Red cell transfusion therapy for anemia in patients with AIDS and ARC: incidence, associated factors, and outcome

The records of the San Francisco General Hospital (SFGH) Blood Bank were reviewed, and 263 likely AIDS and AIDS-related complex (ARC) patients were identified, who received 1545 units of packed red cells (PBRCs) between July 1, 1987, and June 30, 1988. A probability sample of 80 of these patients was selected randomly for detailed chart review. Of this sample, 78 (98%) were confirmed to have AIDS (86%) or ARC (14%). On the basis of the yearly census of the SFGH AIDS clinic, a transfusion incidence of 0.89 PRBC units per patient per year for patients with AIDS and 0.27 PRBC units per patient per year for those with ARC was estimated. Whereas 26 percent of the 177 transfusions studied in detail involved more than one associated (possibly causative) factor, antimicrobial drug therapy, zidovudine therapy, and disseminated Mycobacterium avium complex (MAC) infection were the sole associated factors in 20, 14, and 12 percent of the transfusions, respectively. To assess the role of MAC, the 263 transfused patients were compared with the 574 patients whose blood was submitted to the SFGH Mycobacteriology Laboratory during the same period. Patients whose blood yielded MAC had a relative risk of 5.2 for transfusion-requiring anemia. In 80 percent of cases, the patient returned home after transfusion. Most PRBC transfusions administered to AIDS or ARC patients were optimal therapy.     

Neurological sequelae in children surviving mechanical ventilation in the neonatal period

The incidence of mental defect, visual and hearing disability, major neurological handicap, and such minor neurological handicap as can be detected on examination at 2--9 years without formal intelligence testing, is presented among survivors of neonatal mechanical ventilation at Hammersmith Hospital between the years 1966--1973 inclusive. 77(21%) of 367 children survived, over three-quarters of them being born elsewhere. 3 died before the age of 6 months, 2 suddenly and unexpectedly at home, the third accidentally. 1 child was lost to follow up. 11 (15%) of the remaining 73 children had neurological sequelae as defined. In two-thirds this was moderate to severe. Spastic diplegia may no longer be the commonest form of cerebral palsy among those of low birthweight, particularly those surviving severe neonatal illness.     

Cholestatic jaundice in infancy. The importance of familial and genetic factors in aetiology and prognosis

One hundred and twenty-four infants admitted to hospitals in Norway between 1955 and 1974 during the first 3 months of life with cholestatic jaundice were studied retrospectively. Sixty-four infants had had extrahepatic atresia of the biliary tree and 60 had had intrahepatic cholestasis. This gives an incidence of about 1:9000 live births for cholestasis. In 4 of the 64 infants with extra-hepatic atresia a bile duct-to-bowel anastomosis had been performed but this was successful in only 2. Sixty of these infants had died by their 2nd birthday. Twenty-six of the infants with intrahepatic cholestasis had died by 1978 and the most common causes of death were cholestasis complicated by infection, bleeding, or hepatoma. The survivors aged between 4 and 23 years were followed up in 1978. In about two-thirds of them aetiological factors--such as alpha-1-antitrypsin deficiency, arteriohepatic dysplasia, cholestasis with lymphoedema--and other familial or genetic factors, or infections were found. Four of the 34 survivors are known to have cirrhosis. Twenty patients had biochemical abnormalities, and 12 had normal liver function tests. Two patients could not be examined. Of the 19 patients with familial or genetic aetiological factors, 4 had cirrhosis, 14 had biochemical abnormalities, and only 5 had normal liver function tests. Of 11 survivors with idiopathic disease or septicaemia, none had cirrhosis and only 4 had abnormal liver function tests.     

Malignancies in UK children with HIV infection acquired from mother to child transmission

By April 1995, 302 cases of vertically acquired HIV infection had been reported through the British Paediatric Association Surveillance Unit. Over 50% of these children had developed an AIDS indicator disease, including nine malignancies (seven cases of non-Hodgkin's lymphoma (NHL) and two of Kaposi's sarcoma). There were two other malignancies that were not AIDS indicator diseases. In children less than 5 years of age the incidence of NHL was approximately 2500 times greater than expected in the UK child population. Three children presented with NHL as their AIDS indicator disease and four developed NHL at a median of 14 (range 10-19) months after the initial diagnosis of AIDS. Six of the seven children died at a median of 6.5 (range 2-14) months after the diagnosis of NHL. The seventh child responded to treatment and is alive nearly four years later. Histology was available in five cases, of which four were of B cell and one of T cell origin. Epstein-Barr virus was detected in all three patients with NHL where it was sought; all had B cell lymphomas. Although comparatively rare, malignancies occur in children infected with HIV and may be the presenting illness. Paediatricians now need to consider HIV infection as a predisposing cause of childhood cancer, especially NHL.     

