Liver transplantation in a subject with familial hypercholesterolemia carrying the homozygous p.W577R LDL-receptor gene mutation

Mutations within the low density lipoprotein (LDL)-receptor gene result in familial hypercholesterolemia, an autosomal dominant inherited disease. Clinical homozygous affected subjects die of premature coronary artery disease as early as in early childhood. We identified a girl at the age of five yr with clinical homozygous familial hypercholesterolemia presenting with achilles tendon xanthomas and arcus lipoides. Her total cholesterol reached up to 1050 mg/dL. Molecular characterization of the LDL-receptor gene revealed a homozygous p.W577R mutation. Despite intensive treatment interventions with the combination of diet, statins, colestipol, and LDL-apheresis, the patient developed symptomatic coronary artery disease at the age of 16 yr. Subsequently, orthotopic liver transplantation was performed to cure the defective LDL-receptor gene. Clinical follow-up for almost nine yr post-transplantation revealed excellent liver function, normal liver enzymes, normal LDL-cholesterol, and regression of both tendon xanthomas and symptomatic coronary artery disease. In conclusion, liver transplantation can effectively reduce LDL-cholesterol in a familial hypercholesterolemia recipient with subsequent regression of xanthomas and atherosclerosis. Timing is extremely important in these exceptional cases to exclude the demand for heart transplantation due to severe coronary artery disease. In addition, the identification of the LDL-receptor as etiology of clinical homozygous hypercholesterolemia is a prerequisite once liver transplantation is considered as therapeutic option.     

Urodynamic and ultrasound characteristics of incontinence after radical hysterectomy

AIMS: To test whether symptoms of urinary incontinence after radical hysterectomy could be objectified with urodynamics and ultrasound. METHODS: This case-control study comprised 100 women who underwent radical hysterectomy for cervical cancer without post-operative radiotherapy. Fifty women reporting urinary incontinence were matched with 50 women reporting continence. All women were assessed with ultrasound of the bladder neck movements and urodynamics. RESULTS: No differences were found in ultrasound or urodynamic findings regarding mobility of the bladder neck, maximal detrusor pressure, post-voiding residual urine, flow of urine, or bladder capacity. A significant reduction in urethral pressure at rest and at contraction among the incontinent women was, however, demonstrated. Among urge-incontinent women, urethral pressure at rest was significantly lower than among continent and stress-incontinent women, respectively. Stress-incontinent women had significantly lower urethral pressure at contraction than did urge-incontinent and continent women. CONCLUSIONS: No differences in urodynamic or ultrasound findings were observed between the two groups, except for an overall difference in the intraurethral pressure. A decrease in the urethral pressure could contribute to the characterization of incontinence after radical hysterectomy, indicating that the urethral sphincter mechanism plays a role in the pathophysiology. In this study design, the mobility of the bladder neck did not play any role.     

18F-choline and/or 11C-acetate positron emission tomography: detection of residual or progressive subclinical disease at very low prostate-specific antigen values (<1 ng/mL) after radical prostatectomy

OBJECTIVES: To assess the value of positron emission tomography (PET)/computed tomography (CT) with either (18)F-choline and/or (11)C-acetate, of residual or recurrent tumour after radical prostatectomy (RP) in patients with a prostate-specific antigen (PSA) level of <1 ng/mL and referred for adjuvant or salvage radiotherapy. PATIENTS AND METHODS: In all, 22 PET/CT studies were performed, 11 with (18)F-choline (group A) and 11 with (11)C-acetate (group B), in 20 consecutive patients (two undergoing PET/CT scans with both tracers). The median (range) PSA level before PET/CT was 0.33 (0.08-0.76) ng/mL. Endorectal-coil magnetic resonance imaging (MRI) was used in 18 patients. Nineteen patients were eligible for evaluation of biochemical response after salvage radiotherapy. RESULTS: There was abnormal local tracer uptake in five and six patients in group A and B, respectively. Except for a single positive obturator lymph node, there was no other site of metastasis. In the two patients evaluated with both tracers there was no pathological uptake. Endorectal MRI was locally positive in 15 of 18 patients; 12 of 19 responded with a marked decrease in PSA level (half or more from baseline) 6 months after salvage radiotherapy. CONCLUSIONS: Although (18)F-choline and (11)C-acetate PET/CT studies succeeded in detecting local residual or recurrent disease in about half the patients with PSA levels of <1 ng/mL after RP, these studies cannot yet be recommended as a standard diagnostic tool for early relapse or suspicion of subclinical minimally persistent disease after surgery. Endorectal MRI might be more helpful, especially in patients with a low likelihood of distant metastases. Nevertheless, further research with (18)F-choline and/or (11)C-acetate PET with optimal spatial resolution might be needed for patients with a high risk of distant relapse after RP even at low PSA values.     

