Israel Medical Association Journal

Background: Hypertension is considered resistant if blood pressure cannot be reduced to <140/90 mmHg with an appropriate triple-drug regimen, including an oral diuretic, with all agents administered at maximal dosages. This definition has evolved with the development of new therapies and evidence-based data supporting treatment to lower BP[1] goals.

Objective: To assess whether vitamin C and atorvastatin improve endothelial function and blood pressure control in subjects with resistant arterial hypertension and dyslipidemia.

Methods: Forty-eight hyperlipidemic subjects with RH[2] (office systolic BP >140 mmHg and/or office diastolic BP >90 mm/Hg notwithstanding antihypertensive treatment with three medications in maximal doses) were randomized into three groups to receive additional medication for 8 weeks. Group VTC (n = 17) – mean 24 hour SBP[3] 150.6 ± 5.2 mmHg, DBP[4] 86.1 ± 3.3 mmHg, low density lipoprotein 158.1 ± 24.5 mg/dl) – received vitamin C 500 mg per day; Group ATR (n = 15) – mean 24 hour SBP 153.1 ± 4.8 mmHg, DBP 87.1 ± 6.7 mmHg, LDL[5] 162.6 ± 13.6 mg/dl) – received atorvastatin 20 mg/day; and Group PLA (n = 16) – mean 24 hour SBP 151.1 ± 7.4 mmHg, DBP 84.8 ± 5.9 mmHg, LDL 156.7 ± 26.1 mg/dl – received a placebo. High resolution ultrasound was used to calculate brachial artery flow-mediated dilation, and 24 hour ambulatory BP monitoring was performed at study entry and after 8 weeks.

Results: In the ATR group there were significant reductions of SBP (DSBP1-2: 13.7 ± 5.6 mmHg, P < 0.001), DBP (DDBP1-2: 7.8 ± 5.7 mmHg, P < 0.01), LDL (DLDL1-2: 67.7 ± 28.3 mg/dl, P < 0.001) and improvement of brachial artery FMD[6] (DFMD2-1: 4.2 ± 2.6%). No significant changes in BP, LDL and FMD were observed in the other two groups.

Conclusions: In subjects with RH and dyslipidemia, atorvastatin 20 mg/day compared to vitamin C 500 mg/day may help to achieve better BP control and improve endothelial function in a finite period. A larger trial is needed to assess the drug's efficacy in this population for longer periods.

Histiocytosis of childhood is characterized by localized or generalized proliferation of cells of the mononuclear phagocyte system and the dendritic cell system. In patients with Langerhans cell histiocytosis, the orbita is the most involved site encountered in ophthalmic practice, usually as a lytic lesion in the zygomaticofrontal suture. Patients usually present with acute or chronic periorbital swelling. Electron microscopic findings of Birbeck granules and positive staining for CD1 antigenic determinant confirm the diagnosis.

Background: The prognosis of patients with fulminant hepatic failure without timely liver transplantation is dismal. Given the limited availability of cadaveric organs for urgent transplantation in Israel, adult-to-adult living-donor segmental liver transplantation may be the only alternative.

Objectives: To report our initial experience with urgent lifesaving LDLT[1] in this unique scenario.

Methods: Three adult patients with FHF[2] (two of unknown etiology, one with paracetamol intoxication) were transferred from other institutions and admitted to our intensive care unit. Initial treatment and monitoring included intracranial pressure monitoring and hepatic dialysis using the Molecular Adsorbent Recirculating System. Expeditious potential donor selection included medical, psychosocial and surgical evaluation. Liver volume and vascular anatomic compatibility were assessed with computed tomography angiography.

Results: Between July and October 2003 we performed three procedures of urgent adult-to-adult LDLT. The donors (two uncles, one sister) underwent hepatic resection (two right lobes, one left lateral segment) and recovered well. The recipients underwent total hepatectomy with caval preservation, followed by lobar grafting. All recipients recovered and are alive with good liver function and without any neurologic complications.

Conclusions: Urgent adult-to-adult living-donor segmental liver transplantation can be performed safely and timely as a lifesaving procedure in the setting of comatose patients with FHF.

