Facteurs associés à la létalité chez les patients hospitalisés pour le VIH avancé.

CONTEXT: A unit supported by Médecins Sans Frontières (MSF) cares for patients with advanced HIV at Donka National Hospital, Conakry, Guinea. OBJECTIVE: To determine the factors associated with the occurrence of death in patients hospitalised in the unit between 2017 and 2021. DESIGN: This was a retrospective analysis of routine data from patients hospitalised with advanced HIV. RESULTS: A total of 3,718 patients were included, with a median age of 40 years (IQR 33-51), of whom 2,241 (60.3%) were women. The mean mortality rate was 33.6% (n = 1,240), down from 40% in 2017 to 29% in 2021, but this was not statistically significant. The period most at risk of death was the first 25 days of hospitalisation. Among these patients, TB (43.8%) and toxoplasmosis (11.4%) were the most frequent diagnoses. After multivariate analysis using Cox regression, the factors associated with death were age 25-49 years (adjusted hazard ratio [aHR] 1.60; P = 0.002) or ≥50 years (aHR 1.80; P < 0.001), the presence of respiratory (aHR 1.23; P = 0.001) or abdominal symptoms (aHR 1.26; P < 0.001) and readmission (aHR 0.54; P < 0.001). CONCLUSION: Patients aged 25-49 years or older, or those presenting with respiratory or abdominal signs require increased surveillance, as they are at the greatest risk of dying from the disease, especially during the first 25 days of hospitalisation.

Missed opportunities for earlier diagnosis of rifampicin-resistant tuberculosis despite access to Xpert® MTB/RIF.

OBJECTIVE: To assess the proportion of rifampicin-resistant tuberculosis (RR-TB) patients with potential earlier RR-TB diagnoses in Khayelitsha, South Africa. DESIGN: We conducted a retrospective analysis among RR-TB patients diagnosed from 2012 to 2014. Patients were considered to have missed opportunities for earlier diagnosis if 1) they were incorrectly screened according to the Western Cape diagnostic algorithm; 2) the first specimen was not tested using Xpert® MTB/RIF; 3) no specimen was ever tested; or 4) the initial Xpert test showed a negative result, but no subsequent specimen was sent for follow-up testing in human immunodeficiency virus-positive patients. RESULTS: Among 543 patients, 386 (71%) were diagnosed with Xpert and 112 (21%) had had at least one presentation at a health care facility within the 6 months before the presentation at which RR-TB was diagnosed. Overall, 95/543 (18%) patients were screened incorrectly at some point: 48 at diagnostic presentation only, 38 at previous presentation only, and 9 at both previous and diagnostic presentations. CONCLUSIONS: These data show that a significant proportion of RR-TB patients might have been diagnosed earlier, and suggest that case detection could be improved if diagnostic algorithms were followed more closely. Further training and monitoring is required to ensure the greatest benefit from universal Xpert implementation.

Objective cosmetic and anatomical outcomes at adolescence of feminising surgery for ambiguous genitalia done in childhood.

There are few, if any data on the long-term outcome of feminising genital surgery for children with ambiguous genitalia. We present a retrospective study of cosmetic and anatomical outcomes in 44 adolescent patients who had ambiguous genitalia in childhood and underwent feminising genital surgery. Cosmetic result was judged as poor in 18 (41%) of these patients. 43 (98%) of 44 needed further treatment to the genitalia for cosmesis, tampon use, or intercourse. 23 (89%) of 26 of genitoplasties planned as one-stage procedures required further major surgery. This information must be available to parents and clinicians planning such surgery. Cosmetic genital surgery in infancy needs to be reassessed in the light of these results.

A map of interactions between the proteins of a retrotransposon.

The yeast two-hybrid system and in vitro binding assays were used to characterize 54 potential interactions between the proteins of Tf1, an LTR-retrotransposon found in Schizosaccharomyces pombe. The Tf1 integrase (IN) protein was found to interact strongly with itself and not with other control proteins. In addition, the IN core domain interacted strongly with itself and full-length IN. Interestingly, the two-hybrid analysis detected an interaction between the RNase H domain of reverse transcriptase and IN. The biological implications of these interactions are discussed.

What are the effects of anonymity and secrecy on the welfare of the child in gamete donation?

