Acute pancreatitis associated with the use of lisinopril

OBJECTIVE: To report a case of acute pancreatitis associated with lisinopril use. CASE SUMMARY: A 67-year-old man with no past history of pancreatitis or its associated risk factors developed acute pancreatitis after taking lisinopril for two years. To date, the use of angiotensin-converting enzyme (ACE) inhibitors and development of pancreatitis has been described in the literature with captopril, enalapril maleate, and one case temporally related to lisinopril use. CONCLUSIONS: The use of ACE inhibitors as first-line agents in controlling hypertension and congestive heart failure has increased. In addition to monitoring for efficacy and commonly reported adverse effects, clinicians need to be aware that acute pancreatitis may occur with all ACE inhibitors.     

Stimulation of inositol phosphate production and GTPase activity by compound 48/80 in rat peritoneal mast cells

Phospholipase C activity, GTPase activity and cytosolic-free calcium concentration in mast cells were stimulated by compound 48/80. Accumulation of inositol phosphates in rat mast cells was stimulated by guanosine 5'-[gamma-thio]-triphosphate. Guanosine 5'-[gamma-thio]triphosphate, however, exhibited no effect upon the purified phospholipase C activity and upon phospholipase C in the mast cell homogenate. The stimulatory effect of compound 48/80 upon phospholipase C activity of intact mast cells was observed to have been well correlated with that on GTPase activity of mast cell homogenate. Compound 48/80 exhibited no effect upon the binding of radioactive guanosine 5'-[gamma-thio]triphosphate to mast cell homogenate. Phospholipase C activity was verified by the above results to become affected by compound 48/80 through guanine nucleotide-binding regulatory protein.     

Reproductive factors and risk of brain, colon, and other malignancies in Iowa (United States)

The influence of parity on the risk of cancers of the female breast and reproductive organs is well established. However, non-reproductive sites have received less attention. Mail questionnaire data gathered from incident female cases (169 brain; 332 colon; 260 rectal; 145 kidney; and 169 pancreas cancers), and 821 population-based controls in Iowa (United States) were used to measure the effect of parity and age at first birth on risk of these malignancies. Relative to nulliparous women, ever-parous women were at significantly decreased risk of brain cancer (odds ratio [OR] = 0.44, 95 percent confidence interval [CI] = 0.3-0.7) and of colon cancer (OR = 0.67, CI = 0.5-0.97), after adjustment for age and other risk factors. The OR for the other sites did not differ significantly from 1.0. The lower risk of brain cancer among parous women was similar in younger and older age groups, in patients diagnosed with glioblastoma and astrocytoma, and among ever- and never-smokers. The findings for colon cancer are consistent with observations from other studies. In the context of limited laboratory and clinical evidence implicating hormones in brain neoplasia, these findings may suggest a role for hormonal factors in brain cancer etiology. Hormonal factors deserve more detailed future consideration as risk factors in brain cancer.     

Diethylmaleate produces diaphragmatic impairment after resistive breathing

Formation of oxygen-derived free radicals and activation of the glutathione (GSH) redox cycle has been associated with impaired rat diaphragm performance. Diethylmaleate (DEM) given intraperitoneally irreversibly conjugates with GSH, resulting in marked decreases in tissue concentrations of GSH. We have investigated the effects of acute GSH depletion by DEM on diaphragmatic function during resistive breathing (RB) in the rat. The experimental groups were 1) control, 2) DEM alone, 3) RB, and 4) DEM with RB (DEM + RB). RB was obtained by inspiratory RB until the rats were unable to sustain 70% of maximum airway opening pressure. A portion of the diaphragm was frozen for biochemical assays, and the rest of the diaphragm was prepared for measurement of in vitro contractile properties, including maximum tetanic tension, twitch tension, force-frequency curves, and contraction times. DEM treatment produced a profound depletion of GSH in the DEM and DEM + RB groups. Neither DEM nor RB alone significantly altered diaphragm contractile properties. In DEM + RB rats, however, there was a significant decrease in maximum tetanic tension, twitch tension, and tetanic tension. These data reveal that DEM produced an acute depletion of GSH in the diaphragm without impairment of the muscle in nonstressed rats. In the presence of DEM-induced GSH depletion, RB did result in marked diaphragm impairment. The depletion of GSH and the subsequent impairment in diaphragm contractility after RB suggest that GSH may play an important role in protecting the diaphragm against oxidative stress associated with RB.     

Erythrocyte sodium-lithium countertransport activity and total body insulin-mediated glucose disposal in normoalbuminuric normotensive type 1 (insulin-dependent) diabetic patients

PURPOSE: To assess the potential of a clinical method of optic disc measurement in the detection of early neuroretinal rim loss in glaucoma. METHODS: A method of disc biometry based on indirect ophthalmoscopy was used to estimate disc and neuroretinal rim areas in 81 ocular hypertensive eyes of 43 patients and in 28 fellow eyes with normal visual fields of patients with unilateral visual field loss from primary open-angle glaucoma. The results were compared with those from age-matched visually normal patients. RESULTS: Neuroretinal rim area was significantly smaller in both hypertensive and fellow eye groups compared with controls (P < 0.0001; P = 0.0009). Disc area also was smaller in both groups (P = 0.0034; P = 0.046); however, this was inadequate to explain the differences in rim area, which, when corrected for disc size, were still highly significant (P < 0.0001; P = 0.0001). CONCLUSION: The differences in neuroretinal rim area observed are likely to indicate that a proportion of the eyes studied had suffered a reduction of neuroretinal rim area, which was measurable by this method at a stage before the development of demonstrable visual field loss.     

