The parasite Ichthyophonus sp. in Pacific herring from the coastal NE Pacific.

The protistan parasite Ichthyophonus occurred in populations of Pacific herring Clupea pallasii Valenciennes throughout coastal areas of the NE Pacific, ranging from Puget Sound, WA north to the Gulf of Alaska, AK. Infection prevalence in local Pacific herring stocks varied seasonally and annually, and a general pattern of increasing prevalence with host size and/or age persisted throughout the NE Pacific. An exception to this zoographic pattern occurred among a group of juvenile, age 1+ year Pacific herring from Cordova Harbor, AK in June 2010, which demonstrated an unusually high infection prevalence of 35%. Reasons for this anomaly were hypothesized to involve anthropogenic influences that resulted in locally elevated infection pressures. Interannual declines in infection prevalence from some populations (e.g. Lower Cook Inlet, AK; from 20-32% in 2007 to 0-3% during 2009-13) or from the largest size cohorts of other populations (e.g. Sitka Sound, AK; from 62.5% in 2007 to 19.6% in 2013) were likely a reflection of selective mortality among the infected cohorts. All available information for Ichthyophonus in the NE Pacific, including broad geographic range, low host specificity and presence in archived Pacific herring tissue samples dating to the 1980s, indicate a long-standing host-pathogen relationship.

Cost-effectiveness of the NICE guidelines for screening for latent tuberculosis infection: the QuantiFERON-TB Gold IGRA alone is more cost-effective for immigrants from high burden countries.

NICE (National Institute for Health and Clinical Excellence) guidelines for new entrant tuberculosis (TB) screening recommend chest x ray (CXR) for immigrants from countries with TB incidence >40/10(5), and tuberculin skin test (TST) for people with normal CXR from very high TB prevalence countries. A revised screening policy using first-line QuantiFERON-TB Gold (QFT) in high risk immigrants was piloted in 2007. Initially, TST was offered to immigrants from countries with TB incidence 200-339/10(5), and QFT to those from countries with incidence >340/10(5). When increased resources became available, all immigrants from countries with TB incidence >200/10(5) had QFT. Those with positive QFT were invited for CXR. 1336 immigrant were invited for screening, with a 32% attendance rate. 280 patients had QFT, of which 38% were positive, with <2% being indeterminate. Using the NICE approach, the cost of screening these 280 immigrants would be pound 13,346.75 ( pound 47.67 per immigrant) and would identify 83 cases of latent TB infection (LTBI). Using first-line QFT followed by CXR the cost was pound 9781.82 ( pound 34.94 per immigrant) and identified 105 cases of LTBI. The cost to identify one case of LTBI following NICE guidelines would be pound 160.81 and using the present protocol was pound 93.16. For immigrants from high risk countries QFT blood testing followed by CXR is feasible for TB screening, cheaper than screening using the NICE guideline and identifies more cases of LTBI.

Use of QuantiFERON-TB Gold test in the investigation of unexplained positive tuberculin skin tests.

OBJECTIVES: To investigate the use of new gamma-interferon (IFN-gamma)-based blood tests to determine whether or not a higher-than-expected proportion of positive tuberculin skin tests (TSTs) were due to tuberculosis infection. STUDY DESIGN: When an unexpectedly high proportion of children in a high school in Leeds were found to have positive TSTs, a cohort study was undertaken based on blood tests and long-term follow-up of the affected children. IFN-gamma-based blood tests are reported to be more specific for tuberculosis infection than TSTs. METHODS: One hundred and ninety children, aged 13-14 years, were screened and 28 (15%) had a positive TST. None had any known risk factor for tuberculosis infection. Parental consent was requested for testing with QuantiFERON-TB Gold (Cellestis, Carnegie, Victoria, Australia). Active cases of tuberculosis with any possible connection to the school or the children were sought through the routine diagnosis and reporting service over the next 36 months. RESULTS: Consent was given for 26 children with Heaf Grade 2 results to be tested using QuantiFERON-TB Gold, and blood was obtained from 24 of these children. All tested negative. None of these children developed active tuberculosis, and no cases of active tuberculosis were identified with any connection to the children or the school. CONCLUSION: QuantiFERON-TB Gold testing appeared to identify false-positive TSTs correctly in this group. This supports the recent recommendation to use IFN-gamma-based blood tests in people with positive TSTs to confirm or refute the diagnosis of tuberculosis infection.

