Two Cycles of High Dose Chemotherapy with Autologous Bone Marrow Support for Patients with Locally Advanced Breast Cancer

Abstract: Purpose: To examine the impact of two cycles of high dose chemotherapy (HDC) with autologous bone marrow rescue (ABMR) in the treatment of women with locally advanced breast cancer. Patients and Methods: Twenty-three patients not exhibiting progressive disease to conventional dose therapy (ltx) were eligible for HDC. Conventional dose regimens used were the CAMFTP regimen (n= 6), 5-FU, doxorubicin and cyclophosphamide (n= 3), cyclophosphamide, methotrexate and 5-FU (n= 1), or doxorubicin/cyclophosphamide (n= 13). HDC on each cycle consisted of etoposide 625 mg/m², cyclophosphamide 6 gr/m², carboplatin 2 gr/m² with ABMR. Median age of the patients was 40 years. Results: Seventeen patients (74%) underwent two cycles of HDC; 6 received only one cycle due to insurance refusal to pay for C2 (1), toxicity from C1 (4), death on C1(1). There were 2 transplant-related deaths due to fungal infections 1 each on C1 and C2. Four patients achieved complete remission (CR) with Itx, 18 achieved partial remission (PR), and 1 had stable disease (SD). One patient was converted from PR to CR with HDC. There are 9/23 (39%) patients alive and progression-free with median follow-up of 27 months. (range 21-41 + months). Twelve of the 23 (52%) have progressed at a median of 7 months (range 4-32) from bone marrow transplant (BMT) and there were 2 early deaths (9%). Six patients received only one cycle of HDC and 2 of these are alive and progression-free at 36 and 38 months of follow-up. Of the 17 completing two cycles of HDC, 7/17 (41%) are alive and progression-free with follow-up of 21-41 months. The median progression-free survival (PFS) for the entire group is 13 months and median overall survival is 21 months (range 1–41 + mos). Conclusion: Despite the use of two cycles of HDC with ABMR, systemic relapse remains the major obstacle to cure in women with locally advanced breast cancer; there is a need to develop more effective preparative rgimens.     

Effect of the fragile X anomaly on body proportions estimated by pedigree analysis

Loesch DZ, Sampson ML. Effect of the fragile X anomaly on body proportions estimated by pedigree analysis.
Clin Genet 1993: 44: 82–88. © Munksgaard, 1993
The purpose of this study was to determine the effect of the fragile X syndrome on limb (upper limb length) and facial (ear length) measurements in relation to body height, which was considered as a covariate. The analysis was performed in 52 fragile X Caucasian families, including affected individuals as well as their normal relatives. The maximum likelihood analysis of complex pedigrees, under the assumption of multivariate normality, was used to select the best genetic model and to estimate model parameters. This method allowed us to test various assumptions concerning the effect of normal hereditary variation, as well as of genetic anomaly and other relevant factors, in the mean and variance of a quantitative trait, and to obtain the maximum likelihood parameters for these effects. The results demonstrated that, if the family factor is accounted for in a model, the fragile X condition affects growth of both upper limb length and ear length, disproportionately to body height.     

Epithelial and Stromal Estrogen and Progesterone Receptor Expression in Endometrial Cancer: True Color Computer-Assisted Image Analysis versus Subjective Scoring

Immunohistochemical methods provide the opportunity to evaluate the staining reaction in different histologic compartments of malignant tumors. Eighty-four formalin-fixed, paraffin-embedded and immunohistochemically stained endometrial cancer specimens were assessed for estrogen receptor (ER) and progesterone receptor (PR) expression by conventional light microscopy, a light microscopy scoring system, and by true color computer-assisted image analysis. Measurements of mean optical density (MOD) in the epithelium as well as in the stroma of the tumor were performed. A negative correlation was established between the MOD of ER and PR staining in the nuclei of the epithelium and the MOD of PR staining in the stroma of the tumor vs histological stage (Spearman correlation coefficient −0.32/P< 0.004, −0.23/P< 0.03, −0.26/P< 0.02, respectively) and depth of myometrial invasion (Spearman correlation coefficient −0.34/P< 0.002, −0.24/P< 0.02, −0.25/P< 0.02, respectively). The staining pattern in endometrial cancer was heterogeneous and %PA (percentage of positive stained area) and MOD were therefore linked by multiplication in order to correct for this potentially confounding phenomenon. A negative correlation with histological stage (Spearman correlation coefficient −0.29/P< 0.007) and depth of myometrial invasion (Spearman correlation coefficient −0.34/P< 0.001) was found for PR staining in the stroma of the tumor. MOD and subjective ranking of staining intensity showed a high correlation as well as %PA and subjective estimation of stained surface. ER and PR content in the epithelium and also PR content in the stroma of endometrial cancer appear to be of value in the assessment of steroid hormone receptor status. This may be indicative of stromal–epithelial interaction.     