The complexity of medical problems is a well-recognized phenomenon. In the presence of economic and cultural restrictions, medical decision-making can be particularly challenging. This paper outlines a system of analysis and decision-making for solving such problems, and briefly describes a case study in which the method was used to analyze the case of antibiotic overprescribing in a large health maintenance organization. The purpose of the study was to determine if a technique for problem-solving in the field of engineering could be applied to the complex problems facing primary care. The method is designated Systematic Inventive Thinking and consists of a three-step procedure: problem reformulation, general search-strategy selection, and an application of idea-provoking techniques. The problem examined is the over-prescribing of antibiotics by general practitioners working in Maccabi Healthcare Services, an HMO[1] serving one and a half million patients in Israel. The group of healthcare professionals involved in the discussions generated 117 ideas for improving antibiotic use. Six of these ideas were then implemented in a national campaign in the winter of 2000/1 and 2001/2. During this period, a significant reduction in per-visit antibiotic purchasing was observed for influenza visits (from 79.2 per 1,000 to 58.1 per 1,000, P < .0001), but not for other categories of visits. The SIT[2] methodology is a useful technique for problem-solving and idea generation within the medical framework.

Background: Transcobalamin II is a serum transport protein for vitamin B₁₂. Small variations in TC-II[1] affinity were recently linked to a high homocysteine level and increased frequency of neural tube defects. Complete absence of TC-II or total functional abnormality causes tissue vitamin B₁₂ deficiency resulting in a severe disease with megaloblastic anemia and immunologic and intestinal abnormalities in the first months of life. This condition was described in hereditary autosomal-recessive form. Low serum TC-II without any symptoms or clinical significance was noted in relatives of affected homozygotes.

Objectives: To study 23 members of a four-generation family with hereditary vitamin B₁₂ deficiency and neurologic disorders.

Methods: Thorough neurologic, hematologic and family studies were supplemented by transcobalamin studies in 20 family members.

Results: Partial TC-II deficiency was found in 19 subjects. Apo TC- II (free TC-II unbound to vitamin B₁₂) and total unsaturated B₁₂ binding capacity were low in all tested individuals but one, and holo TC-II (TC-II bound by vitamin B₁₂) was low in all family members. The presentation of the disease was chronic rather than acute. Early signs in children and young adults were dyslexia, decreased IQ, vertigo, plantar clonus and personality disorders. Interestingly, affected children and young adults had normal or slightly decreased serum vitamin B₁₂ levels but were not anemic. Low serum B₁₂ levels were measured in early adulthood. In mid-late adulthood megaloblastic anemia and subacute combined degeneration of the spinal cord were diagnosed. Treatment with B₁₂ injections resulted in a significant improvement. The pedigree is compatible with an autosomal-dominant transmission. This family study suggests a genetic heterogeneity of TC-II deficiency.

Conclusions: We report the first family with a hereditary transmitted condition of low serum TC-II (partial TC-II deficiency) associated with neurologic and mental manifestations in childhood. Partial TC-II deficiency may decrease the amount of stored cobalamin, resulting in increased susceptibility to impaired intestinal delivery of cobalamin and predisposing to clinically expressed megaloblastic anemia at a later age. Partial TC-II deficiency should be suspected in families with megaloblastic anemia and in individuals with neurologic and mental disturbances – despite normal serum vitamin B₁₂ levels. Low serum UBBC[2] and apo TC-II should confirm the diagnosis. Early vitamin B₁₂ therapy may prevent irreversible neurologic damage.

Background: Seroepidemeliogic surveys have provided valuable information on the prevalence and incidence of herpes simplex virus-2 infection in general and in selected populations.

Objective: To review the reliability of traditional diagnostic approaches in herpes simplex virus-2 infection.

Methods: In this cross-sectional study, 472 patients attending a clinic for sexually transmitted disease in 1998-1999 were evaluated for HSV-2 infection through collection of epidemiologic and clinical data.

HSV-2 infection was confirmed by the presence of specific Viral glycoprotein, gG-2, antibody in sera.

Results: The seroprevalence of HSV-2 among clinic attendees was 9.33%. Of these attendees only 22% presented with or reported a history of typical vesicular lesions in the genital area. Infection rate was  higher in patients with multiple sex partners (20.8% vs. 8.7%, P< ( 0.0023 in individuals aged 30 or older (12.6 vs. 6.4%, P = 0.03) and  in the Israeli Jewish population as compared to the Israeli Arab population (11.1% vs. 2.4%, P ~ 0.01). Females with multiple sex partners exhibited higher rates of infection than did their male counterparts (50 vs. 16.1%, P < 0.0275(.

Conclusion: The findings support the need for HSV-2 serologi  testing in patients presenting to STD clinics even when typical genital  lesions are not evident but where risk factors for HSV-2 infection are  identified.
 

Background: The osteoporosis-pseudoglioma syndrome is a rare autosomal recessive disorder characterized by severe juvenile-onset osteoporosis and congenital or early-onset blindness. Other manifestations include muscular hypotonia, ligamentous laxity, mild mental retardation and seizures. The gene responsible was recently identified to be the low density lipoprotein receptor-related family member LRP5 on chromosome 11q11-12.

