A case of trichotillomania (author''s transl)

Five episodes of transient monocular blindness during a six-month period occurred in a 42-year-old black man who had sickle cell trait. Other than the hemoglobin abnormality no cause for the transient monocular blindness was determined.     

Using mutual information to measure coupling in the cardiorespiratory system

Approximately 2,000 infants with sickle cell disease are born each year in the United States. Sickle cell disease is an inherited disorder of red blood cell hemoglobin. Sickle cells increase adhesion and cause blockage in the small blood vessels, resulting in tissue damage. The cells' production of hemoglobin S results in two major pathophysiologic features of sickle cell disorders: chronic hemolytic anemia and vaso-occlusion. These disorders cause ischemic tissue damage and acute and chronic organ failure. Potential complications for children with sickle cell disease include vaso-occlusive events, splenic sequestration, bacterial septicemia from splenic hypofunction, aplastic crisis, pulmonary compromise including acute chest syndrome, renal tubular dysfunction and renal failure, priapism, aseptic necrosis, gallstones, delayed growth and development, leg ulcers, stroke and premature death. Three major sickle cell complications during the first years of life are dactylitis, splenic hypofunction and splenic sequestration. The risk for pneumococcal meningitis is 36 times greater in children with sickle cell anemia than for black children without the disease, and 314 times greater than for white children.     

Protein C activity in Gabonese children with sickle cell disease

Protein C levels were determined in 40 Gabonese children with sickle cell disease, in the steady state and during vasoocclusive crisis. In comparison with 40 healthy controls matched for age and sex, there was a significant decrease in protein C activity in the patients, although no difference was found between protein C levels in the steady state and during crisis.     

Transthoracic forequarter amputation and left pneumonectomy

As survival improves in patients with sickle cell anemia, the prospects of performing cardiac surgical procedures on older patients with this genetic defect increase. We describe the successful management of a 52-year-old patient with sickle cell disease (homozygous for hemoglobin S) and a history of multiple sickle crisis undergoing cardiopulmonary bypass for mitral valve repair. Preoperative partial exchange transfusion followed by total exchange transfusion at the time of operation was performed to reduce the level of hemoglobin S to 5.4% during bypass. Other management strategies included high-flow normothermic bypass with aortic crossclamping, topical hypothermia, and cold crystalloid cardioplegia.     

Echocardiogram in common (single) ventricle: angiographic-anatomic correlation

Common ventricle is a rare congenital anomaly in which the ventricular chamber receives blood from two separate atrioventricular (A-V) valves or a common A-V valve. Diagnosis of common ventricle was established in 55 patients aged 3 months to 33 years (mean 10 years) at cardiac catheterization in all 55 and at operation or autopsy in 24. In common ventricle with two angiographically demonstrable A-V valves (47 patients), the echocardiographic features included: (1) simultaneous recording (in the same sonic beam with the transducer held stationary) of the echoes of an anterior and a posterior A-V valve without an intervening septal echo (45 of 47 patients); (2) absence, on a base to apex scan, of the ventricular septal echo in the usual position separating the A-V valves (47 of 47 patients); (3) recording, in patients with common ventricle and outflow chamber, of this small outflow chamber anterior to the A-V valves (20 of 23 patients); and (4) recording of echographic continuity of the posterior A-V valve and great artery (27 of 31 patients). In common ventricle with a common A-V valve (8 patients), the echocardiographic features included: (1) a single demonstrable A-V valve, located posteriorly in the ventricle, which showed a large amplitude of excursion during diastole; and (2) absence of a second A-V valve echo or ventricular septal echo. Eight patients were studied postoperatively after surgical correction by ventricular septation. Echographic features included visualization of a prosthetic septum that produced a dense echo and divided the common ventricle into "right" and "left" ventricular chambers. This septum had a large excursion anteriorly during systole. Because common ventricle is now amenable to surgical correction, echocardiography should play an important role in assessment of ventricular anatomy in this complex congenital cardiac defect.     

Activation of epidermal growth factor receptor in the early phase after renal ischemia-reperfusion in rat

This article describes 2 white male patients with probable splenic crisis caused by sickle cell trait after travel from sea level to a moderately high altitude. Both did well with return to lower altitude and conservative treatment. Although rare, this entity should be considered in patients presenting to the emergency department with left-sided chest or abdominal pain after travel to moderate or high altitude.     

