Immunity after treatment of human schistosomiasis mansoni. III. Long-term effects of treatment and retreatment

Group mean Schistosoma mansoni reinfection patterns are presented for 2 years after treatment with oxamniquine in 1981 of over 100 9- to 16-year-old Kenyan schoolchildren, and for one year after retreatment in 1983 with either oxamniquine or praziquantel when most (nearly 700) infected people in the whole community were treated. Quality control confirmed comparable Kato egg counts throughout the study. Continuing transmission after 1981 raised prevalence to nearly its original level within 6 months, but intensity remained suppressed throughout the 2 year follow-up and very few children reacquired heavy infections (greater than 400 eggs/g). Age and sex had significant effects: reinfection diminished with age, especially among boys--a pattern not apparently attributable to differential water contact. Children with heavy pretreatment infections tended to develop heavy reinfections but this trend was not statistically significant on a group basis, nor were similar trends during the period of less pronounced transmission following the 1983 community treatment. Oxamniquine was equally effective in children receiving it in both 1981 and 1983, and the efficacy of praziquantel resembled that of oxamniquine. In this area of Kenya, repeated chemotherapy will be needed to contain transmission, probably annually or biennially, unless supplemented with other, effective control measures. These findings confirm the beneficial effects of treating even a limited segment of a community at intervals of a year or more without necessarily stopping transmission. They are also compatible with recent findings on potential immune mechanisms in man.     

GALLSTONE CIRRHOSIS: ARE WE ONLY SEEING THE TIP OF THE ICEBERG?

Gallstones are common and their incidence increases with age.¹ Fifty per cent of these stones are in the common bile duct (CBD) in the elderly.² Most of them are silent but with time there is an increasing chance of developing symptoms which are more likely to be serious in the elderly.³ Failure to relieve mechanical obstruction of bile flow may lead to secondary biliary cirrhosis.⁴ It has been estimated that on average secondary biliary cirrhosis develops some seven years after the onset of obstruction from a stricture, four and half years after gallstone obstruction and 10 months after the onset of malignant stricture.⁵ The characteristic features are the pathological findings of portal-portal linkages, with a pattern of monolobular cirrhosis and the preservation of normal vascular relationships.⁶ Secondary biliary cirrhosis may lead to hepatic insufficiency and portal hypertension with the resultant complications, such as bleeding oesophageal varices, hypersplenism with pancytopenia, ascites and encephalopathy. We describe a patient in whom the diagnosis was not suspected until laparotomy and confirmed only at autopsy.     

Suppurative corneal ulceration in Bangladesh

Suppurative keratitis is an important preventable cause of blindness, particularly in the developing world. This study analyses 142 cases of suppurative keratitis referred to Chittagong Eye Infirmary, Bangladesh. Some 53.5% of cases were bacterial and 35.9% were fungal. The five most common pathogens were: Pseudomonas sp. 24%, Streptococcus pneumoniae 17%, Aspergillus sp. 13%, Fusarium sp. 7% and Curvularia sp. 6%. Gram stain and culture results were consistent in 62.6% of cases. Previous antibiotic treatment was a significant factor for failure of culture isolation and less so for Gram stain failure. On Gram stain, 55.9% of pseudomonal cases were missed, but only 2% of fungal cases were missed. Over all, Gram stain had a sensitivity of 62% and positive predictive value of 84% for bacterial cases, and 98% and 94% for fungal cases, respectively. Fungal ulcers were typically filamentous, but an antecedent history of trauma was not common. The most frequent injury was due to rice grains, but the inoculum appeared to be introduced during eye washing with contaminated water. Pseudomonal ulcers occurred most frequently in the monsoon season, and Fusarium cases were seen only in the hot, dry season.     

Cerebral Emboli during Cardiac Surgery in Children

Background: Microemboli occur commonly during cardiac surgery in adults, and, when present, increase the risk of neuropsychological deficits. Their incidence and significance during correction of congenital heart disease is unknown. The authors hypothesized that microemboli would occur before bypass with right-to-left cardiac shunts and would also occur in large numbers when the aortic crossclamp was released in children during repair of congenital heart defects.

Methods: In 25 children studied with carotid artery Doppler, embolic signals were counted and timed in relation to 13 intraoperative events. Patients were classified as either at high risk (obligate right-to-left shunt or uncorrected transposition of the great arteries) or at low risk (net left-to-right shunt or simple obstructive lesions) for paradoxical (venous to arterial) emboli.

Results: The median number of emboli detected was 122 (range, 2-2,664). Forty-two percent of all emboli were detected within 3 min of release of the aortic crossclamp. The high-risk group had significantly more emboli (median, 66; range, 0-116) during the time interval before cardiopulmonary bypass than did the low-risk group (median, 8; range, 0-73), with P < 0.01. There was no significant difference between the high-and low-risk groups in the total number of emboli detected. There was no apparent association between number of emboli and gross neurologic deficits.     