Parental Activity as Influence on Childrenˋs BMI Percentiles and Physical Activity

Parents play a crucial role in the development of their children’s lifestyle and health behaviour. This study aims to examine associations between parental physical activity (PA) and children’s BMI percentiles (BMIPCT), moderate to vigorous PA (MVPA) as well as participation in organised sports. Height and body weight was measured in 1615 in German children (7.1 ± 0.6 years, 50.3% male) and converted to BMIPCT. Parental BMI was calculated based on self-reported height and body weight. Children’s MVPA and sports participation as well as parental PA were assessed via parental questionnaire. Analysis of covariance (ANCOVA), controlling for age and family income was used to examine the association between parental and children’s PA levels as well as BMIPCT. 39.7% of the parents classified themselves as physically active and 8.3% of children were classified as overweight or obese. Lower BMIPCT were observed with both parents being physically active (44.5 ± 26.3 vs. 50.2 ± 26.9 and 52.0 ± 28.4, respectively). There was no association between parental and children’s PA levels but children with at least one active parent displayed a higher participation in organised sports (102.0 ± 96.6 and 117.7 ± 123.6 vs. 73.7 ± 100.0, respectively). Children of active parents were less likely to be overweight and obese. The lack of association between subjectively assessed parental PA and child MVPA suggests that parental support for PA in children is more important than parents being a role model. More active parents, however, may be more likely to facilitate participation in organised sports. These results underline the importance of the inclusion of parents in health promotion and obesity prevention programmes in children.

Key points

• A higher prevalence of overweight or obese children was found with inactive parents.
• Children’s BMI percentiles were lower if both parents were physically active compared to children whose parents were both inactive or only had one physically active parent.
• Parental activity had no influence on daily time spent at MVPA and time spent in non-organised sports.
• There was a significant association between parental physical activity and the number of minutes per week boys and girls participated in organised sports.
• On average, children who had at least one physically active parent spent significantly more time participating in organised sports than children with inactive parents.

Key words: Health and exercise, effects on body weight, health promotion     

Customised osteotomy guides and endoprosthetic reconstruction for periacetabular tumours

Purpose

We sought to analyse clinical and oncological outcomes of patients after guided resection of periacetabular tumours and endoprosthetic reconstruction of the remaining defect.

Methods

From 1988 to 2008, we treated 56 consecutive patients (mean age 52.5 years, 41.1 % women). Patients were followed up either until death or February 2011 (mean follow up 5.5 years, range 0.1–22.5, standard deviation ± 5.3). Kaplan–Meier analysis was used to estimate survival rates.

Results

Disease-specific survival was 59.9 % at five years and 49.7 % at ten and 20 years, respectively. Wide resection margins were achieved in 38 patients, whereas 11 patients underwent marginal and seven intralesional resection. Survival was significantly better in patients with wide or marginal resection than in patients with intralesional resection (p = 0.022). Survival for patients with secondary tumours was significantly worse than for patients with primary tumours (p = 0.003). In 29 patients (51.8 %), at least one reoperation was necessary, resulting in a revision-free survival of 50.5 % at five years, 41.1 % at ten years and 30.6 % at 20 years. Implant survival was 77.0 % at five years, 68.6 % at ten years and 51.8 % at 20 years. A total of 35 patients (62.5 %) experienced one or more complications after surgery. Ten of 56 patients (17.9 %) experienced local recurrence after a mean of 8.9 months. The mean postoperative Musculoskeletal Tumor Society (MSTS) score was 18.1 (60.1 %).

Conclusion

The surgical approach assessed in this study simplifies the process of tumour resection and prosthesis implantation and leads to acceptable clinical and oncological outcomes.     

High‐sensitive Troponin T measurements early after heart transplantation predict short‐ and long‐term survival

