Israel Medical Association Journal

Background: Hepatis C virus infection is presently an exclusion criterion to classify SjoÈ gren's syndrome; however, there are distinct clinicopathologic and biologic similarities between HCV-related and SS-related chronic inflammation of mucosa-associated lymphoid tissue and lymphoproliferation that suggest common pathogenetic pathways.

Objectives: To determine whether a subset of patients with sicca syndrome and HCV infection may present a true primary SS rather than a distinct clinicobiologic entity.

Methods: We extensively characterized 20 consecutive patients with positive anti-HCV antibodies and heavy subjective dry eye and/or dry mouth symptoms, plus positive unstimulated sialometry and/or Shirmer's test. We then compared these features with those in HCV-negative primary SS controls (classified according to the latest American-European Consensus Group Classification Criteria for SS).

Results: Of the 20 HCV-positive patients with sicca manifesta-tions, 12 (60%) had positive anti-SSA/SSB antibodies (3/12 by enzyme-linked immunosorbent assay and 6/12 by immunoblot) and/or positive salivary gland biopsy (at least 1 focus/4 mm2), which met the strict classification criteria for SS, as in the case of HCV-negative SS controls. Comparing the HCV-positive SS subset with HCV-negative SS controls showed similar female to male ratio (11/1 vs. 46/4), major salivary gland swelling (17% vs. 26%), positive antinuclear antibodies (75 vs. 94%) and positive rheumatoid factor (58 vs. 52%). Significant differences (P< 0.05) were seen in mean age (69 vs. 56 years), liver disease (50 vs. 2%), lung disease (25 vs. 0%), anti-SSA/SSB positivity (25 vs. 90%), and low C3 or C4 (83 vs. 36%). HCV-positive SS patients exhibited a trend for more frequent chronic gastritis (50 vs. 22%), fibromyalgia (33 vs. 14%), peripheral neuropathy (33 vs. 18%), purpura (33 vs. 19%) and cryoglobulinemia (33 vs. 6%).

Conclusions: A major subset of HCV-positive patients with definite subjective sicca symptoms and positive objective tests may indeed present a true, though peculiar, subset of SS. There are strict similarities with key clinical, pathologic and immunologic findings of definite HCV-negative SS. Other features appear more characteristic of HCV infection. When also considering that HCV is sialotropic and may be treated, HCV-related chronic sialadenitis represents a unique opportunity to clarify key pathogenetic events occurring in the large majority of HCV-negative SS; and similarities to typical primary SS, rather than differences, should be taken into account.
 

Background: Despite advances in cancer therapy the treatment of liver tumors remains a challenge. Most patients are poor candidates for surgical resection; both chemotherapy and irradiation have a low success rate and neither is without complications. New minimally invasive techniques for ablation of unresectable tumors have gained attention as effective treatment alternatives. Among these are percutaneous ethanol injection and radiofrequency ablation; both are effective for primary liver tumors and RFA is also effective for hepatic metastases.

Objective: To report our experience with PEI and RFA in the treatment of hepatic lesions.

Methods: The study included 49 lesions in 27 patients: 23 primary lesions in 13 patients treated with PEI and 26 lesions (22 secondary and 4 primary) in 14 patients treated with RFA. PEI was performed on an outpatient basis in the ultrasound suite; RFA was done in hospitalized patients (9 in the ultrasound suite and 4 in the operating room). Patients were followed with triphasic spiral computerized tomography 1 month after treatment and every 3±6 months thereafter.

Results: Complete necrosis was achieved with PEI on the first attempt in 11 of 23 primary lesions (91.3%). In 8.7% (2/23) a second series of treatments was required. Using RFA, complete necrosis was achieved in 85% of lesions (22/26) and partial necrosis in 15% (4/26). Complications included low fever (3 patients), high fever and abscess formation (1 patient), peri-tumoral necrosis (1 patient ) and portal vein thrombosis (1 patient ).

