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A woman with coccidiodal meningitis had two successive pregnancies and was treated with intrathecal amphotericin B. The outcome was successful.

Acetaldehyde-hemoglobin adducts have been suggested as potential markers for alcohol consumption. These adducts were formed in vitro with [14C]acetaldehyde and separated into hemoglobin subunits by cation-exchange chromatography to examine the relative modification of the alpha- and beta-chains. The effect of varying concentrations of acetaldehyde on the relative amounts of polypeptide adducts and on the specific radioactivities of undissociated hemoglobin (Hb) following reaction with hydroxymercurybenzoate (HMB) was also studied. There were linear relationships (P less than 0.05) between increasing levels of [14C]acetaldehyde (0.0, 0.1, 0.2, 0.5 mM) and the radioactivities of the alpha- and one of the two beta-chain adducts (22, 25, 53 dpm/mg Hb and 151, 272, 626 dpm/mg Hb, respectively). Increases in radioactivities of a minor unidentified hemoglobin adduct fraction were also observed. The ratios of specific radioactivities of beta-to alpha-chain (8.8 +/- 1.2 SEM) did not vary with the concentrations of acetaldehyde. Although the amounts of undissociated hemoglobin following reaction with HMB did not increase with increasing concentrations of acetaldehyde, the significant increase of specific radioactivities of this fraction (152, 1967, and 6562 dpm/mg Hb for 0.1, 0.2, and 0.5 mM acetaldehyde, respectively) suggested possible crosslinks within the tetramer or dimer. The amino acid analysis of alpha- and beta-subunit adducts formed with 0.1 and 0.5 mM acetaldehyde showed that unreacted cysteine residues were more often detected at the higher acetaldehyde concentration consistent with the formation of cysteine adducts labile to acid hydrolysis or the shielding of cysteine residues in acetaldehyde-modified Hb against the subunit separation by HMB treatment. Thus acetaldehyde reacts differentially with the alpha- and beta-hemoglobin subunits and with the undissociated hemoglobin molecule.

This is the first case report of cataracts in patients with thalassemia major. Desferrioxamine, an iron-chelating agent is being used with increasing frequency in the treatment of transfusion-induced iron overload. There has been some concern in the literature about possible cataract formation with use of this drug. It is therefore important to document any lens opacities seen prior to administration of desferrioxamine, or record the appearance of lens opacities after its use. The possible eitology of these lens opacities is discussed.

A rapid method of separating viable from nonviable human fetal pancreatic islets prior to transplantation is needed to quantify grafted tissue and optimize the possibility of successful treatment of diabetes mellitus in the recipient. After incubation with 0.04% trypan blue in isotonic Krebs-Ringer buffer solution for 15 min, the percentage of islets that excluded trypan blue was found to correlate well with fractional stimulated insulin secretion rates. The incubation procedure did not alter the subsequent insulin secretory capacity of the islets. Trypan blue exclusion rapidly and reliably identifies viable functional islet tissue prior to transplantation.

Accelerated fibrinogen disappearance in diabetic patients is reversible with normalization of blood glucose. To define the time course of this reversal, we measured 125I-fibrinogen disappearance in 19 diabetic patients experiencing acute changes in blood glucose, as monitored and controlled by a microprocessor-controlled closed loop insulin infusion system (artificial beta cell). The data were corrected for blood volume dilutional changes and fit to a model describing two sequential exponential functions and a single exponential function. The sequential model provided the best fit for all but one patient. This indicates that there were two distinct rates of fibrinogen disappearance and suggests that the time course of reversal of accelerated fibrinogen disappearance in diabetic patients is very rapid, if not immediate. Rapid fibrinogen turnover during hyperglycemia was temporally associated with vascular volume changes, reflected as dilutional changes of 51Cr-RBC concentrations. These findings were also associated with an increase in pulse pressure during hyperglycemia, suggesting blood volume expansion due to an osmotic mechanism. The results of this study suggest a picture of vascular volume expansion and contraction, perhaps secondary to the osmotic effects of hyperglycemia. Accelerated fibrinogen turnover associated with these events may be related to increased vascular permeability and/or increased fibrin formation. These events, in concert, may contribute to the initiation and/or propagation of diabetic vascular sequelae.

