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Biomedical subjects

H N Beaty

Publications and source records attributed to H N Beaty.

At least 37 records · Page 2Linked to original sources

Experimental pneumococcal meningitis. IV. The effect of methyl prednisolone on meningeal inflammation.

This study was undertaken to determine whether adrenal corticosteroids suppress meningeal inflammation in experimental pneumococcal meningitis in rabbits and, if so, whether the mechanism of suppression involves inhibition of chemotactic activity in CSF or modification of granulocyte responses to inflammation mediators. It was found that methyl prednisolone, administered intramuscularly in doses of 15 or 30 mg/kg 24 hr and 48 hr after induction of meningitis, significantly reduced (p less than 0.01) the mass of granulocytes present in the meninges 72 hr after infection, the time of maximum meningeal inflammation. The larger dose of steroid produced approximately twice the suppressive effect of the smaller dose (p less than 0.05). The regime of methyl prednisolone that produced maximal suppression of meningeal inflammation (30 mg/kg/day) did not alter CSF chemotactic activity or chemotactic responsiveness and phagocytic activities of granulocytes from rabbits with meningitis. However, steroid therapy inhibited an increase in granulocyte adherence that was observed in untreated animals with meningitis (p less than 0.05). Thus methyl prednisolone in doses of 15 and 30 mg/kg given daily to rabbits with pneumococcal meningitis produced a suppressive effect on meningeal inflammation that was dose-dependent and was possibly mediated by inhibition of granulocyte adherence.

Animals↗

The spectrum of tuberculous peritonitis.

From 1966 to 1973, a total of 30 cases of tuberculous peritonitis were seen in Seattle-King County. Abdominal pain, swelling, and constitutional symptoms were the most frequent initial complaints. Radiographic abnormalities consistent with tuberculosis were present in 25 cases, and pulmonary disease was proven in ten. An initial tuberculin test with intermediate-strength purified protein derivative of tuberculin was negative in 19 of 27 patients. Six of 13 initial nonreactors still had negative reactions on repeat testing, and four appeared to be anergic when retested one to four months later. Ascites was present in 67% (20) of the 30 patients, and laparotomy was used most frequently to establish the diagnosis. Diagnosis was particularly difficult in 13 alcoholics, in whom the disease was usually unsuspected, the findings in the ascitic fluid were uncharacteristic, and negative tuberculin reactions were frequent. Peritoneal tuberculosis was a contributory cause of death in five cases. Three of these patients, who were also alcoholics, went undiagnosed and untreated. Two patients died of unrelated causes. Twenty-three have done well, and 19 have completed chemotherapy.

Alcoholism↗

Staphylococcus aureus bacteremia. Current clinical patterns.

One hundred and five cases of bacteremia due to Staphylococcus aureus were reviewed to assess the current clinical spectrum of serious staphylococcal disease. Mortality was 21 percent, lower than previously reported. Patients could be separated into two groups according to the presence of identifiable primary staphylococcal infections; 63 bacteremic patients had such lesions, the remaining 42 lacked them. The latter group contained 24 of 26 cases of endocarditis. Illnesses in that group were marked by the presence (in 38 of 42 patients) of staphylococcal foci occurring secondary to bacteremia. Such foci were responsible for five of seven instances of relapse or treatment failure encountered in that group. Secondary staphylococcal foci occurred in only five of 63 patients with primary infections, and the response of this group to conventional therapy for bacteremia was satisfactory. This study suggests that endocarditis has become an unusual complication of identifiable primary staphylococcal infection. A clinical classification based on the presence of such lesions therefore separates bacteremic patients likely to be cured by conventional antibiotic therapy (those with primary infections but no secondary foci) from others (those with secondary foci, suggesting endocarditis) who should receive a more prolonged course of antibiotics.

Adolescent↗

Experimental pneumococcal meningitis. II. Characterization and quantitation of the inflammatory process.

For the systematic study of the role of inflammation in the morbidity and mortality associated with bacterial meningitis, techniques for quantitation of the inflammatory reaction in the meninges of rabbits with experimental pneumococcal infection were developed. The brains of 19 infected animals were removed intact, and the area of inflammation in microscopic sections was quantitated by an electronic X-Y plotter connected to a computer. Exudate was maximal along the ventral surface of the brain at the level of the cerebellum. Inflammation increased progressively with time and peaked at 72 hr. In a separate group of 29 animals, lactic acid dehydrogenase concentrations in cerebrospinal fluid increased significantly during infection, and the rate of increase wirh time coincided with the increase in inflammation documented histologically. The described method of quantitating inflammation in the meninges during experimental meningitis makes it possible to study the increase in granulocyte involvement with time. The establishment of a direct relation between the concentration of lactic acid dehydrogenase in the cerebrospinal fluid and the inflammatory mass validates the use of lactic acid dehydrogenase as an indicator of inflammation.

Animals↗

Experimental pneumococcal meningitis: III. Chemotactic activity in cerebrospinal fluid.

