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C Rudin

Publications and source records attributed to C Rudin.

At least 37 records · Page 2Linked to original sources
PubMed1998

Antiretroviral therapies in pregnancy: maternal, fetal and neonatal effects. Swiss HIV Cohort Study, the Swiss Collaborative HIV and Pregnancy Study, and the Swiss Neonatal HIV Study.

BACKGROUND: Therapies containing two reverse transcriptase inhibitors (RTI) with or without protease inhibitors are used with increasing frequency in pregnant HIV-infected women. OBJECTIVE: To assess the safety of antiretroviral therapy in pregnant women and their newborns. METHODS: All clinical events and laboratory abnormalities in pregnant women on RTI with or without protease inhibitors and in their newborns were collected through an observational study. RESULTS: A total of 37 HIV-infected pregnant women have given birth to 30 children (by 30 April 1998). All received RTI, which were combined with protease inhibitors in 16 cases. Twelve women became pregnant while on treatment. Drugs used were as follows: zidovudine (n = 33), lamivudine (n = 33), stavudine (n = 4), indinavir (n = 9), ritonavir (n = 4), nelfinavir (n = 2) and saquinavir (n = 2). Adverse events during pregnancy were anaemia (n = 15), elevation of transaminases (n = 4), nausea/vomiting (n = 4), glucose intolerance (n = 2), nephrolithiasis (n = 2), diarrhoea (n = 2), hypertension (n = 1), insulin-requiring diabetes (n = 1). Adverse events in neonates were prematurity (n = 10), anaemia (n = 8), cutaneous angioma (n = 2), cryptorchidism (n = 2), transient hepatitis (n = 1). Non-life-threatening intracerebral haemorrhage occurred in a premature baby (33 weeks gestation) exposed during fetal life to zidovudine-lamivudine-indinavir, and in a term baby exposed to stavudine-lamivudine-indinavir. Extrahepatic biliary atresia occurred in one newborn exposed to zidovudine-lamivudine-indinavir. Maternal viral load was below 400 copies/ml in 18 out of 30 patients who delivered. One case of mother-to-child HIV transmission was identified. CONCLUSIONS: In HIV-infected pregnant women treated with two RTI with or without protease inhibitors, one or more adverse events occurred in 29 out of 37 women and in 14 out of 30 babies. In newborns, frequent prematurity, one case of biliary malformation and one intracerebral haemorrhage in a term baby are of concern. These observations do not preclude combination therapies during pregnancy but emphasize the necessity to maintain updated registers on their safety.

Anti-HIV Agents↗
PubMed1998

Cytochrome c induces caspase-dependent apoptosis in intact hematopoietic cells and overrides apoptosis suppression mediated by bcl-2, growth factor signaling, MAP-kinase-kinase, and malignant change.

It has been shown that cytochrome c is released from mitochondria during apoptosis, activates pro-caspase CPP32 (caspase III), and induces DNA fragmentation in mixtures of cytosolic extracts and isolated nuclei. To establish whether cytochrome c can primarily induce apoptosis in intact cells, we used direct electroporation of cytochrome c into murine interleukin-3 (IL-3)-dependent cells. Electroporation of micromolar external concentrations of cytochrome c rapidly induced apoptosis (2 to 4 hours) that was concentration-dependent, did not affect mitochondrial transmembrane potential, and was independent of cell growth. Only certain isoforms of cytochrome c were apoptogenic; yeast cytochrome c and other redox proteins were inactive. Cytochrome c-induced apoptosis was dependent on heme attachment to the apo-enzyme and was completely abolished by caspase inhibitors. Nonapoptogenic isoforms of cytochrome c did not compete for apoptogenic cytochrome c. Although apoptosis induced by IL-3 withdrawal was inhibited by bcl-2 overexpression and expression of an activated MAP-kinase-kinase (MAP-KK), cytochrome c induced apoptosis in the presence of IL-3 signaling, bcl-2 over-expression, expression of activated MAP-KK, and the combined antiapoptotic action of all three. Cytochrome c also induced apoptosis in the leukemic cell line WEHI 3b. However, human HL60 and CEM cells were resistant to cytochrome c-induced apoptosis. HL60 cells did not electroporate, but CEM cells were efficiently electroporated. Our studies with IL-3-dependent cells confirm that the apoptogenic attributes of cytochrome c are identical in intact cells to those in cell extracts. We conclude that cytochrome c can be a prime initiator of apoptosis in intact growing cells and acts downstream of bcl-2 and mitochondria, but that other cells are resistant to its apoptogenic activity. The system described offers a novel, simple approach for investigating regulation of apoptosis by cytochrome c and provides a model linking growth factor signaling to metabolism, survival, and apoptosis control.

