Israel Medical Association Journal

Background: Cigarette smoking is a well-known risk factor for the development of endothelial dysfunction and the progression of atherosclerosis. Oxidative stress and inflammation have recently been implicated in endothelial dysfunction.

Objectives: To assess the concomitant contribution of polymorphonuclear leukocytes to systemic oxidative stress and inflammation in cigarette smokers.

Methods: The study group comprised 41 chronic cigarette-smoking, otherwise healthy males aged 45.0 ± 11.5 (range 31–67 years) and 41 male non-smokers aged 42.6 ± 11.3 (range 31–65) who served as the control group. The potential generation of oxidative stress was assessed by measuring the rate of superoxide release from separated, phorbol 12-myristate 13-acetate-stimulated PMNL[1] and by plasma levels of reduced (GSH) and oxidized (GSSG) glutathione. Inflammation was estimated indirectly by: a) determining the in vitro survival of PMNL, reflecting cell necrosis; b) in vivo peripheral PMNL counts, reflecting cell recruitment; and c) plasma alkaline phosphatase levels, indicating PMNL activation and degranulation.

Results: PMA[2]-stimulated PMNL from cigarette smokers released superoxide at a faster rate than PMNL from the controls. Smokers had decreased plasma GSH[3] and elevated GSSG[4] levels. In vitro incubation of control and smokers' PMNL in sera of smokers caused necrosis, while control sera improved smoker PMNL survival. Smokers' PMNL counts, although in the normal range, were significantly higher than those of controls. Plasma ALP[5] levels in smokers were significantly higher than in controls and correlated positively with superoxide release and PMNL counts.

Conclusions: Our study shows that PMNL in smokers are primed in vivo, contributing concomitantly to systemic oxidative stress and inflammation that predispose smokers to endothelial dysfunction, and explains in part the accelerated atherosclerosis found in smokers.

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[1] PMNL = polymorphonuclear leukocytes

[2] PMA = phorbol 12-myristate 13-acetate

[3] GSH = reduced glutathione

[4] GSSG = oxidized glutathione

[5] ALP = alkaline phosphatase

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: Case-control and prospective studies indicate that an elevated plasma homocysteine level is a powerful risk factor for atherosclerotic vascular diseases. Certain medications can induce hyperhomocystinemia, such as methotrexate, trimethoprim and anti-epileptic drugs. There are few reports indicating an interaction between lipid-lowering drugs (cholestyramine and niacin) and homocysteine. Recently, an interaction was shown between fenofibrate and benzafibrates (a fibric acid derivative) and homocysteine plasma levels.

Objectives: To evaluate the effects of different fibrates on plasma homocysteine levels and to measure the reversibility of this effect.

Methods and Results: We investigated the effects of ciprofibrate and bezafibrate on homocysteine levels in patients with type IV hyperlipidemia and/or low high density lipoprotein levels. While a 57% increase in homocysteine was detected in the ciprofibrate-treated group (n=26), a 17% reduction n homocysteine was detected in the group treated with bezafibrate (n=12). The increase in homocysteine in the ciprofibrate-treated group was sustained for the 12 weeks of treatment and was partially reversible after 6 weeks of discontinuing the ciprofibrate therapy.

Conclusions: These results indicate that an increase In plasma homocysteine levels following administration of flbrates is not a class effect, at least in its magnitude. Moreover, it is reversible upon discontinuation of the treatment.
 

Background: Most corneal damage induced by contact lenses is due to interference with corneal oxygenation.

Objective: To investigate the effect on the rabbit cornea of a rigid gas-permeable contact lens with a newly designed periphery.

Method: We fitted New Zealand white rabbits (n=12) with RGP[1] contact lenses that were identical in all respects except for the design of the periphery. In each animal, one contact lens had an innovative periphery consisting of a microscopic diffractive relief lathed on the back surface; the other contact lens was of a conventional design. The lenses were worn continuously for 7 days. During this experimental period and for 1 additional week we assessed the corneal damage by daily testing lactic dehydrogenase activity in the tears.

Results: On the last day of the experimental week and the first 3 days of the healing period, mean tear LDH[2] activity was significantly lower in the eyes with the new contact lens design than in eyes with the conventional lenses.

Conclusions: The novel periphery design reduces corneal damage resulting from contact lens wear, as reflected by LDH levels in the tears. The new design probably facilitates the flow and exchange of tears under the contact lens, resulting in improved metabolism of the cornea. These findings may also prove applicable to soft contact lenses.

Background: Familial dysautonomia is a genetic disease in which there is a defect in the autonomic and sensory nervous systems. These systems have a major role in the reproductive system.

Objective: To study the inter-relationship of autonomic and sensory dysfunction and gynecological function.

Methods: The gynecological histories of 48 women with familial dysautonomia were analyzed retrospectively. Their mean age was 22.25 years (range 12-47). Thirty-three women (65%) were available for further questioning and investigation of hormonal status.

Results: Menarche had occurred in 32 of the 48 (66.7%). Their average age of menarche was significantly delayed as compared to their unaffected mothers (15.5 vs. 13.6 years respectively, P=0.002). The most prominent finding was the very high prevalence, 81.2%, of premenstrual symptoms. Seven of 26 had premenstrual syndrome symptoms of dysautonomic crisis. Blood sex hormone levels were normal in 27 of the 33 patients studied. None reached natural menopause. One patient had adenomyosis, and another, dysgerminoma. Three patients became pregnant and delivered healthy infants.

Conclusion: Menarche is delayed in women with FD, and the physiological monthly hormonal fluctuations may disturb autonomic homeostasis sufficiently to precipitate dysautonomic crisis.