A perennial concern when using donated gametes in infertility treatment is the effect on the child and his/her family of the traditional anonymity of the donor, and of the secrecy of the procedure. As all involved, from potential parents to carers, wish to maximize the 'welfare of the child' born of gamete donation, conflicting attitudes, sometimes translated into diverging legislations in Europe, are analysed. In the face of the lack of evidence on the consequences of secrecy or openness, it is concluded that future parents are best placed to decide on this matter for the potential children.

Ovarian tissue cryopreservation for patients.

For patients about to receive chemotherapy, radiotherapy or to undergo a surgical procedure, loss or impairment of fertility is a major issue. For males, sperm banking is a standard accepted procedure to circumvent loss or damage to spermatozoa and this has been undertaken in this unit since 1975 (Steele et al., 1995). For women there is no established procedure for gamete storage. Embryo preservation is not an option for single women or even for those in a stable relationship, as treatment would have to be delayed while ovarian stimulation and oocyte retrieval took place. With the general shortage of donor oocytes, the possibility of maturing primordial follicles from fetal ovaries has become a subject for debate (HFEA 1995: Recent deliberations). In animals, the use of frozen ovarian tissue has been encouraging with a report of a live birth in lamb after orthotopic transplantation (Gosden et al., 1995). Media attention to the future prospect for freezing ovarian tissue has meant that pressure from patients is likely to increase either for information or as requests to freeze the ovarian tissue which could irretrievably be lost as a result of surgery and/or treatment. In the absence of well defined procedures and technologies, should women be given the chance to preserve ovarian tissue prior to receiving intensive chemotherapy or radiotherapy?

Molecular cytogenetic analysis of five newly established cervical cancer cell lines using G banding and fluorescence in situ hybridization.

Cervical tumors nearly all have complex karyotypes and more precise cytogenetic information is required to establish whether specific rearrangements occur, and if they are related to the type of HPV infection found. The karyotypes of five recently established cervical cancer cell lines, three from squamous cell carcinomas (two HPV 16 +ve and one HPV 18 +ve), one from an adenocarcinoma (HPV -ve), and one from an adenosquamous carcinoma (HPV 16 +ve), have been analysed using fluorescence in situ hybridization (FISH), with 23 chromosome specific paints, YACs and cosmids as probes, in addition to conventional G banding, in order to identify markers and clarify the breakpoints. Chromosomes 1 and 3 were rearranged in all cell lines. Breakpoints in the squamous lines were all in 3q. but in different regions. Small metacentrics involving chromosome 5 were a del(5q) in one line, and a t(X;5) in another, rather than i(5p). The region 6q21 was involved in three cases and chromosome 9 was rearranged in four. An i(8q) was found in three squamous carcinoma cell lines. Structural changes of 11q were found only in two cases, but a marker 11 representing amplification in the 11q14-22 region was duplicated in the adenosquamous line.

Effect of smoking cessation on cervical lesion size.

BACKGROUND: Cigarette smoking has been postulated as a cofactor in the aetiology of cervical cancer, but a causal role is difficult to establish because of potential confounding by sexual behaviour. We have investigated the effect of cessation or reduction of cigarette smoking on the course of minor-grade cervical lesions. METHODS: In this intervention study 82 women volunteers with minor-grade lesions on colposcopy (cervical intraepithelial neoplasia grade 1 or less) attempted to give up smoking for 6 months. Smoking histories were taken at 3-monthly clinic visits and verified by measurement of salivary cotinine concentrations. At each clinic visit, a photograph of the cervix was taken; the image was digitised and computer-aided image analysis was used to assess lesion size, by investigators unaware of smoking status. FINDINGS: Of the 82 women, 17 stopped smoking completely for at least 6 months and 11 others reduced their smoking consumption by more than 75%. Of these 28 women, 23 (82%) showed a reduction in lesion size of at least 20% or 4 mm2 compared with 13 (28%) of the 47 non-quitters (odds ratio 12.0 [95% Cl 3.9-32.7]). The remaining seven women had unconfirmed smoking histories. There was a significant correlation between the extent of smoking reduction and the change in lesion size (chi2 for trend=31.55, p<0.0001). Adjustment for social class, method of contraception, and stage of menstrual cycle did not affect the results. INTERPRETATION: Our findings support a link between smoking and cervical disease and suggest that smoking cessation could have a beneficial effect on early cervical abnormalities.