We studied the increased levels of hemoglobins AIa+Ib and AIc in five hospitalized diabetic patients to determine whether changes in diabetic control would cause parallel changes in the levels of these hemoglobins. Before control of diabetes the mean fasting blood sugar for all patients was 343 mg per deciliter (range, 280 to 450), and hemoglobin AIc concentration 9.8 per cent (range, 6.8 to 12.1). During optimal diabetic control the blood sugar concentration was 84 mg per deciliter (range, 70 to 100), and hemoglobin AIc concentration 5.8 per cent (range, 4.2 to 7.6). Hemoglobin AIc concentration appears to reflect the mean blood sugar concentration best over previous weeks to months. The periodic monitoring of hemoglobin AIc levels provides a useful way of documenting the degree of control of glucose metabolism in diabetic patients and provides a means whereby the relation of carbohydrate control to the development of sequelae can be assessed.

Six healthy active women in the third trimester of pregnancy participated in a graded exercise protocol to levels of exertion perceived to be equivalent to that of their usual exercise regimen. Fetal heart rate response (FHR) was documented by ultrasound transducer and confirmed (n = 1) by ultrasonic visualization. Resting maternal O2 consumption was 277 +/- 50 (SD) ml/min and rose to 1,132 +/- 202 ml/min at a mean final exercise intensity of 79 +/- 9 W after 12.8 +/- 1.7 min on a cycle ergometer. There was no significant change in maternal serum insulin, growth hormone, glucose, or pH values. Maternal leukocyte count, hemoglobin, and venous lactate levels rose significantly during the exercise (P less than 0.05). FHR prior to exercise was 142 +/- 4 beats/min and decreased to 84 +/- 34 beats/min during exercise. The decrease in FHR was documented within 1 min of initiating exercise in all cases. During exercise, fetal movements were not accompanied by FHR accelerations. Within 1 min following the cessation of exercise, FHR rose to 143 +/- 8 beats/min and fetal movements were accompanied by FHR accelerations. Since the recovery of FHR occurred immediately after cessation of maternal exercise, this level of maternal exercise does not appear to be harmful to the fetus.

Two cases of primary intracerebellar hemorrhage in premature neonates in which diagnosis was established primarily by real-time ultrasound are presented. It is concluded that real-time, portable ultrasound should be the diagnostic method of choice in evaluating the brain in infants on multiple life-support systems.

Seven patients with diabetes mellitus were hospitalized and their blood sugar concentrations regulated as a result of fasting blood sugar, sugar around meals, urinary sugar, and hemoglobin AIC assays. Erythrocyte half-life as measured by 51 Cr increased in all patients from a mean of 27 days to 31 days, while hemoglobin AIC levels decreased from a mean of 10.1% to 5.6%. Leukocyte adherence increased in all patients from a mean of 28% to 51%. Most striking were the changes observed in platelet function in response to epinephrine. The length of the secondary lag phase of platelet aggregation, after a stimulus with final concentration of 70 muM of epinephrine, increased from a mean of 19 seconds to 65 seconds. Studies in additional patients confirmed an inverse correlation between hemoglobin AIC concentration and the secondary lag phase (r = 0.87, P less than 0.001). These studies found that certain secondary sequelas of diabetes can be corrected by strict carbohydrate control and confirmed that hemoglobin AIC assays provide a useful means of showing the degree of control of glucose metabolism in diabetic patients.

Studies in 10 nonketotic diabetic subjects (five juvenile- and five adult-onset) before and after control of carbohydrate metabolism showed a high degree of correlation between hemoglobin AIc (HbAIc) concentrations and serum triglyceride levels. Serum triglyceride levels were found to correlate more closely with Hb AIc (r = 0.91, p less than 0.001) than did serum cholesterol (r = 0.47, p greater than 0.05), thus indicating a more direct relationship to carbohydrate metabolism.

