Interval between insulin injection and breakfast in diabetes

The relationship between the insulin-breakfast interval, postprandial increase in blood glucose, and glycaemic control was studied in 58 children with diabetes. Patients recorded insulin-breakfast intervals in a home diary over a seven day period, and during a 24 hour period at the weekend provided eight serial capillary dried blood spots for glucose analysis. The highest mean blood glucose value occurred two hours after breakfast and showed a significant correlation with fructosamine concentrations. Weekend insulin-breakfast intervals ranged from 2-30 minutes, with 70% reporting intervals of less than 15 minutes. There was a significant correlation between the weekend insulin-breakfast interval and the after breakfast increase in blood glucose with a mean increment of 0.4 mmol/l in the 30 minute group and 7.2 mmol/l in the 2 minute group. Over the whole study period, children with mean insulin-breakfast intervals of two to 12 minutes had a mean fructosamine concentration of 376 mumol/l compared with 341 mumol/l in those with intervals of 15-35 minutes. This study has shown that the interval between insulin injection and breakfast significantly influences the morning postprandial rise in blood glucose and consequently short term glycaemic control. It is therefore important that patients are encouraged to leave an interval of about 30 minutes between insulin injection and breakfast.     

Analysis of clinicopathologic prognostic factors for 157 uterine sarcomas and evaluation of a grading score validated for soft tissue sarcoma

BACKGROUND: Uterine sarcomas (US) are rare and carry a poor prognosis characterized by high rates of local recurrence and metastasis. The aim of this study was to test, for what the authors believe was the first time with US, the prognostic impact of the histologic grade validated by the French Federation of Anticancer Centers (FNCLCC) for soft tissue sarcomas (STS). The grade is the sum of the scores allocated for three major histologic criteria: tumor differentiation, mitotic count, and tumor necrosis. Other histologic and clinical factors were tested as well. METHODS: The study included 157 patients in whom 78 leiomyosarcomas (LMS), 52 malignant mixed müllerian tumors (MMMT), and 27 endometrial stroma sarcomas (ESS) were documented. RESULTS: The median follow-up was 54 months (range, 6-230 months). The median OS and EFS were 33 and 13 months, respectively. The FNCLCC grade validated in soft tissue sarcomas was not a prognostic factor for survival or relapse for any of the US histologic subtypes. For LMS, stage and mitotic count were the only factors that had an influence on survival and relapse. For MMMT, stage and age were the only prognostic factors, and none of the histologic criteria impacted on the outcome. For ESS, the grade defined by Norris and Taylor was an important prognostic factor, particularly for survival. CONCLUSIONS: The FNCLCC grading score could not be used as a prognostic indicator for uterine sarcomas. The diagnosis of US is in itself an unfavorable prognostic factor, except when the diagnosis is low grade ESS.     

High-dose-rate endobronchial brachytherapy effectively palliates symptoms due to airway tumors: the 10-year M. D. Anderson cancer center experience

PURPOSE: To evaluate the toxicity and efficacy of Iridium-192 high-dose-rate (HDR) endobronchial brachytherapy (EBBT) for the palliation of symptoms caused by relapsed or persistent endobronchial tumors. METHODS AND MATERIALS: We reviewed the treatment outcomes between 1988 and 1997 in 175 lung cancer patients who underwent HDR EBBT for recurrent or metastatic tumors at The University of Texas M. D. Anderson Cancer Center. One hundred sixty of these patients had previously received thoracic external-beam irradiation. This updated report includes 74 patients from a previous series. Most patients received 3,000-cGy EBBT delivered at a distance of 6 mm and divided into 2 fractions over 2 weeks. Subjective response was assessed by questionnaire at follow-up. Objective response was assessed by physical examination, bronchoscopy, and chest radiograph. RESULTS: The median actuarial survival for the entire group was 6 months from the time of the first EBBT treatment session. Of the 115 patients (66%) who showed symptomatic improvement, 32% were much improved and 34% were slightly improved. Patients showing improvement survived for significantly longer than those who showed no change or worsening symptoms (7 vs. 4 months, p = 0.0032). Repeat bronchoscopy demonstrated a 78% overall objective response rate that correlated significantly with subjective response and symptom relief. Complications occurred in 19 patients (11% crude rate) with an actuarial complication rate of 13% at 1 year from the time of the first EBBT treatment session. The actuarial hazard for fatal hemoptysis due to EBBT was 5%. CONCLUSION: HDR EBBT effectively palliates most patients' symptoms caused by endobronchial lesions. This relief correlates significantly with an overall survival benefit. Treatment complications appear to be few, even for patients who have received prior external-beam irradiation.     

