Metaplastic sarcomatoid carcinoma of the breast appears more aggressive than other triple receptor-negative breast cancers.

Metaplastic sarcomatoid carcinoma (MSC) of the breast is usually triple receptor (ER, PR, and HER2) negative and is not currently recognized as being more aggressive than other triple receptor-negative breast cancers. We reviewed archival tissue sections from surgical resection specimens of 47 patients with MSC of the breast and evaluated the association between various clinicopathologic features and patient survival. We also evaluated the clinical outcome of MSC patients compared to a control group of patients with triple receptor-negative invasive breast carcinoma matched for patient age, clinical stage, tumor grade, treatment with chemotherapy, and treatment with radiation therapy. Factors independently associated with decreased disease-free survival among patients with stage I-III MSC of the breast were patient age > 50 years (P = 0.029) and the presence of nodal macrometastases (P = 0.003). In early-stage (stage I-II) MSC, decreased disease-free survival was observed for patients with a sarcomatoid component comprising ≥ 95% of the tumor (P = 0.032), but tumor size was the only independent adverse prognostic factor in early-stage patients (P = 0.043). Compared to a control group of triple receptor-negative patients, patients with stage I-III MSC had decreased disease-free survival (two-sided log rank, P = 0.018). Five-year disease-free survival was 44 ± 8% versus 74 ± 7% for patients with MSC versus triple receptor-negative breast cancer, respectively. We conclude that MSC of the breast appears more aggressive than other triple receptor-negative breast cancers.

Twelve-year experience in the investigation and treatment of paragangliomas.

We report a 12-year laboratory experience in the diagnosis of 37 patients with phaeochromocytoma, one with malignant paraganglioma and one with ganglioneuroblastoma. Surgery was performed in eight different hospitals, which underlines the difficulty of ensuring uniformity of investigations. Of the 37 with phaeochromocytoma, 15 were in the right adrenal gland, 12 were on the left, seven were bilateral and three were extra adrenal. Twenty-three were male and 15 were female; the median age was 36 years. Four of five patients with von Hippel-Lindau disease had bilateral adrenal tumours and four had neurofibromatosis. None had multiple endocrine neoplasia. Using essential hypertensive patients as a reference population, diagnostic sensitivity was 80% for noradrenaline, 54.4% for adrenaline, 19.1% for dopamine, 93.3% for total normetanephrine, 33.3% for total metanephrine, 78.7% for 3-methoxy-4-hydroxymandelic acid (HMMA) and 23.5% for homovanillic acid (HVA). However, if each patient's results were taken as a package, the sensitivities were 100% for noradrenaline, 63.6% for adrenaline, 30.3% for dopamine and 89% for HMMA. Seven recent patients had gene analysis. There were six (15.4%) deaths due directly or indirectly to the paraganglioma. Postoperative blood pressures were normal in 74%. The decrement in catecholamine values post-surgery is shown. Urinary noradrenaline values fell by a mean of 94.5% and the use of urinary noradrenaline as a tumour marker is also demonstrated.

Is the American health care delivery system ready for change?

In October 1992, the American College of Physician Executives sponsored a study tour to Berlin, Germany, and Amsterdam, Holland. Meetings were held with government officials, third-party payers, and providers, and on-site visits were made at hospitals, clinics, and academic centers. The purpose was to study the health care delivery system in those countries and to share some insights with the countries' hosts on the U.S. system. In a series of reports that began in the July issue of the journal, 5 of the 10 study tour participants describe their impressions of the tour and of the health care systems in the countries that were visited. In this final report, the implications of the German and Dutch systems for reform of the U.S. health care system are discussed.

Allopurinol fails to protect against gentamicin-induced renal damage in normotensive and spontaneously hypertensive rats.

Recent research suggests the involvement of hydroxyl and superoxide free radicals in the development of gentamicin-induced acute renal tubular necrosis. Xanthine oxidase has been implicated as an important source of superoxide free radicals. Spontaneously hypertensive (Wistar-Kyoto) rats (SHR) have excessive oxidant stress which may render them more sensitive to the proported oxygen free radical producing effects of gentamicin. This study was undertaken to determine if the xanthine oxidase inhibitor allopurinol will ameliorate the effects of gentamicin. Normotensive Wistar-Kyoto (WKY) rats and SHR were administered allopurinol (40 mg/kg twice daily) orally 4 days before and throughout a 12-day gentamicin treatment period. The allopurinol only treatment group demonstrated no noticeable histological or functional changes considered to be indicative of nephrotoxicity. Gentamicin-injected WKY rats and SHR equally demonstrated extensive proximal tubular and glomerular damage characteristic of aminoglycoside-induced kidney damage. Allopurinol failed to protect either rat strain against the histological damage caused by gentamicin. Equivalent alterations in serum creatinine, serum gentamicin, urinary N-acetyl-beta-D-glucosaminidase excretion, body weight, urinary output, and blood pressure occurred in the gentamicin with allopurinol and gentamicin only treatment groups. Our results demonstrate allopurinol does not ameliorate the pathogenesis of gentamicin. SHR do not appear to be more sensitive to the effects of gentamicin induced kidney damage with or without allopurinol as compared with WKY rats.

