Israel Medical Association Journal

Background: Decreased lacrimal gland output may cause dry eye syndrome. Using a rat model, we examined the feasibility of transplanting lacrimal gland cells from newborns.

Objectives: To restore lacrimal gland function in eyes with compromised tear production.

Methods: A model of dry eye in adult rats was developed by unilateral surgical removal of the main lacrimal gland. Tear secretion in both eyes was then assessed by masked Schirmer's test. Lacrimal gland tissue from newborn rats was transplanted into the fibrous connective tissue in which the lacrimal gland had been embedded. Masked Schirmer's test was repeated 4, 8 and 12 weeks after transplantation.

Results: Schirmer's test performed in 13 rats 10 days after unilateral lacrimal gland excision revealed significantly less wetting on the side with excised gland compared with the normal side (P < 0.003). The lack of secreting cells on the operated side was verified histologically. The reduction in tear secretion on the operated side remained significant for 8 weeks on average. In the six rats with transplanted lacrimal gland tissue however, there were no differences in tear reduction between the two eyes at 4, 8 or 12 weeks after the operation (P = 0.81, 0.56 and 0.8, respectively).

Conclusions: Transplantation of lacrimal gland tissue from newborn rats effectively restored eye wetting in this new model. Further research is needed to evaluate this new approach for treating lacrimal gland dysfunction. Using this model might also facilitate evaluation of potential clinical treatments for dry eyes.
 

Objectives: To describe patients with initially misdiagnosed PTP[1] and to emphasize the diagnostic pitfalls of this disorder.

Patients and Results: During a period of 11 years we have diagnosed six patients with PTP, four women and two men. The incidence of PTP was approximately 1:24,000 blood components transfused. We present the detailed clinical course of three of the six patients in whom the diagnosis was particularly challenging. The patients were initially misdiagnosed as having heparin-induced thrombocytopenia, systemic lupus erythematosus complicated by autoimmune thrombocytopenia, and disseminated intravascular coagulation. A history of recent blood transfusion raised the suspicion of PTP and the diagnosis was confirmed by appropriate laboratory workup.

Conclusions: PTP seems to be more frequent than previously described. The diagnosis should be considered in the evaluation of life threatening thrombocytopenia in both men and women with a recent history of blood transfusion.

In Israel, updating of the National List of Health Services is performed on a yearly basis in a systematic and structured mechanism for almost a decade. The existence of such a mechanism is vital for keeping medicine up to date, since many innovative and breakthrough medical technologies continuously and frequently evolve. The 2006 update is unique in several aspects, relating both to the mechanism and to the decision-making process. In this article we describe notable issues that arose during the current process: modifications to the update mechanism, the four-phase increase in allocated resources to fund the addition of new medical technologies (including the addition of finances at the expense of the 2007 planned budget), and public funding for high-cost therapies. Finally, we discuss the impact of medical advances on healthcare costs and a suggested constant annual addition to the budget.

Background: Endobronchial stents are used to treat symptomatic patients with benign or malignant airway obstructions.

Objectives: To evaluate the safety and outcome of airway stent insertion for the treatment of malignant tracheobronchial narrowing.

Methods: The files of all patients with malignant disease who underwent airway stent insertion in our outpatient clinic from June 1995 to August 2004 were reviewed for background data, type of disease, symptoms, treatment, complications, and outcome.

Results: Airway stents were used in 34 patients, including 2 who required 2 stents at different locations, and one who required 2 adjacent stents (total, 37 stents). Ages ranged from 36 to 85 years (median 68). Primary lung cancer was noted in 35% of the patients and metastatic disease in 65%. Presenting signs and symptoms included dyspnea (82%), cough (11.7%), hemoptysis (9%), pneumonia (5.9%), and atelectasis (3%). The lesions were located in the left mainstem bronchus (31%), trachea (26%), right mainstem bronchus (26%), subglottis (14.3%), and bronchus intermedius (2.9%). Conscious sedation alone was utilized in 73% of the patients, allowing for early discharge. Eighteen patients (50%) received brachytherapy to the area of obstruction. Complications included stent migration (one patient) and severe or minimal bleeding (one patient each). Ninety-four percent of the patients reported significant relief of their dyspnea. Three of the four patients who had been mechanically ventilated before the procedure were weaned after stent insertion. Median survival from the time of stent placement was 6 months (range 0.25–105 months).

Conclusion: Stent placement can be safely performed in an outpatient setting with conscious sedation. It significantly relieves the patient's symptoms and may prolong survival.
 

Objectives: To determine whether reliable data could be obtained at lower cost.