Conclusions: Our preliminary results confirm that PEI and RFA are an effective and safe option for treating hepatic tumors in patients unfit for surgery.
 

The addition of methotrexate to treatment protocols in children with acute lymphoblastic leukemia has been found beneficial in preventing central nervous system relapse. However, MTX[1] itself may be associated with neurologic morbidities, the most significant of which is leukoencephalopathy. The present study describes the clinical spectrum of leukoencephalopathy, which ranges from a subclinical disease manifested only radiologically to a progressive, devastating encephalopathy. The interaction of MTX with other components of the treatment protocol is discussed, as is the effect of leucovorin. A summary is presented of the metabolic pathways that may be involved in the development of MTX toxicity. Researchers are still seeking a biochemical marker to aid in the determination of the amount of MTX that may be safely administered.

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Background: Acarbose has become an important adjuvant therapy for diabetic patients. Many of these patients are also treated with digoxin for congestive heart failure or chronic atrial fibrillation

Objective: To evaluate a possible drug interaction between acarbose and digoxin.

Methods: An open-label, analyst-blind, randomized, crossover, two-period study was conducted in 11 healthy subjects. In period I, each subject received one single oral dose of 0.75 mg digoxin. In period ll, they were given acarbose tablets., 60 mg-3 times a day for 12 days. On day 8, one hour after acarbose administration, a single oral dose of 0.75 mg digoxin was administered. The study periods were separated by a 3 week washout interval: Serum. digoxin levels., over. time, in the two periods were compared by standard techniques;

Results: There were no differences in the pharmacokinetic parameters of digoxin in the two periods, apart from a significant increase in the mean maximum serum concentration (Cmax) when digoxin was given with acarbose (5.97 compared to 4.67 g/L, P = 0.02). Simulated steady-state peak levels of digoxin (Cmax,ss) achieved with a daily dose of 0.25 mg digoxin, in the presence.and absence of acarbose, were 2.89 and 2.40 g/L respectively (P =0.05); Simulated steady-state trough (Cmin,ss) and average (Cave,ss) concentrations were similar and within the therapeutic window.

Conclusion: There was no significant pharmacokinetic interaction between digoxin and acarbose at current therapeutic doses in the healthy volunteers. This interaction should be further studied with higher doses of acarbose and at steady-state conditions.
 

Fanconi anemia is a rare autosomal recessive disorder characterized clinically by congenital abnormalities, progressive bone marrow failure, and a predisposition to malignancy. FA cells are sensitive to DNA cross-linking agents. Complementation analysis of FA cells using somatic cell fusion has facilitated the identification of eight complementation groups, suggesting that FA is a genetically heterogeneous disorder. Six genes (FANCA, FANCC, FANCD2, FANCE, FANGF, FANCG) have been cloned so far. The majority of affected patients belong to FA group A. Of the 32 unrelated Israeli patients with FA that we studied, 6 carried the FANCC mutations and 15 the FANCA mutations. Among the Jewish patients, ethnic-related mutations were common. Recent cumulative evidence suggests that the FA proteins are repair proteins. FANCC, FANCA and FANCG bind and interact in a protein complex found in the cytoplasm and nucleus of normal cells. FANCD2 exists in two isoforms; the long active form, FANCD2-L, is absent from FA cells of all complementation groups. FANCD2 co-localized with BRCA1 in unclear foci, probably as part of a large genomic surveillance complex. Studies using FANCA and FANCC knockout mice suggest that bone marrow precursors express interferon-g hypersensitivity and show progressive apoptosis. The definition of the molecular basis of FA in many affected families now enables prenatal diagnosis.

Background: Low density lipoprotein apheresis is used as a complementary method for treating hypercholesterolemic patients who cannot reach target LDL[1]-cholesterol levels on conventional dietary and drug treatment. The DALI system (direct absorption of lipoproteins) is the only extracorporeal LDL-removing system compatible with whole blood.

Objective: To describe our one year experience using the DALI[2] system.

