The immunomodulating action of cyclosporin A in vitro and in vivo on the lymphocytes of patients with alveolitis

The effect of various concentrations of ofloxacin, ciprofloxacin and lomefloxacin on the morphokinetic parameters of the cellular elements of the lung tissue of intact animals (mice, guinea pigs and dogs) was studied under the conditions of the tissue culture. It was shown that in a concentration of 100 micrograms/ml and the exposure time of 24 hours the drugs had no effect on the mobility and structure of the lung tissue cellular elements. When the drugs were used in a concentration of 100 micrograms/ml the mobility rate of the lymphocytes and macrophages proved to by markedly retarded by the end of the 24th hour. In a concentration of 1000 micrograms/ml the drugs killed the cell culture. There were detected no specific differences in the effect of the fluoroquinolones on the cellular elements of the lung tissue of the intact animals.     

Opportunities for promoting palliative medicine in cancer research

OBJECTIVE: To study the effect of cisplatin on plasma concentrations and urinary excretion of carnitine in ten patients with different malignancies treated with chemotherapy. METHODS: Carnitine concentrations were determined using a radioenzymatic assay and other metabolites by routine methods of clinical chemistry. Renal clearances were calculated by dividing urinary excretions by the respective plasma concentrations. RESULTS: Before treatment, all patients had a normal plasma carnitine concentration. During treatment with cisplatin, the plasma total carnitine concentration increased by approximately 30% and normalized 7 days after stopping therapy. Urinary excretion of total carnitine increased by a factor of 10 during cisplatin administration and also normalized 7 days after cessation of chemotherapy. This increase was due to excretion of both free carnitine and acylcarnitine and averaged approximately 1 mmol carnitine per day. Similarly, urinary clearance of total carnitine was increased during therapy with cisplatin by a factor of approximately 8 and returned to normal 7 days after chemotherapy. In comparison, patients with similar malignancies treated with radiotherapy showed no significant increase in renal carnitine excretion. Similar to urinary excretion of carnitine, excretion of glucose and phosphate, two metabolites also reabsorbed by the proximal tubule of the nephron, was increased during therapy with cisplatin. There was a strong linear correlation between urinary excretion of free carnitine and acylcarnitines. CONCLUSIONS: Treatment with cisplatin is associated with a tenfold increase in renal carnitine excretion, most likely due to inhibition of carnitine reabsorption by the proximal tubule of the nephron. Well-nourished patients support this loss of carnitine even after repeated cycles of chemotherapy without developing hypocarnitinaemia. However, cachectic patients with decreased dietary carnitine uptake may develop carnitine deficiency when treated repeatedly with chemotherapies including cisplatin.     

Hearing loss in community-dwelling older persons: national prevalence data and identification using simple questions

OBJECTIVE: To estimate the prevalence of hearing loss among community-dwelling older persons according to clinical criteria and to develop a brief self-report screening instrument to detect hearing loss. DESIGN: Survey. SETTING: National probability sample of noninstitutionalized older persons. PARTICIPANTS: A total of 2506 persons aged 55 to 74 who participated in the National Health and Nutrition Examination Survey. MAIN OUTCOME MEASURES: Hearing loss as defined by Ventry and Weinstein (VW) criteria and by the High Frequency Pure-Tone Average (HFPTA) scale. RESULTS: Hearing loss by VW criteria was present in 14.2% and by HFPTA criteria in 35.1% of those surveyed. The prevalence increased with advancing age and was higher among men and those with less education. A logistic regression model identified six independent factors for hearing loss by VW criteria: age > or = 70 years (adjusted odds-ratio (AOR) 2.7, 95% confidence interval (95% CI) 1.6, 4.4), male gender (AOR 3.0, 95% CI 1.9, 4.8), < or = 12th grade education (AOR 3.8, 95% CI 1.8, 7.7), having seen a doctor for deafness or hearing loss (AOR 8.9, 95% CI 5.3, 14.9), unable to hear a whisper across a room (AOR 3.2, 95% CI 2.0, 5.1), and unable to hear a normal voice across a room (AOR 6.2, 95% CI 2.6, 14.9). A clinical scale based on the logistic model had 80% sensitivity and 80% specificity in predicting hearing loss using VW criteria and 59% sensitivity and 88% specificity in predicting hearing loss using HFPTA criteria. CONCLUSIONS: Hearing loss, as defined by two clinical criteria, is common and can be screened for accurately using simple questions that assess sociodemographic and hearing-related characteristics.     

Neuropsychological outcomes in randomized controlled trials of antiepileptic drugs: a systematic review of methodology and reporting standards

PURPOSE: To systematically review the methodology and use of neuropsychological tests in randomized controlled trials (RCTs) of antiepileptic drugs (AEDs) in patients with epilepsy. METHODS: Trial reports were found by searching Medline 1966-1996 and searching through journals by hand. Inclusion and exclusion criteria were applied, and methodological and neuropsychological test data was extracted by using a proforma. RESULTS: 43 reports met our inclusion criteria, representing 40 RCTs. as three RCTs had generated two reports. Twenty-two were actively controlled, and 18 were placebo-controlled studies. Reporting of basic methods such as randomization method was poor. There has been no uniform approach to the use of neuropsychological tests, and a total of 87 has been used. The Stroop Colour Word Test and the Finger Tapping Test were most commonly used, at 13 times each, but were not used or reported in a uniform manner. CONCLUSIONS: Poor reporting of methods and the use of a plethora of neuropsychological tests create great difficulties for anyone wishing to make sense of currently available data. If we are better to understand the neuropsychological effects of AEDs, a more rational approach is needed, for which recommendations are made.     

