No clinical evidence base to support the hygiene hypothesis.

The hygiene hypothesis is a popular explanation for recent increases in allergy in the western world. This hypothesis suggests that development of allergy (or asthma) could be prevented by exposure to immune stimulants such as viruses, bacteria and endotoxins, in particular in the prenatal period or early childhood. How evidence-based are the observations which support the hygiene hypothesis? All clinical epidemiological indications in favour of the hypothesis are based on observational (cross-sectional and cohort) studies and not on observations in randomised controlled intervention studies. In cross-sectional studies no causal relationships can be assessed with sufficient validity. Also in cohort studies there are validity problems, as the exposure is not determined by chance (by means of randomisation) and could be influenced by behaviour. And behaviour might well be a confounder, since it can be associated with both exposure and outcome. A problem is that, without being appropriately tested in well designed prospective research, the hygiene hypothesis has currently already become so popular in the news media that an increased occurrence of asthma might even be induced as a result of an increased exposure. Although the currently available evidence to support the hygiene hypothesis is poor, it appears that the hypothesis has to some become a matter of faith or ideology. Scientists should take care that messages imparted to the general public do not go beyond or conflict with existing evidence.     

The diagnostic value of symptoms for the identification of patients with an increased risk of colorectal disease. A criteria-based analysis.

In most textbooks of gastroenterology, diseases with their symptoms are discussed. The exact diagnostic value of these symptoms, however, regarding the differentiation between organic and functional disease, is not mentioned. A criteria-based meta-analysis of the few existing studies in this field was done. From the 14 identified studies, there were two that did not find any significant symptoms. In the other studies the diagnostic value of colonic symptoms showed great variability. Methodological deficiencies in these studies are probably responsible for the latter. The generalization of these results into general practice is not straightforward and needs research in general practice patients.     

Distribution of spermatogenesis in the testicles of azoospermic men: the presence or absence of spermatids in the testes of men with germinal failure [published erratum appears in Hum Reprod 1998 Mar;13(3):780]

The aim of the study was to determine whether a prior diagnostic testicle biopsy can predict success or failure of testicular sperm extraction (TESE) with intracytoplasmic sperm injection (ICSI) in patients with non-obstructive azoospermia caused by testicular failure, and what is the minimum threshold of sperm production in the testis which must be surpassed for spermatozoa to reach the ejaculate. Forty- five patients with non-obstructive azoospermia caused by testicular failure underwent diagnostic testicle biopsy prior to a planned future TESE-ICSI procedure. The diagnostic testicle biopsy was analysed quantitatively, and correlated with the quantitative findings of spermatogenesis in patients with normal spermatogenesis, as well as with the results of subsequent attempts at TESE-ICSI. Men with non- obstructive azoospermia caused by germinal failure had a mean of 0-6 mature spermatids/seminiferous tubule seen on a diagnostic testicle biopsy, compared to 17-35 mature spermatids/tubule in men with normal spermatogenesis and obstructive azoospermia. These findings were the same for all types of testicular failure whether Sertoli cell only, maturation arrest, cryptorchidism, or post-chemotherapy azoospermia. Twenty-two of 26 men with mature spermatids found in the prior testis biopsy had successful retrieval of spermatozoa for ICSI, 12 of their partners became pregnant, and are either ongoing or delivered. The study suggests that 4-6 mature spermatids/tubule must be present in the testis biopsy for any spermatozoa to reach the ejaculate. More than half of azoospermic patients with germinal failure have minute foci of spermatogenesis which are insufficient to produce spermatozoa in the ejaculate. Prior diagnostic testicle biopsy analysed quantitatively (for the presence of mature spermatids) can predict subsequent success or failure with TESE-ICSI. Incomplete testicular failure may involve a sparse multi-focal distribution of spermatogenesis throughout the entire testicle, rather than a regional distribution. Therefore, it is possible that massive testicular sampling from many different regions of the testes may not be necessary for successful TESE-ICSI.      

Adhesion inhibitory activity of β-lactoglobulin isolated from infant formulae

β-Lactoglobulin was isolated from infant formulae that were ultra high temperature (UHT) -treated, sterilized or spray-dried. The effect of the isolated β-lactoglobulin on SfaII-fimbriae-mediated adhesion of Escherichia coli to human ileostomy glycoproteins was studied in vitro. β-Lactoglobulin isolated from sterilized formulae was found to perform significantly less well than preparations from spray-dried formulae (p = 0:05). Great heterogeneity was observed in the adhesion inhibitory capacity of β-lactoglobulin isolated from UHT-treated formulae. Therefore, no significant difference was observed between UHT-treated and sterilized formulae or spray-dried formulae (p < 0:10). It can be hypothesized that β-lactoglobulin from spray-dried and some UHT-treated infant formulae may affect the colonization of mucous membranes by E. coli strains causing neonatal septicaemia and meningitis.     

