[Cecal tuberculosis: the importance of a high diagnostic suspicion]. / Tuberculosis cecal: la importancia de una alta sospecha diagnóstica.

Intestinal tuberculosis is less common than pulmonary tuberculosis. Its clinical and endoscopic features are nonspe-cific, so diagnostic suspicion must be high in order to make an early diagnosis and prevent iatrogenia. Pharmacotherapy is often effective, with an excellent clinical and endoscopic evolution. Surgical treatment is reserved for complications. We present the case of cecal tuberculosis diagnosed endoscopically; this is the second case diagnosed in a few months in our center. In this case there were no risk factors, such as recent travel, risk of contacts or inmunosupression.

Tuberculosis cecal: la importancia de una alta sospecha diagnóstica / Cecal tuberculosis: the importance of a high diagnostic suspicion

La tuberculosis intestinal es mucho menos frecuente que la pulmonar. Además, tanto su presentación como el aspecto endoscópico son muy variados, de modo que la sospecha diagnóstica debe ser elevada para un diagnóstico precoz y para evitar la posible yatrogenia. Con el tratamiento antituberculoso convencional la evolución, tanto clínica como endoscópica, suele ser excelente, quedando la cirugía relegada como tratamiento para las complicaciones. Presentamos un caso de tuberculosis cecal diagnosticada endoscópicamente, la segunda diagnosticada en unos meses en nuestro centro. En este caso no había factores de riesgo como viajes recientes, contactos con infectados ni toma de fármacos inmunosupresores (AU)

Intestinal tuberculosis is less common than pulmonary tuberculosis. Its clinical and endoscopic features are nonspecific, so diagnostic suspicion must be high in order to make an early diagnosis and prevent iatrogenia. Pharmacotherapy is often effective, with an excellent clinical and endoscopic evolution. Surgical treatment is reserved for complications. We present the case of cecal tuberculosis diagnosed endoscopically; this is the second case diagnosed in a few months in our center. In this case there were no risk factors, such as recent travel, risk of contacts or inmunosupression (AU)

Addison-disease - an unusual clinical manifestation of CMV-end organ disease in pediatric AIDS.

CMV infection is common in pediatric HIV-1 infected patients. We present a case report, to our knowledge the first pediatric patient, in which Addison-disease due to CMV was suspected during lifetime. We want to point out the importance of routine clinical and laboratory follow up once a HIV-1 infected child is shown to be infected with CMV.

[HIV infection in childhood]. / HIV-Infektion im Kindesalter.

As a result of preventive measures during pregnancy and improved antiretroviral combination treatment, the problem area of HIV infection in childhood has undergone a change in recent years. Thanks to intensive cooperation between obstetricians and pediatricians, mother-to-child transmission of HIV in Germany has been decreased to less than 2%. Improvements in the diagnosis of HIV infection in childhood, infected children have been identified very early, and started on antiretroviral treatment, and prophylactic measures initiated. In the case of life-long anti-HIV treatment beginning in childhood, the same problems as those seen in adults must be expected (development of resistance, adherence, adverse effects).

An effective and safe protocol involving zidovudine and caesarean section to reduce vertical transmission of HIV-1 infection.

OBJECTIVE: To investigate zidovudine prophylaxis with caesarean section to reduce mother-to-infant HIV transmission. INTERVENTIONS: Elective caesarean section before labour, usually at 36-38 weeks of gestation, plus a short oral course of zidovudine, normally starting at week 32, intravenous zidovudine before caesarean section and for 10 days for the neonate (the reduced Berlin regimen). RESULTS: Of 179 mother-infant pairs 104 received no antiretroviral prophylaxis or therapy (control group), 48 received the reduced Berlin prophylaxis regimen, 18 received combination therapy and nine received only part of the prophylaxis regimen. Of the antiretroviral group, 68 were delivered by elective caesarean section. The HIV transmission rate was zero in the antiretroviral group [95% confidence interval (CI) 0-4.7] and 12.6% (6.4-19.0) in the control group. The reduction in vertical transmission was 90% for the Berlin regimen, with an 80 and 70% reduction in risk associated with antiretroviral treatment and caesarean section, respectively. Maternal CD4 cell count but not viral load had some confounding effect on the reduction in risk attributed to caesarean section and the prophylactic regimen. Neonatal haematological abnormalities associated with antiretroviral intervention lasted for up to 7 weeks. Weight and length, although significantly lower at birth, were normal by 6-8 weeks. CONCLUSION: A much reduced three-arm regimen of zidovudine prophylaxis in combination with caesarean section before labour is highly effective in reducing the risk of vertical HIV transmission and is safe for the infant.

