Decline in sperm counts: an artefact of changed reference range of "normal"?

OBJECTIVE--To investigate a reported fall in sperm counts during 1940-90 in relation to the reduced lower reference value of "normal" during the same period by assuming the null hypothesis that no change had occurred in the probability distribution of the sperm concentration. DESIGN--Analysis by using various mathematical models of the probability distribution of sperm concentration together with experimental data which supported a model employing a logarithmic distribution. SUBJECTS--235 men presenting for stimulated in vitro fertilisation at Midland Fertility Services, Aldridge, in 1992 together with samples of 20 ejaculates from each of five men attending the same centre during 1992-3. RESULTS--The effect of the change in lower reference value for the "normal" sperm concentration (from 60 x 10(9) to 20 x 10(9)/l) depended on the probability distribution of the concentration in the population. If that distribution was normal or uniform, then very little of the reported decline was a consequence of the change in lower reference value. If it was heavily skewed, then most or all of the reported decline may have been a consequence of that change. The limited experimental data available indicate that the distribution was heavily skewed. CONCLUSIONS--Depending on the actual distribution of sperm concentration in the population, the reported decline in concentration may have been accounted for entirely or in part by the change in lower reference value. The original evidence does not support the hypothesis that the sperm count declined significantly between 1940 and 1990.     

Ultrastructure de l'endomètre humain normal

Résumé Les auteurs ont étudié les variations morphologiques et métaboliques de 15 endomètres humains normaux prélevés à diverses phases du cycle menstruel.En phase proliférative, les cellules glandulaires ont une activité métabolique de synthèse endogène et acquièrent un important complexe ergastoplasmo-golgien.En phase sécrétoire débutante le glycogène s'accumule dans les cellules glandulaires; son catabolisme fournira les réserves métaboliques nécessaires à l'intense activité de synthèse dont font preuve les cellules glandulaires en phase sécrétoire moyenne.Le matériel synthétisé, présumé mucopolysaccharidique, apparaît dans des vacuoles golgiennes qui migrent ensuite vers le pôle apical de la cellule.L'involution débute dès le 24ème jour et se traduit par la régression de l'activité de synthèse, par l'apparition de foyers autophagiques puis par une hyperhydratation cellulaire.En phase menstruelle certaines cellules se nécrosent totalement, d'autres (les plus nombreuses) régénèrent et participent à un nouveau cycle menstruel.

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Ultrastructure of the normal human endometriumII. The glandular cells

Summary The authors have studied the cyclic morphologic and metabolic variations of 15 normal human endometria.In the phase of proliferation, the glandular cells have a metabolic activity of endogen synthesis and acquire welldeveloped ergastoplasm and Golgi-complexes.In the early phase of secretion, glycogen deposits appear in the glandular cells. Their catabolism will provide the metabolic reserves necessary for the intense synthesis occuring in the glandular cells during the mid secretory phase.The synthezised material — probably mucopolysaccharidic — appears first in Golgi vacuoles which migrate then towards the apical pole of the cell.The cellular involution begins on the 24th day and is characterized by the regression of the synthesis activity, by the appearance of focal necrosis and then by cellular hyperhydratation.In the menstrual phase, while some of the cells undergo total necrosis, others, the majority, regenerate and will participate in a new menstrual cycle.

Nous remercions Monsieur le Professeur Gandar, Directeur de la Clinique Gynécologique et Obstétricale 1 de la Faculté de Médecine de Strasbourg de nous avoir confié, pour examen ultrastructural, le matériel nécessaire à cette étude.     

Ultrastructure de l'endomètre humain normal

Résumé L'étude du chorion cytogène de 15 endomètres humains normaux prélevés à divers moments du cycle menstruel a précisé d'importantes variations des vaisseaux et des cellules.Les vaisseaux subissent une maturation progressive: en phase proliferative moyenne, des pointes d'accroissement se forment à partir du réseau vasculaire profond activé; au milieu du cycle, elles se transforment en capillaires typiques; en phases sécrétoires moyenne et avancée, des péricytes migrent dans le chorion cytogène et se différencient en cellules choriales.Ces cellules choriales, dites fixes, ont une évolution biphasique au cours du cycle menstruel. Au milieu de chacune des phases, proliférative et surtout sécrétoire, les cellules choriales fixes, dites alors fibroblastoïdes, montrent une intense activité de synthèse. A ces périodes de synthèse succède une involution cellulaire, peu marquée en fin de phase proliferative, intense en phase sécrétoire avancée.Les cellules dites prédéciduales sont des cellules choriales fixes involuées et hyperhydratées; elles vont, en phase menstruelle, évoluer de plusieurs façons: la plupart d'entre elles régénèrent, certaines se nécrosent focalement ou totalement, d'autres font preuve d'activité macrophagique, en particulier collagénolytique.

