Measuring quality of life in patients with myocardial infarction or stroke: a feasibility study of four questionnaires in The Netherlands.

OBJECTIVE--To test in patients with a history of myocardial infarction or stroke the feasibility of four quality of life measurements--the Nottingham health profile (NHP), the heart patients psychological questionnaire (HPPQ), the sickness impact profile (SIP), and the hospital anxiety and depression scale (HAD). DESIGN--Subjects were tested and retested after an interval of 14 days: questionnaires were self assessed. SUBJECTS--Participants were randomly selected from the Rotterdam stroke data bank (stroke patients; n = 16, mean (SD) age 66.0 (11.0) years and from the population based Rotterdam study (myocardial infarction; n = 20, mean (SD) age 72.7 (7.9) years, controls; n = 17, mean (SD) age 72.8 (7.3) years. MEASUREMENTS AND MAIN RESULTS--Mean (SD) administration times for the NHP, HPPQ, SIP, and HAD were 7.9 (3.5), 10.5 (4.3), 21.0 (9.8), and 5.5 (2.8) minutes respectively. On average, the test-retest reliability was good, with Spearman correlations ranging from 0.31 to 0.95. In spite of the limited size of the study, all instruments were able to show differences between the study groups. For instance, median SIP total scores for myocardial infarction and stroke patients were 12.4 (interquartile range 7.0-19.1) and 11.4 (5.9-15.4) respectively, compared with 7.7 (3.7-11.3) in the control group (p values of 0.04 and 0.14 respectively). CONCLUSIONS--This study suggests that use of the four instruments tested may be feasible and reliable for assessing aspects of quality of life in patients with a history of a myocardial infarction or stroke.     

Clinical characteristics of severe peripheral neuropathy induced by docetaxel (Taxotere)

Background: Docetaxel, a semi-synthetic taxane may cause a usuallymild sensory neuropathy. We describe the clinical characteristics of fivepatients who developed a more severe neuropathy following treatment withdocetaxel.Patients and methods: All patients were treated in phase II studieswith 100 mg/m² docetaxel in three weekly cycles, withoutsteroid administration.Results: The clinical picture in these patients was dominated by asensory neuropathy, but in one case severe weakness was present. Anotherpatient developed Lhermitte's sign. Signs and symptoms are usually reversibleafter discontinuation of docetaxel administration, but in three patientssymptoms worsened for some time after the end of treatment before improvementoccurred.Conclusion: Severe docetaxel neuropathy may especially occurfollowing treatment with cumulative dosage over 600 mg/m²; inpatients treated with this dosage a moderate or severe neuropathy may not berare.     

Tonsil cryptolysis usingCO2 Swiftlase

Treatment for inflammation of the tonsils has taken a variety of therapeutic forms over the years, ranging from the application of iodine and massage in the preantibiotic era to the tonsillectomy, which prevails today. The architecture of the cryptic tonsil, its clinical implications, and the rationale for a conservative, yet effective treatment modality focusing on the tonsillar crypts are addressed in this article. Also described are the procedures and results of a retrospective clinical study in which conventional tonsillectomy was compared with CO₂ SwiftLase cryptolysis. Although our observations are not based on a prospective, controlled study, the information disseminated here may be useful to otolaryngologists who routinely perform tonsillectomy in their practice, using conventional surgical dissection methods or the CO₂ laser. According to our experience with a population of 120 patients, cryptolysis offers some clear advantages, particularly when performed with the SwiftLase apparatus. The procedure can be performed safely in an ambulatory surgery or office setting under local anesthesia. The cooperative patient avoids the cost and risks of general anesthesia. Limited tissue destruction significantly reduces operative and postoperative complications, discomfort, and recovery time. To conclude, CO₂ SwiftLase cryptolysis is a safe and cost-effective method of treating tonsil pathology without unnecessary sacrifice of the organ, and undue risks and expenses to the patient.^11,12     

Sequence-specific DNA binding of individual cut repeats of the human CCAAT displacement/cut homeodomain protein.