Assessing deleterious ecosystem-level effects of environmental pollutants as a means of avoiding evolutionary consequences

Recent interest has been expressed in the possible need to develop ways to detect and quantify pollutants that affect evolution. Although environmental pollutants clearly can affect evolutionary processes, the evolutionary changes are a response to ecosystem-level toxicity elicited by the pollutant, rather than a direct effect of the pollutant on evolution. Accordingly, emphasis needs to be placed on assessing the adverse effects of environmental pollutants on ecosystem structure and function in order to avoid subsequent evolutionary consequences.     

ANP and bradycardic reflexes in hypertensive rats: influence of cardiac hypertrophy

OBJECTIVES: Beta2-integrin (CD11b/CD18) expression, an indicator of neutrophil activation, has been associated with the development of acute respiratory distress syndrome. Leumedins act directly on leukocytes to inhibit the up-regulated expression of beta2-integrins involved in leukocyte adhesion. We examined the effect of such a new anti-inflammatory agent, NPC 15669 (N-[9H-(2,7-dimethylfluorenyl-9-methoxy)-carbonyl]-L-leucine), on neutrophil-mediated acute lung injury in an animal model. DESIGN: Prospective, randomized, blinded, controlled animal study. SETTING: An animal laboratory in a university setting. SUBJECTS: Adult New Zealand rabbits. INTERVENTIONS: After repeated lung lavages with normal saline to induce acute lung injury, anesthetized rabbits were randomly assigned to one of two groups (n = 6 per group): a) treatment group (pretreated with NPC 15669 [10 mg/kg i.v. bolus] 30 mins before lavage, followed by a continuous infusion [5 mg/kg/hr] for the duration [4 hrs] of the experiment); or b) control group (pretreatment and continuous infusion with placebo). All animals were mechanically ventilated with identical pressure settings over 4 hrs and were killed at the end of the experiment. MEASUREMENTS AND MAIN RESULTS: PaO2, PaCO2, and tidal volumes were repeatedly measured and airway pressure settings were noted every 30 mins. At the end of the experiment, lungs were taken out for measurements of the myeloperoxidase content, for conventional histology (hematoxylin and eosin staining), and for intracellular adhesion molecule-1 immunohistostaining. Pretreatment with NPC 15669 profoundly improved oxygenation from a PaO2 of 52 +/- 5 torr (6.9 +/- 0.7 kPa) to 250 +/- 161 torr (33.3 +/- 21.5 kPa) within 60 mins after lung lavage (p < .05). Oxygenation continued to improve throughout the study, reaching a maximal PaO2 value of 395 +/- 98 torr (52.7 +/- 13.1 kPa) at 4 hrs. In the control group, oxygenation remained poor throughout the observation period. PaO2 values differed significantly (51 +/- 20 torr [6.8 +/- 2.7 kPa] vs. 306 +/- 126 torr [40.8 +/- 16.8 kPa], p < .005) at 90 mins and at all subsequent measurements from those values in the NPC 15669 group. Dynamic lung compliance improved significantly 60 to 90 mins after repeated lung lavage. Histology demonstrated markedly less lung damage (hyaline membrane formation and leukocyte infiltration) in treated animals (p < .05) than in controls. CONCLUSIONS: NPC 15669 seems to block inflammatory reactions by inhibiting the sequestration of neutrophils in acute, ventilator-associated lung injury. As a result, gas exchange and total lung compliance improve. Application of this and similar compounds affecting neutrophil adhesion warrants further investigation as a treatment modality for acute lung injury.     

Protein density and its influence on metabolite concentration and nitrogen retention by Holstein cows in late gestation

Multiparous Holstein cows in late gestation were used in a completely randomized design to test the effects of prepartum protein supply on prepartum N balance, blood metabolite and hormone concentrations, and postpartum intake and milk production. Cows were assigned to one of three isocaloric diets that differed in amount of total dietary crude protein (CP) (10.6, 12.7, or 14.5% of dry matter) but not in CP degradability or solubility. All diets contained the following ingredients: corn silage, chopped grass hay, ground corn, soybean meal, expeller soybean meal, minerals, and vitamins. Following parturition, all cows were offered a similar diet. Nitrogen balance was measured on d 12 to 7 prior to the expected calving date. Cows were bled on d 5 prior to the expected calving date from just prior to feeding to 8 h postfeeding. As dietary CP increased, plasma glucose concentrations increased linearly, but no change was detected in plasma nonesterified fatty acids or serum insulin concentrations. Nitrogen intake, apparent and true digestibilities, fecal and urinary concentration of and N balance increased as the concentration of dietary protein increased. The efficiency of absorbed protein utilization decreased as protein intake increased. No change in postpartum intake or milk production was observed. An increase in N retention in late gestation cows that were in positive N balance did not increase postpartum milk production.