Multilevel and continuous pleural fluid pH likelihood ratios for draining parapneumonic effusions

BACKGROUND: Although clinical practice guidelines endorse the use of pleural fluid pH to select patients with parapneumonic effusions for pleural drainage, no studies have reported likelihood ratios for pleural fluid pH. OBJECTIVES: We derived and tested the value of continuous likelihood ratios for selecting pneumonia patients for pleural drainage. METHODS: Patient level pleural fluid pH results were obtained from a registry of primary studies that assessed the discriminative properties of pH. Multilevel likelihood ratios were calculated for four pH intervals. Continuous likelihood ratios were derived from logistic regression using discrete pH values. Binary, multilevel and continuous likelihood ratios were compared to evaluate the statistical (chi2) and clinical advantages of continuous likelihood ratios. RESULTS: Hundred and ninety-seven pleural fluid pH results were retrieved from published reports and categorized into four pH ordinal intervals. Multilevel likelihood ratios ranged from a low of 0.13 (95% CI, 0.04-0.41) for pH values >7.40 to a high of 15.80 (95% CI, 7.04-35.45) for pH values < or =7.00. Logistic regression derived the following equation for continuous likelihood ratios: exp[-7.168(measured pH - 7.207)]. Continuous likelihood ratios offered more diagnostic information both statistically (p < 0.005) and clinically compared with binary and multilevel likelihood ratios. CONCLUSIONS: Analysis of a patient registry allows the derivation of an exponential equation that calculates continuous likelihood ratios for discrete pleural fluid pH values. Continuous likelihood ratios provide more clinically and statistically significant information compared with binary and multilevel likelihood ratios for calculating posttest probabilities of the need to drain parapneumonic effusions.     

Benign postoperative spindle cell nodule of the urinary bladder? don't think so

According to colleagues specializing in genitourinary pathology, the so-called postoperative spindle cell nodule of the bladder can be extremely difficult to distinguish from a spindle cell sarcomatoid carcinoma. What I have learned in 25 years about spindle cell sarcomatoid carcinoma of the larynx may, by analogy, possibly help with the genitourinary pathology problem.     

Tamoxifen and tamoxifen ethyl bromide induce apoptosis in acutely damaged mammary epithelial cells through modulation of AKT activity

Normal human mammary epithelial cells (HMECs), unlike estrogen receptor-positive (ER+) breast cancers, typically express low nuclear levels of ER (ER-'poor'). We previously demonstrated that 1.0 microM tamoxifen (Tam) induced apoptosis in ER-'poor' HMECs acutely transduced with human papillomavirus-16 E6 (HMEC-E6) through a rapid mitochondrial signaling pathway. Here, we show that plasma membrane-associated E2-binding sites initiate the rapid apoptotic effects of Tam in HMEC-E6 cells through modulation of AKT activity. At equimolar concentrations, Tam and tamoxifen ethyl bromide (QTam), a membrane impermeant analog of Tam, rapidly induced apoptosis in HMEC-E6 cells associated with an even more rapid decrease in phosphorylation of AKT at serine-473. Treatment of HMEC-E6 cells with 1.0 microM QTam resulted in a 50% decrease in mitochondrial transmembrane potential, sequential activation of caspase-9 and -3, and a 90% decrease in AKT Ser-473 phosphorylation. The effects of both Tam and QTam were blocked by expression of constitutively active AKT (myristoylated AKT or AKT-Thr308Asp/Ser473Asp). These data indicate that Tam and QTam induce apoptosis in HMEC-E6 cells through a plasma membrane-activated AKT-signaling pathway that results in (1) decreased AKT phosphorylation at Ser-473, (2) mitochondrial membrane depolarization, and (3) activated caspase-9 and -3.     

