Pulmonary function tests in bronchopleural fistula

A 53-year-old white man underwent a left pneumonectomy for alveolar cell carcinoma. His postoperative course was complicated by pneumonia. At a follow-up clinic visit, the patient complained of a "roaring sound" during respiration. A follow-up PFT did not show the expected loss of volume (nitrogen washout) from a preoperative PFT, suggesting a bronchopleural fistula. A chest x-ray film and xenon lung scan confirmed the diagnosis. The fistula was surgically repaired.     

Palliative radiotherapy--counting the costs of changing practice

"Working for Patients', the government's review of the National Health Service (NHS) advocates reforms which have led inevitably to pressure for medical specialities to review both the outcomes of their services and the resources used in achieving these outcomes. This paper considers these issues in the context of provision of palliative radiotherapy for patients with incurable cancers and presents the results of a study which evaluated the costs of radiotherapy. In addition to producing some of the first detailed cost estimates for the delivery of radiotherapy, this exercise highlighted the methodological and practical difficulties of undertaking such studies. As increasing pressure to evaluate cancer therapy is a prominent feature of a 'post-NHS Review' world, lessons learnt from this study may also be applicable to the audit of other cancer therapies. Efficient audit practices will, of course, have to evaluate the benefits (in terms of enhancements to length and quality of life) as well as the costs of cancer therapies.     

Line bisection judgments implicate right parietal cortex and cerebellum as assessed by fMRI

OBJECTIVE: To use functional MRI (fMRI) to determine which brain regions are implicated when normal volunteers judge whether pretransected horizontal lines are correctly bisected (the Landmark test). BACKGROUND: Manual line bisection and a variant thereof involving perceptual judgments of pretransected lines (the Landmark test) are widely used to assess unilateral visuospatial neglect in patients with neurologic disease. Although unilateral (left) neglect most often results from lesions to right temporoparietal cortex, the normal functional anatomy of the Landmark test has not been convincingly demonstrated. METHODS: fMRI was carried out in 12 healthy right-handed male volunteers who judged whether horizontal lines were correctly prebisected. In the control task, subjects detected whether the horizontal lines contained a transection mark irrespective of the position of that mark. Response was by two-choice key press: on half the trials, subjects used the right, and on half, the left hand. Statistical analysis of evoked blood oxygenation level-dependent responses, measured with echoplanar imaging, employed statistical parametric mapping. RESULTS: Performing the Landmark task showed neural activity (p < 0.05, corrected) in the right superior posterior and right inferior parietal lobe, early visual processing areas bilaterally, the cerebellar vermis, and the left cerebellar hemisphere. Only the latter area showed a significant interaction with hand used. CONCLUSIONS: The right hemispheric dominance observed in inferior parietal cortex is consistent with the results of lesion studies. Right superior parietal cortex, vermis, and left cerebellar hemisphere have not been implicated in neglect, but all appear to play a cognitive role in the Landmark task.     

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.     

Preauricular flap for post burn ear lobe reconstruction - a case report

Burns of the face often affect the ear causing deformation of the pinna or ear lobe due to perichondritis or loss of cartilage and excess scarring. The reconstruction of the ear lobe may be limited due to scarring of the surrounding tissues. We describe a preauricular flap for reconstruction of the anterior and posterior surface of the ear lobe following burn injury. This two stage technique of ear lobe reconstruction by a preauricular flap is not described in the available literature. An inferiorly based preauricular flap was harvested in a young lady who had post burn loss of the right ear lobe. This was folded on itself and sutured to reconstruct both surfaces of the ear lobe. After 6 months, it was released from its attachment at the retromandibular area to define the cheek lobe angle and to shape it. The preauricular flap for ear lobe contouring is a simple and easy technique. An adequate length may be harvested without significant donor site morbidity.     

The conduct of in vitro and in vivo drug-drug interaction studies: a Pharmaceutical Research and Manufacturers of America (PhRMA) perspective.

