Predictors of outcome in an open label, therapeutic trial of high-dose omeprazole in laryngitis.

BACKGROUND: Gastroesophageal reflux is implicated in some cases of laryngitis. There are no established predictors of response to acid suppression therapy in suspected reflux laryngitis. AIM: In a population with laryngitis, the aim is to determine whether (a) omeprazole 20 mg tds (3 months) improves symptoms and laryngitis, and (b) the outcome in response to potent acid suppression can be predicted by esophageal and/or pharyngeal parameters during ambulatory pH monitoring or by other pretreatment variables. METHODS: From the 70 consecutive patients with laryngitis screened, 20 patients met the inclusion criteria (dysphonia >3 months; laryngoscopically demonstrated laryngitis); and 50 patients were excluded because of one or more criteria indicating alternative causes for laryngeal injury. The primary outcome measure was improvement of at least one level in a 4-point laryngitis grading at 3 months. Twenty-four-hour dual, pharyngo-esophageal pH monitoring was performed at baseline. Secondary outcomes (symptom questionnaire; computerized voice analysis) were measured at baseline, and at 6 and 12 wk. RESULTS: Response rates at 6 and 12 wk were 47% and 63%, respectively. GERD symptoms (heartburn (p= 0.03) and regurgitation (p= 0.0001)) improved. However, neither baseline GERD symptoms nor endoscopic findings predicted laryngoscopic or symptomatic response. Neither baseline laryngitis grade (p= 0.46) nor esophageal acid exposure on pH testing (p= 0.3) predicted outcome. Four of 20 patients demonstrated pharyngeal regurgitation on pH testing, all four of whom responded to potent acid suppression (p= 0.2). Computerized voice measures were not predictive of outcome, although fundamental frequency (Fo) was inversely related to baseline laryngoscopic grade. CONCLUSION: In a carefully defined population of patients with laryngitis (a) 63% have a laryngoscopic response to 3 months of potent acid suppression without significant improvement in laryngeal symptoms; (b) neither voice measures, esophageal acid exposure time, symptoms nor severity of laryngitis predict outcome; and (c) although numbers were small, all patients with a positive pharyngeal pH study responded to therapy and pharyngeal pH-metry may prove useful; (4) available evidence supports an empiric trial of high-dose proton pump inhibitors (PPI), for at least 12 wk, as the initial diagnostic step for suspected reflux laryngitis.

The ratio of the water and food consumption of chickens and its significance in the chemotherapy of coccidiosis.

An investigation was made of the relationship between the water and food consumption of healthy and sick chickens Using coccidiosis as a disease model, and uninfected chickens as healthy controls, male birds of an egg-production breed and males and females of a meat-production breed were found to have simultaneously reduced water and food intakes 4 days after infection with Eimeria acervulina or E. maxima, and from 4 to 6 days after infection with E. tenella. This phenomenon was associated with reduction of weight gains and poor food conversion ratios. Whether birds were healthy or sick, and regardless of the degree reduction of dietary intake, there was a more or less constant relationship between their food and water consumption. The ratio of the weights of water and food consumed had a value of about 1.9, with a range of 1.1-2.4. It is concluded that neither water nor food has an advantage over the other as a vehicle for chemotherapy. However, other factors, such as case and speed of administration, and avoidance of adsorption onto food particles, favour the drinking-water route.

Differences between the anticoccidial potencies of monensin in maize-based or wheat-based chicken diets.

Experiments were carried out to investigate why the anticoccidial ionophore monensin is more potent against the coccidium Eimeria tenella in chickens fed on a maize-based diet (as in the USA) than in chickens fed on a wheat-based diet (as in the UK). The explanation seems to be that the pathogenicity of E. tenella is lower in maize-fed chickens than in wheat-fed chickens, whether monensin is present in the diet or not. Possible reasons for this are suggested. The better survival of maize-fed birds may be partly due to protective effects of the higher concentrations of vitamins A and E derived from their diet. Furthermore, the higher concentrations of niacin and riboflavin in wheat than in maize may enhance coccidial pathogenicity. These opposing factors might combine to cause equivalent infection levels to produce more severe coccidiosis in chickens fed on a wheat-based diet than on a maize-based diet.

Predicting personality in adulthood from college MMPI scores: implications for follow-up studies in psychosomatic medicine.

