Assessment of the management of carcinomatous meningitis from breast cancer globally: a study by the Breast International Group Brain Metastasis Task Force.

BACKGROUND: Carcinomatous meningitis (CM) is a severe complication of breast cancer. The Breast International Group (BIG) carried out a survey to describe the approach to CM internationally. PATIENTS AND METHODS: A questionnaire on the management of CM was developed by the Brain Metastases Task Force of BIG and distributed to its groups, requesting one answer per group site. RESULTS: A total of 241 sites responded, 119 from Europe, 9 from North America, 39 from Central/South America, 58 from Asia, and 16 in Australia/New Zealand, with 24.5% being general hospitals with oncology units, 44.4% university hospitals, 22.4% oncology centers, and 8.7% private hospitals. About 56.0% of sites reported seeing <5 cases annually with 60.6% reporting no increase in the number of cases of CM recently. Nearly 63.1% of sites investigate for CM when a patient has symptoms or radiological evidence, while 33.2% investigate only for symptoms. For diagnosis, 71.8% of sites required a positive cerebrospinal fluid cytology, while magnetic resonance imaging findings were sufficient in 23.7% of sites. Roughly 97.1% of sites treat CM and 51.9% also refer patients to palliative care. Intrathecal therapy is used in 41.9% of sites, mainly with methotrexate (74.3%). As many as 20 centers have a national registry for patients with breast cancer with central nervous system metastases and of those 5 have one for CM. Most (90.9%) centers would be interested in participating in a registry as well as in studies for CM, the latter preferably (62.1%) breast cancer subtype specific. CONCLUSIONS: This is the first study to map out the approach to CM from breast cancer globally. Although guidelines with level 1 evidence are lacking, there is a high degree of homogeneity in the approach to CM globally and great interest for conducting studies in this area.

Home-care workers: work conditions and occupational exclusion: a comparison between carers on early-retirement and regular pensions.

The aim of the study was to identify conditions associated with occupational exclusion from home-caring. In a group of 346 home-care workers who responded to a questionnaire, there were 18 newly-retired carers on early-retirement/disability pensions, and 28 carers who had just taken regular retirement. A discriminant analysis was conducted to identify work conditions that differentiated the two groups. The results show that a combination of variables--functional impairment (pain when doing physical work), psychosomatic complaints, and nature of relationship with/attitude to clients--significantly differentiated the two groups. When the discriminant coefficients were applied to other groups--older full-time and part-time employees (n = 224), carers who had undergone job transfers, and carers on long-term sick leave--the order of groups by discriminant-point score was largely as expected. The results are discussed in relation to dilemmas, psychological demands and organizational circumstances prevailing in home-care work.

Clusters of acute appendicitis: further evidence for an infectious aetiology.

BACKGROUND: The aetiology of appendicitis, the commonest cause of acute abdomen, is unknown. Infection has been proposed but the evidence has been unconvincing. The purpose of the present study was to investigate if temporo-spatial clustering and outbreaks, characteristics of infectious diseases, could be found in appendicitis cases in a defined Swedish population. METHODS: Temporo-spatial clustering among 1155 cases from three districts of Jönköping County in 1984-1990 was identified by Knox space-time cluster analysis. Outbreaks were identified by retrospective study of temporal variations in 3590 consecutive cases of acute appendicitis from the city of Jönköping in 1969-1990. RESULTS: Space-time clustering was found among patients with operations less than 60 days apart (observed/expected [O/E]-ratio 1.46, P = 0.016). Subset analysis revealed clustering to be commonest among patients from the same households (O/E-ratio 6.52, P = 0.012), among patients younger than 15 years (O/E-ratio 3.61, P = 0.004) and among females (O/E-ratio 2.28, P = 0.004). Three outbreaks with a significantly increased number of cases were observed during the 22-year study period (O/E-ratio 1.6-2.2, P = 0.001-0.049). CONCLUSIONS: The finding of temporo-spatial interaction and outbreaks among appendicitis cases supports the concept that appendicitis may be caused by infectious agents.

Indications for operation in suspected appendicitis and incidence of perforation.

