Synthesis and biological evaluation of certain new thiazolopyrimidines

A series of 5-methyl-3-phenyl thiazolo[5,4-e][1,2,4]triazolo[1,5-c] pyrimidin-2-thiones and 5-methyl-3-phenyl thiazolo[5,4-e]pyrimidino[3,4-b][1,2,4]triazin-2-thiones were prepared as potential antimicrobial and antitumor agents. Some of the tested compounds showed promising activity. The detailed synthesis, spectroscopic and biological data are reported.     

Treatment outcome with radiation therapy after breast augmentation or reconstruction in patients with primary breast carcinoma

BACKGROUND: Analyses were performed to determine local control and cosmetic outcome of breast carcinoma patients with prosthetically augmented or reconstructed breasts who had received radiation therapy (RT). METHODS: Twenty-one newly diagnosed breast carcinoma patients with prosthetically augmented or reconstructed breasts were treated with external beam RT. All patients received whole breast RT (median dose, 50.4 gray [Gy]) and 19 were boosted to a median dose of 60.4 Gy. A median dose of 50.4 Gy was delivered to the regional lymph nodes in 12 patients. Tissue equivalent bolus material was used in six patients. Seventeen patients received adjuvant systemic therapy. Cosmetic results were evaluated at 3-6-month intervals. RESULTS: With a median follow-up of 32 months, good/excellent cosmetic results were observed in 71% of patients (100% in those with augmented breasts and 54% in those with reconstructed breasts). Four patients (19%) with fair/poor cosmetic outcomes required implant removal and/or revision. Multiple clinical and treatment-related factors were analyzed for their impact on cosmetic outcome. A worsened cosmetic result was observed with increasing stage (P = 0.076), breast reconstruction (vs. augmentation) (P = 0.030), and bolus application (P = 0.016). All patients with fair/poor cosmetic outcomes had time intervals from implant insertion to RT ranging from 53-213 days. Two patients developed an isolated local recurrence within the augmented breast. CONCLUSIONS: Patients with prosthetically augmented breasts can undergo RT and expect good/excellent cosmetic results. Patients with reconstructed breasts are at a significantly greater risk for cosmetic failure. This risk may be related to the higher percentage of patients with advanced disease, those who received bolus application, and those who received earlier delivery of RT (after the cosmetic procedure) in reconstructed breasts.     

Mammary ductal carcinoma in situ with microinvasion

BACKGROUND: The natural history of patients with intraductal carcinoma (DCIS) and microinvasion is poorly defined, and the clinical management of these patients, with particular reference to management of the axilla, has been controversial. Previous studies of this lesion have used varied and/or arbitrary criteria for the evaluation of microinvasion. METHODS: Thirty-eight DCIS lesions with microinvasion (n=29) or probable microinvasion (n=9), diagnosed during the period 1980-1996, were retrospectively analyzed after cases not treated with mastectomy and axillary lymph node dissection were excluded. Microinvasion was defined as a single focus of invasive carcinoma < or = 2 mm or up to 3 foci of invasion, each < or =1 mm in greatest dimension. RESULTS: The patients were all females with a mean age of 56.4 years. DCIS was of comedo (n=31) or papillary (n=7) subtype. Microinvasion was often associated with an altered, desmoplastic stroma (55%) or a lymphocytic infiltrate (39%). The foci of microinvasion ranged from 0.25 to 1.75 mm (mean, 0.6 mm), with an aggregate mean size of 1.1 mm (range, 0.25-2.25 mm). Foci of microinvasion, ranging from 1 to 3 (mean, 1.7), were adjacent to DCIS in 95.3% of cases. The extent of DCIS did not correlate with the number of foci of microinvasion. Axillary lymph node dissections yielded a mean of 19.3 lymph nodes (range, 7-38), and all lymph nodes were negative for metastasis. None of 33 patients, followed for a mean of 7.5 years (range, 1.0-14.4 years), developed local recurrence or metastasis. CONCLUSIONS: The cases of microinvasive carcinoma examined in this study, as defined above, were not associated with axillary lymph node metastases and appeared to be associated with an excellent prognosis. Further study is indicated to determine the appropriate management and long term prognosis of patients with this lesion.     

Maternal depressive disorder and contextual risk: contributions to the development of attachment insecurity and behavior problems in toddlerhood

Research has shown that offspring of depressed caregivers are at increased risk for maladaptive development and emotional difficulties. Specifically, infants and toddlers of depressed mothers have been shown to evidence higher percentages of insecure attachments and more behavioral difficulties than offspring of nondisordered mothers. However, even in studies that reveal significant differences between children of depressed and nondepressed caregivers, a substantial number of children with depressed caregivers do not evidence dysfunction. Such findings have resulted in increased attention to the broader social context in which children of depressed mothers develop. This investigation examined the direct influences of maternal depression on child development, as well as the role of contextual risks that may be particularly heightened in families with depressed parents. Toddlers with depressed mothers evidenced significantly more insecure attachments than did toddlers with nondisordered mothers, and this difference was not accounted for by contextual risk. In predicting child behavior problems, contextual risk was found to mediate the relation between maternal depression and child behavior problems. Father-report data on child behavior corroborated the mother report data. Results are discussed in terms of the diversity of functioning in offspring of depressed caregivers that can be attributed to varied levels of contextual risk accompanying depression.     

Presence of genomes of phage PBV-1 in the mycelia of the fungus Penicillium brevi-compactum

Progressive systemic sclerosis may be associated with focal myocardial fibrosis. Electrocardiographic abnormalities including conduction block are common in progressive systemic sclerosis but whether they are due to direct destruction of the specialized conduction tissue of the heart is uncertain. The conduction systems of 35 patients with progressive systemic sclerosis were studied. Of these 35 patients, 17 (50 per cent) had myocardial fibrosis of the type seen in progressive systemic sclerosis. In 10 of the 17, it was severe. Sinus node fibrosis was present in 13 patients and was nearly as frequent in those with as in those without the progressive systemic sclerosis myocardial lesion. Overlying pericarditis may have contributed to the fibrotic changes within the sinoatrial nodes in seven of the 13 patients. The atrioventricular node and main His bundles were normal. However, fibrotic changes were found in the proximal bundle systems in six patients. In three of the six, severe myocardial progressive systemic sclerosis was present, two had focal fibrous atrophy of the left bundle, and one had complete interruption of the right bundle. In only the latter patient was this reflected in the electrocardiogram which showed a right bundle branch block. Three patients without progressive systemic sclerosis myocardial lesions also had fibrous atrophy of a portion of the proximal left bundle branch, and in one the electrocardiogram showed an isolated left anterior hemiblock. Thus, morphologic abnormalities within the conduction system in our patients are difficult to attribute to progressive systemic sclerosis per se. Furthermore, although conduction abnormalities were more frequent in patients with myocardial disease, specific conduction system disease was not the cause in most patients. As has been noted in ischemic heart disease, the conduction system appears to be relatively spared from the myocardial changes of progressive systemic sclerosis, and the high incidence of conduction disturbances in this condition may be a consequence, rather, of damage to working myocardium.