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Fractures are highly correlated with bone density and inversely correlated with bone turnover markers in autosomal dominant osteopetrosis.

Autosomal dominant osteopetrosis (ADO) is a rare osteosclerotic disorder usually caused by missense variants in the CLCN7 gene, which results in impaired osteoclastic bone resorption. Penetrance is incomplete, and disease severity varies widely, even among relatives within the same family. Although ADO can cause visual loss, osteonecrosis, osteomyelitis, and bone marrow failure, the most common complication of ADO is fracture. We are conducting a natural history study to characterize disease progression and determinants of disease severity. We hypothesized that baseline BMD and bone turnover markers would correlate with self-reported fracture history. We report cross-sectional analysis of baseline data from the natural history study in 54 individuals (42 adults, 12 children). In adults, Z-scores for both volumetric (r&#xa0;=&#x2009;0.87, p&#xa0;<&#x2009;.001) and areal BMD (aBMD) of the LS, and Z-scores for FN, and TH aBMD (r&#xa0;=&#x2009;0.77 to 0.78; p&#xa0;<&#x2009;.001) were correlated with lifetime fracture number. Tartrate resistant acid phosphatase, a marker of osteoclast number, correlated positively with fracture (r&#xa0;=&#x2009;0.52, p&#xa0;=&#x2009;.004) consistent with an adaptive response of higher numbers of osteoclasts among more severely affected individuals. However, fracture number correlated inversely with the bone resorption markers serum C-telopeptide (r&#xa0;=&#x2009;-0.60, p&#xa0;<&#x2009;.001) and urine N-telopeptide/creatinine ratio (r&#xa0;=&#x2009;-0.35, p&#xa0;=&#x2009;.047), suggesting that ADO subjects who have the most reduced osteoclast activity have a greater tendency to fracture. Correlation coefficients between fractures, BMD, and bone turnover markers were similar when limited to the 37 adults with disease-causing CLCN7 variants. There were no statistically significant differences between subjects with the most common CLCN7 variant (G215R), the most common variant in our cohort, compared to other CLCN7 variants with respect to fracture, bone density measures, or biochemical markers of bone turnover. These data demonstrate that bone density and biochemical bone turnover markers are indicators of ADO severity as defined by fracture number.

Humans

Correlated binomial variates: properties of estimator of intraclass correlation and its effect on sample size calculation.

In group randomized studies, the sample size calculations are complicated by within group (worksite, community, etc.) correlation. We compare by simulation the moment method and the more standard ANOVA method of estimating the intraclass correlation. We find the former is less biased for a small to moderate number of clusters but the difference disappears when the appropriate degree of freedom is used for the ANOVA estimator. We propose a simulation approach for sample size determination and illustrate it with an example.

Analysis of Variance

Correlation studies of morphological and biochemical parameters in human ejaculate in various andrological diagnoses. 3rd report. Correlations between morphological and biochemical parameters.

The result of a study of correlations between morphological and biochemical parameters in human ejaculate is presented in conclusion of an extensive study of these parameters. Basing on these results, for which a statistical significance of p less than 0.05 was calculated, it can be stated that higher fructose concentrations are associated with lower sperm density; at the same time, the higher fructose concentrations correlate with a higher percentage of non-motile and of pathologically changed spermatozoa. Similar associations can be established for certain substrates which result from fructolysis. The possibility of diffusion of enzymes from the cellular components must be considered as regards the increased activities of PGK, PGI and ATPase in seminal plasma in the presence of greater sperm density. Reliable conclusions about associations between morphological characteristics and enzyme activities can be expected in the future from appropriate measurements in the cellular elements (spermatozoa, round cells) of the ejaculate. The study results provide a further insight into the biochemistry of seminal plasma and into the associations between morphological and biochemical parameters in the ejaculate.

Acid Phosphatase

Correlation of selected serum constitutents: 2. Consistency of intra-individual correlation values, means, and variances during four months.

