Pathways of apoptosis in human autosomal recessive and autosomal dominant polycystic kidney diseases

Autosomal dominant polycystic kidney disease (ADPKD) is a major cause of end-stage renal disease in adults. Autosomal recessive (AR) PKD affects approximately 1:20,000 live-born children with high perinatal mortality. Both diseases have abnormalities in epithelial proliferation, secretion, and cell-matrix interactions, leading to progressive cystic expansion and associated interstitial fibrosis. Cell number in a kidney reflects the balance between proliferation and apoptosis. Apoptosis results from extrinsic (ligand-induced, expression of caspase-8) and intrinsic (mitochondrial damage, expression of caspase-9) triggers. Previous studies have suggested a role for apoptosis in PKD cyst formation and parenchymal destruction. Mechanisms underlying apoptosis in human ADPKD and ARPKD were examined by quantitative immunohistochemistry and Western immunoblot analyses of age-matched normal and PKD tissues. Caspase-8 expression was significantly greater in small cysts and normal-appearing tubules than in larger cysts in ADPKD kidneys. Caspase-8 also appeared early in the disease process of ADPKD. In ARPKD, expression of caspase-8 was most pronounced in later stages of the disease and was not confined to a specific cyst size. In conclusion, apoptosis in human ADPKD is an early event, occurring predominantly in normal-appearing tubules and small cysts, and is triggered by an extrinsic factor, but it occurs later in ARPKD.     

Coronary artery bypass surgery in patients with impaired left ventricular function. Predictors of hospital outcome

This prospective study evaluates the surgical outcome of 75 consecutive patients with impaired left ventricular function, including an analysis of predictors of the short-term outcome following coronary artery bypass grafting (CABG). Seventy-five patients (mean age 64 +/- 13 years) with coronary artery disease and impaired left ventricular function (left ventricular ejection fraction [EF] < or = 40%) who underwent a coronary artery bypass surgery were prospectively studied. Echocardiography and thallium-201 myocardial scintigraphy were preoperatively performed to measure the left ventricular function and to assess myocardial viability. Postoperative echocardiography was done before discharge and six months later to evaluate recovery of left ventricular function. Five patients (6.7%) died in total: three deaths were cardiac related (4%) and two patients (2.7%) died due to other causes. The left ventricular ejection fraction improved immediately after the operation (from 32.2 +/- 6% to 39.5 +/- 8%, p = 0.01) and showed a sustained improvement at later follow-up (mean = 16.3 +/- 4.5 months) (44.0 +/- 4.0%, p = 0.01). The left ventricular wall motion score improved significantly only at later follow-up (from 12.2 +/- 1.8 to 9.4 +/- 2.0, p = 0.03). In 43 patients of whom a preoperative thallium-201 scintigraphy was available, the presence of extensive reversible defects was correlated with significant improvement in EF. On the other hand, a poor outcome was correlated with the presence of pathological Q waves in the preoperative ECG and with an increased left ventricular end-systolic volume index (> 100 ml/m2). Patients with marked left ventricular dysfunction can safely undergo CABG with a low mortality and morbidity. The presence of extensive reversible defects on preoperative thallium-201 scintigraphy is a strong predictor of postoperative recovery of myocardial function. A poor outcome of surgery can be expected in the presence of pathological Q waves on the preoperative ECG or when the left ventricular endsystolic volume index exceeds 100 ml/m2.     

Floating thumb with double dislocation of carpometacarpal and metacarpo-phalangeal joints

INTRODUCTION

Double dislocations of carpometacarpal and metacarpo-phanlageal joints are rare. We report an unusual case of simultaneous dislocation of both CMC and MCP joints in the thumb.

PRESENTATION OF CASE

A 31 year old male was admitted following a road traffic accident. He was complaining of pain and deformity of right thumb. The X-ray examination revealed simultaneous dislocation of both CMC and MCP joints. He underwent closed manipulative reduction and percutaneous K wire fixation. The wires were removed after six weeks. After a course of physiotherapy he regained full range of pain free movements.

DISCUSSION

The incidence of simultaneous dislocation of both CMC and MCP joints in thumb are associated with high energy injuries. The options of treatment are conservative with cast immobilisation and serial X-rays or operative including closed manipulative reduction and K wire fixation or open reduction and internal fixation.

