Israel Medical Association Journal

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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Background: The implementation of treatment guidelines is lacking worldwide.

Objectives: To examine whether follow-up in a specialized lipid clinic improves the achievement rate of the treatment guidelines, as formulated by the National Cholesterol Education Program and the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure.

Methods: The study group included patients who were referred to the lipid clinic because of hyperlipidemia. At each of five visits over a 12 month period, lipid levels, liver and creatine kinase levels, body mass index, and adherence to diet and medications were measured, and achievement of the NCEP[1] target level was assessed.

Results: A total of 1,133 patients (mean age 61.3 years, 60% males) were studied. Additional risk factors for atherosclerosis included hypertension (41%), type II diabetes mellitus (21%), smoking (17%), and a positive family history of coronary artery disease (32%). All patients had evidence of atherosclerotic vascular disease (coronary, cerebrovascular or peripheral vascular diseases). The low density lipoprotein target of <100 mg was present in only 22% of patients before enrollment, with improvement of up to 57% after the follow-up period. During follow-up, blood pressure control was improved (from 38% at the time of referral to 88% after 12 months, P < 0.001), as was glycemic control in diabetic patients (HgA₁C improved from 8.2% to 7.1% after 12 months, P < 0.001). Improved risk factor control was due to increased compliance to medication treatment (from 66% at enrollment to more than 90% after 12 months), as well as careful attention to risk factor management that translated into a change in the treatment profile during the follow-up. There was an increase in the use of the following medications: aspirin from 68% to 96%, statins from 42% to 88%, beta blockers from 20% to 40%, and angiotensin-converting enzyme inhibitors from 28% to 42%; while calcium channel blocker use decreased from 40% to 30% in patients during follow-up.

Conclusion: Follow-up of patients in a specialized clinic enhances the achievement of LDL[2]-cholesterol treatment goals as well as other risk factor treatment goals, due to increased patient compliance and increased use of medications.

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Background: Obesity is among the well-established risk factors for cardiovascular morbidity and mortality. However, the exact mechanisms are not well understood. Low concentrations of vitamins (fat soluble antioxidants and B vitamins) are linked to accelerated atherosclerosis through increased oxidative stress and homocysteine.

Objective: To compare plasma antioxidant vitamins (carotenoids and vitamin E), B vitamins (folic acid and B12) and homocysteine – all linked to increased cardiovascular morbidity – between patients with severe obesity and lean control subjects.

Methods: We investigated plasma carotenoids, vitamin E, folic acid, B12, and homocysteine in 25 obese patients and their age-matched controls (body mass index 38 ± 3 vs. 21 ± 2 kg/m²), respectively), related to BMI[1] and plasma insulin.

Results: Patients with obesity had normal B vitamins and a non-significant decrease in plasma homocysteine as compared to controls (9.4 ± 2.6 vs. 11.4 ± 4.8 mmol/L, P = 0.07). There was a significant decrease in both plasma carotenoids and vitamin E (0.69 ± 0.32 vs. 1.25 ± 0.72 and 24 ± 10 vs. 33 ± 14 mg/ml, respectively; P < 0.01). Both vitamins were inversely related to BMI and plasma insulin, which was significantly increased in patients with obesity (22 ± 21 vs. 6 ± 2 mU/ml, P < 0.01).

Conclusions: Obese patients with BMI above 35 kg/m² show low plasma antioxidants (carotenoids and vitamin E). This may result in increased oxidative stress and consequently enhanced atherosclerosis in these patients.

The chemical warfare agent sulfur mustard affects primarily the eyes, skin and respiratory tract. Of these, ocular injury is the most immediate and distressing. Learning to recognize ocular injury enables the treating physician to provide early and suitable treatment, which will reduce complications and allow the victim a rapid recovery.

Background: Hyperlipidemia is a major risk factor for coronary heart disease. Reducing low density lipoprotein-cholesterol can significantly reduce the risk of CHD[1], but many patients fail to reach the target LDL-C[2] goals due to low doses of statins or low compliance.

Objectives: To treat high risk patients with atorvastatin in order to reach LDL-C goals (either primary or secondary prevention) of the Israel Atherosclerosis Society.

Methods: In this open-label study of 3,276 patients (1,698 of whom were males, 52%), atorvastatin 10 mg was given as a first dose, with follow-up and adjustment of the dose every 6 weeks. While 1,670 patients did not receive prior hypolipidemic treatment, 1,606 were treated with other statins, fibrates or the combination of both.

