The biology of breast tumor progression. Acquisition of hormone independence and resistance to cytotoxic drugs.

Many breast tumors appear to follow a predictable clinical pattern, being initially responsive to endocrine therapy and to cytotoxic chemotherapy but ultimately exhibiting a phenotype resistant to both modalities. Using the MCF-7 human breast cancer cell line as an example of an 'early' phenotype (estrogen and progesterone receptor positive, steroid responsive, low metastatic potential), we have isolated and characterized a series of hormone-independent but hormone-responsive variants (MIII and MCF7/LCC1). However, these variants remain responsive to both antiestrogens and cytotoxic drugs (methotrexate and colchicine). MIII and MCF7/LCC1 cells appear to mimic some of the critical aspects of the early progression to a more aggressive phenotype. An examination of the phenotype of these cells suggests that some hormone-independent breast cancer cells are derived from hormone-dependent parental cells. The development of a hormone-independent phenotype can arise independently of acquisition of a cytotoxic drug resistant phenotype.     

Variability of body density and body impedance at different frequencies.

Body density and body impedance at 15 selected frequencies ranging from 1 to 1350 kHz were determined in 13 subjects on four consecutive days of the week. Bioelectrical impedance at the same frequencies was also determined in 11 subjects on the same day of the week during four consecutive weeks. Day-to-day variability of body density and body impedance and week-to-week variability of body impedance were studied. Statistical analyses did not reveal significant day- or week-effects in variabilities. The mean within-person variation in body density between days was 0.0019 kg/l (CV 0.2%). Mean within-person variation in body impedance between days was 57 ohms (CV 8.7%) at 1 kHz. At 5, 50 and 100 kHz the within-person variation between days was 16 ohms (CV 2.4%), 12 ohms (CV 2.1%) and 11 ohms (CV 2.0%), respectively. Mean within-person variation between weeks was 44 ohms (CV 2.4%) at 1, 5, 50 and 100 kHz, respectively. Overall the within-subject variability in impedance at all frequencies was higher in females. The larger mean within-person variation in impedance at 1 kHz could only partly be explained by variation in body weight and may be a real error in the measurement. Electrodes with a larger surface area reduced the variability to values comparable with those at higher frequencies. The day-to-day variation in impedance at higher frequencies causes an error in calculated FFM, which is about two times larger compared to the estimated error in FFM by body density.     

Using mark-recapture methodology to estimate the size of a population at risk for sexually transmitted diseases.

To study the spread of sexually transmitted diseases (STDs) using social/sexual mixing models, one must have quantitative information about sexual mixing. An unavoidable complication in gathering such information by survey is that members of the surveyed population will almost certainly have sexual contacts outside that population. The number of these outsiders may be substantial and, hence, important for the modelling process. In this paper, we develop a mark-recapture model for estimating the size of the population at risk for contracting a STD due to direct sexual contact with a specified population targeted by a survey. This mark-recapture methodology provides a reliable method of estimating the number of outsiders. Because not everyone in the targeted population may be sexually active, the size of the sexually active subset, used as the number marked in our tag-recapture formulation, must be estimated, which introduces extra variability. We derive an estimator of the variance of the estimated total number at risk that accounts for this extra variability and an expression for the bias of that estimator. We extend the methodology to stratified surveys and illustrate its use with data collected from a population of university undergraduates to estimate sexual mixing parameters of a deterministic model of the spread of STDs.     

Ischemic monomelic neuropathy: An under-recognized complication of hemodialysis access

During the past 3 years six episodes of ischemic monomelic neuropathy (IMN) have been identified in five patients as a complication of upper extremity dialysis grafts. All patients had long-standing insulin-dependent diabetes, peripheral neuropathy, and brachial artery graft origins, whereas 60% had peripheral vascular disease. Five episodes occurred immediately after graft placement, whereas one was due to a graft-related thromboembolus. Diagnostic delay was common with initial findings attributed to anesthesia, positioning, or surgical trauma. Electrophysiologic studies showed underlying diabetic neuropathy with severe multifocal neuropathy distal to the grafts. Digital pressure indices were reduced but there was no critical ischemia. In three cases ischemia was completely corrected with improvement in one. One patient had proximal balloon angioplasty with no improvement and of the two untreated patients, one improved slightly. Ischemic monomelic neuropathy is a rare but disabling complication of dialysis access in diabetic uremic patients. Its occurrence is unpredictable and diagnostic delay is common. Correction of ischemia is indicated but usually does not improve the neuropathy. Prevention requires further research to more accurately characterize the patients at risk.Presented at the Twelfth Annual Meeting of the Southern California Vascular Surgical Society, Coronado, Calif., September 17–19, 1993.     

