Nondisclosure of human immunodeficiency virus and hepatitis C virus coinfection in a patient with hemophilia: medical and ethical considerations.

This article discusses a medical and ethical dilemma: whether to disclose a positive HIV (human immunodeficiency virus)/HCV (hepatitis C virus) coinfection to an adolescent boy without symptoms with hemophilia despite the objections of his parents. An actual case history is presented and the dilemma faced by the medical team is discussed. Numerous family conferences, all excluding the patient, held during the last 5 years discussed the medical team's obligation for full disclosure, the emerging autonomy of the patient, and the potential for medical disaster (e.g., HIV transmission) if full disclosure were not permitted. Despite this, the family did not agree to allow disclosure. The patient and parents assured us of his sexual inactivity. Legal opinion was sought from the university counsel. The dilemmas are multiple. Is there a convincing argument to insist on disclosure of these facts to this patient, particularly when there is ambiguity regarding the appropriateness of HIV and HCV treatment? Does the ethical argument that he is at potential risk for transmitting HIV/HCV outweigh the rights of the family? What are the rights of the rest of the family? What are the rights of the minor? Is it our ethical responsibility to disclose a probably fatal diagnosis?

Successful treatment of high titer inhibitors in mild hemophilia A with avoidance of factor VIII and immunosuppressive therapy.

We describe two patients with mild hemophilia A (MHA) who developed high titer inhibitor (HTI) following intensive recombinant factor VIII (rFVIII) concentrate replacement for surgery and trauma. Intranasal desmopressin was instituted shortly following immunosuppressive therapy (IST) and activated prothrombin complex concentrate (APCC) in one case, and following APCC alone in the second case. Avoidance of factor VIII (FVIII) coupled with intranasal desmopressin prophylaxis three times a week resulted in undetectable inhibitor levels. Both patients have had no further bleeding episodes and have been maintained on desmopressin prophylaxis prior to activity for the past 2 to 3 years. Recombinant factor VIIa (rFVIIa) was used successfully prior to a second surgery in one patient without complication.

Serologic markers of viral hepatitis A, B, C, and D in patients with hemophilia.

Forty-one patients with hemophilia A were studied for the prevalence of serological markers for hepatitis A, hepatitis B, hepatitis C (non-A and non-B hepatitis), and delta hepatitis (hepatitis D). Ten of 41 (24.4%) patients demonstrated hepatitis A antibody and 31 of 41 (75.6%) patients had a serologic marker for previous hepatitis B infection; four of these 31 patients (13%) also demonstrated antibody to delta agent (hepatitis D). Thirty-seven of 41 (90.2%) patients demonstrated antibody for hepatitis C. Nine of 31 (29%) patients with a hepatitis B marker (no hepatitis B vaccinees) were negative for anti-HBc but positive for anti-HBs; all of these nine patients were HIV antibody positive, although they had no overt immunodeficiency. Twenty-six of 41 (63.5%) patients were HIV antibody positive. Of HIV antibody positive patients, 27%, 88%, and 100% demonstrated evidence of a previous hepatitis A, hepatitis B, or hepatitis C, respectively. Of HIV antibody negative patients; 20%, 53%, and 73% of the patients demonstrated evidence of a previous hepatitis A, hepatitis B, or hepatitis C infections, respectively. The difference between HIV antibody positive and HIV antibody negative groups was not significant for hepatitis A but was significant for hepatitis B (P < 0.001) and hepatitis C (P < .001). Of the 31 patients with a hepatitis B serologic marker, all had antibody to hepatitis C. Of 10 patients, without a hepatitis B serologic marker, only 6 (60%) had antibody to hepatitis C.(ABSTRACT TRUNCATED AT 250 WORDS)

Haemoglobin F and A2 in Nigerian children with sickle cell anaemia.

The concentration of haemoglobins F and A2 in 132 Hb SS children aged 6 months to 16 years and 50 age- and sex-matched controls has been determined. The mean HbF concentration in Hb SS patients and controls were 9.5 per cent (range 1.7-24.5 per cent) and 1.5 per cent (range 0.5-14.4 per cent) respectively while HbA2 concentrations were 2.7 per cent (range 1.6-3.7 per cent) and 2.4 per cent (range 1.3-3.9 per cent) respectively. For 18 Hb SS patients seen in the stable state and during vaso-occlusive crisis, there was no significant difference in HbF concentration between the two states.

Foetal haemoglobin in Nigerian children with sickle cell anaemia. Effect on haematological parameters and clinical severity.

