Ectodysplasin-1 deficiency in a German Holstein bull associated with loss of respiratory mucous glands and chronic rhinotracheitis

A 2-year-old German Holstein bull was identified as a carrier of a mutation within the X-chromosomal ED1 gene, which encodes a TNF-related signalling molecule mainly involved in ectodermal development. The clinicopathological appearance was associated with hypotrichosis, hypodontia, and a reduced number of eccrine glands, in addition to chronic rhinotracheitis and partial squamous metaplasia. Furthermore, for the first time in an ED1-deficient animal, a complete lack of respiratory mucous glands was observed. This suggests that the ED1 gene plays a role in the development of mucous glands, the absence of which resembles a feature of X-linked anhidrotic ectodermal dysplasia (ED1) in human patients.     

Chrysotherapy. suppression of immunoglobulin synthesis

Forty-four subjects with classic or definite rheumatoid arthritis who were on individualized chrysotherapy were observed for changes in serum protein electrophoresis, immunoglobulins, and circulating lymphocyte counts. By paired variate analysis, significant declines from pretreatment values were recorded for the following—electrophoretic protein fractions: gamma, alpha-1, alpha-2, (P < 0.05); immunoglobulins: IgM—53% (P < 0.001), IgG—37% (P < 0.01), IgA—34% (P < 0.001). Rheumatoid factor decreased in 29 of 39 subjects, 15 becoming seronegative (P < 0.001); circulating lymphocytes decreased by 27% (P < 0.001). The maximal suppressive effect on IgG and IgM was not achieved until the third and fourth years of therapy by sustained weekly administration of gold sodium thiomalate (one year cumulative dosage, mean 2106 mg, range 1065–2,885; ≥ 4 year cumulative dosage, mean 8747 mg, range 5,385–15, 160 mg). An immunosuppressive effect is suggested by these results.     

Cystic fibrosis and the phenotypic expression of autosomal dominant polycystic kidney disease

Recent experiments in cultured cyst epithelial cells from kidneys of patients with autosomal dominant polycystic kidney disease (ADPKD) have shown that the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) is present in the apical surface of these cells and mediates chloride (Cl-) and fluid secretion in vitro. To determine whether the presence of CF with the expression of mutated CFTR proteins modifies cyst formation in ADPKD, we studied a large family with both inherited diseases. ADPKD in this family is linked to PKD1. The family is composed of 26 members; 11 members with ADPKD, 4 members with CF, and 2 members with both diseases. Renal volumes measured by computerized tomography (CT), calculated creatinine clearances, and other clinical parameters in the family members with ADPKD and CF were compared with those in the family members with ADPKD alone, as well as to a large population of patients with ADPKD. The patients with CF and ADPKD, but not the CF heterozygote carriers with ADPKD, had less severe polycystic kidney and liver disease, as indicated by normal renal function; smaller renal volume, even when corrected for height and body surface area; and the absence of hypertension and liver cysts. These observations suggest that the coexistence of CF may reduce the severity of ADPKD.     

Laparoscopic nephron sparing surgery: evolution in a decade

OBJECTIVE: To present our experience with laparoscopic nephron sparing surgery (NSS) over a decade. METHODS: Seventy-eight patients underwent NSS since 1994. Two techniques were used-partial nephrectomy without ischemia (group 1) in 29 patients, and with ischemia (group 2) which was in cold or warm ischemia in 24 and 25 patients respectively. The mean tumour size was 1.97 and 2.2 cm in groups 1 and 2 respectively. Renal reconstruction evolved in our hands during this period. We changed many technical details and now we depend more on clips for securing the sutures rather than free hand knotting. RESULTS: The mean operative time was 162 and 216 minutes in groups 1 and 2 respectively. Mean ischemia time for patients with cold and warm ischemia was 44.9 and 33.8 minutes respectively. 3 patients in group 2 were converted to open surgery. Mean blood loss was 254 and 212 ml for group 1 and 2 respectively with two major bleedings in group 2. Minor intra-operative complication occurred in 3 patients, and major and minor postoperative complication in 15 patients. At a mean follow-up of 23.9 and 12.2 months for groups 1 and 2 respectively there was no recurrence. CONCLUSION: Warm and cold ischemia have widened the indications for laparoscopic NSS to more complex tumours and allow renal reconstruction with acceptable complication rate.     

