Apolipoprotein E alleles in nonagenarian subjects in the Belfast Elderly Longitudinal Free-living Ageing Study (BELFAST)

The ApoE gene has three alleles coding for the proteins apoE2, apoE3 and apoE4. E4 has been reported to be associated with hypercholesteraemia, ischaemic heart disease, age-related cognitive decline and Alzheimer's disease. Conversely, the E2 allele has been associated with longevity in French centenarians and their siblings. In this study, we have assessed any shift in the ApoE genotypes in nonagenarian subjects from Belfast where there is a high intrinsic incidence of cardiovascular disease. ApoE phenotypes were determined by electrofocusing and immunoblotting in 114 Senieur-approximated subjects >90 years old and compared with 2071 subjects, 30--65 years of age, recruited from the same geographical area by the MONItoring of CArdiovascular trends study group in Belfast (MONICA). The E4 allele was reduced in the nonagenarian group (X(2)=11.1; P=0.0006), the E3 unchanged and E2 frequency was increased (X(2)=4.0; P=0.047). These results suggest that longevity is negatively associated with the E4 allele and may be associated with carriage of E2.     

Molecular detection and quantification of pertussis and correlation with clinical outcomes in children

Pertussis is an under-recognized serious infection. Conventional cultures are insensitive and of limited utility after antibiotic exposure. We corroborated the utility of real-time polymerase chain reaction (PCR) as a diagnostic tool in pertussis and investigated its role as a prognostic tool by evaluating its benefit in the quantification of pertussis bacterial load. All pertussis-positive PCR tests (n = 104) submitted over 5 years were collected for retrospective study. PCR cycle threshold was compared to quantitative culture in 43. Compared to PCR, the sensitivity of culture was 41%. Our PCR assay reliably quantified bacterial load and was quantitatively reproducible. Higher bacterial load correlated with longer duration of hospitalization (P = 0.0003), and multivariate logistic regression models demonstrated this association to be independent. The study confirmed PCR as a superior diagnostic tool in pertussis. PCR quantification of bacterial load at initial diagnosis predicts later clinical disease severity, suggesting a potential benefit of PCR as a prognostic tool in pertussis.     

Pylephlebitis: Keep it in your differential diagnosis

Pylephlebitis is thrombophlebitis of the portal vein or its tributaries. It is a rare diagnosis that carries a high mortality if not diagnosed and treated before the onset of sepsis. The authors describe a case of pylephlebitis in a patient who represented with sepsis after surgical treatment of perforated appendicitis.     

Subacute Perforation of the St. Jude Riata Implantable Cardioverter–Defibrillator Lead: A Report of Two Pediatric Cases

The Medtronic Riata implantable cardioverter–defibrillator (ICD) lead is a 7-Fr ICD lead shown to have a propensity for cardiac perforation. This report details two pediatric cases of cardiac perforation in patients with a Riata ICD lead. Analysis regarding the effect of ICD implantation techniques on cardiac perforation specific to pediatric patients is discussed.     

Domperidone is more effective than cisapride in children with diabetic gastroparesis

BACKGROUND: Disorders of gastrointestinal motility are commonly detected in patients with insulin-dependent diabetes mellitus and are associated with significant morbidity. They contribute to poor metabolic control of diabetes. AIM: To assess the effect of an 8-week course of domperidone or cisapride on gastric electrical activity, gastric emptying time and dyspeptic symptoms in children with insulin-dependent diabetes mellitus and gastroparesis. METHODS: Dyspeptic symptoms were assessed by a score system, gastric emptying time was measured by ultrasonography and gastric electrical activity was obtained by electrogastrography. Fourteen children received domperidone and 14 received cisapride. The median (range) ages were 11.6 years (5-15 years) and 12 years (6-16.9 years), respectively. Symptom assessment, ultrasonography and electrogastrography were repeated at the end of the trial. Fasting and fed (180 min after feeding) glycaemia and haemoglobin A, C (HbA1c) levels were also measured. RESULTS: At the end of the trial both groups showed a significant decrease in symptomatic score; however, the score was markedly lower in the domperidone group than in the cisapride group (P < 0.01). Domperidone was significantly more effective than cisapride in reducing the gastric emptying time (P < 0.05), normalizing gastric electrical activity (P < 0.05) and decreasing the prevalence of episodes of gastric dysrhythmia (P < 0.01). Domperidone was also more effective than cisapride in improving diabetic metabolic control. No potentially drug-related adverse effects occurred. CONCLUSIONS: In children with insulin-dependent diabetes mellitus complicated by dyspeptic symptoms and gastroparesis, domperidone is superior to cisapride in reversing gastric emptying delay and gastric electrical abnormalities, as well as in improving dyspeptic symptoms and diabetic metabolic control.     

