Electrical Analysis of Fresh,Excised Human Skin: A Comparison with Frozen Skin

Samples of human allograft skin prepared without freezing ("fresh skin) were found to have electrical and sodium ion transport properties which differed only slightly from those of skin which had been similarly treated but stored frozen (frozen skin). The fresh skin samples were less permeable to sodium ions during passive diffusion and less conductive than frozen skin at low current levels. They were more permselective for sodium versus chloride during constant-current iontophoresis and showed slightly more asymmetry in their current–voltage properties. Overall, the electrical behavior of the two tissues was similar enough to support the use of frozen tissue in iontophoresis studies. However, caution should be exercised when considering the use of frozen skin for applications, such as those based on electroosmosis, where the observed differences could have a major impact on the results.     

Examiner Differences in the Mini-Cex

Objective: The objective of this study was to analyze whether faculty ratings of residents, using the mini-CEX oral exam format, differed in stringency or were influenced by the clinical setting. It also sought to learn whether the examiners were satisfied with the format.Method: A mini-CEX encounter consisted of a single faculty member observing a resident conduct a focused history and physical examination in an inpatient, outpatient, or emergency room setting. After asking the resident for a diagnosis and treatment plan, the faculty member rated the resident and provided educational feedback. The encounters were intended to be short and occur as a routine part of the training, so each resident would be evaluated on many occasions by different faculty.Sample: Sixty-four attending physicians evaluated residents from five internal medicine training programs; data were analyzed for 355 mini-CEX encounters involving 88 residents.Results: There were not large differences among the examiners in their ratings. Moreover, there were not great differences among the ratings in terms of the training program with which the examiner was associated, the setting of the mini-CEX, or the nature of the patient. The examiners were generally satisfied with the format and their level of satisfaction was correlated with the residents' perceptions of the format.Conclusion: The mini-CEX adapts itself to a broad range of clinical situations, and these results show that it should produce roughly comparable scores over examiners and settings. This makes it a worthwhile device for evaluation at the local level.This revised version was published online in September 2005 with corrections to the Cover Date.     

Anaesthetic management of an asthmatic child for appendicectomy

A 13-yr-old boy was scheduled for emergency appendicectomy because of abdominal pain. His preoperative medical history was complicated by a recent hospital admission for management of asthma. He had presented to hospital seven days earlier because of dyspnoea, tachypnoea and oxygen desaturation to 77% on room air. Following admission, he required intensive non-ventilatory management of his asthma, including intravenous salbutamol, methylprednisolone, and aminophylline, as well as use of an ipratroprium bromide inhaler and 100% oxygen by mask. He was discharged to the ward, and continued on prednisone (deltacortisone), beclomethasone inhaler, ipratroprium inhaler, and salbutamol inhaler. During his ICU stay, he complained of nonspecific abdominal pain, interpreted as gastro-oesophageal reflux. After four days, he was discharged to the ward. On his sixth hospital day, he began to experience right-sided lower abdominal pain and right shoulder pain. A surgeon was consulted, and the patient was found to have a very tender right lower quadrant with guarding and rebound pain. He was therefore scheduled for appendicectomy; antibiotic therapy with ampicillin, gentamicin, and metronidazole was initiated.     

Epidural anaesthesia for elective Caesarean section does not influence fetal umbilical artery blood flow indices