Genotypic relatedness of yeast isolates from women infected with human immunodeficiency virus and their children.

The objective of this study was to compare polymerase chain reaction (PCR) fingerprinting with other molecular typing methods as an epidemiologic tool to investigate the transmission of Candida strains between HIV-positive mothers and their children. Forty-nine yeast strains (including Candida albicans, Candida glabrata, Rhodotorula rubra, Candida tropicalis, Candida famata, Candida dubliniensis, Saccharomyces cerevisiae) from 30 individuals (15 children and 15 HIV-infected mothers or accompanying person) were isolated. Colonization/infection with yeast was observed in 80% of all individuals in the oral cavity, and in 33% from hand cultures, respectively. Thirteen out of 15 children (86%) and 12 out of 15 adults (80%) were colonized/infected with yeasts. Candida dubliniensis strains were found in four HIV-infected women but not in children. The results with an arbitrarily primed (AP)-PCR mediated genotyping assay using phage M13 core sequence were compared with the hybridization patterns using the species-specific DNA probe CARE-2 for the C. albicans isolates. Typing of non-C. albicans strains was done using AP-PCR in comparison with pulsed-field gel electrophoresis (PFGE). Twenty-six C. albicans strains gave two different genotypes by AP-PCR but 16 genotypes by CARE-2 hybridization. The CARE-2 probe appeared to have a higher discriminatory power compared with the primer 'M13'-mediated AP-PCR in typing C. albicans isolates.

Primäre Kaiserschnittentbindung mit und ohne antiretrovirale Prophylaxe und Prävention der materno-fetalen Transmission von HIV-1.

BACKGROUND: Studies of caesarean section and the rate of perinatal transmission of HIV-1 (RPT) have reported conflicting results if AZT was not administered simultaneously. METHODS: To investigate the probable sources of error, 387 singleton pregnancies of HIV-1-infected mothers were enrolled in a prospective, observational study. To avoid contamination of the fetal mouth with maternal blood at caesarean section, the uterus was opened under careful preparation of the fetal membranes, maintaining their integrity as long as possible. To 105 pregnant women AZT was administered at various gestational ages (median 29th week), depending on the stage of the disease of the mother or obstetrical complications. The majority of newborns received AZT for 10 days I.V. RESULTS: Group 1: For those, for whom vaginal delivery was intended (n=163, RPT=20.2%), this could be realized in 82% of the cases only. There was no significant difference in the RPT (23%-19,5%) between emergency caesarean section and vaginal delivery (odds ratio [OR]=1,25; 95% CI 0,41-3,44). Risk factors of fetal HIV infection (p≤0.05) were delivery <37th week, rupture of membranes (ROM) ≥4 h, labor ≥5 h before delivery, CD4 ≤400 cells/µl, p24 antigenemia, and viral load. Group 2: If an elective caesarean section (n=119) was intended, the RPT (4,2%) was reduced compared to group 1 (OR=0.17; 95% CI 0.04-0,52; p=0.0002); however, in 16% emergency sections had to be performed because labor or ROM occurred before the planned date of elective caesarean section without difference in the RPT (4-5%) (OR 1,35; 95% CI 0,03-14,51). Significant risks (p≤0.05) of fetal infection were preterm labor and viral load. Group 3: If an elec- tive caesarean section under AZT (n=105) was intended, the RPT (1,3%) was significantly different to group 1 (OR=0,08; 95% CI 0.1-0.31; p=0.00003), but not to group 2 (OR=0.44; 95% CI 0.04-2.79). However, an elective caesarean section was feasible only in 74% without significant differences in the RPT (1,3-4%) (OR=2,96; 95% CI 0,04- 235,42). Except for the viral load (p=0.04), no risk factor was associated with fetal infection. CONCLUSIONS: Elective and emergency caesarean section, performed early in parturition under surgical care to avoid contamination, significantly decreases the risk of fetal transmission, irrespec-tive of low CD4 cell counts, p24 antigenemia, viral load and ROM, but not preterm labor. Simultaneous administration of AZT in gestation and to the newborn further reduces the risk of peripartal infections and obviously provides additional safety at caesarean sections.