The relationship of foetal haemoglobin (HbF) to several clinical and haematological parameters in 86 children aged 5 to 16 years who had sickle cell anaemia (SCA) has been examined. The mean HbF level was 6.8 +/- 3.6%. Higher HbF values were significantly associated with fewer blood transfusions, fewer hospital admissions and higher rate of hepatomegaly. A trend for children with higher HbF levels to have better physical development and a more normal haemogram was also noted though this was not statistically significant.

Familial occurrence of cryptorchidism.

A case of Cryptorchidism involving a father and all his four sons who are product of a nonconsanguineous marriage has been described. From a review of the literature, as well as evidence derived from the family history, it is suggested that the mode of inheritance may be autosomal dominant with incomplete penetrance or multifactorial.

The diagnostic value of leukocyte indices and micro-erythrocyte sedimentation rate in neonatal infections.

In an attempt to compare sensitivity, specificity and predictive values of newborn screening tests for sepsis, leukocyte indices derived from healthy African neonates, Manroe's published indices, micro-erythrocyte sedimentation rates (Mini-ESR) and a combination of the Mini-ESR and leukocyte indices of African neonates were applied to 32 infected infants and 20 uninfected neonates studied prospectively. The sensitivity, specificity and predictive values derived from Manroe's indices were 93%, 35% and 69.8% respectively. The corresponding values derived from the indices of African neonates were 84.4%, 95% and 96.4%. Local reference values were thus more specific and predictive. Values obtained by combining Mini-ESR with indices of the African Neonates were 100%, 85% and 94%. The Mini-ESR alone yielded a sensitivity of 96.9%, specificity of 90% and a predictive value of 94%. The mini-ESR alone may therefore be a more valuable test in the sepsis screening of the African neonate.

Physiologic jaundice in the Nigerian neonate.

In the course of a systemic study of physiologic hyperbilirubinaemia, 200 Nigerian newborn infants were evaluated daily over a 12-day period. The pre-term and post-term neonates exhibited a distinct biphasic pattern of hyperbilirubinaemia. Mean peak bilirubin levels of 8.20 mg/dl for the pre-term, 7.15 mg/dl for the post-term and 8.34 for the term were attained on the fourth, third and fifth days, respectively. Term small for gestational age neonates experienced mean peak bilirubin levels of 7.02 mg/dl at the age of 4 days and maintained a sustained elevation for as long as the last day of the study. Higher values of physiologic hyperbilirubinaemia are observed in this study than has been reported for American neonates.

Mini-erythrocyte sedimentation rates in healthy and infected Nigerian neonates.

Normal values for mini-erythrocyte sedimentation rates (mini-ESR) in healthy Nigerian neonates are reported and compared with values obtained for infected neonates. The mean and 95th percentile values, measured in mm/h in healthy neonates in the first week of life, range from 1.8 to 7.7, and in the 4th week of life from 9.1 to 16. The mini-ESR values of the infected neonates were significantly higher than the 95th percentile values of healthy neonates. Because the sensitivity and specificity of the mini-ESR in the diagnosis of neonatal infection are high, its application as an appropriate technology for evaluating suspected cases of infection in the developing countries should be encouraged.

Normal hematological values of the African neonate.

A longitudinal study of normal hematological values of the newborn infant was undertaken in an effort to provide baseline data for assessing the African Neonate with hematological problems. There were 402 neonates, consisting of 304 full-term, 51 preterm and 47 post-term infants. The Hematocrit (Hct), Hemoglobin (Hb), Red Blood Cell Count (RBC), Reticulocyte count (Retic) and Nucleated Red Blood Cell Count (NRBC) were serially determined. The red cell indices, Mean corpuscular Hemoglobin (MCH), Mean Corpuscular volume (MCV) and Mean corpuscular Hemoglobin Concentration (MCHC) were calculated for each neonate. Our results showed that African neonates have lower hematological values than their North American and European counterparts. This was neither a reflection of an intrauterine anemia nor was it due to variables resulting from the timing of cord blood sampling. On the first day of life, the mean Hct was 45.4%; mean Hb was 15.46 gm/dl; and the RBC was 4.02 X 10(6) cells/mm2. The Retics, NRBC and other red blood cell indices do not differ from those of neonates reported from other parts of the world. We suggest therefore that the low hematological values of the African neonate may be intrinsic.

Pattern of leukocytes in the blood of healthy African neonates.

