Widespread lipoplex-mediated gene transfer to vascular endothelial cells and hemangioblasts in the vertebrate embryo.

We report here a method that allows fast, efficient, and low-cost screening for gene function in the vascular system of the vertebrate embryo. Through intracardiac delivery of nucleic acids optimally compacted by a specific cationic lipid, we are able to induce in vivo endothelial cell-specific gain-of-function during development of the vascular network in the chick embryo. When the nucleic acids are delivered during the period of intraembryonic hematopoiesis, aortic hemangioblasts, the forerunners of the hematopoietic stem cells known to derive from the aortic endothelium, are also labeled. Similarly, we show that siRNA could be used to induce loss-of-function in vascular endothelial cells. This gene transfer technique was also applied to the mouse embryo with a high efficiency. The present method allows large-scale analysis and may represent a new and versatile tool for functional genomics.     

Estimation of dynamical model parameters taking into account undetectable marker values

Background  

Mathematical models are widely used for studying the dynamic of infectious agents such as hepatitis C virus (HCV). Most often, model parameters are estimated using standard least-square procedures for each individual. Hierarchical models have been proposed in such applications. However, another issue is the left-censoring (undetectable values) of plasma viral load due to the lack of sensitivity of assays used for quantification. A method is proposed to take into account left-censored values for estimating parameters of non linear mixed models and its impact is demonstrated through a simulation study and an actual clinical trial of anti-HCV drugs.     

Recurrent cardiac intimal sarcoma misdiagnosed as a myxoma or malignant transformation of a cardiac myxoma?

Cardiac intimal sarcoma is extremely rare and aggressive primary malignant cardiac tumors. Here, we reported the case of a young man initially operated for a tumor of the left atrium, causing a dynamic obstruction of the mitral valve and (mis‐)diagnosed as a myxoma at the histopathological analysis. Patient presented a local recurrence at 3 months and was reoperated. Pathology revealed this time the presence of an intimal sarcoma. Patient received adjuvant chemotherapy. Despite a good local control, the 1‐year follow‐up positron emission tomography scan revealed the presence of a metastasis in the left adrenal gland that was surgically resected. This article aims to highlight the risk of misdiagnosis in case of cardiac tumors, the hypothetical concept of malignant transformation of a cardiac myxoma, the aggressive course of the extremely rare cardiac intimal sarcoma, and the therapeutic modalities available to treat this pathology.     

Long-term effects of finasteride on prostate tissue composition

OBJECTIVES: To determine the long-term effects of finasteride treatment on prostate tissue composition; to relate these effects to clinical outcomes; and to test the hypothesis that finasteride exerts a selective or preferential action on the transition zone. METHODS: Nineteen men with symptomatic benign prostatic hyperplasia (BPH) who completed a 6-month double-blind trial of finasteride were enrolled in a 24-month open-label extension study of drug responders. Magnetic resonance imaging and prostate biopsy for morphometric analysis were performed together 70 times: at baseline (n = 19), after treatment periods of intermediate duration (6 to 18 months, n = 32), and after long-term drug treatment (24 to 30 months, n = 19). At baseline, prostate volume averaged 51 cc, of which 57% was transition zone. RESULTS: Decreases in symptom score, dihydrotestosterone and prostate-specific antigen levels, and prostate volume occurred at 6 months (P <0.01), stabilized, and were maintained without further long-term decreases. Prostate epithelium contracted progressively from baseline (19.2% tissue composition; 6.0-cc volume; 3.2 stroma/epithelial ratio) to intermediate (12.5%, 3.3 cc, and 5.6, respectively) to long-term treatment (6.4%, 2.0 cc, and 17.4, respectively, P <0.01 for all). Percent epithelial contraction was similar in the peripheral and transition zones (P = NS). The transition zone remained a relatively constant proportion (53% to 58%) of whole-prostate volume from baseline to long-term observation. CONCLUSIONS: Long-term finasteride treatment (24 to 30 months) results in a marked involution of the prostate epithelium, which continues to progress for many months after clinical effects stabilize. The effect on the epithelium is similar in the peripheral and transition zones for both morphometric and volumetric changes. Progressive contraction of the prostate epithelium appears to constitute the underlying mechanism for sustained action of finasteride.     

The outcome of lumbar discectomy in elite athletes

STUDY DESIGN: An outcomes assessment of 14 elite college athletes who had undergone lumbar disc surgery was performed using the SF-36, a validated questionnaire that assesses quality of life. OBJECTIVES: To determine the outcomes and results of lumbar disc surgery in an elite group of athletes and compare the results with those in the general population and in age-matched control subjects. SUMMARY OF BACKGROUND DATA: Lumbar disc surgery is reported to be a highly successful procedure with excellent results. The outcome in elite athletes has not been assessed and compared with population norms and age-matched control subjects. METHODS: Fourteen athletes from schools in the National Collegiate Athletic Association with a mean age of 20.7, underwent lumbar discectomy for radiculopathy refractory to conservative treatment. Ten had a single-level microdiscectomy, three a two-level microdiscectomy, and one a percutaneous discectomy. Patients were evaluated at a mean follow-up of 3.1 years, underwent a detailed clinical evaluation, and filled out the SF-36 questionnaire. RESULTS: All 14 patients had improvement of pain with elimination of the radicular component, took less medication than before surgery, and returned to recreational sports. Nine patients, all with a single level microdiscectomy, returned to varsity sports. Five athletes prematurely retired from competitive sports because of continued symptoms. Three of the athletes who retired underwent two-level procedures, and one had a percutaneous discectomy. SF-36 scores for bodily pain, physical role, and social and mental health roles were significantly lower in those athletes who retired. Patient scores were also compared with those in a group of noninjured age-and sport-matched college athletes. There were no differences between injured and noninjured athletes, but both groups had scores significantly lower than normal values in an age-matched group for bodily pain, physical role, general health, and social function. CONCLUSIONS: All patients were satisfied with their surgeries, were greatly improved, and were pain free in activities of daily living. For a single-level microdiscectomy, the success rate in elite athletes is excellent, with 90% of athletes able to return to a high level of competition. Two-level disease may be associated with a less favorable outcome.     

