Immune deficiencies in chronic intestinal pseudo-obstruction

Aim: Chronic intestinal pseudo-obstruction has been associated with urinary disorders, myopathy, and ophthalmoplegia in adults and cholelithiasis in children. We observed a high percentage of total-parenteral-nutrition-dependent patients with pseudo-obstruction and recurrent infections requiring gammaglobulin infusions. Methods: AH records for 23 children with chronic intestinal pseudo-obstruction (10 females and 13 males, mean age 9.8 y ± 4.9 y, range 4–24 y) referred for a nutritional evaluation from 1992 to 1995 were reviewed. Chronic intestinal pseudo-obstruction was diagnosed by clinical, radiographic findings and antroduodenal manometry. Intestinal full-thickness biopsies were performed in seven children. Results: Hypogammaglobulinemia was diagnosed in 18 patients (78%): 16 patients had various immunoglobulin deficiencies and 2 had selective antibody deficiency. Intravenous gammaglobulin was administered in 14 patients. Other medical conditions affecting the children are summarized as follows: autonomic dysfunction in 10 patients (43%), recurrent hypoglycemia in 9 (39%), asthma in 9 (39%), cholecystitis in 7 (30%), low serum carnitine level in 6 (26%), urinary dysfunction in 6 (26%), pancreatitis in 5 (22%), behavioral problems in 5 (22%), myopathy in 2 (9%), idiopathic thrombocytopenia in 2 (8%), velopharyngeal insufficiency in 1 (4%), oculocutaneous albinism in 1 (4%), Pierre-Robin syndrome in 1 (4%), and protein C deficiency in 1 (4%). Munchausen syndrome was suspected in two patients. Conclusions: Chronic intestinal pseudo-obstruction appears to be associated with immune deficiencies. It is unclear if the immune deficiencies, intestinal pseudo-obstruction, and the other medical conditions have a common underlying etiology. Repeated infections may be due to impaired immune function in children with chronic intestinal pseudo-obstruction. We recommend screening for immune deficiencies in children with chronic intestinal pseudo-obstruction.     

Inter-rater agreement and reliability of the COSMIN (COnsensus-based Standards for the selection of health status Measurement Instruments) Checklist

Background  

The COSMIN checklist is a tool for evaluating the methodological quality of studies on measurement properties of health-related patient-reported outcomes. The aim of this study is to determine the inter-rater agreement and reliability of each item score of the COSMIN checklist (n = 114).     

Detection of circulating crosslinked fibrin derivatives by a heat extraction-SDS gradient gel electrophoretic technique

A technique has been developed to identify and quantitate unique plasmic degradation products of crosslinked fibrin in plasma. In this method, fibrin derivatives are extracted by heat precipitation and dissolved with disulfide bond reduction, after which the crosslinked gamma-gamma chain remnants are identified by SDS-polyacrylamide gradient gel electrophoresis and quantitated by densitometric analysis. A heterogenous group of gamma-gamma chains with molecular weights between 100,000 and 76,000 daltons was identified in lysates of crosslinked fibrin during plasmic degradation in vitro. Three stages of crosslinked fibrin degradation have been arbitrarily defined based primarily on the extent of degradation of these gamma-gamma polypeptide chains. As little as 20 microgram of crosslinked fibrin digests added to 1 ml of normal plasma could be detected by the heat-extraction--gel- electrophoresis technique, identifying the gamma-gamma derivatives with molecular weights of 96,000, 86,000, 82,000, and 76,000 daltons. Plasmic derivatives of gamma-gamma chains were not found in normal plasma, but they were identified in the plasma of patients with disseminated intravascular coagulation and deep-vein thrombosis, both before and in increased quantity during successful thrombolytic therapy.     

