Layer-specific dendritic regression of pyramidal cells with ageing in the human prefrontal cortex

Huntingtin is the protein product of the gene for Huntington's disease (HD) and carries a polyglutamine repeat that is expanded in HD (>36 units). Huntingtin-associated protein (HAP1) is a neuronal protein and binds to huntingtin in association with the polyglutamine repeat. Like huntingtin, HAP1 has been found to be a cytoplasmic protein associated with membranous organelles, suggesting the existence of a protein complex including HAP1, huntingtin, and other proteins. Using the yeast two-hybrid system, we found that HAP1 also binds to dynactin P150(Glued) (P150), an accessory protein for cytoplasmic dynein that participates in microtubule-dependent retrograde transport of membranous organelles. An in vitro binding assay showed that both huntingtin and P150 selectively bound to a glutathione transferase (GST)-HAP1 fusion protein. An immunoprecipitation assay demonstrated that P150 and huntingtin coprecipitated with HAP1 from rat brain cytosol. Western blot analysis revealed that HAP1 was enriched in rat brain microtubules and comigrated with P150 and huntingtin in sucrose gradients. Immunofluorescence showed that transfected HAP1 colocalized with P150 and huntingtin in human embryonic kidney (HEK) 293 cells. We propose that HAP1, P150, and huntingtin are present in a protein complex that may participate in dynein-dynactin-associated intracellular transport.     

Ankle arthrodesis in patients with rheumatoid arthritis

The results of 26 ankle arthrodeses performed for rheumatoid arthritis on 21 patients were reviewed. Tibiotalar arthrodesis was performed in 14 ankles, and tibiotalocalcaneal arthrodesis was performed in 12. External fixation was used in 20 ankles, and internal fixation was used in six. Followup was available in 24 of 26 ankles (19 patients), and averaged 5 years (range, 2-8 years). There was no pain experienced in 19 ankles; mild, occasional pain was experienced in four ankles; and moderate, daily pain was experienced in one ankle. Daily activities were limited in five patients and recreational activities were limited in 11. All patients reported some difficulty walking on uneven terrain. Nearly all patients were satisfied; two were satisfied with reservations and two were dissatisfied. Union was achieved in 25 of 26 (96%) ankles. Ankle arthrodesis is an effective operation in patients with rheumatoid arthritis. Unlike previous reports, union and complication rates in this series were comparable with rates for arthrodesis for posttraumatic and degenerative arthritis.     

Angiotensin II mediates systemic rebound hypertension after cessation of prostacyclin infusion in sheep

Prostacyclin (or epoprostenol), an arachidonic acid metabolite, is an effective treatment for patients with primary pulmonary hypertension. Interruption of chronic prostacyclin infusion can result in recurrent symptoms of dyspnea and fatigue. The etiology of this phenomenon is unknown. We hypothesized that sympathoadrenal activation could lead to increased vascular tone after abrupt termination of the infusion. To evaluate this effect, we monitored six chronically instrumented, awake sheep during and after infusion of prostacyclin. Prostacyclin decreased mean arterial pressure (MAP) by 14% and increased cardiac output by 33%. After the infusion ceased, MAP rebounded 23% above baseline, and cardiac output decreased by 28% from peak values within 10 min. We were unable to demonstrate an increase in norepinephrine levels after cessation of prostacyclin, nor did alpha-adrenergic blockade affect postinfusion hemodynamics. However, plasma renin activity increased >10-fold at peak infusion and remained elevated for up to 2 h after discontinuation of prostacyclin. Coinfusion of the angiotensin II-receptor antagonist L-158,809 resulted in complete abrogation of the postcessation rise in MAP. We conclude that renin-angiotensin system activation is primarily responsible for systemic hypertension occurring after abrupt cessation of prostacyclin infusion in sheep and that angiotensin II receptor blockade prevents this response. Our data do not support a role for sympathetic nervous system activation in the systemic pressor response after prostacyclin infusion.     

Enterocutaneous fistulas: an unusual solution

Enterocutaneous fistulas are not a minor problem in gastrointestinal tract surgery. Significant reduction of mortality and morbidity has been attained but they still remain high. The authors report three clinical cases in which they sealed and treated enterocutaneous, chronic, iatrogenic fistulas by injecting biological glue (N-Butil 2-Cyanoacrylate-Histoacryl) into the internal opening and fistulous tract. We believe that the technic we propose here, in the proper setting, may be an important contribution to the management of iatrogenic (postoperative) enterocutaneous fistulas.     

