by 31% (p less than 0.05) and 32P-labeled lysophosphatidylinositol by 38% (p less than 0.05). Pertussis toxin inhibited the hormone-induced rise in cytosolic calcium but not the increase in 32P-labeled lysophosphatidylinositol. Exposure to exogenous lysophosphatidylinositol for 5 min increased cytosolic calcium by 40% (p less than 0.05), an effect that was also inhibited by pertussis toxin. 1 beta,25-Dihydroxyvitamin D3 had no effect on either hepatocyte cytosolic calcium or 32P-labeled lysophosphatidylinositol but prevented the 1 alpha,25-dihydroxyvitamin D3-induced increments. The results suggest that a G protein sensitive to pertussis toxin is required for the transduction of the lysophosphatidylinositol signal but not the generation of the signal. The ability of 1 beta,25-dihydroxyvitamin D3 to inhibit the 1 alpha,25-dihydroxyvitamin D3-induced changes in phospholipids suggests that the epimer may compete with 1 alpha,25-dihydroxyvitamin D3 for an initiating receptor.     

Protection against 7,12-dimethylbenzanthracene-induced tumour initiation by protein A in mouse skin.

Protein A is an immunostimulating glycoprotein obtained from Staphylococcus aureus Cowan I. Its antitumour activity is proven in various tumour models. Its ability to provide protection against tumour initiation by the chemical carcinogen 7,12-dimethylbenzanthracene (DMBA) has been investigated in the present study using a mouse skin model of two-stage carcinogenesis. Protein A was administered intraperitoneally (1 microgram/animal 20 g body wt.) twice a week for 2 weeks, prior to initiation by DMBA. The promotion was performed by twice weekly applications of 12-O-tetradecanoyl phorbol-13-acetate (TPA) (3 or 5 micrograms/animal in 100 microliters acetone). Protein A provided significant protection to animals from DMBA-induced tumour initiation as was observed by the decrease in cumulative number of tumours, percent of animals developing tumours, number of tumours per animal and rate of tumour growth. Our data indicate that protein A has anticarcinogenic properties.     

Complications of surgical endoscopy

Background: This study examines the notion that gastrointestinal endoscopy performed by supervised surgical residents is safe. Methods: We reviewed all gastrointestinal endoscopic procedures performed by surgical residents with faculty supervision for complications and deaths occurring up to 30 days following the procedures. Results: The overall complication rate for 9,201 upper and lower endoscopy procedures was 1.4% and 0.42%, respectively. Overall mortality rate was 0.76% for upper endoscopy and 0.6% for lower endoscopy. No mortality was a direct result of a procedure-related complication. Intestinal perforation, drug overdose, bleeding, and aspiration were the most common procedure-related complications. Each resident completed an average of 75 upper endoscopies and 79 lower endoscopies during their training period. Conclusions: Gastrointestinal endoscopy can be performed safely by surgical residents with appropriate supervision. The higher morbidity and mortality of upper endoscopy are most likely related to the underlying disease rather than the procedure. Awareness of common complications and application of appropriate precautions and instruction are critical for minimizing complications. Received 25 March 1996/Accepted: 24 April 1996     

Malnutrition and subsequent ischemic heart disease in former prisoners of war of world war II and the Korean conflict

The harsh treatment of former prisoners of war (POWs) of World War II and the Korean conflict resulted in severe malnutrition. Although rarely linked to specific long-term medical problems, a specific marker of malnutrition, self-reported lower limb edema (presumably due to a vitamin B deficiency) was associated with a three-fold increase in subsequent death attributed to ischemic heart disease (IHD) during the follow-up period from 1967 through 1975. Although there is at present no medical basis for linking edema, which is perhaps a marker for some unmeasured risk factor, to subsequent IHD, this finding may nonetheless have medical implications for the group of former POWs and other populations with severe dietary deficiency. It also suggests there may be a need to reexamine currently held theories on malnutrition and subsequent chronic disease.