Effects of neonatal exposure to the flame retardant tetrabromobisphenol-A, aluminum diethylphosphinate or zinc stannate on long-term potentiation and synaptic protein levels in mice.

Brominated flame retardants such as tetrabromobisphenol-A (TBBPA) may exert (developmental) neurotoxic effects. However, data on (neuro)toxicity of halogen-free flame retardants (HFFRs) are scarce. Recent in vitro studies indicated a high neurotoxic potential for some HFFRs, e.g., zinc stannate (ZS), whereas the neurotoxic potential of other HFFRs, such as aluminum diethylphosphinate (Alpi), appears low. However, the in vivo (neuro)toxicity of these compounds is largely unknown. We therefore investigated effects of neonatal exposure to TBBPA, Alpi or ZS on synaptic plasticity in mouse hippocampus. Male C57bl/6 mice received a single oral dose of 211 µmol/kg bw TBBPA, Alpi or ZS on postnatal day (PND) 10. On PND 17-19, effects on hippocampal synaptic plasticity were investigated using ex vivo extracellular field recordings. Additionally, we measured levels of postsynaptic proteins involved in long-term potentiation (LTP) as well as flame retardant concentrations in brain, muscle and liver tissues. All three flame retardants induced minor, but insignificant, effects on LTP. Additionally, TBBPA induced a minor decrease in post-tetanic potentiation. Despite these minor effects, expression of selected synaptic proteins involved in LTP was not affected. The flame retardants could not be measured in significant amounts in the brains, suggesting low bioavailability and/or rapid elimination/metabolism. We therefore conclude that a single neonatal exposure on PND 10 to TBBPA, Alpi or ZS does affect neurodevelopment and synaptic plasticity only to a small extent in mice. Additional data, in particular on persistence, bioaccumulation and (in vivo) toxicity, following prolonged (developmental) exposure are required for further (human) risk assessment.

Current clinical guideline definitions of airflow obstruction and COPD overdiagnosis in primary care.

The aim of the present study was to establish the agreement between two recommended definitions of airflow obstruction in symptomatic adults referred for spirometry by their general practitioner, and investigate how rates of airflow obstruction change when pre-bronchodilator instead of post-bronchodilator spirometry is performed. The diagnostic spirometric results of 14,056 adults with respiratory obstruction were analysed. Differences in interpretation between a fixed 0.70 forced expiratory volume in one second (FEV(1))/forced vital capacity (FVC) cut-off point and a sex- and age-specific lower limit of normal cut-off point for this ratio were investigated. Of the subjects, 53% were female and 69% were current or ex-smokers. The mean post-bronchodilator FEV(1)/FVC was 0.73 in males and 0.78 in females. The sensitivity of the fixed relative to the lower limit of normal cut-off point definition was 97.9%, with a specificity of 91.2%, positive predictive value of 72.0% and negative predictive value of 99.5%. For the subgroup of current or ex-smokers aged > or =50 yrs, these values were 100, 82.0, 69.2 and 100%, respectively. The proportion of false positive diagnoses using the fixed cut-off point increased with age. The positive predictive value of pre-bronchodilator airflow obstruction was 74.7% among current or ex-smokers aged > or =50 yrs. The current clinical guideline-recommended fixed 0.70 forced expiratory volume in one second/forced vital capacity cut-off point leads to substantial overdiagnosis of obstruction in middle-aged and elderly patients in primary care. Using pre-bronchodilator spirometry leads to a high rate of false positive interpretations of obstruction in primary care.

Overtreatment with inhaled corticosteroids and diagnostic problems in primary care patients, an exploratory study.