Because of the morbidity associated with undiagnosed gestational diabetes (GDM), screening programs are advocated in all pregnancy clinics. The purpose of this study was to elucidate the optimum time to test for diabetes during gestation, the indication for retesting, and the predictive value of a positive screening test for a large (greater than 4000 g) infant. Women (N = 300) were screened at three time points: 9-20 wk, 27-31 wk, and 33-36 wk. An additional group of 300 women were screened at two time points: 27-31 wk and 33-36 wk. The prevalence of GDM in this group was 3.2%. The optimum timing for screening for highest yield was 27-31 wk. Retesting at 33-36 wk appeared cost effective if (1) maternal age was greater than or equal to 33 yr, (2) a positive screen was present at 27-31 wk, and (3) the mother was obese (greater than 120% ideal body wt).

An attempt was made to improve the control of blood glucose in patients with insulin-dependent diabetes mellitus. Ten patients were studied over a period exceeding 8 mo in the outpatient department. Each patient was taught to monitor his or her own blood glucose concentration and was enrolled in an exercise program. In addition, they were taught to calibrate insulin, food, and exercise in terms of the response of the blood glucose. After 3 mo of study, there was a significant decrease in hemoglobin A1c (Hb A1c) values from a mean concentration of 10.3 to 7.6%. Hb A1c values correlated well with mean blood glucose levels (r = 0.86). Dietary analysis revealed that the patients selected a diet consisting of 25% protein, 44% fat, and 31% carbohydrate, but there was a wide range in caloric distribution. There was no correlation between blood glucose control as measured by Hb A1c and caloric distribution. Systolic blood pressures decreased greater than 10 mm Hg. Serum alkaline phosphatase also decreased in each patient as control of blood glucose improved. Three of the patients with abnormalities of nerve conduction measurement at the beginning of the study had a complete return to normal at 8 mo. An outpatient program such as this may be cost effective through the avoidance of diabetes-related hospitalizations and may provide a mechanism whereby larger studies can be designed to define further the relationship of glycemia to the sequelae of diabetes.

Two young patients developed bilateral posterior subcapsular cataracts while receiving oral sodium cyanate for treatment of sickle cell hemoglobinopathy. In one of the patients, lens opacities regressed spontaneously after cyanate therapy was discontinued.

Twenty-four diabetic patients receiving insulin were randomized to 3 groups. Group I began self blood glucose monitoring by meter and switched to visually read strips at 3 months. Group II began self blood glucose monitoring by visually read strips and switched to meter readings at 3 months. Group III monitored urine glucoses for the 6 months of the trial. Professional interaction time was the same for all patients and each patient was placed on the same insulin delivery scheme (3 shots NPH and/or regular). Mean C-peptide levels 6 min following intravenous glucagon was comparable in all 3 groups. Patients monitoring blood glucose showed a significant decrease in glycosylated hemoglobin values (p less than 0.01) from patients monitoring urine at 6 months of the trial. Patients subjectively felt meters were more accurate than visual strips but both groups I and II showed lower glycosylated hemoglobin levels (p less than 0.02 at 6 months) and sequence analysis revealed no sequence effect. The trial confirms that blood glucose monitoring technologies have advantages over urine monitoring in helping patients achieve improved glucose levels. Patients perform equally well in terms of blood glucose "control" whether visually read strips or meters are used for initial teaching or maintenance if patients are instructed appropriately in each methodology. These findings have economic implications for large scale treatment programs.

