An overview of pulmonary fungal infections

An overview of important pulmonary mycoses is presented. Four endemic mycoses occur in restricted geographic areas: histoplasmosis, blastomycosis, coccidioidomycosis, and paracoccidioidomycosis. Three opportunistic mycoses have causative agents that are ubiquitous in nature but cause infection only in compromised hosts: aspergillosis, mucormycosis, and candidiasis. Cryptococcosis is acquired by inhalation but usually presents as a chronic meningitis. Pulmonary sporotrichosis is rare; the usual subcutaneous form of the disease is acquired by inoculation. The clinical features of these infections are discussed, with special emphasis on recent advances in diagnosis and treatment.     

Non-isotopic hybridization assays for bacterial DNA samples

The background problem associated with the use of streptavidin in detecting biotin-labelled probes hybridized to DNA in crude bacterial extracts has been investigated. We have found that streptavidin binds specifically to a limited number of polypeptides which are difficult to remove by rapid extraction processes. Altering the hybridization and detection protocols results in a marked but not complete reduction of non-specific background in streptavidin-biotin assays. Complete elimination of non-specific background was achieved only when streptavidin was replaced with antibodies for the detection of biotinylated or sulphone-modified probes. The antibody-sulphone and streptavidin-biotin dot blot assays described here require 4.5-5 hours to perform and can detect DNA sequences in samples extracted from 2 x 10(7) cells or fewer.     

The oxidation of body fuel stores in cancer patients.

In an attempt to define the mechanism of weight loss in cancer patients, fat and carbohydrate oxidation rates were calculated in 93 patients. Seventy patients with colorectal or gastric cancer were compared with a control group of 23 patients with nonmalignant illness. Twenty-seven patients with cancer and 13 control patients had lost more than 10% of their pre-illness body weight. Fat and carbohydrate oxidation rates were derived from measurements of oxygen consumption, carbon dioxide production, and urinary nitrogen excretion. Patients with cancer had significantly higher fat oxidation rates (p less than 0.01) and significantly lower carbohydrate oxidation rates (p less than 0.05) when compared with controls. Weight-losing cancer patients had significantly higher fat oxidation rates when compared with weight-stable cancer patients (p less than 0.02), weight-stable controls (p less than 0.01), and weight-losing controls (p less than 0.02). Cancer patients with liver metastases (N = 14) had significantly higher fat oxidation rates (p less than 0.01) and significantly lower carbohydrate oxidation rates (p less than 0.01) compared with cancer patients who had localized disease. There were no significant differences among the groups with respect to resting energy expenditure when expressed as kilocalorie per kilogram lean body mass per day. The presence of cancer appears to be associated with abnormal fat and carbohydrate metabolism. The increased rate of fat oxidation seen in patients with cancer, especially those with weight loss or liver metastases, may be a significant factor in the development of cancer cachexia.     

Ischemia-reperfusion-induced muscle damage: Protective effect of corticosteroids and antioxidants in rabbits

We examined the potential protective effect of pretreatment with corticosteroids or antioxidants (ascorbic acid or allopurinol) in rabbits with reper-fusion-induced damage to skeletal muscle after ischemia.

4 hours of limb ischemia induced by a pneumatic tourniquet, followed by reperfusion for 1 hour, caused a considerable amount of ultrastructural damage to the anterior tibialis muscles accompanied by a rise in circulating creatine kinase activity. Pretreatment of animals with depomedrone by a single 8 mg bolus injection led to a preservation of the anterior tibialis structure on both light and electron microscopy. High-dose continuous intravenous infusion with ascorbic acid (80 mg/hr) throughout the period of ischemia and reperfusion also preserved skeletal muscle structure, although allopurinol in various doses had no protective effect.

These data are fully compatible with a mechanism of ischemia/reperfusion-induced injury to skeletal muscle, involving generation of oxygen radicals and neutrophil sequestration and activation. They also indicate that damage to human skeletal muscle caused by prolonged use of a tourniquet is likely to be reduced by simple pharmacological interventions.     

Growth hormone deficiency and hypogonadism in a patient with multiple sclerosis

We describe the case of a 30-year-old female patient with a 7-year hisory of multiple sclerosis, who presented with an 18-month history of secondary amenorrhoea and vague symptoms which included poor sleep and impaired concentration. Endocrine investigations revealed hypogonadotrophic hypogonadism and GH deficiency, a probable consequence of a hypothalamic plaque. This is the first report of hypogonadotrophic hypogonadism and GH deficiency occuring in conjunction with multiple sclerosis. As such, it should raise suspicion of endocrine dysfunction occurring in a condition with such a vast spectrum of disability as multiple sclerosis.     

The effect of dialysate on peritoneal phagocyte oxidative metabolism

The respiratory and oxidative responses of human peritoneal polymorphonuclear leukocytes (PMN) and peritoneal macrophages (PM phi) following exposure to unused continuous ambulatory peritoneal dialysis fluid (CAPD) and early dwell effluent were studied using an open oxygen (O2) electrode system and by measurement of oxygen radical-derived luminol-dependent chemiluminescence. Both cell types responded to stimulation by increasing O2 consumption and by generating chemiluminescence even at external O2 concentrations below 50 microM O2. Oxygen concentrations in the dialysate, as measured by blood gas analysis, were never lower than 118 +/- 8.3 microM O2 even during active peritonitis. Thus oxygen availability does not appear to be rate limiting for phagocyte oxidative metabolism in the peritoneal cavity. Preexposure of both inflammatory cell types to unused fluid or early dwell CAPD effluent significantly reduced both stimulated oxygen uptake and the subsequent ability of these cells to generate chemiluminescence without significantly affecting their viability. Further investigation of this down regulatory phenomenon using unused fluid and laboratory prepared dialysis fluid revealed that low pH (5.3) and high sodium lactate concentration in combination are directly responsible for the suppressive effect of unused fluid and early dwell effluent on cell function. These observations demonstrate that cellular host defense may be impaired early in the dialysis cycle as a result of lactate mediated "stunning" of resident phagocytes. The precise nature of the molecular species responsible for this suppressive effect remains to be identified.