Common acute childhood infections and appendicitis: a historical study of statistical association in 27 English public boarding schools, 1930-1934.

Although the involvement of common childhood infections in the aetiology of acute appendicitis has long been conjectured, supporting evidence is largely restricted to a disparate set of clinical case reports. A systematic population-based analysis of the implied comorbid associations is lacking in the literature. Drawing on a classic epidemiological dataset, assembled by the School Epidemics Committee of the United Kingdom's Medical Research Council (MRC) in the 1930s, this paper presents a historical analysis of the association between termly outbreaks of each of six common childhood infections (chickenpox, measles, mumps, rubella, scarlet fever and whooping cough) and operated cases of acute appendicitis in 27 English public boarding schools. When controlled for the potential confounding effects of school, year and season, multivariate negative binomial regression revealed a positive association between the level of appendicitis activity and the recorded rate of mumps (beta=0.15, 95% CI 0.07-0.24, P<0.001). Non-significant associations were identified between appendicitis and the other sample infectious diseases. Subject to data caveats, our findings suggest that further studies are required to determine whether the comorbid association between mumps and appendicitis is causal.

Official Position of the American Academy of Clinical Neuropsychology Social Security Administration Policy on Validity Testing: Guidance and Recommendations for Change.

UNLABELLED: The milestone publication by Slick, Sherman, and Iverson (1999) of criteria for determining malingered neurocognitive dysfunction led to extensive research on validity testing. Position statements by the National Academy of Neuropsychology and the American Academy of Clinical Neuropsychology (AACN) recommended routine validity testing in neuropsychological evaluations. Despite this widespread scientific and professional support, the Social Security Administration (SSA) continued to discourage validity testing, a stance that led to a congressional initiative for SSA to reevaluate their position. In response, SSA commissioned the Institute of Medicine (IOM) to evaluate the science concerning the validation of psychological testing. The IOM concluded that validity assessment was necessary in psychological and neuropsychological examinations (IOM, 2015 ). OBJECTIVE: The AACN sought to provide independent expert guidance and recommendations concerning the use of validity testing in disability determinations. METHOD: A panel of contributors to the science of validity testing and its application to the disability process was charged with describing why the disability process for SSA needs improvement, and indicating the necessity for validity testing in disability exams. RESULTS: This work showed how the determination of malingering is a probability proposition, described how different types of validity tests are appropriate, provided evidence concerning non-credible findings in children and low-functioning individuals, and discussed the appropriate evaluation of pain disorders typically seen outside of mental consultations. CONCLUSIONS: A scientific plan for validity assessment that additionally protects test security is needed in disability determinations and in research on classification accuracy of disability decisions.

Are certain HLA haplotypes responsible for low testosterone levels in males?

The level of testosterone on 138 HLA typed healthy males and 71 male rheumatoid arthritis patients were analysed. HLA-B15 was associated with a lower mean serum testosterone level in males than any other tissue type. This was observed in both the normal and RA groups.

A study of waiting time for surgery in elderly patients with hip fracture and subsequent in-patient hospital stay.

OBJECTIVE: To establish whether increased waiting time to operation in elderly patients with hip fracture significantly affects postoperative time to discharge. METHODS: Combined prospective and retrospective analysis of theatre logbooks and in-patient data to determine the type, time and date of operation and subsequent in-patient stay. SETTING: A busy district general hospital in the South East Thames Valley area with changing availability of a dedicated trauma list. PATIENTS: 441 elderly patients undergoing hip surgery between May 1995 and March 1997. MAIN OUTCOME MEASURES: Waiting time from booking of operation to surgery and length of postoperative hospital stay. RESULTS: Increased pre-operative wait for emergency hip surgery in elderly patients significantly increases postoperative stay. Roughly doubling pre-operative wait increases postoperative stay by 19% (P < 0.01).

Physiological mass measurements on Skylab 1/2 and 1/3.

Mass measurements of crewmen and objects were made for the first time in space during Skylab. A description of the new devices designed for such measurements and of the technique of their use is detailed. Results from ground-based chamber simulation tests and from those during Skylab II and III show similar patterns of simple metabolic deficits, of a rapid loss during the first few days of flight followed by a reciprocal gain for the first few postflight days, and other transient changes. It is concluded that two major causes of weight loss are present: (1) a fluid redistribution and loss, and (2) metabolic losses. Added to these are short-term changes from transient stress. Smaller, simpler, and cheaper devices have since been designed which should allow mass measurements on virtually any object in almost any spacecraft.