Autoantibodies to polymorphonuclear neutrophil elastase do not inhibit but enhance elastase activity.

Polymorphonuclear neutrophils (PMNs) of patients with active Wegener's granulomatosis and PMN activated in vitro express elastase on their surface as detected by autoantibodies derived from patients with ANCA-positive vasculitis or chronic staphylococcus infections. The PMN-associated elastase was enzymatically active. By affinity-purified autoantibodies to elastase, the enzymatic activity was further enhanced as measured either by a chromogenic peptide or by elastin as substrate. Antibodies to human elastase from mouse or from sheep also enhanced elastase activity, whereas unrelated immunoglobulins had no effect. Taken together, our data indicate that autoantibodies to elastase are not inhibitory but upregulate the elastase activity and thereby might contribute to tissue damage.

[Molecular epidemiology of Candida infections in HIV-infected mothers and their offspring]. / Molekulare Epidemiologie von Candida-Infektionen bei HIV-infizierten Müttern und ihren Kindern.

In a prospective study 15 consecutive children and 12 HIV-infected mothers were examined according to their colonization with Candida species in the oral cavity and on the hands. From 39 samples a total of 49 Candida isolates could be recovered (26 C. albicans, 4 C. glabrata, 9 Rhodotorula rubra, 4 C. dubliniensis, 3 C. tropicalis, 2 C. famata, 1 S. cerevisiae). Antifungal susceptibility testing revealed fluconazole MICs from 0.09 microgram/ml to 100 micrograms/ml. Genotyping was done with an AP-PCR technique using the primer "M13" and "(GACA)4". From the mycologic culture identical yeast isolates were found in 10 families. However, with PCR typing identical findings were seen only in 5 families. A C. albicans isolate resistant to fluconazole in vitro was found in a child and the mother of the same family. It could be summarized that yeast strains are transmitted between HIV infected mothers and their children. With PCR typing diversity among yeast isolates could be demonstrated even between members of the same family.

[Immunologic findings in HIV infected children with bacterial infections]. / Immunologische Befunde bei HIV-infizierten Kindern mit bakteriellen Infektionen.

BACKGROUND: Bacterial infections are a major cause of illness in HIV-infected children. HIV-infected children with severe dysfunction of cellular and humoral immunity are particularly vulnerable. METHODS AND PATIENTS: We conducted a retrospective study to analyse the incidence and spectrum of bacterial infections in HIV-infected children compared to HIV-exposed but not infected controls related to their immunological status. Data collected during 1985 to May 1993 were evaluated considering 333 HIV-infected and 81 controls. RESULTS: During observation time 359 episodes (29% of the visits) of purulent rhinitis were diagnosed in HIV-infected children compared to the controls (53 episodes/8%); p = 0.0001. Comparable results were seen in otitis media. 178 episodes/14% were found in HIV-infected children and 66 episodes/10% in the controls (p = 0.001). 53 episodes/5% of bacterial pneumonia were represented in HIV-infected versus 11 episodes/2% in controls (p = 0.001). The increase of lymphocyte immune defect correlated to an increase of bacterial infections. This alterations were particularly observed in HIV-infected children with bacterial pneumonia. Severe dysfunction of cellular immunity was found in children with recurrent pneumonia compared to children with only one episode of bacterial pneumonia. The proliferate response of peripheral blood lymphocyte to pokeweed mitogen (13,351 cpm versus 3080 cpm); p = 0.009 and Concanavalin A (12,607 cpm versus 2470 cpm); p = 0.01 was significantly reduced in both groups, although the defect was much more pronounced in the group with the recurrent pneumonia. CONCLUSIONS: Our observations results showed that bacterial respiratory tract infections occurred significantly more frequently in HIV-infected children compared to an age related control group. Not only the occurrence of opportunity infections but also severe bacterial infections especially recurrent pneumonia are associated with a defect in cell-mediated immunity.

