Bilateral pneumothorax with pneumomediastinum under anaesthesia in a healthy female

A case of bilateral pneumothorax and Pneumomediastinum developing under general anaesthesia without apparent cause is reported. Possible aetiologic factors and mechanisms of the condition are outlined. Clinical signs and the immediate management of pneumothorax and Pneumomediastinum are discussed.     

Phantom limbs and neural plasticity

The study of phantom limbs has received tremendous impetus from recent studies linking changes in cortical topography with perceptual experience. Systematic psychophysical testing and functional imaging studies on patients with phantom limbs provide 2 unique opportunities. First, they allow us to demonstrate neural plasticity in the adult human brain. Second, by tracking perceptual changes (such as referred sensations) and changes in cortical topography in individual patients, we can begin to explore how the activity of sensory maps gives rise to conscious experience. Finally, phantom limbs also allow us to explore intersensory effects and the manner in which the brain constructs and updates a "body image" throughout life.     

BDNF blocks caspase-3 activation in neonatal hypoxia-ischemia

Hypoxic-ischemic (H-I) injury to the brain in the perinatal period often leads to significant long-term neurological deficits. In a model of neonatal H-I injury in postnatal day 7 rats, our previous data have shown that cell death with features of apoptosis is prominent between 6 and 24 h after H-I and that neurotrophins, particularly BDNF, can markedly protect against tissue loss. During brain development, caspase-3 is required for normal levels of programmed cell death. Utilizing an antibody specific for the activated form of caspase-3, CM1, we now show that caspase-3 is specifically activated in neuronal cell bodies and their processes beginning at 6 h and peaking 24 h following unilateral carotid ligation and exposure to hypoxia in postnatal day 7 rats. Caspase-3 activation began to occur in cortex at 6 h and in striatum and hippocampus at 12-18 h. Caspase-3 activation was also observed in developing oligodendrocytes. Intracerebroventricular injection of BDNF prior to H-I injury almost completely abolished evidence of H-I-induced caspase-3 activation in vivo. Utilizing a specific molecular marker of an apoptotic pathway, these findings demonstrate that H-I injury to the developing brain is a strong apoptotic stimulus leading to caspase-3 activation, that BDNF can block this process in vivo, and that the ability of BDNF to inhibit caspase activation and subsequent apoptosis likely accounts in large part for its protection against neuronal injury in this model.     

Radiation therapy induced changes in apoptosis and its major regulatory proteins, Bcl-2, Bcl-XL, and Bax, in locally advanced invasive squamous cell carcinoma of the cervix.

BACKGROUND AND PURPOSE: Radiation therapy (RT) for cancer induces cell death by apoptosis. The major apoptotic regulatory molecules include Bcl-2, Bcl-XL (antiapoptotic), and Bax (proapoptotic) proteins. Invasive squamous cell carcinoma of the cervix is mainly treated by radiation, and hence our aim was to evaluate the changes induced by RT in the apoptotic index (AI) and to correlate this to the levels of the major pro- and antiapoptotic molecules. MATERIALS AND METHODS: Paired biopsies were obtained in 30 cases of invasive carcinoma cervix before and after 10 Gy RT. The TUNEL assay was performed to detect apoptotic nuclei and Bcl-2, Bcl-XL, and Bax proteins detected by immunohistochemistry (IHC). Statistical analysis was performed using the Spearman rank correlation coefficient test. RESULTS: Following RT, there was a significant increase in the mean AI [2.25 (+/-2.28) in post-RT vs 0.90 (+/-0.53) in the pre-RT group]. Bax, a major proapoptotic protein, was significantly increased following RT (P < 0.05), whereas the antiapoptotic Bcl-XL showed a significant decrease (P = 0.006). There was no significant change in Bcl-2 expression. The Bcl-2 and Bax IHC scores and the Bcl-2/Bax ratio did not correlate with AI in the 2 groups. There was an inverse correlation of Bcl-XL to AI in the pre-RT group (P = 0.003) but not in the post-RT group. CONCLUSIONS: RT for invasive squamous cell carcinoma of cervix results in increased apoptotic cell death with the up-regulation of Bax, a proapoptotic protein, and the down-regulation of Bcl-XL, an antiapoptotic protein, without any significant change in the levels of Bcl-2.     