Laparoscopic partial nephrectomy for hilar tumors: technique and results

BACKGROUND: Laparoscopic partial nephrectomy for hilar tumors is a cutting edge procedure for which little data is available in the current literature. OBJECTIVE: To describe our technique and results of laparoscopic partial nephrectomy for renal hilar tumors. DESIGN, SETTING, AND PARTICIPANTS: Between April 2000 and September 2006, 94 partial laparoscopic nephrectomies were performed at our institution. A total of 18 (19.1%) patients had hilar tumors. A hilar tumor was defined as a lesion suspicious for renal cell carcinoma in contact with a major renal vessel on preoperative cross-sectional imaging. In 3 (16.7%) of the patients, the indication for nephron-sparing surgery was imperative. Mean tumor size was 3cm (range, 2-4.5). Eight (44.4%) surgeries were performed with renal artery perfusion for cold ischemia; the remaining surgeries were performed under warm ischemia. INTERVENTION(S): After occluding the renal artery and controlling the renal vein by using separate rubber band tourniquets, we excised the tumor mass including delicate mobilization away from the blood vessels. Although we used to insert a ureteral stent at the beginning of our experience with laparoscopic partial nephrectomies, we no longer do so. All surgeries were performed by a single urologist (G.J.). MEASUREMENTS: Operative time, ischemia time, blood loss, renal function using the Cockroft formula as well as renal scans, operative and post-operative complications, pathology parameters. RESULTS AND LIMITATIONS: All surgeries were completed laparoscopically. Mean surgical time was 238min (range, 150-420). Mean ischemia times were 42.5min (range, 27-63) and 34.1min (range, 24-56) for the cold and warm ischemia groups, respectively. Estimated intraoperative blood loss was 165ml (range, 50-500). There were two (11%) entries into major vessels during tumor excision, namely a segmental renal artery in one patient and a segmental renal vein in another. Both of these occurrences were managed laparoscopically. One patient necessitated laparoscopic reexploration for urine extravasation in the immediate postoperative period. All postoperative nuclear scans (available in 12 of 18 patients) showed functional kidney moiety. Mean split renal function was 38.6% (range, 24-50) on the operated side. Histopathological examination confirmed renal cell carcinoma in 14 (77.8%) of the patients. One (7.1%) patient had a positive surgical margin on the surface that was adjacent to the renal artery. In a median follow-up of 26 mo (range, 1-59), no local recurrence or systemic progression occurred. CONCLUSION: Laparoscopic partial nephrectomy for hilar tumors is a feasible and safe procedure in the hands of experienced laparoscopic surgeons. Oncological results seem excellent, but further follow-up is needed for accurate long-term assessment of this surgical approach.     

Laparoscopic extended pelvic lymph node dissection for prostate cancer: description of the surgical technique and initial results

OBJECTIVE: In patients with prostate cancer, extended pelvic lymph node dissection (ePLND) yields a higher number of lymph node metastases (LNM) than standard pelvic lymph node dissection (PLND) of the obturator fossa only. We describe our laparoscopic technique of extended lymph node dissection and provide the number and locations of positive lymph nodes from our experience. METHODS: In a total of 35 selected patients with clinically localized prostate cancer, laparoscopic ePLND was performed prior to laparoscopic radical prostatectomy. The template included the genitofemoral nerve up to the bifurcation of the common iliac artery and down to the epigastric artery. In the "split and roll" technique the internal and external iliac arteries including the bifurcation and the external iliac vein were completely mobilized. After freeing the obturator nerve, the entire lymph node package was released from the pelvic side wall. RESULTS: Mean operative time was 90min/patient. The complications were two temporary and reversible neurapraxias (ischiatic nerve and obturator nerve), one deep vein thrombosis, and two lymphoceles. One lymphocele healed conservatively; the second was marsupialized laparoscopically. Eleven (31.4%) patients had lymph node metastases; their mean prostate-specific antigen (PSA) level was 20.3+/-7.0 ng/ml (range: 5.2-39.7 ng/ml) and their median Gleason sum in biopsy was 7 (range: 6-8). Mean size of the LNM was 3.1+/-1.0 mm (range: 0.2-8). In 5 of the 11 patients with LNM these were detected exclusively outside the obturator fossa. LNM were in the obturator fossa only in two (one bilateral), around the external iliac artery only in two, around the internal iliac artery only in two, and around the external iliac artery and internal iliac only in one patient. CONCLUSIONS: Laparoscopic ePLND can be combined with laparoscopic radical prostatectomy. Standardization of the technique facilitates surgery to a great extent. e-PLND detects LNM in a significant number of patients. The majority of LNM are outside the obturator fossa. The transperitoneal approach allows a wide exposure and is the most important factor to enable successful ePLND.     