Current regulatory guidances do not address specific study designs for in vitro and in vivo drug-drug interaction studies. There is a common desire by regulatory authorities and by industry sponsors to harmonize approaches, to allow for a better assessment of the significance of findings across different studies and drugs. There is also a growing consensus for the standardization of cytochrome P450 (P450) probe substrates, inhibitors and inducers and for the development of classification systems to improve the communication of risk to health care providers and to patients. While existing guidances cover mainly P450-mediated drug interactions, the importance of other mechanisms, such as transporters, has been recognized more recently, and should also be addressed. This article was prepared by the Pharmaceutical Research and Manufacturers of America (PhRMA) Drug Metabolism and Clinical Pharmacology Technical Working Groups and represents the current industry position. The intent is to define a minimal best practice for in vitro and in vivo pharmacokinetic drug-drug interaction studies targeted to development (not discovery support) and to define a data package that can be expected by regulatory agencies in compound registration dossiers.     

Optical-thermal simulation of human tonsillar tissue irradiation: clinical implications

BACKGROUND AND OBJECTIVE: Mucosa intact laser tonsillar ablation is an alternative to conventional tonsillectomy. The efficacy of this procedure was demonstrated in canines, but establishing the safety of irradiating human tonsils is paramount. STUDY DESIGN/MATERIALS AND METHODS: An optical-thermal simulation of tonsillar tissue irradiation was previously developed, but the effect of varying parameters was not investigated. The tissue response to irradiation at 5-25 watts for 1 minute and 10 watts for 10 seconds to 162 seconds is simulated. RESULTS: At 15 watts and greater, the peak temperature is over 100 degrees C and the mucosal temperature is over 70 degrees C. At the depth of the tonsil, the temperature does not vary significantly. The peak temperature is at 1 mm. The radial temperature profile is not significantly altered by longer irradiation times. CONCLUSIONS: The optimal dosimetry parameters for irradiation of human tonsillar tissue at 805 nm with the MILTA technique is under 15 watts for approximately 1 minute.     

Hemimegalencephaly with tuberous sclerosis: A longitudinal imaging study

Hemimegalencephaly is a rare cerebral malformation characterized by asymmetry of the hemispheres and cortical dysplasias. We report clinical and imaging findings in a child with hemimegalencephaly involving the right cerebral hemisphere with associated manifestations of tuberous sclerosis complex. Gross abnormal myelination pattern and gyral abnormalities were seen in the enlarged hemisphere. Subsequent scans showed atrophy of the frontoparietal region in the enlarged hemisphere and normal growth of the opposite hemisphere exceeding the size of the abnormal hemisphere in the frontoparietal region. A few white‐matter lesions that were seen in the normal hemisphere on neonatal scan were difficult to appreciate on subsequent MR studies. The white‐matter lesions were better seen in the neonatal period, whereas cortical tubers were better detected at a later age.     

Antineutrophil cytoplasmic antibodies in Wegener's granulomatosis

The prevalence of antineutrophil cytoplasmic antibodies (ANCA) was studied in 12 children with Wegener''s granulomatosis. The serum samples were taken in the active phase of disease and were screened for ANCA by indirect immunofluorescence with normal neutrophils and enzyme linked immunosorbent assay (ELISA) using crude neutrophil extract, proteinase 3, myeloperoxidase, cathepsin G, lactoferrin, and elastase as antigens. Of these 12 patients, 10 were positive for ANCA in the active phase of their illness, and they showed a predominantly cytoplasmic ANCA staining pattern on indirect immunofluorescence. There were high titres of ANCA directed against crude neutrophil extract, proteinase 3, myeloperoxidase, and cathepsin G. IgM isotypes occurred as commonly as IgG isotypes. Therefore, screening for ANCA is usually but not invariably positive in children with Wegener''s granulomatosis. Specific diagnosis still relies on clinical and pathological features, and the value of ANCA in the diagnosis of paediatric Wegener''s granulomatosis requires further study.