OBJECTIVE: To clarify poorly understood epidemiological features of appendicitis. DESIGN: Retrospective study of consecutive cases from a defined population and analysis of data from published studies. SETTING: County of Jönköping, Sweden. 3029 patients who underwent operation in 1984-9 and 4717 patients from the county town who underwent operation in 1970-89, all for suspected appendicitis, plus 48,426 cases from six reported studies. MAIN OUTCOME MEASURES: Incidences specific for age and sex and temporal trends of perforating and non-perforating appendicitis and removal of a normal appendix. Associations between diagnostic accuracy, rate of perforation, and incidences of removal of a normal appendix and of perforating and non-perforating appendicitis. RESULTS: The incidence of appendicitis was 116/100,000 inhabitants. Appendicitis was more common in male patients. The incidence of perforating appendicitis was independent of age, stable over time, and uninfluenced by the rate of laparotomy, whereas the incidence of non-perforating appendicitis was age dependent, decreasing over time, and related to the diagnostic accuracy and rate of removal of a normal appendix. CONCLUSIONS: Perforating and non-perforating appendicitis seem to be separate entities, and appendicitis that resolves spontaneously is common. This may have important implications for managing suspected appendicitis.

Changes in the surgical treatment of gallstones during a 10 year period.

OBJECTIVE: To investigate changes in the surgical treatment of gallstones during a 10 year period. DESIGN: A retrospective study of medical records. SETTING: A community hospital serving a population of 108,000 inhabitants. SUBJECTS: All patients having their first operation for gallstones during the periods 1976-1978 and 1986-1988. RESULTS: The annual frequency of operations for gallstones decreased from 2.01 to 1.13/1,000 inhabitants, and the corresponding frequency of operations on the common duct decreased from 0.39 to 0.28. The percentage of urgent operations increased from 19 to 47. CONCLUSION: A decline in the prevalence of cholelithiasis or a more restrictive attitude of elective operations for gallstones, or both, would explain the overall reduction in surgery for gallstones. The introduction of endoscopic sphincterotomy has considerably changed the treatment of cholelithiasis. The increased age of the patients and higher percentage of urgent operations has not resulted in any increase in postoperative morbidity and mortality.

Diagnostic accuracy and perforation rate in appendicitis: association with age and sex of the patient and with appendicectomy rate.

OBJECTIVE: To see if diagnostic accuracy and perforation rate in acute appendicitis is associated with age and sex of the patients and with the appendicectomy rate. DESIGN: Retrospective study of consecutive patients from a defined population. Study of associations between diagnostic accuracy and perforation rate and appendicectomy rate in published reports. SETTING: Jönköping county, Sweden. SUBJECTS: 3,029 patients operated on for suspected acute appendicitis from 1984-1989. MAIN OUTCOME MEASURES: Findings at laparotomy for acute appendicitis, confirmed with histological examination in 83% of the cases. RESULTS: Diagnostic accuracy was low at the extremes of age and in women (60% compared with 79% in men, p less than 0.001). When all intra-abdominal conditions were considered the percentage of negative laparotomies among women (24%) was twice that among men (12%, p less than 0.001). This difference between the sexes was also seen in nonfertile ages. Perforation rate was higher among men (18% compared with 13%, p less than 0.01) and at extremes of age. According to correlation analysis of published reports the perforation rate is unrelated to either diagnostic accuracy or appendicectomy rate while diagnostic accuracy is inversely associated with the appendicectomy rate. CONCLUSION: A low diagnostic accuracy is a problem mainly at extremes of age and in females. A low appendicectomy rate is associated with a high diagnostic accuracy, while the perforation rate is unaffected. A conservative attitude to exploration therefore seems justified.

Prevalence of gallstone disease in patients with diabetes mellitus. A case-control study.

The prevalence of gallstone disease was analysed in 360 diabetic patients and in 359 control subjects. In 61 (17%) of the diabetic patients and 50 (14%) of the control subjects gallstone disease was verified by previous cholecystography, ultrasonography, or cholecystectomy. The remaining 608 with no history of gallstone disease were invited to have an ultrasound scan of the gallbladder; the prevalence of cholelithiasis was similar among diabetic patients (14.4% n = 28) and control subjects (12.5%, n = 26).

Physical constitution and biochemical characteristics of patients with electively diagnosed gallstone disease.

Physical characteristics and blood glucose and serum lipid concentrations were analysed in 196 patients with electively diagnosed cholelithiasis and 187 age and sex matched controls. A logistic regression analysis showed that women with cholelithiasis had more total body fat and were shorter than the female controls. There were no differences in anthropometric measurements between the men with gallstones and their controls. Patients of both sexes, however, had increased serum triglyceride and decreased serum cholesterol concentrations compared with control subjects.

Effects of increased dietary energy and protein during late gestation on mammary development in gilts.