Following heart transplantation, cardiac biomarkers remain elevated for several weeks eventually as a result of membrane leakage of the donor organ. We now test the predictive power of blood levels of troponin T (TNT) measured by the new hsTNT assay (Roche Diagnostics, Roche Diagnostics, Mannheim, Germany) early after heart transplantation. TNT was determined in 141 cardiac allograft recipients and 40 controls. Our findings demonstrate that patients who died within the first year after transplantation had significantly higher median hsTNT serum levels 6 weeks after transplantation (156 ng/l ± 203 vs. 29 ng/l ± 21, P = 0.0002). Using ROC analysis, a serum hsTNT concentration of 33.55 ng/l 6 weeks after transplantation was found to be the best cutoff to predict death at 1 year (HR 0.16, 95%CI:0.05–0.46, P = 0.001) with a sensitivity of 90.91% and a specificity of 70.97%. In addition, survival at 5 years (HR 0.15, 95% CI 0.06–0.35, P < 0.0001) was significantly better among patients below that cutoff value. In multivariate analysis, hsTNT serum level 6 weeks after transplantation emerged as an independent predictor for first‐year mortality (hsTNT–HR 0.90, 95% CI: 0.81–1.00, P = 0.03). Cardiac troponin T concentrations early after transplantation as measured with a highly sensitive assay represent a strong and independent risk predictor of death after heart transplantation.     

Histidine–tryptophan–ketoglutarate solution for organ preservation in human liver transplantation—a prospective multi-centre observation study

Based on experimental work and clinical small studies, histidine–tryptophan–ketoglutarate (HTK) solution was found to be suitable not only for heart and kidney preservation but also for liver preservation. We decided, therefore, to use this preservation solution for clinical liver preservation in a prospective multi-centre trial. Enrolment to the study was from 1996 to 1999 in four European centres, and the results of 214 patients with HTK-preserved organs were analysed. Analysis showed a primary dysfunction (PDF) rate of 8.8%, with a primary non-function (PNF) rate of 2.3% and initial poor function (IPF) in 6.5%. Patient survival rate at 1 year was 83% and 1-year graft survival rate was 80%. In a univariate and a multivariate analysis PDF, early surgical complications and tendentiously severe infections (septicaemia, pneumonia, cholangitis) were identified as independent risk factors for graft and patient survival. Preservation with HTK can be regarded as an established alternative to preservation with University of Wisconsin (UW) solution when preservation times are short. Definitive assessment of the efficacy of preservation solutions requires further prospective randomised clinical trials that compare HTK and UW.     

Primary signet-ring cell carcinoma of the colorectum

Background Objective of the study was to investigate particular clinicopathological features of colorectal signet-ring cell carcinoma.Methods The data of 34 patients with primary colorectal signet-ring cell carcinoma were compared with those of 4,458 consecutive patients with primary non-signet-ring cell colorectal adenocarcinoma between 1978 and 1999. For outcome analysis patients, after curative resection of signet-ring cell cancer, were matched for age, gender, tumour site and stage with patients suffering from poorly differentiated non-signet-ring cell colorectal adenocarcinoma.Results Signet-ring cell carcinoma patients were significantly younger than patients with non-signet-ring cell colorectal adenocarcinoma (median age 60 years vs 64 years, P=0.033). The most common tumour sites were the rectum (47%) and the right hemicolon (29%). They presented with significantly more advanced tumour stages and a significantly higher frequency of distant metastases (44% vs 21%, P=0.002). The rate of curative resections was significantly lower (35% vs 79%, P<0.001). However, the prognosis after curative resection of signet-ring cell cancer was as poor as in poorly differentiated non-signet-ring cell colorectal adenocarcinoma of the same stage (5-year survival rate 46% vs 57%, p=0.935).Conclusions Colorectal signet-ring cell carcinoma is characterized by diagnosis in more advanced tumour stages resulting in lower rates of curative resection. Prognosis is as poor as in non-signet-ring cell colorectal cancer of low differentiation in the same stage.     

Adipose tissue expression of the lipid droplet-associating proteins S3-12 and perilipin is controlled by peroxisome proliferator-activated receptor-gamma

In a systematic search for peroxisome proliferator-activated receptor-gamma (PPAR-gamma) target genes, we identified S3-12 and perilipin as novel direct PPAR-gamma target genes. Together with adipophilin and tail-interacting protein of 47 kDa, these genes are lipid droplet-associating proteins with distinct expression pattern but overlapping expression in adipose tissue. The expression of S3-12 and perilipin is tightly correlated to the expression and activation of PPAR-gamma in adipocytes, and promoter characterization revealed that the S3-12 and the perilipin promoters contain three and one evolutionarily conserved PPAR response elements, respectively. We furthermore demonstrate that the expression of S3-12 and perilipin is reduced in obese compared with lean Zucker rats, whereas the expression of adipophilin is increased. Others have shown that perilipin is an essential factor in the hormonal regulation of lipolysis of stored triglycerides within adipose tissue. The direct regulation of perilipin and S3-12 by PPAR-gamma therefore is likely to be an important mediator of the in vivo effects of prolonged treatment with PPAR-gamma activators: insulin sensitization, fatty acid trapping in adipose tissue, reduced basal adipose lipolysis, and weight gain.