A year-long double-blind study of 2,3-dihydroxybenzoic acid (2,3-DHB) given orally at a dose of 25 mg/kg four times per day was undertaken in 15 patients with beta-thalassemia major. 2,3-DHB and placebo (mannitol) were tolerated to an equal degree and there were no signs of drug toxicity at the end of 1 year. Efficacy in terms of retardation of iron accumulation could be documented using serial liver biopsies, serum ferritin determinations, or clinical laboratory assessment. Serum iron values increased, as did the iron binding capacity, in the group receiving 2,3-DHB. The increase in iron binding capacity was due to drug interference with the method of determination. Because of the greater efficacy of slow infusions of desferrioxamine in chelating iron when administered slowly, the clinic has shifted its emphasis toward further evaluation of that compound. Nevertheless, in view of the minimal toxicity of 2,3-DHB, further work appears warranted to define its role in the treatment of iron-overload.

The reliability and accuracy of two-compartment temporomandibular joint (TMJ) arthrography was compared with MR imaging on the basis of an analysis of surgical findings obtained from joints that had been studied preoperatively with arthrography or MR or, in some cases, both procedures. Seven hundred forty-three consecutive TMJ arthrograms were successfully obtained in a total of 443 patients by using a single 27-gauge needle and a two-compartment technique in each joint. There was a 100% correlation with surgical findings in 218 radiologically abnormal joints operated on within 90 days of arthrography with respect to the presence or degree of meniscus displacement and normal or abnormal disk morphology and function. In 604 patients 1052 TMJs were studied with high-field-strength surface-coil MR. Surgical findings were available for correlation in 170 of the joints studied. Forty-three joints were studied with both two-compartment arthrography and MR. Eight operated joints had been imaged successfully with both two-compartment arthrography and MR. Both methods of evaluation provided highly reliable and accurate information regarding meniscus position and shape. Arthrography was superior to MR in detecting capsular adhesions and the presence or absence of perforation of the disk or meniscus attachments. Simple meniscectomy (with or without insertion of a temporary Silastic TMJ implant) was the most frequently performed surgical procedure in the series, followed by meniscus repositioning procedures. Joint effusions, failed TMJ implants, and avascular necrosis were demonstrated best with MR. Soft-tissue lesions, including intrinsic degeneration of the meniscus, anomalous muscle development, muscle atrophy, tendinitis, and injuries such as contusions and hematomas, were demonstrated only with MR. Partial-flip-angle GRASS (gradient-recalled acquisition in the steady state) techniques permit both fast scanning and study of functional joint dynamic. Joint fluid may appear as high signal intensity on GRASS images because of T2*-weighting. We recommend MR as the procedure of choice for diagnosis of uncomplicated internal derangements of the TMJ. Two-compartment arthrography with videofluoroscopy is an important ancillary procedure that should be performed whenever capsular adhesions or perforations are suspected and not demonstrated with MR and whenever MR is inconclusive.

Human peripheral blood leukocytes (PBL) were incubated in Cyclosporine, washed, and then tested for their effect in two- and three-party in vitro cultures. In two-party mixed leukocyte reactions (MLRs), CsA pretreatment (70 ng/ml) of either responder or stimulator PBL produced a potent suppression in [3H]-thymidine uptake by responder PBL (greater than 100% specific inhibition). The ability of CsA-pretreated PBL to suppress the MLR was dependent on the concentration of CsA in which the PBL were incubated. CsA was more effective at suppressing the MLR when pretreated stimulator PBL were added, then when added directly to culture. In three-party cultures, CsA pretreatment of one stimulator population (50 ng/ml) resulted in cytotoxic T lymphocytes that effectively lysed target cells from the untreated population but not targets from the CsA-pretreated population. These results indicate that CsA-pretreated cells can be used to suppress an allogeneic response in a relatively antigen-specific manner, and may have implications for clinical transplantation.

The authors report the first study which demonstrates that women with gestational diabetes mellitus (GDM) have increased tortuosity of their retinal vessels. Women with GDM underwent fundus photography and were compared with a normal control group (NC) and a pregnant nondiabetic control group (PC). Five ophthalmologists evaluated the unlabeled photographs, resulting in a combined mean prevalence of tortuosity of 21.6% NC, 24.7% PC, and 60.3% GDM. Statistical analysis showed that the GDM group was significantly different from both the NC and PC groups. Tortuosity was unrelated to acute elevation in blood glucose and was still present at 5 months postpartum.

