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The effect of the interaction of pyrazinamide and probenecid on urinary uric acid excretion in man
Pyrazinamide
Uric acid excretion
Inflammatory bowel disease Crohn’s disease Cecal inflammation Colitis
Graves’ disease
Hashimoto’s thyroiditis
Cirrhosis
Technetium 99
Abnormal pulmonary perfusion pathways found at autopsy in patients with hepatic cirrhosis have been suggested as a major cause of hypoxemia in cirrhosis. In the present study, the pathophysiology of hypoxemia(PaO:, 48.5 to 68 mm Hg) in three patients with hepatic cirrhosis was investigated utilizing conventional cardiopulmonary tests and a special radionuclide technic for detecting shunting through small dilated pulmonary vessels. The results document the presence of dilated pulmonary capillaries and/or arteriovenous communications too small to be detected angiographically. These abnormal vascular channels can account for the observed hypoxemia primarily on the basis of diffusion/perfusion imbalance and to a lesser extent by true shunting. A similar mechanism may be responsible for the hypoxemia commonly found in other patients with cirrhosis.
Wolfe JD, Tashkin DP, Holly FE, Brachman MB, Genovesi MG: Hypoxemia of cirrhosis. Detection of abnormal small pulmonary vascular channels by a quantitative radionuelide method. Am J Med 63: 746-754, 1977.
Quantitative radionuclide method
Hypoxemia
The thyroid glands of four patients with Graves’ disease and five patients with Hashimoto’s thyroiditis were investigated to demonstrate in vivo immune complex deposition. By electron microscopy, electron-dense deposits were observed in the follicular basal lamina-basement membrane-(FBL) often associated with lymphocytic and plasma cell infiltration. A positive correlation was obtained with all cases by immunofluorescent studies using anti-IgG. IgA, IgM, C3 and antithyroglobulin conjugated serums. The staining was of a granular paitem and coincided 10 the FBI_ region. No discrepancies were noted in electron microscopic and immunofluorescent observations between patients with Graves’ disease and Hashimoto’s thyroiditis, and the occasional observation of immune complexes in areas devoid of infiltrate in some patients with Graves’ disease. Morphologically, the deposits were found to be similar to those described in the Obese Strain chickens with spontaneous autoimmune thyroiditis.
Kalderon AE, Bogaars HA: Immune complex deposits in Graves’ disease and Hashimoto’s thyroiditis. Am J Med 63: 729-734, 1977.
Immune complex deposits
Continued on page A103
strictures or contraction and deformation of the cecum. Peritoneal findings consisted of a thickened cecum or an inflammatory mass in the ileOcecal area. Ascites and peritoneal granu1oma.swere less frequent. Confluent.granulomas of varying size were typically found in resected bowel, mesenteric lymph nodes or peritoneum, but prolonged search for caseation necrosis and for mycobacteria was frequently necessary. The diagnosis of tuberculosis was generally not considered before it was demonstrated in tissue resected at surgery or at autopsy. Crohn’s disease was the entity most frequently mistaken for tuberculous enteritis.
pulmonarytuberculosis.Bariumstudiesshowedcharacteristicshortconcentricsmall bowel
The finding of 13 patients with intestinal tuberculosis over the period from 1964 to 1974 in a single hospital suggests that this entity is still more common than generally believed. The patients did not confirm to the profile of the recently immigrated, poor, alcoholic with evidence of active
SchulzeK, Warner HA, Murray D: intestinal tuberculosis. Experience at a Canadian Teaching Institution. Am J Med 63: 735-745, 1977.
Peritoneal granulomas
Tuberculosis intestinal
Complex interactions occur between pyrazinamide and probenecid in man involving both the metabolism and distribution of the drugs, and their effects on renal tubules. Pretreatment with pyrazinamide (PZA) prolonged the half-life (T 112) of probenecid without changing its plasmabinding. As the rate of probenecid metabolism is decreased, its uricosuric action tends to be prolonged and the effect of PZA lessened. The PZA-suppressible urate level is increased to values well above control after the administration of probenecid; it is less after alkalinization of urine, although still larger than the value for PZA-suppressible urate after the administration of PZA alone. The urinary excretion of probenecid is much greater when urine is alkalinized. These observed drug interactions, plus the known effect of probenecid to block secretion of PZA, have to be considered in evaluating the effect of the two drugs given together, compared to the effect of each drug given separately.
Yti TF, Perel J, Berger L, Roboz J, lsraili ZH, Dayton PG: The effect of the interaction of pyrazinamide and probenecid on urinary uric acid excretion in man. Am J Med 63: 723-728, 1977.
