Obesity and subcutaneous fat patterning in relation to survival of postmenopausal breast cancer patients participating in the DOM-project

Summary The effect of obesity and fat distribution on survival of breast cancer patients was studied prospectively in 241 women with a natural menopause who participated in a breast cancer screening project, the DOM-project in Utrecht, The Netherlands. Mean follow-up time was 9.1 years and endpoint of interest was death from breast cancer. Fat distribution was assessed by contrasting groups of subscapular and triceps skinfold thickness.No significant differences in survival time between more obese (Quetelet's index 26 kg/m²) and leaner (Quetelet's index < 26 kg/m²) patients or between patients with central fat distribution and patients with peripheral fat distribution were observed. Analyses were stratified by axillary node status, estrogen receptor status, and way of detection (by first screening or afterwards). Results of the stratified analyses were suggestive of a modifying effect of these factors.The absence of an association between obesity and survival time might be explained by two counteracting mechanisms. On the one hand obesity might be related to impaired survival, due to a tumor growth promoting effect of extra-ovarian estrogens. On the other hand obesity might be related to improved survival in a screened population, because obese patients profit more from screening by earlier detection of tumors than leaner counterparts.     

Improved survival in young women with breast cancer

Background: Young age has been hypothesized to be an adverse prognostic factor for women with breast cancer. This association, based on historical data, may not reflect recent advances in breast cancer management. Methods: A retrospective study was conducted of all women age 30 or younger who underwent definitive operation at our institution for primary operable breast carcinoma during one of two consecutive 20-year periods (1950–1969 or 1970–1989). All cancers were restaged according to current staging criteria. Actuarial survival and recurrence-free survival rates from the two patient eras were compared with each other and with published statistics for older breast cancer patients. Results: Eligibility criteria were met by 81 women from the 1950–1969 era and 146 women from the 1970–1989 era. Histologic diagnoses, tumor sizes, incidence of axillary nodal metastases, number of positive nodes, and American Joint Committee on Cancer stage at presentation were similarly distributed in the two eras. Despite these similarities, improved survival (p=0.009) was observed in the later era. Local recurrences were also more common (p<0.05) in the later era in association with less extensive resections. These local recurrences had an adverse impact on recurrence-free survival in the later era, but no concomitant decrease in overall survival was observed. Node-positive patients who received chemotherapy demonstrated a trend toward improved survival (p=0.06) compared with node-positive patients who did not. Survival for patients in the later era was similar to that for older women as reported in other published series. Conclusions: The stage of presentation of breast cancer in women 30 years or younger appears unchanged from prior decades, but survival has improved in association with the use of less extensive surgical resections and the introduction of cytotoxic chemotherapy. With current treatment, primary operable breast cancer in young women appears to have a similar prognosis to breast cancer in older women.Results of this study were presented at the 47th Annual Cancer Symposium of The Society of Surgical Oncology, Houston, Texas, March 17–20, 1994, and was judged Best Clinical Paper in the Resident/Fellow Essay Contest.     

中国近代西医产科学史

本文阐述了中国西医产科学的发展历史。由于传统封建思想的阻碍,我国现代产科学的起步较晚,１９１１年在福建省建立了我国第一所产科病房。１９３０年以前孕产妇及新生儿死亡率比英美高４～５倍,１９３０年后,建立助产学校,开展孕期保健及骨盆测量,不断改进对病理妊娠的诊断及妊娠合并症的处理,这些均促进了中国近代西医产科学的进步,也为建国后的发展奠定了基础。     

Impact of different doses of ethinyl oestradiol on reduction of final height in constitutionally tall girls

Fifty-two tall girls were treated for constitutionally tall stature with different ethinyl oestradiol (EE) dosages. They were divided into three different treatment groups: group B (100 g EE/day;n=11); group C (300 g;n=25) and group D (500 g;n=16) and compared with an untreated group A (n=21) matched for age, height, bone age (BA) and height prediction. Using the height prediction method TW II, EE treatment reduced final height compared with the untreated girls in a weak dose-dependent manner, 2.3 cm (100 g/day), 3.0 cm (300 g/day), and 3.8 cm (500 g/day). Such a dose dependency was not found on applying the Bayley-Pineau height prediction method (100 g/day: 4.1 cm; 300 g/day: 4.2 cm; 500 g/day: 4.5 cm). However, there was a striking inverse correlation of the BA at the onset of treatment with the height reduction achieved using the TW II method (r: –0.43;P<0.001). Importantly, girls with a BA below 12 years at the onset of treatment experienced a height reduction of more than 6 cm.The EE dose used in the range of 100–500 g/day is not crucial for the amount of height reduction in tall girls. In general high dose EE treatment should be given restrictively, and especially so in girls with a BA (TW2 RUS-ZH) above 12.0 years.     

Reconstructing the life course: health during early old age in a follow-up study based on the Boyd Orr cohort

A method is described for investigating life course influences on health in early old age. The lives of some 300 individuals at present aged 65-75 y have been reconstructed from the archived records of a pre-WWII survey, in which they took part as children, and from lifegrid interviews with the same individuals 60 y later. Despite loss to study at several points those interviewed are shown to be representative of the British population socio-demographically, in comparison with the 1931 and 1991 decennial censuses, and physically, in comparison with the Health Survey for England. Bias is conservative because the most disadvantaged were disproportionately affected by loss to follow-up through death and because non-responders to interview were more disadvantaged as children than the interviewees. Representativeness and conservative bias, it is argued, justify the use of these data for investigating life course influences on health in early old age.     