Clinical and laboratory evaluation of a closed enteral feeding system under cyclic feeding conditions: a microbial and cost evaluation.

Cyclic feeding schedules are now commonly used in conjunction with closed enteral feeding systems. Some manufacturers and clinicians have speculated that closed system cyclic feeding may promote formula contamination via retrograde movement of bacteria during the "no-flow" periods. Using both laboratory and clinical settings, our study evaluated whether retrograde bacterial movement under "no-flow" conditions results in contamination of closed system feeding containers. The clinical phase was conducted with 57 closed system feeding containers used to feed nursing home residents. In both laboratory and clinical testing there was no evidence of container contamination at 36-48 h, nor was there evidence of retrograde movement of bacteria beyond the drip chamber. Formula waste and costs were also analyzed using several 24- or 36-h hang time scenarios. Provided the appropriate container size is used, potential cost savings between $67 to $135 per patient per month may be achieved with the 36-h hang time scenarios. Retrograde movement of bacteria does not appear to be a source of closed system feeding container contamination in systems that incorporate a drip chamber. Using the appropriate size feeding container and systems with at least a 36-h hang time will result in significant cost savings.

Preoperative cardiorespiratory trends in infants with congenital diaphragmatic hernia.

The objective of this study was to determine the cardiovascular and pulmonary adaptations of infants with congenital diaphragmatic hernia (CDH) from birth until delayed surgery through the use of continuous monitoring. Continuous cardiovascular (HR, heart rate variability [HR-SD], BP, blood pressure variability [BP-SD], and oxygen saturation) and ventilatory (minute volume, airway pressure, and effective compliance) measurements were made on-line, using a computerized whole-body plethysmograph-incubator (Vital-trends, VT1000), in nine ventilated infants with CDH. Data collection commenced at birth and continued until surgery. Minute mean values for each variable were recorded. Hourly means were computed from the minute means, averaged across infants each hour over the first 50 hours of life, and regressed against postnatal age. Results showed a significant increase in BP (P < .01), BP-SD (P < .05), HR-SD (P < .04), and pH (P < .02) versus postnatal age, and a decrease in PaCO2 (P < .04), FIO2 (P < .001), Alveolar-arterial oxygen gradient (P < .003), and oxygenation index (P < .002). Infants with CDH show cardiopulmonary trends over the first 2 days of life that are qualitatively similar to those of normal newborn infants. Deviation from these idealized patterns may identify an infant who is not responding satisfactorily to the given therapy and who may require alternative treatment modalities.

Congenital diaphragmatic hernia: survival treated with very delayed surgery, spontaneous respiration, and no chest tube.

This report suggests that stabilization of the intrauterine to extrauterine transitional circulation combined with a respiratory care strategy that avoids pulmonary overdistension, takes advantage of inherent biological cardiorespiratory mechanics, and very delayed surgery for congenital diaphragmatic hernia results in improved survival and decreases the need for extracorporeal membrane oxygenation (ECMO). This retrospective review of a 10-year experience in which the respiratory care strategy, ECMO availability, and technique of surgical repair remained essentially constant describes the evolution of this method of management of congenital diaphragmatic hernia.

Duchenne muscular dystrophy associated with fetal pleural effusion and polyhydramnios.

A case of fetal pleural effusion in a fetus affected with Duchenne muscular dystrophy (DMD) is reported. This case is discussed in the context of the previous observation of frequent stillbirths among male fetuses in DMD families.

Autosomal dominant transmission of autoantibodies to thyroglobulin and thyroid peroxidase.