Endothelin, vasopressin, and substance P like immunoreactivity in cultured and intact epithelium from rabbit trachea.

BACKGROUND: The control of airways reactivity is essential to our understanding of disease processes such as asthma. Many studies have examined the neural control of the airways, but more recently there has been evidence to show that the epithelium lining the airways may influence airways reactivity. METHODS: Rabbit tracheal epithelial cells were dispersed with enzymes, grown in primary culture and fixed. Tissue from intact tracheas was also sampled and fixed. Localisation of the vasoactive substances endothelin-1, arginine-vasopressin, and substance P was investigated by immunolabelling techniques. RESULTS: Scattered immunolabelling to endothelin-1, arginine-vasopressin, and substance P was found throughout the cultures (with < 20% of cells staining positively to each antibody). At the ultrastructural level this immunoreactivity was found in the cytoplasmic matrix. In addition, immunoreactivity of intact tissue to endothelin-1, arginine-vasopressin, and substance P was examined and positively staining cells were found to be scattered through the epithelium. CONCLUSIONS: The presence of these vasoactive substances within the epithelium lining the airways supports the view that epithelial cells may provide an additional mechanism in the control of airways reactivity.     

Seasonal variations in circadian levels of serum prolactin in striped mullet,Mugil cephalus

Plasma concentrations of prolactin were estimated by radioimmunoassay throughout a day at three seasons of the year (summer, fall, and winter) in the striped mullet, Mugil cephalus. Daily rhythms were found at each season. In addition, the patterns of the rhythms with respect to the daily photoperiod differed from one another. The data are consistent with the hypothesis that a seasonal change in the daily rhythm of prolactin has an important role in regulating the seasonal changes in physiology of some animals.     

Ridgecounter: a program for obtaining semi-automated finger ridge counts

Finger ridge count is a valuable quantitative phenotype used in a wide range of biological and anthropological research. However, the scoring of the phenotype is both labour intensive and error prone. This paper describe a freely available software program, RIDGECOUNTER, that can be used to obtain ridge counts from digitized prints (either collected using a digital fingerprint scanner or scanned from an inked print). The program yields semi-automated ridge counts and logs the location of the user-selected core and delta points to aid in the training of new researchers and ensure the repeatability of count. In a validity study of 451 prints, the semi-automated ridge counts of digital prints showed good agreement (r = 0.957) with traditional manual counts of inked-rolled prints (which were obtained 2 years apart and counted by different researchers). In a reliability study of 200 prints, semi-automated ridge counts derived from digital prints collected at two different time points also showed good agreement (r = 0.962) (the prints were obtained 2 years apart and counted by the same researcher). Although designed for use with fingerprints, the program is suitable for use with palm, foot or toe prints using user-defined landmarks.     

Discriminant analysis of dermatoglyphic measurements in fragile X males and females

Two hundred and eight fragile X subjects (92 males and 116 females) and matched Australian (60 males and 32 females) and British (122 males and 118 females) normal samples were used to calculate 4 discriminant functions, based on dermatoglyphic measurements. The most efficient discriminating variables between fragile X and normal males, selected by means of the Wilk's stepwise method, included: ridge counts on fingers 1-3, the hallucal (f) count on soles, the atd angle, and pattern intensities in palmar areas 2, 4 and 5 as well as on fingers 4 and 5. In females, the ridge breadth, the hallucal (e) count, the atd angle and pattern intensities in palmar areas 3-5 as well as on fingers 1, 3 and 5 comprised the final discriminant. The misclassification rate based on distributions of individual discriminant scores in each pair of samples, and on prior probabilities, was lowest (16.8%) in fragile X males compared with the Australian normal subjects. In both female comparisons, this rate approached 44%. A bias to misclassification rates resulting from various analytical procedures and some properties of the data are discussed. We conclude that the discriminant function based on dermatoglyphic measured variables alone is not good enough for assessing carrier probabilities for fragile X, especially in females. However, we have been able to select the best discriminators which may be used, together with other measured body characteristics, to obtain a more powerful discriminant function. Moreover, a consideration of discriminant scores based on dermatoglyphic traits only may help in estimating carrier probabilities.(ABSTRACT TRUNCATED AT 250 WORDS)