This prospective study was completed to determine the influence of epidural anaesthesia on the fetoplacental circulation of normal subjects. Thirty-seven normal pregnant patients at term, undergoing elective Caesarean section, had Doppler measurements of the fetal umbilical artery blood flow velocity before and after epidural anaesthesia using lidocaine 2% without epinephrine. There were no differences in systolic/diastolic, resistance or pulsality indices following epidural anaesthesia. These results suggest that this technique has no adverse effect on fetoplacental circulation in normal non-labouring subjects. Cette étude prospective a pour but de déterminer l’influence de l’anesthésie épidurale sur la circulation foeto-placentaire dans le contexte d’une grossesse normale. Des indices de vélocité du flot de l’artère ombilicale foetale ont été mesurés par Doppler chez trentesept patientes gravides à terme, sans complications, programmées pour une césarienne élective, avant et après une anesthèsie épidurale utilisant la lidocaine 2% sans épinéphrine. Les indices de rapport systole/diastole, de résistance et de pulsatilité sont demeurés inchangés après l’induction de l’anesthésie épidurale. Ces constatations suggèrent que l’anesthésie épidurale n’a pas d’influence sur la circulation foetoplacentaire chez des patientes enceintes normales à terme qui ne sont pas en travail.     

Expression of an ovalbumin-specific V{beta}8.2 TCR transgene inhibits collagen arthritis in B10.Q mice

Previous studies have illustrated the importance of T cellsbearing ß TCRs in the induction and development ofcollagen induced arthritis (CIA) in mice. However, the scopeof TCR usage in CIA has yet to be clearly defined. Given theinherent diversity of the TCR repertoire, the relative flexibilityof the arthritogenic TCR repertoire specific for type II collagen(CII) is not clear. Therefore, we chose to examine the influenceof a highly skewed TCR repertoire on CIA. Arthritis susceptibleB10.Q (H-2^q) mice were mated with C57L (H-2^b) animals expressingan ovalbuminspecific V_ß8.2 TCR transgene (Tg) andTg⁺ offspring were further backcrossed to B10.Q. HomozygousH-2^a/q, V_ß8.2 Tg⁺ mice displayed a high level of V_ß8.2⁺T cells in peripheral blood. However, expression of some endogenousV_ß TCR, such as V_ß14, was still detected.Upon immunization with bovine CII in adjuvant, V_ß8.2Tg⁺ mice were highly resistant to CIA when compared with Tg^–littermates. Analysis of sera demonstrated a marked reductionin antibody specific for homologous mouse CII as well as heterologousbovine CII in Tg⁺ animals. Interestingly, V_ß8.2 Tg⁺mice still mounted good antibody responses following immunizationwith human thyroglobulin, indicating that the skewed TCR repertoireaffected anti-CII but not antithyroglobulin responses. Thus,our findings show that constraints placed on the TCR repertoireInhibit pathogenic responses against CII and suggest that inH-2^q mice the arthritogenlc TCR repertoire bears only limitedflexibility.     

Prevalence of rotavirus antibodies in a non-human primate colony

A total of 51 monkeys maintained in a colony at the Institute of Primate Research (Kenya) and housed in doors with natural lighting in a group cage were used in this study. Monkeys belonging to 3 species were selected at random and blood samples collected. The serum samples were screened for presence of neutralizing antibodies (VTN) to rhesus rotavirus (RRV) by virus neutralization assay. Virus neutralization was determined by 60% reduction in fluorescent focus units (ffu). 96% of the animals screened had naturally occurring antibodies to rhesus rotavirus. Another group of 11 lactating monkeys (5 baboons, 6 vervets) and their infants were screened further for presence of IgG and IgA antibodies in serum and breast milk (mothers). Overall, the mothers had higher titres of both IgG and IgA than the infants. Taken together, these results demonstrate rotavirus infection is endemic in this primate colony. This mimics the human situation, hence, captive non human primates (such as the baboons) could be a suitable model for testing rotavirus candidate vaccines and for investigating the possible application in humans of passive-active immunization strategy.     