Objective: To measure bone density in two siblings with the OPPG[1] syndrome as well as in their family members (parents and siblings).

Methods: Bone mineral density was determined in the lumbar spine (antero-posterior), femoral neck, two-thirds distal forearm (>95% cortical bone) and ultradistal forearm (predominantly trabecular bone) by dual-energy X-ray absorptiometry.

Results: The studies revealed osteoporotic changes both in the patients and the carriers.

Conclusion: The findings demonstrate that OPPG carriers have reduced bone mass, which is a risk factor for development of early osteoporotic changes.

____________________________________

Background: Primary hyperparathyroidism in elderly patients is usually associated with additional co-morbidity that increases operative risk, and thus many geriatric patients are denied the benefit of surgery for a single parathyroid adenoma.

Objectives:  To evaluate the safety and efficacy of accurate single photon emission computed tomography sestamibi scintigraphy, enabling precise localization of a single adenoma, in the geriatric population

Methods: Twenty-two patients aged 70 years and over with biochemically proven PHPT[1] and with a single parathyroid adenoma identified by localization studies (sestamibi SPECT[2] scan and ultrasonography) underwent 23 operations over 29 months (out of a total of 140 patients operated upon during the same period). Immediate preoperative sestamibi scintigraphy and marking of focal adenoma uptake followed by intraoperative hand-held gamma probe were used for the removal of the parathyroid adenoma by unilateral minimal access surgery. Associated major co-morbid conditions and pre- and postoperative calcium, phosphorus and parathormone levels were recorded. Indications for surgery were listed and operative and postoperative complications were noted. The patients were followed for a mean period of 17.7 months using the same parameters.

Results: The 22 patients with PHPT had a mean age of 76.3 ± 5.9 years (range 70–88 years)  and a female to male ratio of 13:9. Associated co-morbidity included ischemic heart disease (n=15), hypertension (n=22), non-insulin-dependent diabetes mellitus (n=9), chronic obstructive pulmonary disease (n=3), and previous neck surgery (n=3). Mean preoperative serum calcium, phosphorous and PTH[3] were 11.7 ± 1.3 mg/dl, 2.5 ± 0.5 mg/dl and 160.9 ± 75.4 pg/ml respectively. In 20 of the 22 patients, surgery was successful in curing PHPT (91%). One patient had persistent hypercalcemia due to a missed adenoma, and repeat operation (by focused minimal access surgery) was successfully performed 2 weeks later. There were no complications and no morbidity postoperatively. Mean postoperative serum calcium, phosphorous and PTH were 9.6 ± 1.2 mg/dl, 3.0 ± 0.5 mg/dl and 35.2 ± 24 pg/ml respectively. In all patients, serum calcium levels remained normal (9.7 ± 1.3 mg/ml) after long-term follow-up (mean 17.7 ± 9.6 months).

Conclusions: Minimally invasive, radio-guided focused parathyroidectomy for a single adenoma is a safe and effective method to cure hyperparathyroidism in the elderly. Success of surgery is directly related to the surgeon's experience and to the precise localization marking provided by sestamibi scintigraphic SPECT localization and concurrent sonographic findings.

Background: The incidence of malignant musculoskeletal tumors during pregnancy is very low. The paucity of data precludes the drawing of solid conclusions regarding a standard approach.

Objectives: To summarize our experience treating 13 pregnant women with malignant soft tissue or bone tumors.

Methods: We conducted a retrospective analysis of 13 cases of patients with either soft tissue or bone sarcoma that developed or progressed during pregnancy or immediately after delivery.

Results: The clinical presentation of the tumors was either a growing mass and/or increasing pain and disability. Most of the masses were located in the lower part of the body and of considerable size. Treatment given during gestation was limited to wide excision of the mass in the 28th week of gestation in one patient. All the patients reported disease progression during gestation. Vaginal delivery was possible in eight patients with no complications, cesarean section was carried out in three women, spontaneous miscarriage occurred in one and termination of pregnancy was performed in one patient.

Conclusions: The diagnostic and therapeutic approaches should be tailored specifically in every pregnant woman in whom sarcoma is suspected.
 

Background: Developments in laparoscopic surgery have rendered it an efficient tool for many complex surgical procedures. In the last few years, laparoscopic adrenalectomy has become a more viable option for removal of adrenal pathology, with many surgeons preferring it to the conventional open technique.

Objectives: To describe the indications, technique, complications and follow-up of patients undergoing laparoscopic adrenalectomy in our department.

