Israel Medical Association Journal

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: Splanchnic nerve stimulation evokes adrenomedullary catecholamine secretion via acetylcholine release and occupation of nicotinic cholinergic receptors on chromaffin cells.

Objectives: To assess whether among cultured adrenomedullary cells there exists a population that tonically secretes acetylcholine. If so, then blockade of enzymatic breakdown of acetylcholine by addition of a cholinesterase inhibitor to the medium would increase occupation of nicotinic receptors by endogenous acetylcholine and thereby induce catecholamine release.

Methods: Primary cultures of bovine adrenomedullary cells in 24-well plates (1 million cells per well) were incubated after 48–72 hours with fresh incubation medium (control), medium with added secretagogues (nicotine, angiotensin II, or K+) or the acetylcholinesterase inhibitor, edrophonium (10-7 to 10-³ M), for 1–20 minutes. Fractional release rates of epinephrine, norepinephrine and dopamine were compared to a control. We also examined whether co-incubation with edrophonium enhanced the effects of the secretagogues. All experiments were performed in quadruplicate and repeated three times.

Results: Nicotine, angiotensin II, and K+ each elicited time-related release of epinephrine, norepinephrine and dopamine by up to fourfold compared to the control. At all tested concentrations, edrophonium had no such effect. Co-incubation with edrophonium also failed to augment the secretory responses to nicotine, angiotensin II, or K+.

Conclusion: Bovine adrenomedullary cells in primary culture do not include a population of tonically active cholinergic cells.

Background: Training in geriatric psychiatry constitutes a fundamental element toward further development of this relatively new branch of medicine. However, it varies both in quantity and quality among different countries, healthcare providers and medical schools.

Objectives: To describe the demographic and professional characteristics of participants in postgraduate diploma courses in geriatric psychiatry, and the perceived contribution of the courses; and to compare these variables among the participants in 1 year and 3 year courses, and between psychiatrists and non-psychiatrists.

Methods: A retrospective self-administered questionnaire was mailed to the 153 physicians who participated in the two courses. The 60 questionnaires completed and returned were analyzed.

Results: Participants in the courses constituted a heterogenous group in terms of demographic and professional characteristics, with no differences between 1 year and 3 year course participants, or between psychiatrists vs. non-psychiatrists (with the exception of more involvement of non-psychiatrists and 1 year course participants in old-age homes). Most responders indicated both the theoretical and practical benefits and application to daily practice of the material learned. Similarly, most responders indicated that after the courses they definitely used general assessment scales to a much greater extent, particularly cognitive scales, as well as operational diagnostic criteria for dementia. Participants in the 3 year course reported more significant use of assessment scales compared with 1 year participants, and 3 year participants and psychiatrists used the cognitive scales more often. There were no other significant differences between 1 year and 3 year participants and between psychiatrists’ and non-psychiatrists’ reports regarding general and more specific contributions of the courses.

Conclusion: Postgraduate diploma courses in geriatric psychiatry seem to have a favorable effect on participants, irrespective of course duration or specialty. However, course duration positively influenced the implementation of assessment scales in general, and cognitive scales in particular. A prospective comparative study on this subject is warranted, with stricter definitions of participants’ pre-course and post-course background, attitudes, knowledge and benefits.
 

Matrix metalloproteinases are a family of enzymes that degrade different components of extracellular matrix. They play an important role in normal physiologic processes of maintaining tissue integrity and remodeling, as in wound healing, processes of development, and regeneration. However, excessive expression of MMP[1] has been observed in many disease states, including rheumatoid arthritis and osteoarthritis, vascular remodeling in atherosclerosis and aortic aneurysm formation, neoplastic processes, macular degeneration and many others.

______________________________

Background: The frequent systemic side effects associated with the use of systemic carbonic anhydrase inhibitors have adversely affected the compliance to treatment in glaucoma patients, obviating their long-term use. The introduction of the topical CAI[1], dorzolamide, has further reduced their use. However, the tolerability of dorzolamide in patients who have been intolerant to systemic CAIs has not been evaluated prospectively.

Objectives: To study the tolerability and efficacy of dorzolamide (a topical CAI) in a selected group of glaucoma and ocular hypertensive patients who have been intolerant to systemic CAI.

Methods: A 3 month prospective study was conducted in 39 patients. Following recruitment, patients were evaluated on the day of switching from systemic CAI to dorzolamide and for five more visits. The SF-36 health assessment questionnaire was used to evaluate changes in well-being and quality of life, and the intraocular pressure was measured periodically.