The role of cognitive-behavioural therapy in the management of pain in patients with sickle cell disease

Painful crisis is the most common manifestation of sickle cell disease and accounts for the second greatest number of admissions with an average length of stay of 7 days in central London. Despite this frequency of admissions, the management of pain is fraught with problems. This is not surprising since the psychological challenges presented by sickle cell disease are manifold, resulting in significant psychological distress for some individuals. This paper considers the literature on the psychosocial impact of sickle cell disease, and the American research evidence which suggests that pain management strategies that incorporate a psychological intervention can significantly reduce psychological distress as well as hospital admissions. Britain has been slow to incorporate psychology in the pain management strategies, and we have embarked on research to fill this gap. Although this research constitutes work in progress, an argument is put forward for utilizing the cognitive-behavioural perspective in the management of pain in sickle cell disease and we conclude by giving a brief summary of pilot work which is both the foundation and justification for the current ongoing research.     

Radionuclide (MUGA) studies of left ventricular functional abnormalities in asymptomatic patients with sickle cell anemia

Radionuclide ventriculography was performed on 10 normal subjects and 39 patients with sickle cell anemia (10 homozygous and 29 heterozygous sicklers) at rest and after exercise. Their left ventricular (LV) function was assessed in both these situations. The results were then compared within the subgroups. The reduction in ejection fraction (EF) response (47.5 +/- 7 at rest and 46.4 +/- 8 at exercise in homozygous patients, and 52.4 +/- 8 at rest and 54.3 +/- 8 at exercise in heterozygous patients) was significant in both the homozygous and the heterozygous groups but more so in the former group. The diastolic filling was also significantly impaired in the homozygous group (PER 2.64 +/- 0.74, PFR 2.13 +/- 0.42 and PFR/HR 0.014 +/- 0.001). The study statistically demonstrates, that LV filling patterns are altered in the sickle cell patients, even in the absence of clinical symptoms relating to LV dysfunction. This fact may prove to be a marker of sickle cell heart disease. Frequent and significant sickling is probably the cause of more pronounced LV functional abnormalities in homozygous sicklers.     

Sickle cell hepatopathy

Hepatic dysfunction is a common finding in patients with sickle cell disease but viral hepatitis appears to be an unusual complication in the adult SS patient. Only five cases of viral hepatitis were recorded in 378 admissions for SS crisis. In contrast, hepatic crisis occurred as a distinct event in 9% of 88 patients with sickle cell anemia. This entity must be differentiated from acute cholecystitis or viral hepatitis. Transiently abnormal results of hepatitic function tests were observed in another 26 patients with extrahepatic crisis. Cirrhosis is relatively common and often the terminal event in SS disease. Choledocholithiasis and cholecystitis are infrequent complications despite the prevalence of gallstones in SS anemia.     

Extensive rodent ulcer (type: solid basal cell carcinoma)

Pulmonary disease, including thromboembolic problems, accounts for a large portion of the morbidity of sickle cell disease. Chronic transfusion therapy is now a part of long-term treatment of sickle cell patients with stroke and chest syndrome. The resultant iron overload must be treated with chelation therapy using deferoxamine. Poor compliance with subcutaneous chelation therapy has necessitated intravenous deferoxamine treatment. We describe two patients with sickle cell disease on such a regimen, who became hypoxic as a result of pulmonary thromboembolism, secondary to venous thrombophlebitis. The thrombophlebitis and subsequent pulmonary embolism probably reflect the hypercoagulable state seen in sickle cell and are not due to the deferoxamine therapy.     

Assessing the validity of serodiagnostic test results

Abnormal adhesion of sickle cells to vascular endothelium may be a factor in the initiation of painful vaso-occlusive crisis. The sickle cell population contains an unusually large number of less dense reticulocytes that are known to be more adhesive than mature red cells, but there is contradictory evidence regarding the adhesiveness of dense sickle cells. We used a flow-based assay of adhesion to cultured human umbilical vein endothelial cells to test the properties of density fractions of sickle cells, prepared either by density gradient or by centrifugation of packed cells. We also examined the effects of incubating sickle cells with or without cyclical deoxygenation on their adhesion. After fractionation on a Percoll-isopaque gradient, the less dense 10% (reticulocyte-rich) cells and the most dense 10% cells adhered in greater number than the remainder (by about twofold). However, after centrifugation of packed cells, the less dense 10% were again more adhesive than the "middle" cells, but the most dense were not. Exposing sickle cells to constituents of the gradient had no consistent effect on adhesion, while centrifugal packing induced a degree of hemolysis, and tended to reduce adhesiveness of the dense fraction previously obtained from a gradient. Incubation in air at 37 degrees C for 15 hr reduced the number of reticulocytes and the adhesiveness of less dense sickle cells compared to those held at 4 degrees C. On the other hand, incubation at 37 degrees C for 15 hr with cyclical deoxygenation caused formation of dense cells and increased adhesiveness compared to incubation without cyclical deoxygenation. We conclude that young, less dense sickle cells are unusually adhesive, but that this adhesiveness is reduced during maturation. However, repeated sickling in vivo causes formation of an abnormally dense subpopulation of cells which either redevelop an increased tendency to adhere to endothelial cells or preserve their initial adhesiveness. Both adhesive cell populations may be implicated in promoting vascular obstruction.     

