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.

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.

A tion of drugs on denervated myoepithelial cells of salivary glands.

1. The pressure in the ducts of the two submaxillary glands was recorded in anaesthetized dogs in which either the superior cervical ganglion had been removed or the chorda-lingual nerve had been cut on one side, 17-30 days earlier. Noradrenaline, adrenaline, phenylephrine, acetylcholine and methacholine were injected to produce pressure rises attributed to contraction of myoepithelial cells.2. After sympathectomy increased pressure responses were obtained with all the drugs, but particularly with noradrenaline. Cocaine increased the effect of noradrenaline on the normal gland but slightly less than sympathectomy.3. Parasympathetic decentralization increased the pressure effects of acetylcholine and methacholine, and in most cases also increased those of the sympathomimetic drugs.4. It is concluded that the myoepithelial cells of this gland normally receive motor impulses from both divisions of the autonomic nervous system, and that many, if not all, of the cells are innervated by both. Disconnecting the gland from the central nervous system by either pathway causes supersensitivity of the classical post-junctional type, and sympathetic ganglionectomy causes in addition a pre-junctional sensitization.

The pharmacology of salivary myoepithelial cells in dogs.

1. Pressure changes in the submaxillary and parotid ducts of dogs, induced by nerve stimulation or intravenous injection of drugs, were studied.2. Pressure rises could be elicited by parasympathetic stimulation and by acetylcholine and methacholine, even when no secretion was evoked. These effects were abolished by atropine.3. Similarly, sympathetic stimulation, adrenaline, noradrenaline and phenylephrine raised the pressure in both glands, also in the absence of secretion. Dihydroergotamine abolished these effects. Isoprenaline increased the pressure in the submaxillary duct, but only when it caused secretion. This effect was abolished by propranolol. In the parotid gland isoprenaline caused neither secretion nor pressure rise. It is concluded that the myoepithelial cells of the two glands are supplied with alpha-adrenoceptors.4. Doses of histamine, bradykinin, kallidin and physalaemin which caused no salivary secretion raised the duct pressure even when dihydroergotamine, propranolol and atropine had been given.5. Angiotensin and 5-hydroxytryptamine increased the pressure only in some experiments. Oxytocin caused very little or no pressure rise. Vasopressin had no effect of its own but reduced the pressure raising effects of nerve stimulation or drugs.

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.

Electron microscopy of watery vacuole formation in rat parotid acinar cells during reflex stimulation.

Reflex stimulation from eating hard chow caused variable degrees of watery vacuolation, most conspicuously in animals that had eaten the most food; this was accentuated by eating in the cold. Some vacuolation occurred in the absence of sympathetic impulses but there was much more in glands receiving both parasympathetic and sympathetic impulses. Vacuole formation was often associated with, but not dependent upon, a degree of acinar degranulation. The vacuoles appeared to originate either from the inner side of the Golgi apparatus, near condensing vacuoles, or from ballooning within the rough endoplasmic reticulum; some vacuoles appeared to arise close to secretory granules. Certain cellular components, including secretory granules, entered the contents of vacuoles, which also often had connections with lumina. Many basally-located vacuoles were large and bounded only by a tenuous layer of cytoplasm which was contained by the basal lamina. Vacuole formation may be related to strong stimulation of susceptible cells, which occurs to a variable extent during natural reflex secretion, as well as during artificial stimulation. Thus, under normal conditions, certain macromolecular components might enter saliva via this route and not solely by exocytosis. Leakages from acinar vacuoles could also occur into the glandular interstices, accounting for some of the parotid amylase found in peripheral blood.

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.

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.

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.

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.

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.

Endoscopic findings in patients with ulcer-like dyspepsia.

One hundred and sixty-seven patients in a single general practice who presented with ulcer-like dyspepsia were offered an upper gastrointestinal fibre endoscopy. Twenty-two patients had a peptic ulcer while only three had a gastric ulcer. One patient had a carcinoma of the cardia, one an adenocarcinoma in the body of the stomach and one a carcinoma at the ampulla of Vater. In another 55 patients the main findings at endoscopy were edema/reddening or erosions in the antral or duodenal mucosa. Endoscopic findings were normal in 46 patients. Malignancies were found only in patients over 50 years of age and only 4 ulcers were seen in patients under 40. The clinical findings of presence of night pain, pain relief after food intake and history of peptic ulcer were more common in patients with an existing peptic ulcer than in those with a normal endoscopy.