Behavioral audiograms of homozygous med(J) mutant mice with sodium channel deficiency and unaffected controls

Complete behavioral audiograms were determined for med(J) mice (F1 offspring of C57BL/6JxC3HeB/FeJ) and unaffected controls from the same F1 background. The med(J) mutation results in greatly reduced levels of Scn8a voltage-gated sodium channels, which causes abnormal conduction of action potentials throughout the nervous system and may account for the virtual absence of spontaneous bursting activity in the dorsal cochlear nucleus. The med(J) mice also have tremors, display dystonic postures, and drag their hind legs. The mice were tested using a conditioned suppression/avoidance procedure, with minor modifications of the apparatus made to accommodate the motor-impaired med(J) mice. Thresholds were repeatedly obtained up to the age of 50 weeks to determine if the animals developed a hearing loss with age. The results indicate that med(J) mice have normal thresholds, with the first signs of hearing loss (detectable at 80 kHz) appearing for both the med(J) and normal mice by 48 weeks. Neither the med(J) nor the normal mice could hear below 1 kHz, indicating that house mice fall into the group of mammals with poor low-frequency hearing. The results also demonstrate that the conditioned suppression/avoidance procedure is well suited for assessing hearing in severely impaired, as well as normal, mice and that it can provide for the rapid determination of thresholds necessary to follow changes in hearing that may occur as the result of age, disease, mutation, or drugs.     

Chronic obstructive pulmonary disease: on an exponential curve of progress

The last 50 years have witnessed major progress in our understanding of the underlying nature of chronic obstructive pulmonary disease (COPD) and approaches to care. During the last 10 years, however, there has been an explosive expansion of knowledge related to this disorder. Large-scale epidemiologic studies show that COPD is the fourth leading cause of death in the United States and will be the fifth leading health burden worldwide by the year 2020. We have also learned that COPD is an inflammatory disorder of small airways, which presents new opportunities for therapy involving interfering with the early components of the inflammatory cascade. Unfortunately, most clinicians fail to perform spirometric screening of at-risk individuals, so most patients first present with COPD during a sudden exacerbation of the disease. Worldwide interest is emerging in promoting earlier diagnosis and finding new pharmacologic interventions to halt the progression of airway and parenchymal damage. In this review, evidence is presented that we are on the upward limb of an exponential curve of progress in managing COPD, which will produce major advances in our ability to recognize and treat this disorder in its earliest stages.     

An investigation of sensory deficits underlying the aphasia-like behavior of macaques with auditory cortex lesions

Bilateral auditory cortex lesions in Japanese macaques result in an aphasia-like deficit in which the animals are unable to discriminate two forms of their coo vocalizations. To determine whether this deficit is sensory in nature, two monkeys with bilateral lesions were tested for their ability to discriminate frequency and frequency change. The results indicated that although the animals were able to discriminate between sounds of different frequencies, they were unable to determine whether a sound was changing in frequency. Because the animals' coo vocalizations differ primarily in the predominant direction of their frequency change and not in their absolute frequency content, the aphasia-like deficit of animals with bilateral auditory cortex lesions appears to be a sensory disorder.     

Transverse myelitis associated with restless legs syndrome and periodic movements of sleep responsive to an oral dopaminergic agent but not to intrathecal baclofen

Periodic limb movement disorder (PLMD) and restless legs syndrome (RLS) are related sleep disorders that occur with increased frequency in spinal cord disease. Effective treatment may be obtained with dopaminergic or opioid drugs, while anticonvulsants, benzodiazepines, and possibly baclofen may be helpful. This report describes a patient who developed RLS and PLMD after acute transverse myelitis associated with infectious mononucleosis, and failed to respond to intrathecal baclofen. All symptoms of RLS/PLMD resolved after treatment with pergolide.     

1,25-dihydroxycholecalciferol in renal osteodystrophy. Epiphysiolysis--anticonvulsant therapy

Three children with azotaemic renal osteodystrophy were treated with 1,25-dihydroxycholecalciferol (1,25(OH)2D3). All showed clinical, biochemical, and radiological improvement within 6 months of starting treatment. There were no complications. The dose of 1,25(OH)2D3 required was 0-5 microgram per day for 2 children aged 22 and 30 months, and 2 microgram per day for a 15-year-old boy. 2 of the patients were receiving phenobarbitone and phenytoin and in one of them prior treatment with dihydrotachysterol 0-5 mg daily and 6 microgram 1alpha-hydroxycholecalciferol (1alphaOHD3) daily had failed to induce improvement. In one patient, in whom serial iliac bone samples were available, 2 microgram 1,25(OH)2D3 resulted in histological improvement in previously severe osteomalacia. 1,25(OH)2D3 appears to be an effective and safe drug in the treatment of uraemic osteodystrophy.