Thirty-two gilts were used to evaluate the effects of increased dietary energy and CP during late gestation on mammary development. On d 75 of gestation, gilts were assigned randomly in a 2 x 2 factorial arrangement to adequate (5.76 Mcal ME/d) or increased (10.5 Mcal ME/d) energy and adequate (216 g CP/d) or increased (330 g CP/d) protein. On d 105 of gestation, gilts were slaughtered and total mastectomies were performed. Mammary tissue was separated into mammary parenchymal and mammary extraparenchymal stromal tissue and analyzed for DNA, RNA, protein and lipid. No interactions between dietary energy and protein level were detected (P greater than .20). When adjusted for number of mammary glands and maternal BW (weight of the sow less the weight of the fetuses), mammary parenchymal weight was 27% greater (P less than .03) in gilts fed adequate energy than in gilts fed increased energy, but mammary extraparenchymal stroma weight was unaffected by dietary energy level. Total mammary parenchymal DNA was 30% greater in gilts fed adequate energy than in gilts fed increased energy (P less than .03). Total mammary parenchymal RNA (P less than .02) and total mammary parenchymal protein (P less than .02) also were greater in gilts fed adequate energy than in gilts fed increased energy. Dietary protein level did not affect mammary variables measured, except that increased dietary protein tended to reduce mammary extraparenchymal stromal weight (P less than .09). Increased dietary protein between d 75 and d 105 of gestation did not benefit mammary development, but increased dietary energy was detrimental to development of mammary secretory tissue.

Effect of energy source fed to sows during late gestation on neonatal blood metabolite homeostasis, energy stores and composition.

Four experiments utilizing 49 primiparous and 34 multiparous sows were conducted to evaluate the effect of feeding either starch, soybean oil or medium-chain triglyceride (MCT) during late gestation (d 100 to parturition) on neonatal fasting blood glucose homeostasis (Exp. 1 and 2), d-100 maternal circulating insulin, glucagon and glucose concentrations (Exp. 3 and 4), neonatal energy stores (Exp. 3 and 4) and colostrum composition (Exp. 1, 2, 3 and 4). In all cases, sows were fed 7.2 Mcal/d of a diet that supplied 279 g of protein daily. During fasting, pigs from MCT-fed dams had higher blood glucose concentrations (P less than .05) than pigs from starch-fed dams. No differences between treatments were observed for total carcass fat, liver glycogen or carcass glycogen of pigs killed prior to suckling. In general, colostrum fatty acid profiles were influenced by diet; however, the shifts in fatty acids differed for experiments. Starch-fed sows had higher blood insulin and lower blood glucagon (P less than .05) than lipid-supplemented sows; however, sow blood glucose remained constant across treatments. This study indicates that any positive effects of feeding soybean oil to sows during late gestation are most likely mediated by a change in fatty acid composition of colostrum; any beneficial properties of MCT feeding most likely are mediated through improved blood glucose maintenance of the neonate when it is subjected to fasting conditions.

Effects of immunizing gilts against zearalenone on height of vaginal epithelium and urinary excretion of zearalenone.

Two experiments were conducted to develop a vaginal epithelium bioassay for zearalenone (Z) and to determine whether immunization against Z would prevent Z mycotoxicosis. Eleven gilts were ovariectomized and allotted by weight to dietary doses of 50, 150 or 350 micrograms Z/kg BW daily for 3 d. All doses of Z increased height of the vaginal epithelium. Height of the vaginal epithelium in gilts fed 150 or 350 micrograms Z/kg BW increased more than that in gilts fed 50 micrograms Z/kg BW. Twenty-four gilts then were ovariectomized and allotted to be immunized or not immunized. A Z-bovine serum albumin conjugate was injected into gilts to achieve immunization. Ten weeks after initial immunization, antibodies to Z were detected after a 1:10(7) dilution at greater than .1 absorbance units using an enzyme-linked immunosorbent assay, and gilts were allotted by weight to diets with no Z or 150 micrograms Z/kg BW daily for 3 d. Immunization alone had no effect on height of vaginal epithelium, but after 3 and 10 d, immunized gilts fed Z had higher vaginal epithelium than did nonimmunized gilts fed Z. Immunized gilts excreted a larger percentage of ingested Z than nonimmunized gilts did. Therefore, immunizing gilts against Z potentiated both the estrogenic effects of Z and urinary excretion of Z equivalents.

Determination of zearalenone and related metabolites in porcine urine by modified enzyme-linked immunosorbent assay.

