T-cryptantigen (TCA) activation in surgical neonates: a hidden problem.

The Thomsen-Friedenreich cryptantigen (TCA) is located on the surface of all red cells, but is concealed by a layer of neuraminic acid. When bacteria that produce neuraminidase disrupt this coating, the TCA can be exposed and activated. If blood products containing antibody to the TCA are subsequently administered, haemolysis can result. While the relationship between TCA and necrotising enterocolitis (NEC) is well described, the incidence of TCA activation in other forms of sepsis in surgical neonates is not known. In a prospective study, 117 patients admitted to the Surgical Neonatal Nursery were examined for evidence of TCA activation. Of the 117 babies, 69 were clinically non-septic and only 1 had weak TCA activation (1.4%). Forty-eight were clinically or bacteriologically septic; 8 of these demonstrated TCA activation (17%), 3 of whom died. Forty of the septic group showed no evidence of TCA activation although 27 grew organisms on culture; 17 in this group died. Two of the TCA-activated babies received unwashed red cells, and both haemolysed; 4 TCA-activated babies received washed red cells and none haemolysed. Although 1 of the well babies in this study demonstrated TCA activation, we would not recommend routine TCA testing on clinically well babies. We would, however, recommend routine testing in all clinically septic infants, as 17% showed signs of TCA activation in this study. We would also suggest the adoption of a selective transfusion policy in TCA-activated patients to avoid the risk of haemolysis. This may help to reduce unnecessary morbidity and mortality in a high-risk group of neonates.

An outbreak of hepatitis A among South African patients with hemophilia: evidence implicating contaminated factor VIII concentrate as the source.

We report an outbreak of hepatitis A in nine South African hemophiliacs treated exclusively with infusions of factor VIII concentrate. The solvent/detergent (S/D) method (which does not inactivate nonenveloped viruses) was used for virus eradication. In three of six patients studied at a molecular level hepatitis A virus (HAV) complementary DNA (cDNA) amplified from serum by reverse transcription-polymerase chain reaction (RT-PCR) was identical to HAV cDNA in 1 of 14 lots (no. 53) of factor VIII tested. The plasma for lot 53 was obtained from donors in the United States: 1 of 12 samples of this source material contained the same HAV cDNA sequences. In another two patients receiving lot 53, the degree of identity between HAV cDNA in serum and that in factor VIII was only 88% and 89%, respectively, and in the sixth patient, who did not receive lot 53, it was 90%. The degree of HAV cDNA homology among five patients in an independent point-source outbreak of hepatitis A was 100%, and that in nine patients who acquired this infection sporadically in Johannesburg, Egypt, or Russia, was 93% to 100%. Whether the three hemophiliacs with low HAV cDNA homology with lot 53 acquired the infection from other unidentified virus strains contaminating factor VIII or from extraneous sources is unknown. This study provides further evidence that factor VIII concentrate prepared by the S/D method may be contaminated by the HAV, in this instance at source, and may cause hepatitis in recipients. Proof of a cause-and-effect relationship will, however, depend on animal inoculation studies.

Racial differences in the seroprevalence of hepatitis A virus infection in Natal/KwaZulu, South Africa.

The age- and race-specific seroprevalence of hepatitis A virus (HAV) infection was determined by radioimmunoassay (RIA) in 786 subjects between the ages of 6 months to 60 years. More than 50% of African children were seropositive by the age of 5 years. In blood donors (17-60 years), 50% (93/187) of Whites, 67% (110/163) of Indians, 85% (117/137) of Coloureds, and 91% (115/127) of Africans were seropositive. There was a significant difference in the seroprevalence of HAV infection between White blood donors and blood donors from the other three racial groups [Coloureds (P < 0.0001), Africans (P < 0.0001), and Indians (P < 0.001)] and between Indians and Coloureds (P < 0.0001) and Indians and Africans (P < 0.0001). There was no significance difference in HAV infection between Coloureds and Africans (P < 0.200). Eighty-seven per cent (32/37) of rural Africans had previous infection. In the African population HAV infection is acquired in childhood. There are significant racial differences in the seroprevalence of HAV infection. The surveillance of HAV infection may be used as a valuable yardstick to monitor the changing standards of hygiene and socioeconomic conditions of a community in transition in South Africa and to make rational public health decisions regarding a hepatitis A vaccination policy.

Hepatitis C virus antibodies among risk groups in a South African area endemic for hepatitis B virus.

