Immunohistochemical profile of endometrioid adenocarcinoma of the uterus: ER, PR, HER-2, Ki-67 and their prognostic value

76 endometrioid adenocarcinomas of the uterine body were studied. Expression of the above markers is of essential value together with metastatic involvement of regional lymph nodes, stage of the disease and pathogenetic variant for determining prognosis of carcinoma aggressiveness and disease outcome. Positive hormonal-receptor status of the tumor is characterized by well-differentiated tumor cells, small depth of invasion, rare metastases to regional lymph nodes and higher survival (5 year--81%) of patients comparing with cases where ER and PR were not determined (53%). On the contrary, overexpression of oncoprotein HER-2 and Ki-67 higher than median (42%) was associated with high tumor aggression resulting finally in a significant fall in the survival (from 75% to 58% and from 79% to 60%, respectively). Combination of HER-2 overexpression with a high level of Ki-67 is particularly unfavourable (5-year survival--43%).     

Phase I clinical study of LL-D49194α1 with retrospective pharmacokinetic investigations in mice and humans

Summary LL-D491941 is a new cytotoxic antibiotic selected for clinical phase I study because of its impressive pre-clinical anti-tumour activity and its low toxicity profile in experimental animals. A total of 15 patients were treated in centres in Glasgow and Amsterdam at doses ranging from 0.25 to 4 mg/m². One minor response was noted in a patient with colonic carcinoma. The study was suspended following the discovery of unexpected cardiotoxicity. As this toxicity was not consistent with the standard (EORTC) European Organisation for Research and Treatment of Cancer toxicology profile, we chose to investigate the pharmacokinetics of LL-D491941 in mice and humans in more detail to try to explain this phenomenon. A major difference in plasma protein binding was discovered between mice and patients, with a suggestion of non-linear kinetics being noted at higher doses in humans. It is likely that these differences in drug handling account for the unexpected and serious toxicity encountered in this trial.     

Docetaxel: a new active agent in the therapy of metastatic breast cancer

Breast cancer is the most common malignancy in women, accounting for about 18% of female cancers, and over half a million new cases are diagnosed worldwide each year. Its incidence increases with age and is currently rising. Although the increased availability of screening programs has allowed earlier detection and treatment of primary breast cancers, many patients relapse with metastases after apparently successful treatment of their primary tumor and over 15,000 women in the UK and about 50,000 in the USA die from advanced disease each year. The natural course of breast cancer is very variable even after the development of metastases, and depends on a variety of tumor characteristics and prognostic factors. This is reflected in the large number of treatments currently employed. However, despite this wide choice and considerable research over the years, treatment of metastatic breast cancer (MBC) prolongs average survival times only slightly. Current therapy is aimed at achieving a balance between producing maximal tumor shrinkage to produce the most effective possible palliation of symptoms, and minimizing adverse effects. Anticancer chemotherapy is the preferred option in patients who do not respond to hormones, those with hormone-independent tumors, those with aggressive breast cancer subtypes. A variety of anticancer chemotherapy regimens, using both single and combined agents, have been shown to be effective in achieving tumor regression in MBC. Anthracyclines (doxorubicin, epirubicin) are the most active of the established monotherapies, typically producing response rates of 50-60% during initial (first-line) treatment for metastatic disease, but being effective in fewer than 25% of patients requiring second-line therapy. The drawbacks of anthracyclines include dose-limiting cumulative cardiotoxicity and the development of resistant tumor clones after the use of anthracyclines for adjuvant or first-line therapy, especially if subsequent courses are required within a year. The success of these established chemotherapeutic agents depends greatly on the number and location of metastatic sites. Lymph node and soft tissue secondaries tend to respond well, while visceral metastases (especially in the liver) carry a particularly poor prognosis despite treatment. The outlook for patients with metastases involving more than two organ systems is also bleak. Although some patients can live for years with metastatic disease, the average survival time in patients with MBC is 18-24 months, while in those with liver metastases, life expectancy averages only 6 months. High-dose anticancer chemotherapy with granulocyte-colony stimulating factor (G-CSF) or autologous bone marrow transplantation has allowed the dose intensity of anthracyclines to be increased, and has improved the response rate to about 70% in selected patients with MBC. However, this approach has not been proven to improve survival, involves the risk of greater toxicity and drug-related mortality, and patients with reduced clearance of anthracyclines due to hepatic dysfunction from liver metastases may not be suitable candidates. A number of new anticancer agents have also recently been introduced in an attempt to improve on the performance and avoid the tolerability problems associated with anthracyclines. Among these, antitubulin agents (taxoids and vinorelbine) have shown highly promising activity in MBC. This paper reviews the preclinical, phase I and phase II data for one taxoid, docetaxel. Docetaxel (Taxotere) belongs to the taxoid class of cytotoxic agents, the development of which began more than 20 years ago. In 1971, paclitaxel (Taxol) was identified as the active compound of the crude extract of the bark of the Pacific Yew tree Taxus brevifolia. However, at that time the development of paclitaxel was hampered because of the limited source of the drug and difficulties with isolation, extraction and formulation. The second active taxoid, docetaxel, was isolated by Potier et al. in 1986. Docetaxel is prepared from a non-cytotoxic precursor, extracted from the needles of the European Yew tree Taxus baccata, that is condensed with a chemically-synthesized side-chain. As the docetaxel precursor is freely available because of the regenerating capacity of the needles the development of docetaxel has thus been rapid.     