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Ultrastructure of the normal human endometriumI. The stroma

Summary 15 human endometria during the normal menstrual cycle have been investigated. Important alterations of the vessels and the stroma cells occur.The vessels are the site of gradual maturation. In the mid proliferative phase, growing capillaries rise from the deep-seated vascular system. In the middle of the cycle, they change into typical capillaries. In the mid and late secretory phases, pericytes leave the walls of the capillaries and differentiate into stroma cells.These stroma cells undergo a biphasic cyclic evolution. The middle of the proliferative and particularly of the secretory phase is marked by an intensive synthetic activity of the stroma cells which are called, at this time, fibroblastoïd stroma cells. These two periods of synthesis are followed by cellular involution, mild in the proliferative, intense in the secretory phase.The so-called predecidual cells are hyperhydrated involuted stroma cells. In the menstrual phase they behave very differently of: the majority regenerates, some predecidual cells are the site of focal or total necrosis, others show a macrophagic activity which is conspicuous in some cells having a collagenolytic activity.

Nous remercions Monsieur le Professeur Gandar, Directeur de la Clinique Gynécologique et Obstétricale 1 de la Faculté de Médecine de Strasbourg de nous avoir confié, pour examen ultrastructural, le matériel nécessaire à cette étude.     

Is coarse-to-fine strategy sensitive to normal aging?

Theories on visual perception agree that visual recognition begins with global analysis and ends with detailed analysis. Different results from neurophysiological, computational, and behavioral studies all indicate that the totality of visual information is not immediately conveyed, but that information analysis follows a predominantly coarse-to-fine processing sequence (low spatial frequencies are extracted first, followed by high spatial frequencies). We tested whether such processing continues to occur in normally aging subjects. Young and aged participants performed a categorization task (indoor vs. outdoor scenes), using dynamic natural scene stimuli, in which they resorted to either a coarse-to-fine (CtF) sequence or a reverse fine-to-coarse sequence (FtC). The results show that young participants categorized CtF sequences more quickly than FtC sequences. However, sequence processing interacts with semantic category only for aged participants. The present data support the notion that CtF categorization is effective even in aged participants, but is constrained by the spatial features of the scenes, thus highlighting new perspectives in visual models.     

"GOLD or lower limit of normal definition? a comparison with expert-based diagnosis of chronic obstructive pulmonary disease in a prospective cohort-study"

Background

The Global initiative for chronic Obstructive Lung Disease (GOLD) defines COPD as a fixed post-bronchodilator ratio of forced expiratory volume in 1 second and forced vital capacity (FEV1/FVC) below 0.7. Age-dependent cut-off values below the lower fifth percentile (LLN) of this ratio derived from the general population have been proposed as an alternative. We wanted to assess the diagnostic accuracy and prognostic capability of the GOLD and LLN definition when compared to an expert-based diagnosis.

Methods

In a prospective cohort study, 405 patients aged ≥ 65 years with a general practitioner''s diagnosis of COPD were recruited and followed up for 4.5 (median; quartiles 3.9; 5.1) years. Prevalence rates of COPD according to GOLD and three LLN definitions and diagnostic performance measurements were calculated. The reference standard was the diagnosis of COPD of an expert panel that used all available diagnostic information, including spirometry and bodyplethysmography.

Results

Compared to the expert panel diagnosis, ''GOLD-COPD'' misclassified 69 (28%) patients, and the three LLNs misclassified 114 (46%), 96 (39%), and 98 (40%) patients, respectively. The GOLD classification led to more false positives, the LLNs to more false negative diagnoses. The main predictors beyond the FEV1/FVC ratio for an expert diagnosis of COPD were the FEV1 % predicted, and the residual volume/total lung capacity ratio (RV/TLC). Adding FEV1 and RV/TLC to GOLD or LLN improved the diagnostic accuracy, resulting in a significant reduction of up to 50% of the number of misdiagnoses. The expert diagnosis of COPD better predicts exacerbations, hospitalizations and mortality than GOLD or LLN.

Conclusions

GOLD criteria over-diagnose COPD, while LLN definitions under-diagnose COPD in elderly patients as compared to an expert panel diagnosis. Incorporating FEV1 and RV/TLC into the GOLD-COPD or LLN-based definition brings both definitions closer to expert panel diagnosis of COPD, and to daily clinical practice.     

