Effect of treatment sequence with radiotherapy and the antiestrogen EM 800 on the growth of ZR 75 1 human mammary carcinoma in nude mice

We demonstrated previously that continuous administration of EM-800, a SERM having pure antiestrogenic activity in the mammary gland and endometrium in combination with monthly radiotherapy caused a greater inhibition of human ZR 75 1 tumor growth in nude mice than either therapy used alone. To further optimize therapy, we have now examined the effect of various treatment sequences to determine the optimal treatment regimen in the same model. EM 800 was given at the maximally effective oral dose of 300 microg daily. External beam radiation therapy (RTX) was carried out (2 Gy/tumor/day, 5 days per week for 3 weeks) for a total of 30 Gy/tumor delivered directly to the tumor while shielding the rest of the animal body. There was no evidence of RTX-related morbidity. Continuous treatment with EM 800 was initiated either 3 weeks before or at the same time as RTX, immediately after RTX, or 3 weeks before and immediately after RTX. After 156 days of treatment, EM 800 alone caused a 75% decrease in average tumor area, an effect equivalent to that achieved by ovariectomy. RTX alone, on the other hand, caused a transient 30% decrease in tumor area regardless of treatment sequence, whereas combined treatment with EM 800 and RTX was superior to either treatment alone. Combined treatment with EM 800 and RTX both started on Day 1 caused the greatest (88%), most rapid (50% in 2 weeks) and sustained decrease in tumor size. The present data indicate that optimal reduction in breast tumor size is achieved by continuous administration of EM 800 and RTX started simultaneously on Day 1.     

Precise intraoperative location of gastrointestinal bleeding with a hand-held counter. Work in progress

The nuclear medicine bleeding scan is frequently insufficient to locate sites of bleeding precisely, in spite of its great sensitivity. A small, hand-held Geiger-Müller counter, placed directly on exposed intestine in the operating room, enables precise location of the probable bleeding site. In three patients, the technique allowed a minimal amount of intestine to be resected, distinguished between large- and small-intestinal hemorrhage, and eliminated other foci as sites of bleeding.     

Utility of thromboelastography and/or thromboelastometry in adults with sepsis: a systematic review

Introduction

Coagulation abnormalities are frequent in sepsis. Conventional coagulation assays, however, have several limitations. A surge of interest exists in the use of point-of-care tests to diagnose hypo- and hypercoagulability in sepsis.We performed a systematic review of available literature to establish the value of rotational thromboelastography (TEG) and thromboelastometry (ROTEM) compared with standard coagulation tests to detect hyper- or hypocoagulability in sepsis patients. Furthermore, we assessed the value of TEG/ROTEM to identify sepsis patients likely to benefit from therapies that interfere with the coagulation system.

Methods

MEDLINE, EMBASE, and the Cochrane Library were searched from 1 January 1980 to 31 December 2012. The search was limited to adults, and language was limited to English. Reference lists of retrieved articles were hand-searched for additional studies. Ongoing trials were searched on http://www.controlled-trials.com and http://www.clinicaltrials.gov. Studies addressing TEG/ROTEM measurements in adult patients with sepsis admitted to the ICU were considered eligible.

Results

Of 680 screened articles, 18 studies were included, of which two were randomized controlled trials, and 16 were observational cohort studies. In patients with sepsis, results show both hyper- and hypocoagulability, as well as TEG/ROTEM values that fell within reference values. Both hyper- and hypocoagulability were to some extent associated with diffuse intravascular coagulation. Compared with conventional coagulation tests, TEG/ROTEM can detect impaired fibrinolysis, which can possibly help to discriminate between sepsis and systemic inflammatory response syndrome (SIRS). A hypocoagulable profile is associated with increased mortality. The value of TEG/ROTEM to identify patients with sepsis who could possibly benefit from therapies interfering with the coagulation system could not be assessed, because studies addressing this topic were limited.

Conclusion

TEG/ROTEM could be a promising tool in diagnosing alterations in coagulation in sepsis. Further research on the value of TEG/ROTEM in these patients is warranted. Given that coagulopathy is a dynamic process, sequential measurements are needed to understand the coagulation patterns in sepsis, as can be detected by TEG/ROTEM.     

Immediate food hypersensitivity reactions on the first known exposure to the food

We report 8 infants with immediate hypersensitivity reactions to foods (milk, egg, or peanut), occurring at the first-known exposure. Each developed symptoms within the first hour, but these generally settled within 2 hours. Sensitisation to the food concerned was demonstrated by positive immediate allergen skin prick tests in every case. Symptoms experienced included irritability, erythematous rash, urticaria, angio-oedema, vomiting, rhinorrhoea, and cough. Five infants were being followed prospectively and 4 were clinically tolerant of the food by age 16 months. The most likely route of sensitisation was via breast milk. None of the infants experienced similar reactions while being breast fed, suggesting that the reaction was dose dependent. As 5 out of a group of 80 infants being followed prospectively developed an immediate reaction at their first known exposure to a food, this appeared to be a not uncommon presentation of food hypersensitivity in infancy.     

Growth hormone resistance in uremia

Growth retardation is a major complication in children with uremia. Protein restriction, calorie deficit, metabolic acidosis, renal osteodystrophy, and endocrinologic disturbances contribute to the growth failure. The effect of these factors on growth retardation can be attenuated in part by therapy with vitamin D metabolites, adequate nutrition, alkalization, and dialysis. Linear growth in children with uremia is markedly retarded despite normal or increased levels of circulating serum growth hormone. An increased growth hormone level in children with uremia is due to normal growth hormone secretion from the pituitary gland and impaired growth hormone clearance in the kidney. However, the elevated growth hormone level does not lead to a commensurate rise in serum insulin-like growth factor I (IGF-I); the serum IGF-I level is decreased or normal in relation to the degree of renal failure. This discrepancy suggests growth hormone resistance in the liver in uremia. Recent molecular techniques open a new era in studying the gene expression for growth hormone or IGF-I. There is no doubt today that growth hormone treatment has the beneficial effect of growth promotion in children with uremia, which also suggests endogenous growth hormone resistance in target organs or target cells in uremia.