Non-invasive diagnosis of early pulmonary disease in PECAM-deficient mice using infrared pulse oximetry

Pulse oximetry is a common tool for detecting reduced pulmonary function in human interstitial lung diseases. It has not previously been used in a mouse model of interstitial lung disease. Further, platelet endothelial cell adhesion molecule deficient mice rarely show symptoms until disease is advanced.Using blood oxygen saturation, different stages of disease could be identified in a non-invasive manner. These stages could be correlated to pathology. Collagen deposition, using Picrosirius Red, did correlate with blood oxygen saturation. These studies are the first to show the use of an infrared pulse oximetry system to analyze the progression of a fibrotic interstitial lung disease in a mouse model of the human diseases. Further, these studies show that an early alveolar damage/enlargement event precedes the fibrosis in this mouse model, a stage that represents the best targets for disease analysis and prevention. This stage does not have extensive collagen deposition. Most importantly, targeting this earliest stage of disease for therapeutic intervention may lead to novel treatment for human disease.     

The needs and supportive networks of the dying: an assessment instrument and mapping procedure for hospice patients.

If institutional systems that provide end-of-life care are to survive the demands of managed care, they will need to tie together methods of assessing the needs of the dying, leading to a new understanding of the functioning of a patient's existing helping networks. This paper presents the preliminary findings of a research project conducted at a Midwest hospice. The study utilized a cross sectional correlational survey of patients' needs via the Early Risk and Resiliency Inventory (ERRI), while mapping their helping networks with a Circles of Care Ecomap. It addressed the question, "What is the relationship between the needs of the dying and the formal and informal support provided?" Study findings supported the contention that higher need patients utilized the more expensive institutional services rather than relying on available natural networks; and statistical analysis of the study instrument suggested the creation of a new conceptual domain of psychospiritual need.     

Cerebral palsy rates among low-birthweight infants fell in the 1990s

Using a population-based register, this study sought to ascertain changes in the rate and severity of cerebral palsy (CP) in a geographically defined area of the UK among infants weighing less than 1500 g and born between 1984 and 1995. There were 417414 live births in the area, which included Berkshire, Buckinghamshire, Northamptonshire, and Oxfordshire. Of the 898 children with CP (526 males, 372 females), 194 (21.6%) weighed less than 1500 g at birth. The overall CP rate for neonatal survivors fell from 2.5 out of every 1000 in 1984 to 1986 to 1.7 in 1993 to 1995. The rate for those weighing less than 1000 g rose to 90 out of every 1000 neonatal survivors in 1987 to 1989 and then fell to 57 in 1993 to 1995. A similar pattern is seen among infants weighing 1000 to 1499 g at birth, the rate rising to 77 in 1987 to 1988 and then falling to 40 in 1993 to 1995. The rate of severe motor disability among infants weighing less than 1500 g also decreased (24.6 in 1984-1986 to 12.5 in 1993-1995). The relation of these findings to changes in perinatal care in the early 1990s is not known.     

Spontaneous esophageal perforation presenting as meningitis

This report describes a unique case of spontaneous esophageal perforation (Boerhaave's syndrome) presenting as meningitis. After a delay in diagnosis (16 days), the patient was successfully treated with debridement, primary closure, and drainage. Although rare, central nervous system infections have been reported in association with esophageal perforation caused by instrumentation, trauma, and malignancy. We report this case of spontaneous esophageal perforation giving rise to meningitis.     

Evaluation of downstaging in the detection of cervical neoplasia in Kolkata,India