Comparison of hypoxia transcriptome in vitro with in vivo gene expression in human bladder cancer.

Hypoxia-inducible genes have been linked to the aggressive phenotype of cancer. However, nearly all work on hypoxia-regulated genes has been conducted in vitro on cell lines. We investigated the hypoxia transcriptome in primary human bladder cancer using cDNA microarrays to compare genes induced by hypoxia in vitro in bladder cancer cell line EJ28 with genes upregulated in 39 bladder tumour specimens (27 superficial and 12 invasive). We correlated array mRNA fold changes with carbonic anhydrase 9 (CA IX) staining of tumours as a surrogate marker of hypoxia. Of 6000 genes, 32 were hypoxia inducible in vitro more than two-fold, five of which were novel, including lactate transporter SLC16A3 and RNAse 4. Eight of 32 hypoxia-inducible genes in vitro were also upregulated on the vivo array. Vascular endothelial growth factor mRNA was upregulated two-fold by hypoxia and 2-18-fold in 31 out of 39 tumours. Glucose transporter 1 was also upregulated on both arrays mRNA, and fold changes on the in vivo array significantly correlated with CA IX staining of tumours (P=0.008). However, insulin-like growth factor binding protein 3 mRNA was the most strongly differentially expressed gene in both arrays and this confirmed its upregulation in urine of bladder cancer patients (n=157, P<0.01). This study defines genes suitable for an in vivo hypoxia 'profile', shows the heterogeneity of the hypoxia response and describes new hypoxia-regulated genes.

Phase I trial of intravesical Suramin in recurrent superficial transitional cell bladder carcinoma.

Suramin is an antitrypanosomal agent with antineoplastic activity, but with serious systemic side effects. We administered Suramin intravesically to determine a concentration with low toxicity but with evidence of a pharmacodynamic effect, to recommend a dose level for phase II trials. This was an open-labelled, non-randomized dose-escalation phase I study. In all, 12 patients with a history of recurrent superficial bladder cancer were grouped into four dose levels (10-150 mg ml(-1) in 60 ml saline). Six catheter instillations at weekly intervals were used. Cystoscopy and biopsy were performed before and 3 months after the start of treatment. Suramin was assayed using high-performance liquid chromatography, vascular endothelial growth factor (VEGF) using ELISA (enzyme-linked immunosorbent assay), and urinary protein profile using surface-enhanced laser desorption ionisation mass spectroscopy (SELDI). Minimal systemic absorption of Suramin was found at the highest dose of 150 mg ml(-1). Urinary VEGF was affected by Suramin at doses above 50 mg ml(-1), corresponding to the estimated threshold of saturation of Suramin binding to urine albumin. SELDI showed a specific disappearance of urinary protein peaks during treatment. Intravesical Suramin shows lack of toxicity and low systemic absorption. The results of this phase I trial support expanded clinical trials of efficacy at a dose of 100 mg ml(-1) intravesically.

Bladder management and risk of bladder stone formation in spinal cord injured patients.

PURPOSE: We determined by statistical analysis whether method of management is associated with risk of bladder stone formation in spinal cord injured patients. MATERIALS AND METHODS: A retrospective cohort study was performed of 457 patients admitted to Stoke Mandeville Hospital Spinal Injuries Center between 1985 and 1990 with more than 6 months of followup. Analysis included Cox regression and Poisson regression. RESULTS: Relative to those patients treated with intermittent self-catheterization, the hazard ratio was 10.5 (p <0.0005, 95% confidence interval 4.0-27.5) for patients with suprapubic catheters and it was 12.8 (p <0.0005, 95% confidence interval 5.1-31.9) for those with indwelling urethral catheters. The absolute annual risk of stone formation in patients with a catheter was 4% compared with 0.2% for those on intermittent self-catheterization. However, having formed a stone, the risk of forming a subsequent stone quadrupled to 16% per year. Bladder stones were no more likely to form in patients with suprapubic catheters compared to those with indwelling urethral catheters (hazard ratio 1.2, p = 0.6). CONCLUSIONS: In spinal cord injured patients long-term catheterization is associated with a substantial increased risk of bladder stone formation. This increased risk occurs independently of age, sex and injury level. Degree of injury (complete or incomplete) was considered in the model. Catheter type (suprapubic or urethral) did not change this risk significantly if at all.

