Optical analysis of glutamate spread in the neuropil.

Fast synaptic communication uses diffusible transmitters whose spread is limited by uptake mechanisms. However, on the submicron-scale, the distance between two synapses, the extent of glutamate spread has so far remained difficult to measure. Here, we show that quantal glutamate release from individual hippocampal synapses activates extracellular iGluSnFr molecules at a distance of >1.5 µm. 2P-glutamate uncaging near spines further showed that alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-Rs and N-methyl-D-aspartate (NMDA)-Rs respond to distant uncaging spots at approximately 800 and 2000 nm, respectively, when releasing the amount of glutamate contained in approximately five synaptic vesicles. The uncaging-induced remote activation of AMPA-Rs was facilitated by blocking glutamate transporters but only modestly decreased by elevating the recording temperature. When mimicking release from neighboring synapses by three simultaneous uncaging spots in the microenvironment of a spine, AMPA-R-mediated responses increased supra-additively. Interfering with extracellular glutamate diffusion through a glutamate scavenger system weakly reduced field synaptic responses but not the quantal amplitude. Together, our data suggest that the neuropil is more permissive to short-range spread of transmitter than suggested by theory, that multivesicular release could regularly coactivate nearest neighbor synapses and that on this scale glutamate buffering by transporters primarily limits the spread of transmitter and allows for cooperative glutamate signaling in extracellular microdomains.

HIV drug resistance levels in adults failing first-line antiretroviral therapy in an urban and a rural setting in South Africa.

OBJECTIVES: Urban and rural HIV treatment programmes face different challenges in the long-term management of patients. There are few studies comparing drug resistance profiles in patients accessing treatment through these programmes. The aim of this study was to perform such a comparison. METHODS: HIV drug resistance data and associated treatment and monitoring information for adult patients failing first-line therapy in an urban and a rural programme were collected. Data were curated and managed in SATuRN RegaDB before statistical analysis using Microsoft Excel 2013 and stata Ver14, in which clinical parameters, resistance profiles and predicted treatment responses were compared. RESULTS: Data for 595 patients were analysed: 492 patients from a rural setting and 103 patients from an urban setting. The urban group had lower CD4 counts at treatment initiation than the rural group (98 vs. 126 cells/µL, respectively; P = 0.05), had more viral load measurements performed per year (median 3 vs. 1.4, respectively; P < 0.01) and were more likely to have no drug resistance mutations detected (35.9% vs. 11.2%, respectively; P < 0.01). Patients in the rural group were more likely to have been on first-line treatment for a longer period, to have failed for longer, and to have thymidine analogue mutations. Notwithstanding these differences, the two groups had comparable predicted responses to the standard second-line regimen, based on the genotypic susceptibility score. Mutations accumulated in a sigmoidal fashion over failure duration. CONCLUSIONS: The frequency and patterns of drug resistance, as well the intensity of virological monitoring, in adults with first-line therapy failure differed between the urban and rural sites. Despite these differences, based on the genotypic susceptibility scores, the majority of patients across the two sites would be expected to respond well to the standard second-line regimen.

Endoscopic calcaneoplasty.

Endoscopic calcaneoplasty offers access to the retrocalcaneal space, thereby making it possible to remove inflamed retrocalcaneal bursa as well as the posterosuperior part of the calcaneus in applicable cases of painful hindfoot. In this study, endoscopic calcaneoplasty was performed in 21 procedures in 20 patients. All of the patients had typical complaints of inflammation of the retrocalcaneal bursa that were unresponsive to nonoperative treatment for more than 6 months. In all patients a superior calcaneal angle of more than 75 degrees and positive parallel pitch lines were present on the lateral calcaneal radiograph. The mean follow-up was 3.9 years (range, 2 to 6.5). There were no surgical complications and no postoperative infections. One patient had a fair result, 4 patients had good results, and the remaining 15 patients had excellent results. Whether this operation is performed by endoscopic or open technique, enough bone must be removed to prevent impingement of the bursa between the calcaneus and Achilles tendon. Endoscopic calcaneoplasty is a minimally invasive technique performed in an outpatient setting and combined with a functional rehabilitation program. The procedure has low morbidity. Patients have a short recovery time and quickly resume work and sports.

Cautious surgery for discoid menisci.

This retrospective study reviewed the outcomes of 43 knees in 38 patients with discoid menisci treated from 1977 to 1989. Patients underwent either no treatment, trimming, or subtotal or total resection. Approximately 40% of patients who underwent meniscectomy or partial meniscectomy had a fair or poor rating after an average follow-up of 6.5 years. Pathology demonstrating mucoid fibrinous degeneration within the discoid meniscus was found in many cases, showing abnormal meniscal tissue. Only one third of these knees had symptoms of locking, and only 20 (63%) of 32 had a positive arthrogram, demonstrating the diagnostic difficulties encountered with the discoid meniscus. Patients with a discoid meniscus who are symptomatic should undergo arthroscopy. A partial meniscectomy should be performed to achieve a smooth meniscus and a strong, stable peripheral rim.

Cutaneous glands of male and female impalas (Aepyceros melampus): seasonal activity changes and secretory mechanisms.

