Protease and plasminogen activator activity in human bladder carcinoma

The ability of human bladder tissue extracts to cleave 14C-labelled globin in the absence and in the presence of plasminogen was assayed to quantify non-specific protease and plasminogen activator (PA) activity, respectively. In normal human bladder tissue the non-specific protease activity was approximately 2-fold higher than in tissue samples obtained from transitional cell carcinoma of the bladder (TCC). In contrast, PA activity was almost 4-fold higher in TCC than in normal transition cell epithelium. Acid-treated urine from 19 patients with TCC of the bladder exhibited significantly higher levels of plasminogen activator activity than similarly treated urine from controls. These results indicate that malignant transformation of the bladder epithelial tissue results in elevated levels of PA in the tissue and in urine. Further studies are needed to assess the potential of PA determination in the management of bladder cancer patients.     

Stress protection by external fixation of the rabbit tibia

Osteopenia of the tibia and femur caused by an external fixator in the tibia was studied in 14 rabbits. Eight rabbits were treated with a complete unilateral external fixator in one tibia, whereas the other tibia served as control. The other 6 animals had one leg operated on with inserting of all the pins but without the frame. This technique was chosen to compare osteopenia caused by stress protection and the effect of the pins. After 6 weeks, we found a 7 percent reduction in the bone mineral content in the tibial diaphyseal segment between the pins of the external fixator and no bone loss in the tibia that were operated on with only pins. In the femurs, there was a smaller decrease in the bone mineral content: respectively 3.2 percent (complete frame) and 2.9 percent (only pins). On all the operated on tibiae, there was an increase in the bone mineral content around the pins both proximally and distally.     

Use of metoclopramide, domperidone, and cisapride in the management of diabetic gastroparesis

The pathophysiology, diagnosis, and treatment of diabetic gastroparesis are reviewed, and the mechanisms of action, pharmacokinetics, clinical efficacy, adverse effects, and dosage of metoclopramide, domperidone, and cisapride are described. Diabetic gastroparesis is a state of delayed gastric emptying that reportedly affects 20-30% of diabetic patients. Symptoms include nausea, early satiety, postprandial bloating and fullness, and vomiting. Diabetic gastroparesis has been managed most successfully with drugs that stimulate gastric emptying. Of the three agents studied--metoclopramide, domperidone, and cisapride--only metoclopramide is commercially available in the United States. The clinical efficacy of metoclopramide, domperidone, and cisapride has been well documented in several placebo-controlled trials. Metoclopramide effectively decreases mean gastric emptying time, although tolerance to this stimulation of gastric emptying may develop with long-term therapy. However, symptomatic relief persists with long-term therapy because of metoclopramide's antiemetic properties. Domperidone, which has also been shown to stimulate gastric motility and to possess antiemetic properties, improves symptoms in patients suffering from diabetic gastroparesis. Cisapride appears to have continued beneficial effects on gastric motility with long-term therapy. All three agents have favorable adverse-effect profiles. Although metoclopramide is currently the first-line agent for the management of gastroparesis, domperidone and cisapride both possess properties that may make them useful alternatives in patients who are unresponsive to or cannot tolerate metoclopramide therapy.     

INTERACTIONS BETWEEN THE CIRCULATORY EFFECTS OF CENTRAL HYPOVOLAEMIA AND ARTERIAL HYPOXIA IN CONSCIOUS RABBITS

1. Eight conscious rabbits were repeatedly subjected to progressive reduction in central blood volume by gradually inflating a thoracic inferior vena caval-cuff so cardiac index (CI) fell at a constant 8.5% of baseline/min. 2. Caval-cuff inflations were performed after 10 min exposure to 100, 21, 12–14 and 8–10% O₂, with and without the addition of 3–4% CO₂, in randomized order. 3. The haemodynamic response to progressive reduction in central blood volume was biphasic. In Phase I, systemic vascular conductance index (SVCI) fell linearly, supporting mean arterial pressure (MAP). When CI had fallen to a critical level, Phase II occurred in which SVCI rose abruptly, MAP plummeted and respiratory drive progressively increased. 4. During Phase I, there were independent linear relationships between Pao₂ (but not Pao₂) and the rates at which SVCI and MAP changed during the progressive fall of CI. The higher the level of Pao₂, the greater was the rate of fall of SVCI and the less the rate of fall of MAP. 5. There was an inverted U-shaped effect of Pao₂, on the level of CI at which Phase II occurred: (a) during hyperoxia (100% O₂), Phase II occurred later than during normoxia (21% O₂); and (b) across the normoxic and hypoxic gas mixtures (21–8% O₂, with and without added CO₂), there was an independent linear relationship between Pao₂ (but not Pao₂ or Pao₂×Pao₂) and the level of CI at which Phase II occurred. That is, the lower the level of Pao₂, the later was the onset of Phase II. This interaction is best explained by an increased level of central sympathetic vasoconstrictor drive during hypoxia.     

Single-dose oral omeprazole for reduction of gastric residual acidity in adults for outpatient surgery

Omeprazole is a substituted benzimidazole that causes dose-dependent intracellular inhibition of gastric acid secretion in humans. This double-blind study examined the effect of omeprazole in decreasing gastric acidity and gastric residual volume in outpatient adults. Unpremedicated outpatients, ASA I-III, 18 years or older (n = 17), were randomly assigned to receive omeprazole 80 mg, or placebo by mouth the night before scheduled elective outpatient surgery. The patients were fasted for 8 h prior to surgery. After the patient was anesthetized, an orogastric tube was inserted with proper placement verified by auscultation for gastric sounds. Gastric residual contents were withdrawn into a Luken's trap, and pH was then determined and gastric volume indexed to weight (ml.kg-1). Data were analyzed by a t-test, with P less than 0.05 considered statistically significant. Patient characteristics of both groups were similar. There was a statistically significant difference between the two groups for pH (P = 0.02), but not between the two groups for gastric volume indexed to weight (P = 0.07).