A loudspeaker-driven system for rapid and multiple solution exchanges in patch-clamp experiments

A new and inexpensive system allowing rapid and synchronized changes of solutions around a membrane patch or a cell under voltage-clamp conditions is described. Four plastic capillary tubings (OD 640 m; ID 430 m) were glued together horizontally and attached to a coil of a commercially available loudspeaker. Servo-control of the position of the coil allowed the mouth of any of the capillaries to be positioned near the pipette tip within 6 ms. A high flow speed of the test solution was crucial to achieve rapid solution exchange. At a flow speed of 5 cm/s, complete exchange of the external environment of a frog ventricular cell was achieved within 20–30 ms. The time course of solution change was found to be 3–5 times faster at the tip of an open patch pipette. To preserve the physical integrity of the cell, the cell was usually perfused by a control capillary at a slow velocity (0.2 –0.4 cm/s) and test solutions flowing out of adjacent capillaries at high velocity (4–5 cm/s) were applied to the cell only for short periods. Determination of the three-dimensional contamination profile around the mouth of the control capillary allowed the optimal conditions for the use of the system to be established and possible sources of contamination to be avoided between adjacent capillaries with unmatched flow speeds. Successive and multiple changes in external solutions could be easily synchronized with voltage-clamp depolarizations to examine the time course of the effect of drugs on voltage-operated ion channels. An example of this application is given with rapid applications of the dihydropyridine agonist (-)BayK 8644 to the L-type Ca²⁺ channel current in frog ventricular myocytes.     

Double-stem silicone implant arthroplasty of all metatarsophalangeal joints in patients with rheumatoid arthritis

Double-stem silicone implants have been used to reconstruct destroyed hallux metatarsophalangeal joints (MTPJ) for many years. When smaller implants became available, they were used to reconstruct the lateral four MTPJ. An arthroplasty of all MTPJ was performed using these implants in 44 patients (72 feet) with rheumatoid arthritis (RA). The mean age of patients was 46 years (range, 21 to 66) and 84% were female. Previous surgery had been performed on 28% of the feet. All patients were followed prospectively for an average of 67 months (range, 36 to 111). The patients were evaluated clinically and radiographically; results were recorded on a standardized foot form that allowed computer analysis of the data. The results showed improvement in the hallux valgus angle from 41.6 degrees to 16.1 degrees postoperatively, with no loss of correction over time. Similarly, other forefoot deformities, such as plantar callus and lateral toe abnormalities, all improved both clinically and radiographically. The pain, walking, and function scores all improved, with the greatest improvement being pain relief. Radiographic analysis showed some evidence of fracture in seven hallux (9.7%) and nine lateral toe (3%) implants. Only three toes with implant fracture had some pain at follow-up examination. Three other lateral toe implants were removed for pain. There was no evidence of deep infection or silicone synovitis. Other complications included superficial infection, delayed wound healing, and second surgery for heterotopic bone excision.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pulmonary responses to exercise in pregnancy

The pulmonary responses of 88 pregnant women were compared to those of 39 nonpregnant control subjects during different exercise intensities. At rest the pregnant women had higher tidal volumes, oxygen consumption, carbon dioxide production, and respiratory exchange ratio. With increased work loads the pregnant volunteers have consistently lagged behind the nonpregnant control subjects for every parameter, which indicates a decrease in pulmonary reserve and inability to exercise anaerobically.     

The antioxidant and neuroprotective effects of the Psychotria camptopus Verd. Hook. (Rubiaceae) stem bark methanol extract contributes to its antiepileptogenic activity against pentylenetetrazol kindling in male Wistar rats

A substantial number of epileptic patients are resistant to the current medication thus necessitating the search for alternative therapies for intractable forms of the disease. Previous studies demonstrated the acute anticonvulsant properties of the methanol extract of the stem bark of Psychotria camptopus (MEPC) in rats. This study investigated the effects of MEPC on pentylenetetrazole-kindled Wistar rats. Kindling was induced by intraperitoneal injection of pentylenetetrazole (37.5 mg/kg) on every alternate day, 1 h after each daily oral pretreatment of rats (8?≤?n?≤?10) with MEPC (40, 80 and 120 mg/kg), vehicle or diazepam (3 mg/kg) for 43 days. The kindling development was monitored based on seizure episodes and severity. Rats’ brains were collected on day 43 for the determination of oxidative stress parameters. The histomorphological features and neuronal cell viability of the prefrontal cortex (PFC) and hippocampus were also assessed using H&E and Cresyl violet stains. Chronic administration of pentylenetetrazole time-dependently decreased the latency to myoclonic and generalized seizures, and increased seizure scores and the number of kindled rats. MEPC and diazepam significantly increased the latencies to myoclonic jerks and generalized tonic-clonic seizures. These substances also reduced seizure score and the number of rats with PTZ-kindling. MEPC improved glutathione status and decreased lipid peroxidation in the brains of kindled rats. MEPC also exhibited neuroprotection against pentylenetetrazole-induced hippocampal and PFC neuronal damages. These results suggest that P. camptopus has antiepileptogenic activity, which might be related to the augmentation of antioxidant and neuroprotective defense mechanisms, and further confirm its usefulness in the management of epilepsy.