Oral ondansetron decreases vomiting after tonsillectomy in children

Vomiting is a common, unpleasant aftermath of tonsillectomy in children. Intraoperative intravenous ondansetron (OND) reduces vomiting after this operation. Our doubleblind, placebocontrolled, randomized investigation studied the effect of the oral form of OND on vomiting after outpatient tonsillectomy in children. We studied 233 healthy children age 2–14 yr undergoing elective tonsillectomy. Subjects were given placebo (PLAC) or OND 0.1 mg · kg^?1 rounded off to the nearest 2 mg one hr before surgery. Anaesthesia was induced with either propofol or halothane/N₂O. Vecuronium 0.1 mg · kg^?1 was administered at the discretion of the anaesthetist. Anaesthesia was maintained with halothane/N₂O, 50 μg · kg^?1 midazolam iv and 1–1.5 mg · kg^?1 codeine im. At the end of surgery, residual neuromuscular blockade was reversed with neostigmine and atropine. All episodes of inhospital emesis were recorded by nursing staff. Rescue antiemetics in the hospital were 1 mg · kg^?1 dimenhydrinate ivfor vomiting × 2 and 50 μg · kg^?1 droperidol iv for vomiting × 4. Parents kept a diary of emesis after discharge. Postoperative pain was treated with morphine, codeine and/or acetaminophen. The two groups were similar with respect to demographic data, induction technique and anaesthesia time. Oral OND (n = 109) reduced postoperative emesis from 54% to 39%, P < 0.05. This effect was most dramatic inhospital, where 10% of the OND-patients and 30% of the PLAC-group vomited, P < 0.05. The OND-subjects required fewer rescue antiemetics, 7% vs 17%, P < 0.05. In conclusion, oral ondansetron decreased the incidence of vomiting after outpatient tonsillectomy in children.     

An Early Onset Rehabilitation Program for Children and Adolescents after Traumatic Brain Injury (TBI): Methods and First Results

Survived traumatic brain injuries (TBI) are one of the most serious challenges to the patient's future life. Recent literature increasingly questions the long believed protective effects of functional cerebral plasticity in children. Although TBI in children and adolescents is frequent, they are less frequently admitted to rehabilitation centers as in-patients than adults. This emphasizes the role of out-patient treatment. The progressing study described here aims to achieve a contribution to a comprehensive approach in TBI-rehabilitation for youngsters. A two-stage multimethodal program, starting with stimulation in coma while the patient is on the intensive care unit, and neuropsychological therapy after regaining consciousness is to be evaluated in a controlled, prospective and randomized study. After including nearly 50 % of the planned sample (100 persons), some preliminary results can be mentioned with all applicable caution. The effectiveness of the applied therapy can be stated here with respect to the posttraumatic development of intellectual abilities in the 6- and 12 months follow ups. Moreover, in the control group development of psychopathological alterations was found to a considerable degree and also lower ratings in a quality of life questionnaire, compared to the experimental group. It is expected to prove these differences statistically, after the total sample has been included, and thus equal distributions have been achieved in all predictive variables.     

Tunicamycin Dissociates Depolarization-induced Calcium Entry From Transmitter Release. Involvement of Glycosylated Protein(s) in the Process of Neurosecretion in PC-12 Cells

