Effect of ranitidine on gastric acid hypersecretion in an infant with short bowel syndrome

We studied the effect of ranitidine given in graded bolus intravenous doses on gastric acid hypersecretion in an unfed 3-month-old male with short bowel syndrome. We measured gastric volume and H+ serially for 12 h following each bolus and correlated inhibition of H+ secretion with plasma ranitidine concentration. In the first 4 h post drug, doses of 0.3, 1.0, 2.0, and 4.0 mg/kg resulted in 78, 93, 97, and 98% inhibition, respectively. The cumulative 12-h effect of the drug was to inhibit H+ secretion 67, 63, 72, and 87%. The IC50 for H+ secretion was between 50 and 100 ng/ml, and the IC90 between 130 and 150 ng/ml. Volume of gastric secretions was reduced by approximately 50% by all ranitidine doses. Because gastric acid hypersecretion interferes with nutrient absorption, the infant was treated with ranitidine during a 5-week trial of enteral feeding. A decrease in the antisecretory effect of ranitidine apparent at the end of the treatment period temporally related to an increase in oxyntic mucosal function. No adverse drug effects were observed during treatment.     

An integrated approach to the treatment of chiasmatic-hypothalamic gliomas

The treatment of visual pathway gliomas is controversial. The many retrospective studies reporting outcome data for patients with chiasmatic/hypothalamic gliomas are difficult to interpret for several reasons. First the natural history of these tumors is erratic with some reports suggesting that most visual pathway gliomas are hamartomas and follow an indolent course, and others reporting 10-year survival rates of close to 60%. Second, earlier studies did not clearly indicate which patients had neurofibromatosis type 1 (NF1) and recent evidence suggests that the natural history of optic gliomas is more favorable in patients with NFL Third the methods and accuracy of diagnosis have changed dramatically and patients diagnosed before and after the[/p] advent of CT/MR imaging have often been included in the same series.While surgical resection is usually not a viable option for definitive treatment of these tumors, recent studies have shown favorable results after subtotal resection in selected patients. The efficacy of radiotherapy has not been unequivocally demonstrated and treatment-related morbidity has become a major concern, in particular, adverse effects on cognition and growth. Chemotherapy has been advanced as an viable alternative to avoid or delay the adverse affects of RT, but the long-term outcome benefits and adverse effects of treatment are just being defined. Despite the limitations of currently available information, sufficient data are now available to rational management quotelines for the majority of children with chiasmatic/hypothalamic gliomas.     

Differences between pregnant and nulliparous rats in basal and stress levels of metallothionein

The present experiment was designed to examine the influence of pregnancy on basal and stress levels of serum and liver metallothionein (MT). Eighteen-day pregnant rats showed higher serum MT levels and lower liver MT levels than nulliparous rats, suggesting that a great MT mobilization from the liver into the serum was present in the former rats. Serum MT levels were not changed by either restraint or starvation. It is unlikely that the lower liver MT levels showed by pregnant rats were due to competition by progesterone for glucocorticoid receptors, as previously suggested, since the corticosterone/progesterone ratio was unchanged in pregnant rats. Liver MT response to food and water deprivation with or without restraint was somewhat different in nulliparous and pregnant rats. Thus, food and water deprivation for 24 h caused higher liver MT induction in pregnant than in nulliparous rats. When food and water deprivation was accompanied by restraint stress a further increase in liver MT was observed in nulliparous but not in pregnant rats. This suggests that food and water deprivation may be a more severe stress in pregnant rats because of the additional demands of the growing fetuses. Fetal liver MT was increased by restraint stress but not by food and water deprivation. The role of Zn influx into the liver is discussed.     

Prevalence of leptospiral infection in Texas cattle: implications for transmission to humans

Of 1193 Texas slaughterhouse cattle serum samples assayed for anti-leptospiral antibodies by microscopic agglutination testing, 262 (22%) reacted with serovar pomona and 179 (15%) with serovar hardjo. Of 300 urine samples tested for leptospiral DNA by a polymerase chain reaction assay, 106 (35%) were positive. The high prevalence of leptospiral infection of cattle represents potential threats to human health and agricultural economics.     

Troglitazone antagonizes metabolic effects of glucocorticoids in humans: effects on glucose tolerance,insulin sensitivity,suppression of free fatty acids,and leptin

