Non-tuberculous mycobacteria in cystic fibrosis

BACKGROUND—The clinical significance of thepresence of non-tuberculous mycobacteria in the sputum of patients withcystic fibrosis is unclear. A retrospective case-control study wasperformed to assess possible risk factors for non-tuberculousmycobacteria and its impact on clinical status in patients with cystic fibrosis.
METHODS—The records of all patients attending theLeeds cystic fibrosis clinics who were positive for non-tuberculousmycobacteria were examined. Each case was matched with two controls forsex, age, and respiratory function at the time of the firstnon-tuberculous mycobacteria isolate. Details of respiratory function,nutritional status, antibiotic and corticosteroid therapy,Shwachman-Kulczycki (S-K) score, Northern chest radiographic score, andthe frequency of isolation of other bacteria and fungi were collectedfrom two years before to two years after the first non-tuberculousmycobacteria isolate. The patients' genotype and the presence ofdiabetes mellitus were also recorded.
RESULTS—Non-tuberculous mycobacteria were isolatedfrom 14 patients out of a cystic fibrosis population of 372 (prevalence = 3.8%). No significant effect of non-tuberculous mycobacteria wasseen on respiratory function, nutritional status, or S-K score. There was a significant association with the number of intravenous antibiotic courses received before the first isolate with cases receiving, onaverage, twice as many courses as controls (cases 6.64, controls 2.86, 95% CI for difference 1.7 to 5.9). No significant difference was seenbetween cases and controls for Northern scores, previous steroidtherapy, or the incidence of diabetes mellitus.
CONCLUSIONS—Non-tuberculous mycobacteria infectionin patients with cystic fibrosis is uncommon and its clinical impactappears to be minimal over a two year period. Frequent intravenousantibiotic usage is a possible risk factor for colonisation withnon-tuberculous mycobacteria.

     

The role of scintigraphy in urinary tract infection

There is controversy regarding the role of radiological imaging for urinary tract infection (UTI). The "gold standard" has been the intravenous pyelogram (IVP). Yet, the IVP has a very limited value with only about 25% of children with pyelonephritis demonstrating abnormalities. Ultrasound (US) has recently been advocated as a replacement for the poorly sensitive and poorly specific IVP. However, comparative studies between US and IVP indicate only an equivalent sensitivity and specificity. Cortical scintigraphy with Technetium-99m glucoheptonate (99mTc GH) or 99mTc dimercaptosuccinic acid (99mTc DMSA) has also been advocated as a means of differentiating parenchymal (pyelonephritis) from nonparenchymal (lower UTI) involvement in UTI. The clinical presentation may be misleading especially in the infant and child in whom an elevated temperature, flank pain, shaking chills, or an elevated sedimentation rate are often lacking. The clinician attempts to localize the site of infection for it has a direct bearing upon the therapy. A collecting system infection can often be eradicated with a single oral dose of an appropriate antibiotic, whereas renal parenchymal involvement requires IV therapy for an extended interval. Cortical scintigraphy can localize the site of infection with a high degree of accuracy. Recent studies report a sensitivity of 86% and specificity of 81% of pyelonephritis. This is in contrast to the IVP with a sensitivity of only 24% and US with a sensitivity of only 42%. The scintigraphic appearance of parenchymal infection of the kidney is a spectrum of minimal to gross defects reflecting the degree of histologic involvement that spans from a mild infection to frank abscess. Cortical scintigraphy can be used to monitor the evolution of scarring following infection. Cortical scintigraphy with 99mTc DMSA or 99mTc GH is the method of choice for the initial evaluation of UTI. Not only does it have a very high sensitivity and specificity for differentiating parenchymal from collecting system disease, but it also provides an accurate quantitative measurement of function and in combination with radioiodinated orthoiodohippurate renography and Lasix (furosemide; Abbott Laboratories, North Chicago) diuresis will also differentiate significant obstruction from stasis. The use of radionuclide techniques opens new vistas for the investigation of UTI. Cortical scintigraphy should become the gold standard by which other technologies, therapy, and theoretical considerations of pyelonephritis are measured.     

Dietary factors related to physical fitness among navy shipboard men

Abstract This study examines the relationship between habitual dietary practices and performance on the physical readiness test required of active duty Navy personnel. Participants were 1,013 men (mean age = 26.2 years) stationed aboard nine Navy ships. The men completed a self-report survey of lifestyle and dietary habits and were evaluated on four tests of physical fitness: 1.5-mile Run, Sit-ups, Sit-reach, and Percent Body Fat. A standardized Overall Fitness score was also computed for each person. Results indicated that the participants tended to skip breakfast, ingest moderate amounts of caffeine, and favor a high-fat, low-fiber diet. Fitness scores were associated with a number of dietary variables, including caffeine intake, between-meal snacking, and overeating (all negatively related to fitness, p <.01), and having a general "nutrition orientation" (positively related to fitness, p <.001). The relationships were confounded by the influence of age, exercise, and smoking, but even after controlling for these, diet was a significant predictor of fitness (p <.001).     