A computer-operated following ellipsometer.

This paper describes the construction and performance of a computer-operated following ellipsometer. By modifying a conventional ellipsometer and operating it with a process control computer, the polarizer and analyzer null positions can he located in about one second with a resolution of 0.01 degrees . This instrument has been used successfully for in situ studies of the buildup and removal of thin anodic oxide films. As the growth of a film is monitored, the computer also plots the null positions of an X-Y recorder and stores all the experimental data for later printing, punching on cards, or replotting along with theoretical curves.

Forecasting epidemic pathways for measles in Iceland: the use of simultaneous equation and logit models.

Six measles transmission chains between pairs and triplets of medical districts in Iceland are identified using monthly data for the 26 years from 1945 to 1970. The years studied are divided into two halves, a calibration period (1945-1957) and a forecast period (1958-1970). Some simultaneous equation models of the chains are developed and fitted using three-stage least squares. The resulting one month ahead forecasts are presented in terms of the expected case levels and as the probability of epidemics occurring. A single equation probability model using a logistic transformation is then formulated and compared with the simultaneous equation approach. The results obtained from the Icelandic study confirm in practice the advantages theoretically expected from setting up forecasting models containing geographically based chain transmission components.

Disappearance of HLA and platelet-specific antibodies in acute leukaemia patients alloimmunized by multiple transfusions.

Alloimmunization by platelet transfusions was studied in 154 patients with acute leukaemia. 17 patients had HLA antibodies at initial presentation induced by previous transfusions or pregnancies; one of these also had platelet-specific antibodies and one other patient had platelet-specific antibodies alone. A further 38 patients developed HLA antibodies during therapy; three also had platelet-specific antibodies and two patients developed platelet-specific antibodies alone. Of these, 37 patients with HLA antibodies including three with platelet-specific antibodies and one patient with platelet-specific antibodies alone survived their initial therapy and formed the basis of this study. Antibodies once detected persisted throughout the study in seven of the 37 patients with HLA antibodies including one patient with platelet-specific antibodies and in the patient with platelet-specific antibodies alone. HLA antibodies disappeared after discontinuation of transfusions in six patients, and after switching to HLA matched platelet transfusions and leucocyte-poor blood in eight patients; two of the latter patients also had platelet-specific antibodies which disappeared. The other 16 patients with HLA antibodies lost their antibodies despite continued transfusions.

Detection of granulocyte antibodies using flow cytometric analysis of leucocyte immunofluorescence.

Antigranulocyte antibodies are involved in the pathophysiology of a number of clinical disorders, which include: febrile transfusion reactions, severe pulmonary reactions to transfusion, auto-immune neutropenia, drug-induced neutropenia, and iso-immune neonatal neutropenia. Owing to the inherent difficulties of manipulating granulocytes in vitro, many of the serological techniques described for the detection of antigranulocyte antibodies are complex and sometimes difficult to reproduce. We describe the detection of alloreactive granulocyte antibodies using flow cytometric analysis of donor leucocyte suspensions in an indirect immunofluorescent test. The technique provides a semiquantitative detection of granulocyte antibodies in two groups of patients studied and, by providing as a comparison the reactivity on the corresponding mononuclear leucocytes, allows the distinction between granulocyte-specific antibodies and antibodies directed against the histocompatibility antigens.

Ureteric obstruction caused by pelvic actinomycosis.

Ureteric obstruction is a well-known complication of actinomycosis, however its management in previous case reports has been very variable and sometimes mutilating. We report a rare case presenting with ischiorectal abscess that was successfully treated by JJ stenting and penicillin.

The role of lysosomes and microtubules in cardiac protein degradation.