Sleep, age, and shiftwork experience

The effects of age and shiftwork experience (never, past, present) on sleep were studied in a sample of 3236 wage earners and retired workers by means of a questionnaire. The sample was composed of 32-, 42-, 52-, and 62-year-old subjects, and included both sexes and various occupational statuses. Age resulted in a continuously increasing frequency of sleep disturbances and hypnotic use, except for difficulty getting back to sleep and early awakening, which peaked at 52 years and then decreased at 62 years, thus suggesting a 'retirement effect'. Current and past shiftworkers reported more problems with falling asleep and early awakening than subjects who had never worked on shifts. This is a likely explanation of why the effect of age was massive in the latter group and much less pronounced in the former groups. There were no clear effects of the length or recency of shiftwork experience. This finding does not support the hypothesized permanent effect of shiftwork experience on subsequent sleep. Females had higher complaint rates at every age. There was little interaction between age and sex, but women were affected more by shiftwork as they got older, particularly as to hypnotic consumption. Some of the results support the hypothesis that a selection process excludes workers who are no longer able to cope with the demands of shiftwork.     

Extracellular fluid and its proteins: dehydration, shock, and recovery

This review highlights characteristics of extracellular fluid (ECF) that are often overlooked. ECF has, in addition to plasma and interstitial fluid (ISF) surrounding cells, a third large compartment, the ISF of skin and connective tissue. This acts as a reservoir that gives up ECF to plasma volume (PV) in order to sustain circulation in the event of either shock or dehydration. While Starling forces drive filtration, ECF is returned to PV more by lymph and less by Starling forces than previously appreciated. Lymph return to PV is dependent on physical activity and muscle contraction to overcome gravity. Regional change in metabolic rate alters the need for oxygen and nutrients that is met by a regional increase in capillary blood flow. Blood flow is controlled by vasoactive compounds released in response to a drop in PO₂; these relax capillary smooth muscle to increase blood flow and delivery of oxygen and nutrients. Plasma proteins, including albumin, are filtered into the interstitium through larger pores than those filtering ECF. The rate of protein filtration is set by size and charge of these larger endothelial pores and by size and charge of proteins. Charge of these pores, hence albumin permeability, is regulated by many of the same vasoactive compounds that control capillary flow. As a consequence, in response to gravitational stress and other forms of shock that reduce effective circulation, albumin as well as ECF is rapidly shifted from plasma and sequestered in ISF. When this has occurred, as in burn shock, restoration is better effected by generous expansion of ECF with Ringer’s solution alone, rather than with Ringer’s solution supplemented with human serum albumin or other colloid. Restoring both PV and ISF volume restores lymph circulation and returns sequestered albumin to PV. Received: 12 November 1998 / Revised: 30 March 1999 / Accepted: 2 April 1999     

Morphometrical analysis of hemosiderin deposits in relation to wound age

A morphometrical analysis of the extent of hemosiderin deposits in 71 human skin wounds with post-infliction intervals between 2 days and 7 months was performed. Earliest positive findings were detectable in a lesion aged 3 days, and with increasing wound age an increase in the amount of hemosiderin occurred. A value of more than 20% of the microscopic field with hemosiderin deposits was found earliest 8 days after wounding and therefore the detection of considerable amounts of hemosiderin (arbitrarily defined as 20% or more of the evaluated area) indicates a minimum wound age of approximately 1 week. Since the extent of hemosiderin formation depends upon the extent of the initial hemorrhage and a physiological reduction in the amount of this pigment with advanced wound age, slight or absent hemosiderin deposits cannot provide information on the post-infliction interval.     

Drug Distribution in Obesity and following Bariatric Surgery: A Literature Review

Background: The pharmacokinetic variables of drug clearance and volume of distribution are usually corrected for body weight or surface area. Only recently have the relationships which exist between body size, physiologic function and pharmacokinetic variables been evaluated in the obese population. These effects are not widely known, and data on this and the effects of bariatric surgical procedures are scantily documented in the surgical literature. Methods: Literature review. Results: Drugs with a low or moderate affinity for adipose tissue have a moderate increase in the volume of distribution (Vd), and this correlates with the increase in lean body mass (LBM). Highly lipophilic drugs, with some exceptions, show the expected increase in Vd and prolongation of elimination half-life, indicating a marked distribution into adipose tissue. Drug absorption, in general, is slowed by delayed gastric emptying and is normal when gastric emptying is normal or increased. Most drug absorption occurs in the small intestine where duration of drug/mucosal contact is the most important factor. Conclusions: Drugs whose distribution is restricted to LBM should utilize a loading dose based on ideal body weight (IBW). For those drugs which distribute freely into adipose tissue, the loading dose should be based on total body weight (TBW). Adjustment of the maintenance dose depends on clearance rates. In a few cases dosage adjustment depends on pharmacodynamic data, since drug clearance does not conform to these recommendations, for reasons which remain to be defined. Following bariatric surgery, in the absence of delayed gastric emptying or uncontrolled diarrhea, drug absorption rates are usually comparable to the non-operated patient.