Orbital pseudotumor of the levator muscle.

A 58-year-old white man with chronic progressive external ophthalmoplegia developed proptosis and an improvement in his ptosis from a mass in the superior orbit. A biopsy showed the mass to consist of an inflammatory mass of the levator palpebrae superioris muscle. As the inflammatory mass responded to periorbital and systemic steroids, the ptosis recurred. Inflammatory pseudotumor of the levator muscle is extremely unusual and has not been reported previously in patients with chronic progressive external ophthalmoplegia.

Filamentary keratitis and stromal neovascularization associated with brain-stem injury.

Three cases of filamentary keratitis were associated with brain-stem injuries. Severe stromal neovascularization developed in two cases. There was corneal sensation in the involved eyes. The first case resolved spontaneously over a 20-month period after stromal neovascularization. Two patients responded rapidly to treatment with soft contact lenses. The vascularization resolved in both cases, but much sooner in the eyes treated with the soft contact lenses.

Chloramphenicol levels in cerebrospinal fluid in meningitis.

Chloramphenicol was found to cross the blood-brain barrier into the cerebrospinal fluid of children with pyogenic meningitis effectively both at days 2 and 10 of therapy. It is recommended as the drug of choice in the treatment of children with Haemophilus influenzae meningitis.

Enkephalins in large bowel malignancy and in acute appendicitis.

Leucine and methionine enkephalins were measured by biological assay in normal colon, adenocarcinoma of the colon, carcinoma of the caecum, and in normal and inflamed appendix. Methionine enkephalin levels in both the adenocarcinomas and inflamed appendices were significantly higher than in normal controls. No significant change occurred in leucine enkephalin levels. The caecal tumours were anaplastic and contained no demonstrable opioid activity.

Nocturnal ulcer pain associated with slow-wave sleep.

It is suggested that the early-morning growth-hormone release associated with slow-wave sleep is due to inhibition of somatostatin secretion from the hypothalamus. It is also associated with inhibition of gastrointestinal somatostatin, causing a release of gastrin and insulin. Because the levels of glucocorticoid hormones are concurrently low, the insulin effect is unopposed and increases gut motility through augmented vagal tone. This results in an increased delivery of acid to the duodenum. In duodenal-ulcer patients, whose duodenal buffering capacity is reduced because of a relative deficiency of secretin response, this leads to pain.

A dual action of 5-hydroxytryptamine on the ovarian suspensory ligament of the rat.

5-Hydroxytryptamine has a dual effect on the spontaneously contracting rat ovarian ligament, in vitro, a contraction which is antagonized by the prior administration of methysergide and a relaxation of the ligament observed in the methysergide-treated preparation. The relaxatory effect was not antagonized by propranolol or tetrodotoxin but treatment of the ligament with indomethacin abolished this response. Prostaglandins of the E series produced an inhibition, and PGF2alpha a contraction of the ligament. Thin layer chromatographic separation indicates that 5-HT causes the release of a PGE2-like substance which relaxes the ovarian suspensory ligament.

Hydatid disease transmission in California. A study of the Basque connection.

A descriptive epidemiologic and anthropologic study was designed to determine by field observation and interview the extent of Basque involvement in the sheep industry of California, the nature of the sheep and dog husbandry practices of California Basques as they might influence Echinococus granulosus transmission, and the "folk knowledge" of hydatid disease possessed by California Basques, particularly as it might indicate the early presence of this infection in California and provide evidence for or against possible intensification or spread of transmission in the recent past. Basques were found to dominate the sheep industry of California's Central Valley from Sacramento south, but to be virtually absent from other sheep-raising areas of the state. In contrast to most other California sheep ranchers, Basques practice a transhumant form of husbandry in which bands of sheep are moved from location to location under the control of contract Basque shepherds from Spain and France and a number of sheep dogs.