Results: Within 4 weeks of switching from systemic CAI to dorzolamide, the mean health assessment scores improved significantly in seven of the eight categories of the SF-36, and remained generally unchanged for the rest of the study. No significant differences were noted between the mean IOP[2] on day 0 and the following measurements throughout the 84 days of dorzolamide therapy.

Conclusion: In glaucoma patients who were intolerant to systemic CAI, topical CAI dorzolamide offers a similar efficacy and better tolerability.

Background: High frequency oscillatory ventilation has proved valuable in recruiting and sustaining lung volume; the combined treatment may augment nitric oxide delivery to target vessels. NO[1] therapy lowers pulmonary resistance and improves oxygenation.

Objective: To retrospectively review data on changes in oxygenation – indicated by arterial/alveolar PO₂ ratio, oxygenation index, and outcome – in a cohort of 10 infants with hypoxemic respiratory failure in whom nitric oxide inhalation was instituted in a compassionate-use protocol after deteriorated oxygenation.

Methods: NO inhalation was administered at a range of 0.12–122 days of life using the SensorMedics system in 10 infants who developed hypoxemic respiratory failure associated with a variety of lung diseases while on HFOV[2].

Results: The infants' birthweight was 1,717 ± 1,167 g and their gestational age 31.1 ± 6.5 weeks. Mean exposure to NO inhalation was 14.2 days and ranged from 3–59 days. Oxygenation index decreased from 39.3 ± 13.2 to 12.7 ± 6.9 (P < 0.0002) after NO therapy. Despite an initial prompt response to NO inhalation, two patients died of progressive intractable respiratory failure and one term infant died of extrapulmonary complications (hypoxic ischemic encephalopathy grade III and multiorgan failure).

Conclusion: Our results indicate that the combined treatment of HFOV and NO inhalation is superior to HFOV alone for improving oxygenation in a selected cohort of infants ventilated for a variety of lung diseases.

Background: Venous thromboembolic diseases are treated initially with low molecular weight heparin followed by oral coumarins.

Objectives: To investigate an orally available direct thrombin inhibitor for the acute treatment of venous thromboembolism as well as for prophylaxis of recurrent events.

Methods: The direct thrombin inhibitor ximelagatran was compared with subcutaneous LMW[1] heparins followed by oral warfarin in a double-blind randomized prospective multicenter trial in patients with acute VTE[2]. A pharmacokinetic study was performed in the VTE patients. For assessing the prevention of recurrent VTE, double-blind prospective randomized studies were conducted as follows: a) ximelagatran compared to warfarin for 6 months, and b) prolonged anticoagulation of ximelagatran vs. placebo for 18 months after termination of 6 months coumarin therapy.

Results: Two dose-finding studies and the pharmacokinetic analysis of ximelagatran in acute VTE were completed. About 2,500 patients were randomized to investigate 2 x 36 mg ximelagatran versus 2 x 1 mg/kg body weight enoxaparin followed by warfarin. The study hypothesized that the efficacy was equal in both treatment regimens for recurrent VTE documented by objective methods. The second study, with 1,234 patients, aimed to demonstrate a reduced incidence of recurrent thromboembolic events documented by objective methods after 18 months of treatment with 2 x 24 mg ximelagatran daily compared to placebo.

Conclusion: These large-scale clinical trials will soon yield the results of the comparison between oral ximelagatran and subcutaneous LMW heparin for treatment of acute VTE, and of warfarin for prophylaxis of recurrent events for 6 months and for a prolonged prophylaxis for another 18 months.

______________________________

[1] LMW = low molecular weight

[2] VTE = venous thromboembolism

Background: Matrix metalloproteinases are proteolytic enzymes that degrade extracellular matrix components. Numerous studies have demonstrated that individual MMPs[1] play a crucial role in tumor invasion and metastasis.

Objective: To examine the expression of MMPs and their inhibitor TIMP-2 in neoplastic and normal thyroid tissues.

Methods: We examined 33 cases of thyroid tumor (papillary, follicular and medullary carcinoma, follicular adenoma and multinodular goiter). MMP protein content and activity were measured by enzyme-linked immunosorbent assay and gel zymography. Immunohistochemistry was also performed.

Results: The thyroid tissues examined secreted MMP-2 and 9 as well as TIMP-2, but only MMP-2 was significantly higher in papillary carcinoma cases compared to the adjacent normal tissue or to the other tumor entities. Increased MMP-2 immunohistochemical staining was demonstrated in the neoplastic papillary epithelial component. No significant difference was seen between papillary carcinomas with lymph node metastases and those without.

Conclusions: Increased MMP-2 expression may be useful as a diagnostic marker to differentiate papillary carcinoma from other thyroid neoplasms, but it cannot serve as a useful prognostic marker.