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March 2005
Z. Samra, O. Ofer and H. Shmuely
 Background: Methicillin-resistant Staphylococcus aureus is a major nosocomial pathogen worldwide. Vancomycin is the traditional drug of choice, but decreasing susceptibility to vancomycin and other glycopeptides has been reported since 1996.

Objectives: To test the in vitro activity of linezolid (oxazolidinone) and other antimicrobial agents against MRSA[1] isolates recovered from hospitalized patients.

Methods: We tested 150 MRSA isolates recovered from hospitalized patients. The minimal inhibitory concentration of vancomycin, teicoplanin, pristinamycin (quinupristin-dalforistin), and linezolid was determined by the Etest method. Susceptibility to other antibiotics was tested by the disk diffusion method.

Results: All isolates were sensitive to vancomycin, teicoplanin, pristinamycin, and linezolid. The MIC90 was 2.0 mg/ml for vancomycin and teicoplanin (range 0.5–2.0 mg/ml and 0.125–2.0 mg/ml, respectively), and 0.5 mg/ml for pristinamycin and linezolid (range 0.125–0.75 mg/ml and 0.125–0.5 mg/m, respectively). Of the other antibiotics, fusidic acid showed the best in vitro activity, with 96.7% susceptibility, associated with trimethoprim/sulfamethoxazole (85.8%) and minocycline (84%). Penicillin was associated with the lowest susceptibility (1.3%), associated with ofloxacin (3%) and erythromycin (14%). An increase in the minimal inhibitory concentration value of vancomycin was associated with a significant decrease in resistance to TMP-SMZ[2] (P < 0.01) and an apparent increase in resistance to other antibiotics.

Conclusion: The excellent in vitro activity of linezolid and its reported in vivo effectiveness renders it an important therapeutic alternative to vancomycin in the treatment of MRSA infection.

__________________

[1] MRSA = methicillin-resistant Staphylococcus aureus

[2] TMP-SMX = trimethoprim/sulfamethoxazole

Z. Feldbrin, M. Singer, O. Keynan, V. Rzetelny and D. Hendel
Background: Coccygectomy is an uncommon procedure that many surgeons are reluctant to perform due to its proximity to the anus and the risk of rectal perforation and infection.

Objectives: To evaluate the diagnostic accuracy and outcome of coccygectomy.

Methods: We retrospectively reviewed the operative results in nine patients (seven females and two males) who underwent coccygectomy for coccygodynia in the last 5 years following conservative treatment failure.

Results: The outcome of the procedure was excellent in five patients, good in one patient and poor in two patients.

Conclusions: It is mandatory to perform bone scanning in every patient with coccygodynia and before coccygectomy in order to rule out the presence of malignancy. Coccygectomy is recommended for patients with isolated coccygodynia.

D. Antonelli, S. Atar, N.A. Freedberg and T. Rosenfeld
Background: Torsade de pointes is rarely associated with chronic amiodarone treatment, despite the effect of amiodarone on QT interval prolongation.

Objective: To identify risk factors and associated conditions that may cause TdP[1] in patients on chronic amiodarone treatment.

Methods: We reviewed the data of six consecutive patients on chronic amiodarone treatment who were admitted to the intensive cardiac care unit due to syncope and TdP.

Results: The patients’ median age was 73.5 years, and five were women. Concomitantly, loratadine was given to two patients and trazodone to one patient. Associated and attributing conditions to the development of TdP were hypokalemia in three patients, drug-induced bradycardia in one and reduced left ventricular function in four.

Conclusions: TdP associated with chronic amiodarone treatment may occur when amiodarone is co-administered with drugs that may potentially prolong QT interval. Additional risk factors for amiodarone-associated TdP include female gender, hypokalemia, reduced left ventricular function and bradycardia.

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[1] TdP = torsade de pointes

J. Cohen, D. Starobin, G. Papirov, M. Shapiro, E. Grozovsky, M.R. Kramer and P. Singer
Background: While increasing numbers of patients require prolonged mechanical ventilation, resources for weaning are either limited (ICU beds) or inadequate (general wards).

Objectives: To report on our initial experience over a 7 month period with an eight-bed mechanical ventilation weaning unit.