BACKGROUND: Underdiagnosis and undertreatment of patients with asthma or chronic obstructive pulmonary disease are widely discussed in the literature. Not much is known about the possible overdiagnosis and consequently the overtreatment with inhaled corticosteroids (ICS). Aim. This study investigates how often ICS are prescribed without a proper indication and how big the diagnostic problem is caused by inappropriate prescription and use of ICS. METHODS: All patients referred to a primary care diagnostic centre during 6 months who used ICS without a clear indication were included. Their GPs were questioned about the reasons for prescribing ICS. If still no diagnosis could be assessed, GPs were advised to stop ICS and renew spirometry after a steroid-free period of at least 3 months. After 1 year, the use of ICS was evaluated and the diagnoses were reassessed. RESULTS: Of all referred patients (2271), 1171 used ICS, 505 (30%) without a clear indication. After 1 year, final results showed that 11% of all patients originally using ICS had no indication to use ICS and had successfully ceased using this mediation. For 15%, the reasons for using ICS remained unclear. CONCLUSIONS: Overtreatment with ICS in primary care seems to be considerable, which falsely labels patients as asthmatic and which generates unnecessary costs and possible side effects. The awareness of GPs of the need for proper diagnostic testing before prescribing ICS needs to be improved. Overtreatment with ICS in primary care patients can be diminished by systematically supporting the GP in the diagnostic procedures and decision making.

Use of the rhomboid major muscle flap for esophageal repair.

A 16-year-old boy sustained vehicular blunt trauma with delayed esophageal rupture that resulted in empyema and an esophagopleurocutaneous fistula. Diverting esophagostomy, gastrotomy, and transpyloric jejunostomy were performed, and these procedures permitted satisfactory nutritional support of the patient. Staged direct closure of the esophagus buttressed by a rhomboid muscle flap preserved normal esophageal function. Both clinical application and cadaver dissections have demonstrated that the rhomboid flap has an excellent blood supply and that it can be used to repair lesions on either side in the upper half of the esophagus. Because this flap is extrathoracic, it is not usually distorted by intrathoracic sepsis or previous thoracic incisions. The rhomboid major muscle flap is an excellent alternative to conventional autogenous grafts for esophageal repair.

Subxiphoid pericardiotomy. A safe, accurate, diagnostic and therapeutic approach to pericardial and intrapericardial disease.

The records of 36 patients who underwent subxiphoid pericardiotomy were reviewed to determine the safety, accuracy, and utility of the procedure. No deaths were attributed to the operation, and complications were minimal. Most operations were performed under local anesthesia. Findings at operation accurately defined which patients required further surgery and which did not. Although clinical, radiographic, and physical findings are inaccurate in determining the nature and extent of pericardial and intrapericardial pathology, a definitive diagnosis was obtained in all diagnostic procedures. Only one patient needed a second operation, attesting to the effectiveness of subxiphoid drainage as a therapeutic modality.

Bronchoscopy in the critically ill surgical patient.

Sixty-seven bronchoscopic examinations were performed in a busy surgical intensive care unit on 51 patients, and the techniques, morbidity, and outcome were prospectively analyzed to assess the efficacy and safety of the procedure in this particular patient population. General surgical trauma, cardiothoracic, and orthopedic patients were included. Fifty-three (79%) procedures were performed with the flexible instrument, while 14 patients (21%) underwent rigid endoscopy. Forty-six patients were being mechanically ventilated; 30 had endotracheal tubes, and 16 had tracheostomies. Suspected lobar collapse (60%), persistent pulmonary infiltrates (3%), suspected aspiration (21%), and suspicion of airway trauma (12%) were the primary clinical indications for bronchoscopy. No deaths occurred. Complications were seen in 16 per cent of the procedures and 17 per cent of the patients. There were arrhythmias (other than sinus tachycardia) in seven procedures (11%) and one episode each of hypertension, self-limited endobronchial bleeding, mediastinal emphysema, and increased intracranial pressure. Significant improvement was demonstrated for patients with lobar collapse but not for those with mild atelectasis or pulmonary infiltrates on radiographs taken within 24 hours. Overall, 39 patients (58%) improved radiographically, while 38 patients (42%) did not. Differences in arterial PO2 measured before and after bronchoscopy between groups ventilated with an FiO2 of 1.0, and those who were not did not achieve statistical significance (P less than 0.05).

Patient-oriented intervention in addition to centrally organised checkups improves diabetic patient outcome in primary care.