The potential for improved abdominal procedures and approaches for tubal occlusion.

Methods of sterilization by the abdominal route are reviewed. There are wide variations in practice which reflect experience, training and resources in different countries. Clip sterilization comes nearest to fulfilling the criteria of a satisfactory method, whether performed by laparoscopy or minilaparotomy. The development of the Cambridge clip seems to offer the prospect of a significant improvement in reliability and safe application while microlaparoscopy and a smaller clip would facilitate the use of local anesthesia and decrease morbidity.

In-vitro cervical mucus-sperm penetration tests and outcome of infertility treatments in couples with repeatedly negative post-coital tests.

The results of in-vitro cervical mucus-sperm penetration tests and cross-hostility tests in 178 couples with repeatedly negative post-coital tests were recorded. Using a protocol of three cycles with intra-uterine inseminations (IUI) followed by three cycles with ovulation induction + IUI, the association between the cause of infertility, results of the in-vitro tests and the outcome of infertility treatment was investigated. We found that repeatedly negative post-coital tests are a good indicator of a cervical mucus-sperm penetration problem. The cross-hostility test clearly differentiates the abnormal factor in this interaction, and a good performance of the donors' spermatozoa in the cervical mucus correlates with increased pregnancy rate. In male factor infertility, failure of the husbands' spermatozoa to penetrate cervical mucus was not indicative of a deficient fertilization potential in vivo. In these patients a serious attempt should therefore be made to reverse the infertility by treatment with IUI or ovulation induction + IUI before attempting assisted reproduction. Women with polycystic ovaries and repeatedly negative post-coital tests should be investigated for sperm receptivity of the cervical mucus. Low receptivity of the cervical mucus may imply that endometrial receptivity and oocyte quality are also low. Ovulation induction and not IUI alone should therefore be used as the preferred mode of treatment to improve pregnancy rate.

The potential for improved abdominal procedures and approaches for tubal occlusion.

Methods of sterilization by the abdominal route are reviewed. There are wide variations in practice which reflect experience, training and resources in different countries. Clip sterilization comes nearest to fulfilling the criteria of a satisfactory method, whether performed by laparoscopy or minilaparotomy. The development of the Cambridge clip seems to offer the prospect of a significant improvement in reliability and safe application while microlaparoscopy and a smaller clip would facilitate the use of local anesthesia and decrease morbidity.

A revised structure for the disialosyl globo-series gangliosides of human erythrocytes and chicken skeletal muscle.

Disialosyl globo-series gangliosides have previously been isolated from chicken skeletal muscle (E. L. Hogan, R. D. Happel, and J.-L. Chien (1982) Adv. Exp. Med. Biol. 152, 273-278; S. Dasgupta, J.-L. Chien, E. L. Hogan, and H. van Halbeek (1991) J. Lipid Res. 32, 499-506) and human erythrocytes (S. K. Kundu, B. E. Samuelsson, I. Pascher, and D. Marcus (1983) J. Biol. Chem. 258, 13857-13866). In both cases, the structure of this ganglioside was proposed to be NeuAc alpha 2-->3(NeuAc alpha 2-->6)Gal beta 1-->3GalNAc beta 1-->3Gal alpha 1-->Gal alpha 1-->4Gal beta 1-->1Cer (V3NeuAcV6NeuAcGb5Cer). We have reinvestigated the human erythrocyte antigen and now propose an alternative structure differing in the location of the NeuAc alpha 2-->6 residue: NeuAc alpha 2-->3Gal beta 1-->3 (NeuAc alpha 2-->6)GalNAc beta 1-->3Gal alpha 1-->4Gal beta 1-->4Glc beta 1-->1 Cer (V3NeuAcIV6NeuAcGb5Cer). This novel structure is supported by results of 1H-NMR spectroscopy, negative ion fast atom bombardment mass spectrometry, and methylation linkage analysis with capillary gas chromatography--mass spectrometry in both electron impact and chemical ionization modes. Furthermore, based on new results from negative ion fast atom bombardment mass spectrometry and linkage analysis, we propose that the chicken skeletal muscle antigen also has this revised structure, differing only in ceramide composition. The terminal tetrasaccharide of these gangliosides is identical to that of GD1 alpha, NeuAc alpha 2-->3Gal beta 1-->3(NeuAc alpha 2-->6)GalNAc beta 1-->4Gal beta 1-->4Glc beta 1-->1 Cer(IV3NeuAcIII6NeuAcGg4Cer), previously identified in a rat ascites hepatoma cell line (T. Taki, Y. Hirabayashi, H. Ishikawa, S. Ando, K. Kon, Y. Tanaka, and M. Matsumoto (1986) J. Biol. Chem. 261, 3075-3078) and a murine lymphoma cell line with low metastatic potential (K. Murayama, S. B. Levery, V. Schirrmacher, and S. Hakomori (1986) Cancer Res. 46, 1395-1402), although they appear to be immunologically distinct.