Glucocorticoids induce insulin resistance in humans, whereas thiazolidinediones enhance insulin sensitivity. Although the effects of glucocorticoids and thiazolidinediones have been assessed in isolation, interaction between these drugs, which both act as ligands for nuclear receptors, has been less well studied. Therefore, we examined the metabolic effects of dexamethasone and troglitazone, alone and in combination, for the first time in humans. A total of 10 healthy individuals with normal glucose tolerance (age 40 +/- 11 years, BMI 31 +/- 6.1 kg/m(2)) were sequentially studied at baseline, after 4 days of dexamethasone (4 mg/day), after 4-6 weeks on troglitazone alone (400 mg/day), and again after 4 days of dexamethasone added to troglitazone. Key metabolic variables included glucose tolerance assessed by blood glucose and insulin responses to an oral glucose tolerance test (OGTT), insulin sensitivity evaluated via hyperinsulinemic-euglycemic clamp, free fatty acids (FFAs) and FFA suppressibility by insulin during the clamp study, and fasting serum leptin. Dexamethasone drastically impaired glucose tolerance, with fasting and 2-h OGTT insulin values increasing by 2.3-fold (P < 0.001) and 4.4-fold (P < 0.001) over baseline values, respectively. The glucocorticoid also induced a profound state of insulin resistance, with a 34% reduction in maximal glucose disposal rates (GDRs; P < 0.001). Troglitazone alone increased GDRs by 20% over baseline (P = 0.007) and completely prevented the deleterious effects of dexamethasone on glucose tolerance and insulin sensitivity, as illustrated by a return of OGTT glucose and insulin values and maximal GDR to near-baseline levels. Insulin-mediated FFA suppressibility (FFA decline at 30 min during clamp/FFA at time 0) was also markedly reduced by dexamethasone (P = 0.002). Troglitazone had no effect per se, but it was able to normalize FFA suppressibility in subjects coadministered dexamethasone. Futhermore, the magnitudes of response of FFA suppressibility and GDR to dexamethasone were proportionate. The same was true for the reversal of dexamethasone-induced insulin resistance by troglitazone, but not in response to troglitazone alone. Leptin levels were increased 2.2-fold above baseline by dexamethasone. Again, troglitazone had no effect per se but blocked the dexamethasone-induced increase in leptin. Subjects experienced a 1.7-kg weight gain while taking troglitazone but no other untoward effects. We conclude that in healthy humans, thiazolidinediones antagonize the action of dexamethasone with respect to multiple metabolic effects. Specifically, troglitazone reverses both glucocorticoid-induced insulin resistance and impairment of glucose tolerance, prevents dexamethasone from impairing the antilipolytic action of insulin, and blocks the increase in leptin levels induced by dexamethasone. Even though changes in FFA suppressibility were correlated with dexamethasone-induced insulin resistance and its reversal by troglitazone, a cause-and-effect relationship cannot be established. However, the data suggest that glucocorticoids and thiazolidinediones exert fundamentally antagonistic effects on human metabolism in both adipose and muscle tissues. By preventing or reversing insulin resistance, troglitazone may prove to be a valuable therapeutic agent in the difficult clinical task of controlling diabetes in patients receiving glucocorticoids.     

Abnormal neurologic maturation in adolescents with early-onset schizophrenia

OBJECTIVE: This study evaluated neurologic functioning in adolescents with schizophrenia with onset of psychosis before age 13. METHOD: The authors administered a structured neurologic examination to 21 adolescents with early-onset schizophrenia and 27 healthy age- and sex-matched comparison subjects. RESULTS: The adolescents with schizophrenia had a high frequency of neurologic abnormalities. Neurologic signs decreased with age in the healthy comparison subjects but not in the subjects with schizophrenia. CONCLUSIONS: The adolescents with schizophrenia had a high burden of neurologic impairment and a pattern of abnormalities similar to that of adults with schizophrenia. The persistence of neurologic signs in the adolescents with schizophrenia, which faded with age in the healthy comparison adolescents, supports earlier evidence of a delay in or failure of normal brain development during adolescence.     

Fungal infections of the spine. Report of eleven patients with long-term follow-up

BACKGROUND: Fungal infections of the spine are noncaseating, acid-fast-negative infections that occur primarily as opportunistic infections in immunocompromised patients. We analyzed eleven patients with spinal osteomyelitis caused by a fungus, and we developed suggestions for treatment. METHODS: All patients with a fungal infection of the spine treated by the authors over a sixteen-year period at three teaching institutions were evaluated. There was a total of eleven patients. Medical records and roentgenograms were available for every patient. Long-term follow-up of the nine surviving patients was performed by direct examination by the authors or by the patient's primary physician. RESULTS: For ten of the eleven patients, the average delay in the diagnosis was ninety-nine days. Nine patients were immunocompromised secondary to diabetes mellitus, corticosteroid use, chemotherapy for a tumor, or malnutrition. The sources of the spinal infections included direct implantation from trauma (one patient), hematogenous spread (four patients), and local extension (two patients). The infection followed elective spine surgery in three patients, and the cause was unknown in one. Paralysis secondary to the spine infection developed in eight patients. Ten patients were treated with surgical debridement. All eleven patients were treated with systemic antifungal medications for a minimum of six weeks. One patient died of generalized sepsis at thirty-three days, and another patient died of gastrointestinal hemorrhage at five months. After an average of 6.3 years of follow-up, the infection had resolved in all nine surviving patients. CONCLUSIONS: Treatment of fungal spondylitis is often delayed because of difficulty with the diagnosis. Delay in the diagnosis led to poorer results in terms of neurologic recovery in our study. Performing fungal cultures whenever a spinal infection is suspected might hasten the diagnosis. Patients should be given a guarded prognosis and informed of the many possible complications of the disease.     

An evaluation of alcohol attendances to an inner city emergency department before and after the introduction of the UK Licensing Act 2003

Background  

The Licensing Act 2003 (The Act) was implemented on the 24th November 2005 across England and Wales. The Act allowed more flexible and longer opening hours for licensed premises. We investigated the effect of The Act on alcohol related attendances to an inner city emergency department in Birmingham, UK.