An open-label,phase 2 study evaluating the efficacy and safety of the anti-IGF-1R antibody cixutumumab in patients with previously treated advanced or metastatic soft-tissue sarcoma or Ewing family of tumours

BackgroundCixutumumab (IMC-A12), a fully human immunoglobulin G1 (IgG1) monoclonal antibody, exerts preclinical activity in several sarcoma models and may be effective for the treatment of these tumours.MethodsIn this open-label, multicentre, phase 2 study, patients with previously treated advanced or metastatic rhabdomyosarcoma, leiomyosarcoma, adipocytic sarcoma, synovial sarcoma or Ewing family of tumours received intravenous cixutumumab (10 mg/kg) for 1 h every other week until disease progression or discontinuation. The primary end-point was the progression-free survival rate (PFR), defined as stable disease or better at 12 weeks. In each tier of disease histology, Simon’s optimum 2-stage design was applied (PFR at 12 weeks P0 = 20%, P1 = 40%, α = 0.10, β = 0.10). Stage 1 enrolled 17 patients in each disease group/tier, with at least four patients with stable disease or better required at 12 weeks to proceed to stage 2.ResultsA total of 113 patients were enrolled; all tiers except adipocytic sarcoma were closed after stage 1 due to futility. The 12-week PFR was 12% for rhabdomyosarcoma (n = 17), 14% for leiomyosarcoma (n = 22), 32% for adipocytic sarcoma (n = 37), 18% for synovial sarcoma (n = 17) and 11% for Ewing family of tumours (n = 18). Median progression-free survival (weeks) was 6.1 for rhabdomyosarcoma, 6.0 for leiomyosarcoma, 12.1 for adipocytic sarcoma, 6.4 for synovial sarcoma and 6.4 for Ewing family of tumours. Among all patients, the most frequent treatment-emergent adverse events (AEs) were nausea (26%), fatigue (23%), diarrhoea (23%) and hyperglycaemia (20%).ConclusionsPatients with adipocytic sarcoma may benefit from treatment with cixutumumab. Cixutumumab treatment was well tolerated, with limited gastrointestinal AEs, fatigue and hyperglycaemia.     

Results of the tension-free vaginal tape procedure for stress incontinence: Patient''s perspective

BACKGROUND: To evaluate the results of the tension-free vaginal tape procedure (TVT) from a patient's perspective. METHODS: Between May 1999 and January 2002, 90 patients underwent a TVT for genuine stress incontinence (GSI) and mixed incontinence. Prior to the procedure, GSI was confirmed by clinical examination and urodynamic studies. Results were then audited from patient notes and the same patients were sent questionnaires to examine results from a patient perspective. RESULTS: Overall response rate to the questionnaire was 70 (77%). The mean age of the patients was 50.4 years (range 31-83 years). Sixty-one patients had spinal anesthesia, seven had general anesthesia and two had local anesthesia. Mean hospital stay was 3.36 days (range 2-14 days) and mean period from the operation to the time of the survey and audit was 16.34 months (range 3-28; SD 6.92). Thirty-nine (56%) of the 70 patients who answered said that the operation had cured their incontinence, 16 (23%) had an improvement in their symptoms, 7 (10%) had worsening of their symptoms and 8 (11%) felt that the operation did not make any difference. The overall success rate according to the patients' perspective was 79%, whereas our audit showed an overall success rate of 86% (77% and 82%, respectively, when we compared only the 66 patients who had both notes and replies available for analysis). CONCLUSION: Although a patient's perception regarding the success of TVT tends to differ from that of a clinician, it was not found to be statistically significant (P = 0.22, McNemar test). The TVT is a very successful operation, but realistic cure rates should be offered to patients.     

Changing nurses' pain assessment practice: a collaborative research utilization approach*

It is not uncommon for a decade to pass between the time a research problem is identified and the time that research-based solutions are translated into standards for care This quasi-experimental study demonstrated the effectiveness of a collaborative research utilization model directed towards the transfer of specific research-based knowledge (pain assessment) into practice for the purpose of helping to solve pain management problems At the same time, nurses who participated in the model significantly improved their competency in research utilization and their attitudes towards research when compared to a control group who did not participate in the model     

Outbreak of ceftazidime resistance caused by extended-spectrum beta-lactamases at a Massachusetts chronic-care facility.