Bioactivation and irreversible binding of the cognition activator tacrine using human and rat liver microsomal preparations. Species difference

Tacrine's [1,2,3,4-tetrahydro-9-acridinamine monohydrochloride monohydrate, (THA)] metabolic fate was examined using human and rat liver microsomal preparations. Following 1-hr incubations with human microsomes, [14C]THA (0.4 microM) was extensively metabolized to 1-hydroxyTHA with trace amounts of 2-, 4-, and 7-hydroxyTHA also produced. Poor recovery of radioactivity in the postreaction incubates suggested association of THA-derived radioactivity with precipitated microsomal protein. After exhaustive extraction, 0.034, 0.145, 0.126, and 0.012 nmol eq bound/mg protein/60 min of THA-derived radioactivity was bound to human liver preparations H109, H111, H116, and H118, respectively. Preparations H109 and H118 were lower in P4501A2 content and catalytic activity as compared with preparations H111 and H116. Incubations of equimolar [14C]1-hydroxyTHA with human liver microsomes also resulted in binding to protein, although to a lesser extent than observed with THA. [14C]THA (0.4 microM) was incubated for 1 hr with rat liver microsomes (1 microM P-450) prepared from noninduced (N), phenobarbital (PB), isoniazid (I), and 3-methylcholanthrene (3-MC)-pretreated animals. In all incubations, 1-hydroxyTHA was the major biotransformation product detected. After exhaustive extraction, 0.048, 0.054, 0.049, and 0.153 nmol eq/mg protein/60 min of THA-derived radioactivity was bound to microsomal protein from N, PB, I, and 3-MC pretreated rats. Increased binding with 3-MC induced rat liver preparations suggests the involvement of the P-450 1A subfamily in THA bioactivation. Glutathione (5 mM) coincubation inhibited the irreversible binding of THA-derived radioactivity in both human and 3-MC-induced rat liver preparations, whereas human epoxide hydrase (100 micrograms/incubate) had a relative minor effect. A mechanism is proposed involving a putative quinone methide(s) intermediate in the bioactivation and irreversible binding of THA. A species difference in THA-derived irreversible binding exists between human and noninduced rat liver microsomes, suggesting that the rat is a poor model for studying the underlying mechanism(s) of THA-induced elevations in liver marker enzymes found in clinical investigations.     

Venous angiography is needed to interpret inferior petrosal sinus and cavernous sinus sampling data for lateralizing adrenocorticotropin-secreting adenomas

Bilateral simultaneous venous sampling of ACTH from the inferior petrosal sinus is a reliable test for diagnosing Cushing's disease, but is not reliable for lateralizing ACTH-secreting pituitary adenomas. We reviewed 23 consecutive patients with Cushing's disease who underwent venous angiography of the cavernous and inferior petrosal sinuses followed by bilateral simultaneous venous sampling of ACTH in the inferior petrosal and cavernous sinuses. Venous drainage was bilaterally symmetric in 14 patients (61%) and asymmetric in 9 (39%). The most common asymmetric pattern (6 patients) was for blood from both cavernous sinuses to drain into the right inferior petrosal sinus, with no significant drainage into the left. Cavernous sinus sampling in 21 patients correctly lateralized the tumor in 12 cases of symmetric venous drainage, but in only 3 cases of asymmetric drainage. Inferior petrosal sinus sampling in all 23 patients correctly lateralized the tumor in 12 cases of symmetric drainage, but in only four cases of asymmetric drainage. Overall, venous sampling correctly lateralized 70% of the tumors. Incorrect lateralization in cases of asymmetric venous drainage is probably attributable to shunting of blood toward the side of dominant venous drainage. Our findings illustrate the need for venography in all patients undergoing venous sampling of ACTH because an understanding of the venous drainage patterns is essential to correctly interpret venous sampling data and warn physicians that the lateralization data may be incorrect or unreliable.     

Parathyromatosis: a rare yet important cause of persistent or recurrent hyperparathyroidism

BACKGROUND: Parathyromatosis is described by as small nodules of hyperfunctioning parathyroid tissue scattered in the soft tissues of the neck and/or mediastinum. Seeding of hypercellular parathyroid glands during surgical excision and overgrowth of parathyroid rests left behind during ontogenesis are the most likely causes of this rare phenomenon. To characterize the clinical presentation and management of this rare condition, we report on a patient with uremia and persistent hyperparathyroidism occurring after total parathyroidectomy. METHODS: The records of one man with parathyromatosis treated from 1989 to 1993 were reviewed. In addition, a review of the literature was undertaken. RESULTS: Findings at the patient's final operation (a median sternotomy) included multiple nodules of hyperplastic parathyroid tissue scattered throughout the thymus. The characteristics of this histologically benign tissue are consistent throughout various case reports in the literature. CONCLUSIONS: This case presentation shows the physiologic significance of parathyromatosis, particularly in the setting of kidney failure. The importance of meticulous handling of potentially hyperplastic parathyroid glands and routine cervical thymectomy among this subset of patients is emphasized.