To assess the long-term predictive utility of Minnesota Multiphasic Personality Inventory (MMPI) content scales, 1,960 individuals who had completed the MMPI in college in 1964 or 1965 were administered two measures of adult personality, the NEO Personality Inventory (NEO-PI) and the Cook and Medley MMPI Hostility scale, in 1988. A comparison group of 274 men and women in the Baltimore Longitudinal Study of Aging were given both MMPI and NEO-PI between 1981 and 1987. Predictive correlations between MMPI scales and NEO-PI factors were qualitatively similar to concurrent correlations, but approximately half as large in magnitude. Theoretically, these correlations were interpreted to mean that about half the variance in basic dimensions of personality is stable from college age into middle adulthood. Practically, the relatively modest correlations suggest that predictive studies of medical outcomes probably require large samples, and that baseline data from adults (e.g., over age 30) may be more useful for future studies. The combination of stability and change suggests that the decade of the 20s may be a particularly fruitful time to conduct research on interventions to alter personality and their effects on health outcomes.

A caution on the use of the MMPI K-correction in research on psychosomatic medicine.

The MMPI K scale is widely used to screen for invalid responses and to adjust substantive scale scores for defensiveness. In a normal volunteer sample, correlations of MMPI clinical scales and the Cook-Medley Hostility (HO) scale with self-reports and peer ratings on the NEO Personality Inventory (NEO-PI) were decreased rather than increased by K-correction. Similarly, in a medical sample, structured interview-based ratings of Potential for Hostility were better predicted by uncorrected HO scores than by K-corrected HO scores. Finally, in a prospective study of mortality among lawyers, uncorrected HO scores were a significant predictor of all-cause mortality; K-corrected scores were not. The data suggest that, under some circumstances, the K scale may measure substantive traits rather than defensiveness, and should be used and interpreted with caution. Its use is probably contraindicated for most research on psychiatrically normal subjects.

Evaluation of a mixture of trimethoprim and sulphaquinoxaline for the treatment of poultry: safety and palatability studies.

The safety of a 1:3 mixture of trimethoprim (TMP) and sulphaquinoxaline (SQX) for administration in food or water was assessed in broiler chickens, chicks of an egg laying strain and breeding fowl. The only effects recorded in six-week-old broilers medicated for seven days at levels ranging from 16 to 133 mg TMP plus SQX per kg bodyweight were decreases in water or food consumption, probably caused by unpalatability at overdosage levels, and associated decreases in weight gain and packed cell volume at an achieved overdose level of 4.4 times the recommended use concentration (RUC). Breeding fowl medicated at levels of 1 X or 3 X RUC for 14 days showed slightly reduced reproductive performance reflected by lowered egg production, egg weight and hatchability. These effects were temporary and performance equal to that of unmedicated birds was re-established by 14 days after medication ceased. Week-old chicks medicated for five days at levels from 0.7 to 4.7 X RUC showed normal growth rate over 12 days. Eleven-day-old chicks could not distinguish medicated from unmedicated water.

Evaluation of a mixture of trimethoprim and sulphaquinoxaline for the treatment of bacterial and coccidial diseases of poultry.

Representative experiments from work undertaken to develop a synergistic mixture of trimethoprim and sulphaquinoxaline for the preventive treatment of certain poultry diseases are described. Sulphaquinoxaline in the diet for four days was shown to achieve at least an 85 per cent higher blood level than nine other sulphonamides in chicks, and the efficacies of various trimethoprim/sulphaquinoxaline regimes in the diet or in the drinking water were demonstrated against pasteurellosis, colisepticaemia and five kinds of coccidiosis. Regimes for bacterial diseases were begun one day before infection but those for coccidial diseases were begun on the same day as infection or later. Overall, a total dose of 30 mg/kg bodyweight/day (trimethoprim/sulphaquinoxaline = 1:3) controlled these seven diseases. The same treatment was also shown to control sulphaquinoxaline-resistant strains of Escherichia coli and Eimeria acervulina. Although both drinking water and food were used for drug administration, twice the inclusion rate was required in food to that in water for equivalent efficacy. The significance of different modes of expression of dosages for bacterial and coccidial diseases is explained.

Pyrazolo[3,4-d]pyrimidine ribonucleosides as anticoccidials. 3. Synthesis and activity of some nucleosides of 4-[(arylalkenyl)thio]pyrazolo[3,4-d]pyrimidines.