Incidence of insulin dependent diabetes mellitus in Karachi, Pakistan

OBJECTIVES: To determine the incidence of insulin dependent diabetes mellitus (IDDM) among children aged up to 16 years residing in the city of Karachi, Pakistan, during the five years from 1989 to 1993. DESIGN: Retrospective study of incidence using hospital and clinic records. SETTING: The city of Karachi, Pakistan. SUBJECTS: Children satisfying standard criteria for the diagnosis of IDDM, attending treatment facilities for the first time during the study period. MAIN OUTCOME MEASURES: The incidence of IDDM in this population and its variation by age and sex. RESULTS: The incidence of IDDM in this population is 1.02/100000 per year, which is one of the lowest incidence rates yet reported. CONCLUSIONS: The very low incidence of IDDM, contrasted with the substantially higher incidence among migrants, supports the view that environmental factors are the major determinants of variations in the incidence of this condition between populations.     

Height and weight in cystic fibrosis: a cross sectional study. UK Cystic Fibrosis Survey Management Committee

Cross sectional data reporting the height, weight, and body mass index of UK patients with cystic fibrosis are presented. During the first decade of life height and weight in patients with cystic fibrosis are maintained at about 0.5 SD below those of the general population, which reflects an improvement over earlier published observations. Postpubertal stature and weight maintenance in the cystic fibrosis population still show substantial deficits which may be related to treatment.     

Improvement in appropriate autologous donations with local education: 1987 to 1989

Preoperative autologous blood donation for elective surgery patients at university hospitals was underused in the past. More recently, national educational efforts have been made. To test the impact of local surgeon interviews and education, in 1988 the same local educational program was instituted at three university hospitals; three community hospitals were used as controls. Donation by appropriate patients of interviewed surgeons (elective surgery, crossmatch recommended, no contraindications to donation) increased from 24 percent (44/180) to 40 percent (88/222) (p = 0.002) and 15 percent (21/143) to 32 percent (41/127) (p = 0.001) at two university hospitals where the investigator-educators were on site, but not at the three community hospitals. Between 1987 and 1989, donation rates at all six hospitals remained low among patients for whom autologous donation was (probably) less appropriate. Donation rates for type and screen procedures were 3.0 percent (131/4587) in 1987 and 3.0 percent (199/6606) in 1989 (p = 0.67). Donation rates for "no blood order" procedures were 0.2 percent (15/9429) in 1987 and 0.1 percent (9/11,239) in 1989 (p = 0.14). It can be concluded that appropriate autologous blood donations increased at university hospitals where surgeons were individually interviewed and educated by an investigator on site. However, despite this increase, apparently eligible elective surgery patients in 1989 still failed to donate. This situation deserves additional investigation.     

Two cases of Robertsonian translocations in oligozoospermic males and their consequences for pregnancies induced by intracytoplasmic sperm injection

Two case histories are presented documenting structural chromosome abnormalities in infertile males. The abnormalities were detected only after application of intracytoplasmic sperm injection (ICSI) was repeatedly unsuccessful or resulted in an abnormal pregnancy. A mosaic Robertsonian translocation 45,XY,der(13;13)(q10; q10)/46,XY,t(13;13)(p10;p10), der(13p;13p) incompatible with normal offspring was found in a male with extreme oligozoospermia after three subsequent ICSI treatments were unsuccessful and one had resulted in a spontaneous abortion. A second case involved a Robertsonian translocation 45,XY,der(13;14)(q10;q10) which was detected in a male with extreme oligozoospermia after ultrasound abnormalities were found in an ICSI-induced twin pregnancy. Amniocentesis showed an unbalanced 46,XY,+13,der(13;14)(q10;q10) karyotype in one twin and a Robertsonian 45,XX,der(13;14)(q10;q10) karyotype in the other twin. Chromosome analysis of males with abnormal sperm characteristics is advised prior to ICSI.      

Molecular genetic analysis of the gene encoding the trifunctional enzyme MTHFD (methylenetetrahydrofolate-dehydrogenase, methenyltetrahydrofolate-cyclohydrolase, formyltetrahydrofolate synthetase) in patients with neural tube defects

It is now well recognized that periconceptional folic acid or folic acid containing multivitamin supplementation reduces the risk of neural tube defects (NTDs). Recently we were able to show that homozygosity for a thermolabile variant of the enzyme methylenetetrahydrofolate reductase is associated with an increased risk for spina bifida in patients recruited from the Dutch population. However, this genetic risk factor could not account for all folic acid preventable NTDs. In an attempt to identify additional folate related enzymes that contribute to NTD etiology we now studied the methylenetetrahydrofolate dehydrogenase gene on chromosome 14q24 which encodes a single protein with three catalytic properties important in the folate metabolism. The cDNA sequence of 38 familial and 79 sporadic patients was screened for the presence of mutations by single strand conformation polymorphism (SSCP) analysis followed by sequencing. Two amino acid substitutions were identified. The first one (R293H) was detected in a patient with familial spina bifida and not in 300 control individuals. The mutation was inherited from the unaffected maternal grandmother and was also present in two younger brothers of the index patient, one of them displaying spina bifida occulta and the other being unaffected. The second change turned out to be an amino acid polymorphism (R653Q) that was present in both patients and controls with similar frequencies. Our results so far provide no evidence for a major role of the methylenetetrahydrofolate-dehydrogenase (MTHFD) gene in NTD etiology. However, the identification of a mutation in one family suggests that this gene can act as a risk factor for human NTD.