The inheritance of autoantibodies to thyroglobulin and thyroid peroxidase (thyroid microsomal antigen) has been reevaluated with newly developed ultrasensitive assays that depend on the direct interaction between antibody and radiolabeled antigen. In a study of 16 families with autoimmune thyroid disease, autoantibodies to thyroid peroxidase (TPO) were found to be inherited as a dominant Mendelian trait in females with reduced penetrance in males. Similar results were obtained with thyroglobulin (Tg) autoantibodies. Genetic linkage analysis of the loci for TPO and Tg autoantibodies with 28 polymorphic serological markers (including HLA and Gm allotypes) was carried out in 9 families. LOD scores for some serological markers (such as Gm) were uninformative, but linkage with other markers, notably the HLA antigens -A, B, -DR, -DQ, and BF on chromosome 6, could be excluded. Further studies using a comprehensive panel of gene probes to analyze DNA from families with autoimmune thyroid disease should permit the localization of the gene cluster responsible for regulating the ability to produce autoantibodies to TPO and Tg in man.

Psychosocial characteristics of candidates for the prospective evaluation of radial keratotomy (PERK) study.

The National Eye Institute Prospective Evaluation of Radial Keratotomy (PERK) Study is a multicenter clinical trial for the evaluation of radial keratotomy. This article describes the questionnaire data collected on PERK patients and compares them with a similar group of myopic persons studied during the Rand Health Insurance Experiment (heretofore referred to as the Rand study). The PERK patients are young, white myopes who dislike being dependent on corrective lenses but perceive themselves to be more visually impaired than do comparable Rand study myopes. Most female subjects and a plurality of the male subjects have tried contact lenses and quit wearing them mainly because use of the lenses was inconvenient or bothersome. There is no evidence that patients are psychologically or socially deviant. Both male and female subjects expressed a fear of being without vision and cited impatience with the lenses as their major motivation for wanting surgery.

Three types of alpha-melanocyte-stimulating hormone: bioactivities and half-lives.

Three types of alpha-melanocyte-stimulating hormone (alpha MSH) that differ in the acetyl status of the N-terminal serine have been found in the neurointermediate lobe of the pituitary gland and in the brain: desacetyl alpha MSH, which lacks an acetyl group; monoacetyl alpha MSH, in which the amino group of the serine is acetylated; and diacetyl alpha MSH, in which both amino and hydroxy groups of the serine are acetylated. We compared the lipolytic and melanotropic actions of these three peptides, and their rates of disappearance from plasma, both in vitro and in vivo. The following differences were found. a) For in vitro lipolytic actions on rabbit adipose tissue slices, the potencies differed according to the order diacetyl = monoacetyl greater than desacetyl. On rabbit isolated adipocytes, however, the three peptides were equipotent. b) For in vivo lipolytic action in the rabbit, not only potency but also kinetics differed. Diacetyl alpha MSH had the slowest onset, longest duration, and greatest potency. The desacetyl variant had the quickest onset, shortest duration, and least potency. c) The half-life for elimination from rabbit plasma both in vitro and in vivo was shortest for the desacetyl form and longest for the diacetyl peptide. d) For in vitro melanotropic effect on frog skin, kinetics of action were the same for all three peptides, but potency differed according to the order diacetyl = monoacetyl greater than desacetyl. Thus acetylation of alpha MSH alters lipolytic and melanotropic potencies in vitro and lipolytic potency and kinetics in vivo. These differences result in part from the fact that acetylation slows the degradation of the tridecapeptide both inside and outside the circulation.

Measurement of muscle mass in humans: validity of the 24-hour urinary creatinine method.

