Should we take a history of prior treatment, and check sputum status at 2-3 months when treating patients for tuberculosis?

SETTING: Pinetown, South Africa (1975-1983). OBJECTIVE: To determine the value of previous treatment history and sputum smear examination at 2-3 months in predicting treatment failure and relapse in tuberculosis patients treated with four drugs given twice weekly for six months under direct observation. DESIGN: Four cohort studies among 562 ambulant adults with culture positive pulmonary tuberculosis, designed to test the effectiveness of isoniazid 600-900 mg, rifampicin 600 mg, pyrazinamide 2-3 g, and streptomycin 1-2 g, given twice weekly. The same drug regimen was given to all patients irrespective of previous treatment history. Therapy was not changed if smears remained positive at 2-3 months. RESULTS: Positive predictive values of a history of previous treatment for a positive smear at 2-3 months (18.3%), treatment failure (5.2%), and relapse (9.4%) were poor. Although patients with positive smears at 2-3 months were more likely to fail therapy than patients with negative smears (relative risk=4.5, 95% Confidence Interval [CI]: 1.6-12.8), positive predictive value for treatment failure was only 12.5%. Although relapse was more frequent in patients with positive smears than those with negative smears (9.7% vs 6.2%; P=0.4), most patients who relapsed had been smear negative at 2-3 months (18/21). CONCLUSION: A four-drug rifampicin-containing regimen can safely be given twice weekly under direct observation to both new and retreatment cases, and the 2-3 month smear examination can safely be omitted.

Directly observed therapy for tuberculosis given twice weekly in the workplace in urban South Africa.

Effective models of delivery of directly observed therapy (DOT) for tuberculosis in resource-poor settings are needed. Intermittent chemotherapy may be an important component of DOT delivered in the community as it means fewer visits to supervisors. There is no published evidence on the efficacy of twice weekly therapy given from the start of treatment without an intensive daily phase. We analysed data from 3 large cohort studies in a migrant, urban workforce in South Africa between 1975 and 1983. All patients received 4 drugs (isoniazid, rifampicin, pyrazinamide and streptomycin) twice weekly under direct observation by a nurse in the workplace. Of 444 patients, 378 (85.1%) completed treatment. Cure could be assessed in 362, and 348 (96.1%, 95% confidence interval 93.7-97.8%) were bacteriologically cured. Sputum status was assessed at 2-3 months in 343 patients and 309 (90.1%) were sputum negative. Eighteen patients relapsed (5.7%; 2.9/100 patient-years of observation). DOT can be effectively delivered to a migrant, urban workforce, and 4-drug therapy given twice weekly under direct observation is efficacious.

Beta-adrenergic stimulation of gastrin release mediated by gastrin-releasing peptide in rat antral mucosa.

The present studies were directed to examine the effects of beta-adrenergic and cholinergic stimulation on gastrin release and to assess the potential role of gastrin-releasing peptide in exerting these effects, utilizing incubated rat antral mucosa. Rat antral mucosa was incubated at 37 degrees C in Krebs-Henseleit bicarbonate buffer, pH 7.4, continuously gassed with 95% O2-5% CO2. After 1 h media were sampled for radioimmunoassay measurement of gastrin content. Inclusion of carbachol (2.5 X 10(-6) M) in culture medium increased medium gastrin concentration by 106 +/- 28% (P less than 0.01); addition of specific antibodies to gastrin-releasing peptide to the culture medium did not affect carbachol-stimulated gastrin release. Inclusion of isoproterenol (10(-9) M) in culture medium did not affect somatostatin release into the medium, but increased medium gastrin by 234 +/- 24% (P less than 0.001). However, in contrast to carbachol, addition of antibodies to gastrin-releasing peptide to culture medium decreased isoproterenol-stimulated gastrin release by 67 +/- 9% (P less than 0.001). Results of these studies indicate that, under the conditions of these experiments, beta-adrenergic, but not muscarinic, stimulation of gastrin release may be mediated, at least in part, through gastrin-releasing peptide.

Effect of GRP on beta-adrenergic-stimulated gastrin and somatostatin release in the isolated rat stomach.