Hurricane Hugo blows down the broccoli: Preschoolers' post-disaster play and adjustment

This article reports highlights from over 200 parents' observations of their preschoolers' play and verbalizations in the year following Hurricane Hugo. Commonly reported activities included reenactment and discussion of the event in multiple mediums, personification of Hugo, and expression of fears related to storms. Precocious concern for others, insight, and vocabulary were also noted. In these intact, relatively high functioning families, parents seemed able to facilitate their youngsters' adjustment without outside intervention.Portions of this report were presented in earlier form at the 1991 Society for Research in Child Development meeting in Seattle, Washington.     

Temporomandibular joint: morphology and signal intensity characteristics of the disk at MR imaging

Magnetic resonance (MR) imaging has been used in the temporomandibular joint (TMJ) primarily to define the disk position. This report examines altered morphology and signal intensity characteristics of the TMJ disk as they relate to the severity of internal derangement. Two hundred sixteen joints in 133 patients with a history of such derangement. were imaged with MR. Disk position, signal intensity, morphology, and the presence of osteoarthritis were determined for each joint. The normal disk was not anteriorly displaced and had a normal "bow-tie" shape. A grade 1 disk was anteriorly displaced and had a normal shape; a grade 2 disk was anteriorly displaced and had an abnormal shape. Forty (19%) joints were considered normal; none of these exhibited osteoarthritis. One hundred thirty-nine (64%) joints were grade 1; osteoarthritis was found in 17%. Thirty-seven (17%) were grade 2; osteoarthritis was found in 95%. All forty normal joints had high or intermediate signal intensity in the disk. Osteoarthritic joints had a higher percentage of disks with diminished intensity (P less than .0001). Severe or untreated osteoarthritis is known to be a complication of TMJ internal derangements; hence this grading system seems to correlate with the severity of internal derangement.     

Relationship of oxidative damage to the hepatocarcinogenicity of the peroxisome proliferators di(2-ethylhexyl)phthalate and Wy-14,643

Quantitative comparisons of the time course of biochemical andmorphological changes induced by peroxisome proliferators resultingin low and high incidences of hepatic cancer have not been conductedpreviously under bioassay conditions. [4-Chloro-6-(2,3 xylidino)-2-pyrimidyl-thio]aceticacid (Wy-14,643) at 0.1% in the diet produced a much higherincidence of hepatic cancer in male rats than 1.2% di(2-ethylhexyl)phthalate(DEHP) in the diet. Both diets, however, caused similar degreesof peroxisome proliferation. To investigate this differencein carcinogenicity, H₂O₂-detoxification mechanisms and indicesof oxidative damage were evaluated in male F-344 rats fed 1.2%DEHP or 0.1% Wy-14,643 for up to one year. DEHP or Wy-14,643treatment increased hepatic catalase activity 25% from 8 to365 days. DEHP or Wy-14,643 treatment decreased hepatic glutathioneperoxidase activity by 50% from 8 to 365 days. Glutathione concentrationswere not affected by 151 days of DEHP or Wy-14,643 feeding.The similar effects of DEHP and Wy on H₂O₂ detoxification enzymesand glutathione concentrations suggests that these factors arenot responsible for the widely different carcinogenicities ofWy-14,643 and DEHP. Hepatic vitamin E concentrations were 50%lower in rats receiving Wy-14,643 for 151 days as compared torats fed DEHP or control diets. Lipofuscin, which was containedwithin lysosomes, was increased 3-fold after 39 days of DEHPand remained at this level up to 365 days of treatment. In comparison,lipofuscin was increased 4-fold after 18 days of Wy-14,643 andcontinued to accumulate in a linear manner reaching values 30-foldover controls after 365 days of treatment. DEHP treatment for39–365 days increased the activities of the lysosomalenzymes -fucosidase, ß-galactosidase and N-acetylglucosaminidase50–100%. The same enzyme activities were increased 4-foldafter 39–365 days of Wy-14,643. Lysosomal cathepsin Bactivity was unchanged by DEHP but doubled by 151 and 365 daysof Wy-14,643. Acid phosphatase activity was unchanged by DEHPbut increased by 50% after 151 and 365 days of Wy-14, 643. Inaddition, conjugated dienes were increased (45%) only in ratsreceiving Wy-14,643 for 151 and 365 days. These data show forthe first time that the magnitude and time course of lipofuscindeposition, induction of lysosomal enzymes and conjugated dieneaccumulation, is correlated closely with the degree of carcinogenicity.Wy-14,643-induced decreases in hepatic vitamin E concentrationscould contribute to the observed accumulation of conjugateddienes at later time points. The data suggest that lipofuscinaccumulation is an early biomarker that is quantitatively predictiveof the carcinogenicity of the peroxisome proliferators DEHPand Wy-14,643.     

