Israel Medical Association Journal

Obstructive sleep apnea syndrome is a major public health hazard affecting 2–4% of the adult population; only 10% of these patients are recognized by healthcare providers. In the last decade the number of referrals for polysomnography increased threefold in Israel, compared to 12-fold worldwide, and is expected to increase even more in the coming years. This constant demand for PSG[1] studies is beyond the current capacity of sleep laboratories, thus preventing diagnosis for most patients with suspected OSAS[2]. In the current review, we examine problems facing decision-makers on how to treat the increasing flood of patients presenting with symptoms suggestive of sleep-disordered breathing. We evaluate the cost-effectiveness of current technologies for OSA diagnosis, i.e., laboratory versus at-home technologies. We conclude that no current alternative exists to the use of PSG for OSA diagnosis. When at-home technologies are suggested for OSAS diagnosis, data should be provided on factors influencing its cost-effectiveness, e.g., accuracy rates of diagnosis, relative cost of human resources, and case-mix of patients tested. Since PSG remains the gold standard for diagnosis of OSAS, in Israel resources should be allocated to increasing the volume of beds for PSG studies in order to increase access to diagnosis and treatment, which in turn provides better quality of life, saves scarce resources of the healthcare system, prevents unnecessary accidents and increases workers’ productivity.

Background: Prone sleeping has been recognized as a risk factor for sudden infant death syndrome. Ten years ago, non-prone sleeping was recommended in many countries around the world including Israel. The rate of infants sleeping prone and the rate of parents' adherence with the recommendations have not been studied.

Objectives: To study infants' sleep position and parents’ adherence to recommendations, and to identify risk factors for prone sleeping following the campaign to prevent prone sleeping in the Israeli population.

Methods: We conducted a longitudinal telephone survey with the parents of 608 randomly selected 2 month old infants, repeated at 4 and 6 months.

Results: Non-prone sleeping decreased from 75% to 67% and 63% at 2, 4 and 6 months respectively. There was a significant relationship between prone positioning and the use of a home apnea monitor at 2 months (P = 0.038, odds ratio 1.37, 95% confidence interval 0.94–2.15). Other risk factors for prone sleeping were the level of religious practice, with ultra-Orthodox Jews having the highest prevalence (2 months: OR[1] 2.78, 95% CI[2] 1.75–4.55) and higher parity – especially in families with more than five children (P = 0.041).

Conclusions: The prone sleeping position is relatively high in Israel. Groups at high risk were closely associated with the level of religiousness and parity. Efforts to promote supine sleeping should be directed towards identifiable groups.

Background: The external approach is the golden standard for sinonasal tumor removal but it is associated with several side effects, including facial scars, intracranial and extracranial complications, a long hospitalization period and high costs. Endoscopic sinus surgery enables resection of benign and selected malignant sinonasal tumors and has the advantages of no facial scars, better functional and structural preservation of the sinonasal complex, minimal trauma to surrounding tissue, a shorter hospitalization stay and lower costs.

Objectives: To evaluate the advantages and limitations of endoscopic resection of benign and malignant sinonasal tumors, their recurrence and complication rates.

Methods: The medical and radiology records of 56 patients who underwent endonasal endoscopic resection of benign and malignant sinonasal tumors between 1996 and 2003 were retrospectively reviewed. Tumors located in the center of the nose and sinuses were endoscopically resected.

Results: Six cases of malignant tumor and 50 cases of benign tumor underwent resection by ESS[1]. One of the patients with malignant tumor died, the remainder showing no evidence of disease on follow-up of 3–60 months (mean 26.8 months). Inverted papilloma was the most common benign tumor (40 patients). Seven patients (18%) had recurrence followed by endonasal resection. No major complications were recorded. Hospitalization stay was 2–7 days (mean 3.6 days).

Conclusions: Endoscopic resection of benign sinonasal tumors that are centrally located in the nose and sinuses should be considered before the external approach is used. In very carefully selected cases of malignant tumors ESS is oncologically acceptable, but more experience is needed for discerning the indications for endoscopic resection of malignant tumors. The complication rate for endoscopic resection is low, there are no facial scars, hospitalization stay is short, and costs are low.

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: 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.
 

Cancer is a multi-step disease involving a series of genetic alterations that result in the loss of control of cell proliferation and differentiation. Such genetic alterations could emerge from the activation of oncogenes and the loss or malfunctioning of tumor suppressor gene activity. Our understanding of cancer has greatly increased through the use of DNA tumor viruses and their transforming proteins as a biological tool to decipher a cascade of events that lead to deregulation of cell proliferation and subsequent tumor formation. For the past ten years our laboratory has focused on the molecular biology of the human neurotropic papovavirus, JCV. This virus causes progressive multifocal Ieukoencephalopathy, a fatal neuro­degenerative disease of the central nervous system in immunocompromised patients. JCV is a common human virus that infects more than 80% of humans but does not induce any obvious clinical symptoms. The increased incidence of acquired immune deficiency syndrome and the use of immunosuppressive chemotherapy have dramatically raised the incidence of PML. The coincidental occurrence of malignant astrocytes and oligodendrocytes in PML patients, coupled with the induction of glioblastoma in JCV-intected non­human primates, provides intriguing speculation on the association between JCV and CNS malignancies. In this report we discuss clinical data and laboratory observations pointing to the direct involvement of JCV in cancer.

The novel neuropeptides hypocretin/orexin have recently been located on the lateral hypothalamus cells. This system has been linked to the regulation of both feeding and sleep, and recent studies have found an association between a defect in these neuropeptides and narcolepsy. We conducted a MED­LINE review of all the articles published since the discovery of hypocretin/orexin peptides, narrowing the field to the relation­ship between these neuropeptides and sleep. The finding of a deletion in the transcription of the hypocretin receptor 2 gene in narcoleptic Doberman pinschers and the development of a knockout of the hypocretin gene in mice pointed to the relevance of this system in the sleep-wake cycle. We provide further evidence of the role of the hypocretin/orexin system in narcolepsy and in sleep regulation and present an integrative model of the pathophysiology of narcolepsy. The discovery of the link between these peptides and narcolepsy opens new avenues to both the understanding of sleep mechanisms and therapeutic implications for sleep disorders.