A comparison of the sensitivity of diagnostic criteria for polymyalgia rheumatica

OBJECTIVE: To compare the performance of the several different diagnostic criteria sets currently in use for polymyalgia rheumatica (PMR). METHODS: 213 patients attending eight rheumatological centres in eight different European countries were studied. All had recently been referred and were considered by the senior investigator at each centre, selected because of their experience in treatment of PMR, to have this condition. By use of a standard international proforma, the requisite diagnostic points in each criteria set were sought. Sensitivity for each criterion from each set was then calculated, as well as the sensitivity of each criteria set as a whole. RESULTS: Of four criteria sets compared, the Bird (1979) criteria performed best with a sensitivity of 99.5%, and the Hunder (1982) criteria second best, with sensitivity of 93.3%. These both performed significantly better than the two other criteria sets, though each of these was admittedly developed for rather specialised reasons. CONCLUSIONS: Although this study compares homogeneity, we suggest the Bird 1979 or Hunder 1982 criteria should be used whenever possible. Studies that have used alternative criteria may have less sensitivity in diagnosis.     

Regulation of Migration of Human Colonic Myofibroblasts

Background and Aim: The migration of mesenchymal cells to areas of mucosal or submucosal tissue damage is an essential factor for wound healing in the intestine. Thus far, neither migration inducing factors nor signal transduction cascades involved in the migration of colonic myofibroblasts (CMF) have been studied in detail. Methods: Primary CMF were isolated from the mucosa of surgical specimens or endoscopic biopsies. Migration assays of CMF were performed in the modified 48-well Boyden chamber. Secreted growth factors were quantified by ELISA. Results: CMF secrete autocrine or paracrine migration stimulating factors. Culture supernatant of CMF collected after 24, 48, and 72 h (=conditioned media) stimulated the migration of CMF ( 48.9 &#45 4.5; 60.3 &#45 5.3 and 67.8 &#45 6.4 cells/hpf, respectively). Heating of conditioned media to 95°C or addition of cycloheximide during the conditioning period abolished migration. Addition of PDGF-AB (2.5-50 ng/ml) or IGF-I (10-300 ng/ml) to CMF conditioned media further increased the migration of CMF to a maximum of 177 and 160%, respectively, when compared to the migration induced by conditioned medium alone. Addition of EGF (2.5-50 ng/ml) or TGF- &#103 1 (1-50 pg/ml) caused an increased CMF migration up to 139 and 128%, respectively. MCP-1 (5-50 ng/ml) and bFGF (10-200 ng/ml) had no effect on CMF migration. Conclusion: The growth factors PDGF-AB, IGF-I, EGF and TGF- &#103 1 stimulate the migration of CMF. However, factors secreted by CMF are essential for their ability to migrate in response to these growth factors. The identification of physiologically relevant migration inducing factors may help to elucidate the network of interactions and the complex mechanisms involved in intestinal wound healing or fibrosis.     

Cardiac responses induced during thought-based control of a virtual environment.

Cardiac responses induced by motor imagery were investigated in 3 subjects in a series of experiments with a synchronous (cue-based) Brain-Computer Interface (BCI). The cue specified right hand vs. leg/foot motor imagery. After a number of BCI training sessions reaching a classification accuracy of at least 80%, the BCI experiments were carried out in an immersive virtual environment (VE), commonly referred as a "CAVE". In this VE, the subjects were able to move along a virtual street by motor imagery alone. The thought-based control of VE resulted in an acceleration of the heart rate in 2 subjects and a heart rate deceleration in the other subject. In control experiments in front of a PC, all 3 subjects displayed a significant heart rate deceleration of the order of about 3-5%. This heart rate decrease during motor imagery in a normal environment is similar to that observed during preparation for a voluntary movement. The heart rate acceleration in the VE is interpreted as effect of an increased mental effort to walk as far as possible in VE.