Swiss recommendations for the management of varicella zoster virus infections.

Infections with varicella zoster virus (VZV) are common viral infections associated with significant morbidity. Diagnosis and management are complex, particularly in immunocompromised patients and during pregnancy. The present recommendations have been established by a multidisciplinary panel of specialists and endorsed by numerous Swiss medical societies involved in the medical care of such patients (Appendix). The aim was to improve the care of affected patients and to reduce complications.

[Adnexitis and pelvic inflammatory disease]. / Adnexitis und "Pelvic Inflammatory Disease".

Pelvic inflammatory disease and upper genital tract infection describe inflammatory changes in the upper female genital tract of any combination: endometritis, salpingitis, tubo-ovarian abscess, peritonitis in the small pelvis. The International Infectious Disease Society for Obstetrics and Gynecology recommends a revision of the CDC guidelines taking into account the type of germ or the triggering agent and the seriousness of the disease. Infections with Chlamydia trachomatis and Neisseria gonorrhoeae are increasing worldwide. They are one of the main causes of tubal sterility, chronic abdominal pain and ectopic pregnancies. More than 30% of the infections are subclinical and asymptomatic. Therefore it is most recommendable to generally screen young, sexually active women with any of the risks mentioned above. Antibiotic therapy should be started as early as possible, in case of doubt even probatively, and should cover a broad spectrum of germs. C. trachomatis and N. gonorrhoeae should be treated according to resistance testing. In uncomplicated cases, hospitalization is unnecessary, ambulant therapy is sufficient.

[Acute fatty liver in pregnancy: clinical and histopathological course. Case report]. / Akute Schwangerschaftsfettleber: Klinischer und histopathologischer Verlauf. Kasuistik

Acute fatty liver of pregnancy is a rare disease which may be letal if diagnosis is missed. The pathogenesis is not completely clear, but there is some evidence that some cases have been associated with a genetic deficiency of fatty acid beta-oxidation. Other predisposing factors include primiparity, multiple pregnancy, male fetal sex and pre-eclampsia. Clinical presentation and laboratory findings are often unspecific. Increasing serum aminotransferases are characteristic in the early stage of the disease. Liver biopsy establishes the diagnosis and typically shows microvesicular, centrilobular fatty changes of hepatocytes. Differential diagnosis includes the HELLP-Syndrome, cholestasis of pregnancy, pre-eclampsia and viral or drug induced hepatitis. Without adequate treatment liver failure with coagulopathy and encephalopathy may develop. Two cases of acute fatty liver in pregnancy in an early stage are presented. Clinical and histopathological findings as well as diagnostic and therapeutic procedures are discussed.

Expression of members of the multidrug resistance protein family in human term placenta.

The placenta serves, in part, as a barrier to exclude noxious substances from the fetus. In humans, a single-layered syncytium of polarized trophoblast cells and the fetal capillary endothelium separate the maternal and fetal circulations. P-glycoprotein is present in the syncytiotrophoblast throughout gestation, consistent with a protective role that limits exposure of the fetus to hydrophobic and cationic xenobiotics. We have examined whether members of the multidrug resistance protein (MRP) family are expressed in term placenta. After screening a placenta cDNA library, partial clones of MRP1, MRP2, and MRP3 were identified. Immunofluorescence and immunoblotting studies demonstrated that MRP2 was localized to the apical syncytiotrophoblast membrane. MRP1 and MRP3 were predominantly expressed in blood vessel endothelia with some evidence for expression in the apical syncytiotrophoblast. ATP-dependent transport of the anionic substrates dinitrophenyl-glutathione and estradiol-17-beta-glucuronide was also demonstrated in apical syncytiotrophoblast membranes. Given the cellular distribution of these transporters, we hypothesize that MRP isoforms serve to protect fetal blood from entry of organic anions and to promote the excretion of glutathione/glucuronide metabolites in the maternal circulation.

Maternal drug abuse and human term placental xenobiotic and steroid metabolizing enzymes in vitro.