The present studies were directed toward examining the effects of gastrin-releasing peptide (GRP) on acid secretion and on beta-adrenergic-stimulated gastrin and somatostatin release using the isolated vascularly perfused rat stomach. Including pentagastrin in perfusion buffer increased acid output from 2.2 +/- 0.4 mueq H+/h during control perfusion to 18.8 +/- 1.8 mueq H+/h (P less than 0.01). No significant changes in acid secretion were detected when either GRP or specific antibodies to GRP were included in perfusate in the absence or presence of pentagastrin. Inclusion of 10(-9) M isoproterenol in the perfusate did not change acid output with respect to control; however, gastrin and somatostatin release into the portal venous effluent was significantly enhanced. Peak gastrin and somatostatin concentrations observed at 15 min were 753 +/- 43% (P less than 0.001) and 345 +/- 43% (P less than 0.01), respectively, of basal levels. When antibodies to GRP were included in perfusate containing isoproterenol, gastrin and somatostatin release into the portal venous effluent was significantly inhibited. The results of these studies indicate that GRP does not affect basal or pentagastrin-stimulated gastric acid secretion in the isolated perfused rat stomach. However, under the conditions of these experiments, beta-adrenergic stimulation of gastrin and somatostatin release appears to be mediated, at least in part, through GRP.

Effect of antibodies to somatostatin on acid secretion and gastrin release by the isolated perfused rat stomach.

The present studies were directed toward examining the effect of somatostatin on gastrin release and acid secretion by the isolated vascularly perfused rat stomach. Rat stomachs were perfused in situ with Krebs-Ringer bicarbonate buffer containing 10% ovine erythrocytes and gassed with 95% O2-5% CO2. Inclusion of pentagastrin in the perfusion buffer increased acid output from 2.2 +/- 0.4 microEq H+/h during control perfusion to 18.8 +/- 1.8 microEq H+/h (p less than 0.01). In order to determine the effect of somatostatin on acid secretion and gastrin release, specific antibodies to somatostatin were included in the perfusate. Inclusion of antibodies to somatostatin in the buffer without pentagastrin did not significantly enhance acid output; however, gastrin concentration in the portal venous effluent increased from 15.1 +/- 2.0 to 25.2 +/- 5.2 pg/ml at 45 min (p less than 0.05). When antibodies to somatostatin were perfused in the presence of pentagastrin, acid output increased by 32% to 24.9 +/- 1.2 microEq H+/h (p less than 0.05); however, no change in gastrin concentration over basal was detected in the portal effluent. Results of these studies indicate that the capacity of the isolated rat stomach to secrete acid permits direct assessment of factors involved in the regulation of acid secretion. Under the conditions of these experiments, gastric somatostatin inhibits basal gastrin release and directly inhibits pentagastrin-stimulated acid secretion without affecting gastrin release.

Pentagastrin-stimulated gastric acid secretion by the isolated perfused rat stomach.

The purpose of this present study was to develop a method for stimulation of acid secretion by the isolated perfused rat stomach. Rat stomachs were perfused in situ via the abdominal aorta and celiac axis with Krebs-Ringer bicarbonate buffer in the presence or absence of 10% ovine erythrocytes. The gastric lumen was perfused with distilled water and gastric contents were collected at frequent intervals through a catheter at the pylorus. Sixty minute gastric acid output in response to various concentrations of pentagastrin was determined by titration of gastric contents with 0.01 N NaOH to pH 7.0. During arterial perfusion with Krebs-Ringer bicarbonate buffer in the absence of ovine erythrocytes gastric acid output was 2.50 +/- 0.58 SEM microEq H+/h, which did not increase in response to perfusion with Krebs-Ringer bicarbonate buffer containing pentagastrin. However, inclusion of 10% ovine erythrocytes in the arterial perfusate resulted in substantial stimulation of gastric acid by pentagastrin: maximal acid output, achieved with a pentagastrin dose of 0.6 microgram/kg/h, was 23.5 +/- 3.73 microEq H+/h (p less than 0.01). The results of the present study demonstrate the capacity of the isolated vascularly perfused rat stomach to secrete acid and provide a model for studying interactions of gastrointestinal regulatory peptides and their physiologic roles in the regulation of gastric acid secretion.

The bond strengths of resin systems to etched enamel.

This study was undertaken to compare the resin-enamel bond strengths of seven anterior restorative resins using the acid-etch technique. Six of the materials (Restodent, Enamelite, Smile, Nuva-System, Concise, and Adaptic) were composite resins. Only one, Sevriton, was an unfilled resin. Of the seven, only Sevriton and Smile were not designed for the acid-etch technique. Of the materials tested, Sevriton and Enamelite had the weakest bonds. There was no significant difference in the bond strength among Nuva-System, Smile, and Restodent; the bonds of all these were stronger than those of Sevriton and Enamelite. Concise showed a significantly greater bond strength than all the other materials in the study except Adaptic and the Nuva-System. The resin-enamel bond strength of Adaptic was of a greater magnitude than that of all other test materials.