Quantitative exercise technetium-99m tetrofosmin myocardial tomography for the identification and localization of coronary artery disease

The aim of this study was to evaluate the accuracy of quantitative 1-day exercise-rest technetium-99m tetrofosmin tomography in the identification of patients with coronary artery disease (CAD) and in the detection of individual stenosed coronary vessels. Sixty-one patients with suspected CAD who underwent coronary angiography and 13 normal volunteers were studied. All patients were submitted to two i.v. injections of^99mTc-tetrofosmin, one at peak exercise (370 MBq) and the other (1110 MBq) at rest 3 h after exercise (images 15–30 min after injection for both studies). All patients with CAD (0% luminal stenosis) (n=50) had an abnormal^99mTc-tetrofosmin tomogram. Only one patient without significant coronary narrowing showed abnormal findings. Overall sensitivity, specificity and diagnostic accuracy in the detection of individual stenosed vessels were 77%, 93% and 85%, respectively. Sensitivity and diagnostic accuracy in the identification of individuals stenosed coronary vessels were significantly higher (P<0.05) in patients with single-vessel disease (n=21) than in those with multivessel disease (n=29). Sensitivity, specificity and accuracy for detecting individual diseased vessels were similar in patients without previous myocardial infarction (n=26) and in those with previous myocardial infarction (n=35). In myocardial territories related to non-infarcted areas (n=128), sensitivity and specificity in the detection of stenosed vessels were 70% and 95%, respectively. In infarcted areas (n=55), sensitivity and specificity in the detection of stenosed vessels were 85% (P=NS vs non-infarcted areas) and 75% (P<0.05 vs non-infarcted areas), respectively. Finally, sensitivity was significantly lower (P<0.05) in vascular territories supplied by vessels with moderate stenosis (50%–75%) than in those supplied by vessels with severe stenosis (>75%). The results of this study demonstrate that quantitative 1-day exercise-rest^99mTc-tetrofosmin single-photon emission tomographic imaging is a suitable and accurate technique to identify patients with CAD and to detect individual stenosed coronary vessels.     

Chick gonadogenesis following early surgical bursectomy

Left ovaries of bursectomized chick embryos were examined on the 17th day of incubation in comparison to normal and sham-operated controls, by histological and histochemical observations. The results show that in bursectomized embryos the cortex appears irregulary developed, with a significant decrease in the mean thickness and in the percentage of the secondary sex cords in the total cortical area. Furthermore, the germinal epithelium appears thicker and the subcortical medulla and the tunica albuginea more compact. The greater activity of the enzyme ⁵–3-hydroxysteroid dehydrogenase ( ⁵3HSD) found in ovaries of bursectomized embryos (histochemical method) could be related to an endocrine dismetabolism affecting the cortical development. On the basis of these results and those of other authors, some hypotheses are advanced. In particular, an action of the bursal factor on GTH receptors could be the factor responsible of the enhanced steroidogenic activity altering the hormonal environment.     

A characterization of the activity of α-1,3,5-triglycidyl-s-triazinetrione,a novel antineoplastic compound

Summary To extend initial results on the antineoplastic activity of -1,3,5-triglycidyl-s-triazinetrione (TGT, NSC 296934), a novel triepoxidic derivative, this compound was tested in a series of murine transplantable tumors. Repeated daily treatments with well-tolerated systemic doses of this chemical produced substantial retardation in tumor growth and significant prolongation of survival in the line 16 mammary, M5067 ovarian, and Madison 109 lung carcinomas and in mFS6 fibrosarcoma. Very marked activity was also seen in the P815 mastocytoma, B16 melanoma, line 38 colon carcinoma, and an intracerebrally transplanted ependymoblastoma, with high proportions of cures after one or two injections in IP transplanted SL2 lymphoma and line 26 colon carcinoma. It is concluded that the high level of antineoplastic effectiveness and the wide spectrum of TGT activity together with its novel structural characteristics could be of clinical significance.     