Iron-balance and dose-response studies of the oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1) in iron-loaded patients with sickle cell disease

Several life-threatening complications of the common disorder sickle cell disease require management with red blood cell transfusions and, hence, long-term iron-chelating therapy. The efficacy of the oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1) has not previously been determined in patients with sickle cell disease. We compared the efficacy of L1 to that of standard-dose subcutaneous deferoxamine in four regularly transfused patients with homozygous sickle cell disease, who had evidence of severe iron overload and a history of poor compliance with deferoxamine. Determination of 24-hour urinary iron excretion conducted over 5 days immediately after transfusion showed that the mean daily urinary iron excretion induced by L1 at 75 mg/kg/d (0.48 +/- 0.23 mg/kg) was equivalent to that induced by deferoxamine at 50 mg/kg/d (0.39 +/- 0.06 mg/kg). In two of three patients studied, a significant (P < .025) increase in mean daily urinary iron excretion was achieved when the dose of L1 was increased to 100 mg/kg/d. Total iron balance studies, which quantitated both urinary and stool iron excretion on L1 and deferoxamine, determined that mean total daily iron excretion induced by deferoxamine (0.88 +/- 0.05 mg/kg) was significantly greater (P < .05) than that induced by L1 (0.53 +/- 0.17 mg/kg), attributable to the significantly greater stool iron excretion during deferoxamine treatment (0.50 +/- 0.16 mg/kg/d) compared with that measured during L1 treatment (0.12 +/- 0.08 mg/kg/d, P < .01). Stool iron excretion accounted for a significantly greater percentage of total iron excretion during deferoxamine treatment (59% +/- 20%) than during L1 treatment (23% +/- 14%, P < .01). These iron balance studies are the first to compare total iron excretion induced by L1 with that achieved by deferoxamine. They demonstrate that the mean total daily iron excretion during L1 treatment (0.53 +/- 0.17 mg/kg) is sufficient to maintain net negative iron balance in most regularly transfused patients with sickle cell disease. Because long-term compliance with L1 has been shown previously to be superior to that with deferoxamine in patients with homozygous beta-thalassemia, the use of L1 should increase the long-term effectiveness of iron chelation in patients with sickle cell disease.     

Season and migration alters the corticosterone response to capture and handling in an Arctic migrant, the white-crowned sparrow (Zonotrichia leucophrys gambelii)

PURPOSE: Blood pressure in individuals who have sickle cell disease has been reported to be lower than published normal values. We determine whether and to what degree this is true, using data obtained as part of a large natural history study. PATIENTS AND METHODS: Blood pressure was measured annually for 3,317 subjects with sickle cell disease who were 2 years old or older. Values obtained were compared with those reported by the National Health and Nutrition Examination Survey I and II (NHANES I and II). They were further analyzed with respect to age, sex, height, weight, hematologic diagnosis, blood urea nitrogen and creatinine, stroke, and death. RESULTS: Blood pressure was significantly lower in subjects with sickle cell anemia than published norms for age, race, and sex, a difference that increased with age. It correlated with body mass index, hemoglobin, measures of renal function and age, but the strength of the correlation varied among age and sex subgroups. The risk for occlusive stroke increased with systolic but not diastolic pressure. Mortality was related to elevated blood pressure in males (P < 0.05) and to a lesser extent in females (P = 0.10). In subjects with hemoglobin SC disease, blood pressure also deviated from normal but to a lesser degree. CONCLUSION: Blood pressure is generally lower than normal in individuals with sickle cell anemia. Those with high values relative to this population had an increased risk of stroke and death. Blood pressure should be monitored but values obtained must be assessed relative to the lower values expected for patients with this disease. Those with blood pressure values above 140/90 mm Hg should be evaluated and considered for treatment.     

Plasma and red cell lipids in sickle cell disease

Lipids, in particular phospholipids, are essential components of membrane systems, and the measurement of phospholipids and cholesterol in plasma and tissues is helpful in diagnosis. Phospholipids represent about 60 to 70% of total red cell (RBC) lipids, while about 25% is free cholesterol. Lipids in RBC are present in a dynamic state of equilibrium, and the RBC have the capacity for rapid exchange of lipids with plasma in several ways. The present study examined the cholesterol and phospholipid levels of plasma and erythrocytes in male patients with sickle cell anemia and in healthy male individuals of comparable age. This was performed with a view to detecting possible differences that might be related to some of the RBC abnormalities which accompany the disease. The results show that plasma lipids are significantly reduced in patients with sickle cell anemia and that RBC cholesterol was higher in sickle cell patients than in normal subjects.     