CONCLUSION

The option of treating this rare injury with closed manipulative reduction and percutaneous K wiring gives excellent and predictable results.     

Effects of sleeve gastrectomy in high fat diet-induced obese mice: respective role of reduced caloric intake,white adipose tissue inflammation and changes in adipose tissue and ectopic fat depots

Background

Sleeve gastrectomy (SG) has become a popular bariatric procedure. The mechanisms responsible for weight loss and improvement of metabolic disturbances have still not been completely elucidated. We investigated the effect of SG on body weight, adipose tissue depots, glucose tolerance, and liver steatosis independent of reduced caloric intake in high-fat-diet-induced obese mice.

Methods

C57BI/6 J mice fed a high fat diet (45 %) for 33 weeks were divided into three groups: sleeve gastrectomy (SG, 13 mice), sham-operated ad libitum fed (SALF, 13 mice) and sham-operated pair fed (PFS, 13 mice). The animals were humanely killed 23 days after surgery.

Results

In SG mice, food intake was reduced transiently, but weight loss was significant and persistent compared to controls (SG vs. PFS, P < 0.05; PFS vs. SALF, P < 0.05). SG mice showed improved glucose tolerance and lower levels of liver steatosis compared with controls (area under the curve, SG vs. PFS, P < 0.01; PFS vs. SALF, P < 0.05) (liver steatosis, SG vs. PFS, P < 0.05; PFS vs. SALF, P < 0.01). This was associated with a decrease in the ratios of the weight of pancreas, epididymal and inguinal adipose tissues to body weight, and an increase in the ratio of brown adipose tissue weight to body weight. Epididymal adipose tissue was also infiltrated by fewer activated T cells and by more anti-inflammatory regulatory T cells. Serum levels of fasting acyl ghrelin were still significantly decreased 3 weeks after surgery in SG mice compared to PFS mice (P < 0.05).

Conclusions

Reduced white adipose tissue inflammation, modification of adipose tissue development (brown vs. white adipose tissue), and ectopic fat are potential mechanisms that may account for the reduced caloric intake independent effects of SG.     

Cryopreservation of ram semen facilitates sperm DNA damage: relationship between sperm andrological parameters and the sperm chromatin structure assay

We hypothesized that cryopreservation and incubation in conditions that mimic the female genital tract following insemination increases the susceptibility of ram sperm DNA to denaturation. Ram sperm samples (n = 12) underwent the sperm chromatin structure assay (SCSA) and semen quality tests, including motility parameters, viability, and chlortetracycline fluorescence (CTC) patterns. We also assessed correlations between SCSA variables and semen quality parameters. Analyses were performed for both fresh and cryopreserved samples at 0, 3, and 20 hours of incubation in synthetic oviductal fluid (SOF; 39 degrees C, 5% CO(2)). The SCSA variables, mean alpha t (X alpha(t)) and standard deviation of alpha t (SD alpha(t)), were higher because of cryopreservation (P <.05, P <.001, respectively) after 20 hours in SOF. For both fresh and frozen spermatozoa, SCSA values (X alpha(t), SD alpha(t), and the percentage of cells outside the main population of alpha(t) [%COMP alpha(t)]) increased during incubation in SOF. Motility was negatively correlated with both SD alpha(t) and %COMP alpha(t), ranging from -0.39 (P <.01) to -0.59 (P <.001) for both fresh and cryopreserved semen; viability also was negatively correlated with X alpha(t), SD alpha(t), or %COMP alpha(t) (-0.36; P <.05, -.40 and -.46; P <.01, respectively) in fresh semen. The %COMP alpha(t) was positively correlated to the percentage of CTC pattern AR (P <.001) and negatively correlated to the percentages of patterns F and B (-0.33 to -0.60, P <.05 to P <.001). Variation among ejaculates within ram was observed (P <.01). Cryopreservation clearly facilitates DNA damage in physiological conditions. The low to moderate correlations between SCSA variables and classical semen quality parameters indicate that the SCSA provides additional information to standard tests for evaluating ram sperm quality.     