The process of regulated secretion in PC-12 cells is tightly coupled to calcium entry, which is absolutely dependent on extracellular Ca2+([Ca2+]ex). Tunicamycin treatment of the cells dissociated depolarization-triggered Ca2+ influx from depolarization (high K+)-induced transmitter release into two distinct and independent phases. Deplarization-evoked Ca2+ influx was not affected by tunicamycin treatment (1 microg/ml, 72 h), whereas depolarization-evoked transmitter release was strongly inhibited (> 60%), suggesting at least a two-step process, and the participation of glycosylated protein(s) in the actual fusion/secretion step. Similarly, bradykinin-mediated transmitter release was linearly related to and absolutely dependent on Ca2+ entry, and was inhibited by tunicamycin treatment (> 80%), whereas bradykinin-evoked Ca2+ entry was not impaired, indicating that glycosylated protein(s) are essential for bradykinin-evoked release at a step subsequent to Ca2+ influx. The heavily glycosylated alpha2 subunit of the dihydropyridine-sensitive channel, which was used to monitor tunicamycin inhibition of glycosylation, was not expressed in the tunicamycin-treated cells, as shown by Western blot analysis. This observation allowed us to conclude that the alpha1 subunit of the heteromeric dihydropyridine voltage-sensitive Ca2+ channel, which is responsible for Ca2+ entry, is also fully functional when not assembled with its corresponding alpha2 subunit. The molecular properties of the alpha2 subunit, whose role in the complex structure of the channel is not yet understood, are shown for the first time for the L-type Ca2+ channel of PC-12 cells. Similar to cardiac and skeletal muscle cells, the alpha2 subunit appears to be a glycosylated polypeptide of molecular weight 170 kD and to display a characteristic mobility shift to 140 kD under reducing conditions.     

Tissue Inhibitor of Metalloproteinase-1 Concentrations are Attenuated in Peritoneal Fluid and Sera of Women with Endometriosis and Restored in Sera by Gonadotropin-Releasing Hormone Agonist Therapy

Objective: To establish tissue inhibitor of metalloproteinase-1 (TIMP-1) concentrations in peritoneal fluid (PF) and sera of women with endometriosis and compare them to disease-free controls.

Design: Prospective randomized study.

Setting: Academic medical center.

Patient(s): Women with laparoscopically documented endometriosis and disease-free women of reproductive age.

Intervention(s): Peritoneal fluid and sera were collected, and some women received gonadotropin-releasing hormone agonist (GnRH-a) therapy for endometriosis.

Main Outcome Measure(s): Peritoneal fluid and sera TIMP-1 concentrations were measured with a specific RIA.

Result(s): The TIMP-1 concentrations were significantly lower in PF and sera of women with endometriosis compared with disease-free women. The GnRH-a therapy restored serum TIMP-1 concentrations.

Conclusion(s): Aberrant expression and localization of TIMP-1 may derange the proteolytic milieu of the peritoneal cavity and contribute to the etiology and underlying physiologic sequelae associated with endometriosis. Measurement of TIMP-1 in serum may aid in diagnosing endometriosis and assist with monitoring treatment efficacy in women with this disease.     

Prevalence of potentially severe drug-drug interactions in ambulatory patients with dyslipidaemia receiving HMG-CoA reductase inhibitor therapy.

BACKGROUND: Drug-drug interactions (DDIs) are a well known risk factor for adverse drug reactions. HMG-CoA reductase inhibitors ('statins') are a cornerstone in the treatment of dyslipidaemia and patients with dyslipidaemia are concomitantly treated with a variety of additional drugs. Since DDIs are associated with adverse reactions, we performed a cross-sectional study to assess the prevalence of potentially critical drug-drug and drug-statin interactions in an outpatient adult population with dyslipidaemia. METHODS: Data from patients with dyslipidaemia treated with a statin were collected from 242 practitioners from different parts of Switzerland. The medication list was screened for potentially harmful DDIs with statins or other drugs using an interactive electronic drug interaction program. RESULTS: We included 2742 ambulatory statin-treated patients (mean age +/- SD 65.1 +/- 11.1 years; 61.6% males) with (mean +/- SD) 3.2 +/- 1.6 diagnoses and 4.9 +/- 2.4 drugs prescribed. Of those, 190 patients (6.9%) had a total of 198 potentially harmful drug-statin interactions. Interacting drugs were fibrates or nicotinic acid (9.5% of patients with drug-statin interactions), cytochrome P450 (CYP) 3A4 inhibitors (70.5%), digoxin (22.6%) or ciclosporin (cyclosporine) [1.6%]. The proportion of patients with a potential drug-statin interaction was 12.1% for simvastatin, 10.0% for atorvastatin, 3.8% for fluvastatin and 0.3% for pravastatin. Additionally, the program identified 393 potentially critical non-statin DDIs in 288 patients. CONCLUSIONS: CYP3A4 inhibitors are the most frequent cause of potential drug interactions with statins. As the risk for developing rhabdomyolysis is increased in patients with drug-statin interactions, clinicians should be aware of the most frequently observed drug-statin interactions and how these interactions can be avoided.     

