Pancreatic insufficiency due to antituberculous therapy.

OBJECTIVE: To describe a case of chronic pancreatic insufficiency related to antituberculous therapy. CASE SUMMARY: A 57-year-old man developed rash, fever, and hepatitis (aspartate aminotransferase 369 IU/L, alanine aminotransferase 506 IU/L), 6 weeks after starting isoniazid, rifampin, ethambutol, and pyrazinamide. He also developed severe metabolic acidosis secondary to diabetic ketoacidosis and lactic acidosis (serum bicarbonate 7 mEq/L, glucose 1778 mg/dL, and lactate 4.0 mEq/L). Acute pancreatitis was diagnosed on the basis of a mildly elevated amylase concentration (392 U/L) and radiologic evidence of pancreatic inflammation. He developed pancreatic insufficiency with steatorrhea and an abnormal secretin test. He continues to require pancreatic enzyme replacement and insulin therapy. Rechallenge was not performed. DISCUSSION: Hypersensitivity syndromes have been reported for various drug therapies, including antituberculous agents. Hypersensitivity syndrome reactions are characterized by fever, rash, and internal organ involvement. Rifampin has been reported to cause acute pancreatitis in up to 2.7% of patients. Drug-induced chronic pancreatitis, however, is reported to be extremely rare. This is the first reported case of chronic pancreatic insufficiency occurring in the setting of a hypersensitivity syndrome reaction to antituberculous drugs. CONCLUSIONS: Chronic pancreatic insufficiency should be considered as a possible long-term sequelae of a hypersensitivity syndrome reaction to antituberculous therapy.

Single-fiber electromyography in diabetic peripheral polyneuropathy.

In this study we examined the value of single-fiber electromyography (SFEMG) in assessing the degree of reinnervation in diabetic patients with clinical neuropathy. Relationships between reinnervation and the degree of metabolic control, and/or duration of diabetes were examined. Thirty-six insulin-dependent diabetics and 54 non-insulin-dependent diabetics underwent SFEMG examination of the tibialis anterior muscle, as well as conventional nerve conduction studies of the upper and lower limbs. All patients examined exhibited some abnormality of SFEMG even in the presence of normal nerve conduction studies found in 18% of patients. In diabetic patients, the jitter in the tibialis anterior muscle correlated positively with glycosylated hemoglobin; whereas lower limb nerve conduction studies did not correlate with this measure of diabetic control. These data suggest that SFEMG is a sensitive measure of nerve function and reinnervation and that it may reflect the dynamic changes in metabolic status in diabetic patients.

Overt diabetic neuropathy: repair of axo-glial dysjunction and axonal atrophy by aldose reductase inhibition and its correlation to improvement in nerve conduction velocity.

Clinically overt diabetic neuropathy is characterized by neuroanatomical changes of the node of Ranvier and myelinated axons, and by decreased nerve conduction velocity. Sural nerve biopsies were obtained from 16 neuropathic diabetic patients participating in a 12-month randomized, placebo-controlled, double-blind clinical trial of the aldose reductase inhibitor sorbinil. One sural nerve biopsy was obtained at baseline and a second biopsy at the termination of the trial. Ten sorbinil-treated patients showed significant improvement in axo-glial dysjunction, a characteristic lesion of the node of Ranvier. Axonal atrophy assessed by three independent morphometric techniques also exhibited significant recovery in the sorbinil-treated patients. No change was demonstrated in any of these structural parameters in six placebo-treated patients. The improvement in sural nerve conduction velocity in sorbinil-treated patients correlated with the product of the quantitative improvements in axo-glial dysjunction and axonal atrophy. We conclude that the activated polyol-pathway plays a sustaining role in nerve fibre damage in diabetic neuropathy, and that structural lesions such as axo-glial dysjunction and axonal atrophy which are reversible following intervention with an aldose reductase inhibitor, constitute the morphological basis for nerve conduction slowing in overt diabetic neuropathy.

Hormonal and metabolic responses during coronary artery bypass surgery: role of infused glucose.

Anesthesia, surgery, and hypothermia are conventionally considered the major stress factors in the metabolic and hormonal responses to cardiac surgery. We compared these responses in 14 nondiabetics during and for 24 h after coronary artery bypass surgery; 8 received cardioplegic solutions (C+), and 6 did not (C-). The mean intraoperative glucose load in C+ was 106 g compared to 32 g in C-; postoperatively both groups received 50 g. Marked hyperglycemia (31.8 +/- 4.8 mmol/L) occurred during hypothermia in C+, but dropped to 18.9 mmol/L before surgery ended and to 11.2 +/- 1.1 mmol/L by 2 h postop. In contrast, C- showed constant mild hyperglycemia of 8.3-9.8 mmol/L throughout, significantly less than C+ until 1 h postop. Insulin was suppressed by 55% only during hypothermia, peaking with rewarming in C+ at 2,849 +/- 911 vs. 639 +/- 251 pmol/L in C- (P less than 0.05); as with glycemia, values were comparable after 2 h postop. The pancreatic beta-cell thus responded to hyperglycemia during restoration of normothermia, resulting in a rapid decline in glycemia. This occurred despite elevations in antiinsulin factors in both groups; GH was 14 +/- 4 micrograms/L, cortisol was 607 +/- 38.6 nmol/L, norepinephrine was 11.5 +/- 3.7 nmol/L, epinephrine was 13,863 +/- 3,875 pmol/L, and FFA were 0.36 +/- 0.05 g/L. Early postop, a secondary rise in stress hormones occurred in both groups. Maximal cortisol values were at 4 h (1,186 +/- 140 nmol/L) and peaks of norepinephrine (6.50 +/- 1.66 nmol/L), epinephrine (7,969 +/- 3,602 pmol/L), and FFA (0.27 +/- 0.03 g/L) occurred. The only significant glucagon elevation was at 24 h (C+, 464 +/- 53 ng/L; C-, 350 +/- 241 ng/L; P less than 0.02), Thus, 1) many metabolic responses during coronary artery bypass surgery are influenced by the glucose-containing cardioplegic solution; 2) hypothermia suppresses insulin secretion, but it responds thereafter despite marked elevations of catecholamines, and is associated with decreasing glycemia despite elevated antiinsulin factors; 3) a lesser but highly significant stress response corresponds to awakening from anesthesia; and 4) glucagon plays a minor role in intraoperative hyperglycemia; the rise at 24 h is unexplained.