Methods: The hospital files of 30 patients who underwent the procedure were reviewed. There were 19 females and 11 males with a mean age of 45 years. Indications for surgery differed and included hypersecreting adenoma, pheochromocytoma, suspected malignancy, and incidentaloma.

Results: Of the 31 laparoscopic adrenalectomies performed, 11 were right, 18 were left, and 1 was bilateral. The conversion rate to an open procedure was 3%. The mean duration of procedure was 120 minutes. Only one patient required blood transfusion. Complications occurred in 20% of patients, all reversible. There was no mortality. Mean hospitalization duration was 3.4 days, and median follow-up 17 months. There were no late complications. All patients operated on for benign diseases are alive.

Conclusions: Laparoscopic adrenalectomy appears to be a useful tool for the treatment of a range of adrenal pathologies.

Background: Non-gonococcal urethritis is the most common clinical diagnosis for men seeking care at sexually transmitted disease clinics.

Objective: To identify the pathogens involved in NGU[1] among males attending an Israeli STD clinic.

Methods: During 19 months spanning September 1996 to July 1998 we investigated a cohort of 238 male patients attending the Bnai Zion Medical Center STD[2] clinic with a clinical presentation of urethritis. Intraurethral swab specimens were tested for Neisseria gonorrhea, Ureaplasma urealyticum, Mycoplasma hominis, and Trichomonas vaginalis by culture and for herpes simplex virus by antigen detection. First voiding urine for Chlamydia trachomatis was done by polymerase chain reaction. The specific seropositivities of HSV[3] types 1 and 2 were tested by enzyme-linked immunosorbent assay.

Results: From among 238 males with dysuria or urethral discharge an etiology for urethritis was found for 71 (29.8%). N. gonorrhea was recovered in only three men (4.2%). In the remaining 68 NGU patients C. trachomatis (35/68, 51.5%) and U. urealyticum (31/68, 45.6%) were the most common infecting and co-infecting pathogens (P < 0.0001). M. hominis and T. vaginalis were found in 9/68 (13.2%), and 1 patient, respectively. HSV was recovered from the urethra in 7/68 males (10.3%) – 3 with HSV-1, 2 with HSV-2, and 2 were seronegative for HSV. None of these males had genital lesions. Although a single etiologic agent was identified in 45/68 infected men (66.2%), co-infection was common: 2 organisms in 15 (22%) and 3 organisms in 8 (11.8%).

Conclusion: C. trachomatis and U. urealyticum were the most common infecting and co-infecting pathogens in this cohort of men with NGU. Unrecognized genital HSV infections are common in males attending our STD clinic and symptomatic shedding of HSV occurs without genital lesions. Still, the microbial etiology in this group remains unclear in many patients despite careful microbiologic evaluation.

Background: Imaging-guided core needle biopsy is a well-established technique for the diagnosis of bone and soft tissue tumors and tumor-like lesions in specialized orthopedic oncology centers.

Objective: To present our results of computed tomography-guided core needle biopsy with assessment of the accuracy of the technique.

Methods: Between July 1998 and October 2000, 215 CT-guided core needle biopies were performed and histologically examined in the Unit of Bone and Soft Tissue Pathology, Tel Aviv Sourasky Medical Center. There were 80 soft tissue and 135 bony lesions. All biopsies were performed by the same radiologist and the histologic examination by the same pathologist.  To assess the accuracy of the procedure, we compared the diagnosis at biopsy with the diagnosis after definitive surgery (when available).

Results: Bone core needle biopsy (n = 135) showed malignancy in 89 cases (primary or recurrent bone sarcoma, lymphoma, myeloma, metastatic carcinoma or melanoma). There were 29 benign lesions. In 17 cases the result was inconclusive and an open incisional biopsy was performed. Of the 80 soft tissue biopsies, 35 were malignant (25 soft tissue sarcomas, 6 lymphomas, 4 metastatic carcinomas); 40 were benign (myositis ossificans, neurofibroma, desmoid tumor, schwannoma, hematoma and others), and 5 were inconclusive and followed by an open incisional biopsy. The core needle biopsy histologic diagnosis was compared with that of the definitive surgery and the diagnostic accuracy was 90%. Only three samples initially diagnosed as benign turned out to be malignant. No significant complications occurred during the procedures.

Conclusions: CT-guided CNB[1] of musculoskeletal lesions is a safe and effective procedure that assures sufficient and proper material for histologic examination. The accuracy of this method in our center was 90%. Tumor sampling is extremely important, especially in soft tissue sarcomas, and cores should be taken in different directions, including areas of necrosis. The processing is quick, especially for bone CNB, and diagnosis can be achieved within 24 hours. The material undergoes excellent fixation and the immunostains are reliable.