We evaluated the impact of maternal drug abuse at term on human placental cytochrome P450 (CYP)-mediated (Phase I) xenobiotic and steroid-metabolizing activities [aromatase, 7-ethoxyresorufin O-deethylase (EROD), 7-ethoxycoumarin O-deethylase (ECOD), pyrene 1-hydroxylase (P1OH), and testosterone hydroxylase], and androstenedione-forming isomerase, NADPH quinone oxidoreductase (Phase II), UDP-glucuronosyltransferase (UGT), and glutathione S-transferase (GST) activities in vitro. Overall, the formation of androstenedione, P1OH, and testosterone hydroxylase was statistically significant between control and drug-abusing subjects; we observed no significant differences in any other of the phase I and II activities. In placentas from drug-abusing mothers, we found significant correlations between ECOD and P1OH activities (p < 0. 001), but not between ECOD and aromatase or P1OH and EROD activities; we also found significant correlations between blood cotinine and UGT activities (p < 0.01). In contrast, in controls (mothers who did not abuse drugs but did smoke cigarettes), the P1OH activity correlated with ECOD, EROD (p < 0.001), and testosterone hydroxylase (p < 0.001) activities. Our results (wider variation in ECOD activity among tissue from drug-abusing mothers and the significant correlation between P1OH and ECOD activities, but not with aromatase or EROD activities) indicate that maternal drug abuse results in an additive effect in enhancing placental xenobiotic metabolizing enzymes when the mother also smokes cigarettes; this may be due to enhancing a "silent" CYP form, or a new placental CYP form may be activated. The change in the steroid metabolism profile in vitro suggests that maternal drug abuse may alter normal hormonal homeostasis during pregnancy.

[Cardiovascular disease in pregnancy]. / Kardiovaskuläre Erkrankungen in der Schwangerschaft.

There is a heterogeneous population of young women with cardiovascular disease contemplating pregnancy. Many of the conditions are rare and require teams with expertise in the management of such patients. A specific congenital or acquired cardiovascular anomaly and its physiology must be understood. The nature of prior surgical procedures and the residua and sequelae following therapy are essential to manage a pregnant woman with cardiovascular disease. Physiologic changes during pregnancy and after delivery must be known. Counseling includes maternal and fetal risk stratification and genetic counseling regarding inherited disorders. The outcome of pregnancy is favourable in many women with good functional class. These patients can be reassured. A multidisciplinary approach may be crucial to manage this population during pregnancy, labour, delivery and in the postpartum period to avoid serious maternal and fetal complications. Women with intermediate and high risk pregnancy must be followed and managed in a high risk pregnancy unit and a team from obstetricians, cardiologists, anesthetists, pediatricians, neonatologists and cardiac surgeons who are skilled in high risk pregnancies. Vaginal delivery is the method of choice in many women (class 1 woman) and cesarean section is seldom a cardiac indication. Contraindications for pregnancy are: poor maternal functional class, poor ventricular function, severe cyanosis without pulmonary hypertension (oxygen saturation < or = 85%), pulmonary vascular disease, severe mitral stenosis, severe left ventricular outflow tract obstruction, Marfan syndrome with aortic dilatation (> 40 mm) and aortic valve involvement (moderate to severe aortic regurgitation), symptomatic hypertrophic obstructive cardiomyopathy. Preconception counseling must be offered if unfavourable outcome is likely. Tubal ligation is probably the safest and most appropriate method of sterilization if there is a high risk pregnancy.

Xeno-oestrogens and phyto-oestrogens induce the synthesis of leukaemia inhibitory factor by human and bovine oviduct cells.