Fetal hemoglobin in normal adults and β-thalassemia heterozygotes

Summary A recently developed high performance liquid chromatographic (HPLC) procedure using a weak cation exchanger (PolyCAT) in columns of different sizes was used to quantify fetal hemoglobin (Hb F) in blood of normal adults and -thalassemia (-thal) heterozygotes with ten different types of mutations. Preparative PolyCATHPLC greatly facilitated the characterization of isolated Hb F, i.e., the determination of the relative quantities of the ^G and ^A chains. The method is accurate and allows quantitation of Hb F at the 0.5% level; preparative PolyCAT-HPLC allows isolation of (nearly) pure Hb F from blood samples with low (< 1%) Hb F. Adult Hb F levels were determined in 69 normal adults (including 24 diabetics); Hb F levels fell below 1% except for subjects with abnormal -^G-^G arrangement and a CT mutation at position -158 relative to the Cap site of both ^G genes. The effect of the same mutation in the normal-^G-^A-arrangement was variable. Certain -thal mutations (namely, those at positions -29;-88; IVS-I-1; IVS-II-1) were associated with high Hb F levels in heterozygotes, while those at nucleotide (nt) positions IVS-I-6; IVS-I-110; codon 24; codon 39; codons 41/42; IVS-II-745 were not. ^G values varied and often fell into two groups (high ^G and low ^G); high ^G values were not associated with high Hb F values. The chromatographic procedure is ideally suited for Hb A₂ quantitation. Average values of Hb A₂ in -thal heterozygotes with any one of nine of the ten mutations were twice that of normals; the one exception was the -thal heterozygote with the IVS-I-6 (TC) mutation with an average low Hb A₂ value of 3.6%.     

Do normal plasma neurotensin concentrations increase ileal output?

Infusions of neurotensin increase ileal secretion in experimental animals, and the volume of ileal effluent in patients with ileostomies. The aim of the present study was to determine whether normal postprandial plasma concentrations of neurotensin increase the volume of fluid leaving the ileum. Basal and peak postprandial plasma neurotensin concentrations were 23 (17-36) and 39 (25-43) pmol/l (median and range) respectively in five subjects with ileostomies and 15 (3-27) and 32 (15-82) pmol/l respectively in nine normal subjects. Infusion of neurotensin for 30 min at a rate of 6.3 pmol/kg/min into six patients with ileostomies increased ileostomy output about 10-fold, and produced a significant decrease in the concentration of solid material, but plasma neurotensin concentrations rose to 237 (82-422) pmol/l during infusion at this rate. Infusion of neurotensin at 2.3 pmol/kg/min, producing plasma levels of 60 (16-108), had no significant effect the amount or nature of ileostomy effluent. We conclude that normal postprandial plasma concentrations of neurotensin are unlikely to influence the volume of fluid leaving the ileum.     

Quantifying ‘normal’ shoulder muscle activity during abduction

The purpose of this experiment was to obtain electromyographic (EMG) activity from a sample of healthy shoulders to allow a reference database to be developed and used for comparison with pathological shoulders. Temporal and intensity shoulder muscle activation characteristics during a coronal plane abduction/adduction movement were evaluated in the dominant healthy shoulder of 24 subjects. Surface and intramuscular fine wire electrodes recorded EMG activity from 15 shoulder muscles (deltoid × 3, trapezius × 3, subscapularis × 2, latissimus dorsi, pectoralis major, pectoralis minor, supraspinatus, infraspinatus, serratus anterior and rhomboids) at 2000 Hz for 10 s whilst each subject performed 10 dynamic coronal plane abduction/adduction movements from 0° to 166° to 0° with a light dumbbell. Results revealed that supraspinatus (?.102 s before movement onset) initiated the movement with middle trapezius (?.019 s) and middle deltoid (?.014 s) also activated before the movement onset. Similar patterns were also found in the time of peak amplitude and %MVC with a pattern emerging where the prime movers (supraspinatus and middle deltoid) were among the first to reach peak amplitude or display the highest %MVC values. In conclusion, the most reproducible patterns of activation arose from the more prime mover muscle sites in all EMG variables analysed and although variability was present, there emerged ‘invariant characteristics’ that were considered ‘normal’ for this group of non pathological shoulders. The authors believe that the methodology and certain parts of the analysis in this study can be duplicated and used by future researchers who require a reference database of muscle activity for use as a control group in comparisons to their respective pathological shoulder group.     