CCAAT displacement protein (CDP), a nuclear protein of 180-190 kDa, contains a triplicated motif, the cut domain, similar (80-90% conserved) to three repeats of 60-65 amino acids first identified in Drosophila cut, a homeo-domain protein involved in cell-fate decisions in development. Cut repeats bind DNA and exhibit subtle differences in target-site recognition. DNA sequences specifically bound by cut repeats were isolated by PCR-mediated DNA target-site selection. Sequences selected for cut repeat 2 and 3 (CR2 and CR3) binding are A+T-rich and favor an ATA motif with similar, but not identical, flanking base preferences. CR2 and CR3 discriminate among similar target sequences. CR1, which is more divergent from CR2 and CR3, displays the most restricted pattern of DNA sequence recognition. Methylation interference analysis demonstrates different protein-DNA contacts for CR1 and CR3 binding to a target sequence. Thus, CDP/cut is a complex protein whose DNA-binding properties reflect the combinatorial interaction of four domains (three cut repeats and one homeodomain) with target DNA sequences.     

Supramolecular organization of the mammalian translation system.

Although evidence suggests that the protein synthetic machinery is organized within cells, this point has been difficult to prove because any organization that might exist is lost upon preparation of the cell-free systems usually used to study translation in vitro. To examine this process under conditions more representative of the intact cell, we have developed an active protein-synthesizing system using Chinese hamster ovary (CHO) cells permeabilized with the plant glycoside saponin. This procedure renders cells permeable to trypan blue and exogenous tRNA, but there is little release of endogenous macromolecules. Protein synthesis in this system proceeds at the same rate as that in intact cells and is about 40-fold faster than that in a cell-free system prepared from the same cells. Active protein synthesis in this system requires the addition of only Mg2+, K+, and creatine phosphate, with a small further stimulation by ATP and an amino acid mixture; no exogenous macromolecules are necessary. The proteins synthesized in this system are indistinguishable from those made by the intact cell, and the channeling of aminoacyl-tRNA observed in vivo is maintained. Our data suggest that the permeabilized cell system retains the protein-synthesizing capabilities of the intact cell and presumably its internal structure as well. Studies with this system demonstrate that the protein-synthesizing apparatus is highly organized and that its macromolecular components are not freely diffusible in mammalian cells.     

Autoregulation by eicosanoids of human Kupffer cell secretory products. A study of interleukin-1, interleukin-6, tumor necrosis factor-alpha, transforming growth factor-beta, and nitric oxide.

OBJECTIVE: Methods employed previously to analyze the secretory behavior of rodent Kupffer cells (KC) were used to examine the human KC's secretory response to lipopolysaccharide (LPS). SUMMARY BACKGROUND DATA: As the resident hepatic macrophage, the KC resides at the interface between the portal and systemic circulations. Consequently, this cell may play an integral role in the immune response to antigens and bacteria in the sinusoid. Study of cytokine production by the KC has relied predominantly on the rat as the source of these cells. Whether human KCs respond similarly to rat KCs after LPS stimulation has been a matter of speculation. METHODS: Kupffer cells obtained from seven human livers were tested under conditions identical to those used to study rat KCs. Kupffer cells rested for 12 hours after isolation were stimulated with LPS (2.5 micrograms/mL). Arginine concentration in the culture medium varied from 0.01 to 1.2 mM. To examine the role of eicosanoids, parallel culture wells received indomethacin (10 microM). Culture supernatants were assayed for interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta), prostaglandin E2 (PGE2), and nitric oxide. RESULTS: Similar to the rat KC, LPS-stimulated human KCs released IL-1, IL-6, TNF-alpha, TGF-beta, and PGE2. However, unlike rat KCs, nitric oxide could not be detected, regardless of whether the human KCs were exposed to LPS, interferon-gamma (INF-gamma), or LPS + IFN-gamma. Similar to rat KCs, indomethacin prevented PGE2 release while significantly upregulating TNF-alpha, IL-1, and IL-6, but not TGF-beta, consistent with an autoregulatory control of eicosanoids over proinflammatory cytokines. As has been shown in the rat, physiologic levels of L-arginine (0.01 mM) significantly enhanced LPS-induced PGE2 secretion relative to the response in medium containing standard L-arginine concentration (1.2 mM); however, unlike the rat KC, the human's cytokine response to LPS was not downregulated by this enhanced PGE2 release. CONCLUSIONS: Although many functional features are shared by rat and human KCs, significant differences do exist. Such discrepancies reinforce the need to proceed with caution when generalizing from the results obtained in other species to human physiology.     

