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.

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.

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.

The natural history of cervical intraepithelial neoplasia as determined by cytology and colposcopic biopsy.

The smears preceding the histologic diagnosis of cervical intraepithelial neoplasia (CIN 3) were examined in 100 consecutive cases from an intensively screened population. In 60 patients, negative cytology has been recorded prior to the development of dysplasia; in 27 this had occurred within two years of the histologic diagnosis. These findings suggest that the transition time from epithelial normality to CIN 3 may be shorter than has been generally assumed; therefore, the intensity and frequency of screening should be reviewed.

Abortion and sterilization.

PIP: This discusses activities current in England under the abortion law of April 1968. In England and Wales in 1969 there were 54,013 recorded abortions and 15 related deaths. Since then both the number of deaths and the number of abortions have been increasing. This abortion increase is partly attributed to the adverse publicity regarding the pill which has caused many women to give up oral contraceptives. Complications have included incomplete removal of the products of conception, sepsis, hemorrhage, and perforation of the uterus. There have been wide variation in interpretations of the law by different hospitals and staffs. Sterilization operations are being done in increasing number for both men and women. Carefully worded consent forms are now in use to insure patient understanding and consent. Psychological changes may follow sterilization, but are relatively uncommon. Physicians should do all possible to help women avoid unwanted pregnancies and thereby reduce the demand for termination.^ieng

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

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.

The measurement of plasma oestradiol and progesterone in women with amenorrhoea treated with gonadotrophins.

PIP: Estradiol was measured in 4 amenorrheic women during treatment with human menopausal gonadotropin (HMG) and progesterone during treatment with human chorionic gonadotropin (HCG) to determine if ovulation was dependent on estradiol patterns. The 4 women had been amenorrheic for at least 12 months and were treated with 27 courses of HMG 150-750 U, without or with HCG 10,000 U, increasing the doses of HMG until ovulatio n occurred. Estradiol was measured by a double competitive binding technique using high-affinity rabbit uterine receptor. Estradiol was measured on Day 7 after 3 HMG injections, then related to progesterone measured on Day 15 after HCG injected on Day 7. Responses were categorized into 2 groups: a group with estradiol below 30 ng/100 ml plasma with no progesterone response, and a group of 16 courses of treatment with estrogen 30-120 ng/100 ml and progesterone 10-65 ng/ml. Results in successive treatments in individuals were sometimes inconsistent. The estradiol curves on Day 7-8 could be classified as dropping in 7 courses, constant in 2, and increasing in 2. 2 women became pregnant in cycles with declining estradiol on Days 7-8. A multiple pregnancy spontaneously aborted and was marked by higher than normal estradiol (80 ng/100 ml) and progesterone (50 ng/ml) during gonadotropin treatment. This type of study may improve monitoring of women undergoing gonadotropin treatment.^ieng

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?

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.

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.

Amenorrhoea after discontinuing combined oestrogen-progestogen oral contraceptives.

Out of 210 women seen at the Middlesex Hospital with secondary amenorrhoea the 63 who developed it after stopping oral contraceptives were fully investigated. Five had organic disease sufficient to account for the amenorrhoea (one had severe diabetes, one a pituitary tumour, and three premature ovarian failure); two patients had galactorrhoea (one of whom also had the pituitary tumour); two had anorexia nervosa.Of the 63 women 40 (63%) had suffered from amenorrhoea or prolonged or irregular menstrual cycles before taking the pill, and this suggested that combined oestrogen-progestogen oral contraceptives should be used with caution for women with irregular menstruation.Nineteen patients wished to become pregnant and 12 have so far done so after treatment with clomiphene or gonadotrophins.In another study 204 women recorded when their first menstrual cycle occurred after stopping the pill. Seventy-four had a cycle longer than five weeks but only five exceeded three months, and only one of the five had more than six months' amenorrhoea. These results confirm that the incidence of amenorrhoea after stopping oral contraceptives is low.