Long-term follow-up of ventriculoureteral shunts for treatment of hydrocephalus

We report on an 18-week fetus with cyclopia, alobar holoprosencephaly, complex congenital heart defect, anal atresia, oligosyndactyly, cystic hygroma, and skeletal abnormalities with trisomy 4. Structural anomalies were detected on routine ultrasound of the pregnancy of a 17-year-old G3 P1 TAB1 woman with sickle cell trait. Trisomy 4 conceptuses usually miscarry in the first trimester. We are aware of no other reports of a fetus with trisomy 4 and cyclopia. Causal association of chromosome abnormalities and holoprosencephaly sequence may be more apparent in embryos and early fetuses than term fetuses because of poor viability of affected conceptuses.     

Preceding His-atrial interval as a determinant of atrioventricular nodal conduction time in the human and rabbit heart

This investigation shows that atrioventricular (A-V) nodal conduction time (A-H interval), both in the human and in the isolated rabbit heart, is determined mainly by the length of the preceding His-atrial (H-A) interval. The A-H intervals obtained during atrial extrasystolic stimulation at different basic rates, during Wenckebach cycles and during both transient and steady state responses to stepwise increases in stimulation frequency were plotted against the corresponding H-A intervals. The A-H intervals were found to have nearly the same duration provided they were preceded by the same H-A interval. The only important difference appeared in the short H-A interval range as a shortening of the A-H interval at faster basic rates. This facilitating effect of frequency, which was found in the majority of cases, is compatible with the similarly frequency-dependent shortening of the functional refractory period of the A-V node.     

Multiple accessory pathways in patients with the pre-excitation syndrome

We have studied 135 patients with the pre-excitation syndrome and have demonstrated evidence of multiple accessory pathways in 20 patients. Five patients had two distinct accessory atrioventricular (A-V) connections, associated with enhanced A-V node conduction in one patient. Twelve patients had a single accessory A-V connection associated with enhanced A-V conduction. In one of these there was an additional fasciculo-ventricular connection. One patient had an accessory A-V connection associated with a nodoventricular bundle. Two patients had fasciculo-ventricular connections combined with enhanced A-V conduction. The latter two patients had electrocardiograms suggestive of a complete accessory A-V connection. Patients with enhanced A-V conduction had shorter cycle lengths during reciprocating tachycardia, primarily because of a short A-H during the dysrhythmia, than those without such conduction. In addition, patients with enhanced A-V conduction demonstrated more rapid conduction from atrium to His bundle during induced atrial fibrillation and two developed life-threatening ventricular responses during atrial fibrillation. A nodo-ventricular pathway was documented to participate in reciprocating tachycardia in one patient. Surgery was undertaken in 13 patients. In 11, the intraoperative mapping studies confirmed the preoperative predictions. In two patients, the presence of a second accessory A-V connection was documented after ablation of one.     

Effect of cholecystokinin-pancreozymin (CCK-PZ) on glycoprotein secretion from mouse gallbladder epithelium: an ultrastructural and cytochemical study

L-Azetidine-2-carboxylic acid, the naturally occurring lower homologue of L-proline, is incorporated into hemoglobin S (sickle hemoglobin) in vitro. Sickle erythrocytes from patients with sickle cell anemia incubated with L-[3H] azetidine-2-carboxylate synthesized radiolabeled hemoglobin which when isolated from cell lysates, co-chromatographed with hemoglobin S on DEAE-cellulose columns. The alpha/beta ratio of azetidine carboxylate incorporation into the globin chains of sickle hemoglobin was 0.94, which is consistent with the presence of four proline residues in each polypeptide chain. Incorporation of azetidine carboxylate into hot trichloroacetic acid-insoluble material in sickle erythrocytes indicated that the homologue was present in the polypeptide backbone of the globin chains of sickle hemoglobin. Amino acid analysis of the hot trichloroacetic acid-insoluble material from sickle erythrocytes which had been incubated with radiolabeled azetidine carboxylate indicated that 75% of the radioactivity could be accounted for as intact homologue while 20% of the radioactivity co-chromatographed with alanine. These results suggest that azetidine carboxylate is incorporated unaltered into hemoglobin S in addition to being metabolized to alanine in sickle erythrocytes prior to incorporation into protein. The kinetics of thermal precipitation of hemoglobin S (oxygen ligand) into which radioactive azetidine carboxylate or radioactive proline had been incorporated in vitro is identical. This observation, together with the behavior of hemoglobin S and the globin chains from hemoglobin S containing azetidine carboxylate during ion-exchange chromatography, indicates that homologue replacement of prolyl residues does not significantly alter the overall charge or stability of the hemoglobin S tetramer. Azetidine carboxylate did not inhibit uptake of radiolabeled proline by sickle erythrocytes suggesting that the homologue does not adversely affect amino acid transport in these cells.