Xanthogranulomatous pyelonephritis

A four years-old boy with Xanthogranulomatous pyelonephritis was surgically treated at the Pediatric Surgery Unit of the Santa Casa de Misericórdia of Maceió. Comments are made upon pathology, pre-operative diagnostic difficulties, differential diagnosis, and the rare occurrence in children.     

Outcomes of a cardiovascular nutrition counseling program in African-Americans with elevated blood pressure or cholesterol level

OBJECTIVE: To evaluate a cardiovascular nutrition education package designed for African-American adults with a wide range of literacy skills. DESIGN: Comparison of a self-help group and a full-instruction group; each group received nutrition counseling and clinical monitoring every 4 months. SUBJECTS: Three hundred thirty African-American adults, aged 40 to 70 years, with elevated cholesterol level or high blood pressure were randomly assigned to the self-help or full-instruction group; 255 completed the 12-month follow-up. INTERVENTIONS: Counseling to reduce intake of dietary fat, cholesterol, and sodium was based on Cardiovascular Dietary Education System (CARDES) materials, which included food-picture cards, a nutrition guide (self-help and full-instruction group), a video and audiotape series, and 4 classes (full-instruction group only). MAIN OUTCOME MEASURES: Changes in lipid levels and blood pressure after 12 months. STATISTICAL ANALYSES PERFORMED: Primary analyses consisted of repeated-measures analysis of variance to examine effects of time and randomization group on outcomes. RESULTS: Total cholesterol and low-density lipoprotein cholesterol level decreased by 7% to 8% in the self-help and full-instruction groups of men and women (P < .01). The ratio of total cholesterol to high-density lipoprotein cholesterol (HDL-C) decreased in both groups of women and in the men in the full-instruction group (P < .01). In full-instruction and self-help participants with elevated blood pressure at baseline, systolic blood pressure decreased by 7 to 11 mm Hg and diastolic blood pressure decreased by 4 to 7 mm Hg (P < .01). Outcomes did not differ by literacy scores but were positively related to the reported initial frequency of using CARDES materials. APPLICATIONS/CONCLUSIONS: These results suggest that periodic nutrition counseling based on CARDES materials used for home study can enhance management of lipid levels and blood pressure in African-American outpatients.     

3-Nitropropionic acid induces a spectrum of Huntington's disease-like neuropathology in rat striatum

Systemic administration of the mitochondrial toxin 3-nitropropionic acid (3-NP) to rats results in selective striatal lesions and serves as an experimental model of Huntington's disease (HD). However, the effects of the 3-NP treatment are unpredictable and result in lesions of variable severity. The present study was aimed at further characterizing the variability of the striatal lesions induced by systemic administration of 3-NP using osmotic pumps. Hematoxylin-eosin (HE) and Nissl stains as well as immunohistochemical labelling of astrocytes and striatal neurones were performed to analyse the neurotoxic effects of 3-NP. In general, chronic systemic administration of 3-NP resulted in obvious bilateral striatal lesions, which ranged from mild to severe, together with a subtle, but detectable behavioural lesion. Severe type lesions showed marked neuronal loss and an increased expression of glial fibrillary acidic protein (GFAP) in astrocytes surrounding the lesion area, whereas in the core of the lesion GFAP-immunoreactivity was absent. The mild type lesion was characterized by a substantial loss of striatal neurones and an increased expression of GFAP-positive astrocytes throughout the lesion. In a number of 3-NP-treated animals, neither type of lesion was observed, although these animals demonstrated behavioural changes in the paw test compared to controls. In the striatum of these tested 3-NP-treated animals, compromised rk' neurones were detected, suggestive of subtle and early 3-NP-induced neuronal injury. Similar dark neurones were also detected in mild and severe lesions and were immunocytochemically characterized as gamma-aminobutyric acid (GABA) and substance P containing spiny neurones, which belong to the neuronal population that is affected in early HD. These results indicate that systemic administration of 3-NP to rats may result in a spectrum of striatal pathology of which the morphology of the mild type lesion resembles the characteristic HD neuropathology most closely.     