Serial leukocyte counts were performed on 107 full-term, 40 preterm and 35 postterm African neonates during the first 4 weeks of life. In addition, WBC differential counts were done on 85 of these neonates, selected randomly. Both the absolute and relative amounts of each cell type were determined. The main features of leukocyte counts during the neonatal period were: a mean leukocyte count of 12,580 cells/mm3 (range 3,500-20,500) on day 1, with no statistical difference observed between any two of the three groups studied; a decline in mean leukocyte count by day 7 which remained stable throughout the neonatal period, and a neutrophil count of 5,670 cells/mm3 (range 980-12,900) on day 1. This figure is much lower, both in relative and absolute numbers, than that reported for babies in Europe and North America. Lastly, the lymphocyte count was consistently higher than in comparable reports from Europe and North America. The constant leukocyte count, particularly that of neutrophils, may be of importance in detecting infected African neonates.

The limits of physiological anemia in the African neonate.

In order to determine the limits of physiological anemia in the African neonate, the hematological values of 402 healthy neonates were determined. It was observed that although the African neonate had much lower hematological values at birth when compared with their North American and European counterparts, the eventual nadir reached is approximately the same. The hematocrit, hemoglobin and red blood cell count of preterm infants on the first day of life were comparable to those of full-term and postterm infants. However, the preterm infants had a more precipitous drop in these values and, consequently, reached a nadir much lower than full-term and postterm infants. The nadir was reached between 6 and 8 weeks in each group. In all three groups, recovery was spontaneous and preceded by a rise in reticulocyte count. It is also significant that by 16 weeks of life, no significant difference exists between the values for preterm, full-term and postterm infants.

Brief clinical report: ring-11 chromosome: phenotype-karyotype correlation with deletions of 11q.

The cytogenetic evaluation of a female infant with congenital anomalies led to the identification of the second reported case of a ring-11 chromosome. Unlike the previously described case, in which the patient had only minimal clinical findings and no demonstrable loss of material from the ring, our patient had numerous anomalies that were associated with a substantial deficiency of 11q material. The different phenotypes in these two cases represent variation in the amount and location of the chromosomal material lost during the genesis of the ring. The manifestations of this patient and the deletion of region q24 leads to qter from the ring-11 identify a specific chromosome deletion syndrome referred to as del (11q) syndrome.

Familial occurrence of congenital pulmonary lymphangiectasis. Genetic implications.

Congenital pulmonary lymphangiectasis (CPL) is a rare, generalized disease of the lung, consisting of lymphatic cysts in the subpleural and interlobular connective tissue. This disorder typically manifests a clinical picture of acute respiratory distress with cyanosis shortly after birth, with death occurring in the neonatal period. Several cases of this disorder have been described in the literature, but there has been no family with more than one affected child. We report the first instance, to our knowledge, of familial cases of CPL, which raises an important question regarding a possible genetic component in this disorder. The implications of this are discussed.

Omphalocele in half-siblings.

A family is described in which half-siblings, a boy and a girl born to unrelated mothers and a phenotypically normal father, were affected with omphalocele. The suggested mode of transmission remains unclear. Prenatal diagnosis to detect an affected fetus should be offered to relatives of omphalocele-affected individuals.

A syndrome of microcephaly and cataracts in four siblings. A new genetic syndrome?

We describe a syndrome of microcephaly, with extreme failure to thrive, (severe spasticity), kyphoscollosis, cataracts, and hip dysplasia in four siblings. The syndrome could be a new one, although it has several features resembling those described by Lowry et al. It is suggested that this syndrome is inherited as an autosomal-recessive condition.

The study of genetic variation in Nigeria. II. The genetics of polydactyly.

The analysis of polydactyly in the Nigerian population has revealed a frequency of 22.78 per thousand, with slight variations from one region of the country to another. All polydactyly was post-axial and most was of type B. Although we expected this frequency to be the same in both males and females, we observed that females have a significantly lower frequency (17.92 per thousand) than the males (27.08 per thousand). This condition appears to be inherited as an autosomal dominant gene with a penetrance of 64.9%, and highly variable expressivity. There does not seem to be any phenotypic difference between individuals who are homozygous and those who are heterozygous for the gene.

Genetic variation in Nigeria. I. The genetics of phenylthiourea tasting ability.

Phenylthiourea (PTC) taste sensitivity thresholds have been measured for 2,013 Nigerians using a modified sorting technique. The frequency of non-tasters was observed to be 12.5% and the t gene frequency was 0.354. There was a significant difference between the sexes at the 0.01 level for the overall population. However, when the data are analyzed according to the geographical origin of the subject, the sex difference is found only in one of three geographical regions. Also, there may be geographical influences on PTC taste sensitivity, although this was not statistically significant. The estimates reported in this population differ considerably from some of the previously published estimates for black populations.