Measuring muscle mass is an important component of the nutritional assessment examination and a suggested index of this body space is the 24-h urinary excretion of creatinine. The method originated from studies in a variety of animal species in whom early workers found a parallelism between total body creatine and urinary excretion of creatinine. Assuming that nearly all creatine was within muscle tissue, that muscle creatine content remained constant and that creatinine was excreted at a uniform rate, an obvious "corollary" was that urinary creatinine was proportional to muscle mass. The so-called "creatinine equivalence" (kg muscle mass/g urinary creatinine) ranged experimentally from 17 to 22. One of the limiting factors in firmly establishing this constant and its associated variability was (and is) the lack of another totally acceptable noninvasive technique of measuring muscle mass to which the creatinine method could (or would) be compared. An improved understanding of creatine metabolism and a variety of clinical studies in recent years has tended to support the general validity of this approach. However, specific conditions have also been established in which the method becomes either inaccurate or invalid. While creatinine excretion may serve as a useful approximation of muscle mass in carefully selected subjects, there remains a need for accurate and practical indices of muscle mass for use in the individuals in whom the method cannot be reliably applied.

Rationale for and design of the National Eye Institute Prospective Evaluation of Radial Keratotomy (PERK) Study.

A five-year, multicenter, collaborative clinical trial of radial keratotomy for myopia is being carried out at nine clinical centers. The study, funded by the National Eye Institute, is recruiting approximately 500 patients aged 21 years or older with -2.00 to -8.00 diopters of physiologic myopia who also meet other clearly defined eligibility criteria. Surgeons use a diamond-bladed micrometer knife to make eight radial incisions in the anterior cornea. The diameter of the central clear zone is determined by the amount of myopia and the depth of the incisions by intraoperative ultrasonic pachymetry. Investigators other than the surgeon gather all pre- and post-operative data. Examinations include measurement of visual acuity with standardized charts, verification of refractions by a second observer, measurement of corneal curvature by keratometry and photokeratoscopy, quantitation of glare with a glare tester, and measurement of the size of individual endothelial cells from specular photomicrographs with a computerized digitizer. A formal psychometric questionnaire is used to evaluate the patients' subjective response. Physician monitors insure adherence to the protocol during site visits and members of the Data and Safety Monitoring Board oversee the progress of the study. Biostatisticians at the Coordinating Center insure complete data collection, process the data, and assist in the interpretation of results.

Prognostic significance of terminal transferase activity in childhood acute lymphoblastic leukemia: a prospective analysis of 164 patients.

Whether the level of terminal deoxynucleotidyl transferase (TdT) activity in mononuclear cells from bone marrow and peripheral blood has prognostic significance has been analyzed prospectively in 164 children with T and non-T, non-B marked acute lymphoblastic leukemia (ALL). TdT was measured at diagnosis to assess its value as a predictor of duration of remission and length of survival. It was measured repeatedly during remission to assess whether it could predict relapse. Ninety-seven percent of the children achieved a complete remission of their disease, and 40% relapsed during the study. The level of TdT activity in blasts at diagnosis varied 1000-fold from patient to patient. There was no statistically significant relationship between TdT activity in cells at diagnosis and the achievement of complete remission, the duration of remission, or length of survival. TdT activity was significantly increased in the bone marrow of 65% of patients at the time of marrow morphological relapse, but was rarely increased in marrow from patients with isolated testicular or central nervous system relapse. Wide fluctuations in TdT activity were characteristically seen in mononuclear cells from the marrow and peripheral blood of patients with ALL at all stages of their disease. An isolated high value of TdT activity in the bone marrow or peripheral blood cannot be taken as evidence of impending relapse. Quantitative measurements of TdT activity alone on mononuclear cells from bone marrow and peripheral blood are helpful in differential diagnosis, but cannot guide therapy of children with ALL.

Clinical and pharmacokinetic evaluation of parenteral moxalactam in infants and children.