Immunohistochemical expression of DNA repair proteins in familial breast cancer differentiate BRCA2-associated tumors.

PURPOSE: Morphologic and immunohistochemical studies of familial breast cancers have identified specific characteristics associated with BRCA1 mutation-associated tumors when compared with BRCA2 and non-BRCA1/2 tumors, but have not identified differences between BRCA2 and non-BRCA1/2 tumors. Because BRCA1 and BRCA2 genes participate in the DNA repair pathway, we have performed an immunohistochemical study with markers related to this pathway to establish the profile of the three groups. MATERIALS AND METHODS: We have studied two tissue microarrays that include 103 familial and 104 sporadic breast tumors, with a panel of DNA repair markers including ATM, CHEK2, RAD51, RAD50, XRCC3, and proliferating cell nuclear antigen. RESULTS: We found more frequent expression of CHEK2 in BRCA1 and BRCA2 tumors than in non-BRCA1/2 and sporadic tumors. We found absence of nuclear expression and presence of cytoplasmic expression of RAD51 in BRCA2 tumors that differentiate them from other familial tumors. We validated these results with a new series of patient cases. The final study with 253 familial patient cases (74 BRCA1, 71 BRCA2, 108 non-BRCA1/2), and 288 sporadic patient cases, has allowed us to confirm our preliminary results. Because BRCA2 tumors present a specific immunohistochemical profile for RAD51 and CHEK2 markers that is different from non-BRCA1/2 tumors, we have built a multivariate model with these markers that distinguish both tumors with an estimated probability of at least 76%. CONCLUSION: Our results suggest that BRCA2 tumors demonstrate more cytoplasmic and less nuclear RAD51 staining, and increased CHEK2 staining. This pattern may distinguish BRCA2 from familial non-BRCA1/2 tumors.     

Influence of Documented Lead Poisoning on Environmental Modification Programs in Newark,New Jersey

Data from the Newark, New Jersey Childhood Lead Poisoning Program suggest that the major consequence of the program has been early intervention rather than the amelioration of environmental contamination. During 1975 to 1976, the authors investigated housing for 253 black and Hispanic children with blood levels over 60 Mg/100 ml. Of these, 115 had moved or had given incorrect addresses and were lost to follow-up, 22 were in the same homes but did not make themselves available and in 16 instances, the houses were boarded up or had been destroyed by fire. Of the remaining 100 children, 31% suffered from symptoms potentially related to lead poisoning and 57% of the children were still living in the same dwelling in which the c h id was affected. Only one-fourth of the houses had been properly abated, i. e., the problem of environmental lead had been corrected, and one-fourth of the houses were not investigated at all by health authorities. These data support the concern that lead poisoning will not be effectively combated until the environmental issue is fully addressed.     

A new instrument for assessing the quality of studies on prevalence

There are numerous scientific articles of studies on the prevalence of disorders with non-standardised examination and diagnostic protocols. Because their quality is heterogeneous, a new instrument has been developed for the assessment of such studies. The new instrument is based mainly on statistical criteria. The points assigned for each of the main criteria according to the information gained from each paper are summed up to form a Total Quality Score (TQS). The interrater reliability of the instrument was tested by employing Kappa and Interrater Correlation Coefficient (ICC) statistics. The latter was assessed on the results of three independent investigators. The new quality instrument appeared to be easy to use, and the instructions were comprehensible. The ICC_(2,1) for the TQS ranged between 0.94 and 1.00 indicating almost perfect agreement between the investigators. The reliability of the new instrument enables its use for scientific review purposes. In this way, its validity will also be tested. The instrument could be adopted for assessment of scientific articles of studies on the prevalence of disorders in many, similar, scientific areas.