Interobserver variation in the evaluation of neurological signs: observer dependent factors.

Introduction - Interobserver variation among four observers in evaluation of eight selected neurological signs was investigated. Material & methods - Two hundred and two consecutive unselected inpatients were examined by two senior neurologists and two trainees, all without knowledge of the neurological case history. The signs examined were: anisocoria, jerky eye movements, facial palsy, elbow extension force, finger-nose test, Barré sign, knee jerk, and extensor plantar reflex. Observed agreement rates and kappa coefficients were calculated in order to compare the interobserver variability among neurologists and trainees, and to evaluate differences in the interobserver variability between signs. Results - Observed agreement rates varied from 0.80 to 0.95 for neurologists and from 0.65 to 0.98 for trainees. For neurologists kappa coefficients ranged from 0.40 to 0.67 and for trainees from 0.22 to 0.81. The neurologists had higher kappa values than the trainees in 5 signs, but this difference was only statistically significant for jerky eye movements. For the individual signs the observed agreement rates were between 0.50 and 0.93 for all four examiners combined, and overall kappa values varied from 0.32 to 0.71 with highest agreement for facial palsy and lowest for knee jerk. Conclusion - The magnitude of the interobserver and intersign variation indicates that the interpretation of the neurological signs tested, without knowledge of the case history, should be done with some caution.     

An occipito-temporal syndrome in adolescents with optimally controlled hyperphenylalaninaemia

Summary The study included 16 adolescents with optimally controlled hyperphenylalaninaemia (McKusick 26160), of whom six did not require treatment according to conventional criteria. All except the two patients with lowest median serum phenylalanine level throughout childhood (most values at 200–300 µmol/L) had white matter abnormalities detectable with magnetic resonance imaging. The lesions were particularly prominent in the watershed regions between the posterior and middle cerebral arteries. In most patients with moderate or severe hyperphenylalaninaemia frontal white matter lesions were present as well. Normal proton magnetic resonance spectra indicated that the lesions were stable. Occipital EEG abnormalities were frequent, and deficient performance on a pattern-recognition test was a characteristic neuropsychological finding. Serum phenylalanine levels at about 300 µmol/L or below throughout childhood and early adolescence may be required to avoid lesions. The present study demonstrates the limitations of even an optimally controlled dietary regimen in hyperphenylalaninaemia.     

Sweet's syndrome—therapy with cyclosporin

We report the case of a 39-year-old female patient suffering from Sweet's syndrome after an upper respiratory tract infection. Cyclosporin A at a dose of 10 mg/kg per day was given as initial treatment. Skin lesions and general malaise resolved within 9 days. The cyclosporin dose was decreased within 21 days, without recurrence of the eruption. Cyclosporin is a potent inhibitor of T lymphocytes, but affects granulocyte and monocyte functions as well. Success of treatment in our case shows that cyclosporin represents an alternative to steroid treatment in patients with Sweet's syndrome.     

Noninvasive assessment of metabolism in wounded skin by 31P-NMR in vivo.

Phosphorus-31 nuclear magnetic resonance techniques using shallow penetrating coils have been used to noninvasively monitor severity and metabolic changes over time in skin wounds in rats. Ratios of phosphocreatine (PCr) to inorganic phosphate (Pi) indicate energy status in both thermal wounds and surgical flaps. In partial and full-thickness scald wounds, reductions in PCr/Pi ratios correlated with burn depth and improved over time postinjury, suggesting wound revascularization. No decrease in intracellular pH was noted in these wounds; the phosphate shifts may be primarily the result of tissue degradation followed by restoration of the microvasculature. Distal regions of caudally based dorsal 3 x 10 cm full-thickness skin flaps reveal progressively lower PCr/Pi ratios to 3-6 hours after elevation as well as drops in pH up to 0.5 units, presumably as a result of anaerobic glycolysis in these tissues. After 24 hours, the intracellular pH returned to normal (7.1-7.2) and the PCr/Pi ratios approached 70%-90% of the well-perfused proximal regions within 3-7 days. These results indicate the establishment of a microvasculature from the underlying bed as the distal regions survive as free grafts. The data demonstrate the potential usefulness of the technique in noninvasive measurement of the biochemical response to injury and wound healing in living organisms.     

