Identification of a 5' splice site mutation in the RPGR gene in a family with X-linked retinitis pigmentosa (RP3)

We have identified a novel RPGR gene mutation in a large Dutch family with X-linked retinitis pigmentosa (RP3). In affected members, a G-->T transversion was found at position +1 of the 5' splice site of intron 5 of the RPGR (retinitis pigmentosa GTPase regulator) gene. Analysis of this mutation at the RNA level showed cryptic splicing upstream of the mutation in exon 5 leading to a frameshift and downstream termination codon. Identification of the causative mutation in this family has facilitated the detection of females at risk of having an affected son.     

First experiences with HLA-matched corneal grafts in high risk cases

In highly vascularized corneas the number of graft failures caused by irreversible rejections is higher than in non- or slightly vascularized corneas. The importance of antigen compatibility is demonstrated, especially in these high risk cases.Ten highly vascularized corneas were grafted with HLA-matched donor material; only one reversible rejection was seen in this group.Nine non- or slightly vascularized corneas were grafted with donor material chosen at random. Retrospective HLA matching was performed. Three irreversible rejections were seen in this group. The number of HLA incompatibilities was high.     

Gonadal function recovery in very long-term male survivors of childhood cancer

BackgroundAlthough gonadal toxicity has been reported, no data are available on recovery of gonadal function in very long-term survivors of childhood cancer. Inhibin B is a novel reliable serum marker which has been shown to be of value in childhood cancer survivor studies to identify risk groups for impaired gonadal function, but consecutive long-term follow-up studies using serum inhibin B as a marker are not available.ObjectiveTo evaluate possible recovery of gonadal dysfunction over time in adult male survivors of childhood cancer.MethodsIn this retrospective study, adult male long-term childhood cancer survivors (n = 201) who visited our outpatient late effects clinic were included and we used inhibin B as a surrogate marker for gonadal function.ResultsMedian age at diagnosis was 5.9 years (range 0.0–17.5) and discontinuation of treatment was reached at a median age of 8.2 years (range 0.0–20.8). Inhibin B levels were first measured after a median follow-up time of 15.7 years (range 3.0–37.0). Median interval between the first (T1) and second measurement (T2) was 3.3 years (range 0.7–11.3). Median inhibin B level was 127 ng/L (range 5–366) at T1 and 155 ng/L (range 10–507) at T2. The prediction model suggests that inhibin B levels do not normalise in survivors with a very low Inhibin B level at T1.ConclusionsOur results suggest that recovery of gonadal function is possible even long after discontinuation of treatment. However, this recovery does not seem to occur in survivors who already reached critically low inhibin B levels after discontinuation of treatment.     

MMP-7-Bestimmung im Urin basierend auf Siliziumchiptechnologie

Background

Early detection of metastases in muscle-invasive bladder cancer is crucial. Current imaging techniques provide only limited sensitivity for the detection of low volume metastases. Molecular markers and new rapid analysis techniques are therefore needed to improve metastasis detection sensitivity. High urinary matrix metalloproteinase 7 (MMP 7) levels were previously shown to be correlated with the presence of lymph node metastases. In the present study we applied a new innovative antibody-based electrical biochip technology for the quantitative detection of urinary MMP 7.

Materials and methods

Preoperative urine samples were acquired from 30 bladder cancer patients (15xN0 and 15xN1-2) who underwent cystectomy because of muscle-invasive bladder cancer. In addition, urine samples of 15 age-matched healthy individuals were also collected. The MMP 7 analyses were performed using electrical biochip technology and a standard ELISA technique in parallel.

Results

Urinary MMP 7 concentrations measured by biochip technology were significantly higher in patients with metastatic bladder cancer compared to those with organ-confined cancer. The sensitivity for the detection of lymph node metastases was over 70 % using the biochip technology.

Conclusions

These results confirm MMP 7 as a promising metastasis marker in bladder cancer. The new electrical biochip technology provides a rapid and reliable quantitative method for measurement of protein markers in urine.     

Secondary monoclonal gammopathy of undetermined significance after allogeneic stem cell transplantation in multiple myeloma

In the course of multiple myeloma, patients may develop a M-protein band different from the original: secondary monoclonal gammopathy of undetermined significance. In this retrospective single center analysis, we describe the occurrence and clinical relevance of secondary monoclonal gammopathy of undetermined significance after allogeneic stem cell transplantation (post-transplant monoclonal gammopathy of undetermined significance). A total of 138 patients who had undergone 139 allogeneic stem cell transplantations (39.6% in the upfront setting and 60.4% for relapsed multiple myeloma) were included in the study. Sixty-seven (48.2%) patients developed secondary monoclonal gammopathy of undetermined significance, after a median latency of 6.9 months. Secondary monoclonal gammopathy of undetermined significance occurred more often in patients who achieved at least very good partial response after allogeneic stem cell transplantation, compared to partial response or less (54.8% vs. 26.5%; P=0.005). The incidence was also higher in the upfront setting as compared to relapsed disease, or with a sibling donor compared to matched unrelated donor, but less often after T-cell depletion. Importantly, development of post-transplant monoclonal gammopathy of undetermined significance as a time-dependent variable independently predicted for superior progression-free and overall survival (median progression-free survival 37.5 vs. 6.3 months, P<0.001; median overall survival 115.3 vs. 31.0 months, P=0.004). Clinicians should be aware of the benign nature of this phenomenon, and secondary monoclonal gammopathy of undetermined significance should not be confused with relapse or progression of disease. (Trial registered with trialregister.nl; HOVON 108: NTR 2958.)     

Oculocutaneous albinism and anterior chambre cleavage malformations. Not a coincidence

We report on 6 patients out of a group of 86 albinos, with an additional eye defect: an anterior chamber cleavage disorder, i.e. a frequency of 7%. Given this high percentage of the coexistence of these two, we believe that this is not a coincidence.     

The Zeiss-loop stone extraction: minimal invasive and effective or obsolete?

Purpose  

Through the introduction of ureterorenoscopy (URS) and extracorporal shock wave lithotripsy (ESWL) into stone treatment, the Zeiss-loop procedure has lost more and more its importance. Current guidelines recommend on the level of an expert-opinion, that stone extraction without endoscopic-visual control should not be performed anymore. Nevertheless, stone extraction using the Zeiss-loop is still being performed in our clinic and therefore we wanted to determine its position in stone treatment in the age of URS and ESWL.