Israel Medical Association Journal

Objectives: To minimize ventilatory limitation during training of patients with severe COPD[1] by applying bi-level positive pressure ventilation during training in order to augment training intensity (and effect).

Methods: The study group comprised 19 patients (18 males, 1 female) with a mean age of 64 ± 9 years. Mean forced expiratory volume in 1 second was 32 ± 4% of predicted, and all were ventilatory-limited (exercise breathing reserve 3 ± 9 L/min, normal >15 L/min). The patients were randomized: 9 were assigned to training with BiPAP[2] and 10 to standard training. All were trained on a treadmill for 2 months, twice a week, 45 minutes each time, at maximal tolerated load. Incremental maximal unsupported exercise test was performed before and at the end of the training period.

Results: BiPAP resulted in an increment of 94 ± 53% in training speed during these 2 months, as compared to 41 ± 19% increment in the control group (P < 0.005). Training with BiPAP yielded an average increase in maximal oxygen uptake of 23 ± 16% (P < 0.005), anaerobic threshold of 11 ± 12% (P < 0.05) and peak O₂ pulse of 20 ± 19% (P < 0.05), while peak exercise lactate concentration was not higher after training. Interestingly, in the BiPAP group, peak exercise ventilation was also 17 ± 20% higher after training (P < 0.05). Furthermore, contrary to our expectation, at any given work rate, ventilation (and tidal volume) in the BiPAP group was higher in the post-training test as compared to the pre-training test, and the end tidal partial pressure of CO₂ at 55 watts was lower, 40 ± 4 and 38 ± 4 mmHg respectively (P < 0.05). No improvement in exercise capacity was observed after this short training period in the control group.

Conclusion: Pressure-supported ventilation during training is feasible in patients with severe COPD and it augments the training effect. The improved exercise tolerance was associated with higher ventilatory response and therefore lower P_ETCO₂[3] at equal work rates after training.

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[1] COPD = chronic obstructive pulmonary disease

[2] BiPAP = bi-level positive pressure ventilation

[3] P_ETCO₂ = end tidal partial pressure of CO₂
 

Background: Continuous positive airway pressure is the treatment of choice for patients with obstructive sleep apnea syndrome.

Objective: To determine the factors influencing treatment initiation with a CPAP[1] device in a healthcare system in which co-payment is required.

Methods: A total of 400 adult patients with OSAS[2] who required CPAP therapy completed questionnaires at three different stages of the diagnostic and therapeutic process: CPAP titration study (stage 1), patient adaptation trial (stage 2), and purchase of a CPAP device (stage 3). Logistic regression was used to analyze the variables influencing CPAP use at the different stages of the diagnostic and therapeutic processes.

Results: Only 32% of the patients who underwent CPAP titration study purchased a CPAP device. The number of subjects who purchased a CPAP device increased gradually as monthly income increased, 28% vs. 62% in the “very low” and “very high” income levels respectively. Reporting for the titration increased in patients with excessive daytime sleepiness and an Epworth Sleepiness Scale score above 9 (odds ratio = 1.9, P = 0.015). Higher socioeconomic status increased reporting to stage 2 (OR[3] = 1.23, P = 0.03) and CPAP purchase (stage 3, OR = 1.35, P = 0.002). Excessive daytime sleepiness increased reporting to stage 2 (OR = 2.28, P = 0.006). Respiratory disturbance index above 35 increased CPAP purchasing (OR = 2.01, P = 0.022). Support from the bed partner, referring physician and sleep laboratory team increased CPAP purchasing.

Conclusions: A supportive environment for a patient with OSAS requiring CPAP is crucial to increase initiation of CPAP treatment. Minimizing cost sharing for the CPAP device will reduce inequality and may increase CPAP treatment initiation.

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.

Background: In patients with Graves’ ophthalmopathy, orbital decompression surgery is indicated for compressive optic neuropathy, severe corneal exposure, or for cosmetic deformity due to proptosis. Traditionally this has been performed through a transantral approach, but the associated complication rate is high. More recently, endoscopic orbital decompression has been performed successfully with significantly fewer postoperative complications.