Results: After 6 weeks of treatment, 70% of the patients who did not receive prior hypolipidemic medications and who needed primary prevention reached target LDL-C levels. Interestingly, a similar number of patients on prior hypolipidemic treatment reached the LDL-C goals for primary prevention. The patients treated with other statins, fibrates or both did not reach the LDL-C treatment goals. Only 34% of all patients who needed secondary prevention reached the ISA[3] LDL-C target of 100 mg/dl. Atorvastatin proved to be completely safe; only two patients had creatine kinase elevation above 500 U/L, and another six had mild CK[4] elevation (<500 U/L). None of the patients had clinical myopathy, and only one had to be withdrawn from the study.

Conclusion: Atorvastatin is a safe and effective drug that enables most patients requiring primary prevention to reach LDL-C goal levels, even with a low dose of 10 mg. Patients in need of secondary prevention usually require higher doses of statins.

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Background: Femoral hip fractures are a common occurrence in the elderly. Of the various fracture patterns, intertrochanteric injuries have the lowest rate of complications. Case reports of ensuing subcapital fracture have all been linked to incorrect placement of fixation devices or to osteomyelitis, while cases of avascular necrosis have only been reported rarely in the literature and are considered to occur at the rare rate of 0.8%.

Objectives: To check the incidence and outcome of AVN[1] in intertrochanteric hip fractures.

Methods and Results: In a retrospective analysis of patients who had surgical treatment for intertrochanteric fractures, 10 patients (0.5%) underwent dynamic hip screw fixation for intertrochanteric fractures and subsequently developed painful AVN as their primary presentation. Three of these patients were also found to have subcapital fractures. On revision of the primary fixation no fault was found with nail placement.

Conclusions: The reported rate of AVN may be understated since many patients have limiting factors that prevent them from consulting a physician when in pain, and one-third of these patients die within 2 years. Therefore, we suggest that hip pain following fixation of an intertrochanteric fracture should prompt the clinician to consider the rare possibility of AVN or subcapital fracture.

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[1] AV = avascular necrosis

Background: Genetic factors have been shown to play a major role in the development of peak bone mass, with hereditability accounting for about 50-85% of the variance in bone mass. Numerous candidate genes were proposed to be involved in osteoporosis, but the precise genes and their relative contribution remain unknown.

Objectives: To gain insight into the genetic basis of idiopathic low bone mineral density in Israeli patients by analyzing the impact of two candidate genes: polymorphism of the vitamin D receptor gene and polymorphism A986s in the calcium-sensing receptor gene.

Methods: We analyzed 86 Jewish Israeli patients with LBMD[1]: 38 premenopausal women and 48 men, and compared the allelic pattern distribution with that of the general population (126 men and 112 women). Genotyping of the VDR[2] gene was performed in three polymorphic sites using restriction enzymes, and allelic analysis of A986s polymorphism in the CaSR[3] gene was performed using the denaturing gradient gel electrophoresis technique.  

Reaults: In LBMD women the distributions of VDR alleres in Apal polymorphism were AA=7/28, Aa=16/28 and aa=5/28; in TaqI polymorphism TT=10/31, Tt=16/31 and tt=5/31; and in BsmI polymorphism BB=7/32, Bb=14/32 and 11/32. In LBMD men the distributions were AA=17/39, Aa=21/39 and aa=1/39; in TaqI polymorphism TT=12/42, Tt=23/42 and tt=7/42; and in BsmI polymorphism BB=12/41 Bb=18/41 and bb=11/41. The distributions of all these polymorphisms in the control groups were not significantly different. Adjusting for the independent age and gender parameters confirmed that these three polymorphisms of the VDR gene did not have a significant effect on bone mineral density. Thirty percent (24/79) of LBMD patients of either sex displayed heterozygosity of the CaSR A986s polymorphism, compared with 40 of 203 controls (19.7%) (P=0.059). Adjusting for age and gender in these patients revealed a significant difference in the femoral neck BMD[4] between homozygotes and heterozygotes (P=0.002). The age at menarche of the LBMD women was found to predict 61% of the variance of femoral neck BMD.