Probenecid
Uric acid excretion
Inflammatory bowel disease Crohn’s disease Cecal inflammation Colitis
Graves’ disease
Hashimoto’s thyroiditis
Cirrhosis
Technetium 99
Abnormal pulmonary perfusion pathways found at autopsy in patients with hepatic cirrhosis have been suggested as a major cause of hypoxemia in cirrhosis. In the present study, the pathophysiology of hypoxemia(PaO:, 48.5 to 68 mm Hg) in three patients with hepatic cirrhosis was investigated utilizing conventional cardiopulmonary tests and a special radionuclide technic for detecting shunting through small dilated pulmonary vessels. The results document the presence of dilated pulmonary capillaries and/or arteriovenous communications too small to be detected angiographically. These abnormal vascular channels can account for the observed hypoxemia primarily on the basis of diffusion/perfusion imbalance and to a lesser extent by true shunting. A similar mechanism may be responsible for the hypoxemia commonly found in other patients with cirrhosis.
Wolfe JD, Tashkin DP, Holly FE, Brachman MB, Genovesi MG: Hypoxemia of cirrhosis. Detection of abnormal small pulmonary vascular channels by a quantitative radionuelide method. Am J Med 63: 746-754, 1977.
Quantitative radionuclide method
Hypoxemia
The thyroid glands of four patients with Graves’ disease and five patients with Hashimoto’s thyroiditis were investigated to demonstrate in vivo immune complex deposition. By electron microscopy, electron-dense deposits were observed in the follicular basal lamina-basement membrane-(FBL) often associated with lymphocytic and plasma cell infiltration. A positive correlation was obtained with all cases by immunofluorescent studies using anti-IgG. IgA, IgM, C3 and antithyroglobulin conjugated serums. The staining was of a granular paitem and coincided 10 the FBI_ region. No discrepancies were noted in electron microscopic and immunofluorescent observations between patients with Graves’ disease and Hashimoto’s thyroiditis, and the occasional observation of immune complexes in areas devoid of infiltrate in some patients with Graves’ disease. Morphologically, the deposits were found to be similar to those described in the Obese Strain chickens with spontaneous autoimmune thyroiditis.
Kalderon AE, Bogaars HA: Immune complex deposits in Graves’ disease and Hashimoto’s thyroiditis. Am J Med 63: 729-734, 1977.
Immune complex deposits
Continued on page A103
strictures or contraction and deformation of the cecum. Peritoneal findings consisted of a thickened cecum or an inflammatory mass in the ileOcecal area. Ascites and peritoneal granu1oma.swere less frequent. Confluent.granulomas of varying size were typically found in resected bowel, mesenteric lymph nodes or peritoneum, but prolonged search for caseation necrosis and for mycobacteria was frequently necessary. The diagnosis of tuberculosis was generally not considered before it was demonstrated in tissue resected at surgery or at autopsy. Crohn’s disease was the entity most frequently mistaken for tuberculous enteritis.
pulmonarytuberculosis.Bariumstudiesshowedcharacteristicshortconcentricsmall bowel
The finding of 13 patients with intestinal tuberculosis over the period from 1964 to 1974 in a single hospital suggests that this entity is still more common than generally believed. The patients did not confirm to the profile of the recently immigrated, poor, alcoholic with evidence of active
SchulzeK, Warner HA, Murray D: intestinal tuberculosis. Experience at a Canadian Teaching Institution. Am J Med 63: 735-745, 1977.
Peritoneal granulomas
Tuberculosis intestinal
Complex interactions occur between pyrazinamide and probenecid in man involving both the metabolism and distribution of the drugs, and their effects on renal tubules. Pretreatment with pyrazinamide (PZA) prolonged the half-life (T 112) of probenecid without changing its plasmabinding. As the rate of probenecid metabolism is decreased, its uricosuric action tends to be prolonged and the effect of PZA lessened. The PZA-suppressible urate level is increased to values well above control after the administration of probenecid; it is less after alkalinization of urine, although still larger than the value for PZA-suppressible urate after the administration of PZA alone. The urinary excretion of probenecid is much greater when urine is alkalinized. These observed drug interactions, plus the known effect of probenecid to block secretion of PZA, have to be considered in evaluating the effect of the two drugs given together, compared to the effect of each drug given separately.
Yti TF, Perel J, Berger L, Roboz J, lsraili ZH, Dayton PG: The effect of the interaction of pyrazinamide and probenecid on urinary uric acid excretion in man. Am J Med 63: 723-728, 1977.
Probenecid