The mechanisms and regulatory factors involved in cardiac proteolysis are incompletely understood. Agents that interfere with lysosomal function (e.g., chloroquine, leupeptin, methyladenine) cause a 25-30% reduction in the overall rate of protein degradation. In the same hearts, however, the rate of myosin breakdown remains unchanged. Disaggregation of micro-tubules with colchicine is accompanied by a 15% reduction in the rate of degradation of total protein and of myosin. In the same hearts, the degradation of "organellar" protein, including mitochondrial cytochromes, is reduced by over 30%. Thus, it appears that the degradation of different classes of cardiac proteins may be accomplished and regulated by different processes. Lysosomes are important in overall proteolysis, but appear not to be involved in the regulation of myosin breakdown. Microtubules are also involved in the proteolytic process, and appear to be especially important for the breakdown of proteins from mitochondria and perhaps other organelles.

Inhibition of cardiac proteolysis by colchicine. Selective effects on degradation of protein subclasses.

1. The effect of colchicine (2.5 microM) on cardiac protein turnover was tested with foetal mouse hearts in organ culture. 2. Colchicine had no effect on protein synthesis, but inhibited total protein degradation by 12-18%. Lumicolchicine, which lacks colchicine's ability to disaggregate microtubules, but shares its non-specific effects, did not alter protein degradation. 3. The colchicine-induced inhibition of protein degradation was accompanied by significant changes in cardiac lysosomal enzyme activities and distribution. 4. Colchicine inhibited the degradation of organellar proteins, including mitochondrial cytochromes, more than that of cytosolic proteins. 5. Colchicine decreased the rate of myosin degradation and the rate of proteolysis of the total protein pool to a similar extent. Since the regulation of myosin degradation does not involve lysosomes, this suggests that colchicine affects non-lysosomal as well as lysosomal pathways. 6. Release of branched-chain amino acids from colchicine-treated hearts was disproportionately decreased, suggesting that colchicine increased their metabolism. 7. It is concluded that colchicine, via its actions on microtubules, exerts important inhibitory effects on cardiac proteolysis. Colchicine is especially inhibitory to the degradation of organellar proteins, including mitochondrial cytochromes. Its inhibitory effects may be mediated in part via lysosomal mechanisms, but non-lysosomal mechanisms are probably involved as well.

Mechanisms of degradation of myofibrillar and nonmyofibrillar protein in heart.

The degradation of cardiac proteins is known to be altered by many physiological and pathological interventions, but the precise intracellular processes that regulate proteolysis and the relative roles of different proteolytic pathways in degrading different classes of protein remain poorly understood. Agents that interfere with lysosomal function produce major decreases in total protein breakdown; thus, lysosomes and lysosomal proteinases seem to be important in proteolysis. However, these same agents cause no change in the degradation of myofibrillar proteins, suggesting that this class of proteins is not dependent on lysosomal pathways for its turnover.

Antenatal management of severe feto-maternal alloimmune thrombocytopenia: HLA incompatibility may affect responses to fetal platelet transfusions.

In feto-maternal alloimmune thrombocytopenia (FMAIT), severe hemorrhage, particularly intracranial haemorrhage (ICH), may occur before delivery. Management strategies to prevent ICH in high-risk pregnancies include maternal administration of intravenous Ig with or without steroids and fetal platelet transfusions. This report describes a patient who lost three fetuses with ICH because of FMAIT due to anti-HPA-1a. ICH occurred earlier in successive pregnancies (at 28, 19, and 16 weeks of gestation) despite maternal treatment with intravenous Ig and steroids from 14 weeks of gestation in the third pregnancy. The fourth pregnancy was managed by administering weekly intraperitoneal injections of Ig to the fetus from 12 to 18 weeks of gestation. At 18 weeks, there was no evidence of ICH, but the fetal platelet count was only 12 x 10(9)/L. Serial fetal platelet transfusions were started, but there were poor responses because of immune destruction of the transfused platelets by maternal HLA antibodies. There were improved responses to transfusions prepared from the mother and from HLA-compatible HPA-1a-negative donors. At 35 weeks of gestation, a normal infant was delivered by Caesarean section after 20 platelet transfusions. There was prolonged thrombocytopenia in the baby for 15 weeks after birth, probably due to transfer of HPA-1a antibodies in the transfusions of unwashed maternal platelets. The optimal management of pregnancies likely to be severely affected by FMAIT is still evolving. Intensive management was successful in this case, but a successful outcome cannot be guaranteed in severely affected cases. This is the first time that HLA incompatibility has been found to complicate fetal transfusion therapy.