IgG antibodies (AB) to insulin have been reported to influence insulin requirements and control in patients who have taken insulin for prolonged periods of time. Nineteen pregnant type I diabetic patients (C-peptide less than 0.03 pmol/ml) were studied in their fifth week of gestation after the establishment of normoglycemia. Mean age was 27.5 yr and duration of diabetes, 14.2 yr (range: 1-23 yr). IgG AB to beef and pork insulin were measured. IgG AB to insulin were encountered in all diabetic patients (range: 103-6736 microU/ml). None of the nondiabetic pregnant controls in their fifth week of gestation (N = 17) had detectable (greater than 50 microU/ml) AB levels. The antibody titer did not affect the insulin requirement (P greater than 0.2, NS) or ability to achieve normoglycemia. AB levels were correlated with years of treatment with conventional insulin preparations (r = 0.73; P less than 0.001). At 5 wk postmenstruation the mean AB level in the patients with less than 10 yr duration of diabetes (N = 7) was 727 microU/ml and mean insulin requirement was 0.7 U/kg/24 h. In the group of patients with greater than 10 yr duration of diabetes (N = 12) the mean antibody titer was 3716 microU/ml and the insulin requirement was also 0.7 U/kg/24 h. IgG AB to insulin increase with increasing duration of treatment with beef/pork insulin. IgG AB do not affect the insulin requirement or the ability to achieve normoglycemia during early pregnancy.

A fluorigenic high performance liquid chromatographic (HPLC) method was used to determine plasma (PA) and hemoglobin-associated (HbAA) acetaldehyde levels following a pulse of 0.3 g/kg ethanol to volunteers from whom bloods were drawn serially for 8 hours on the clinical research unit. On discharge from the research unit, the volunteers were instructed to avoid ethanol for 28 days. The results were compared to previously published results in teetotalers and alcoholic individuals reporting for treatment at an inpatient detoxification facility. Following ethanol ingestion, the peak levels of ethanol and both plasma and hemoglobin-associated acetaldehyde were detected at the 30 min time point and plasma levels were less than those associated with hemoglobin (31 +/- 16 S.D. and 159 +/- 48 S.D. nmol/g respectively, p less than 0.001). PA and HbAA returned to baseline values following ethanol ingestion within 3.5 hours. PA returned to within 1 standard deviation of levels found in teetotalers by 5 days, whereas HbAA remained elevated for the 28 days of the study. These data provide evidence that measurement of PA and HbAA may provide a useful marker for relatively acute and chronic ethanol ingestion respectively.

The methods available for and the clinical usefulness of measuring glycosylated proteins in pregnancy complicated by diabetes is reviewed. The need for standardization of reference ranges for pregnancy and for highly accurate and precise methods of measurement is emphasized. Measurement of glycosylated proteins is useful in patients with established diabetes to identify pregnancies at risk for complications known to be associated with significant hyperglycaemia. These include spontaneous abortion and malformations, foetal loss due to premature labour or intrauterine death, and macrosomia and other neonatal morbidities. The use of glycosylated protein measurements as a diagnostic test for gestational diabetes appears limited.

The stabilities of 14C-acetaldehyde with various hemoglobin fractions (HbA1a + b, HbA1a, and HbA0) were examined by determining amounts of adducts remaining after dialysis at 4 degrees C for various time intervals. Significant differences were found in the stabilities of adducts formed with various hemoglobin fractions. Acetaldehyde adducts formed with HbA1a + b were more stable to dialysis than adducts formed with HbA0 or HbA1c (7-8% of total adducts formed with HbA1a + b were stable to dialysis, compared with 4-5% stable adducts formed with either HbA0 or HbA1c). While only 37-57% of the trichloroacetic acid (TCA) precipitable adducts from HbA0 or HbA1c samples were stable to dialysis, 72-75% of TCA precipitable adducts from HbA1a + b were retained after dialysis. Posttranslational modification of hemoglobin by phosphorylated glycolytic intermediates appears to alter the physical properties of hemoglobin following further modification with acetaldehyde. In view of the increased amounts of glycosylated proteins found in patients with diabetes, these observations may be relevant to the pathogenesis of the sequelae of diabetes and/or alcoholism and the influence of one chronic illness on the other.