Methods: Sixty-nine patients requiring MV[1] for >10 days were admitted to the unit (nurse:patient ratio 1:4). Data collected included reason for MV, duration of hospital stay, and MVWU[2] course. Outcome results (successful weaning and mortality) were compared to those in historic controls (patients ventilated in the general wards over a 4 month period prior to the MVWU; n = 100).

Results: The mean age of the patients was 68 ± 16.6 years and hospital stay prior to MVWU admission 28.6 ± 24.2 days (range 10–72). The main reasons for MV included acute exacerbation of chronic obstructive pulmonary disease (31%) and recent pneumonia (28%). Mean MVWU stay was 13.5 ± 15.7 days (range 1–72 days). Thirty-four patients (49%) underwent tracheostomy. Fourteen patients required admission to the ICU[3] due to deterioration in their status. Twenty-nine patients (42%) were successfully weaned and discharged to the wards. A further 20 patients were transferred to the chronic ventilation unit of a regional geriatric rehabilitation hospital, where 5 were subsequently weaned and 15 required prolonged ventilation. Compared to controls (matched for age and reason for mechanical ventilation), more MVWU patients underwent successful weaning (49% vs. 12%, P < 0.001) and their mortality rate (n = 12) was significantly lower (17% vs. 88%, P < 0.001).

Conclusion: The higher level of care possible in a MVWU may result in a significantly improved rate of weaning and lower mortality. The assessment of long-term outcome in patients discharged to pulmonary rehabilitation centers requires further investigation.

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[1] MV = mechanical ventilation

[2] MVWU = mechanical ventilation weaning unit

[3] ICU = intensive care unit

M. Ben-Haim, M. Carmiel, N. Lubezky, R. Keidar, P. Katz, A. Blachar, A. Nomrod, P. Sorkine, R. Oren, J.M. Klausner and R. Nakache
Background: Adult-to-adult living donor liver transplantation is becoming an alternative to cadaveric transplantation in urgent and elective settings. Donor selection crucially affects donor safety and recipient outcome.

Objective: To present our algorithm of urgent and elective donor selection.

Methods: Urgent selection is expeditious and protocol‑based. Elective selection permits a comprehensive process. Both include medical, psychosocial and surgical-anatomic evaluations. Liver volumes and vascular anatomy are evaluated with computerized tomographic angiography. Informed consent is obtained after painstaking explanations. Independent institutional committees review and approve all cases.

Results: Between July 2003 and June 2004 we evaluated 43 potential live donors for 12 potential recipients (fulminant hepatic failure, n=5; chronic end-stage liver disease, n=6); primary graft non-function, n=1). Thirty-three candidates (76%) were excluded due to blood type incompatibility (n=14, 42%), incompatible anatomy (n=8, 24%) – including problematic volume distribution (n=2) or vascular anatomy (n=6) – psychosocial issues (n=4, 12%), or medical co-morbidity (n=7, 22%). Five recipients (FHF[1], n=4; chronic ESLD[2], n=1) were successfully transplanted from living donors. In the acute setting, two patients (FHF, PGNF[3]) died in the absence of an appropriate donor (cadaveric or living donor). In the elective group, one patient died of unexpected variceal bleeding and one received a cadaveric graft just before the planned living donor transplantation was performed. One candidate was transplanted overseas and two cases are scheduled. The ratio of compatibility for donation was 34% (10/29) for blood type-compatible candidates.

Conclusions: Donor selection for living donor liver transplantation is a complex, labor-intensive multidisciplinary process. Most exclusions are due to blood type incompatibility or anatomic details. Psychosocial aspects of these donations warrant special attention.

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[1] FHF = fulminant hepatic failure

[2] ESLD = chronic end-stage liver disease

[3] PGNF = primary graft non-function

A.L. Alkalay, H.B. Sarnat, L. Flores-Sarnat and C.F. Simmons
Profound neonatal hypoglycemia is one of the leading causes of brain injury. Hypoglycemic encephalopathy is caused by lack of glucose availability to brain cells. Although sharing a similar pathogenesis with hypoxic-ischemic encephalopathy, hypoglycemic brain insult has distinctive metabolic, brain imaging, electroencephalographic, and histopathologic findings.