Proliferation and apoptosis in malignant and normal cells in B-cell non-Hodgkin's lymphomas

We have examined apoptosis and proliferation in lymph node cell suspensions from patients with B-cell non-Hodgkin's lymphoma using flow cytometry. A method was developed which allowed estimation of the fractions of apoptotic cells and cells in the S-phase of the cell cycle simultaneously with tumour-characteristic light chain expression. Analysis of the tumour S-phase fraction and the tumour apoptotic fraction in lymph node cell suspensions from 95 B-cell non-Hodgkin's lymphoma (NHL) patients revealed a non-normal distribution for both parameters. The median fraction of apoptotic tumour cells was 1.1% (25 percentiles 0.5%, 2.7%). In the same samples, the median fraction of apoptotic normal cells was higher than for the tumour cells (1.9%; 25 percentiles 0.7%, 4.0%; P = 0.03). The median fraction of tumour cells in S-phase was 1.4% (25 percentiles 0.8%, 4.8%), the median fraction of normal cells in S-phase was significantly lower than for the tumour cells (1.0%; 25 percentiles 0.6%, 1.9%; P = 0.004). When the number of cases was plotted against the logarithm of the S-phase fraction of the tumour cells, a distribution with two Gaussian peaks was needed to fit the data. One peak was centred around an S-phase fraction of 0.9%; the other was centred around 7%. These peaks were separated by a valley at approximately 3%, indicating that the S-phase fraction in NHL can be classified as 'low' (< 3%) or 'high' (> 3%), independent of the median S-phase fraction. The apoptotic fractions were log-normally distributed. The median apoptotic fraction was higher (1.5%) in the 'high' S-phase group than in the 'low' S-phase group (0.8%; P = 0.02). However, there was no significant correlation between the two parameters (P > 0.05).     

Social support and hostility as predictors of depressive symptoms in cardiac patients one month after hospitalization: a prospective study

OBJECTIVE: Hospitalization for cardiac disease is associated with an increased risk for depression, which itself confers a poorer prognosis. Few prospective studies have examined the determinants of depression after hospitalization in cardiac patients, and even fewer have examined depression within the weeks after hospital discharge. The present study assessed the prospective relations among perceptions of social support and trait hostility in predicting symptoms of depressive symptoms at 1 month after hospitalization for a diagnostic angiography in 506 coronary artery disease (CAD) patients. METHOD: A series of structural equation models 1) estimated the predictive relations of social support, hostility, and depressive symptoms while in the hospital to symptoms of depression 1 month after hospitalization, and 2) compared these relations across gender, predicted risk classification, and age. RESULTS: Social support assessed during hospitalization was independently negatively associated with depressive symptoms 1 month after hospitalization, after controlling for baseline symptoms of depression, gender, disease severity, and age. Hostility was an indirect predictor of postdischarge depressive symptomology by way of its negative relation with social support. This pattern of relations did not differ across gender, predicted risk classification, and age. CONCLUSIONS: Our findings suggest that a patient's perceived social support during hospitalization is a determinant of depressive symptoms 1 month later. The relation of social support and hostility to subsequent depressive symptoms was similar across a variety of populations.     

Increased concentration of Na,K-pumps in skeletal muscles of patients with chronic obstructive lung disease. Significance of magnesium depletion and treatment with glucocorticoids

Patients with COLD may develop Mg depletion due to inadequate nutrition or treatment with diuretics and beta 2-agonists. In 36 consecutive COLD patients skeletal muscle concentrations of Mg and K were reduced by 22% and 14%, respectively, compared to 23 age- and sex-matched controls (p < 0.001). Patients receiving diuretics showed a further reduction of muscle Mg (-31%) and K (-27%) compared to controls. The mean concentration of Na,K pumps was increased by 31% (p < 0.001), while a more pronounced increase (+61%) was seen in 12 intensive care patients receiving high dosages of glucocorticoids. Thus muscle concentrations of Mg and K are reduced in COLD patients and are associated with an upregulation of the Na,K-pump concentration. It is plausible that this upregulation may be caused by glucocorticoid treatment. The clinical benefits of glucocorticoids may therefore in part be due to an increased activity and capacity of the Na,K-pump and thereby in a possible enhancement of muscle force.     

Coincident DiGeorge anomaly and renal agenesis and its relation to maternal diabetes

We describe 2 cases of DiGeorge anomaly with bilateral renal agenesis-one, who also had hemivertebrae, in an infant of an insulin-dependent diabetic mother (IDDM). In a review we identified 2 other instances of this combination, both in IDDMs. The currently accepted notion that DiGeorge anomaly and renal agenesis are developmental field defects, coupled with their coincidence in IDDM, suggests that this combination is an association.     

Displaced intra-articular fractures of the calcaneus treated non-operatively. Clinical results and analysis of motion and ground-reaction and temporal forces

Twenty-seven patients who had a unilateral displaced intra-articular fracture of the calcaneus were managed with a cast instead of with reduction or an operation. The clinical result after a mean of six years (range, two to ten years) was excellent in five patients, good in five, fair in seven, and poor in ten. The sixteen patients who were re-examined for this study and for whom the gait was analyzed demonstrated abnormalities in ground-reaction force with regard to vertical force (F3) and temporal force factors (T2, T3, T6, and T9). Analysis of temporal and distance factors showed a trend toward a decreased proportion of single-limb support on the involved side. Three-dimensional motion analysis of the ankle and hindfoot was performed with electrogoniometers as the subject walked on a level surface, on a 10-degree side-slope, and up and down stairs. Motion was decreased in the sagittal, coronal, and transverse planes during walking on level ground and on a side-sloping surface. Significant decreases in motion in these planes were also seen during walking up and down stairs. Although these patients did not have a subsequent reconstructive operation, most had a residual functional deficit.