Unaided visual inspection or "downstaging" has been suggested as a potential alternative method for cervical cancer screening in developing countries. Our study was designed to evaluate the accuracy of downstaging to detect cervical neoplasia in a low-resource setting. A total of 6,399 women aged 30-64 years were screened with downstaging by trained nonmedical health workers. Two thresholds were used to define positive downstaging: "low threshold" when any visible abnormality on the cervix was considered positive and "high threshold" when selected abnormalities such as bleeding on touch, bleeding erosion, hypertrophied oedematous cervix, congested stippled cervix and growth or ulcer constituted the positive test. All women underwent a colposcopy examination. Biopsies were directed when colposcopy revealed abnormal lesions. True disease status was defined as histologically proven moderate dysplasia and worse lesions. Since all the participants received a diagnostic (reference) investigation (biopsy and/or colposcopy), sensitivity, specificity and predictive values were estimated directly. Low- and high-threshold downstaging were positive in 1,585 (24.8%) and 460 (7.2%) women, respectively. The sensitivities of low- and high-threshold downstaging to detect high-grade precursors and invasive cancers were 48.9% and 31.9%, respectively. The specificities were 75.8% and 93.3%, respectively. These results indicate that downstaging is not suitable as an independent primary screening modality for cervical neoplasia.     

Phase I and pharmacological study of the oral farnesyltransferase inhibitor SCH 66336 given once daily to patients with advanced solid tumours

A single-agent dose-escalating phase I study on the farnesyl transferase inhibitor SCH 66336 was performed to determine the safety profile and recommended dose for phase II studies. Plasma pharmacokinetics were determined as well as the SCH 66336-induced inhibition of farnesyl protein transferase in vivo. SCH 66336 was given orally once daily (OD) without interruption to patients with histologically-confirmed solid tumours. Routine antiemetics were not prescribed. 12 patients were enrolled into the study. Dose levels studied were 300 mg (6 patients) and 400 mg (6 patients) OD. Pharmacokinetic sampling was performed on days 1 and 15. Although at 400 mg OD only 1 patient had a grade 3 diarrhoea, 3 out of 6 patients interrupted treatment early due to a combination of various grade 1-3 toxicities (diarrhoea, uremiacreatinine, asthenia, vomiting, weight loss) indicating that this dose was not tolerable for a prolonged period of time. At 300 mg OD, the same pattern of toxicities was observed, but all were grade 1-2. Therefore, this dose can be recommended for phase II studies. Pharmacokinetic analysis showed that peak plasma concentrations as well as the AUCs were dose-related, with increased parameters at day 15 compared with day 1, indicating some accumulation upon multiple dosing. Plasma half-life ranged from 5 to 9 h and appeared to increase with increasing dose. Steady state plasma concentrations were attained by day 14. A large volume of distribution at steady state suggested extensive distribution outside the plasma compartment. There is evidence of inhibition of protein prenylation in some patients after OD oral administration of SCH 66336. SCH 66336 can be safely administered using a continuous oral OD dosing regimen. The recommended dose for phase II studies using this regimen is 300 mg OD.     

Extracorporeal membrane oxygenation for unprotected left main stenting in a patient with totally occluded right coronary artery and severe left ventricular dysfunction

We report a case of unprotected left main stenting in an elderly female with severe left ventricular dysfunction and a totally occluded right coronary artery using hemodynamic support with the Extracorporeal Membrane Oxygenator (ECMO). There were no procedural complications and at 6-month follow-up, the patient was doing well with no cardiovascular events. Stenting of unprotected left main and the use of ECMO in high-risk coronary intervention are reviewed.     

Endoscopy in Patients Receiving Radiation Therapy to the Thorax

Radiation therapy for thoracic malignancies is often complicated by radiation-induced esophagitis. Symptoms of radiation esophagitis are nonspecific and include dysphagia, odynophagia, and chest pain. Patients receiving radiation therapy are also at risk for infectious esophagitis, which can be indistinguished clinically from radiation-induced esophagitis. We retrospectively reviewed data on patients who had esophagitis symptoms during or after thoracic radiation therapy and were referred for upper endoscopy. We sought to determine how often infectious esophagitis or cancer was present, as compared to radiation-induced esophagitis alone. Twenty-four upper endoscopies were performed on 16 patients over a three-year period to evaluate esophagitis symptoms. Forty-four percent of the patients endoscoped had infectious esophagitis or recurrent cancer diagnosed by endoscopy. No complications occurred from the procedures. Esophagoscopy is a safe procedure that should be considered, to exclude infection or cancer, in patients who develop esophagitis symptoms during or after thoracic radiation.