Radioxenon standards used in laboratory inter-comparisons.

Preparation methods for (133)Xe standards of activity concentration and the results of the 2014 (133)Xe laboratory inter-comparison exercise are described. One element of the quality assurance/quality control (QA/QC) program for laboratories of the International Monitoring System (IMS) will be regular inter-comparison exercises. However, until recently, no activity concentration standards for benchmarking were available. Therefore, two (133)Xe activity concentration reference standards were produced independently by Idaho National Laboratory and Seibersdorf Laboratories and used for the 2014 laboratory inter-comparison exercise. The preparation of a complementary (127)Xe activity concentration standard as well as a (127)Xe laboratory inter-comparison exercise suggests (127)Xe as a suitable isotope for QA/QC of remote IMS noble gas stations.

Interferon-gamma receptor deficiency mimicking Langerhans' cell histiocytosis.

Two patients who were initially given a diagnosis of Langerhans' cell histiocytosis on the basis of the clinical, radiologic, and biopsy findings had mycobacterial infection subsequently identified. The correct diagnosis of dominant partial interferon-gamma receptor deficiency was established.

A high uptake eye and foot screening service for an urban population.

AIMS: A community diabetes eye screening service using slit-lamp biomicroscopy and colour fundus photography was set up in 1993 at the Barnsley District General Hospital Diabetes Centre with a foot screening service being added in 1994. The service is available for all diabetic patients in the Barnsley health district (encompassing 220,000 people). After 4 1/2 years, a survey was carried out to establish the uptake of this service. METHODS: All diabetic patients on the local diabetes register were checked for attendance at the eye screening service or the Barnsley District General Hospital Eye Department. Questionnaires were sent to general practitioners to establish what screening was received by those attending neither of these services. RESULTS: More than 10% of patients were found to be incorrectly registered. Of the 4000 correctly registered diabetic patients, 62% were screened annually by this service and 25% were under the care of the Department of Ophthalmology. Half of the remaining 13% were screened at other hospitals or by opticians or general practitioners and the other half were either too old or ill to be screened or were non-compliant. CONCLUSIONS: This service has a high uptake, and is recommended for a circumscribed urban population.

Early diagnosis of severe combined immunodeficiency syndrome.

Infants with severe combined immunodeficiency syndrome (SCIDS) have a greatly improved prognosis if diagnosed and treated before they develop overwhelming infection. Clinical and laboratory data on 45 patients with SCIDS were retrospectively reviewed to assess the value of absolute lymphocyte counts in making an early diagnosis. Ninety infants matched for age, sex, and presenting symptoms were used as controls. Thirteen (29%) infants with SCIDS were diagnosed at birth as previous siblings had been affected; 32 (71%) were diagnosed after the development of symptoms. Eighteen (56%) of these remained undiagnosed until after 6 months of age. The first symptoms occurred at a median of 5 weeks (range 1 day to 8 months) and the first admission to hospital was at 4 months (range 1 week to 16 months). Symptoms included respiratory infection (91%), vomiting and diarrhoea (81%), failure to thrive (88%), candidiasis (50%), and skin lesions (28%). The mean lymphocyte count was 1.71 x 10(9)/l compared with 7.2 x 10(9)/l in controls. Excluding one child with Omenn's syndrome (lymphocyte count 23.3 x 10(9)/l, all symptomatic infants with SCIDS had lymphocyte counts less than 2.8 x 10(9)/l at presentation. The median delay between the first abnormal lymphocyte count and diagnosis was seven weeks (range one day to 13 months). Twenty eight (88%) of 32 infants would have been diagnosed before 6 months of age if investigated after the first low lymphocyte count. These data indicate that low lymphocyte counts are predictive of SCIDS. Paediatricians are urged to pay attention to the absolute lymphocyte counts in all infants in whom a full blood count is performed. Those with lymphocyte counts persistently less than 2.8 x 10(9)l should be investigated for SCIDS.

Resolution of hepatic abscess after interferon gamma in chronic granulomatous disease.

