Linkage analysis of extended high-risk pedigrees replicates a cutaneous malignant melanoma predisposition locus on chromosome 9q21.

Three predisposition genes have been identified for cutaneous malignant melanoma (CMM), but they account for only ∼25% of melanoma clusters/pedigrees. Linkage analyses of melanoma pedigrees from many countries have failed to identify significant linkage evidence for the remaining predisposition genes that must exist. The Utah linkage analysis approach of using singly informative extended high-risk pedigrees combined with high-density single-nucleotide polymorphism (SNP) markers has successfully identified significant linkage evidence for two regions. This is, to our knowledge, the first genome-wide linkage analysis of the extended Utah high-risk CMM pedigrees, and it provides confirmation of linkage for a chromosome 9q region previously reported in Danish pedigrees. This report confirms that linkage analysis for common disorders can be successful in analysis of high-density markers in sets of singly informative high-risk pedigrees.

The natural history of lower urinary tract dysfunction in men: minimum 10-year urodynamic follow-up of untreated bladder outlet obstruction.

OBJECTIVES: To assess the long-term outcomes of untreated bladder outlet obstruction (BOO), assuming that, if there is little or no deterioration, a conservative approach to management is justified, as there is little information on the natural history of untreated BOO and lower urinary tract symptoms (LUTS) in men, and studies to date suggest that neither BOO nor LUTS inevitably progress to a stage at which prostatectomy is required. PATIENTS AND METHODS: Men aged >45 years who were investigated in our department between 1972 and 1986, diagnosed with BOO, and who initially opted for no specific treatment were invited for repeat symptomatic and urodynamic evaluation. Identical methods of assessment were used, allowing results to be compared directly. RESULTS: In all, 1068 men were initially diagnosed with BOO; 428 (40%) of these died. Of the 170 men who initially opted for a conservative approach and attended for repeat assessment, 141 (83%) remained untreated, with a mean follow-up of 13.9 years. The only significant urodynamic changes were a reduction in detrusor contractility and an increased prevalence of detrusor overactivity. Most patients reported no change in their symptoms but a significant minority experienced a gradual deterioration. Of the 29 men in whom the conservative approach failed, 22 proceeded to surgery for LUTS, and seven for acute urinary retention. CONCLUSIONS: Patients with untreated BOO do not significantly deteriorate urodynamically in the long term, with only a minority deteriorating symptomatically. These findings justify a conservative approach to men with LUTS associated with BOO.

The natural history of lower urinary tract dysfunction in men: minimum 10-year urodynamic follow-up of untreated detrusor underactivity.

OBJECTIVES: To assess the long-term symptomatic and urodynamic outcomes of men with untreated detrusor underactivity (DUA) as there has been little long-term follow-up information on men with DUA, a cause of lower urinary tract symptoms (LUTS) in a significant minority of men. PATIENTS AND METHODS: Neurologically intact men aged > 18 years who were investigated in our department between 1972 and 1986, diagnosed with DUA, and who initially opted for no specific treatment were invited for a repeat symptomatic and urodynamic evaluation. Identical methods of assessment were used, allowing results to be compared directly. RESULTS: In all, 224 men were initially diagnosed with DUA; 87 (39%) of these died. Of the 69 men who initially opted for a conservative approach and attended for repeat assessment, 58 (84%) remained untreated, with a mean follow-up of 13.6 years. There were no significant changes in symptoms over the follow-up. The only significant urodynamic finding was an increase in the proportion of patients with detrusor overactivity, but with no apparent worsening of chronic retention. Of the 11 men in who failed the conservative approach, eight proceeded to surgery for LUTS, and three for acute urinary retention. CONCLUSIONS: These results provide important information on the natural history of DUA. In men with DUA presenting with LUTS there are few symptomatic and urodynamic changes with time.

The natural history of lower urinary tract dysfunction in men: minimum 10-year urodynamic followup of transurethral resection of prostate for bladder outlet obstruction.

PURPOSE: Despite long-term symptomatic and uroflowmetry studies following transurethral prostate resection (TURP) there are sparse pressure flow data. Consequently there is minimal information to account for the long-term symptomatic failure and flow rate decrease seen with time following early improvements after surgery. MATERIALS AND METHODS: Men older than 45 years who were investigated at our department between 1972 and 1986, diagnosed with bladder outlet obstruction and elected surgical intervention were invited for repeat symptomatic and urodynamic assessment. Identical methods were used, allowing direct comparison of results. RESULTS: A total of 1,068 men were initially diagnosed with bladder outlet obstruction, of whom 428 (40%) died in the interim. Of the men who were followed 217 underwent TURP with a mean followup since surgery of 13.0 years. A significant, sustained decrease in the majority of symptoms and improvements of urodynamic parameters was seen. Long-term symptomatic failure and decreased flow rate were principally associated with detrusor under activity (DUA) rather than obstruction. Presentation predictive factors for the future development of DUA were decreased detrusor contractility and a lesser degree of obstruction. CONCLUSIONS: This unique long-term study provides valuable information on surgically treated bladder outlet obstruction. The association of long-term failure following surgery with DUA emphasizes the importance of pressure flow studies before repeat surgery. However, our faith in the long-term efficacy of TURP is justified.