Colorectal hemangioma: radiologic findings

The authors correlated radiographs with the clinical and histologic data of 12 patients with colorectal hemangioma. All patients presented with rectal bleeding, which was chronic in seven. Phleboliths were also visible in seven cases, which correlated with chronic bleeding in five. On barium studies, three masses were soft and three produced rigid narrowing. The atypical features of rigid luminal narrowing, which might mimic a carcinoma, and hypovascularity correlated with chronic bleeding or visible phleboliths, which suggest the correct diagnosis of colorectal hemangioma.     

Early human thymocyte proliferation is regulated by an externally controlled autocrine transforming growth factor-beta 1 mechanism

Early thymocytes undergo extensive proliferation after their entry into the thymus, but cellular interactions and cytokines regulating this intrathymic step remain to be determined. We analyzed the effects of various T-cell growth factors and cellular interactions on in vitro proliferation of early CD2+CD3/TCR-CD4-CD8- (triple negative [TN]) human thymocytes. Freshly isolated TN cells were then assayed for their growth capacity after incubation with CD2I+III-monoclonal antibody (MoAb), recombinant human interleukin-2 (IL-2), IL-7, and/or IL-4. These cells displayed significant proliferative responses with IL-4, IL- 7, or CD2-MoAb+IL-2. The addition of recombinant transforming growth factor beta (TGF beta) or autologous irradiated CD3+CD8+CD4- cells to TN cell cultures dramatically decreased their growth responses to IL-2 and IL-7, whereas IL-4-induced proliferation was less sensitive to growth inhibition. We thus asked whether the CD8+ cell-derived inhibitory effect was due to TGF beta. The addition of neutralizing anti-TGF beta MoAb completely abolished CD8+ cell-derived inhibition of TN cell growth. Analysis of CD8+ cell-derived supernatants indicated that these cells had low TGF beta 1 production capacity, whereas TN cells secrete significantly high levels of TGF beta 1. Cell fixation studies showed that TN cells were the source of the TGF beta. TGF beta 1 released from TN cells was in the latent form that became the active inhibitory form through interaction of TN cells with CD8+ cells. Together, these data suggest a role for TGF beta 1 as an externally controlled, autocrine inhibitory factor for human early thymocytes, with a regulatory role in thymic T-cell output.     

Concomitant chemoradiation in patients with cervix cancer

Cervical cancer is the 2nd most common cancer among women, behind breast cancer. Concomitant chemoradiation has been assessed in more than 15 randomised clinical trials. A meta-analysis for overall survival showed a statistically significant difference in favour of chemoradiotherapy: relative risk (RR) = 1.20, 95% confidence interval (CI) = 1.14-1.26, p < 0.001, p hetero = 0.21). Disease-free survival was also statistically significantly higher in favour of chemoradiotherapy: RR = 1.26, 95%CI = 1.17-1.35, p < 0.001). The benefit was more pronounced in trials including a higher proportion of stage I and II patients. Concomitant chemoradiotherapy showed a significant benefit for both local control and distant metastasis. Gastrointestinal and haematological toxicities were significantly more frequent in the chemoradiotherapy group. Details of late toxicity were sparse and therefore it was not possible to conclude on an increase of late complication rate with concomitant chemoradiotherapy. The inclusion criteria were not the same in all the trials, resulting in populations with varying distributions in disease stages. In addition, the treatment schemas for both radiotherapy and chemotherapy used in these trials were different. These results were obtained with chemotherapy based on various molecules, including cisplatin, either alone or with other cytotoxic drugs, such as 5-fluorouracil. For a similar level of benefit, the combination of cisplatin, 5-fluorouracil and hydroxyurea was more toxic than cisplatin alone in one trial in which the two protocols were compared. Future randomised trials should also aim to establish optimal chemotherapy regimens for combination with radiotherapy.     