Objective: To report our experience of endoscopic orbital decompression in patients with severe Graves’ ophthalmopathy.

Methods: Three patients (five eyes) underwent endoscopic orbital decompression for Graves’ ophthalmopathy at Soroka Medical Center between the years 2000 and 2002. The indications for surgery were compressive optic neuropathy in three eyes, severe corneal exposure in one eye, and severe proptosis not cosmetically acceptable for the patient in one case. An intranasal endoscopic approach with the removal of the medial orbital wall and medial part of the floor was performed.

Results: In all five eyes an average reduction of 5 mm in proptosis was achieved. Soon after surgery, visual acuity improved in the three cases with compressive optic neuropathy, and exposure keratopathy and cosmetic appearance improved. The diplopia remained unchanged. No complications were observed postoperatively.

Conclusions: Endoscopic orbital decompression with removal of the medial orbital wall and medial part of the floor in the five reported eyes was an effective and safe procedure for treatment of severe Graves’ ophthalmopathy. A close collaboration between ophthalmologists and otorhinolaryngologists skilled in endoscopic sinus surgery is crucial for the correct management of these patients.

Background: Pulmonary disease is the most frequent cause of morbidity and mortality in cystc fibrosis patients. New techniques such as non-invasive positive pressure ventilation have resulted in prolongation of life expectancy in CF[1] patients with end-stage lung disease.

Objectives: To determine the role of NIPPV[2] in CF patients awaiting lung transplantation.

Methods: Between 1996 and 2001 nine CF patients (5 females) with end-stage lung disease were treated with bi-level positive airway pressure ventilation in the "spontaneous" mode.

Results: The patients' mean age at initiation of BiPAP[3] was 15 years (range 13–40 years) and the mean duration of BiPAP usage was 8 months (range 3–16 months). Four patients underwent successful lung transplantation, three patients died while awaiting transplantation, and the remaining two are still on NIPPV while waiting for transplantation. Patients' body mass index increased significantly (P < 0.05) during BiPAP therapy (from 16.1 to 17.2 kg/m²). Blood pH, p_aCO₂, and bicarbonate improved significantly (from 7.31 to 7.38, 90.8 to 67.2 mmHg, and 48.9 to 40.3 mEq/L, respectively). Pulmonary function tests were not affected by BiPAP usage. The patients experienced a significant alleviation in morning headaches and improvement in quality of sleep (P < 0.003). There were no major complications during BiPAP usage.

Conclusions: We demonstrated that long-term NIPPV can stabilize and improve physiologic parameters such as ventilation, arterial blood gases and body mass index, as well as subjective symptoms such as sleep pattern, daily activity level, and morning headaches in CF patients with end-stage lung disease. Further prospectively controlled studies are needed to evaluate the potential of BiPAP therapy and its influence on morbidity and mortality in the post-lung transplantation period.

Background: The highly tissue-specific trafficking of normal and malignant lymphocytes to particular organs is mediated by adhesion molecules, or “homing receptors.” Among our patients with B cell chronic lymphocytic leukemia 15% demonstrate predominantly splenic manifestations and are classified as stage II(S).

Objective: To investigate whether expression of cell surface adhesion molecules can distinguish stage II(S) patients from stage 0 or stage 0 and I CLL[1] patients.

Methods: Expression of adhesion molecules belonging to different families was studied in CD19-positive cells isolated from the blood of 42 patients by dual color flow cytometry. The families included: immunoglobulin superfamily (CD54, CD58), integrin family (β1, β2 and β3 chains, CD11a, CD11c CD49d), selectin family (L-selectin), and lymphocyte homing receptor family (CD44).

Results: The average percentage of leukemic cells expressing CD11c in the 23 patients with stage II(S) was 25.7 compared with 13.2% in the 14 patients with stage 0 disease (P = 0.047). The average percentage of leukemic cells expressing CD44 in patients with stage II(S) was 90.5 compared with 77.2% in patients with stage 0 (P = 0.007) and 80% in patients with stages 0 and I together (n=19, P = 0.008). Other adhesion molecules tested did not show a statistically significance difference in expression between the different disease stages.