Analysis of HLA–ABC locus-specific transcription in normal tissues

We developed a novel human leukocyte antigen HLA–ABC locus-specific quantitative real-time polymerase chain reaction (PCR) to determine the locus-specific gene expression of HLA–ABC in peripheral blood leukocytes (PBLs, n?=?53), colon mucosa (n?=?15), and larynx mucosa (n?=?15). Laser-assisted tissue microdissection allowed us to study the selected cells without interference from surrounding stroma. We report evidence on the specificity of the technique, describing the HLA–ABC locus-specific gene expression patterns found in the PBLs and two solid tissues studied. PBLs showed a higher gene expression of HLA-B than of HLA-A or HLA-C (p?=?4.7?×?10^?10 and p?=?1.6?×?10^?6, respectively). In solid tissue, HLA-A and HLA-B gene expressions were similar and HLA-C expression lower. In particular, in larynx mucosa, significant differences were found between HLA-A and HLA-C expressions and between HLA-B and HLA-C expressions (p?=?6.5?×?10^?4 and p?=?8.1?×?10^?4, respectively). The same differences were observed in colon mucosa, but significance was not reached (p?=?0.08 and p?=?0.06, respectively). Differences in locus-specific regulation may be related to the control of cytotoxic responses of NK and CD8 positive T cells. Gene expression of HLA–ABC specific locus showed no intra-individual variability, but there was a high inter-individual variability. This may result from differences in the expression of common regulatory factors that control HLA–ABC constitutive expression.     

Distribution of L-tryptophan in normal and glucose — loaded mice

Summary L-tryptophan is an essential amino acid in food, but is also widely used as a drug on the basis of several physiological actions. Lately, tryptophan's uses as a drug and as a food supplement have been discontinued in several countries due to its severe side-effects.In the present study, the distribution of tryptophan in mice was studied with special attention on the target organs, where the drug has been shown to have pathological or physiological effects.The results showed that several organs took up tryptophan and that glucose loading increased the accumulation. An interesting finding was that the highest concentration of tryptophan was found in the pancreas. The hypophysis and adrenal glands were also sites of accumulation. Within the brain the highest accumulation was found in the cerebrum. High concentrations were also seen in the gastrointestinal tract and bone marrow.The connection between the accumulation of tryptophan and its normal and pathophysiological effects is discussed.     

H1° histones of normal and cancer human cells

Summary H1° histones were purified by preparative sodium dodecyl sulfate polyacrylamide gel electrophoresis from human lung carcinoma (line DMS79), human hepatoblastoma (HepG2), human adult lung and human adult and fetal liver. The purified human H1° histones were analyzed for their amino acid composition and terminal residues. The comparative analysis of the amino acid compositions of the different human H1° histones showed that: (a) all the H1° preparations have the characteristically high lysine content associated with a low arginine content, which distinguishes outer histones from core histones; (b) H1° is distinguishable from other H1 histones by the presence of methionine and histidine; (c) H1° histones from human adult, fetal and cancer cells are very similar in amino acid composition, and in cancer cells the level of the H1° histone is not inversely related with cell growth rate nor with the expression of the -fetoprotein gene.     

Carbohydrate utilization by normal and γ-sterilized Dacus oleae

Non-sterilized adult olive fruit flies were able to survive and reproduce on mannose, glucose, fructose, sucrose, melibiose, trehalose, maltose, melezitose, and sorbitol, out of a series of 23 carbohydrates γ-sterilized flies were able to utilize the same carbohydrates with the exception of melezitose, indicating that sterilization with a 10 Krad dose did not affect their ability to utilize various carbohydrates. Since these carbohydrates are common constituents of the fly's natural food sources, the released sterile flies should be able to survive satisfactorily in the field. The possible presence of three carbohydrases is discussed.     

Spontaneous micronucleus frequency and age: what are normal values?

Micronucleus frequency in epidemiological studies of human exposure has become a preferred biomarker. A generally recognized observation is that micronucleus frequency increases with age. One requirement for comparison of data, which is being generated in many countries, is some common agreement about what constitutes a typical or normal background frequency of micronuclei. This is also a requirement when examining any individual value, especially one which might be considered an outlier. A mean value for normal micronucleus frequency with age is developed via the analysis of multiple studies, all of which employed large population bases and generally were conducted with the intent of determining population values. The result is presented here, with the understanding that it may over- or under-estimate the actual values in certain populations.     

“Axonal spheroids” in the spinal cord of normal rabbits

Summary Within the gray matter and the white matter of the spinal cord of apparently healthy rabbits, myelinated and unmyelinated axonal swellings, so called axonal spheroids, occur. Most of the spheroids contain mitochondria, dense bodies, vesicles and fragments of the tubular or smooth endoplasmic reticulum. In myelinated spheroids the process of swelling is effected by slippage of the myelin leaflets. At the periphery of the unmyelinated parts of the spheroids, synapses are regularly found. The presynaptic terminal bouton is formed by the spheroid. A few myelinated and unmyelinated spheroids are packed with fine granular material while mitochondria are lacking. The axonal spheroids may represent a physiological, perhaps age dependent phenomenon.Dedicated to Prof. Dr. Berta Scharrer on the occasion of her 70^th birthdayThe author wishes to thank Mrs. Helga Zuther-Witzsch, Mrs. Elisabeth Schöngarth and Miss Hildegard Schöning for excellent technical assistance. Supported by the Deutsche Forschungsgemeinschaft, Projekt Le 69/7-13