Electron spin resonance spectroscopy reveals alpha-phenyl-N-tert-butylnitrone spin-traps free radicals in rat striatum and prevents haloperidol-induced vacuous chewing movements in the rat model of human tardive dyskinesia

The typical antipsychotic drug haloperidol causes vacuous chewing movements (VCM) in rats, which are representative of early-Parkinsonian symptoms or later-onset extrapyramidal side effects of tardive dyskinesia (TD) in humans. Haloperidol (HP) has been hypothesized to potentiate increases in oxidative stress or free radical-mediated levels of toxic metabolites in rat striatum while simultaneous upregulating dopamine (DA)-D2 receptors leading to presumed DA supersensitivity. Alpha(alpha)-Phenyl-N-tert-butylnitrone (PBN) is an antioxidant used to combat oxidative stress and measure increases in PBN spin-adduct activity. Thus, the aim of this study was to investigate whether VCMs are related to upregulation of DA-D2 receptors or to increased levels of free radicals produced during oxidative stress, and whether PBN had any protective effects. Rats received daily chronic (28 day) i.p. injections of saline, haloperidol (2 mg/kg), PBN (150 mg/kg), or haloperidol + PBN. The VCM model was used to measure extrapyramidal side effects of drug treatments. Electron spin resonance (ESR) spectroscopy was performed to compare concentrations of free radical species in rats receiving injections of HP + PBN. To examine the upregulation of DA-D2 receptors, binding assays were carried out to assess the increase in DA-D(2) receptor numbers with respect to VCMs following treatment of rats injected with HP, PBN, and HP + PBN. Results of these experiments show that HP-induced VCMs in rats results from increases in oxidative cellular events and may not be related to increases in striatal DA-D(2) receptors.     

Postoperative assessment of the univentricular repair by dynamic radionuclide studies

Background

The purpose of this investigation was to determine the role of radionuclide studies in evaluating postoperative Fontan hemodynamics and to quantify its diagnostic accuracy.

Methods

One hundred five patients (105), aged 11 months to 35 years old, who had undergone univentricular repair, underwent first-pass and multigated acquisition scan 1 month to 10 years after univentricular repair. Forty-five patients with evidence of Fontan failure underwent radionuclide studies using Technetium-99 m as well as cardiac catheterization (group 1). The remaining sixty randomly selected patients with excellent functional status received radionuclide studies alone (group 2). The receiver operating characteristic curve analysis was done to quantify the diagnostic accuracy of the first-pass study.

Results

There was paradoxical filling of the right lung after femoral injection in all cases of tunnel or conduit obstruction. A first-pass transit time of 16 to 25 seconds (mean ± standard deviation [SD] = 18.82 ± 2.69) was always associated with Fontan failure and high right atrial pressure (range = 20 to 24 mm Hg, mean ± SD = 22.02 ± 1.58). A first-pass transit time of 16 seconds was associated with a sensitivity of 100% and a specificity of 93.33%. The predictive accuracy of a positive or negative result was 91.8% and 100% respectively. The area measured under the receiver operating characteristic curve indicates that 99.41% (SE ± 0.0035) of the time, the value of first-pass time is higher for the Fontan failure group (group 1) compared to the normal group (group 2; p = 0.000).

Conclusions

Our data indicate that Fontan circuit can be reliably evaluated for both anatomic and functional flaws by radionuclide studies; radionuclide first-pass time may be used to predict the chances of Fontan failure postoperatively as well as its presence; and in the presence of atrial fibrillation with fast ventricular rate, analysis using first-pass radionuclide may be impossible and gated equilibrium radionuclide angiocardiography may be the preferred method. Inspection of the systemic ventricular time-activity curve is of crucial importance in this regard.     

Three part posterior fracture dislocation of the hip without fracture of the femoral head: review of literature and a case report

This case report describes a rare posterior dislocation of the hip with fractures of the ipsilateral femoral neck and greater trochanter, without fracture of the femoral head, in a young adult male following a railway accident. This patient was managed within 6h of injury by open reconstruction. This unusual injury has not been reported previously. Cases of posterior fracture dislocation of the hip with a fracture of the femoral neck without fracture of the femoral head were reviewed from the literature. Mechanism of injury, controversies regarding operative procedures and appropriate surgical approach are discussed. The authors also believe that this injury pattern merits inclusion in the existing classification system of fracture dislocation of hip for management and prediction of outcome.     