Methods: The study sample consisted of 50 patients with mild to severe stable COPD]1[. All underwent pulmonary function test and the cardiopulmonary exercise test, 6 minute walk and 15 step exercise oximetry test as part of their regular follow-up visit. Functional capacity was graded according to each test separately and the functional capacities obtained were correlated.

Results: The results showed that most of the patients had severe COPD according to pulmonary function tests (mean forced expiratory volume in the first second 46.3 ± 19.9% of predicted value). There was a good correlation between the cardiopulmonary exercise test and the 6 minute walk functional capacity classes (r = 0.44, P = 0.0013). We did not find such correlation between the 15 step exercise oximetry test and the cardiopulmonary exercise test (r = 0.07, P = 0.64).

Conclusions: The study shows that the 6 minute walk is a reliable and accurate test in the evaluation of functional capacity in COPD patients.

Objectives: To evaluate the national Israeli experience with lung transplantation in patients with CF[1].

Methods: We reviewed the medical charts of all CF patients who underwent lung transplantation between January 1996 and June 2005 at the two Israeli centers that performed this procedure.

Results: Eighteen transplantations were performed in 17 patients. Mean patient age at transplantation was 25.3 ± 9.1 years, and mean duration of follow-up in survivors (n=14) was 37.2 months (range 1–113 months). The actuarial survival rate was 88% at 1 year and 74% at 5 years. Pulmonary function, expressed as percent of predicted normal forced expiratory volume in 1 sec, improved from 22.4 ± 8.1% to 76 ± 16.8% at one year after transplantation. Bronchiolitis obliterans syndrome was diagnosed in 5 patients (29%), of whom 2 died and 2 are currently candidates for retransplantation. Median time to onset of BOS[2] was 34.2 months (range 17–64 months).

Conclusion: In Israel, the early and intermediate-term results of lung transplantation for cystic fibrosis are encouraging. BOS remains a major complication that threatens long-term outcome.

Background: New drugs have significantly improved the prognosis and quality of life of patients with pulmonary arterial hypertension. However, PAH[1] associated with autoimmune disease, particularly progressive sclerosis, remains a very serious problem

Objectives: To evaluate whether the course of the disease and survival is significantly different in patients with PAH related to autoimmune disease as compared to other patients with PAH and to determine the prognostic factors in these patients.

Methods: We retrospectively compared 24 patients with PAH associated with autoimmune disease to 42 patients with other causes of PAH. We focused on the clinical and hemodynamic parameters and on the outcome.

Results: The early mortality rate was slightly higher in patients with PAH associated with autoimmune disease (13% after the first year, 25% after the fifth year). The prognostic factor was a shorter distance on the 6 minutes walking distance test (r = 0.2, P = 0.01).

Conclusions: The early detection of PAH associated with autoimmune disease should encourage earlier and more aggressive treatment than in idiopathic PAH.

In the last few decades there has been a tendency towards reinstitutionalization.

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

Background: Unexplained pulmonary hypertension is assumed to occur mainly in young adults.

Objectives: To describe the features of the disease in older patients and compare them to those in PHT[1] patients of all ages.

Methods: We conducted a retrospective evaluation of the files of patients over 65 years of age in whom UPHT[2] was diagnosed between 1987 and 1999 at two PHT centers serving a population of 4 million. Patients were followed for survival until March 2003. Clinical variables of the study patients were compared to those in PHT patients of all ages.

Results: The study group included 14 patients, 10 females and four males, with a mean age of 70.5 ± 6.7 years. The calculated mean annual incidence of UPHT for the study population was one new case per year per million persons. Seven patients (50%) had systemic hypertension. The mean interval from onset of symptoms to diagnosis was 8.3 months. At diagnosis, 64% of patients had functional capacity of III-IV according to the New York Heart Association classification, and 43% had right heart failure. Mean systolic pulmonary artery pressure was 80 ± 21 mmHg, peripheral vascular resistance 11.7 ± 7 mmHg/L/min, cardiac index 2.16 ± 0.81, and mean right atrial pressure 10.5 ± 5.9 mmHg. Median survival time was 43 months; survival rates for 1 year, 3 years and 5 years were 92.6%, 50%, 40%, respectively. Compared to data from the U.S. National Institute of Health Registry, UPHT in older patients is more common in females, but the incidence as well as clinical, hemodynamic and survival parameters are similar to those in PHT patients at any age.

Conclusions: UPHT occurs in the elderly more frequently than previously thought, with similar features in PHT patients of all ages. The coexistence of systemic and pulmonary hypertension warrants further investigation.

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.