A mouse model for Luminal epithelial like ER positive subtype of human breast cancer

Background  

Generation of novel spontaneous ER positive mammary tumor animal model from heterozygous NIH nude mice.     

Bouveret's syndrome: A rare complication of cholecystolithiasis

Bouveret's syndrome is obstruction of the stomach or the duodenum from a gallstone that has migrated through a biliogastric or bilioduodenal fistula. This rare syndrome has been described in a number of case reports     

Treatment recommendations in patients diagnosed with high‐risk cutaneous squamous cell carcinoma

Non‐melanoma cutaneous cancers occur at an epidemic rate in Australia. With an ageing population, more Australians will develop these cancers and at an increasing rate. In the majority of cases local treatment is highly curative. However, a subset of the population will be diagnosed with a high‐risk cutaneous squamous cell carcinoma. These can be defined as patients at risk of having subclinical metastases to regional lymph nodes based on unfavourable primary lesion features (including inadequately excised and recurrent lesions), patients with metastatic squamous cell carcinoma to regional lymph nodes, and squamous cell carcinoma in immunosuppressed patients. The mortality and morbidity associated with high‐risk cutaneous squamous cell carcinoma is usually as a consequence of uncontrolled metastatic nodal disease and, to a lesser extent, distant metastases. Radiotherapy has an essential role in treating these patients and in many cases the addition of adjuvant radiotherapy may be life saving. It is therefore important that all clinicians treating skin cancers have an understanding and awareness of the optimal approach to these patients. The aim of this article is to present treatment recommendations based on an overview of the current published literature.     

The significance of soluble interleukin-2 receptor in monitoring disease relapse in patients with nasopharyngeal cancer

BACKGROUND: Soluble interleukin-2 receptor alpha (sIL-2R alpha) is a well-known indicator of T-cell activation noted to be increasing in nasopharyngeal cancer. However, the significance of sIL-2R alpha in monitoring disease relapse is unclear. This study was initiated to address this issue. METHODS: Serum of 56 patients with NPC, which underwent either primary, salvage, or palliative treatments, from 1992 to 1993 at the Cancer Center, Veterans General Hospital-Taipei, were collected from our serum bank. According to their disease status at the time of study, at least two years after last treatments, the 56 patients were divided into four groups. The remission group represented those in remission at the time of study (n = 24). The metastasis group represented those with distant metastasis present at the time of study (n = 17). The recurrence group represented those with locoregional recurrence present at the time of study (n = 11). The combined group represented those with locoregional recurrence as well as distant metastasis (n = 4). The seral sIL-2R alpha concentrations of the 56 NPC patients were determined with enzyme-linked immunoabsorbent assay. The combined group was excluded in our statistical analysis. We performed statistical analysis on the differences of paired serum sIL-2R alpha concentrations between different periods of the diseases. The first analysis was on the differences of sIL-2R alpha concentrations between diagnosis and post-radiotherapy periods for 13 out of 24 patients in the remission group and 7 out of 11 patients in the recurrence group. The second analysis was on the differences of sIL-2R alpha concentration between follow-up before detection-of-relapse and after detection-of-relapse for 5 out of 17 patients in the metastasis group and six out of 11 patients in the recurrence group. RESULTS: The first statistical analysis revealed no significant differences of sIL-2R alpha concentrations for the remission group (P = 0.946) and the recurrence group (P = 0.156) between diagnosis and post-radiotherapy periods. The second statistical analysis revealed no significant differences of sIL-2R alpha concentrations between before and after detection-of-relapse for the recurrence group, neither (P = 0.438). The results for the metastasis group were different. The sIL-2R alpha concentrations were shown to increase after the detection of metastasis for the 5 paired samples from the metastasis group, although the Wilcoxon signed ranks test on the differences only showed borderline significance (P = 0.063). CONCLUSIONS: Our findings show that sIL-2R alpha would be of no value in monitoring the development of locoregional recurrence but might be useful in monitoring distant metastasis. Although our current limited data did not provide strong support for the role of sIL-2R alpha in monitoring metastasis, it might be delineated in the future by collecting more data.      

Measurement of cytochrome P450 2A6 and 2E1 gene expression in primary human bronchial epithelial cells

Bronchogenic carcinomas arise from bronchial epithelial cells (BECs). Inhalation exposure of BECs to nitrosamines in cigarette smoke is an important exogenous risk factor for malignant transformation of BECs. Thus, an important endogenous risk factor is likely to be the capacity of BECs to metabolize nitrosamines. Among the cytochrome P450 enzymes capable of metabolizing nitrosamines, CYP2A6, CYP2E1 and CYP2B6 are expressed in BECs. In this study, we used quantitative RT-PCR to evaluate expression of CYP2A6 and CYP2E1 in primary human BECs from 12 non-smokers and eight smokers. CYP2A6 was expressed in 20/20 cases and quantifiable in 18/20 cases, with a mean level of 580 mRNA/10(6) beta- actin mRNA. CYP2E1 expression was observed in 9/20 cases, but in all cases it was expressed at levels below our limit of quantification (10 mRNA/10(6) beta-actin mRNA). There was significant (P < 0.05) 20-fold inter-individual variation in expression of CYP2A6. Further, the mean level of CYP2A6 among smokers (260 mRNA/10(6) beta-actin mRNA) was significantly lower than among non-smokers (740 mRNA/10(6) beta-actin mRNA). It is hypothesized that: (i) inter-individual variation in CYP2A6 gene expression may contribute to inter-individual variation in risk for bronchogenic carcinoma; (ii) smoking may reduce the level of expression of CYP2A6 in the BECs of some individuals; and (iii) CYP2A6 is more important than CYP2E1 for metabolic activation of nitrosamines in bronchial epithelial cells.      