Coronary risk factors in middle-aged men as related to smoking, coffee intake and physical activity.

The relationship between lifestyle and coronary risk factors in blood was investigated in 165 middle-aged men. Plasma fibrinogen, serum triacylglycerols (TG), and apolipoprotein B (apo B) were higher, and high density lipoprotein cholesterol (HDLc) lower in smokers (n = 69) than in non-smokers (n = 96). By linear regression analysis there was a significant positive association between degree of smoking and either total cholesterol (TC), apo B, or plasma fibrinogen, whereas smoking was inversely related to HDLc. Smoking and coffee intake were positively correlated with an atherogenic index, reflecting the balance between low and high density lipoproteins. Sedentary men (n = 59) had higher mean TC, apo B, and atherogenic index than physically active men (n = 104). Smokers used salt more often than non-smokers. Physically active men used vegetables more often than sedentary men. Combining several habits into a "bad habit" score gave a high level of significance for its association with TC, apo B, and the atherogenic index. The results indicate that lifestyle may influence several blood factors involved in atherosclerosis development.     

No effect of a Taql polymorphism in DNA at the endothelin I (EDN1) locus on normal blood pressure level or variability

Endothelin is a peptide reported to be one of the most potent vasoconstrictors known. Presumably, endothelin could play a role in the physiological regulation of blood pressure in healthy or hypertensive people. We have studied a normal restriction fragment length polymorphism (RFLP) at the endothelin-I (EDN1) locus detected with the restriction enzyme TaqI. In three different series comprising 166, 120 and 207 unrelated individuals, we found no evidence for association between genotype in this polymorphism and level of systolic or diastolic blood pressure. In two series of 156 and 117 monozygotic (MZ) twin pairs, respectively, there was no difference between genotypes in within-pair variation in systolic or diastolic blood pressure. Thus neither "level gene" nor "variability gene" effects of normal genes at the EDN1 locus could be detected with the polymorphism analyzed, in healthy population samples.     

T gamma/delta lymphocytes in renal transplant recipients.

T gamma/delta lymphocytes are able to perform allospecific cytotoxicity and natural killer cytotoxicity in vitro. However, very little is known about their function in vivo. To investigate the possible involvement of T gamma/delta lymphocytes in the immune response to renal allografts, fine-needle aspiration biopsies and peripheral blood of 15 renal transplant recipients were studied during the first 4 weeks after transplantation. In addition peripheral blood of patients before transplantation, half a year and one year after transplantation was studied. No increase in the percentage of T gamma/delta lymphocytes in the fine-needle aspiration biopsies, including those taken during acute rejection episodes, was found. A significant decrease in the percentage of T gamma/delta lymphocytes was observed in peripheral blood after transplantation. We conclude that T gamma/delta lymphocytes seem to play no major role in the immune response to renal allografts.     

Medically equipped emergency ambulance units at "H?pital Civil de Charleroi". Four years' activity

In narrow collaboration with the so-called "900 Service", the civil Hospital of Charleroi provides, since 1971, medical attendance for two emergency medical aid flying squads. Five hospital doctors belonging to this "900 Service" alternately assume, night and day, such responsibilities. Their background is reanimation anesthesia. Medical attendance is assumed on the ground of gravity criterions which are appreciated by a switchboard operator working at the Telephone calls' Centre. The number of such emergency medical attendances is gradually increasing: 377 in 1974, 489 in 1975, 973 in 1976, 1661 in 1977, 2135 in 1978. The proportion of "flying" attendances assumed for sheer medical affections is also gradually increasing in regard to those assumed for traumatological causes. The daily average of such "flying interventions" reaches 5.8 with a daily peak record of 15, which unquestionably shows that such an organised medical service is definitely positive. One should concede that a better selection among such emergency telephone calls could make the good results now recorded even better. The way to improve this selection could be achieved if the operator were a physician as this is the case in France with the S.A.M.U. services. In theory, such an improvement could be reached through a Regional Centre for Emergency Medical Aid, such a Centre being activated by both local medical and hospital forces interdependent in the pursuit of the same goal i.e. "Cases of Emergency".