R. Percik, J. Serr, G. Segal, S. Stienlauf, H. Trau, B. Shalmon, A. Shimoni and Y. Sidi
Z. Habot-Wilner, J. Moisseiev, H. Bin and B. Rubinovitch
M. Leitman, E. Peleg, R. Krakover, E. Sucher, S. Rosenblath, R. Zaidentstein and Z. Vered
February 2005
E. Aizen, G. Kagan, B. Assy, R. Iobel, Y. Bershadsky and A. Gilhar

Background: Alteration of innate and acquired immunity can play a role in the mechanism involved in the development of dementia. Epidemiologic studies indicate that the use of non-steroidal anti-inflammatory drugs can delay the onset or slow progression of Alzheimer disease.

Objectives: To determine whether the use of NSAIDs[1] is associated with natural killer activity alteration in AD[2] and multi-infarct vascular dementia patients, as compared with non-demented elderly and healthy young people.

Methods: In this prospective open study four groups of subjects (AD, VD[3], non-demented elderly, and healthy young people) were treated with an NSAID drug (rofecoxib 12.5 mg/day or ibuprofen 400 mg twice daily) for 7 days. Natural killer cell cytotoxicity was measured after flow cytometry analysis before and after treatment.

Results: Of the 49 subjects studied, 15 had a diagnosis of AD (3 men, 12 women; mean age 83.5 ± 8.1 years), 15 had a diagnosis of multi-infarct VD (7 men, 8 women; mean age 75.5 ± 8.4), 13 were non-demented elderly (1 man, 12 women; mean age 80.2 ± 7.2), and 6 were healthy young volunteers (3 men, 3 women; mean age 36.8 ± 4.4). While all examined subjects showed decreased NK[4] cell cytotoxicity after treatment, this decrease was most prominent and statistically significant in elderly patients suffering from vascular dementia –  from an average of 30.5 ± 11.8% before treatment to 22.5 ± 16% after treatment (P = 0.04). The decrease in NK cell cytotoxicity was only moderate and not statistically significant in all other elderly and young subjects. Young healthy volunteers exhibited a significantly higher total NK cytotoxicity before and after treatment compared to all age groups (P < 0.001).

Conclusion: These findings suggest that NSAIDs decrease NK activity in vascular dementia patients. Our findings also suggest that natural killer activity alteration cannot explain the ability of anti-inflammatory drugs to delay the onset or slow the progression of AD.

 






[1] NSAIDs = non-steroidal anti-inflammatory drugs



[2] AD = Alzheimer disease



[3] VD = vascular dementia



[4] NK = natural killer


H. Tulchinsky, A. Keidar, G. Goldman, J.M. Klausner and M. Rabau

Background: Restorative proctocolectomy eliminates the risk of colorectal cancer in patients with familial adenomatous polyposis. Complications and extra‑intestinal manifestations are inherent to the procedure.

Objectives: To evaluate operative procedures, complications, early and late results and long-term functional outcome in FAP[1] patients operated in our department.

Methods: The study group included all patients with FAP who were operated between 1988 and 2003. Demographic data, length of follow‑up, complications, colorectal cancer, pouch function and extracolonic manifestations were recorded.

Results: Median age at surgery was 33 years (range 13–61 years). The final operative breakdown was: 48 proctocolectomies, 41 ileal pouch-anal anastomoses, 2 Kock’s pouch, 5 permanent ileostomies, and 2 colectomies with ileorectal anastomosis. There was no perioperative mortality. Early and late complications occurred in 20 and 9 patients, respectively. Twelve patients required re‑operation. Colorectal carcinoma was diagnosed in eight patients, three of whom were in an advanced stage. The mean follow‑up was 74 months (range 3–288 months). Four patients were lost to follow‑up. Extracolonic manifestations developed in 38 patients, including desmoid tumors (in 12), duodenal adenomas (in 9), pouch adenomas (in 5), and rectal stump adenomas (in 3). Two patients died (4%) because of desmoid tumor and malignant fibrous histiocytoma. At last follow‑up, 37 IPAA[2] patients have (median) six bowel movements/24 hours and good fecal control.

Conclusions: Restorative proctocolectomy can be performed with low mortality, acceptable morbidity, and good functional results. Patients should be closely followed after surgery for development of other manifestations of the syndrome. Relatives of the affected patients should be referred to a specialist multidisciplinary clinic.