Methods: LDL apheresis was used in 13 patients due to inability to reach target LDL-C levels on conventional treatment. They included seven patients with familial hypercholesterolemia, three who had adverse reactions to statins, and three patients with ischemic heart disease who did not reach LDL-C target level on medical treatment.

Results: The average triglyceride, total cholesterol, high density lipoprotein-C and LDL-C levels before and after treatment in all patients were: 170 ± 113 vs. 124 ± 91, 269 ± 74 vs. 132 ± 48, 42 ± 8 vs. 37 ± 7.9, and 196 ± 77 vs. 80 ± 52 mg/dl, respectively. Comparing the results of a subgroup of seven patients who had previously been treated with plasma exchange, it is noteworthy that while the reduction in triglyceride, total cholesterol and LDL-C are comparable, the effect on HDL[3]-C concentration was less apparent: from an average of 39.7 ± 8.7 and 23 ± 5.7 mg/dl before and after plasma exchange to an average of 43.9 ± 8.1 and 38.4 ± 7 mg/dl before and after LDL apheresis, respectively. Five patients developed treatment-related adverse events: three experienced allergic reactions manifested as shortness of breath, urticaria and facial flushing; one patient developed rhabdomyolysis, an adverse reaction that was not reported previously as a result of LDL apheresis; and one patient had myopathy with back pain. All untoward effects occurred during the first few treatment sessions.

Conclusions: LDL apheresis using the DALI system is highly efficacious for the treatment of hypercholesterolemia. It is associated with a significant number of side effects occurring during the first treatment sessions. In patients not experiencing adverse effects in the early treatment period, it is well tolerated, and can provide remarkable clinical benefit even after short-term therapy.

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Because of its high case-fatality rate, its very high transmission potential, and the worldwide shortage of effective vaccine, smallpox tops international lists of over a dozen possible bioterror and biologic warfare agents. In a scenario involving aerosol variola virus release, tens to hundreds of first-generation cases would ensue, as would hundreds to thousands of subsequent cases resulting from person-to-person transmission. A smallpox outbreak in Israel must not be regarded as a doomsday event: the methods of smallpox outbreak control are known and will be implemented. The rapidity with which organized outbreak control measures are competently executed will determine how many generations of cases occur before the outbreak is brought under control. Planning, vaccine stockpiling, laboratory expansion, professional training and public education, all carried out well in advance of an epidemic, will minimize the number of casualties. The reinstitution of routine smallpox vaccination in Israel, as in other countries, must be given serious consideration, since it has the potential for eliminating the threat of smallpox as a bioterror agent.

Background: The ear is the most frequent organ affected during an explosion. Recognition of possible damage to its auditory and vestibular components, and particularly the recovery time of the incurred damage, may help in planning the optimal treatment strategies for the otologic manifestations of blast injury and preventing deleterious consequences.   

Objective: To report the results of the oto-vestibular initial evaluation and follow-up of 17 survivors of a suicidal terrorist attack on a municipal bus.

Methods: These 17 patients underwent periodic ear inspections and pure tone audiometry for 6 months. Balance studies, consisting of electronystagmography (ENG) and computerized dynamic posturography (CDP) were performed at the first time possible.

Results: Complaints of earache, aural fullness and tinnitus resolved, whereas dizziness persisted in most of the patients. By the end of the follow-up, 15 (55.6%) of the eardrum perforations had healed spontaneously. Hearing impairment was detected in 33 of the 34 tested ears. Recovery of hearing was complete in 6 ears and partial in another 11. ENG and CDP were performed in 13 patients: 5 had abnormal results on CDP while the ENG was normal in all the patients. The vertigo in seven patients resolved in only one patient who was free of symptoms 1 month after the explosion.

Conclusion:  Exposure to a high powered explosion in a confined space may result in severe auditory and vestibular damage. Awareness of these possible ear injuries may prevent many of the deleterious consequences of such injuries.