Animals↗
PubMed1998

Does pregnancy influence the course of HIV infection? Evidence from two large Swiss cohort studies.

The question whether the natural history of HIV infection in women is affected by pregnancy has not so far been convincingly answered. We used prospective cohort data to compare pregnant and nonpregnant HIV-infected women during follow-up within the Swiss HIV Cohort Study (SHCS) and the Swiss Collaborative HIV and Pregnancy Study (SCHPS). Pregnant women were eligible if a CD4 cell count had been made before conception had taken place. Additional inclusion criteria were a pregnancy completed to delivery during follow-up and an observation period of at least 6 months after delivery. Thirty-two women who fulfilled these criteria were compared with 416 controls, matched for age and CD4 cell count at entry, who had not been pregnant during follow-up. Mean follow-up time was 4.8 years for pregnant women and 3.6 years for controls. The rate of any AIDS-defining event was higher in pregnant women (rate ratio [RR] from Cox regression, 1.92; 95% confidence interval [CI], 0.80-4.64) but this did not reach statistical significance (p = .15). A statistically significant difference (p = .008) emerged only for one AIDS-defining event, recurrent bacterial pneumonia (RR, 7.98; 95% CI, 1.73-36.8). The rate of death was similar in the two groups (RR, 1.14; 95% CI, 0.48-2.72; p = .8). Our results thus indicate that, after taking CD4 cell counts before conception into account, acceleration of disease progression is inconsistent among HIV-infected women who become pregnant during follow-up.

AIDS-Related Opportunistic Infections↗
PubMed1998

Prevention of vertical HIV transmission: additive protective effect of elective Cesarean section and zidovudine prophylaxis. Swiss Neonatal HIV Study Group.

OBJECTIVE: To study the effect of elective Cesarean section and zidovudine prophylaxis on vertical HIV transmission. DESIGN: Prospective study. SETTING: Obstetric and paediatric clinics in Switzerland. PARTICIPANTS: Children of mothers with HIV infection identified before or at delivery. INTERVENTIONS: Routine use of elective Cesarean section for HIV-infected parturients by some Swiss centres since 1985. National recommendation for zidovudine prophylaxis in mid-1994. MAIN OUTCOME MEASURE: HIV infection status of children. RESULTS: In a cohort of 494 children born at least 6 months before the analysis date, 67 out of 414 children with known infection status were found to be infected, giving an overall transmission rate of 16.2% [95% confidence interval (CI), 13.0-18.51. Elective Cesarean section with intact membranes and without previous labour was associated with a lower transmission rate of 6% [odds ratio (OR), 0.29; 95% CI, 0.12-0.70; P = 0.006 versus other delivery modes]. Transmission rate was intermediate after spontaneous delivery or non-elective Cesarean section (18%), and higher after obstetric interventions (27%; test for trend, P < 0.001). Since mid-1994, 78% of all women with registered pregnancies have received some form of zidovudine prophylaxis. Transmission rate was reduced from 17 to 7% after any zidovudine exposure (OR, 0.4; 95% CI, 0.11-1.41). Combined use of elective Cesarean section and zidovudine resulted in a 0% transmission rate (none out of 31), compared with 8% (seven out of 86) after elective Cesarean section without zidovudine, 17% (four out of 24) after zidovudine alone, and 20% (55 out of 271) after no intervention. CONCLUSIONS: Elective Cesarean section and zidovudine prophylaxis appear to have an additive effect in the prevention of vertical HIV transmission.

Abortion, Induced↗
PubMed1998

A dose-response study of a live attenuated varicella-zoster virus (Oka strain) vaccine administered to adults 55 years of age and older.