Hepatitis and cholestasis in infancy: clinical and nutritional aspects

A major complication of cholestasis is fat malabsorption related to decreased intestinal bile acids, which leads to malnutrition and fat-soluble vitamin deficiency. The impaired excretion of bile acids leads to a low intraluminal micellar concentration that causes long-chain triglyceride lipolysis and absorption to be ineffective. Medium-chain triglycerides (MCTs) are more readily absorbed when there are low concentrations of bile acids and therefore are a good source of fat calories; MCTs can be administered as MCT-containing formulas. In those children who are unable to take sufficient calories by mouth, it is important to start nocturnal enteral feeding to improve nutritional status. In infants with cholestasis, the absorption of fat-soluble vitamins (A, D, E and K) that require bile acids is also impaired, and supplementation is mandatory. Vitamin K deficiency may be responsible for hypoprothrombinaemia, which may lead to bleeding diathesis, Vitamin K (phytomenadione) should therefore be promptly administered intravenously, at a dose of 1 mg. Chronic vitamin E (α-tocopherol) deficiency is associated with a progressive neuromuscular syndrome that can cause cerebellar ataxia, areflexia and peripheral neuropathy. Supplements are given orally in doses of 3–5 times the normal requirement if cholestasis is incomplete. In complete cholestasis, supplements must be given intramuscularly at monthly intervals. In infants who fail to thrive, dietary supplements of carbohydrate polymers and MCTs are required.     

Soluble CD40 ligand plasma levels in lung cancer.

PURPOSE: Tumor-induced platelet activation may cause the release of various cytokines, including CD40 ligand (CD40L). Activation of the CD40/CD40L pathway in human tumors may result in thrombin generation, which is known to be involved in angiogenesis. Thus, we investigated whether soluble (s)CD40L levels are increased in patients with lung cancer as a result of platelet and/or coagulation activation. EXPERIMENTAL DESIGN: Citrated plasma samples were obtained from 120 patients with different stages and histotypes of lung cancer and 60 age- and sex-matched control subjects. sCD40L, sP-selectin (marker of platelet activation), prothrombin fragment 1 + 2, and thrombin-antithrombin III complex levels (both markers of coagulative activation) were measured in all samples. RESULTS: Patients with lung cancer had median sCD40L levels higher than in control subjects (0.46 versus 0.13 ng/ml; P < 0.0001), although correlation with the stage of disease was not evident. Nonetheless, sCD40L levels were significantly higher in squamous cancer compared with adenocarcinoma (0.75 versus 0.27 ng/ml; P < 0.05). Moreover, median sCD40L levels were higher in stage IV compared with nonmetastatic squamous lung cancer (1.02 versus 0.61 ng/ml; P < 0.05). sCD40L levels significantly correlated with sP-selectin (P < 0.001), prothrombin fragment 1 + 2 (P < 0.001), or thrombin-antithrombin III complex (P < 0.05) in squamous lung cancer, but only sP-selectin (P = 0.011) was independently related to sCD40L. CONCLUSIONS: These findings indicate that elevated sCD40L levels can be preferentially found in patients with advanced squamous cancer and provide evidence that increased levels of this cytokine are associated to the occurrence of in vivo platelet activation.     

Value of P-glycoprotein and clinicopathologic factors as the basis for new treatment strategies in high-grade osteosarcoma of the extremities.

PURPOSE: To evaluate the prognostic value of P-glycoprotein and clinicopathologic parameters in a large series of high-grade osteosarcoma (OS) patients treated at the Rizzoli Institute. PATIENTS AND METHODS: With the use of immunohistochemistry, P-glycoprotein was assessed in 149 patients with primary, nonmetastatic, high-grade OS who were homogeneously treated with chemotherapy protocols based on doxorubicin, high-dose methotrexate, and cisplatin and the addition of ifosfamide in the postoperative phase. RESULTS: P-glycoprotein positivity was found in 47 of 149 cases (32%) and was significantly associated with a higher incidence of relapse and a worse outcome, as was age younger than 12 years and tumor volume greater then 150 mL at diagnosis. Multivariate analysis further confirmed the prognostic value of these parameters, which all were independent adverse prognostic factors. Event-free survival and proportional hazards regression analyses confirmed that overexpression of P-glycoprotein at clinical onset is the most important adverse prognostic factor for high-grade OS patients treated with these chemotherapy protocols. CONCLUSION: Increased P-glycoprotein levels, together with tumor volume and age, should be taken into consideration to identify, at time of diagnosis, subgroups of OS patients with a higher risk of recurrence. This subgroup identification will constitute the basis for drawing individualized treatment protocols on the basis of risk evaluation, with the aim of using more aggressive chemotherapy, or combination chemotherapy with other adjuvants, only in those patients for which more aggressive regimens are strictly necessary and warranted.     

