Hyponatremic seizures after suprapubic catheter placement in 7-year-old child.

We report a case of hyponatremic seizures in a 7-year old boy with spina bifida following cystoscopy and suprapubic catheter placement. Immediate postoperative cystogram and pelvic computed tomogram (CT) after the development of seizures demonstrated a fluid collection from the suprapubic catheter site into the anterior abdominal wall. The subsequent reabsorption of free water from the fluid collection, with the contribution of postoperative hypotonic intravenous fluid administration and possible transient inappropriate antidiuretic hormone (ADH) secretion resulted in acute dilutional hyponatremia and consequent seizures. Strategies to prevent hyponatremia in children during urological procedures, with emphasis on the importance of reserving free water as the irrigation fluid are discussed.

Continuous epidural butorphanol relieves pruritus associated with epidural morphine infusions in children.

We examined the efficacy of epidural butorphanol to either prevent or relieve pruritus associated with epidural morphine infusion in children. Forty-six children were randomized to receive either epidural morphine (M) or epidural M with butorphanol (B) for postoperative analgesia. They received bupivacaine and either M 50 microg.kg-1 or the same dose of M plus B 10 microg.kg-1. Following surgery, a continuous infusion of 0.1% bupivacaine with either M 20 microg.ml-1 or M 20 microg.ml-1 + B 4 microg.ml-1 was given at a rate of 0.3 ml.kg-1.h-1. Pain scores and pruritus scores were recorded every 4 h during epidural infusion. Subjects with a pruritus score=2 received diphenhydramine 0.5 mg.kg-1 i.v. and were switched to an alternate epidural infusion; subjects receiving M (group M) were switched to M+B while subjects receiving M+B (group B) were switched to hydromorphone (H) 4 microg.ml-1. There was no difference in the initial incidence of pruritus (group M 11/18; group B 13/28). No subject in group M required a second change of epidural infusion because of continued pruritus after being switched to M+B; five of 13 subjects in group B continued to experience pruritus after being switched to H and required a second change of epidural infusion or an alternate analgesic modality (P=0.038). The median pruritus score in the first 24 h after changing epidural infusions was 0 in subjects in group MDelta (changed from M to M+B) and 1 in subjects in group BDelta (changed from M+B to H; P=0.012). While the median sedation score in the first 24 h was 1 in both groups, there was a greater incidence of sedation scores of 2 in group B than group M (28% vs 12.3%; P=0.021). B 10 microg.kg-1 was not effective in preventing pruritus associated with bolus epidural administration of M 50 microg.kg-1 in children. B 1.2 microg.kg-1. h-1 was effective in relieving pruritus associated with continuous epidural infusion of M 6 microg.kg-1.h-1.

Benzofuran based PDE4 inhibitors.

Replacement of the 3,4-dialkoxyphenyl substructure common to a number of PDE4 inhibitors with a 2-alkyl-7-methoxybenzofuran unit is described. This substitution can result in either enhancement or substantial reductions in PDE4 inhibitory activity depending on the system to which it is applied. An in vitro SAR study of a potent series of 4-(2-heteroaryl-ethyl)-benzoiurans 26 is also presented.

Risk of malignancy in women with systemic lupus erythematosus.

OBJECTIVE: To estimate the risk of malignancy in a cohort of patients with systemic lupus erythematosus (SLE) from a university medical center. METHODS: The cohort consisted of patients with lupus who were residents of Allegheny County and who were seen at the University of Pittsburgh, 1981-91. Cases of cancer were identified by a postal survey and review of medical records. The expected number of malignancies in the lupus cohort were estimated from age, sex, and race adjusted census and cancer incidence data from Allegheny County. Standardized incidence ratios and 95% confidence intervals for all cancers were calculated. RESULTS: Six (2.7%) malignancies were observed in the 219 lupus patients from Allegheny County during the observation interval (1981-91) and after the first visit at the University of Pittsburgh. The expected number of malignancies was 4.42. The standardized incidence ratio for cancer in the lupus cohort from Allegheny County was 1.36 (95% confidence interval 0.50-2.96). The frequency of malignancy was not increased in the small number of patients who had received immunosuppressive drugs before the diagnosis of cancer. Non-Hodgkin's lymphoma occurred in one patient, who also had Sjögren's syndrome, and in one patient before entry into this study who was treated with FK-506 following renal transplant. No bladder cancers were observed during the study interval. CONCLUSION: The overall frequency of malignancy was not increased in this medical center cohort of patients with lupus during a mean followup interval of 5.2 yrs. Longterm followup and a multicenter effort is needed to refine risk estimates of cancer in patients with lupus.

Lyme disease acquired in Europe and presenting in CONUS.