Predicting pregnancy and spermatogenesis by survival analysis during gonadotrophin treatment of gonadotrophin-deficient infertile men

BACKGROUND: Predictors of fertility or spermatogenesis during gonadotrophin therapy of gonadotrophin-deficient men remain poorly defined. METHODS AND RESULTS: In order to evaluate potential predictors, this study evaluated 29 consecutive gonadotrophin-deficient men all desiring paternity who received 43 courses of therapy in one centre between 1982 and 1998. The Kaplan-Meier survival analysis estimates of median (SE) time to a sperm concentration of >0, >5 and >20 x 10(6)/ml were 5.5 (1.1), 12.4 (2.3) and 29.1 (1.9) months respectively. Conception occurred in 22/43 cycles (with eight men achieving two pregnancies) with a median (SE) Kaplan-Meier estimate of 20.5 (4.7) months. The median sperm concentration at conception was 5.0 (SE 2.0; range 0.0-59.5) x 10(6)/ml. Multivariate correlated Cox proportional hazards models predicting these same sperm thresholds and conception were developed by forward stepwise variable selection with verification of the model by backward stepping. Larger testicular volume, prior gonadotrophin therapy, completion of puberty, older age, the absence of adverse fertility factors and the absence of multiple pituitary hormone deficiency predicted a favourable response. Multivariate modelling suggests that the two most important predictors of sperm output are testicular volume and pubertal status. The most important potentially modifiable predictor was prior gonadotrophin therapy. The efficacy of recombinant and urinary FSH were similar. Prior androgen therapy and partner's age did not appear to be significant. CONCLUSIONS: Since prolonged treatment may be required to induce spermatogenesis, attention to these predictors may allow appropriate early use of advanced reproductive technologies.     

Minimal progesterone support required for the maintenance of pregnancy in mice

A study of the degree of progesterone support required for the maintenance of various stages of pregnancy was undertaken in mice. Mated females were ovariectomized at various stages of pregnancy and progesterone and oestradiol support provided by s.c. Silastic implants with known release characteristics. In the earliest stages of pregnancy (days 1-5), very low concentrations of progesterone (<25% of normal physiological values) were sufficient to maintain pre-implantation stages and allow implantation. In the immediate post-implantation period (days 5-9), the development of implantation sites and decidualization required considerably higher progesterone support. In mid-pregnancy (days 11-14), progesterone alone could not maintain pregnancy unless present in very high amounts; however, the presence of oestradiol during this period lowered the progesterone requirements to well within the physiological range. This effect of oestradiol started on day 11 but required the level of oestradiol support to be kept within strictly defined limits, with high concentrations inducing abortion. Progesterone alone was able to maintain pregnancy from day 15. These results indicate that the minimal progesterone support required for pregnancy in mice varies considerably at different stages of pregnancy and is at least partly modulated by oestradiol.      

PCR-Based assay to quantify human immunodeficiency virus type 1 DNA in peripheral blood mononuclear cells

An assay that quantifies the amount of human immunodeficiency virus type 1 (HIV-1) DNA in peripheral blood mononuclear cells has been developed. PCR amplification of the HIV-1 DNA is performed in the presence of an internal quantitation standard, and colorimetric detection of the amplified product is performed with microwell plates. The copies of HIV-1 DNA are normalized to total genomic DNA input. The assay has an analytical sensitivity of 10 input copies per amplification reaction and a three-log detection range. In an analysis of sequential samples from patients on combination therapy, HIV-1 DNA was quantifiable for all individuals tested, including those with undetectable plasma HIV-1 RNA. In a separate study, a comparison of HIV-1 DNA levels was made with a group of long-term survivors and progressors. The mean HIV-1 DNA levels were lower in the long-term survivors than in the progressors (P, 0.04). The mean HIV-1 RNA levels were also lower, but the difference was not statistically significant (P, 0.164). A quantitative DNA assay will provide an additional tool to gain insight into the natural history of infection and the continued efficacy of potent antiretroviral therapies.     

Premature ovarian failure

Premature ovarian failure (POF) causing hypergonadotrophic hypogonadism occurs in 1% of women. In majority of cases the underlying cause is not identified. The known causes include: (a) Genetic aberrations, which could involve the X chromosome or autosomes. A large number of genes have been screened as candidates for causing POF; however, few clear causal mutations have been identified. (b) Autoimmune ovarian damage, as suggested by the observed association of POF with other autoimmune disorders. Anti-ovarian antibodies are reported in POF by several studies, but their specificity and pathogenic role are questionable. (c) Iatrogenic following surgical, radiotherapeutic or chemotherapeutic interventions as in malignancies. (d) Environmental factors like viral infections and toxins for whom no clear mechanism is known. The diagnosis is based on finding of amenorrhoea before age 40 associated with FSH levels in the menopausal range. Screening for associated autoimmune disorders and karyotyping, particularly in early onset disease, constitute part of the diagnostic work-up. There is no role of ovarian biopsy or ultrasound in making the diagnosis. Management essentially involves hormone replacement and infertility treatment, the only proven means for the latter being assisted conception with donated oocytes. Embryo cryopreservation, ovarian tissue cryopreservation and oocyte cryopreservation hold promise in cases where ovarian failure is foreseeable as in women undergoing cancer treatments.