Israel Medical Association Journal

Backgound: Colchicine is widely used for treating gout and familial Mediterranean fever. However, studies in animal models have reported ill effects of colchicine on the central nervous system, including cognitive function.

Objectives: To evaluate the cognitive status of elderly FMF[1] patients on long-term colchicine treatment.

Methods: The study group consisted of 55 FMF patients aged 74 ± 5, attending an FMF outpatient clinic and receiving colchicine treatment for 25.1 ± 8.9 years. The Mini-Mental State Examination was used for cognitive evaluation. Patients' scores were compared with accepted age- and education-adjusted cutoff scores, population-based norms, and scores of a matched control group of 56 subjects.

Results: Individually, all colchicine-treated FMF patients scored well above the age- and education-corrected cutoff scores. Overall, there was a large difference, 5.0 ± 1.6, from the expected cutoff points, in favor of the study group scores (P < 0.001). The individual scores of the control group were also above the cutoff points, however with a lower but still statistically significant difference (3.71 ± 1.15 points, P < 0.001). Compared to population-based norms adjusted by age and education, the study group had significantly higher mean MMSE[2] scores (27.2 ± 2.2 vs. 25.5 ± 2.4, P < 0.001). The control group’s scores were also somewhat higher than expected, but not significantly so.

Conclusions: Our results do not support the view that prolonged colchicine treatment may be associated with cognitive impairment. On the contrary, it is possible that long-term colchicine treatment may even confer protection against cognitive decline in patients with FMF.

Objectives: To report our experience with three patients who developed autoimmune disease following prostatectomy.

Patients: Three patients presented with autoimmune phenomenon soon after a prostectomy for BPH[1] or prostatic carcinoma: one had clinically diagnosed temporal arteritis, one had leukocytoclastic vasculitis, and the third patient developed sensory Guillian-Barré syndrome following prostatectomy.

Conclusions: In view of the temporal association between the removal of the prostate gland and the autoimmune process, combined with previously known immunohistologic features of BPH, a cause-effect relationship probably exists.

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[1] BPH = benign prostatic hypertrophy

Background: Heterotopic ossification is a common complication of hip surgery and musculoskeletal or brain traumas.

Objectives: To confirm by in vivo study that colchicine inhibits osteoblast cell proliferation with marked decrease in tissue mineralization.

Methods: Heterotopic ossification was induced in three groups of New Zealand white rabbits (females, 6 months old, weight 3–3.5 kg) by injecting 2 ml bone marrow drawn from the iliac crest into their right thigh muscle. To prevent heterotopic ossification, colchicine (0.25 mg/day) was administered orally for 4 weeks to two groups of adult rabbits: group A (preload group) – 1 week preceding bone marrow injection; group B – on day of injection; and group C – control group.

Results: After 4 weeks the rabbits were evaluated by radiographs and ultrasound for evidence of heterotopic ossification. At the end of the study histologic samples were taken from all the thighs. Imaging and histologic studies showed, with statistical significance, almost complete prevention of heterotopic ossification formation in group A (preload) and a marked decrease in group B, when compared with the controls in whom large new bone had formed at the injection site. These results indicated the inhibitory effects of colchicine on a bone-forming process in soft tissue such as heterotopic ossification.

Conclusions: The role of colchicine in preventing heterotopic ossification in other bone-forming conditions, such as hip arthroplasty or pelvic trauma, and after brain trauma, remains to be evaluated in a clinical setting.

Objectives: To assess patient satisfaction, subjective long-term continence and complications after AMS 800 artificial urinary sphincter implantation.

Methods: The medical records of 34 patients who underwent artificial urinary sphincter implantation for radical prostatectomy (n=23), simple prostatectomy (n=9) or neurogenic disease (n=2) between 1995 and 2003 were studied retrospectively. Median follow-up was 49 months (range 3–102 months). Records were analyzed for urinary sphincter survival and complications. Quality of life and continence assessment was done by mailing an impact questionnaire.

Results: In 4 of the 34 patients (11.7%) the device was removed due to infection. One of the four had surgical revision elsewhere, and the other three were not interested in re-implantation of the device. Two patients (5.9%) underwent revisions due to mechanical failure. One patient died and three patients were not located. Twenty-seven out of a possible 30 patients (88%) completed the questionnaire; 22 (85%) achieved social continence (0–2 pads daily), and one patient had subjective difficulty activating the device. Subjective improvement and patient satisfaction was rated as 4.22 and 4.11, respectively (scale 0 to 5).
Conclusions: Artificial urinary sphincter implantation is an efficacious option for sphincter-related incontinence. This study documents the positive impact of artificial urinary sphincter implantation on quality of life with acceptable complications; these results are comparable to other published studies.

Background: Familial Mediterranean fever is an autosomal recessive disease characterized by recurrent attacks of fever and serositis. The disease is caused by mutations in the MEFV gene, presumed to act as a down-regulator of inflammation within the polymorphonuclear cells.

Objectives: To present the results of 412 FMF patients genotyped for three MEFV mutations, M694V, V726A and E148Q.

Results: The most frequent mutation, M694V, was detected in 47% of the carrier chromosomes. This mutation, especially common among North African Jewish FMF[1] patients, was not found in any of the Ashkenazi (East European origin) patients. Overall, one of the three mutations was detected in 70% of the carrier chromosomes. M694V/M694V was the most common genotype (27%), followed by M694V/V726A (16%). The full genotype could be assessed in 57% of the patients, and one disease-causing mutation in an additional 26%. Only one patient with the E148Q/E148Q genotype was detected despite a high carrier rate for this mutation in the Jewish population, a finding consistent with a low penetrance of this genotype. The M694V/M694V genotype was observed in 15 patients with amyloidosis compared to 4 amyloidosis patients with other genotypes (P < 0.0001).

Conclusions: Because of low penetrance and as yet other undetermined reasons, mutation analysis of the most common MEFV mutations supports a clinical diagnosis in only about 60% of patients with definite FMF.

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Background: Familial Mediterranean fever is a genetic disorder manifested by recurrent attacks of peritonitis, pleuritis and arthritis, and characterized by clinical, histological and laboratory evidence for localized and systemic inflammation. Colchicine treatment usually prevents the attacks and the associated inflammation. Inflammation of atherosclerosis and ischemic heart disease.

Objective: To study the effect of inflammation and its prevention on occurrence of IHD, using FMF as a model.

Methods and Patients: We studied the presence of IHD and its risk factors in 290 FMF patients aged 40 years or more, and in two control groups – 233 spouses of the FMF patients’ and 126 patients with inflammatory diseases obtained from other outpatient clinics. FMF patients were also compared with age and gender-matched individuals from the population reference data of the Israel Ministry of Health.

Results: The prevalence of IHD in FMF patients was significantly lower than in the group of controls from other outpatient clinics (15.5% vs. 30.2% P< 0.05) and comparable with their spouses (11.2%) and with the matched general population in Israel (16%).

Conclusion: These findings suggest that despite the evidence of recurrent inflammation, colchicines-treated FMF patients are not more predisposed to IHD than the normal population.