Stage-specific glycosphingolipids from amastigote forms of Leishmania (L.) amazonensis. Immunogenicity and role in parasite binding and invasion of macrophages.

Neutral glycosphingolipids (GSLs) from amastigote forms of Leishmania (L.) amazonensis were isolated, and their structures and biological properties were characterized. Based on various immunochemical methods, these GSLs were shown to be expressed at certain stages of amastigote development. GSLs were extracted and purified from amastigotes of hamster foot lesions by established procedures. Three mouse monoclonal antibodies (MoAbs) specific for carbohydrate epitopes of these GSLs were established, and their inhibition of parasite binding and macrophage invasion was analyzed. MoAb ST-3 inhibited 80% of macrophage invasion by amastigotes and 60% of that by promastigotes. Since GSLs reacting with MoAb ST-3 were found in amastigotes but not in promastigotes, ST-3 reactivity with promastigotes presumably depends on an epitope present on an unidentified promastigote glycoconjugate. MoAbs ST-4 and ST-5 inhibited 60-80% of macrophage invasion by amastigotes but were not effective in preventing macrophage invasion by promastigotes. Fab fragments of ST-3 inhibited invasion of cultured mouse macrophages by amastigotes (80%) or promastigotes (60%). The GSL with the simplest structure recognized by these MoAbs was isolated and characterized (by negative ion fast atom bombardment-mass spectrometry, gas chromatography-mass spectrometry of the permethylated compound, degradation with exoglycosidases, and 1H NMR) as the novel globoseries structure Gal beta 1-->3Gal alpha 1-->4Gal beta 1-->4Glc beta 1-->Cer, which has beta 1-->3Gal in place of the beta 1-->3GalNAc of globoside. The ceramide contains a 16:0 fatty acid and d18:1 sphingosine as the long chain base. The MoAbs also reacted with a series of GSLs from amastigote forms of L. amazonensis, with longer carbohydrate chains, probably containing identical end groups Gal beta 1-->3Gal alpha 1-->R. Expression of surface GSLs may render amastigote forms more effective than promastigotes in binding and invading host macrophages, thus enhancing the infectious process.

Effects of age, gravidity and male infertility status on cumulative conception rates following artificial insemination with cryopreserved donor semen: analysis of 2998 cycles of treatment in one centre over 10 years.

The effects of age, gravidity and male infertility status on cumulative conception rates after donor insemination were investigated in an analysis of 2998 treatment cycles undertaken on 443 patients. It was found that the cumulative conception rates after 3, 6 and 12 cycles of treatment were 21, 40 and 62% respectively for patients < 30 years of age compared with 17, 26 and 44% for those aged > or = 30 years (P = 0.008). There was also a significant difference (P < 0.001) in results depending on course of treatment and the cumulative conception rates were 19% after 3 cycles, 33% after 6 cycles and 54% after 12 cycles of treatment in the first course of treatment compared with 40, 67 and 79% respectively in those who returned for subsequent courses of treatment after having achieved a donor insemination pregnancy in the first treatment course. Gravidity and male infertility status (azoospermia or oligozoospermia/asthenozoospermia) did not significantly affect the cumulative conception rates.

Quantitative determination of acid-labile DNA in cervical intraepithelial neoplasia.