Decreased cell-mediated immune (CMI) response to varicella-zoster virus (VZV) is correlated with an increased risk of reactivation of latent virus from dorsal root sites, leading to herpes zoster. The cell-mediated and humoral immunogenicity of three concentrations (3200, 8500, and 41,650 pfu/dose) of a live attenuated VZV vaccine (Oka strain; VZV/Oka) was compared with a control pneumococcal polysaccharide vaccine in 200 healthy adults who were > or = 55 years old. Six weeks after vaccination, the VZV-specific CMI response (as measured by stimulation index values and precursor cell frequencies) was enhanced in all VZV/Oka vaccine groups compared with the control group (for all VZV/Oka groups combined vs. controls, tested with VZV crude antigen: stimulation index, P < .001; precursor cell frequency, P < .001). Geometric mean titers of anti-VZV antibodies increased in all VZV/Oka vaccine groups but remained unchanged in the control vaccine group. No dose effect of VZV/Oka vaccine was observed for CMI or humoral responses.

Aged↗
PubMed1998

Renal transplantation in the management of bilateral Wilms' tumour (BWT) and of Denys-Drash syndrome (DDS).

BACKGROUND: Wilms' tumour (WT) occurs bilaterally in approximately 5-7% of affected children. In some patients, complete surgical removal of the malignant tissue cannot be achieved without bilateral total nephrectomy. In Denys-Drash syndrome (DDS), bilateral nephrectomy is indicated both because of the associated nephropathy usually progressing rapidly to end-stage renal failure and because of the high risk of WT development in any residual renal tissue. METHODS: Case records of patients with a diagnosis of either bilateral WT (BWT) or DDS, who underwent bilateral nephrectomy and subsequent renal transplantation between 1980 and 1996 at the Hospital for Sick Children, London, were reviewed. RESULTS: Allogeneic renal transplantation was performed in two children with BWT and four with DDS, three of whom had developed unilateral WT by the time their kidneys were removed. Renal transplantation was performed 15-49 months after bilateral nephrectomy at a mean age of 45 (26-76) months, with a minimum of 1 year tumour-free survival after completion of chemotherapy in those with WT. One patient died after renal transplantation. Five children had a favourable outcome, with a mean follow-up of 80 (29-121) months post-renal transplantation. CONCLUSION: Advances in dialysis and transplantation programmes for young children offer the potential for a marked improvement in the prognosis for patients with BWT and for those with DDS.

Child, Preschool↗
PubMed1998

[HIV infection: relevant pediatric aspects].

After 15 years of intense AIDS research several fascinating new findings have recently produced real hope for people infected with HIV and new optimism among scientists. A second group of powerful antiretroviral drugs (proteinase inhibitors) has been introduced. These drugs can virtually stop viral replication when used in combination with other drugs (nucleoside or non-nucleoside reverse transcriptase inhibitors), which also almost totally eliminates the emergence of HIV-resistance. New moleculargenetic methods (plasma HIV-RNA assays) made a new marker to quantify and survey therapeutic effects and to accurately predict individual progression of HIV infection available. These new instruments also provided us with a more realistic imagination about pathogenesis and viral dynamics in HIV infection. In neonates prophylactic antiretroviral treatment of pregnant women already prevents two thirds of vertically acquired infections, and the vertical transmission rate may well continue to decline with new prophylactic regimens and/or other interventions (e.g. cesarean section). Given these splendid innovations, a huge impact on prognosis can well be anticipated in the near future.

Adolescent↗
PubMed1998

[Decision guides for antiretroviral treatment in pregnancy].

HIV-infected adults can now be offered highly active antiretroviral combination therapies. Major advances in understanding the pathogenesis of HIV-infection have led to earlier onset of treatment during the course of HIV infection. Most of the new antiretroviral drugs are not approved for use in newborns and infants. Zidovudine monotherapy during pregnancy, during labor and for the newborn, has been shown to reduce vertical HIV transmission by almost 70%. Zidovudine monotherapy is at present considered obsolete for the treatment of HIV-infected adults. Thus, during pregnancy, both the interests of the HIV-infected mother and the fetus/newborn must be taken into account. Clinical data to solve this dilemma are not available. In general, standard antiretroviral treatment should not be withheld from pregnant HIV-infected women, but prescription has to be the result of careful discussion of the risks and benefits of such treatment during pregnancy. The final decision about treatment, whether primarily for the mother, to reduce vertical transmission or both, has to be taken by the pregnant women. This discussion and information must involve physicians with important experience in the treatment of HIV-infected patients.