Thirty-four infants and children ranging in age from 2.5 to 180 months (mean, 40 months) were treated with parenteral moxalactam (150 mg/kg per day) for suspected or proved bacterial infections outside the central nervous system. Six patients infected with Haemophilus influenzae b, nine infected with Staphylococcus aureus, three infected with Streptococcus pneumoniae, one infected with Streptococcus pyogenes, one infected with Enterobacter aerogenes, one infected with Fusobacterium nucleotum, and one infected with Staphylococcus epidermidis, microaerophilic streptococcus, and Propionibacterium sp. were clinically and bacteriologically cured. One patient with polymicrobial pansinusitis did not respond to moxalactam. No patients developed meningitis. All of the isolates tested were inhibited by less than or equal to 5 micrograms of moxalactam per ml, except for one Staphylococcus epidermidis isolate which was resistant to greater than 20 micrograms/ml. Five patients had transient neutropenia which resolved after the drug was discontinued. The mean peak serum level was 106 micrograms/ml at 15 min after a 50-mg/kg dose. The mean elimination half-life was 91.2 min. These data indicate that this dosage of moxalactam is a safe and effective treatment for bacterial infections outside the central nervous system.

Response to exercise in patients taking psychotropic drugs. Arrhythmias and the QT interval (QT wave peak).

Psychotropic drugs may prolong the QT interval, potentially predisposing to ventricular arrhythmias and/or sudden death. Exercise prescribed as therapy for depression may also prolong the QT interval and augment arrhythmia risk. To determine QT-interval (QT wave peak, or QTPK) response to exercise in patients receiving psychotropic drugs, treadmill exercise testing was performed on 20 mentally competent psychiatric inpatients clinically free of heart disease. Twenty-four-hour ambulatory ECGs were performed within one day of exercise testing to detect arrhythmias during routine daily activities. Exercise test results for psychiatric patients were compared with those of normal subjects receiving no medication. Separate regression lines relating heart rate of QTPK interval, calculated for each group, showed no significant difference. No serious arrhythmias occurred during routine daily activities or exercise. Patients without heart disease taking psychotropic drugs have appropriate QTPK-interval shortening with exercise.

Penetration of cefoxitin into cerebrospinal fluid of infants and children with bacterial meningitis.

Three consecutive doses of 75 mg of cefoxitin per kg were given intravenously every 6 h (225 mg/kg), in addition to penicillin or ampicillin, to 24 patients on days 4 and 5 and 9 and 10 of therapy for meningitis. Haemophilus influenzae b was isolated from cerebrospinal fluid (CSF) of 21 patients, Streptococcus pneumoniae from 2 patients, and Neisseria meningitidis from 1 patient. The median minimal inhibitory and bactericidal concentrations of cefoxitin for 16 isolates of H. influenzae b were 0.312 and 0.625 micrograms/ml, respectively. Sixteen of 18 isolates of H. influenzae b and S. pneumoniae were killed by 2.5 micrograms of cefoxitin per ml. Mean levels in CSF peaked at 1 h at 6 and 4.9 micrograms/ml on days 5 and 10, respectively. CSF levels on days 5 and 10 were greater than or equal to twice the median minimal inhibitory and bactericidal concentration in 20 and 18 patients, respectively. However, bacterial levels in CSF were greater than or equal to 2.5 micrograms/ml in only 11 of 23 patients on days 5 and 10. No significant adverse effects were found. These data indicate that at this dosage, cefoxitin may not reach levels in the CSF required for killing all susceptible strains of H. influenzae b and S. pneumoniae.

Influence of quantity of granulocytes transfused on response.

Data from 165 infectious &/or febrile episodes in granulocytopenic patients given granulocyte transfusions wee reviewed to determine what factors influenced clinical outcome and if there was any correlation between clinical improvement and dose of granulocytes given. Factors not related to granulocyte dose that influenced survival and clinical improvement included sex, the type of infecting organism and marrow recovery during the 3 weeks after the initiation of granulocyte transfusions. Patients infected with organisms other than Pseudomonas, females and those whose marrows recovered all had a significantly higher frequency of clinical improvement and survival. All 52 patients with marrow recovery survived the 21-day study period and 94% improved compared to only 59% survival and 48% improvement in those whose marrows did not recover. This observation indicates granulocyte transfusion therapy is a poor substitute for normal granulopoiesis.