Antibodies to neutrophil elastase: a study in patients with vasculitis.

Whether antibodies to elastase (EL) exist in autoimmune disease is controversial, due in part to inadequate methods used to determine antibody titers. We have developed a highly sensitive and specific enzyme-linked immunosorbent assay, using immobilized EL and mouse monoclonal antibodies for standardization. The specificity of the enzyme-linked immunosorbent assay was confirmed by absorption studies and Western blot analysis. Using this enzyme-linked immunosorbent assay, antibodies to EL were found in antineutrophil cytoplasmic antibody-positive vasculitis patients to a higher degree than reported in the literature (in eight of 108 patients with Wegener's granulomatosis and in 15 of 78 patients with microscopic polyangiitis). Patients with Wegener's granulomatosis or microscopic polyangiitis and antibodies to EL had significantly more severe renal involvement, as indicated by the higher frequency of dialysis dependency. Also in contrast to reported data, antibodies to EL were found less frequently in patients with systemic lupus erythematosus (nine of 64 patients). Binding of systemic lupus erythematosus sera to uncoated plates, giving a nonspecific reaction, was seen quite frequently, which might explain the discrepancy.

Pharmacokinetics of orally administered zidovudine in HIV-infected children and adults.

The pharmacokinetics of oral zidovudine in HIV-infected children and adults are reported. Fourty-six patients were investigated. For data analysis three groups of similar size were formed: young children 4 months-4 years, n = 15 (group 1), older children up to 13 years, n = 16 (group 2) and young adults, n = 15 (group 3). After a single oral dose repeated blood samples were taken 1/2 hourly during a period of 4 hours and zidovudine concentrations in plasma were determined by high performance liquid chromatography. For better comparison of dose dependent parameters peak concentrations (Cmax) and the area under the time-concentration curves (AUC) were normalized either to the dose/body weight (bw) or the dose/body surface area (bs), respectively. Time to reach peak concentrations and mean terminal elimination half-life times (t1/2 beta = 63.4 +/- 47.6, 74.9 +/- 54.9 and 56.9 +/- 16.4 min in group 1, 2 and 3, respectively, mean +/- SD) were not significantly different between the three groups. With normalization to dose/bw young children in comparison to adults had significantly lower Cmax (2.7 +/- 1.3 vs. 4.6 +/- 2.4 mumol/l, p = 0.016) and AUC (226 +/- 108 vs. 373 +/- 224 mumol.min/l, p = 0.038). Group 2 gave intermediate values. However, with normalization to dose/bs differences in Cmax (6.5 +/- 3.3, 7.3 +/- 4.2 and 6.8 +/- 3.6 mumol/l, in group 1, 2, and 3, respectively) and AUC (563 +/- 313, 691 +/- 351 and 555 +/- 342 mumol.min/l, in group 1, 2 and 3) were not significant between the three groups. It is likely that changes in body water content with age may account for most of these differences observed. In conclusion, a similar pharmacokinetic profile was found in children older than 3 months as compared to older children or adults.

[Labor, method of delivery and maternofetal transmission of HIV]. / Wehen, Geburtsmodus und maternofetale Transmission von HIV.