BACKGROUND: Logistic support to general practitioners improves the care processes for patients with diabetes but is not sufficient to meet all criteria. AIM: To introduce patient-oriented interventions by a practice nurse in general practices which already use logistic support to improve the care processes for patients with diabetes. DESIGN OF STUDY: A controlled before-after study with delayed intervention in the control group. SETTING: 51 practices (n = 23 for the intervention and n = 28 for the control group) in the south of The Netherlands and 900 of their patients with type 2 diabetes. METHODS: Data were collected on the results of the checkups (fasting blood glucose, glycosylated haemoglobin (HbA1C), cholesterol, cholesterol/high-density lipoprotein ratio, triglycerides, creatinine, blood pressure, fundus photo, foot exam and body mass index), smoking status, physical activity and medication use. The effect of the patient-oriented intervention was analysed in a mixed model with repeated measurement covariance structure. RESULTS: The HbA1C improved in the intervention group (from 7.3 to 7.1), while that of the control group deteriorated (from 7.2 to 7.3). The percentage of patients with an HbA1C >or=8.5 was halved after the intervention (from 13 to 6). Patients in the intervention group started to exercise more besides their daily activities compared with the control group. The need for medication increased more in the control group than in the intervention group (more changes to insulin and more defined daily dose (DDD) oral medication). CONCLUSION: Patient-oriented interventions in addition to logistic support have a positive effect on diabetic patient outcomes.

Purulent mediastinal abscess secondary to Ludwig's angina.

A case of Ludwig's angina dissected along deep cervical fascial planes into the mediastinum caused a virulent mediastinitis and abscess. Computed tomography precisely delineated the extent of the infection. Incomplete débridement resulted in a residual abscess and persistent systemic sepsis that culminated in the patient's death. Aggressive antibiotic treatment of the orofacial cellulitis along with complete mediastinal drainage are recommended for optimal outcome.

The role of the individual administrator in famine relief: Three case studies.

A series of hypotheses on the role of the individual administrator in famine relief are proposed and three are examined with respect to case studies of famines in India (1896 and 1906-1907), Uganda (1908) and Lombok (1940). While the evidence is not conclusive, the focus upon the role of the individual administrator offers additional insights into the compexities of official response to famines.

Intra-aortic balloon counterpulsation for cardiogenic shock from cardiac contusion.

Two patients who sustained cardiac contusions secondary to blunt chest trauma developed refractory cardiogenic shock. Use of intra-aortic balloon counterpulsation improved circulatory dynamics in each case and one patient survived. Requirements for inotropic agents were diminished or eliminated, cardiac output was increased, acidosis was reversed, and the electrocardiogram reverted to normal. Although balloon counterpulsation is most effectively employed in patients with ischemic cardiac deficits, its early application coupled with appropriate pharmacologic treatment is also effective in raising low cardiac output that results from myocardial trauma.

Traumatic injury of the proximal superior mesenteric artery.

Injuries of the proximal superior mesenteric artery (SMA) are relatively uncommon, but extremely perplexing lesions. Fifteen consecutive patients with this injury, 13 injuries from gunshot wounds and two injuries from blunt trauma, have been treated. Associated lesions and massive blood loss were common, averaging 3.6 injuries and 4800 ml per patient, respectively. Methods of SMA repair include lateral arteriorrhaphy (11 patients), primary reanastomosis (3 patients), and saphenous vein grafts (1 patient). Two of three patients whose injuries included segmental loss of the SMA that required a primary end-to-end anastomosis suffered subsequent thrombosis. Second-look operations were performed in five patients with two of these requiring a further reconstructive procedure. The only late death occurred in a patient with a severe head injury and a failure of his SMA repair, which potentially could have been prevented by a second-look procedure. There were five deaths (33%), with four occurring from acute hemorrhages and one late death occurring following intestinal necrosis and sepsis. Malabsorption or other late intestinal complications did not occur. Our experience 1) supports the concept that proximal SMA lesions must be repaired, 2) suggests that primary anastomosis to repair arterial defects is associated with a high failure rate, and 3) demonstrates that the second-look operation is a useful adjunct in improving survival in these patients.