Conclusions: In Israeli Jewish men and premenopausal women VDR gene alleles do not seem to be associated with lower lumbar spine or femoral neck BMD. A trend towards heterozygosity for a CaSR polymorphism missense mutation was noted in the LBMD patients. Age at menarche in the LBMD women was found to be an important predictor of BMD. A significant difference was found between LBMD women and healthy control women towards heterozygosity for a CaSR polymorphism, as well between homozygotes and heterozygotes for a CaSR polymorphism in BMD. The significance of these findings and their applicability to a larger population awaits further studies.

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Background: Long-term follow-up in apical hypertrophic cardiomyopathy is rare.

Objective: To study the natural history of the disease.

Methods: We followed 11 patients, 5 women and 6 men, for 5-20 years.

Results: At presentation all 11 patients had typical features of apical hypertrophic cardiomyopathy, with dyspnea in 3 and chest pains in 8, of whom 5 were typical of angina and 3 had myocardial infarction. R-wave voltage and T-wave negativity progressively decreased in magnitude at serial electrocardiograms in four patients. Perfusion defects were detected on thallium myocardial scintigraphy in three, increased apical uptake in two, and normal in one patient. Apical aneurysm with normal coronary arteries developed in a patient who had sustained ventricular tachycardia. All of the 10 catheterized patients had normal coronaries except for one with significant left anterior descending artery stenosis and another with a minor lesion. Symptomatic sustained ventricular tachycardia was found in two patients, one of whom required the implantation of an internal cardioverter-defibrillator.

Conclusions: Apical hypertrophic cardiomyopathy may develop morphologic and electrocardiographic changes with life-threatening arrhythmias necessitating close follow-up and treatment.

Background: The exact value of follow-up ultrasonogra­phy and computed tomography in the non-operative manage­ment of blunt splenic injuries is not yet defined. Although follow-up studies have been recommended to detect possible complications of the initial injury, evidence shows that routine follow-up CT scans usually do not affect management of these patients.

Objective: To determine whether follow-up imaging influences the management of patients with blunt splenic injury.

Methods: Between 1995 and 1999, 155 trauma patients were admitted with splenic trauma to a major trauma center. Excluded from the study were trauma patients with penetrating injuries, children, and those who underwent immediate laparotomy due to hemodynamic instability or associated injuries. The remaining trauma patients were managed conservatively. Splenic injury was suspected by focused abdominal sonography for trauma, upon admission, and confirmed by CT scan. The severity of splenic injury was graded from I to V. The clinical outcome was obtained from medical records.

Results: We identified 32 adult patients (27 males and 5 females) with blunt splenic injuries who were managed non-operatively. In two patients it was not successful, and splenectomy was performed because of hemodynamic dete­rioration. The remaining 30 stable patients were divided into two groups: those who had only the initial ultrasound and CT scan with no follow-up studies (n= 8), and those who under­went repeat follow-up ultrasound or CT scan studies (n = 22). The severity of injury was similar in both groups. In the second group follow-up studies showed normal spleens in 2 patients, improvement in 11, no change in 8, and deterioration in one. All patients in both groups were managed successfully with good clinical outcome.

Conclusion: In the present series the follow-up radiologi­cal studies did not affect patient management. Follow-up imaging can be omitted in clinically stable patients with blunt splenic trauma grade I-III.
 

Background: The incidence of spinal failure necessitating general anesthesia and endotracheal intubation following spinal anesthesia for cesarean section is extremely low. Aspiration prophylaxis prior to spinal anesthesia is often recommended in case of spinal failure or excessive spinal block requiring the emergency administration of general anesthesia.

Objectives: To determine the incidence of endotracheal intubation following spinal anesthesia for cesarean section.

Methods: We retrospectively reviewed the pen-operative course of parturients undergoing cesarean section under spinal anesthesia at our institution from February 1991 to December 1993. If spinal failure occurred, 10 ml of sodium bicarbonate was administered by mouth prior to induction of general anesthesia.

Results: Among the 743 cases that we reviewed, spinal failure occurred in 15 patients (2%) because of inadequate analgesia in 14 patients (1.9%) and unexpected prolonged surgery for hysterectomy in one patient (0.1%). No patient required intubation due to excessive spinal block. In none of the patients was a record of pulmonary aspiration identified.

Conclusions: The extremely low incidence of spinal failure or excessive block necessitating endotracheal intuba­tion suggests that routine aspiration prophylaxis may not be necessary prior to spinal anesthesia. However, these results should be confirmed by a prospective, controlled study on larger populations. An antacid should be readily available and administered whenever general anesthesia is required.