DNA probe technology: implications for service planning in Britain

For certain genetic conditions DNA testing identifies carriers and determines the risk status of foetuses, thus helping parents to make more informed prenatal decisions. Data, collected from three genetic centres in England and Wales from August 1986 to July 1990, are used to describe trends in demand for DNA testing, the impact of DNA tests on carrier risk assessment, and the use of DNA tests in relation to pregnancy outcome. Altogether the data include 23,388 subjects and 681 pregnancies in 8738 families divided into five cohorts by year of entry and referral. The most frequent gene disorders referred to the genetic centres are currently being tested or will soon be tested. For these disorders the initial high level of activity has declined and may have reached steady state. Demand for DNA services is high for cystic fibrosis and Duchenne muscular dystrophy, intermediate for Huntington's disease, and low for adult polycystic kidney disease, phenylketonuria and tuberous sclerosis. Based on these findings we suggest that demand for DNA tests will be high in serious, untreatable and slow progressing conditions with early onset; intermediate for conditions affecting intellect and neurological integrity with later onset; and low for treatable, late-onset conditions, or those for which there is evidence of heterogeneity, and variable penetrance. It would be helpful to assess the extent to which this view of demand is confirmed when the new disorders being DNA tested are considered and for the pattern of activity of DNA testing for some types of cancer. Since no DNA centre could offer a fully comprehensive testing service, it is recommended that a structure is created to audit overall activity, assist in policy formulation, and influence supraregional service organisation, in order that the spread of DNA services be planned as effectively as possible. This structure would facilitate monitoring of the evolution of contract specifications agreed by commissioners and providers on a regional basis.     

The effect of mutation on linkage disequilibrium

The standard formula for the approach to linkage equilibrium between two diallelic loci, initially at disequilibrium, is expressed in terms of their probability of recombination (Li, 1955). By a simple extension, we show how to incorporate the effects of mutation at one or both loci. It can thereby be inferred that in general these effects are unlikely to be of major importance, contrary to some recent suggestions.     

The fit of fixed partial dentures joined by infrared soldering.

This study determined the accuracy of fit of three-unit fixed partial dentures joined by an infrared soldering technique compared with one-piece fixed partial denture castings and individually cast crowns. Wax patterns of prepared Ivorine teeth, maxillary left central incisor and maxillary left canine, were injection molded; a plastic rod was used as a pontic. One group of patterns was cast as one-piece dentures; the other group was sectioned in the connector area, cast individually and then joined by infrared soldering. Castings were seated on their respective dies, embedded in epoxy resin, and sectioned. Gap distances between the casting and the die were measured at specified marginal sites with a profile projector. Results showed that the fit of infrared-soldered fixed partial dentures was significantly better than that of one-piece castings and was comparable with the fit of single crowns. The gap openings measured in all castings were within the range of clinical acceptability.     

A method for electrical simulation of radionuclide dilution curves

Scientific Research Institute for Radiomeasuring Equipment, Kiev. Translated from Meditsinskaya Tekhnika, No. 2, pp. 21–24, March–April, 1992.     

Infantile depression,nonorganic failure to thrive,and DSM-III-R: A different perspective

A controversy exists regarding the classification of nonorganic failure to thrive within the psychiatric nomenclature. There are a number of DSM-III-R diagnoses that may be applied to NOFTT, including Reactive Attachment Disorder of Infancy (RADI) and Major Depressive Disorder (MDD). The behaviors characteristic of NOFTT are symptomatic of depression, and are similar to those exhibited by infants with anaclitic depression as well as those of the adult with depression. The correspondence of the behaviours of NOFTT and the DSM-III-R criteria for Major Depression are reviewed, as are the conceptual and therapeutic reasons to view NOFTT infants as suffering from Depression.