Recombinant interferon gamma has been used prophylactically in children with chronic granulomatous disease, but its role in the treatment of acute infective episodes has not been defined. A 3 year old boy presented with multiple candidal liver abscesses and was given intravenous antifungal treatment and he showed initial improvement. After six weeks his erythrocyte sedimentation rate and C reactive protein remained raised, and a computed tomogram showed a single abscess in the left lobe of the liver from which pus was drained and Staphylococcus aureus isolated. During the next eight months the abscess persisted despite appropriate intravenous antibiotics and percutaneous drainage. Subphrenic extension precluded definitive surgery. Nine months after initial presentation recombinant interferon gamma 0.05 mg/m2 intravenously was commenced three times a week. Complete resolution occurred within two months. It is concluded that interferon gamma is useful in treating infective episodes, and further study of the use of prophylactic antimicrobial treatment and intermittent interferon gamma during acute episodes is now required.

Maternal factors in HIV transmission.

In order to identify features associated with an increased risk of transmission of HIV from seropositive women to their offspring, 70 children of 58 HIV seropositive mothers were studied. Fifty-six children were followed prospectively from pregnancy; in 14 identified after the puerperium, obstetric notes were reviewed and stored serum was tested. Twelve infants of 10 mothers were HIV infected. Risk of transmission was increased in the first year after seroconversion; 5/9 infants born at this time were infected compared with 7/61 born subsequently (P < 0.001). Progression to stage IV in transmitters was more likely, occurring in the mothers of 9 infected children at a median of 3 years (range 0.5-6.5) and in mothers of 19 non-infected children at a median of 5 years (range 1-7) (P = 0.032). Maternal CD4+ counts < 400 x 10(6)/l were found in 7/12 transmitting and 7/49 non-transmitting pregnancies (P < 0.01). Differences in HIV antigenaemia did not reach significance. These factors may influence the counselling of mothers regarding their child's and their own prognosis.

Zidovudine therapy in combination with intravenous immunoglobulin in HIV infected children.

There is little published data on concomitant use of zidovudine and intravenous immunoglobulin (IV IgG). In this paper we review our experience of four HIV-1 infected children treated with zidovudine for periods of 19-33 months (mean 26.5 months) subsequent to starting IV IgG for period of 18-20 months (mean 19 months). In these children the only clear benefit we found was in one child who had developed HIV encephalopathy which resolved after starting zidovudine. The respective roles of zidovudine and intravenous immunoglobulin in HIV-1 infected children need to be clarified in larger comparative trials.

Virus infections of the respiratory tract in HIV-infected children.

In order to determine whether the rates of respiratory viral infection and the severity of respiratory symptoms in HIV-infected children were higher than those in noninfected children, nose and throat swabs for viral isolation were taken at 3-month intervals during the first 2 years of life from 50 children born to HIV-infected women. Similar samples were obtained during the first year of life from 19 control children born to HIV seronegative mothers. Of the 50 children, five proved to be HIV-infected while 45 were presumed to be uninfected. HIV-infected children had significantly more respiratory symptoms and a higher proportion of samples from which viruses were isolated than the non-HIV-infected children. Also, more infected episodes required admission to hospital in the HIV-infected group. There was no such difference between the non-HIV-infected and the control children. Three HIV-infected children received intravenous immunoglobulin therapy. Among these the proportion of positive samples for viral isolation was greater before than after treatment began. These results suggest that HIV-infected children are more susceptible to recurrent viral infection and that passive immunotherapy may be of benefit to such children.

Use of intravenous immunoglobulin in acquired immune deficiency syndrome.

Patients infected with the human immunodeficiency virus (HIV) may have an antibody deficiency and a deficiency of cellular immunity. Intravenous immunoglobulin (IVIG) preparations may benefit HIV-infected children and adults with recurrent bacterial infections at doses of 200 to 400 mg/kg every 2 to 4 weeks. In addition, IVIG (1 to 2 g/kg) is effective at raising platelet counts to hemostatic levels in HIV-infected patients with idiopathic thrombocytopenic purpura and life-threatening bleeding. Indirect evidence also suggests that IVIG may be effective in preventing Pneumocystis carinii pneumonia. Finally, recent studies suggest that specific anti-HIV antibody preparations may have a therapeutic role, either as immunoglobulin concentrates or as immunoadhesions and immunotoxins. However, further investigations are needed to exclude antibody enhancement of HIV infection by the Fc receptor or the complement receptor.