Lyme disease is recognized in many parts of the world, including large areas of North America, Europe, Asia and Australia. Diagnosis and treatment of the disease is essential to avoid the debilitating and potentially life-threatening long-term effects of the infection; however, many physicians may not be aware of the international scope of the disease. This is particularly important for military physicians whose patients may visit or live in endemic areas and whose activities may bring them in contact with the organism. We report here the case of a soldier with near-fatal Lyme carditis acquired in Europe and presenting in Massachusetts.

Primary prevention of childhood lead poisoning: a goal for the 1990s.

Childhood lead poisoning remains a common problem in America today. The U.S. Department of Health and Human Resources has recently released a strategic plan on eliminating childhood lead poisoning, and health care professionals should become familiar with the basic elements of the plan.

The development of a novel series of (quinolin-2-ylmethoxy)phenyl-containing compounds as high-affinity leukotriene receptor antagonists. 3. Structural variation of the acidic side chain to give antagonists of enhanced potency.

This paper is the third in a series outlining the development of orally active sulfido peptide leukotriene antagonists containing a (quinolin-2-ylmethoxy)phenyl moiety. In this work the systematic variation of the acid side chain substituents led to dramatic and reproducible changes in the oral activity of these compounds, presumably due to alterations in their pharmacokinetic properties. The most potent compound identified, 5-[4-[4-(quinolin-2-yl-methoxy)phenyl]-3-methylbutyl]tetrazole (32), represents a convergence of good in vitro antagonist activity and a 3-10-fold improvement in oral potency over the current clinical candidate 2. The new findings from these optimization studies are as follows: oxygen substitution in the acid side chain was not necessary for antagonist activity, in vitro and in vivo activity was enhanced by alkyl or phenyl substitution on the gamma-carbon of the acid side chain of para-substituted (quinolin-2-ylmethoxy)phenyl derivatives, and free rotation about the side chain carbon atom adjacent to the (quinolin-2-ylmethoxy)phenyl ring was required for activity. The lead compound of this report (32) is a competitive inhibitor of [3H]LTD4 binding to receptor membrane purified from guinea pig lung (Ki = 12 +/- 3 nM) and of the spasmogenic activity of LTC4, LTD4, and LTE4 in guinea pig lung strip. Dosed orally in guinea pigs, this compound blocks LTD4-induced bronchoconstriction (ED50 0.8 mg/kg) and antigen-induced systemic anaphylaxis (ED50 = 1.2 mg/kg).

The inhibition of 5-lipoxygenase by RG 6866.

The generation of leukotrienes C4, D4 and E4 from arachidonic acid is dependent upon the activity of 5-lipoxygenase (5-LOX). The effects of RG 6866 (N-methyl-4-benzyloxyphenylacetohydroxamic acid) on the activity of guinea pig 5-LOX in vitro and in vivo were determined in the present study. The generation of 5-hydroxy-6,8,11,14-eicosatetraenoic acid (5-HETE) from arachidonic acid by isolated guinea pig peritoneal polymorphonuclear (PMN) cells was inhibited by incubation with RG 6866 (IC50 = 0.20 microM). A similar effect (IC50 = 0.23 microM) was observed when 5-HETE production was measured in a supernatant fraction from PMNs. Additionally, the compound did not inhibit 3H-LTD4 binding to guinea pig membranes. In actively sensitized guinea pigs pretreated with indomethacin, propranolol and pyrilamine, RG 6866 inhibited antigen-induced systemic anaphylaxis and LTD4-dependent bronchoconstriction in a dose-dependent manner following oral administration. In the pulmonary anaphylaxis model, significant (p less than 0.05) inhibition of the mortality was observed within 30 min and maintained through four hours after treatment with RG 6866 (50 mg/kg i.g.). Finally, orally administered RG 6866 inhibited the formation of LTC4 in these animals with an ED50 = 24.0 mg/kg. These findings indicate that RG 6866 is an inhibitor of 5-LOX both in vitro and in vivo.

Cardiopulmonary effects of celiprolol and bisoprolol in serotonin-infused cats.

The effects of celiprolol and bisoprolol on cardiopulmonary function in serotonin-infused cats were compared. Celiprolol reversed the bronchoconstrictive effect of serotonin at doses greater than or equal to 1.0 mg/kg. Also, decreases in mean arterial pressure and heart rate were noted after administration of 3-10 and 10 mg/kg celiprolol, respectively. In contrast, bisoprolol tended to induce bronchoconstriction. Reductions in mean arterial pressure and heart rate were observed with 1 or 3 mg/kg. Bisoprolol administration at 10 mg/kg was lethal. The unique ability of celiprolol to induce bronchodilation enhances its therapeutic potential.