Human ankle cartilage deformation after different in vivo impact conditions

Recently, the general finding of increased ankle cartilage stiffness to loading has been challenged, suggesting the need for the investigation of different in vivo loading conditions. Therefore, the objectives of the present study were to determine ankle (talar) cartilage deformation after in vivo loading using 3D volume change calculation and to establish any difference in volume change between four weight-bearing exercises. The four exercises represented increasing impact (bilateral knee bends <unilateral knee bends <drop jumps) as well as two types of loading: dynamic and static loading (i.e. unilateral knee bends and unilateral static stance). Based on MRI, 3D reconstructions of talar cartilage were generated to determine 3D volumes before and after four exercises in 13 healthy subjects (bilateral and unilateral knee bends, static unilateral stance, drop jumps). Mean talar deformation (volume decrease) was 8.3% after bilateral knee bends (P = 0.001), 7.7% after unilateral knee bends (P = 0.020), 14.6% after unilateral static stance (P < 0.001), 12.5% after drop jumps (P = 0.001). Statistical analysis also revealed deformation to be significantly higher after unilateral static stance than after unilateral knee bends (P = 0.017). These results suggest that talar cartilage endures substantial deformation during in vivo loading characterized by more deformation (i.e. higher volume change) after static than after dynamic loading.     

Laparoscopic Solution for Early Gastric Cancer in a Morbidly Obese Patient

During preoperative work-up for laparoscopic gastricbypass in a morbidly obese female, gastroscopy visualizedtwo small ulcers in the antrum. Biopsies diagnosedadenocarcinoma of the diffuse type. Stagingwas performed, and endoscopic ultrasonographyshowed early gastric cancer. A laparoscopic neartotalgastrectomy with D1 resection and perigastriclymph node dissection and full omentectomy in combinationwith a gastric bypass, was peformed. Thisapproach respects the oncologic and bariatric principlesand gives a combined solution for the patient.     

Rising PSA in patients with minor LUTS without evidence of prostatic carcinoma: a missing link?

Objectives To determine the role of pressure flowmetry in patients without bothersome lower urinary tract symptoms (LUTS), rising prostate-specific antigen (PSA) levels and diagnosed as having clinical benign prostatic hyperplasia (BPH) after negative (multiple) extended multi-site biopsy. Methods The study enrolled patients with minor LUTS who were referred to our urological practice by their general practitioner because of a rising PSA level (≥4 ng/ml). After exclusion of clinical prostatic carcinoma by digital rectal examination and transrectal ultrasound, all patients underwent at least one set of extended multi-site biopsies to exclude T1c prostate cancer. Patients with negative biopsies (clinical BPH) were subjected to pressure flowmetry whereafter those with bladder outlet obstruction underwent TURP. Results The study included 82 patients, with a mean age of 64.8 years (50.2–78.2 years), satisfying the inclusion criteria. Urodynamic analysis showed that all patients had bladder outlet obstruction. After TURP, eight patients (9.8%) were diagnosed as having histologically proven prostate cancer; 74 patients (90.2%) were diagnosed as having BPH. Patients of the BPH group had a mean preoperative PSA level of 8.8 ng/ml (4.3–25.8 ng/ml) and a mean international prostate symptom score of 8.8 (2–18). The mean detrusor pressure at maximum flow in BPH patients was 89.5 cmH₂O (20–200 cmH₂O). Conclusions An increased PSA in patients with minor or no LUTS, clinical BPH and negative extended multi-site prostate biopsy is strongly correlated to bladder outlet obstruction. Therefore, patients with these characteristics should be treated with TURP.     

Detection of heterozygous SALL1 deletions by quantitative real time PCR proves the contribution of a SALL1 dosage effect in the pathogenesis of Townes-Brocks syndrome

Townes-Brocks syndrome (TBS) is an autosomal dominantly inherited disorder characterized by ear, anal, limb, and renal malformations, and results from mutations in the gene SALL1. All SALL1 mutations previously found in TBS patients create preterminal termination codons. In accordance with the findings of pericentric inversions or balanced translocations, TBS was initially assumed to be caused by SALL1 haploinsufficiency. This assumption was strongly contradicted by a Sall1 mouse knock-out, because neither hetero- nor homozygous knock-out mutants displayed a TBS-like phenotype. A different mouse mutant mimicking the human SALL1 mutations, however, showed a TBS-like phenotype in the heterozygous situation, suggesting a dominant-negative action of the mutations causing TBS. We applied quantitative real time PCR to detect and map SALL1 deletions in 240 patients with the clinical diagnosis of TBS, who were negative for SALL1 mutations. Deletions were found in three families. In the first family, a 75 kb deletion including all SALL1 exons had been inherited by two siblings from their father. A second, sporadic patient carried a de novo 1.9-2.6 Mb deletion including the whole SALL1 gene, and yet another sporadic case was found to carry an intragenic deletion of 3384 bp. In all affected persons, the TBS phenotype is rather mild as compared to the phenotype resulting from point mutations. These results confirm that SALL1 haploinsufficiency is sufficient to cause a mild TBS phenotype but suggest that it is not sufficient to cause the severe, classical form. It therefore seems that there is a different contribution of SALL1 gene function to mouse and human embryonic development.     

A complex submicroscopic chromosomal imbalance in 19p13.11 with one microduplication and two microtriplications

Complex chromosomal rearrangements [CCRs] are considered very rare, but are being detected with an increasing frequency because of the enhanced resolution of novel molecular karyotyping techniques like array-CGH. This report describes a patient carrying a unique CCR involving one duplication and two triplications in a 3.2 Mb region on 19p13.11. The patient presented with microcephaly, velopharyngeal insufficiency, dysmorphism, mental retardation and a muscular ventricular septal defect. We show that CCRs are likely to be more frequent than hitherto appreciated. This has important consequences for genotype–phenotype correlations and warrants caution before labelling imbalances as “simple”.     

Less efficient elementary visuomotor processes in 7- to 10-year-old preterm-born children without cerebral palsy: an indication of impaired dorsal stream processes

Follow-up studies of preterm children without serious neurological complications have consistently found deficits in visuomotor skills. To determine whether these deficits may be related to impaired elementary visuomotor processes, we investigated movement programming and execution of simple pointing movements in 7- to 10-year-old preterm (<34 weeks g.a. and/or b.w. <1800 g) and full-term children. Such detailed analysis of simple pointing movements provides information on the extent to which processes associated with dorsal and/or cerebellar functions are impaired. Multi-level analysis showed that movement programming and execution were slowed in the 7-, 9-, and 10-year-old preterm groups. This indicates impaired dorsal visual stream functioning in preterm children, but do not rule out impaired cerebellar functioning. At 8 years of age, there were no differences between the two groups in movement execution time. This could have reflected a transition in the development of movement control in the control group, which has been associated in typically developing children with a decrease in motor speed. Interestingly, a similar decrease was not found in the preterm group at 8 years of age.