Pressure support ventilation vs spontaneous ventilation via ProSeal™ laryngeal mask airway in pediatric patients undergoing ambulatory surgery: a randomized controlled trial

Aim: To investigate the advantages of using pressure support ventilation (PSV) vs spontaneous ventilation via ProSeal? laryngeal mask airway in children undergoing ambulatory surgery. Background: In our ambulatory surgical unit, the use of unassisted spontaneous breathing via laryngeal mask airway is a common anesthetic technique during general anesthesia. However, this may be associated with inadequate ventilation. PSV is a ventilatory mode that is synchronized with the patient’s respiratory effort and may improve gaseous exchange under general anesthesia. Materials and methods: After the approval from the ethics committee, a randomized controlled trial involving 24 pediatric patients was conducted in our ambulatory surgical unit. They were randomized into two groups, namely Group PSV (receiving PSV) and Group SV (unassisted spontaneous ventilation). Outcome measures included intraoperative respiratory and hemodynamic parameters as well as recovery room data. Results: There were no significant differences in baseline characteristics between the two groups. Patients in Group PSV had lower ETCO₂ (42.8 ± 5.8 vs 50.4 ± 4.0, P = 0.001) and higher expiratory tidal volume per kg bodyweight (8.3 ± 1.8 ml kg^?1 vs 5.8 ± 0.8 ml kg^?1, P = 0.001) compared with patients in Group SV. There were no significant differences in other respiratory and hemodynamic parameters or recovery room data between the two groups. Conclusion: Pressure support ventilation via ProSeal? laryngeal mask airway during general anesthesia improves ventilation in pediatric patients undergoing ambulatory surgery. However, this did not translate to a difference in clinical outcome among our study patients.     

Late spontaneous recanalization of a symptomatically occluded internal carotid artery two years after extra-intracranial bypass. Case report and review of the literature

Spontaneous recanalization of the internal carotid artery (ICA) is rarely observed. Mainly case reports are published. Most often early recanalization occurs within days or weeks and only a few cases of late recanalization months or years after detected occlusion are reported. Symptomatic bilateral ICA occlusion is regarded as an acceptable indication for extra-intracranial (EC-IC) bypass. The authors report on a case with bilateral symptomatic ICA occlusion and EC-IC bypass >2 years prior to detected spontaneous leftsided recanalization. Spontaneous recanalization unmasking a high degree ICA stenosis at the carotid bifurcation allowed a successful subsequent surgical recanalization in this patients. Mechanisms of early and late recanalization as well as treatment options are discussed.     

Breast-conserving therapy with adjuvant paclitaxel and radiation therapy: feasibility of concurrent treatment

As commonly used, adjuvant paclitaxel after doxorubicin in high-risk breast cancer patients results in a prolonged delay of the onset of radiation therapy after breast-conserving surgery. Concurrent delivery of breast irradiation with paclitaxel would allow for earlier initiation of radiation. We report on the toxicity of concurrent paclitaxel and breast irradiation after doxorubicin and cyclophosphamide. Twenty-four patients were treated with concurrent breast radiation and paclitaxel. All patients received four cycles of doxorubicin and cyclophosphamide followed by four cycles of paclitaxel, 175 mg/m2 every 3 weeks. The radiation therapy started after the first cycle in 3 patients, after the second cycle in 16, and after the third in 5. The breast received 4680-5040 cGy external beam irradiation, followed by a boost of 1000-2000 cGy. Fifteen patients received supraclavicular irradiation, and a posterior axillary supplement was used in five patients. Median follow-up after completion of irradiation was 11.5 months (range 2-29 months) with 21 patients followed >or=6 months, 12 followed >or=12 months, and 7 followed >or=18 months. Using Radiation Therapy Oncology Group (RTOG) acute toxicity scoring criteria, 7 patients experienced grade 1 skin and/or soft tissue reactions and 17 patients had grade 2 reactions. The average total duration of radiation treatment was 49 days (range 41-57 days). Only eight patients had radiation therapy interruptions for a median of 3.5 days (range 2-8 days): two more than 5 days. None had a chemotherapy dose reduction. One patient discontinued paclitaxel after the third cycle due to bilateral upper extremity neuropathy. No cases of pneumonitis or brachial plexopathy were seen. Concurrent treatment with every 3-week paclitaxel and breast irradiation was well tolerated. Additional study is needed to determine optimal timing, long-term toxicity, and potential benefits of concurrent radiation therapy and paclitaxel.