 






[1] FAP = familial adenomatous polyposis



[2] IPAA = ileal pouch-anal anastomosis


E. Aizen, G. Kagan, B. Assy, R. Iobel, Y. Bershadsky and A. Gilhar

Background: Alteration of innate and acquired immunity can play a role in the mechanism involved in the development of dementia. Epidemiologic studies indicate that the use of non-steroidal anti-inflammatory drugs can delay the onset or slow progression of Alzheimer disease.

Objectives: To determine whether the use of NSAIDs[1] is associated with natural killer activity alteration in AD[2] and multi-infarct vascular dementia patients, as compared with non-demented elderly and healthy young people.

Methods: In this prospective open study four groups of subjects (AD, VD[3], non-demented elderly, and healthy young people) were treated with an NSAID drug (rofecoxib 12.5 mg/day or ibuprofen 400 mg twice daily) for 7 days. Natural killer cell cytotoxicity was measured after flow cytometry analysis before and after treatment.

Results: Of the 49 subjects studied, 15 had a diagnosis of AD (3 men, 12 women; mean age 83.5 ± 8.1 years), 15 had a diagnosis of multi-infarct VD (7 men, 8 women; mean age 75.5 ± 8.4), 13 were non-demented elderly (1 man, 12 women; mean age 80.2 ± 7.2), and 6 were healthy young volunteers (3 men, 3 women; mean age 36.8 ± 4.4). While all examined subjects showed decreased NK[4] cell cytotoxicity after treatment, this decrease was most prominent and statistically significant in elderly patients suffering from vascular dementia –  from an average of 30.5 ± 11.8% before treatment to 22.5 ± 16% after treatment (P = 0.04). The decrease in NK cell cytotoxicity was only moderate and not statistically significant in all other elderly and young subjects. Young healthy volunteers exhibited a significantly higher total NK cytotoxicity before and after treatment compared to all age groups (P < 0.001).

Conclusion: These findings suggest that NSAIDs decrease NK activity in vascular dementia patients. Our findings also suggest that natural killer activity alteration cannot explain the ability of anti-inflammatory drugs to delay the onset or slow the progression of AD.






[1] NSAIDs = non-steroidal anti-inflammatory drugs

[2] AD = Alzheimer disease

[3] VD = vascular dementia

[4] NK = natural killer


H. Tulchinsky, A. Keidar, G. Goldman, J.M. Klausner and M. Rabau
 Background: Restorative proctocolectomy eliminates the risk of colorectal cancer in patients with familial adenomatous polyposis. Complications and extra‑intestinal manifestations are inherent to the procedure.

Objectives: To evaluate operative procedures, complications, early and late results and long-term functional outcome in FAP[1] patients operated in our department.

Methods: The study group included all patients with FAP who were operated between 1988 and 2003. Demographic data, length of follow‑up, complications, colorectal cancer, pouch function and extracolonic manifestations were recorded.

Results: Median age at surgery was 33 years (range 13–61 years). The final operative breakdown was: 48 proctocolectomies, 41 ileal pouch-anal anastomoses, 2 Kock’s pouch, 5 permanent ileostomies, and 2 colectomies with ileorectal anastomosis. There was no perioperative mortality. Early and late complications occurred in 20 and 9 patients, respectively. Twelve patients required re‑operation. Colorectal carcinoma was diagnosed in eight patients, three of whom were in an advanced stage. The mean follow‑up was 74 months (range 3–288 months). Four patients were lost to follow‑up. Extracolonic manifestations developed in 38 patients, including desmoid tumors (in 12), duodenal adenomas (in 9), pouch adenomas (in 5), and rectal stump adenomas (in 3). Two patients died (4%) because of desmoid tumor and malignant fibrous histiocytoma. At last follow‑up, 37 IPAA[2] patients have (median) six bowel movements/24 hours and good fecal control.

Conclusions: Restorative proctocolectomy can be performed with low mortality, acceptable morbidity, and good functional results. Patients should be closely followed after surgery for development of other manifestations of the syndrome. Relatives of the affected patients should be referred to a specialist multidisciplinary clinic.

____________________________

[1] FAP = familial adenomatous polyposis

[2] IPAA = ileal pouch-anal anastomosis

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