HLA antigen frequencies in children born to HIV-infected mothers.

Tissue-typing for HLA-A, B, and DR antigens was carried out on 53 babies, 47 of them unrelated, born to mothers known to be HIV-infected from intravenous drug usage or sexual contact with drug users. These babies were followed up to assess whether HLA phenotype was associated with vertical transmission of HIV infection or disease progression. Of the 47 unrelated babies, eight became infected with HIV. The frequency of HLA-DR3 was three times higher in the HIV-positive infants compared to the HIV-negative infants (43 per cent vs 15 per cent) in our study population. Conversely, HLA-A3 was three times less common in the HIV-positive infants (12.5 per cent vs 42 per cent). A comparison of HLA antigens between our study group babies and babies born to healthy mothers unselected for HIV status revealed higher proportions of HLA-B18, B7, and DR2 in the study group. Moreover, the combination, A3, B7, DR2 was four times commoner in our study population relative to controls (RR = 3.9; p less than 0.003), but was found only in babies who were not HIV infected. The combination A1, B8, DR3, in contrast, was found less often than expected in our study group (RR = 0.39) and was disproportionately represented amongst the infected babies. We have observed an unexpectedly low (6 per cent) mother-to-infant transmission rate of HIV among prospectively studied intravenous drug users. We speculate that the unusually high ratio of the common antigen combinations (often halotypes), A3, B7, DR2 to A1, B8, DR3 in this population may be contributory.

Increased expression of the CD45RO (memory) antigen on T cells in HIV-infected children.

Expression of the CD45RO putative memory cell antigen on CD4 (helper) and CD8 (cytotoxic/suppressor) lymphocytes of children born to HIV-infected women was investigated using the UCHL1 antibody. Significantly raised numbers of CD45RO+ CD8 lymphocytes were found in all nine of the infected children compared with uninfected and control children. Expression of CD45RO on CD4 lymphocytes was variable; absolute numbers were not increased, although the percentage was increased in four out of nine infected children. All the infected children except two (who had comparatively low numbers of CD45RO+ CD8 cells) were clinically well, which suggests that an increase in CD45RO+ CD8 cells may be indicative of a functionally active immune response against HIV.

Diagnosis of Pneumocystis carinii pneumonia from non-invasive sampling of respiratory secretions.

An infant infected with HIV presented with fever, tachypnoea, hypoxia, and radiological evidence of bilateral pneumonitis. Fluorescent antibody technique identified Pneumocystis carinii within 24 hours from secretions obtained by nasopharyngeal aspiration. This rapid, non-invasive method should be the first line investigation of suspected P carinii pneumonia in immunocompromised patients.

Hyperviscosity in HIV infected children--a potential hazard during intravenous immunoglobulin therapy.

A four year old boy with symptoms of HIV infection and serum IgG of 53.2 g/l had been treated for 16 months with regular infusions of intravenous immunoglobulin (IV IgG). During one such infusion he developed temporary neurological symptoms and signs suggestive of the hyperviscosity syndrome. Serum relative viscosity was raised at 5.0 (normal range 0.42-2.78). Subsequent IV IgG infusions given at a slower rate have been without adverse reactions. In a study of eight HIV infected children including the index case, and 20 children not infected with HIV, serum relative viscosity was significantly raised in the HIV infected children (p less than 0.01; students t-test). Viscosity correlated with total serum IgG, which was raised in all HIV infected children, and with serum IgM. In HIV infected children with very high levels of serum IgG a slow rate of IV IgG infusion should therefore be chosen due to the possibility of hyperviscosity.

The polymerase chain reaction in the diagnosis of vertically transmitted HIV infection.