A direct competitive enzyme-linked immunosorbent assay (ELISA) was modified for the determination of zearalenone and zearalenois in porcine urine. In the modified procedure, standard or unknown concentrations of zearalenone were added to all wells, followed by rapid addition of zearalenone-horseradish peroxidase conjugate, whereas in previous methods, zearalenone and zearalenone-horseradish peroxidase were mixed and then added to microtiter wells. The modification increased the number of urine samples that could be analyzed per assay. The linear portion of the modified ELISA standard curve covered the range of 10-500 ng zearalenone/mL. Average recovery of zearalenone from spiked urine was 91, 101, 95, 107, 136, 112, and 120% for 1, 10, 25, 50, 100, 250, and 500 ng zearalenone/mL urine, respectively. Mean within-assay coefficient of variation for each concentration of zearalenone in 5 standard curves was 5.95%. Between-assay coefficients of variation for concentrations of zearalenone equivalents in lower and upper regions of the standard curve were 10.9% (n = 18) and 8.8% (n = 20), respectively. Analysis of urine samples showed that a gilt excreted 5.3% of ingested zearalenone in the 8 h following ingestion, with an average excretion rate of about 100 micrograms zearalenone equivalents/h.

Effects of streptozocin-induced diabetes on sympathetic and parasympathetic stimulation of parotid salivary gland function in rats.

Diabetes was induced with streptozocin in male Wistar rats. After 4-6 mo, parotid salivary flow was induced by stimulating bipolar electrodes (3-5 V for 2 ms) on either the auriculotemporal nerve (5 Hz) or the cervical sympathetic trunk (10 Hz). During parasympathetic stimulation, flow rates were 443 +/- 287 microliters/30 min in diabetic animals compared to 657 +/- 134 microliters/30 min in controls (P less than .01). Although parotid flow rates during parasympathetic stimulation were well maintained in controls, they decreased rapidly in most diabetic rats. Parotid secretory response to sympathetic stimulation was also reduced in diabetic compared with control animals (40 +/- 16 microliters/30 min and 82 +/- 50 microliters/30 min, respectively, P less than .01). In contrast to results obtained with direct neural stimulation, no differences in threshold dose or total saliva were observed when cholinergic (methacholine) and peptidergic (physalaemin) agonists were administered intravenously. Response threshold for an adrenergic agonist (epinephrine) was significantly increased in diabetes. Electron microscopy showed axoplasmic abnormalities in nonmyelinated axons in diabetic glands but not in control glands. Although most nerve profiles appeared normal, neuroaxonal abnormalities were found in every diabetic animal. The ultrastructural findings and the similar responses to methacholine and physalaemin suggest that autonomic neuropathy may be a factor in the abnormal response of the parotid gland to parasympathetic nerve stimulation.

Evaluation of anamnestic data in patients referred for oral cholecystography.

The knowledge about how patients are selected for elective gallbladder investigations is limited. In this study the anamnestic data of 817 patients referred for an elective cholecystography have been compared with those of 789 matched controls. Other diseases in the medical history were commonly seen, and different gastrointestinal symptoms occurred frequently in the patients. Only 207 (23%) patients presented with a gallstone disease, and no symptom was commoner in these patients than in the patients with normal cholecystograms. The low positive yield could be due to liberal and unclear indications for oral cholecystography. Many gallstones detected this way may in fact be asymptomatic, which should be borne in mind when a cholecystectomy is considered.

Utero-placental transfer of octanoic, palmitic and linoleic acids during late gestation in gilts.

The transfer across the swine uterus and placenta of [1-14C]octanoic acid, [9,10(n)-3H]palmitic acid and [1-14C]linoleic acid was studied in five gilts and their fetuses during late gestation following a single bolus injection. Only trace amounts of labeled fatty acids were found in fetal plasma lipid. The highest fetal plasma lipid values were less than 1.2% of the peak maternal values. The concentration of plasma free fatty acids (FFA) and fatty acid profiles in the umbilical artery (FA) and vein (FV) and uterine artery (UA) and vein (UV) were compared. There were no measurable umbilical arterio-venous differences. Concentrations of FFA in FA and FV were about 40% of the UA and UV values (187, 194, 73, 82 microEq/liter for UA, UV, FA and FV, respectively). Fetal plasma contained larger amounts of 14:0, 16:1, 18:1 and 20:4, whereas maternal plasma contained larger amounts of 18:0 and 18:2. There was difference between fetal and maternal plasma for 16:0 and 18:3; the latter was present only in minute amounts. In conclusion, only trace amounts of FFA cross the swine placental tissues during late gestation; therefore, their contribution to fetal energy supply or lipid storage appears limited.