The prevalence of anti-HCV was studied in a South African area endemic for hepatitis B virus. A total of 35,685 volunteer blood donors (22,034 whites, 9,218 Asians, 3,077 Africans, 1,356 coloureds), 71 haemophiliacs, 84 chronic dialysis patients, 100 antenatal attenders, 212 nurses, and 20 HIV-positive male homosexuals were tested for anti-HCV. Repeat positive second generation Ortho HCV EIA was used to determine HCV status for the blood donors; Abbott-II HCV EIA combined with a neutralisation test was used for the other risk groups. Antibody to hepatitis B core antigen (anti-HBc) was also tested in the haemophiliacs, nurses, and chronic dialysis patients. Seroprevalence for the blood donor population was 0.16, 0.34, 0.75, and 0.22% for whites, Asians, Africans, and coloureds, respectively. Of the risk groups tested, 39.4% of haemophiliacs and 4.8% of chronic dialysis patients were positive; of the remainder tested none was positive. Fifty percent of nurses, 47.9% of haemophiliacs, and 22.6% of dialysis patients had serological evidence of past exposure to hepatitis B virus (anti-HBc positive). These findings indicate a low prevalence of anti-HCV in the blood donor population, thus probably resulting in a low prevalence in groups exposed to blood and blood derivatives. The overall difference in prevalence between the race groups was significant (P < 0.0001). The high prevalence of hepatitis B virus compared to the low prevalence of HCV suggests that the main modes of transmission of the two viruses are probably different.

Iron and folate status of pregnant black women in Gazankulu.

A limited nutritional survey was carried out in 229 first attenders at an antenatal clinic in Gazankulu during the winter of 1984. Haemoglobin concentrations equal to or less than 11 g/dl were found in 33% of these women, the prime reason being folate deficiency. Serum folate concentrations were less than a 3.5 ng/ml in 60% of subjects and less than 3.0 ng/ml in 48%. A mean corpuscular volume of 100 fl or more, which reflects a defect in red cell DNA synthesis, was present in 35%. Iron related measurements indicated that only 17% were also iron deficient but the figure is certainly an underestimate, since the presence of folate deficiency tends to mask concomitant iron deficiency. The findings underline the need for folate and iron supplementation in pregnancy; the very high prevalence of significant folate deficiency also indicates that serious consideration should be given to the fortification of maize meal with folic acid.

Dissociation of methionine synthetase (EC 2.1.1.13) activity and impairment of DNA synthesis in fruit bats (Rousettus aegyptiacus) with nitrous oxide-induced vitamin B12 deficiency.

1. The effect of methylcobalamin inactivation by the anaesthetic gas nitrous oxide on the activity of the cobalamin-dependent methionine synthetase (5-methyltetrahydrofolate homocysteine methyltransferase; EC 2.1.1.13) reaction, and on DNA synthesis, in the fruit bat Rousettus aegyptiacus, was examined. 2. Methionine synthetase activity in the liver of bats exposed to N2O-oxygen (50:50, v/v) for 90 min/d averaged 32% of that of controls after 4 d of exposure and only 5% after 12-14 weeks of exposure. 3. DNA synthesis in the bone marrow, as reflected by the deoxyuridine suppression test, was unaffected by 4 d of exposure to N2O and only minimally affected after 5-10 weeks of exposure. 4. These results suggest that DNA synthesis in the fruit bat is unusually resistant to inhibition of methionine synthetase and imply the existence of a non-methylated circulating folate pool in this species.

Ferritin in breast milk of black urban and rural mothers.

Ferritin levels in serum and milk were investigated in series of 15 urban and 18 rural black mothers. No mother was anaemic. Mean serum ferritin levels in the urban and rural groups were 57 +/- 55 ug/l and 25 +/- 28 ug/l (mean +/- SD). Corresponding milk ferritin concentrations were 21 +/- 22 ug/l and 29 +/- 30 ug/l respectively. The significance of ferritin in human milk is discussed.

Acute megakaryoblastic leukaemia with 3q inversion and elevated thrombopoietin (TSF): an autocrine role for TSF?

A patient with acute megakaryoblastic leukaemia is described in whom exactly the same paracentric inversion of 3q was detected as in three previously documented cases. The patient's serum thrombopoietin (TSF) was significantly raised. Based on these findings we postulate a role for a gene (? oncogene) on chromosome 3q in thrombopoietin production. Abnormalities of 3q may assist in delineating a subgroup of acute nonlymphocytic leukaemia, namely acute megakaryoblastic leukaemia.

Serum vitamin B12 binders in South African blacks with hepatocellular carcinoma.

Sera from 242 South African blacks with hepatocellular carcinoma were assayed for unsaturated vitamin B12 binding capacity (UBBC) and vitamin B12 activity. Six patients were younger than 20 years of age, and 24% were younger than 30 years of age. Eighty-four percent of the patients had a slightly raised UBBC and 86% had a slightly elevated vitamin B12 value, but in no patient was an exceptionally high UBBC present. Serum UBBC and vitamin B12 were not higher in younger patients, and raised UBBC values were not related to serum alpha-fetoprotein values. Serum UBBC and vitamin B12 concentrations were not significantly different in patients with and without coexisting cirrhosis. In none of the patients with a UBBC above 3000 pg/ml was the fibrolamellar variant of hepatocellular carcinoma present. The authors conclude that South African blacks with hepatocellular carcinoma do not secrete an abnormal vitamin B12 binding protein.