Comparison of molecular abnormalities in bronchial brushings and tumor touch preparations

BACKGROUND: Preneoplastic lung lesions and early-stage lung carcinomas are associated with molecular abnormalities. The authors performed a pilot study to evaluate the use of DNA fluorescence in situ hybridization (FISH) probes to ascertain whether these biomarkers can predict nonsmall cell lung carcinoma (NSCLC). METHODS: Fourteen bronchial brushings ipsilateral to the tumor (BB/Ts), tumor touch imprints, and touch imprints of the bronchus adjacent to the tumor obtained from 15 patients with early-stage NSCLC were analyzed. The LAVysion multicolor probe set consisting of probes to 5p15, 6, 7p12, and 8q2 and the in-house probes 3p22.1 and 10q22 was used. Using the LAVysion multicolor probe set, 25 epithelial cells were counted and considered positive if > 5 cells were abnormal. Using 3p22.1 and 10q22, > or = 100 nuclei per slide were scored. The results were tabulated as the percentage of cells with deletions compared with the centromeric probes 3 and 10. Greater than 2% of the deletions were positive for 3p22.1 and 10q22. Bronchial washings from patients without lung tumors were used as controls. RESULTS: The BB/Ts were negative for malignant cells by cytologic evaluation and the LAVysion probe set; however, the combined in-house probes for 3p22.1 and 10q22 tested on BB/Ts predicted cancer in 100% of cancer patients. FISH positivity in the lung cancers was 100% for 3p22.1 deletions, 79% for 10q22 deletions, and 57% for LAVysion probes. When compared with the bronchial epithelium, tumor cells showed a 3.7-fold excess of 3p22.1 deletions, a 2-fold excess of 10q22 deletions, and a 12.6-fold excess of abnormal cells. CONCLUSIONS: The current study indicated that detection of molecular abnormalities in bronchial epithelial cells via FISH was very useful in identifying patients at high risk for developing lung carcinoma. The molecular abnormalities identified in the BB/Ts were detected at elevated levels in the tumor specimens.     

Anatomy of pelvic and para-aortic nodal spread in patients with primary fallopian tube carcinoma

BACKGROUND: To describe characteristics of patients with nodal spread and the anatomy of pelvic and para-aortic node involvement in primary fallopian tube carcinoma. STUDY DESIGN: Between 1985 and 2003, 19 women with primary fallopian tube carcinoma underwent systematic bilateral pelvic and para-aortic lymphadenectomy up to the level of the left renal vein. Initial lymphadenectomy (without chemotherapy) was performed in 6 patients and in 13 patients lymphadenectomies were performed after chemotherapy at the time of second-look operation. RESULTS: Nine patients had nodal involvement: four in the pelvic area and eight in the para-aortic nodes. Two, one, and six patients had stages I, II, or III disease, respectively. When para-aortic nodes were involved, the left para-aortic chain above the level of the inferior mesenteric artery was the site most frequently involved (six patients). CONCLUSIONS: In patients with primary tubal carcinoma, the left para-aortic chain above the level of the inferior mesenteric artery is the most frequently involved. Lymphadenectomy should involve all pelvic and para-aortic chains up to the level of the left renal vein, even in patients with stage I disease.     

Reproducibility and validity of a Yan-style portable citric acid cough challenge

Although many different methods of measuring cough reflex sensitivity have been published, few are simple enough to use outside of a hospital or laboratory environment. The aim of this study was to develop a simple, quick, and portable cough challenge, assess its reproducibility, and compare its results with those measured by an existing established hospital protocol. Twenty-five volunteers performed cough challenges based on an established hospital dosimeter protocol, and, on a separate occasion, by a protocol inhaling citric acid from DeVilbiss 40 hand-held nebulisers (citric acid concentrations of 10-3000 mM). Reproducibility of the hand-held cough challenge was assessed in 11 volunteers. Cough thresholds were consistently higher by the hand-held method than by the hospital dosimeter method. The geometric mean citric acid concentrations causing two coughs (threshold D2) were 3.14 and 2.77 log mM, respectively (p<0.001). The geometric mean (95% CI) difference between the tests was 0.51 log mM (0.18-0.83) of the average of the two values. Cough D2 thresholds attained by the two techniques did, however, show significant correlation (r=0.95, p<0.0001). The coefficient of repeatability for the hand-held method was 0.40 log mM. Administering citric acid from DeVilbiss 40 hand-held nebulisers offers a rapid, portable, and reproducible cough challenge in healthy volunteers. The results correlate well with an existing Mefar dosimeter challenge, but give two to three times greater cough thresholds.