Useful predictors of bile duct stones in patients undergoing laparoscopic cholecystectomy. McGill Gallstone Treatment Group.

OBJECTIVE: The authors determined the most useful predictors of common bile duct (CBD) stones as diagnosed by endoscopic retrograde cholangiopancreatography (ERCP) in patients who underwent laparoscopic cholecystectomy (LC). METHODS: Prospective and retrospective collection of historical, biochemical and ultrasonographic data was used. Receiver operating characteristics curve analysis was used to determine optimal biochemical cut-off values. Multivariate analysis using logistic regression with generation of the best model identifying independent predictors of CBD stones also was employed. Prospective validation of the model was performed on an independent group of patients. RESULTS: Endoscopic retrograde cholangiopancreatographies were performed before LC in 106 patients, and after LC in 33. Only four of ten clinical variables evaluated independently predicted the presence of CBD stones. The optimal model predicted a 94% probability of CBD stones in a patient older than 55 years of age who presented with an elevated bilirubin (over 30 mumol/L) and positive ultrasound findings (a dilated CBD, and a CBD stone seen on ultrasound). This model was validated prospectively in a subsequent series of 49 patients in which the probability of CBD stone was only 8% when all four predictors were absent. CONCLUSIONS: The identified independent clinical predictors of a CBD stone helps select a population of symptomatic gallstone bearers who benefit most from cholangiographic assessment.     

A subgroup of patients with chronic pancreatitis overexpress the c-erb B-2 protooncogene.

OBJECTIVE: Chronic pancreatitis (CP) is a chronic condition associated with pancreatic fibrosis. A small subgroup of patients with CP develop enlargement of the head of the pancreas (EHP). This study examined some of the mechanisms that may lead to the development of EHP. SUMMARY BACKGROUND: The c-erb B-2 protooncogene encodes a 185-kDa transmembrane growth factor receptor (p185) that regulates cell growth and differentiation. METHODS: The authors analyzed c-erb B-2 expression in samples obtained from the head of the pancreas from 26 patients with CP (5 women, 21 men) using immunohistochemical and molecular technique. A diagnosis of CP with EHP was made when the vertical pancreatic head diameter was greater than 4 cm (14 patients), as determined by contrast-enhanced computed axial tomography scan. Pancreatic tissues from 15 healthy organ donors served as control subjects. RESULTS: In all patients without EHP and in the healthy control subjects, p185 immunoreactivity was present at low levels. In contrast, strong p185 immunoreactivity was observed in acinar and ductal cells in all patients with EHP. By in situ hybridization, c-erb B-2 messenger ribonucleic acid (mRNA) grains were expressed at high levels in patients with CP with EHP in both ductal and acinar cells. Northern blot analysis demonstrated a 4.5-fold increase (p < 0.001) in c-erb B-2 mRNA levels in patients with EHP compared with patients without EHP and healthy control subjects. Southern blot analysis did not reveal c-erb B-2 gene amplification or rearrangement. CONCLUSIONS: These findings indicate the c-erb B-2 is not overexpressed in most patients with CP. However, its overexpression in patients with CP with EHP suggest that c-erb B-2 may contribute to the pathophysiologic processes that lead to pancreatic head enlargement.