Conclusions: The higher expression of CD44 and CD11c in cells of CLL patients with predominantly splenic manifestations may account for the tendency of their lymphocytes to home to the spleen.

Background: The Israeli Blood Pressure Control program was initiated to enhance the control of modifiable risk factors among high risk hypertensive patients followed by general practitioners in Israel.

Objective: To report the baseline results of the state of the treatment regarding blood pressure management, lipid and glucose control as well as obesity and smoking cessation among the patients.

Methods: Hypertensive patients were screened in 30 general practice clinics supervised by family medicine specialists seeing 1,000–5,000 patients each. Between 50 and 250 hypertensive patients were diagnosed at each participating clinic. Blood pressure levels, body mass index, lipid and glucose levels, as well as target organ damage and medications were recorded for all patients.

Results: Of the 4,948 patients registered, 2,079 were males (42%). Mean age was 64.8 ± 12. Blood pressure control was achieved in only 33.1% of total hypertensive patients. Low density lipoprotein control was achieved in 31.1% of all patients, and glucose control in only 28.5%% of diabetic patients (glucose < 126 mg/dl); 20.7% of the diabetics had glucose levels above 200 mg/dl. In this group of patients 38.9% were obese (BMI[1] >30 kg/m²). While there were more obese females than males (48.0% vs. 35.6%), no difference was found in blood pressure, lipid or glucose control between the genders.

Conclusion: Risk factor management of hypertensive patients attending general practice clinics in Israel is not optimal, especially among those with diabetes or in need of secondary prevention measures. A long-term intervention program for high risk patients in the community is needed to improve the current situation.

Background: Recent advances in immunosuppressive therapy have led to a substantial improvement in the outcome of kidney transplantation. Living unrelated donors may become a source of additional organs for patients on the kidney waiting list.

Objectives: To study the impact of combination of calcineurin inhibitors and mycophenolate-mofetile, together with steroids, on outcomes of living related and unrelated transplants. 

Methods: Between September 1997 and January 2000, 129 patients underwent living related (n=80) or unrelated (n=49) kidney transplant. The mean follow-up was 28.2 months. Immunosuppressive protocols consisted of MMF[1] with cyclosporine (41%) or tacrolimus (59%), plus steroids. Patient and graft survival data, rejection rate, and graft functional parameters were compared between the groups.

Results: LUD[2] recipients were older (47.8 vs. 33.6 years) with higher number of re-transplants (24.5% vs. 11.2% in LRD[3] recipients, P < 0.05). Human leukocyte antigen matching was higher in LRD recipients (P < 0.001). Acute rejection developed in 28.6% of LUD and 27.5% of LRD transplants (P = NS). Creatinine levels at 1, 2 and 3 years post-transplant were 1.6, 1.7 and 1.7 mg/dl for LRD patients and 1.5, 1.5 and 1.3 mg/dl for LUD recipients (P = NS). There was no difference in patient survival rates between the groups. One, 2 and 3 year graft survival rates were similar in LRD (91.3%, 90% and 87.5%) and LUD (89.8%, 87.8% and 87.8%) recipients.

Conclusions: Despite HLA[4] disparity, rejection and survival rates of living unrelated transplants under current immunosuppressive protocols are comparable to those of living related transplants.

Vasopressin is a potent endogenous vasoconstrictor that increases blood pressure and systemic vascular resistance. The administration of exogenous vasopressin during closed and open cardiopulmonary resuscitation in humans was shown to be more effective than optimal doses of epinephrine in several clinical studies. We summarize here the recent experimental and clinical data on the use of vasopressin in cardiopulmonary resuscitation and septic shock. As the use of vasopressin in human resuscitation is now in its early stages, it is expected that accumulated future experience will shed more light regarding the risk-benefit aspects of its use.