Comparison of responses evoked by mild indirect cooling and by sound in the forearm vasculature in patients with homozygous sickle cell disease and in normal subjects.

In normal individuals, novel or noxious stimuli commonly evoke the pattern of the alerting or defence response which includes cutaneous vasoconstriction, but vasodilatation in forearm skeletal muscle. We have compared cardiovascular responses evoked by sound and by indirect cooling in 60 patients with homozygous sickle cell (SS) disease and in 30 control subjects with normal haemoglobin genotype (AA). A sound of 90 dB, 1 kHz for 30s evoked an increase in hand and forearm cutaneous vascular resistance (HCVR and FCVR) in SS patients and an increase in HCVR in AA subjects, as assessed from Doppler flowmetry. Meanwhile, a decrease in forearm vascular resistance (FVR) assessed by venous occlusion plethysmography, occurred in 14 out of 30 AA subjects and 25 out of 60 SS patients, indicating vasodilatation in forearm muscle; an increase in FVR occurred in the remainder. The proportions of SS patients and AA subjects who showed an increase in FVR (53% vs 57%) were not significantly different. Cooling increased HCVR and FCVR in SS patients and increased FCVR in AA subjects; a decrease in FVR indicating vasodilatation, occurred in 12 out of 30 AA subjects, but in only 10 out of 60 SS patients. The proportion of SS patients who showed an increase in FVR to cooling was greater than in AA subjects (83% vs 60%, P < 0.05). Thus, SS patients are just as capable of showing the muscle vasodilatation of the alerting response to sound as AA subjects. That few SS patients showed muscle vasodilatation in response to cooling is consistent with the view that reflex vasoconstrictor responses to cooling are particularly strong in SS patients. This, in turn, is consistent with our hypothesis that the reflex vasoconstrictor response to cooling acts as a trigger for the painful crisis of SS disease by diverting blood flow away from active bone marrow.

Treatment of sickle cell disease in early childhood in Jamaica.

The Jamaican sickle cell cohort study, based on neonatal diagnosis of all cases of sickle cell disease among 100,000 consecutive births, has identified acute splenic sequestration (ASS) and pneumococcal disease as the most important complications in early life. The etiology of ASS is unknown and prophylaxis is therefore not possible. For first attacks, attention has been directed to parental education to achieve earlier diagnosis. Recurrent attacks may be prevented by prophylactic splenectomy. A controlled trial on the prevention of pneumococcal disease has indicated many pneumococcal septicemias in children given the 14 valent pneumococcal vaccine between the ages of 6 months and 3 years. No pneumococcal isolations occurred during the same period in children given monthly long-acting prophylactic penicillin. A controlled trial of folate supplementation for 1 year in children aged 6 months to 4 years indicated no difference between control and treatment groups in hemoglobin levels or weight and height velocity. The MCV was 4 fl less in the supplemented group. A controlled trial of feeder vessel photocoagulation in the therapy of proliferative retinopathy indicated significantly less vitreous hemorrhage in treated patients, but choroidal neovascularisation was a common complication of xenon arc therapy, and retinal tears commonly followed the use of the Argon laser. A new trial of scatter therapy is in progress.

A trial of folate supplementation in children with homozygous sickle cell disease.

A double blind controlled trial of supplementation with folic acid has been performed in 117 children with homozygous sickle cell (SS) disease aged 6 months to 4 years over a 1 year period. No megaloblastic change was observed in either group. At the end of the study period the folate supplemented group showed no significant differences in haemoglobin, growth characteristics, or in the proportion of children affected by major or minor infections, acute splenic sequestration, dactylitis or episodes of bone or abdominal pain. However, the folate supplemented group showed a significantly lower mean cell volume and the placebo group contained a significant excess of children experiencing multiple episodes of dactylitis. The results are compatible with mild folate deficiency in some patients in the placebo group but the absence of striking effects on haematology or growth suggest that the policy of regular folate supplementation in children with SS disease should be critically reviewed.

Central retinal artery occlusion without retrobulbar hemorrhage after retrobulbar anesthesia.

Four patients had central retinal artery occlusions after retrobulbar anesthesia with lidocaine HCl was administered before photocoagulation. One of these four had two separate episodes of closure. Only one had permanent visual loss, and none had evidence of retrobulbar hemorrhage. Each patient had a severe hematologic or vascular disorder. We think that direct trauma to the central retinal artery behind the globe, the pharmacologic or compressive effects of the injected solution, or both caused the occlusions in these patients.

Renal function in patients over 40 with homozygous sickle-cell disease.

Renal function was examined in 25 patients aged 40-64 with homozygous sickle-cell (SS) disease. Investigations included intravenous urography and measurement of blood urea and creatinine concentrations and creatinine and protein excretion in 24-hour collections of urine. Serum creatinine concentrations did not differ significantly from those of 25 other patients with SS disease aged 18-39 years, but serum urea concentrations were significantly higher (p less than 0.001). Intravenous urography showed loss of caliceal cupping (nine patients), irregular renal outline (five), and cystic extension from the calix (one). Six patients had creatinine clearances below the fifth percentile for age and sex. Proteinuria was more common in these patients, and haemoglobin concentrations were much lower than in the 19 patients without renal insufficiency (mean 5.6 v 8.2 g/dl; p less than 0.001). Haemoglobin concentration was strongly correlated with creatinine clearance (r=0.70), particularly with clearances below 100 ml/min/1.73 m2 (r=0.96; p less than 0.001). A possible mechanism of renal insufficiency in SS disease is cortical scarring, which is asymptomatic, not associated with hypertension, and accompanied by only minor proteinuria. A falling haemoglobin concentration is a sensitive and early indicator of renal impairment in SS disease.