The presence of HIV-1 DNA sequences in DNA from peripheral blood mononuclear cells (PBMCs) was investigated in a two-stage polymerase chain reaction ('double' PCR) using four sets of nested primers. The PBMCs tested were obtained from 46 children born to HIV-seropositive mothers, seven 'control' children born to HIV-seronegative mothers and seropositive fathers, and 45 healthy adult blood donors who were HIV seronegative. Nine of the children had symptomatic HIV infection and other laboratory features characteristic of HIV infection: all nine were PCR-positive with each set of primers in each of their 22 blood samples tested. The remaining 44 children had no clinical or laboratory evidence of HIV infection, and each of their 50 samples was PCR-negative with each set of primers, as were all blood donor samples. PCR-positive samples were tested in more detail using two of the sets of primers, which spanned hypervariable regions in the env gene. Polyacrylamide gel electrophoresis of DNA amplified from these regions yielded patterns of amplified DNA length variation which were characteristic for each child, and which changed little with time (in serial samples obtained over periods of 3-7 months). This excluded contamination as a cause of PCR positivity. This is the first report of the use of a double PCR for the diagnosis of HIV infection. The results demonstrate the specificity of this PCR method in diagnosis, with failure to reveal in this cohort any cases of vertically transmitted HIV-1 infection in addition to those already confirmed by conventional laboratory techniques.

Vertical transmission of HIV: a prospective study.

Forty nine infants of HIV seropositive women were followed up for a median of 24 months, together with 24 controls. The infection status of 11 index children under 18 months of age was indeterminate; 34 were presumed uninfected while four showed clinical and laboratory evidence of HIV disease. Based on current definitions of HIV infection and excluding children under 18 months old as well as those who had not been studied from birth, two out of 28 children were infected. The estimated rate of maternofetal transmission was therefore 7.1%. In children with proved infection, sequential laboratory data showed that hypergammaglobulinaemia was noted as early as 6 months and often predated clinical signs. This observation, in the presence of non-specific clinical findings, was helpful in alerting the paediatrician to a diagnosis of HIV infection.

Intravenous immunoglobulin in HIV infection: evidence for the efficacy of treatment.

Eight children with symptoms of HIV infection were treated for 12-26 months (median 14 months) with infusions of intravenous immunoglobulin (200 mg/kg) every three weeks. Significant improvement was noted in all children in terms of weight gain, number of infectious episodes, and days spent in hospital. This resulted in a 49% saving in cost on treatment compared with costs accrued previously during inpatient admissions. Immunoglobulin concentrations, which were raised at the start of treatment were not altered, and T4 counts continued to decline slowly. HIV core antigen was detected in four children before treatment, but all became core antigen negative after treatment was commenced, this effect being sustained in three. Intravenous immunoglobulin therefore has major clinical benefit, and by reducing viral activity may delay disease progression.

Hepatic microsomal enzyme induction and adrenal crisis due to o,p'DDD therapy for metastatic adrenocortical carcinoma.

Two cases are described in which metastatic adrenocortical carcinoma associated with Cushing's syndrome was treated with mitotane (o,p'DDD). The first patient had initially been treated by bilateral adrenalectomy and, whilst responding to mitotane biochemically and by remission of metastases, experienced repeated episodes of adrenal crisis requiring a substantial increase in steroid therapy. The second patient failed to respond to the drug, but evidence of hepatic enzyme induction was noted during its administration. It is suggested that hepatic microsomal enzyme induction can occur in association with treatment with mitotane and that this can lead to an increased destruction of exogenous steroid with clinical consequences.

The management of children born to human immunodeficiency virus seropositive women.

Increasing numbers of children born to human immunodeficiency virus (HIV) antibody-positive women are being identified, but guidelines as to their management are lacking. We have therefore established a paediatric counselling and screening clinic for managing such children in Edinburgh. During a period of 3 years, 49 infants and children of 43 HIV seropositive women have been seen. After a median follow-up period of 23 months, four children were found to have clinical evidence of HIV disease which was non-specific and could have been missed had they not been regularly monitored. Thus, close surveillance of infants born to seropositive women is important. Identifying a single clinic where this is done has allowed experience to accumulate on issues beyond the medical management of these infants as well as contributing to the clinical care of infants with symptoms. Based on this experience, we have developed guidelines for managing children born to HIV antibody-positive women.