Haematologic parameters as risk factors for cardiac infarction, in an occupational health care setting

It is still controversial, whether moderately high haematocrit (Ht) and haemoglobin (Hb) values are risk factors for coronary heart disease. Using the computerized data-system of the Periodical Medical Examination (PME) of Phillips' International Electrical Company, a case-control study was carried out. Cases were male workers (n = 104, from 50 to 60 years of age) who had suffered a first, non-fatal myocardial infarction, and who had had a PME prior (on the average 16 months) to the occurrence of infarction. For each case two age-matched healthy controls were selected from the PME-attendancy list (= 208). For each subject information was abstracted from the PME-records about haematologic parameters and covariates (smoking, cholesterol, blood pressure, pulse-rate, weight, height, FEV5, consumption of antihypertensive agents). After dichotomizing the haematocrit and haemoglobin values at their whole sample means (0.46 l/l and 9.7 mmol/l respectively) in "low" (lower than or equal to the mean) and "high" (greater than the mean), crude odds-ratio's of 2.7 (95% CI: 1.6-4.6) and 2.1 (95% CI: 1.2-3.6) were found for Ht and Hb respectively, when comparing "high" with "low" levels. The associations between Ht and Hb, and the occurrence of myocardial infarction were still present after controlling for covariates using multiple logistic regression models, entering the continuous variables with their exact values. After adjustment, mean corpuscular volume (MCV) also appeared to be correlated with infarction. Our results confirm the hypothesis that moderately high haematocrit and--to a lesser extent--haemoglobin and MCV-values are risk factors for the occurrence of myocardial infarction.     

Mutations in the retinal guanylate cyclase (RETGC-1) gene in dominant cone-rod dystrophy

The dominant cone-rod dystrophy gene CORD6 has previously been mapped to within an 8 cM interval on chromosome 17p12-p13. The retinal- specific guanylate cyclase gene (RETGC-1), which maps to within this genetic interval and previously was implicated in Leber's congenital amaurosis, was screened for mutations within this family and in a panel of small families and individuals with various cone and cone- rod dystrophy phenotypes. A missense mutation (E837D) was identified in affected members of the CORD6 family, as well as a second missense mutation (R838C) in three other families with dominant cone-rod dystrophy. RETGC-1 is only the fourth gene to be implicated in cone-rod dystrophy and this is the first report of dominant mutations in this gene.      

Interpretation of diagnostic data: an unexplored field in general practice

In interpreting diagnostic information the differences between morbidity patterns in general practice and those in hospitals must be taken into consideration. This article demonstrates the importance of prevalence for predictive values of complaints, symptoms and test results. When the general practitioner refers patients to the specialist, these values may change, and it is also possible that associations between symptoms and diagnoses are distorted by selection bias. Moreover, attention must be paid to the differences in clinical stages encountered in general practice and specialist practice. It is concluded that a large part of the `diagnostic field' of general practice has still to be discovered and developed.     

Effect of timing of oocyte denudation and micro-injection on survival, fertilization and embryo quality after intracytoplasmic sperm injection

In human in-vitro fertilization (IVF), the oocytes are surrounded by cumulus and corona cells at the time of insemination so that their maturity cannot easily be evaluated. The best IVF results are obtained if the oocytes are inseminated 2-6 h after retrieval. In the intracytoplasmic sperm injection (ICSI) procedure, the oocytes are denuded by enzymatic and mechanical treatment in order to be able to perform the injection. As a consequence, the nuclear maturity of the oocytes can be evaluated and only those that have extruded the first polar body are injected. However, metaphase-II oocytes that have not yet reached cytoplasmic maturity cannot be recognized. The purpose of this study was to investigate the effect of different timing of cumulus- corona cell removal and injection on the outcome of ICSI. For this we allowed the oocytes to complete in-vitro cytoplasmic maturation in two different culture conditions: (i) surrounded by their cumulus and corona cells or (ii) totally denuded. We performed three different studies on sibling oocytes obtained after a standardized buserelin/human menopausal gonadotrophin (HMG) protocol. We investigated the effect of early (1-2 h after retrieval) and late (5-6 h after retrieval) oocyte denudation and injection on the survival and fertilization of the injected oocytes and on embryo cleavage after fertilization. We found no statistically significant differences between early and late injection, indicating that after a standardized buserelin/HMG protocol the metaphase-II oocytes do not need time for further cytoplasmic maturation. Furthermore, a different timing of cumulus-corona cell removal has no effect on the outcome of ICSI, suggesting that the surrounding cells are not necessary for survival, fertilization and cleavage after ICSI.