Laser energy threshold for thermal vascular injury in a port-wine stain skin model

Monte Carlo simulation of laser energy deposition in a port-wine stain (PWS) skin model and numerical solution of the thermal diffusion equation have been used to calculate threshold energies for thermal injury of PWS blood vessels for different vessel sizes and laser pulse durations. It has been assumed that an average vessel temperature rise of 65 C causes thermal injury to the blood vessel. The result is that for a certain combination of wavelength, pulse duration and incident energy density, only a limited range of blood vessel sizes can be injured optimally. Higher energy densities are required to injure smaller vessels with the same pulse duration, spot size and wavelength. This gives support to the mechanisms of selective photothermolysis suggested previously by Anderson and Parrish, although their model was based on the cooling behaviour of instantaneously heated vessels. The authors hypothesize that different laser parameter settings that match the individual PWS vessel anatomy during treatment will be used in the future, instead of many treatments with the same laser parameters. This could lead to less treatment sessions and to an improved predictability of clinical results.     

Factor analysis of the psychosocial items of the EORTC QLQ-C30 in metastatic breast cancer patients participating in a psychosocial intervention study

The underlying factor structure of a subset of 12 items, which comprise the psychosocial subscales of the EORTC QLQ-C30 was explored in a group of women, all with metastatic breast cancer who were participating in a psychosocial intervention study. Two main factors were identified in this exploratory factor analysis, representing emotional distress and functional ability dimensions. A preliminary assessment of the external validity of the two factor structure was undertaken. The results support the validity of a summative emotional distress and functional ability score in this sample of patients. The functional ability score discriminated well for subgroups defined by clinical status indicators (e.g., performance status, pain, chemotherapy treatment, fatigue). The emotional distress subscale discriminated with respect to suffering, fatigue and sleep disturbance. Both subscales converged with related concepts measured by independent instruments, providing support for convergent validity. Summative index scores may be advantageous for application in particular research situations; applying quality adjustments in health policy analyses; for screening purposes; to monitor populations and make comparisons across broad groups and as stratification variables in clinical trials. Further research to confirm the 2 factor structure is required in other samples before the interpretation can be accepted with confidence.     

Guanine to adenine mutations in patients with lattice corneal dystrophy Nachweis einer Punktmutation im Keratoepithelin-Gen

Background: Lattice dystrophy is an autosomal-dominantly inherited disease. A mutation of the gene coding for kerato-epitheline has been found in patients with this stromal dystrophy. In codon 124 a Guanine to Adenine mutation of the nucleotide 417 has been described. We looked for this mutation in a family with lattice dystrophy treated in our clinic.     

Characterization of AUCs from Sparsely Sampled Populations in Toxicology Studies

Purpose. The objective of this work was to develop and validate blood sampling schemes for accurate AUC determination from a few samples (sparse sampling). This will enable AUC determination directly in toxicology studies, without the need to utilize a large number of animals. Methods. Sparse sampling schemes were developed using plasma concentration-time (Cp-t) data in rats from toxicokinetic (TK) studies with the antiepileptic felbamate (F) and the antihistamine loratadine (L); Cp-t data at 13–16 time-points (N = 4 or 5 rats/time-point) were available for F, L and its active circulating metabolite descarboethoxyloratadine (DCL). AUCs were determined using the full profile and from 5 investigator designated time-points termed critical time-points. Using the bootstrap (re-sampling) technique, 1000 AUCs were computed by sampling (N = 2 rats/point, with replacement) from the 4 or 5 rats at each critical point. The data were subsequently modeled using PCNONLIN, and the parameters (k_a, k_e, and V_d) were perturbed by different degrees to simulate pharmacokinetic (PK) changes that may occur during a toxicology study due to enzyme induction/inhibition, etc. Finally, Monte Carlo simulations were performed with random noise (10 to 40%) applied to Cp-t and/or PK parameters to examine its impact on AUCs from sparse sampling. Results. The 5 time-points with 2 rats/point accurately and precisely estimated the AUC for F, L and DCL; the deviation from the full profile was ~10%, with a precision (%CV) of ~15%. Further, altered kinetics and random noise had minimal impact on AUCs from sparse sampling. Conclusions. Sparse sampling can accurately estimate AUCs and can be implemented in rodent toxicology studies to significantly reduce the number of animals for TK evaluations. The same principle is applicable to sparse sampling designs in other species used in safety assessments.