Mediastinitis in heart transplantation.

Between March 1985 and December 1991, mediastinitis developed in 12 of 420 cardiac transplantation patients (2.8%). The mortality rate in this group of patients was 8.3% (1/12). Actuarial survival (1 year, 75%; and 5 years, 65%) was not significantly different from that of the group without mediastinitis (1 year, 88%; and 5 years, 75%). A higher percentage of the patients in the group with mediastinitis were listed as UNOS status 1 (50% versus 35%) and had a history of previous sternotomies (58% versus 44%). The presentation of mediastinitis was typical. Computed tomographic scanning with or without aspiration was a valuable adjunct in the diagnosis of mediastinitis. Induction immunotherapy with minimal steroids in the perioperative period was used in all patients. This may contribute to the patients' ability to mount an appropriate and effective response to infection, permitting earlier diagnosis. The debridement irrigation technique used in 8 of 12 patients had a low success rate of 33%, whereas the debridement muscle flap technique used in 4 of 12 was 100% successful in eliminating infection.     

Influence of bradykinin B1 and B2 receptors in the immune response triggered by renal ischemia–reperfusion injury

Bradykinin B1 receptors are exclusively expressed in inflamed tissues. For this reason, they have been related with the outcomes of several pathologies. Ischemia–reperfusion injury is caused by the activation of inflammatory and cytoprotective genes, such as macrophage chemoattractant protein-1 and heme oxygenase-1, respectively. This study was aimed to analyze the involvement of bradykinin B1 and B2 receptors (B1R and B2R) in tissue response after renal ischemia–reperfusion injury. For that, B1R (B1−/−), B2R (B2−/−) knockout animals and its control (wild-type mice, B1B2+/+) were subjected to renal bilateral ischemia, followed by 24, 48 and 120 h of reperfusion. At these time points, blood serum samples were collected for creatinine and urea dosages. Kidneys were harvested for histology and molecular analyses by real-time PCR. At 24 and 48 h of reperfusion, B1−/− group resulted in the lowest serum creatinine and urea levels, indicating less renal damage, which was proved by renal histology. Renal protection associated with B1−/− mice was also related with higher expression of HO-1 and lower expression of MCP-1. In conclusion, the absence of B1R had a protective role against inflammatory responses developed after renal ischemia–reperfusion injury.     

Arteriosclerotic changes in the myocardium, lung, and kidney in dogs with chronic congestive heart failure and myxomatous mitral valve disease.

BACKGROUND: The occurrence of small vessel arteriosclerosis in the myocardium, kidney, and lung in dogs with naturally occurring myxomatous mitral valve disease has not been previously investigated systematically. METHODS: Twenty-one dogs with naturally occurring congestive heart failure and 21 age-matched, sex-matched, and weight-matched control dogs underwent extensive pathological and histopathological examination. Morphometry and scoring of tissue sections were used to measure arterial narrowing and fibrosis in the myocardium, kidney, and lung; and intimal thickness and plaque formation in the aorta and pulmonary artery. RESULTS: Dogs with congestive heart failure had significantly more arterial narrowing in the left ventricle (P < .003), lung (P < .0001), and kidney (P < .02); intimal-medial thickening in the pulmonary artery (P = .04); and fibrosis in the left ventricle (P < .0001) than control dogs. However, they did not have more plaque formation or intimal-medial thickening in the aorta than controls. There was significantly more arterial narrowing in papillary muscles than in all other locations in dogs with congestive heart failure (P < .002). In control dogs, arterial changes were less pronounced and did not differ in different locations. CONCLUSIONS: Dogs with naturally occurring myxomatous mitral valve disease have significantly more arterial changes in the myocardium, lung, and kidney, and significantly more fibrosis in the myocardium than control dogs. This could have important implications in the management of myxomatous mitral valve disease and raises interesting questions about the occurrence and importance of intramural small vessel disease in humans with primary mitral valve prolapse.     

Reporting of performance indicators of mammography screening in Europe.