Within a prospective study of the course of HIV-infection in women, 80 HIV-infected women without AIDS were delivered of 80 children between 1985 and September 1992. The median of the age of gestation was 38 weeks. Until 1988 Caesarean section was chosen as mode of delivery (45 women). Later when the mode of delivery appeared to have no influence on the frequency of maternofetal HIV transmission, vaginal delivery was preferred (35 women). None of the infants was breastfed. Three infants --delivered vaginally--died within the first 6 months of life before their infection status could be determined. Seventy-seven children could be observed for 18 months or longer regularly every three months. 10 of the 77 children were found to be HIV- infected by serological, virological and clinical criteria. Taking into account the mode of delivery, of 32 children who were delivered vaginally or by emergency Caesarean section 8 were found to be HIV-infected. None of 26 children delivered by elective Caesarean section after an uneventful pregnancy is infected. In 19 women Caesarean section was performed within 2 hours after onset of labour or after episodes of preterm labour which required hospital admission for treatment. Two children of these women are infected. No differences of CD4+ cell counts and p24 antigenaemia could be determined between the mothers of the three groups. The risk of fetal HIV infection was increased by preterm labour (p < 0.01) and the mode of delivery (p < 0.01). A correlation between loss of CD4 cells in the mother and increased risk of infection for the child is seen in children born spontaneously or delivered by emergency Caesarean section (p < 0.001). No correlation was found between the length of labour at delivery, the time of the rupture of membranes before birth as well as of the parity and the risk of fetal infection in that group. These findings point to labour as an important factor which increases the risk of maternofetal transmission of HIV. The onset of labour is accompanied by dramatic immunological alterations as a sudden increase of chemotactics and inflammatory cytokines at the maternofetal interface. The accumulation and stimulation of maternal immune cells will--if these cells are carriers of HIV--result in production and release of infectious HIV. This virus may accumulate in the maternofetal interface or gain access to the amniotic cavity. Since amniotic fluid is swallowed by the fetus, the largest potential port of entry for HIV in the fetus are the fetal lungs and the gastrointestinal tract. For the prevention of maternofetal transmission of HIV delivery before onset of labour or alternatively the protection of the fetus during parturition by means of potent antiviral compounds can be considered.

Vertical human immunodeficiency virus transmission: a study of placental pathology in relation to maternal risk factors.

We examined 48 placentas of human immunodeficiency virus (HIV)-exposed pregnancies morphologically for HIV-specific changes and immunohistologically for the presence of HIV antigen and RNA. Findings were correlated to infectious states of the children and maternal risk factors. Few HIV antigen-positive Hofbauer cells and HIV RNA positive syncytiotrophoblast and Hofbauer cells were detected. HIV-positive cells in the placenta did not correlate with intrauterine infection and maternal immunologic parameters. Light microscopically, we found two changes: immaturity of the terminal villi and allantois vasculopathy. These changes, however, are not HIV specific. Our results show that vertical HIV transmission cannot be diagnosed by morphological examination of the placenta.

Chemotaxis of polymorphonuclear neutrophils (PMN) in patients suffering from recurrent infection.

PMN function was tested in patients suffering from recurrent infections. In 65 out of 240 patients lack of oxygen radical production or reduced chemotactic activity was found. In most cases the reduction was transient and associated with clinical impairments of the patients. Only a few patients had primary cellular defects. In one of those patients the expression of beta 2 integrins was reduced, while PMN of the other patients expressed beta 2 integrins normally. Thus, cellular defects other than the reduced expression of beta 2 integrins might also result in impaired chemotactic activity.

[Cerebral symptoms in pre- or perinatally HIV-infected children]. / Zerebrale Symptome bei prä- oder perinatal mit HIV 1 infizierten Kindern.

Eight of 13 children pre- or perinatally infected with the HIV virus subsequently developed neurological symptoms. Three children also had other nonspecific symptoms (fever, lymphadenopathy, diarrhoea, hepatosplenomegaly, failure to thrive and mucocutaneous thrush). Five children developed illnesses associated with AIDS (opportunistic infections, cachexia and lymphocytic interstitial pneumonia). The neurological abnormalities predominantly affected motor functions, only later also involving sensory ones. Motor, cognitive and language development was impaired in all eight children. A loss of developmental milestones occurred in three children with HIV encephalopathy: they have since died. In all the children the HIV infection caused symptoms within the first year, progressing more quickly in the three with encephalopathy. There were no discernible risk factors to account for the difference in the course of the disease.