Erythematous Bullous Lesions on the Dorsa of the Hands Due to Contact Exposure to Ibutilide Fumarate for Injection

While waiting to observe the response to ibutilide fumarate by a patient with atrial fibrillation, a nurse preparing the intravenous solution inadvertently spilled the drug on the hands of a medical resident. The resident immediately wiped his hands dry with disposable paper towels. Several hours later he sensed tingling and itching over the area, and the next day two erythematous bullous lesions were present on the dorsal surfaces of both hands. A single application of topical steroid was applied to the affected areas. The lesions were kept clean and dry, and healed completely in approximately 10 days. This is an unusual allergic reaction due to contact with ibutilide fumarate.     

The Use of Cervicography in the Follow-up of Cervical Intraepithelial Neoplasia Treated by CO2 Laser

Summary: After treatment for cervical intraepithelial neoplasia (CIN) the follow-up of patients would be simplified if colposcopy could be safely omitted. A study of 50 patients was performed to determine the feasibility of such an approach. Cervical cytology, cervicography and colposcopy, with or without biopsy, was performed in each patient. From the results the following criteria for colposcopy were adopted: (a) patients thought to have CIN on cytology or cervicography, (b) inadequate cervicography picture (vagina covering cervix or poor quality photograph), (c) high-risk factors present (immunosuppression, after cone biopsy, postmenopausal). In this study the number of colposcopies would have been reduced from 50 to 11 if these criteria were adopted. Cervical cytology combined with cervicography is a reasonable alternative to colposcopy and we feel this is a technique worth pursuing for the follow-up of patients treated for CIN.     

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.     

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.     

Treatment of motoneuron degeneration by intracerebroventricular delivery of VEGF in a rat model of ALS

Neurotrophin treatment has so far failed to prolong the survival of individuals affected with amyotrophic lateral sclerosis (ALS), an incurable motoneuron degenerative disorder. Here we show that intracerebroventricular (i.c.v.) delivery of recombinant vascular endothelial growth factor (Vegf) in a SOD1(G93A) rat model of ALS delays onset of paralysis by 17 d, improves motor performance and prolongs survival by 22 d, representing the largest effects in animal models of ALS achieved by protein delivery. By protecting cervical motoneurons, i.c.v. delivery of Vegf is particularly effective in rats with the most severe form of ALS with forelimb onset. Vegf has direct neuroprotective effects on motoneurons in vivo, because neuronal expression of a transgene expressing the Vegf receptor prolongs the survival of SOD1(G93A) mice. On i.c.v. delivery, Vegf is anterogradely transported and preserves neuromuscular junctions in SOD1(G93A) rats. Our findings in preclinical rodent models of ALS may have implications for treatment of neurodegenerative disease in general.     

Identification of a Thymidylate Synthase Gene within the Genome of Chilo Iridescent Virus

The thymidylate synthase (TS, EC 2.1.1.45) is essential for the de novo synthesis of dTMP in pro- and eucaryotic organisms. Consequently it plays a major role in the replication of the DNA genome of a cell or a DNA virus. The gene encoding the TS of Chilo iridescent virus (CIV) was identified by nucleotide sequence analysis of the viral genome and was mapped within the EcoRI CIV DNA fragments G and R. Computer assisted analysis of the DNA nucleotide sequence between the genome coordinates 0.482 and 0.489 revealed an open reading frame (ORF) of 885 nucleotides. This ORF was found to encode a polypeptide of 295 amino acid residues (33.9 kDa) that showed significant homologies to known TS of different species including mammals, plants, fungi, protozoa, bacteria, and DNA viruses. The highest amino acid homologies were found between the CIV-TS and the TS of herpesvirus ateles (54.0%), Saccharomyces cerevisiae (51.8%), herpesvirus saimiri (51.0%), rhesus monkey rhadinovirus (50.7%), mouse (50.5%), rat (50.2%), varicella-zoster virus (50.2%), equine herpesvirus 2 (50.0%), and the human TS (48.4%). The CIV-TS contains six amino acid domains that are highly conserved in the TS of other species. Within these domains the major amino acid residues are present for which a functional role has been reported. The CIV-TS was found to be more closely related to the TS of eucaryotes than to the TS of procaryotes indicating the phylogenetic origin of the CIV-TS gene. The identification of a TS gene in the genome of CIV is the first report of a viral TS that is not encoded by a herpesvirus or a bacteriophage.     

Rapid identification of female carriers of DMD/BMD by quantitative real-time PCR

Recently developed PCR systems offer online-monitoring of amplification and allow simple and reliable DNA quantification. We have used the LightCycler system to develop a simple and rapid method for direct identification of female carriers of deletions and duplications in the dystrophin gene. The challenge resides in the ability to identify the presence of a deleted or duplicated allele over the background contributed by the normal allele. Quantification is based on the determination of the ratio between potentially deleted/duplicated dystrophin exons and non-deleted/-duplicated reference exons using the unspecific dsDNA-dye SYBRgreen I. In a retrospective study, we evaluated our method in female relatives of DMD/BMD patients with known carrier status by comparative analysis of deleted or duplicated versus non-deleted/-duplicated exons. Carrier status was accurately attributed in 100% of cases, the mean ratios being 0.52+/-0.12 for deletion carriers (expected value: 0.5) and 1.56+/-0.18 for duplication carriers (expected value: 1.5) vs. 1.022+/-0.17 for non-carriers (expected value: 1.0). The method proved to be simple, rapid, reliable, and cost-effective. It may be used for direct determination of deletions/duplications in potential DMD/BMD carriers and may easily be adapted for other genetic conditions involving deletions and duplications.