Recombinant toxin DAB389EGF is cytotoxic to human pancreatic cancer cells

Few malignancies have frustrated the persistent efforts of the oncologist like pancreatic cancer. Pancreatic cancer is usually unresectable at the time of diagnosis because of metastasis or local extension. Despite the aggressive nature of this deadly disease, systemic treatment options are limited. Even the recent introduction of the deoxycytidine analogue gemcitabine does not extend median survival of responders beyond a year. Clearly, alternative, more effective regimens are needed for treating pancreatic carcinoma. In pancreatic cancer, there is overexpression of growth factors and growth factor receptors, including epidermal growth factor receptor (EGFR). Targeted toxins consist of a targeting polypeptide covalently linked to a peptide toxin. DAB(389)EGF is a fusion protein composed of the catalytic and translocation domains of diphtheria toxin fused via a His-Ala linker to human epidermal growth factor (EGF). The authors have previously shown that DAB(389)EGF is selectively toxic to EGFR-overexpressing cells, including human brain tumour and lung carcinoma cell lines. Pancreatic adenocarcinoma should be responsive to this fusion protein based on its EGFR overexpression. However, the cytotoxic effect of DAB(389)EGF on human pancreatic carcinoma cell lines has yet to be explored. The authors describe preliminary data showing the potent cytotoxicity of DAB(389)EGF to human pancreatic carcinoma cell lines. Because of the nonspecific toxicity to liver and kidney (which possess EGFR) of systemic administration, they also propose a potential novel drug delivery system for direct toxin implantation into pancreatic tumours using endoscopic ultrasound guided fine-needle injection (EUS-FNI). Hopefully, the use of these targeted therapeutic approaches in combination with other modalities may further extend survival and quality of life in patients with pancreatic adenocarcinoma.     

Passiflora: a review update

This review describes the morphology, microscopy, traditional and folklore uses, phyto-constituents, pharmacological reports, clinical applications and toxicological reports of the prominent species of the genus Passiflora. Flavonoids, glycosides, alkaloids, phenolic compounds and volatile constituents have been reported as the major phyto-constituents of the Passiflora species. A few species of Passiflora have been used for curing various ailments, the most important being Passiflora incarnata Linneaus which possesses significant CNS depressant properties. The studies performed by the authors with the newly isolated benzoflavone (BZF) moiety from P. incarnata have been discussed. In the concluding part, various virgin areas of research on the species of this genus have been highlighted with a view to explore, isolate and identify the medicinally important phyto-constituents which could be utilized to alleviate various diseases affecting the mankind.     

Social factors and obesity: an investigation of the role of health behaviours

OBJECTIVES: This study evaluated a behavioural model of the relation between social factors and obesity, in which differences in body mass index (BMI) across sociodemographic groups were hypothesized to be attributable to social group differences in health behaviours affecting energy expenditure (physical activity, diet and alcohol consumption and weight control). METHODS: A total of 8667 adults who participated in the 1995 Australian National Health and Nutrition Surveys provided data on a range of health factors including objectively measured height and weight, health behaviours, and social factors including family status, employment status, housing situation and migration status. RESULTS: Social factors remained significant predictors of BMI after controlling for all health behaviours. Neither social factors alone, nor health behaviours alone, adequately explained the variance in BMI. Gender-specific interactions were found between social factors and individual health behaviours. CONCLUSIONS: These results suggest that social factors moderate the relation between BMI and weight-related behaviours, and that the mechanisms underlying sociodemographic group differences in obesity may vary among men and women. Additional factors are likely to act in conjunction with current health behaviours to explain variation in obesity prevalence across sociodemographic groups.     

Distal spinal muscular atrophy of upper limb (Hirayama disease) associated with high serum lead levels

Hirayama disease causes unilateral or asymmetrical bilateral distal weakness and atrophy of upper limbs. We report a 6 1/2-year-old female with Hirayama disease and associated high serum lead levels. This report highlights the occurrence of this condition in younger children and the need to further study the role of lead in its pathophysiology.     

Low-birth-weight neonates exhibit a physiological set-point to regulate CO2: an untapped potential to minimize volutrauma-associated lung injury

The objective of this article is to determine whether low-birth-weight (LBW) infants have the capacity to modulate minute ventilation to achieve a CO (2) set-point within ranges acceptable to clinicians during a procedure designed to identify the best dynamic compliance loops. By using dynamic flow-loop mechanics, we performed a prospective stepwise reduction of tidal volume (by reduction of peak inspiratory pressure, keeping end-expiratory pressure constant), in a group of LBW infants to identify the steepest slope of the dynamic flow-loop. We used flow-synchronized, assist-control mechanical ventilation with termination sensitivity set at 5%. Vital signs and blood gases were assessed every 15 minutes at each stepped-pressure change during the first hour after enrollment and after 12 hours, to evaluate oxygenation and ventilation. Peak inspiratory pressure (PIP) was selected at the lowest level that achieved target range blood gases. The acute reduction of PIP and the resulting lower tidal volume was initially associated with an increase in the spontaneous respiratory rate in the first hour that also was associated with a significant decrease in patient-selected inspiration time. After 12 hours, the spontaneous respiratory rate returned to baseline; the peak PaCO(2) was 43.8 +/- 2.03 (mean +/- SEM). LBW infants have the capacity to alter respiratory rate to change minute ventilation in response to a reduction of tidal volume created by lowering the PIP. Using this model of endogenous CO(2) challenge in ventilated infants, we conclude that LBW neonates have the capacity to select a CO(2) set-point. This approach suggests an important avenue through which a clinician can minimize volutrauma through a reduction of PIP and use of expiratory trigger to limit excessive PIP and an overall lower mean airway pressure.     

Malignant melanoma of the vagina: report of two cases

Two rare cases of malignant melanoma, (one amelanotic) arising in the vagina in middle-aged group are being reported. Clinical, histopathological and immunohistochemical studies supported the diagnosis. The neoplasm is highly malignant & carries a poor prognosis.