Using a modified Feulgen hydrolysis procedure and integrating microdensitometry, the acid-labile nuclear DNA in exfoliated cervical epithelial cells was quantified in a range of histologically confirmed cervical intraepithelial neoplasia (CIN), invasive cancer, and normal controls. The mean relative optical densities obtained for each sample group showed an increase from normal epithelium, through CIN grades, to invasive cancer. Although there was some overlap between groups, the difference in the overall mean values between the adjacent groups was statistically significant. The sensitivity of the test was 87.1% with a specificity of 99.2% and a predictive value of 99.5%, with no false negatives in the severe dysplasia and cancer groups. Quantitative data allows the threshold value to be altered to vary the sensitivity and specificity according to prevailing requirements. This suggests the possibility of using quantitative acid-labile DNA measurements to improve existing screening for cervical precancer.

HIV and preconceptional counselling.

PIP: This article provides a general discussion of a variety of different features of HIV infection and the not widely accepted concept of preconception counseling. The focus is on testing, counseling and counselors, infertility clinics, promotion of awareness, attitudes to HIV testing, education, parameters for counseling, the risk of coitus and the value of contraceptive usage in the presence of HIV, accurate and understandable information, attitudes of children, legal significance, and the effect of disaster on the family and relationships. The author is concerned with the need to provide testing facilities, and prepregnancy testing. The risk of HIV infection adds to the importance of planned pregnancy and counseling in family planning and selecting appropriate methods. Informed and responsible decisions require adequate consideration of all the issues and information currently available. Preconceptual counseling clinics tend to be small in number, but the health care professionals serving the population in need must be well educated in the knowledge of obstetrics and the behavior of HIV infection/AIDS. Infertility clinics are one potential source of contact with those at high risk of HIV. A national campaign to emphasize the need to seek advice on family planning for those at risk of HIV is necessary in countries where HIV is widespread. Preconception counseling is possible only after there is awareness of risk of HIV infection and the risks of pregnancy. Confounding policies for testing and counseling are attitudes of politicians and officials which may reflect the general welfare rather than individual welfare or public opinion and attitudes of pressure groups which may not reflect the general welfare. 2 issues are of concern: that risk by accurately assessed, and terms like safe sex avoided. The following understandable information needs to be provided; a woman's risk with an HIV positive husband, a woman's pregnancy risk, a father's risk with an HIV infected partner, the fetal risk (estimated at 30%), prognosis for an infected child, the effect on family of having an infected child, possible cures/effective treatment in the future, the effect of relationships and parents work/life, the possibility of an orphaned child or loss of a parent, adverse effects of factors on pregnancy, the relevance of any treatment, and children's welfare with harmful parent lifestyles. Counselors must be aware of the influence of race, religion, class, and the pressures in prostitution for unprotected sex. Legal issues may arise between parent and child, or in counselor negligence. Caring for a handicapped child and the nature of discrimination against those with AIDs must be approached openmindedly. An informed decision must be an available option.^ieng

Outcome of pregnancy in underweight women after spontaneous and induced ovulation.

Low maternal weight before pregnancy and poor weight gain during pregnancy are known to result in an increased prevalence of low birthweight infants. Low body weight is also an important cause of amenorrhoea. The hypothesis that amenorrhoeic underweight women who become pregnant after induction of ovulation are more at risk of delivering low birthweight infants than underweight women who ovulate spontaneously was investigated. Forty one pregnant women in whom ovulation had been induced and 1212 in whom ovulation was spontaneous were studied. Women ovulating spontaneously whose weight was normal and who showed good weight gain during pregnancy (greater than 450 g a week) had the lowest incidence (6%) of babies who were small for gestational age. Underweight women (body mass index less than 19.1) who ovulated spontaneously had a threefold increased risk of delivering babies who were small for gestational age (18%). Overall, the women in whom ovulation had been induced had an even higher risk of babies who were small for dates (25%), and the risk was greatest (54%) in those who were underweight. The outcome of pregnancy is related to weight before conception, which in many cases reflects nutritional state; lack of spontaneous ovulation indicates an increased risk of producing a small for dates infant. The most suitable treatment for infertility secondary to weight related amenorrhoea is therefore dietary rather than induction of ovulation.

Quantitative assessment of cervical neoplasia by hydrolysed DNA assay.

A hydrolysed component of DNA was measured in cervical smears from 187 women. The results clearly distinguished patients with cervical intraepithelial neoplasia and invasive carcinoma from a control group. This method could be automated.