Adult↗
PubMed1995

[HIV and pregnancy].

Since 1990 216 HIV-infected pregnant women have been enrolled in an ongoing nationwide study named "HIV and Pregnancy" financed by the Swiss Federal Office of Health (No. 90-7007 and 93-7131). Of a total of 228 recorded pregnancies 154 continued to parturition. Until now it has been definitively established whether or not 89 offsprings have been infected with HIV by their mothers. According to clinical and immunological findings most of the pregnant women are still in early, stable stages of HIV-infection (stages II and III of the CDC classification system in 94% of the subjects; mean CD4-cell count around 600/microliters). HIV infection was the consequence of an intravenous substance abuse in two thirds of the women. Detailed interviews revealed an alarming negligence with regard to compliance with safer sex recommendations and contraception. Advisory services of specialized AIDS information centers have very rarely been called on. In our group, the vertical transmission rate shows a statistically significant correlation with low maternal anti-HIV-p24 antibody titers, high serum neopterin- and IgA-concentrations, and also with the use of forceps and vacuum in vaginal delivery. Maternal substance abuse but not HIV infection itself resulted in an incidence of preterm deliveries roughly twice as high as in the normal Swiss population.

Abortion, Induced↗
PubMed1995

[Pneumocystis carinii pneumonia in infants with vertically acquired HIV infection in Switzerland].

OBJECTIVE: Review of incidence, clinical picture, therapy, and outcome of Pneumocystis carinii pneumonia (PCP) in infants with vertically-acquired HIV infection in Switzerland. METHODS: Inquiry among members of the Swiss Pediatrics AIDS Group, review of the data base of the Swiss Neonatal HIV Study and retrospective analysis of the charts from infants with PCP. RESULTS: Since 1986 PCP has been diagnosed in 10 out of 107 infants with vertically-acquired HIV infection. PCP occurred in 7 infants at the age of 3-6 months and in 3 at the age of 9-11 months. 4 infants showed symptoms related to HIV infection before developing PCP. Before the development of PCP, infection with HIV had been ascertained in 6 infants. In 2 the diagnosis was still unclear and in the 2 remaining the risk of HIV infection was not known. None of the infants was on primary prophylaxis against PCP. Signs and symptoms of PCP included cough and tachypnea (100%) as well as high fever up to 40 degrees C (90%). Transcutaneous oxygen saturation was 70-95%. Chest X-rays revealed interstitial infiltrates in 6 infants, localized infiltrates in 2 and interstitial as well as localized infiltrates in 2. The CD4+ cell count was, with one exception, < 1500/microliters, i.e. below the normal value for age. Side effects of high dose cotrimoxazole were noted in 6 patients. 5 infants required intubation and mechanical ventilation. 4 infants died due to PCP, including 3 of those who required intubation and mechanical ventilation. CONCLUSIONS: PCP in infants with vertically-acquired HIV infection preferentially occurs at the age of 3 to 6 months and is often lethal, especially in patients requiring intubation. Evaluation for HIV infection should be done as early as possible in order to introduce primary PCP prophylaxis in infants at risk for this opportunistic infection.

AIDS-Related Opportunistic Infections↗
PubMed1995

[Toxoplasmosis and pregnancy--findings from umbilical cord blood screening in 30,000 newborn infants].