Ribonucleosides of 4-(alkylthio)-1H-pyrazolo[3,4-d]pyrimidines have been shown to be useful anticoccidial agents [Krenitsky, T. A.; Rideout, J. L.; Koszalka, G. W.; Inmon, R. B.; Chao, E. Y.; Elion, G. B.; Latter, V. S.; Williams, R. B. J. Med. Chem. 1982, 25, 32. Rideout, J. L.; Krenitsky, T. A.; Elion, G. B. U.S. Patent 4299 283, 1981]. In that study, the unsaturated 4-allylthio and 4-crotylthio derivatives (19 and 20) were shown to be more active in vivo against Eimeria tenella than their saturated congeners; therefore, some unsaturated (arylalkyl)thio derivatives were synthesized and investigated as anticoccidial agents. The novel compounds in this study (2 to 18) were prepared by the alkylation of 4-mercapto-1-beta-D-ribofuranosyl-1H-pyrazolo[3,4-d]pyrimidine (1), which was prepared by an enzymatic method. The (E)-4-cinnamylthio derivative (2) and the 5'-monophosphate (18) were the most active compounds against E. tenella in vivo. None of the analogues with substituents in the aryl moiety (3 to 13) was more active than 2 in vivo. The geometry about the double bond was important, since the (Z)-4-cinnamylthio derivative (14) was inactive both in vitro and in vivo. The 4-(3-phenylpropynyl)thio and 4-(5-phenyl-2,4-pentadienyl)thio derivatives (15 and 16) were at least as active as 2 in vitro; however, they were less active than 2 in vivo. Compound 2 was effective in vivo against E. tenella, E. necatrix, E. maxima, and E. brunetti; these species of Eimeria were controlled when 2 was given in the diet at levels upt to 100 ppm. Infections in vivo due to E. acervulina were controlled by 2 only at about 800 ppm. The broad spectrum of anticoccidial activity shown by 2 represents a significant improvement over the activities reported for related compounds [Krenitsky, T. A.; Rideout, J. L.; Koszalka, G. W.; Inmon, R. B.; Chao, E. Y.; Elion, G. B.; Latter, V. S.; Williams, R. B. J. Med. Chem. 1982, 25, 32].

Changes in the collagen of rat heart in copper-deficiency-induced cardiac hypertrophy.

Groups of rats were maintained from weaning on copper-supplemented or copper-deficient diets. After 2, 4, 6, 8 or 12 weeks animals were killed, their hearts were removed and the solubility and phenotype composition of the collagen of the hearts was studied. In the hearts from the copper-supplemented animals 35 to 45% of the collagen could be extracted after two treatments with pepsin but up to 74% could be extracted from the hypertrophied copper-deficient hearts. Almost all of the increase in the soluble material was found in the first pepsin extract. Electrophoretic analysis of the extracts showed that in the copper-supplemented hearts the ratio of Type III/Type I collagen increased about threefold between 2 and 6 weeks after weaning but by 8 weeks it had returned to about the level found at 2 weeks and was maintained at this level to the end of the experimental period. In the copper-deficient hearts the ratio of Type III/Type I collagen had increased about fivefold by 6 weeks after weaning and from 8 weeks to the end of the experimental period it remained at two to three times the value found in the copper-supplemented hearts. There was an indication that the relative proportion of Type V collagen was reduced in the copper-deficient hearts. The possible significance of these results in relation to the known pathological effects of copper deficiency on the cardiovascular system is discussed.

The enhancement by dietary zinc deficiency of the susceptibility of the rat duodenum to colchicine.

1. The incidence of colchicine-induced lesions in the germinal epithelium oof the rat duodenum was studied in young rats in an early stage of zinc deficiency and in their pair-fed controls. At both dose levels of colchicine used, a marked increase in the amount of cell damage was observed in the duodenum of Zn-deficient rats as compared with the pair-fed, control (Zn-supplemented) rats. 2. No statistical interaction between Zn and colchicine was demonstrable, and no lesions were found in the duodenum of animals that had not been treated with colchicine. 3. The results are discussed in relation to the effects of Zn deficiency in animals and the possible involvement of Zn in the maintenance of the integrity of microtubular structures.

Rat fighting behavior: serum dopamine- -hydroxylase and hypothalamic tyrosine hydroxylase.

Male Sprague-Dawley rats were subjected to 4 weeks of daily periods of immobilization stress. One of two experimental groups was allowed 1 month of recovery. After 4 weeks of stress, there was a significant increase in shockinduced fighting, in the activity of serum dopamine-beta-hydroxylase, and in the activity of hypothalamic tyrosine hydroxylase. The concentration of hypothalamic norepinephrine was not decreased. After 4 weeks of recovery, only serum dopamine-betahydroxylase activity returned to normal; it therefore appears that longterm stress may increase central catecholamine synthesis. possibly resulting in a persistent increase in aggressive behavior.