Impairment of vascular endothelial function by high-potassium storage solutions

High-potassium cold storage solutions are currently used to preserve myocardial function during heart transplantation. However, the effects of high potassium concentration on vascular endothelial function are not well known. We therefore tested vascular rings for endothelial-dependent and endothelial-independent relaxation during storage in normokalemic, normothermic buffers and then in buffers supplemented with 10 to 110 mmol/L KCl. Maximal endothelial-dependent relaxation was significantly reduced at all high potassium concentrations. Endothelial-independent relaxation was impaired only with 80 and 110 mmol/L KCl buffers. Both endothelial-dependent relaxation and endothelial-independent relaxation returned to normal values after washout of excess potassium. Similarly, endothelial-dependent relaxation and endothelial-independent relaxation were assessed in rings after 24 hours of hypothermic storage in normokalemic Krebs buffer, and in buffers containing 20 and 110 mmol/L KCl. Maximal endothelial-dependent relaxation was significantly reduced after preservation in the high-potassium solutions, whereas endothelial-independent relaxation was not impaired. We conclude that there is significant impairment of endothelial function after cold storage in a high-potassium buffer. Inadequate washout of potassium during normothermic conditions may lead to further functional impairment of vascular responsiveness. A low-potassium storage medium is recommended for improved vascular protection.     

Long crocidolite asbestos fibers cause polyploidy by sterically blocking cytokinesis

Asbestos has been described as a physical carcinogen in that its carcinogenic effects appear to be related primarily to fiber dimensions. It has been hypothesized that long asbestos fibers may interfere with chromosome distribution during cell division, causing genomic changes that lead to cell transformation and neoplastic progression. Using high-resolution time-lapse light microscopy and serial-section electron microscopy, we have followed individual crocidolite asbestos fibers through the later stages of cell division in LLC-MK2 epithelial cells, and have detailed for the first time their effect on cytokinesis. We found that long fibers (15-55 microgram), trapped by the cleavage furrow, sterically blocked cytokinesis, sometimes resulting in the formation of a binucleated cell. The ends of blocking fibers were usually found within invaginations of the newly formed nuclei. Nuclear envelope-fiber attachment was evident when a chromatin strand ran with the fiber into the intercellular bridge. Such strands may break, causing chromosome structural rearrangements. Our data are the first to show that individual crocidolite fibers can cause genomic changes by sterically blocking cytokinesis and that fiber length and affinity for the nuclear envelope are important factors. Such genomic changes may be among the initial events leading to asbestos-induced cancers.     

Acute gastric dilatation with infarction and perforation. Report of fatal outcome in patient with anorexia nervosa

This is a report of a 22-year-old woman with treated anorexia nervosa who died of complications of acute gastric dilatation-that is, infarction and perforation with severe and irreversible shock. Binge eating and drinking, precipitated by emotional crises, contributed to her acute gastric dilatation. This complication of anorexia nervosa has been previously reported, but, unlike the others, this case ended fatally. The literature is reviewed.     

Hypnotic trance. The old and the new

SCFE is the most common hip abnormality in adolescence. The subsequent development and severity of degenerative changes is related to the degree of slippage and to delay in diagnosis. Awareness of this diagnostic possibility in the population at greatest risk and knowledge of subtle and early radiographic findings will allow prompt diagnosis and treatment of SCFE. Follow-up radiographic examination should be used to evaluate for physeal fusion and any complications, including progression of the slip, hardware complications, chondrolysis, avascular necrosis, and secondary osteoarthritis.     

Novel method for processing respiratory specimens for detection of mycobacteria by using C18-carboxypropylbetaine: blinded study

A novel method for processing respiratory specimens to improve culture and acid-fast staining of mycobacteria is introduced. This new method utilized N,N-dimethyl-N-(n-octadecyl)-N-(3-carboxypropyl)ammonium inner salt (Chemical Abstract Service no. 78195-27-4), also known as C18-carboxypropylbetaine (CB-18). In a blinded, five-center study, CB-18-based processing was compared to the standard method combining NALC and NaOH (NALC/NaOH). A total of 573 respiratory specimens were tested. Individual specimens were split approximately equally; the host institutions processed half of each specimen by the NALC/NaOH method, while the other half was processed with CB-18 at Quest Diagnostics--Baltimore. A total of 106 specimens were culture positive for acid-fast bacilli (AFB). Replacement of the primary decontamination agent with CB-18 caused changes in all diagnostic parameters. Aggregate culture sensitivity improved by approximately 43% (P < 0.01), and smear sensitivity improved by approximately 58% (P < 0.01). The sensitivity of smear relative to that of M. tuberculosis isolates exceeded 93% (P < 0.01) when specimens were processed with CB-18. The average times to a positive result were reduced by 7.3 days in liquid culture (P < 0.01) and 5.3 days on solid media (P < 0.05); however, the CB-18 method had a 20.8% contamination rate in liquid culture versus a rate of approximately 7.5% with NALC/NaOH processing. There were also unusual reductions in liquid culture sensitivity and smear specificity among CB-18-processed specimens. The characteristics of the latter parameters suggested that refinement of the CB-18 processing method should allow further improvements in culture sensitivity. This study showed that the CB-18 method has the potential to improve both smear and culture detection for these important human pathogens.     