Conservative surgery for Stage I ovarian carcinoma in women of childbearing age

Objective To assess the results of a policy of tailored conservative surgical management for young women with stage I ovarian carcinomas.
Design Retrospective study.
Participants Ninety-nine women aged 40 years or younger who underwent either primary surgery in our department or were referred after primary surgery performed elsewhere.
Methods Of the 99 women in our study, 56 underwent fertility-sparing surgery and 43 more radical surgery. Minimal requirements for conservative management were adequate staging and complete information about the therapeutic options. Factors important in the choice of the treatment were, age, wish to preserve fertility, histologic type and grade, and the stage of the tumour.
Results Conservative treatment was conducted in 84% of nulliparous and in 33% of parous women; 62% of grade 1 tumours, 48% of grade 2, and 50% of grade 3 were treated conservatively. With a median follow up of seven years, we observed five recurrences (9%) of carcinoma in women treated conservatively and five (12%) in those treated more radically. Two women (one in each treatment arm) were saved after recurrence. Two recurrences after conservative surgery involved the residual ovary (3.6%). Two women developed borderline tumour in the contralateral ovary and both were treated by surgery.
Conclusion After adequate staging and accurate information is given to the patient, conservative treatment may be safe in some women with early ovarian cancer. The risk of recurrence in the contralateral ovary is low. Conservative surgery may be also considered in some Stage I grade 3 tumours and in some women with stage IC tumours.     

Maximum tolerable doses of intravenous zidovudine in combination with 5-fluorouracil and leucovorin in metastatic colorectal cancer patients

Background: Experimental studies have demonstrated that 5-fluorouracil(5-FU) enhances zidovudine (AZT)-induced DNA strand breaks and cytotoxicity.Phase I studies have demonstrated that the maximum tolerable dose (MTD) of AZTis 8000 mg/sqm when administered i.v. over two hours after weekly 5-FU +l-leucovorin (LV), and that this combination has promising antitumor activity.The purpose of this study was therefore to evaluate the antitumor activity ofweekly bolus 5-FU + LV + AZT, administered at its MTD, and to determinewhether 5-FU enhances AZT-induced DNA strand breaks in blood nuclear cells.Patients and methods: Twenty-nine chemotherapy-naïve metastaticcolorectalcancer patients with measurable disease entered the study to evaluate theactivity of a weekly 5-FU 500 mg/m² i.v. bolus + LV 250mg/m² i.v. two-hour infusion + AZT 8000mg/m² i.v. two-hour infusion. In 10 different patients, whoduring three different weeks received 5-FU + LV, AZT and 5-FU + LV + AZT, DNAstrand breaks in blood nuclear cells were determined by a fluorescent analysisof DNA unwinding.Results: Treatment was generally well tolerated and WHO grades III–IVtoxicities, consisting mostly of diarrhea (17%), were uncommon. Onepatient died of severe diarrhea with consequent hypokalemia and cardiacarrhythmia. All patients were considered evaluable for response, and 3(10%) complete and 10 (35%) partial responses were observed, foran objective response rate of 45% (95% confidence limit interval26%–64%). Both 5-FU + LV and AZT decreased the percentageof double stranded DNA in nuclear blood cells. The greatest effect wasobserved with 5-FU + LV + AZT, which reduced the percentage of double strandedDNA to 50% and 36% after 24 and 48 hours, respectively, and thisinteraction between 5-FU + LV and AZT was found to be cumulative.Conclusions: These studies demonstrate that the present dose and scheduleof AZT in combination with 5-FU + LV has significant activity in metastaticcolorectal cancer and that the combination of 5-FU + LV with AZT increases theamount of DNA damage. Therefore, AZT in combination with 5-FU + LV warrantsfurther study in colorectal cancer.