Goserelin as ovarian protection in the adjuvant treatment of premenopausal breast cancer: a phase II pilot study

The aim of the present trial was to investigate the protective effects on ovarian function, and the efficacy and tolerability of goserelin added to adjuvant chemotherapy for early breast cancer. Following surgical treatment, 64 premenopausal patients with early breast cancer received goserelin 3.6 mg (every 28 days for 1 year) and an adjuvant treatment which was chosen according to the patient's prognosis. Median age was 42 years (range 27-50). ECOG performance status was 0-1 in all patients. Twenty-eight patients (44%) had estrogen receptor (ER)+ tumors and 36 (56%) patients had ER- tumors. Fifty-two (81%) patients had stage II disease and 12 (19%) had stage III disease. Eighteen patients received cyclophosphamide, methotrexate and 5-fluorouracil chemotherapy, 46 patients received an anthracycline-based regimen, and nine of them received high-dose chemotherapy and autologous peripheral blood progenitor cell transplantation. Fifty-one patients (80%) were irradiated. ER+ patients also received tamoxifen for 5 years. Serum estradiol was suppressed to values below 40 pg/ml in all patients. After a median follow-up of 55 months, 86% of patients had resumed normal menses, 84% of patients were disease-free and 94% were alive. The 1-, 3- and 5-year projected recurrence-free survival rates were 100, 81 and 75%, respectively. Five years after treatment one patient had a pregnancy that ended with a normal childbirth. No unexpected adverse events were reported. These data show that the addition of goserelin to adjuvant therapy of premenopausal patients with early breast cancer is well tolerated and protects long-term ovarian function.     

Ulcerative colitis after statin treatment

Statin treatment is widely used in both primary and secondary prevention of diseases in which hyperlipidaemia is a major risk factor, for example, ischaemic heart disease. The development of ulcerative colitis as an adverse reaction to simvastatin is reported, which, despite withdrawal of the drug, proved fatal. The adverse reaction profile of the statins is reviewed, which suggests that this is a class effect and not one limited to simvastatin.     

Modulation of behavioral sensitization to cocaine by NAALADase inhibition

Sensitization to cocaine has been attributed to alterations in excitatory amino acid and dopamine neurotransmission in the mesolimbic system. The present study sought to determine whether inhibition of NAALADase, an enzyme that cleaves glutamate from the endogenous neuropeptide, N-acetyl-aspartyl-glutamate (NAAG), attenuates sensitization to the psychomotor stimulant effects of cocaine. Rats received daily injections of cocaine (20.0 mg/kg/day; i.p.) or saline for 5 days. Fifteen minutes prior to these injections they received an i.p. injection of the NAALADase inhibitor, 2-PMPA (50.0-100 mg/kg), or vehicle. Locomotor activity and stereotypy produced by a challenge dose of cocaine (15.0 mg/kg) were assessed 3 days later. Acute cocaine administration increased locomotor activity in control animals. In animals with a prior history of cocaine administration, the behavioral response to cocaine was significantly enhanced. In animals that had received 2-PMPA in combination with cocaine, the enhancement of cocaine-induced locomotor activity was attenuated. No alteration in cocaine-evoked activity was observed in animals that had received once daily injections of 2-PMPA, alone. Acute administration of 2-PMPA also did not modify saline-induced locomotor activity or activity produced by an acute cocaine challenge. These data demonstrate that NAALADase inhibition attenuates the development of sensitization to the locomotor-activating effects of cocaine. Furthermore, this action cannot be attributed to an antagonism of the acute effects of cocaine.