A two-phase model for controlled drug release from biphasic polymer hydrogels

A comprehensive two phase model is developed to describe the sustained release of a solute or drug from a biphasic hydrogel substrate. Such a material consists of a continuous hydrophilic phase (polymer backbone in water) and a dispersion of spherical microdomains made of the hydrophobic side chains of the polymer organised in a micelle like fashion. The solute or drug is assumed to be encapsulated within the dispersed microdomains, and to diffuse from the interior to the surface of the microdomain where it exchanges following a Langmuir isotherm. Mass transfer to the bulk phase occurs by desorption of the drug from the surface through a driving force that is proportional to the difference of surface and bulk concentration. Accordingly the drug is released to the surroundings by diffusion through the bulk. Depending on the values of the Langmuir constant and assuming well stirred behaviour in the interior of the microdomain, the present model results in either of the two asymptotic models developed in previous studies. The results of a parametric study show that the desired steady state flux of a specific drug to the surroundings may be obtained given appropriate values of structural properties of the material. This conclusion is further supported when using this model to simulate earlier experimental results. The polymer structural properties can be manipulated easily during the fabrication of dispersed-phase networks, as indicated by preliminary experiments.     

High risk of breast carcinoma after irradiation of young women with Hodgkin's disease

BACKGROUND: Treatment-associated second neoplasms have emerged as a major threat to the continued survival of patients cured of Hodgkin's disease. In this study, the authors investigated the risk of breast carcinoma in an irradiated Hodgkin's disease population. METHODS: One hundred and eleven women younger than 60 years presenting between 1964 and 1984 with Stage I and II Hodgkin's disease who received mantle irradiation were retrospectively analyzed and compared with an age specific population. Median follow-up was 18 years (range, 10-30 years), and the median age at initiation of therapy was 24 years. Kaplan-Meier actuarial risks, relative risks (RRs) (the ratio of the observed to the expected cases) with 95% confidence intervals (CIs), and the log rank test for trends were calculated. RESULTS: Fourteen women developed breast carcinoma: 8 of 33 patients younger than 20 years at the time of irradiation, 5 of 48 patients age 20 to 29 years, and 1 of 30 patients age 30 years or older. Actuarial calculation predicted a 34.0% (CI, 14.2-53.8) risk of breast carcinoma at 25 years after therapy for the youngest group, 22.3% (CI, 4.1-40.5) for the group of intermediate age, and 3.5% (CI, 0-10.1) for the oldest group. The RR of breast carcinoma was 56 (CI, 23.3-107) for those 19 years or younger at the time of treatment, 7.0 (CI, 2.3-16.4) for those age 20-29 years, and 0.9 (CI, 0-5.3) for those 30 years and older. Excluding 1 patient who was age 38 years at the time of irradiation, the remaining 13 breast carcinomas were tightly clustered in women irradiated between the ages of 14 through 25, and were detected in years 11 through 25 after treatment, with 7 occurring in years 15 through 18. CONCLUSIONS: Women younger than 30 years, particularly those younger than 20 years, who have received mantle irradiation for Hodgkin's disease require meticulous follow-up for breast carcinoma. The high incidence of breast carcinoma in this patient population should be considered when making treatment decisions in young women with early stage Hodgkin's disease.     

The treatment of osteoarthritis of the knee with pulsed electrical stimulation

OBJECTIVE: The safety and effectiveness of pulsed electrical stimulation was evaluated for the treatment of osteoarthritis (OA) of the knee. METHODS: A multicenter, double blind, randomized, placebo controlled trial that enrolled 78 patients with OA of the knee incorporated 3 primary efficacy variables of patients' pain, patients' function, and physician global evaluation of patients' condition, and 6 secondary variables that included duration of morning stiffness, range of motion, knee tenderness, joint swelling, joint circumference, and walking time. Measurements were recorded at baseline and during the 4 week treatment period. RESULTS: Patients treated with the active devices showed significantly greater improvement than the placebo group for all primary efficacy variables in comparisons of mean change from baseline to the end of treatment (p < 0.05). Improvement of > or = 50% from baseline was demonstrated in at least one primary efficacy variable in 50% of the active device group, in 2 variables in 32%, and in all 3 variables in 24%. In the placebo group improvement of > or = 50% occurred in 36% for one, 6% for 2, and 6% for 3 variables. Mean morning stiffness decreased 20 min in the active device group and increased 2 min in the placebo group (p < 0.05). No statistically significant differences were observed for tenderness, swelling, or walking time. CONCLUSION: The improvements in clinical measures for pain and function found in this study suggest that pulsed electrical stimulation is effective for treating OA of the knee. Studies for longterm effects are warranted.     

Bromine-76 and carbon-11 labelled NNC 13-8199, metabolically stable benzodiazepine receptor agonists as radioligands for positron emission tomography

NNC 13-8241 has recently been labelled with iodine-123 and developed as a metabolically stable benzodiazepine receptor ligand for single-photon emission computed tomography (SPECT) in monkeys and man. NNC 13-8199 is a bromo-analogue of NNC 13-8241. This partial agonist binds selectively and with subnanomolar affinity to the benzodiazepine receptors. We prepared 76Br labelled NNC 13-8199 from the trimethyltin precursor by the chloramine-T method. Carbon-11 labelled NNC 13-8199 was synthesised by N-alkylation of the nitrogen of the amide group with [11C]methyl iodide. Positron emission tomography (PET) examination with the two radioligands in monkeys demonstrated a high uptake of radioactivity in the occipital, temporal and frontal cortex. In the study with [76Br]NNC 13-8199, the monkey brain uptake continued to increase until the time of displacement with flumazenil at 215 min after injection. For both radioligands the radioactivity in the cortical brain regions was markedly reduced after displacement with flumazenil. More than 98% of the radioactivity in monkey plasma represented unchanged radioligand 40 min after injection. The low degree of metabolism indicates that NNC 13-8199 is metabolically much more stable than hitherto developed PET radioligands for imaging of benzodiazepine receptors in the primate brain. [76Br]NNC 13-8199 has potential as a radioligand in human PET studies using models where a slow metabolism is an advantage.