Chemotactic activity was assayed in CSF of rabbits with pneumococcal meningitis to further characterize the inflammatory response in this infection. CSF chemotactic activity was detected in increasing levels for 72 hr after infection. Activity was stable at 56 degrees and was inactivated by agents which denature proteins. Gel filtration demonstrated two chemotactically active fractions in infected CSF with mol wts of approximately 3000 and 11,000. Bacterial products appear to account for a portion of the observed CSF chemotactic activity, but the role of host factors remains to be clarified.

Animals↗

Effect of experimental pneumococcal meningitis on respiration and circulation in the rabbit.

Pathophysiological studies in bacterial meningitis in man have been limited by clinical variability and the necessity for immediate therapy. After the development of a reliable animal model of pneumococcal meningitis, we studied respiration and circulation in 25 anesthetized New Zealand white rabbits during untreated pneumococcal meningitis and in 33 healthy controls. In meningitis, we found increased lactic acid in cerebrospinal fluid (CSF). Increased ventilation, perhaps due to CSF lactic acid accumulation, resulted in respiratory alkalosis; the concomitant lowering of Pco(2) acted as a homeostatic mechanism to restore pH toward normality in the CSF. Hyperventilation increased with the duration of the illness. Cardiac output was also increased with decreased peripheral vascular resistance but with only slight reduction in mean systemic and pulmonary arterial pressures. In the final hour of life, peripheral vascular resistance fell further; ventilation declined and then abruptly ceased while cardiac activity continued. Lactic acid accumulation in the CSF, found in both experimental and human pneumococcal meningitis, may cause the hyperventilation found in this disease and may contribute to death.

Acidosis↗

Evaluation of cefazolin, a new cephalosporin antibiotic.

Cefazolin sodium was tested in vitro against 308 isolates of Enterobacteriaceae, Pseudomonas aeruginosa, Neisseria meningitidis, Haemophilus influenzae, Staphylococcus aureus, and enterococcus. Broth and agar dilution and disk diffusion techniques were used with at least two sizes of inocula of organisms. Cefazolin was also studied in the treatment of 85 hospitalized patients with a variety of serious infections. In concentations of 5 mug or less/ml, cefazolin inhibited and killed more than 90% of isolates of Enterobacteriaceae with the exception of indole-positive Proteus and Enterobacter species. No isolate of P. aeruginosa and only a few of Enterobacter and enterococci were killed by 25 mug of cefazolin/ml, a concentration readily attainable in serum with a 500-mg dose given intramuscularly. Penicillin-susceptible as well as penicillin-resistant isolates of S. aureus were killed by 1 mug or less of cefazolin per ml; however, 25 mug/ml was required to kill 100% of the strains when the inoculum size was increased 100-fold. Cefazolin treatment appeared effective in 82 of 85 patients, including four with endocarditis. Pain was minimal after intramuscular injection, and thrombophlebitis was not observed in those treated intravenously. No patient developed a positive Coombs test, and no evidence of renal toxicity was apparent in clinical studies.

Adolescent↗

Minocycline in the chemoprophylaxis of meningococcal disease.

An outbreak of meningococcal disease occurred among basic combat trainees at Fort Lewis, Wash., in the first 3 months of 1971. After five recruits developed meningitis within a 2-week period, 8,721 recruits were given 100 mg of minocycline every 12 hr for 5 days. No new cases of meningococcal disease occurred for almost 5 weeks. Then six additional cases occurred among recruits who had entered training after the initial course of minocycline and who had not received the drug. Minocycline was given to all 6,130 of these men, and again occurrence of new cases was halted abruptly. One week later, group C polysaccharide vaccine was administered to all recruits in the first 6 weeks of training and subsequently to all new entering trainees. No new cases of meningitis occurred in the next 3 months. Surveys showed that minocycline significantly lowered the meningococcal carrier rate for 4 to 5 weeks. No strains of Neisseria meningitidis, among 341 isolated after minocycline treatment, were resistant to the drug. Prophylaxis with minocycline clearly interrupted the course of this outbreak due to sulfa-resistant meningococci. Although immunization is the preferred method of prophylaxis, minocycline may be useful until a suitable polyvalent vaccine is available.

Disease Outbreaks↗

Ampicillin and tetracycline in the treatment and prophylaxis of chronic bronchitis.

Ampicillin and tetracycline, in doses of 2 g a day, were compared in the treatment of acute exacerbations of chronic bronchitis. Seventy-nine patients were followed for 3 to 29 months and were treated for 118 exacerbations. Clinical improvement occurred after 10 days of treatment with either drug in over 80% of the cases. Haemophilus influenzae and Diplococcus pneumoniae were eradicated from the sputum more than 60% of the time, but in general there was a poor correlation between bacteriological clearing and clinical response. The effect of chemoprophylaxis with ampicillin and tetracycline in doses of 1 g a day on the frequency of acute exacerbations of bronchitis was compared with that of a placebo. Seven hundred eighty prophylactic regimens, consisting of one capsule every 12 hr for 5 days beginning with the first sign of a cold, were prescribed for 76 patients. Irrespective of the regimen, an acute exacerbation of bronchitis was encountered at approximately 13% of the follow-up visits to the clinic.

Ampicillin↗