The cutaneous glands of the forehead and the metatarsus were studied by histological and histochemical methods and electron microscopy in adult male and female impalas in various seasons of the year. All glandular areas consist of apocrine and holocrine glands, which, however, occur in different proportions. Our findings in the apocrine gland cells suggest (1) the synthesis and exocytosis of a glycoproteinaceous secretory product stored in secretory granules, (2) typical apocrine secretion of the transformed apical cytoplasm, and (3) transepithelial fluid transport. The Golgi apparatus and apical membrane have binding sites for several lectins (PNA, HPA, RCA I, WGA). Cytokeratins 7, 14 and 19 are expressed at various intracellular localizations, suggesting an active role in the secretory mechanisms. The glands of the male forehead show marked seasonal changes in activity that are correlated with the main phases of the reproductive cycle, with the highest cellular activity occurring during the rut in April/May. The female forehead glands are only moderately developed and do not undergo seasonal changes. The metatarsal glands are of equal size in males and females and show no seasonal changes in activity. This study supports the hypothesis that (1) forehead glands in the male have a signaling role in the rut and (2) the metatarsal glands have a more general, probably social role maintaining and restoring contact between herd members.

Clinical assessment of asymptomatic knees: comparison of men and women.

Two hundred ten adults, 100 women and 110 men, were recruited on the condition of always having asymptomatic knee joints. These recruits were initially solicited by newspaper advertisement. The women were recruited in 3 weeks, but additional efforts and 3 months were necessary to assemble the group of men. The volunteers underwent a uniform comprehensive medical history questionnaire, physical examination, and plain film radiographs. The data collected were subjected to computerization and statistical analysis. Although these subjects were always asymptomatic, only 4.5% of 200 women's knees and 21% of 220 men's knees had no "positive" physical findings. The findings of hypermobile patella, patellar crepitus, and lateral patellar position on Merchant x-ray view were common. Findings not present or infrequent in these asymptomatic subjects and potentially pathological were patellar J-sign, decreased range of motion, asymmetrical ligamentous laxity, McMurray's sign, compartmental crepitus, and severe degenerative arthritis or loose bodies on radiograph. The findings in women were different from those observed in men. This gender-specific information should be helpful in patient management but also useful and timely for establishing practice guidelines, treatment algorithms, and outcome study instruments.

Cancellous bone grafting of large osteochondral defects: an experimental study in dogs.

Autogenous cancellous bone was evaluated as a material to repair large osteochondral defects in 20 adult mongrel dogs. In one knee, the bone graft was used to fill an osteochondral cylindrical defect (10 mm diameter x 10 mm deep) created in the femoral trochlea. A similar lesion was created in the contralateral knee but was left untreated for spontaneous healing. Four animals were killed at each of five periods (2, 4, 8, 12, and 24 weeks), and the healing response of the defects was evaluated by gross anatomic inspection, plain film radiography, high-resolution radiography, and histology. The results of this study suggest that the use of a cancellous bone graft accelerates the repair of large osteochondral defects and produces more uniform filling of the defect than the ungrafted control. The reparative surface of the grafted lesions also differed from that of controls, having uniform coverage with histochemical-positive staining fibrocartilage at 8 weeks, a finding not observed in any control defect through the length of this study, 24 weeks.

The popliteal bursa (Baker's cyst): an arthroscopic perspective and the epidemiology.

The purpose of this study was to establish the incidence of the anatomic structure, the popliteal bursa, in patients undergoing arthroscopy and to determine the relationship to associated clinical and pathological factors. Diagnostic arthroscopy was used to identify the presence of the popliteal bursa in 187 consecutive patients (195 knees). Thirty-seven percent of knees had a popliteal bursa identified by the communication with the posterior medial compartment. The cause of the popliteal bursa was not established by this study. This study refuted the causes proposed by others. The existing erroneous conclusions concerning the cause of the popliteal bursa were probably attributable to the failure to recognize the common continuity of the bursa and the knee joint. When the popliteal bursa is present (37%), it becomes symptomatic by responding to the intraarticular disease because of its continuity with the knee joint.

Vincula of the biceps tendon in the glenohumeral joint: An arthroscopic and anatomic study.

An anatomic structure frequently observed during glenohumeral joint arthroscopy is described as the vincula of the long head of the biceps brachia tendon. These vincula were present in 24.3% of 411 shoulders (390 patients) undergoing shoulder arthroscopy. There was single vinculum in 56 shoulders, two vincula in 32, three in 12, and four in one shoulder. Younger age is a significant predictor of the presence of vincula. The presence of vincula was also related to subacromial impingement and glenoid labrum tearing. The absence of vincula was related to the diagnosis of rotator cuff tearing. The gross and microscopic structure is similar to the vincula of the finger flexor tendons.

The use of Compton scattered gamma rays for tomography.

A method of tomographic imaging of soft tissues by the use of Compton scattering of gamma rays is described. A highly collimated source (800 Ci of 60Co) and collimated detectors are used. Spatial resolutions of the order of 0.5 cm or better are achieved, with a density resoution of 2.0% to 4%. Experimental tests with dogs have shown internal organs in sagittal, coronal and transverse section. No contrast or radioactive material is required. Tests have shown that the regional dose for humans will be about 0.25 to 1 rad for one scan.