Blood viscosity was investigated in alloxan-diabetic dogs and in dogs made experimentally hyperglycemic by a galactose-rich diet. The diabetics were prospectively assigned to levels of glycemic control ranging from poor to good. After up to 5 years of study, the blood viscosity of hyperglycemic diabetic animals was significantly greater than normal at both high (100 sec-1) and low (0.1 sec-1) shear rates. Blood viscosity at the low shear rate correlated closely with fibrinogen concentration, (r = 0.75; p less than 0.02) but not with HbA1 concentration (r = 0.14) in the diabetics. Galactosemic animals likewise had elevated blood viscosity at the low shear rate, but the correlation of viscosity with fibrinogen concentration in those animals was not statistically significant (r = 0.42). Plasma viscosity tended to be elevated in both diabetes and galactosemia, but not to a statistically significant degree.

Total hemolytic complement (CH50) and activation of the alternate mechanism were measured in eight patients before and after splenectomy and compared to similar measurements made in a control group of patients following other abdominal surgery. In the splenectomy group, alternate-pathway-mediated activation of C3 was significantly different from the controls. The mean five-day postsplenectomy value of 16 percent for the immunoelectrophoretic conversion of C3 to C3i was depressed (p<0.001) from the presplenectomy value of 85 percent and five-month postsplenectomy level of 71 percent (p<0.01). The difference between presplenectomy and five-month postsplenectomy values was not significant. Further, activation of C3 in patients five days postsplenectomy was significantly less (p<0.01) than in the five-day postoperative controls. In both the splenectomized patients and control group, five-day postoperative determinations indicated an increase in CH50 values and a decrease in degree of activation of Factor B. The spleen appears to manufacture certain substances required for activation of C3 via the alternate mechanism. That the manufacture is eventually assumed by other immune-competent organs is shown by the eventual increase of activation toward preoperative levels five months postsplenectomy. This defect in C3 activation may account for the tendency of splenectomized patients to have an increased incidence of bacterial infections and sepsis in the postoperative period.

Patients have been shown to be able to monitor their blood glucose and administer insulin to optimize and normalize blood glucose levels. There are now three reflectance meters available whose measurements correlate well with laboratory measurement of blood glucose, with a correlation coefficient between 0.92 and 0.97. A stepwise approach toward blood glucose control has been found to be most valuable. The initial phase of the program involves patients performing blood glucose measurements before and 1 h after each meal, in addition to times when patients feel hypo- or hyperglycemic. This phase of the program demonstrates the vagaries of glucose control and emphasizes to the patients the dichotomy between symptoms and actual glucose levels. The patient is also taught during this period the risk factors associated with hyperglycemia that may contribute to vascular disease in the future. Subsequently, insulin is adjusted so that patients are given an insulin regimen that will coordinate peaks of insulin with peaks of blood glucose associated with a meal pattern. Patients are taught by health professionals and in a group setting to calibrate insulin calories and exercise depending on blood glucose readings. Such a program is received enthusiastically by patients and physicians. The major disadvantage lies in the cost of the meter and the reagent strips. Nevertheless, such programs may be cost effective because of the avoidance of diabetes-related hospitalizations.