We examined whether inter-individual differences in correlation coefficients previously found among subjects truly reflect consistent inter-individual differences or are time-related within an individual. The consitutents studied in this investigation were (a) the enzmes aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase; and (b) the non=protein nitrogen-containing constituents urea, uric acid, and creatinine. Ten healthy women were each subjected to 15 venipunctures over a five-week period (Series I), and, after a two-month interval, were again subjected to 15 venipunctures over a second five-week period (Series II). Before statistical analysis, the data were corrected for the batch-to-batch (day-to-day) arnalytical variation. There was a signiificant (P less than .05) change in the covariance structure (variances or correlation coefficients, or both) between the two series in four of the 10 subjects for the combination of enzymes, and in three other subjects for the combination of nonprotein nitrogen constitutents. Although we found a significant (P lees than .05) average intra-individual variation in the mean values from series to series in the cases of the three enzymes and urea, the magnitude of the inter-series variation in means was relatively small. CV's were: alkaline phosphatase, 3.4%; lactate dehydrogenase, 2.3+; aspartate aminotransferase, 3.3%; urea, 5.0%; uric acid, 1.0%; and creatinine, 1.2%.

Adult

Doxorubicin sensitivity pattern in a panel of small-cell lung-cancer cell lines: correlation to etoposide and vincristine sensitivity and inverse correlation to carmustine sensitivity.

The aim of our investigations is to evaluate whether the sensitivity patterns of small-cell lung-cancer (SCLC) cell lines in vitro can be used in evaluating new drugs and in selecting drugs for the optimization of combination therapy. In our attempts to obtain a panel of cell lines demonstrating differential patterns in sensitivity, we have developed three SCLC lines exhibiting different types of multidrug resistance (MDR). In the present investigations we compared the sensitivity patterns shown by five wild-type SCLC lines and three MDR lines in response to six different types of drugs: doxorubicin, cytarabine, carmustine, cisplatin, vincristine, and etoposide. In the wild-type SCLC cell lines, the range of variation in sensitivity to all drugs was within a factor of 10. Cell lines showing low sensitivity to doxorubicin also exhibited low sensitivity to etoposide and vincristine, and vice versa. In contrast, the pattern of sensitivity to carmustine was almost the opposite of that to doxorubicin. A tendency to an inverse relationship between doxorubicin and carmustine sensitivity was also observed when doxorubicin sensitivity was reduced in near stationary cells and in cells exposed to the metabolic inhibitor 2-deoxy-D-glucose. In agreement with the pattern observed for the wild-type lines, all of the MDR sublines demonstrated collateral sensitivity to carmustine. As to cytarabine, the wild-type lines expressed a sensitivity pattern similar to that shown in response to doxorubicin. Interestingly, the opposite pattern was found in the MDR lines, as all three demonstrated cytarabine hypersensitivity. The combination of alkylating agents and "MDR" drugs are of proven clinical benefit in the treatment of solid tumors, as is the combination of anthracycline and cytarabine in acute myeloid leukemia. The experimentally derived sensitivity data on cytarabine, alkylating agents, and MDR drugs (i.e., etoposide, doxorubicin, vincristine) thus resemble the clinical experience with these drugs, and we conclude that the use of a clonogenic assay on the described panel of SCLC cell lines can give valuable information for the selection of agents for combination therapy.

ATP Binding Cassette Transporter, Subfamily B, Mem

[Interspecies study of statistical correlations existing between the pineal gland size and weight and brain and body weight in two groups of mammals. Interspecies study of correlations between the pineal gland and brain in the rat and in man].

Network analysis procedures have been applied to study the cell patterns on the dorso medial and ventral lateral formation of the inferior colliculus of different species, i-e: Cat, Tat and Monkey. The results suggests the existence of important interspecific differences, more particularly in the primates. These differences are more obvious in the dorso medial formation. The functionnal implications of these results are discussed.

Animals

[Cytodiagnosis of the uterine portio vaginalis according to WHO nomenclature. I. Correlative revision of cytological and histological diagnoses as quality control of selected materials. Frequency and possible reasons for the lack of correlation of cytological and histological diagnoses].

Smears from the uterine cervix have been evaluated for neoplastic changes on the basis of descriptive terms. The material was obtained by a single gynecologist using a standardized sampling technique and the results were compared with the respective histological diagnoses. Material which was found to be unsuitable for technical reasons was excluded from this study. A 98.7% agreement between cytological and histological findings was noted. Discrepancies between cytological and histological findings were essentially due to differing dysplastic changes in the deeper layers of the surface epithelium and the cervical glands, which were not sampled by the smears on the surface layer. In a few cases the discrepancies could not be explained but they disappeared after several years of observation. The practitioner should be acquainted with the nomenclature used by cytologists. In his turn, the cytologist should be familiar with the pathological anatomy of the organ in question.

Cell Biology