During a 4-month period in late 1988, we isolated ceftazidime-resistant strains of Klebsiella pneumoniae and other members of the family Enterobacteriaceae from 29 patients at a chronic-care facility in Massachusetts. Ceftazidime resistance resulted from two distinct extended-spectrum beta-lactamases of the TEM type which efficiently hydrolyzed the cephalosporin: YOU-1 with a pI of 5.57 and YOU-2 with a pI of 5.2. Genes encoding these enzymes were present on different but closely related high-molecular-weight, multiple antibiotic resistance plasmids of the H12 incompatibility group and were transferable by conjugation in vitro. Agarose gel electrophoresis of extracts from clinical isolates indicated that this outbreak arose from plasmid transmission among different strains of the family Enterobacteriaceae rather than from dissemination of a single resistant isolate. Isolation rates of ceftazidime-resistant organisms transiently decreased after use of this drug was restricted, but resistant isolates continued to be recovered 7 months after empiric use of ceftazidime ceased.     

Extraradicular cemental fragments in the alveolar bone of prehistoric American Indians: report of three cases

Heretofore unreported, grossly observable structures composed of cementum were found in the superficial alveolar bone--but not attached to the tooth root--in three prehistoric American Indian skeletons from South Dakota. The macroscopic, radiographic, and histologic morphology of these fragments is described and compared with other cemental structures that occur in the alveolar process.     

Dexamethasone in addition to metoclopramide for chronic nausea in patients with advanced cancer: a randomized controlled trial

Chronic nausea occurs in most patients with advanced cancer. This study was done to assess the antiemetic effects of dexamethasone in patients with chronic nausea refractory to metoclopramide. Secondary outcomes included appetite, fatigue, and pain. Fifty-one patients who had nausea (> or = 3/10 on a 0-10 scale) for > or = 2 weeks despite 48 hours of oral metoclopramide therapy (40-60 mg/day) were enrolled. Patients received 20 mg/day dexamethasone (DM) orally (n = 25) or placebo (n = 26) for severe nausea in addition to metoclopramide (60 mg/day orally). At baseline the mean nausea intensity ratings in the DM and placebo groups were 8.0 and 7.4. At Day 8 they were 2.1 and 2.0, respectively. At Day 3 and Day 8, the mean difference in nausea intensity for the DM and placebo groups was 4.5 and 2.9 (P = 0.16) and 5.9 and 5.7 (P = 0.85), respectively. Improvement in appetite and fatigue were observed on Day 3 and Day 8 in both groups as compared with the baseline. Pain, vomiting, well-being, and quality of life remained unchanged in both groups at both times. We conclude that DM was not superior to placebo in the management of chronic nausea in our patients with advanced cancer.     

Analysis of p53 mutations in a large series of lymphoid hematologic malignancies of childhood

p53 mutations are found in a wide variety of cancers, including hematologic malignancies. These alterations apparently contribute to development of the malignant phenotype. We analyzed a large series of lymphoid (330 cases) and a smaller series of myeloid (29 cases) malignancies of childhood for p53 mutations by single-strand conformational polymorphism (SSCP) following polymerase chain reaction. Samples with abnormal SSCP were reamplified and analyzed by direct sequencing method. p53 mutations were detected within the known mutational hotspots (exons 5 to 8) in 8 of 330 lymphoid malignancies, and in none of 29 myeloid malignancies, showing that the frequency of p53 mutations in childhood lymphoid malignancies was very low (8 of 330 cases [2%]). Four of these patients had very aggressive, fatal acute lymphocytic leukemia (ALL). None of 13 infants and none of 48 patients with T-lineage leukemia had detectable p53 mutations in their ALL cells. Exceptionally, p53 mutations were comparatively frequent in a small sample of B-cell non-Hodgkin's lymphomas (2 of 8 cases). Mutations were detected in samples from two patients with ALL at relapse; these were not detected in samples at initial diagnosis from the same patients, suggesting that p53 mutations may be associated with progression to a more malignant phenotype. Seven of eight alterations of p53 were missense mutations, and seven of eight samples may be heterozygous for the mutant p53, indicating that p53 protein may act in a dominant negative fashion.