In bovine oviduct cells 17beta-oestradiol can induce the synthesis of leukaemia inhibitory factor (LIF), a glycoprotein essential for embryo implantation. Therefore substances which are structurally similar to 17beta-oestradiol and possess oestrogenic activity may also modulate LIF synthesis and influence the reproductive process. We used primary cultures of bovine and human oviduct cells (epithelial cells:fibroblasts 1:1) to compare the effects of 17beta-oestradiol, phyto-oestrogens (genistein, biochanin A, daidzein, formononetin, and equol) and xeno-oestrogens [polychlorinated biphenyls (PCB): trichlorobiphenyl, 4-hydroxy-trichlorobiphenyl and 4-hydroxy-dichlorobiphenyl] on LIF synthesis. Immunoreactive LIF-enzyme-linked immunosorbent assay was used to determine the concentration of LIF in the culture medium. Similar to 17beta-oestradiol, genistein (0.02-2 micromol/l) induced LIF synthesis in bovine oviduct cells in a concentration-dependent manner. Equol, biochanin A and daidzein (2 micromol/l), 4-hydroxy-trichlorobiphenyl and 4-hydroxy-dichlorobiphenyl (0.01-10 micromol/l) but not formononetin (2 micromol/l) also induced LIF synthesis in bovine cells. Phyto-oestrogens and xeno-oestrogens also induced LIF synthesis in human oviduct cells (P < 0.05). The stimulatory effects of PCB, phyto-oestrogens and 17beta-oestradiol were blocked by ICI 182,780 (1 micromol/l). Moreover, 17beta-oestradiol, 4-hydroxy-trichlorobiphenyl, 4-hydroxy-dichlorobiphenyl, genistein, tamoxifen and ICI 182,780 displaced [(3)H]17beta-oestradiol from cytosolic oestrogen receptors in bovine oviduct cells. These results suggest that phyto-oestrogens and PCB mimic the effects of oestradiol in inducing LIF synthesis by bovine and human oviduct cells and that these stimulatory effects are oestrogen receptor-mediated. Environmental oestrogens act as endocrine modulators/disrupters and may induce deleterious effects on the reproductive process by influencing LIF synthesis in a non-cyclic fashion leading to tubal infertility.

[Ureteral stent placement in hydronephrosis during pregnancy]. / Die retrograde Ureterschienung bei Schwangerschafts-hydronephrose.

In this study we describe 22 cases of retrograde ureteral stent placement in pregnant women with therapy-resistant flank pain due to hydronephrosis. Eleven were primiparous and one patient expected twins. Eight of 22 patients presented symptoms of pyelonephritis. In 21 cases the hydronephrosis was located on the right and in 4 cases it was bilateral. Maximal lower calix diameter was 12 mm (range 9-22 mm). With the exception of two cases, sonographically controlled stent placement was performed under local anesthesia without sedation. All patients were painfree within 6 days and were given prophylactic low doses of antibiotic until the day of delivery. Renal function remained within the normal limits. Double-J stent displacement occurred in 3 patients - of which one underwent nephrostomy. Postnatal examination demonstrated urolithiasis in 4 of 19 patients. This study provides evidence for effectiveness of retrograde ureteral Double-J stent placement as a therapeutic option in cases of severe symptomatic hydronephrosis during pregnancy with a low morbidity rate.

[Gynecological infections in general practice]. / Gynäkologische Infekte in der Praxis.

Although infections of the lower female genital tract are common, they only rarely pose diagnostic and therapeutic problems for the experienced clinician. If there is no response to primary therapy, however, or in cases of recurrence further steps are indicated. Sexually transmitted diseases are characterized by common involvement of the upper genital tract by ascending infection. Appropriate therapeutic measures including treatment of the partner are important in order to prevent severe acute and chronic diseases.

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.

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.

Successful treatment of fetal megavesica in the first half of pregnancy.

OBJECTIVE: Our goal was to assess fetal kidney function in fetuses with megavesica diagnosed during the first half of pregnancy before treatment. STUDY DESIGN: In a prospective interventional study 9 fetuses with megavesica diagnosed during the first half of pregnancy underwent vesicocentesis. Fetal urine biochemical markers (urine electrolytes, osmolarity, and beta 2-microglobulins) were determined after diagnostic vesicocentesis of the fetal megavesica. RESULTS: Surprisingly, in four fetuses who underwent sampling at 13 to 18 postmenstrual weeks, vesicocentesis proved both diagnostic and therapeutic. Pregnancy proceeded with normal amniotic fluid volume, a normal-sized urinary bladder with normal dynamics, and normal postnatal renal function. A fifth fetus had trisomy 18. In three of the remaining four fetuses in whom sampling was performed at 16 to 20 postmenstrual weeks, biochemical markers indicated a poor prognosis. In the remaining fetus marginal results of biochemical studies prompted intrauterine treatment, but death from respiratory problems ensued after premature delivery at 31 weeks. CONCLUSIONS: Fetal megavesica in the first half of pregnancy is an indication for an immediate diagnostic vesicocentesis. This is the first report emphasizing early diagnosis of fetal megavesica with subsequent fetal vesicocentesis and demonstrating that this minimally invasive procedure can be life-saving if performed in early pregnancy.