Nonheme iron in sickle erythrocyte membranes: association with phospholipids and potential role in lipid peroxidation

Previous studies documented the abnormal association of heme and heme proteins with the sickle RBC membrane. We have now examined RBC ghosts and inside-out membranes (IOM) for the presence of nonheme iron as detected by its formation of a colored complex with ferrozine. Sickle ghosts have 33.8 +/- 18.2 nmol nonheme iron/mg membrane protein, and sickle IOM have 4.3 +/- 3.0 nmol/mg. In contrast, normal RBC ghosts and IOM have no detectable nonheme iron. The combination of heme and nonheme iron in sickle IOM averages nine times the amount of membrane- associated iron in normal IOM. Kinetics of the ferrozine reaction show that some of this nonheme iron on IOM reacts slowly and is probably in the form of ferritin, but most (72% +/- 18%) reacts rapidly and is in the form of some other biologic chelate. The latter iron compartment is removed by deferoxamine and by treatment of IOM with phospholipase D, which suggests that it represents an abnormal association of iron with polar head groups of aminophospholipids. The biologic feasibility of such a chelate was demonstrated by using an admixture of iron with model liposomes. Even in the presence of tenfold excess adenosine diphosphate, iron partitions readily into phosphatidylserine liposomes; there is no detectable association with phosphatidylcholine liposomes. To examine the bioavailability of membrane iron, we admixed membranes and t-butylhydroperoxide and found that sickle membranes show a tenfold greater peroxidation response than do normal membranes. This is not due simply to a deficiency of vitamin E, and this is profoundly inhibited by deferoxamine. Thus, while thiol oxidation in sickle membranes previously was shown to correlate with heme iron, the present data suggest that lipid peroxidation is related to nonheme iron. In control studies, we did not find this pathologic association of nonferritin, nonheme iron with IOM prepared from sickle trait, high-reticulocyte, postsplenectomy, or iron-overloaded individuals. These data provide additional support for the concept that iron decompartmentalization is a characteristic of sickle RBCs.     

Abnormalities of peripheral nerve conduction in relation to thiamine status in alcoholic patients

Thiamine status was evaluated using the erythrocyte transketolase activation assay in 20 alcoholic patients admitted on a voluntary basis to a Detoxification Unit. Electromyographic evaluation revealed significant reductions of motor and sensory conduction velocities in the alcoholic group. 38% of alcoholic patients showed significant erythrocyte transketolase activation deficits indicative of severe thiamine deficiency. In the case of peroneal nerve, reduced conduction velocities were negatively correlated with abnormal transketolase parameters. These findings are consistent with a contributory (but not exclusive) role of thiamine deficiency in the pathogenesis of alcoholic peripheral neuropathy. Deficiencies of other vitamins as well as direct neurotoxic effects of alcohol could also be involved in this phenomenon.     

The effects of chronic treatment with the dihydropyridine, Bay K 8644, on hyperexcitability due to ethanol withdrawal, in vivo and in vitro.

1. The effects of chronic treatment with the dihydropyridine, Bay K 8644, were studied on the ethanol withdrawal syndrome, in vivo and in vitro. 2. Addition of racemic Bay K 8644 to the drinking mixture, throughout the chronic ethanol treatment, decreased the behavioural excitability seen during ethanol withdrawal in vivo. 3. All the signs of hyperexcitability in field potentials in the isolated hippocampal slice, caused by ethanol withdrawal, were decreased by the chronic administration of Bay K 8644. 4. These effects resembled those previously reported for chronic administration of calcium channel antagonists; racemic Bay K 8644 has both calcium channel activating and antagonist properties. 5. Measurement of brain levels of Bay K 8644 at the end of the chronic treatment showed that the compound reached micromolar concentrations during the treatment, but none could be detected in the tissues at the time of the above measurements. 6. It is possible that the results might be explained by predominance of the calcium channel antagonist properties of this compound, owing to the high central concentrations achieved during the treatment. Tolerance to the calcium channel activating properties of Bay K 8644 may also have occurred during the chronic treatment.     

Serum ionic fluoride levels in haemodialysis and continuous ambulatory peritoneal dialysis patients

High serum fluoride (F-) in patients with chronic renal failure (CRF) and end-stage renal disease (ESRD) is associated with risk of renal osteodystrophy and other bone changes. This study was done to determine F- in normal healthy controls and patients with ESRD on haemodialysis (HD) or peritoneal dialysis (PD). Seventeen healthy controls (12 males, 5 females) and 39 ESRD patients on dialysis (17 males, 22 females) were recruited in the study in a community with 47.4 +/- 3.28 microM/l (range 44-51 microM/l) of F- content in drinking water. Control subjects showed a mean serum F- concentration of 1.08 +/- 0.350 microM/l. Males in control group showed slightly higher F- levels (1.15 +/- 0.334, range 0.55-1.9 microM/l) than females (0.92 +/- 0.370, range 0.6-1.5 microM/l). Mean serum F- concentration did not correlate significantly with age and sex among control subjects, whereas such correlation was observed in patients with ESRD on dialysis. Mean serum F- concentration was significantly higher in patients on dialysis (2.67 +/- 1.09, range 0.8-5.2 microM/l) than normal controls. When grouped according to sex, the mean serum F- concentration in males (3.05 +/- 1.04, range 1.8-5.2 microM/l) was significantly higher than females (2.38 +/- 1.08, range 0.8-5.2 microM/l). When patients were grouped according to age, it was observed that F- concentration was significantly higher in patients with age groups 21-70 (2.86 +/- 1.05) than those with age group 13-20 years (1.42 +/- 0.531). Thus F- concentration correlated with age and sex, being higher in males and above 20 years. Despite appreciable clearance of F- (39-90%) across the peritoneum, patients on CAPD showed higher serum F- concentration than those on HD (3.1 +/- 1.97 vs 2.5 +/- 1.137 microM/l). Of the total 39 patients on dialysis 39% had their serum F- concentration above 3.0 microM/l, posing the risk of renal osteodystrophy.