Cord blood screening for congenital toxoplasmosis was performed prospectively on 30,000 samples collected between 1986 and 1994 in the region of Basel, Switzerland, covering up to 95% of all births. Congenital infection was suspected in cases of serum with specific antitoxoplasma IgM or IgA or with a level of specific IgG above 300 IU/ml as measured by EIA from Sanofi-Pasteur. The percentage of cases to be screened declined from 2.5 to 1.2% and the cases of confirmed congenital toxoplasmosis from 0.073 to 0.033% during the observation period. This observation may be due to several reasons, such as improved primary prevention or more frequent diagnosis and treatment during pregnancy. In 178 cases of cord blood serology suspicious for acute toxoplasmosis, an enquiry with the gynecologist in charge of the pregnant woman was carried out. 126 mothers (71%) presented with a confirmed immunity against Toxoplasma gondii early in pregnancy and screening of the child was not needed. From 37 pregnancies (21%) no information was available. 15 out of 24 confirmed cases of toxoplasmosis of the mother during pregnancy were detected by cord blood analysis. In 17 of 24 cases of maternal toxoplasmosis treatment with spiramycin, pyrimethamine/sulfadoxine or both was performed. 10 of 17 newborns from mothers treated during pregnancy had elevated toxoplasma IgG titres at birth, but only one child was infected. 7 newborns had an inconspicuous toxoplasma serology at birth and were not infected. 7 cases of toxoplasmosis during pregnancy were detected by the check back and remained untreated; 4 out of 7 newborns had congenital toxoplasmosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Protozoan↗
PubMed1995

Calcifying arteriopathy in the basal ganglia in human immunodeficiency virus infection.

Echogenic stripes in the basal ganglia were identified sonographically in a 4-month-old infant with human immunodeficiency virus (HIV) infection. This lenticulostriate arteriopathy correlated well with histologically identified early alterations of HIV encephalopathy in children. At 3 years and 5 months, CT examination performed after three seizures showed calcification in the area of the sonographically affected arteries but no signs of progressive encephalopathy. The child's mental and motor development have remained normal until now. Cerebral sonography performed in early infancy may allow identification of HIV encephalopathy even before its clinical manifestation.

AIDS Dementia Complex↗
PubMed1995

[Pregnancies in HIV infected women in Switzerland].

In a national multicentre study, 229 pregnancies in 219 HIV-positive women were prospectively followed up between January 1, 1990, and October 30, 1993. 69.8% were infected by intravenous drug abuse and 91.5% were asymptomatic (CDC classes II and III) in early pregnancy. 48 (21.0%) were first discovered to be HIV-infected during the index pregnancy: 46 of these had risk factors. The present epidemiologic development does not seem to warrant a general HIV-screening in pregnancy at this time. 71 pregnancies (31%) were terminated; 158 children were born, 17 (23.3%) of the 73 definitely classified are HIV-infected. An asymptomatic HIV infection with a sufficiently high (> 200/microliters) CD4 cell count has no proven influence on the pregnancy. Otherwise, however, maternal infectious diseases can lead to prematurity. For mothers with i.v. drug abuse, there is a significantly higher incidence of prematurity and fetal growth retardation. The maternal HIV infection can be transmitted to the child either during pregnancy or at delivery. The incidence of vertical transmission in our study was 23.3%; the most predictive parameter for a prenatal HIV transmission is a low anti-p24 antibody titre. The risk of intrapartum transmission seems to be somewhat, but not significantly, reduced for primary Caesarean sections. Recently, prophylaxis with Zidovudin during pregnancy, beginning after the 14th GW, was found to reduce vertical HIV-transmission by 66%. Since the virus can also be transmitted through mothers' milk, HIV-positive mothers should not nurse their babies. Maternal infections are significantly more frequent in HIV-positive women, and are a risk factor for prematurity.(ABSTRACT TRUNCATED AT 250 WORDS)

Abortion, Induced↗
PubMed1995

The neonatal progeroid syndrome (Wiedemann-Rautenstrauch) and its relationship to Pelizaeus-Merzbacher's disease.

The neuropathology of a clinically well-documented case of the neonatal progeroid syndrome Wiedemann-Rautenstrauch is described. The most striking feature was a nearly complete absence of mature myelin in the brain. When immunohistochemistry for myelin basic protein was applied, some subcortical nerve fibres were accompanied by immature myelin sheaths. The neuropathology corresponds exactly to that of Pelizaeus-Merzbacher disease (Seitelberger type). Furthermore, this morphology, with the presence of myelin basic protein in the absence of mature myelin sheaths is reminiscent of the early stages of myelination in the newborn. From a brief review of the literature on Wiedemann-Rautenstrauch syndrome, we conclude, that the neuropathology of the syndrome is heterogeneous, and that there is relationship between the progeroid aspect and pathological myelination.

Brain↗