A sex difference in serum cobalamin and transcobalamin levels.

In healthy young adults, serum levels of cobalamin, unsaturated and total cobalamin binding capacity, and transcobalamin (TC) II are significantly higher in females, while TC III is higher in males. These findings have relevance to the reference values in normals for these tests.

Transition from a hunter-gatherer to a settled lifestyle in the !Kung San: effect on iron, folate, and vitamin B12 nutrition.

In 1969 a group of hunter-gatherer San were studied (Am J Clin Nutr 1971;24:229-42). Their state of hematological nutrition was excellent with a negligible incidence of iron, folate, or vitamin B12 deficiency. A genetically and linguistically similar San community who have been settled for the past 15 yr were the subjects of the present study. Anemia, due in the main to iron and/or folate deficiency, has become more common. Alcoholism has become rife in both sexes and all age groups. Our findings show that a settled lifestyle has resulted in a significant deterioration in the San's hematological nutrition.

Vitamin B12 levels in the prolonged use of sodium nitroprusside.

Long-term (greater than 48 h) sodium nitroprusside (SNP) infusion significantly reduced cobalamin (vitamin B12) levels in 23 patients treated in a CCU after myocardial infarction. There was no evidence of vitamin B12 deficiency or SNP toxicity. Low vitamin B12 levels should not limit the use of SNP, because prolonged infusion of SNP at maximum doses of 2.5 micrograms/kg X min did not adversely affect hemodynamic stability.

Effect of a vitamin B-12-deficient diet on lipid and fatty acid composition of spinal cord myelin in the fruit bat.

The effects of vitamin B-12 deficiency on lipids and fatty acids of spinal cord myelin were studied in control and vitamin B-12-deficient fruit bats. Very low plasma and brain vitamin B-12 concentrations were present in animals fed the vitamin B-12-free, all fruit diet. Myelin was isolated from the spinal cord of control and vitamin B-12-deficient animals (n = 3 pools) by means of a flotation method in a discontinuous sucrose gradient. The molar concentration of cholineglycerophosphatide was significantly lower in the deficient bats than in the controls. The molar cholesterol: phospholipid ratio in the deficient bats was also significantly lower. The odd-chain fatty acid 15:1 was not detected in cholineglycerophosphatide from the controls, but comprised 1.4% of the total fatty acids in the deficient group. The odd-chain fatty acids 15:0, 17:1 and 19:0 were present in slightly higher amounts in cholineglycerophosphatide of deficient bats. Lipid and fatty acid differences were related to the vitamin B-12-requiring methionine synthetase and methylmalonyl CoA mutase reactions.

Cobalamin inactivation by nitrous oxide produces severe neurological impairment in fruit bats : protection by methionine and aggravation by folates.

Nitrous oxide, which inactivates cobalamin when administered to fruit bats, results in severe neurological impairment leading to ataxia, paralysis and death. This occurs after about 6 weeks in animals depleted of cobalamin by dietary restriction, and after about 10 weeks in cobalamin replete bats. Supplementation of the diet with pteroylglutamic acid caused acceleration of the neurological impairment - the first unequivocal demonstration of aggravation of the neurological lesion in cobalamin deficiency by pteroylglutamic acid. The administration of formyltetrahydropteroylglutamic acid produced similar aggravation of the neurological lesion. Supplementation of the diet with methionine protected the bats from neurological impairment, but failed to prevent death. Methionine supplementation protected against the exacerbating effect of folate, preventing the development of neurological changes. These findings lend support to the hypothesis that the neurological lesion in cobalamin deficiency may be related to a deficiency in the methyl donor S-adenosylmethionine which follows diminished synthesis of methionine.

A comparison of serum transcobalamin levels in white and black subjects.

Serum transcobalamins (TC) have been measured in 82 white and 79 Black healthy adults, 170 white and 73 Black pregnant subjects and in cord blood samples from 33 whites and 13 Blacks. Healthy Black adults had significantly higher mean TC I, TC II, and TC III levels than white adults of the same sex. These differences in mean TC levels persisted at all stages of pregnancy. Mean cord blood levels of TC II and TC III were significantly higher in Blacks than in whites. No environmental factors could be identified to account for these differences, which are probably genetically determined.

Levels of transcobalamins I, II, and III during pregnancy and in cord blood.

The levels of unsaturated serum transcobalamins (TC I, TC II, and TC III) of 193 women at various stages of pregnancy and the puerperium, and of 33 specimens of cord blood, have been measured. In addition, seven subjects were studied serially through pregnancy. The pattern of changes was similar in both groups. TC I and TC III rose steadily during pregnancy and fell in the puerperium, while TC II decreased in the 2nd trimester, rose sharply in the 3rd and fell in the puerperium. The changes in the individual TCs probably result from a complex of hormonally induced changes in binder production, release, or catabolism, and the effect of hydraemia.