Identification of nitric oxide synthase in human and bovine oviduct.

Nitric oxide synthase (NOS) is responsible for the biological production of nitric oxide (NO) in several organs. NOS activity has also been localized in the reproductive tract, although direct evidence for its presence in the human or bovine oviduct is still lacking. In the present study, four different techniques were used to identify the presence of NOS activity in human (n = 11) and bovine (n = 9) oviduct: (i) conversion of [3H]-L-arginine to [3H]-L-citrulline; (ii) production of nitrite/nitrate (NO2/NO3; stable NO metabolites); (iii) identification of NADPH-diaphorase activity; and (iv) immunostaining with antiserum to endothelial NOS. Cytosolic extracts from human ampullary segments of the Fallopian tube, obtained from post-partum patients (n = 4), converted [3H]-L-arginine to [3H]-L-citrulline (21.0 +/- 8.8 fmol/mg protein/min). This conversion rate was significantly (P < 0.05) reduced in the presence of either EDTA or N-monomethyl-L-arginine monoacetate (L-NMMA), an inhibitor of NOS activity. When bovine (n = 3) ampullary segments were incubated for 36 h in Hanks' balanced salt solution, the concentration of NO2/NO3 in the medium was increased (P < 0.05) if segments were pretreated with lipopolysaccharide (LPS; an inducer of inducible NOS), but not after treatment with LPS + L-NMMA. Additionally, epithelial cells cultured from ampullary segments showed positive staining both for NADPH-diaphorase activity and with antiserum to endothelial NOS. The results of the present study provide direct evidence for the presence of both the Ca(2+)-dependent constitutive form of NOS, as well as the inducible form of NOS activity in human and bovine oviduct. Since the oviduct plays a key role in the reproductive process, it is possible that the two forms of NOS may be involved in the physiological regulation of oviduct function.

[HIV and pregnancy]. / HIV und Schwangerschaft.

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.

Elevated alpha-fetoprotein and human chorionic gonadotropin as a marker for placental trisomy 16 in the second trimester?

In a series of 2961 consecutive cases with second-trimester biochemical triple screening for Down's syndrome and neural tube defect (NTD), ten (0.3 per cent) showed an apparent increased risk for both conditions. Three cases had chromosomal abnormalities, namely trisomy 16 confined to the placenta. Since placental trisomy 16 as well as cases with increased alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG) are associated with (intrauterine growth retardation (IUGR), oligohydramnios, and fetal demise, at least some cases with this atypical biochemical profile could be explained by this chromosomal abnormality. From our results we recommend that in cases with increased risk for both Down's syndrome and NTD, fetal karyotyping should preferably be done on a placental biopsy, especially when ultrasound in the absence of anomalies demonstrates early IUGR.

[Pregnancies in HIV infected women in Switzerland]. / Schwangerschaften bei HIV-infizierten Frauen in der Schweiz.

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)

[Premature labor in HIV infected women. Swiss "HIV and Pregnancy" Study Group]. / Frühgeburtlichkeit bei HIV-infizierten Frauen. Schweizerische Arbeitsgruppe "HIV und Schwangerschaft".

In the Swiss Study "HIV and pregnancy" we observed 153 singleton pregnancies of HIV-positive women. 23 (15%) of those ended with a premature delivery. For drug addicts (n = 100), the incidence of prematurity, 20%, significantly higher than in those free of drugs (n = 53) with 5.6%. The most frequent cause of prematurity was premature labor or rupture of the membranes (n = 13), followed by maternal illness (n = 8) and fetal complications (n = 2). Women with premature delivery tended to have lower CD4 cell counts than those with term delivery (29.4% vs 12.0% with < 200 CD4 cells/microliters). Low CD4 cell counts and drug consumption are two independent but cumulative risks for severe infections. 16 of the 153 women (12 with, 4 without drug consumption) had severe infections during pregnancy; in 4 cases (25%), this led to prematurity. The most common infection was pneumonia (14/16), further one case of pyelonephritis and one of cerebral toxoplasmosis. Two of these 16 infants (12.5%) were HIV-positive. We could not confirm a relationship between prematurity and vertical HIV transmission. Of the HIV-classified children, 3/18 (16.7%) premature infants and 16/74 (21.6%) term infants were infected.