We compared short-term indicators for service mammography screening in Europe. Data were available from 17 programmes, although not all programmes provided a comprehensive reporting. More than 90% of the target population had been screened within the last 3 years in the WE trial, whereas only two-thirds of women in England and Copenhagen had been screened within the last 3 years, which will delay or reduce the effect of screening compared with the trial. Participation was highest in sparsely populated areas. Detection rates at first screen reached three times the baseline in Copenhagen, the Netherlands and North-West England. The clinical characteristics of screen-detected cases were badly reported. Given their importance for the long-term effect of screening, further data are warranted. Sensitivity and specificity could be measured only indirectly; they showed, however, considerable variation between programmes. Fyn, Florence and Stockholm had succeeded in combining high specificity with high sensitivity. With different recall policies, different proportions of women will experience a false-positive test; expected numbers after three screens were 14%, 10% and 1%, for England, Copenhagen and the Netherlands, respectively. Based on the observed wide variation in short-term indicators, a similar wide variation is expected in the effect of screening on breast cancer mortality.     

Expression of NCAM mRNA and polypeptides in aging rat brain

In aging brain, degenerative as well as compensatory regenerative processes are believed to occur. The neural cell adhesion molecule NCAM is involved in developmental and regenerative processes in the brain. However, the role of NCAM in aging brain has not been characterized. In this study, the expression of NCAM mRNAs and polypeptides was investigated in aging rat brain. The 7.4 and 6.7 kb NCAM mRNAs were selectively downregulated during postnatal development, and the 5.2 and 2.9 kb NCAM mRNAs were upregulated. However, from postnatal day 40 to old age no change in NCAM mRNA classes was observed. The fraction of NCAM mRNA containing the VASE exon increased postnatally but remained stable during adult life. VASE, which is believed to modulate the binding capacity, seemed to be relatively more abundant in the 7.4 and 6.7 kb NCAM mRNAs, encoding transmembrane NCAM forms, than in the 5.2 and 2.9 kb NCAM mRNAs, coding for glycosyl phosphatidylinositol (GPI) linked NCAM. Conversely, insertion of exons a and AAG between exons 12 and 13, a region containing two fibronectin type III repeats, seemed to be more pronounced in 5.2 and 2.9 kb NCAM mRNAs than in the 7.4 and 6.7 kb mRNAs. During postnatal development an increase in the fraction of 6.7 kb NCAM mRNA containing the exons a and AAG was observed. However, during aging the fraction of NCAM mRNAs containing this exon combination seemed constant. At the protein level, NCAM-A was downregulated both during development and aging. No changes were observed during aging in the composition of soluble NCAM forms in the brain, cerebrospinal fluid or blood plasma. The amount of NCAM in rat brain decreased during postnatal development, but remained at a constant level from postnatal day 40 to old age.To conclude, several changes in NCAM expression occur during early postnatal development emphasizing the important role of this molecule in the morphogenetic processes. During aging, a significant selective downregulation of NCAM-A was observed indicating that in general only minor regenerative processes occur in the brain.     

Loss of Anticoagulant Effect of Heparin During Circulation of Human Blood In Vitro

Device-induced thrombogenesis was studied in an in vitro model using human blood circulated through an artificial ventricle. A new constant pressure filtration technique was used to detect circulating microemboli, the activated partial thromboplastin time (APTT) test was used to monitor the blood for the presence of anticoagulant activity of heparin, and hemolysis was quantified by measuring the plasma free hemoglobin level. Circulation of blood through a 20-ml stroke volume pneumatically driven ventricle for 6-9 h resulted in a significant reduction of APTT, indicating the loss of the anticoagulant effect of heparin. Microemboli concentration was minimal until the APTT decreased below 125 s, at which time the microemboli concentration increased rapidly. This was presumed to be due to the formation of thrombi following a decrease in heparin activity. A significant increase in hemolysis was also noted when blood was pumped. None of these changes was noted in the nonpumped control blood. Spontaneous loss of heparin activity in blood circulated by a pneumatically driven pump may have clinical implications and may help understanding of the problems associated with device-induced thrombogenesis.