Comparison of two strategies for surfactant prophylaxis in very premature infants: a multicenter randomized trial

INTRODUCTION: Previous trials of surfactant therapy in premature infants have demonstrated a survival advantage associated with prophylactic therapy as an immediate bolus, compared with the rescue treatment of established respiratory distress syndrome. The optimal strategy for prophylactic therapy, however, remains controversial. When administered as an endotracheal bolus immediately after delivery, surfactant mixes with the absorbing fetal lung fluid and may reach the alveoli before the onset of lung injury. This approach, however, causes a brief delay in the initiation of standard neonatal resuscitation, including positive pressure ventilation, and is associated with a risk for surfactant delivery into the right main stem bronchus or esophagus. As an alternative approach, surfactant prophylaxis may be administered in small aliquots soon after resuscitation and confirmation of endotracheal tube position. Although this strategy has substantial logistical advantages in clinical practice, its efficacy has not been established. OBJECTIVE: The purpose of this study was to determine whether the established benefits of the immediate bolus strategy for surfactant prophylaxis could still be achieved using a postventilatory aliquot strategy after initial standard resuscitation and stabilization. DESIGN: Multicenter randomized clinical trial with patients randomized before delivery to immediate bolus or postventilatory aliquot therapy. PARTICIPANTS: Inborn premature infants delivered to mothers at an estimated gestational age of 24[0/7] to 28[6/7] weeks. INTERVENTIONS: Those infants who were randomized to the immediate bolus strategy were intubated as rapidly as possible after birth, and a 3-mL intratracheal bolus of calf lung surfactant extract (Infasurf) was administered before the initiation of positive pressure ventilation. Those infants who were randomized to the postventilatory aliquot strategy received standard resuscitation measures with intubation by 5 minutes of age, if not required earlier. At 10 minutes after birth, 3 mL of surfactant was administered in 4 divided aliquots of 0.75 mL each. Patients in both groups were eligible to receive up to three additional doses of surfactant as rescue therapy in the neonatal intensive care unit, if needed. OUTCOME MEASURES: The primary outcome variable was survival to discharge to home. Secondary variables included neonatal complications and requirement for oxygen therapy at 36 weeks' postmenstrual age. RESULTS: Among three centers, 651 infants were enrolled and randomized before delivery. Survival to discharge to home was similar for the two strategies for surfactant therapy as prophylaxis: 76% for the immediate bolus group and 80% for the postventilatory aliquot group. In a secondary analysis, the rate of supplemental oxygen administration at 36 weeks' postmenstrual age was 18% for the immediate bolus group and 13% for the postventilatory aliquot group. CONCLUSIONS: Survival to discharge to home was similar with immediate bolus and postventilatory aliquot strategies for surfactant prophylaxis. Because of its logistical advantages in the delivery room and its beneficial effects on prolonged oxygen requirements, we recommend the postventilatory aliquot strategy for surfactant prophylaxis of premature infants delivered before 29 weeks' gestation.     

Foot pathology in insulin dependent diabetes

OBJECTIVES--Foot pathology is a major source of morbidity in adults with diabetes. The aim of this study was to determine if children with insulin dependent diabetes have an increased incidence of foot pathology compared with non-diabetic children. DESIGN--Questionnaire, clinical examination, and biomechanical assessment. SUBJECTS--67 diabetic children and a comparison group matched for age, sex, and social class. RESULTS--We found significantly more foot pathology in the children with diabetes (52 children) than the comparison group (28 children); with more biomechanical anomalies (58 children with diabetes, 34 comparison group); and a higher incidence of abnormal skin conditions (53 children with diabetes, 27 comparison group). Forty two children with diabetes had received foot health education compared with 27 in the comparison group, but the study revealed ignorance and misconceptions among the diabetic group, and previous contact with a podiatrist was minimal. CONCLUSIONS--The survey suggests that children with diabetes have an increased incidence of foot pathology justifying greater input of podiatric care in the hope of preventing later problems.     

The role of radiation therapy in Gravesophthalmopathy ‘

Gravesophthalmopathy ‘ can occur in 25–30% of patients with hyperthyroidism. This condition can result in serious visual disturbance and disfigurement. The treatment options for symptomatic disease are oral corticosteroids or orbital irradiation. Ten patients with Gravesophthalmopathy ‘ were treated with external beam radiotherapy at Saint Lukes Hospital from March 1991 to February 1994. Eight of these patients had excellent response with minimal morbidity. We believe that orbital radiotherapy is effective and well tolerated, and should replace corticosteroid therapy as the initial treatment modality in these patients.