Seven patients with homozygous cystinuria were studied on a metabolic ward to determine the effect of dietary manipulation on urinary cystine excretion. Isocaloric diets were calculated based on body weight and activity. Balance studies were performed for 5 days on a low protein diet (9.4 +/- 1.0% total calories) with equal amounts of animal and plant protein sources and an additional 5 days on a high protein (27 +/- 3.0% of total calories) with 70% animal protein. A significant (p less than 0.01) decrease in the excretion of 1/2-cystine, histidine, 3-methylhistidine, 1-methylhistidine, lysine, and ornithine plus arginine occurred on the low protein diet. The mean excretion of 1/2-cystine on the high protein diet was 6.13 +/- 1.48 mMoles per 24 hours which decreased to 4.89 +/- 1.06 mMoles per 24 hours on the low protein diet (p less than 0.001). Thirty seven percent of urine collections during the study were less than 2 liters/24 hours despite the fact that patients were encouraged to drink enough fluid to make 3 liters of urine/24 hours. For patients whose customary diet is high in animal protein, a more vegetarian diet may significantly reduce urinary cystine excretion. Cystine excretion in patients with cystinuria may be significantly different from day to day if animal protein consumption is variable.

The aim of this study has been to develop a test system for attachment of pneumococci to pharyngeal cells. Cells scraped from a healthy person were washed and quantitated, bacteria added and after incubation the suspension was washed and the number of adhering bacteria counted. Among strains from different infectious foci the highest number of strains with adhesive capacity was found in the otitis media group. Capacity to attach to the pharyngeal mucosa might be a virulence factor of pneumococci causing otitis media. There was a lack of distinct relation between capsular serotype and adhesive capacity indicating that the polysaccharide is not primarily responsible for the binding to epithelial cells. If attachment to the pharyngeal mucosa is a first step necessary for colonization and subsequent invasion of the tissues, then antibiotics in the secretions preventing such colonization might be of protective value in otitis-prone children.

2,3-Dihydroxybenzoic acid (2,3-DHB) inhibits the second wave of platelet aggregation release of serotonin, and malonaldehyde production. The effect is concentration dependent and reversible in vitro and in vivo. 50% inhibition of platelet aggregation induced in vitro with 70 micron adrenaline was obtained with 1.5 mM 2,3-DHB. Malonaldehyde production was inhibited by 50% with 0.4 mM 2,3-DHB. Serotonin release was 50% inhibited by 50% with 0.08 mm 2,3-DHB. Neither desferrioxamine nor various benzoic acid derivatives with iron-chelating properties showed the effect. Only benzoic acid derivatives with the potential to terminate free radical reactions through the formation of an ortho- or paraquinone structure inhibit the second wave of platelet aggregation. These studies support the concept that the second wave of platelet aggregation is mediated through free radical reactions.

Total hemolytic complement activity (CH50), immuno-electrophoretic conversion of Factor B (C3PA), and of C3 were studied in 16 patients with sickle cell disease in a steady state, eight patients in crisis, and ten patients with β-thalassemia major anemia maintained on a constant transfusion regimen. Patients with sickle cell disease in a steady state have moderatley 56 (percent) depressed conversion of Factor B in addition to markedly decreased conversion of C3 in four of ten patients. One of the three sickle cell patients and two of the four thalassemia patients with low C3 conversion levels have died subsequent to the studies. The combination of chronically decreased Factor B conversion in the face of markedly decreased C3 conversion may make these patients occasionally vulnerable to overwhelming infection analagous to the situation seen in postsplenectomy cases.

Two patients with sickle cell disease who had been maintained on sodium cyanante therapy for periods of 440 and 600 days on dosages up to 44 and 41 mg/kg per day developed a motor and sensory neuropathy. In both, definite abnormalities of myelinated and unmyelinated fibers were found. In one, the predominant abnormality of myelinated fibers was segmental demyelination and remyelination; in the other, there were histological features typical of axonal degeneration. It seems unlikely that the brunt of the metabolic derangement was on Schwann cells in the first case and on the nerve cell in the second. Probably, in both cases, the primary effect was on the nerve, with Schwann cell changes being concomitant or secondary. The clustered distribution of the segmental demyelination favors the latter.