Effects of nortriptyline and paroxetine on QT variability in patients with panic disorder

This study investigated beat-to-beat QT variability in patients with panic disorder before and after treatment with nortriptyline (n = 13) and paroxetine (n = 16), using an automated algorithm to compute QT intervals. An increase in QT variability appears to be associated with symptomatic patients with dilated cardiomyopathy and also with an increased risk for sudden cardiac death. QTvi (QT variability index: a log ratio of QT variance normalized for mean QT over heart rate variability normalized for mean heart rate) was significantly higher in supine posture in patients with panic disorder treated with nortriptyline (P = 0.006) but not paroxetine. Thus paroxetine may be a better drug of choice especially in patients with coexisting cardiac disease. These findings are important especially in view of the recent reports of increased risk for cardiovascular mortality and sudden death in patients with anxiety and depression. QTvi can be a valuable noninvasive measure of temporal repolarization lability, especially to study the side effects of medications which affect cardiac autonomic function.     

Scintigraphic evaluation of colonic transit in two patients with idiopathic chronic constipation

Bowel transit in two women with protracted constipation was evaluated after oral administration of In-111 DTPA in water. Serial abdominal images were obtained for as long as 96 hours to assess transit through the stomach, small bowel, and colon. In both patients, large bowel transit was delayed. A pattern of colonic inertia was observed in one patient, whereas retention in the distal colon was seen in the other patient. Both patients underwent total colectomy with marked symptomatic relief. Colonic transit studies of these patients are presented, and the literature is reviewed.     

Immunization with DNA coding for gp100 results in CD4 T-cell independent antitumor immunity

BACKGROUND: Xenogeneic DNA immunization can exploit small differences in expressed protein sequence resulting in immune recognition of self-molecules. We hypothesized that immunizing mice with xenogeneic DNA coding for the human melanosomal membrane glycoprotein gp100 would overcome immune ignorance or tolerance and result in tumor immunity. We also investigated the immunologic mechanisms of the antitumor immunity. METHODS: C57BL/6 mice were immunized with DNA coding for human gp100, mouse gp100, or control vector by gene gun. After immunization, mice were challenged with a syngeneic melanoma expressing gp100, and tumor growth was analyzed. Mice deficient in major histocompatibility complex class I or class II molecules were similarly studied to assess the immunologic mechanism of the tumor protection. RESULTS: There was significant tumor protection after vaccination with xenogeneic human gp100 DNA. Class I, but not class II, major histocompatibility complex molecules were required for tumor immunity. In addition, mice immunized with human gp100 demonstrated autoimmunity manifested as coat color depigmentation. CONCLUSIONS: Immunization with xenogeneic DNA coding for the melanosomal glycoprotein gp100 results in tumor protection and autoimmune depigmentation. These results show that xenogeneic DNA vaccines can lead to cancer immunity without CD4(+) T-cell help with potential implications for rational vaccine design.     

Prospective technical validation and assessment of intra-tumour heterogeneity of a low density array hypoxia gene profile in head and neck squamous cell carcinoma

Background and purposeTumour hypoxia is associated with a poor prognosis in head and neck squamous cell carcinoma (HNSCC), however there is no accepted method for assessing hypoxia clinically. We aimed to conduct a technical validation of a hypoxia gene expression signature using the TaqMan Low Density Array (TLDA) platform to investigate if this approach reliably identified hypoxic tumours.Materials and methodsTumour samples (n = 201) from 80 HNSCC patients were collected prospectively from two centres. Fifty-three patients received pimonidazole prior to surgery. TaqMan Low Density Array-Hypoxia Scores (TLDA-HS) were obtained by quantitative real-time PCR (qPCR) using a 25-gene signature and customised TLDA cards. Assay performance was assessed as coefficient of variation (CoV).ResultsThe assay was sensitive with linear reaction efficiencies across a 4log₁₀ range of inputted cDNA (0.001–10 ng/μl). Intra- (CoV = 6.9%) and inter- (CoV = 2.0%) assay reproducibility were excellent. Intra-tumour heterogeneity was lower for TLDA-HS (23.2%) than for pimonidazole (67.2%) or single gene measurements of CA9 (62.2%), VEGFA (45.0%) or HIG2 (39.4%). TLDA-HS in HNSCC cell lines increased with decreasing pO₂. TLDA-HS correlated with Affymetrix U133 Plus 2.0 microarray HS (p < 0.01) and positive pimonidazole scores (p = 0.005).ConclusionsGene expression measurements of hypoxia using a 25-gene signature and TLDA cards are sensitive, reproducible and associated with lower intra-tumour heterogeneity than assaying individual genes or pimonidazole binding. The approach is suitable for further assessment of prognostic and predictive capability in clinical trial material.