Efficacy of esmolol in the treatment and transfer of patients with supraventricular tachyarrhythmias to alternate oral antiarrhythmic agents

The efficacy and safety of esmolol, a titratable intravenous beta-adrenergic blocking agent with a short elimination half-life (t 1/2 = 9.0 min) was evaluated in a multicenter open-label study for the treatment of supraventricular tachyarrhythmias (heart rate greater than 100 bpm). The study also investigated the feasibility of transferring patients from esmolol to alternate oral antiarrhythmic agents without loss of therapeutic response. Of the 113 patients studied, 95 (84%) achieved therapeutic response (reduction in heart rate of 15% or more or conversion to sinus rhythm). Most of these patients (93%) achieved the therapeutic response at esmolol doses of 200 micrograms/kg/min or lower. Transfer from esmolol to an oral antiarrhythmic agent(s) was studied in 76 patients. Alternate antiarrhythmic agents used in this study were digoxin (N = 25), propranolol (N = 21), verapamil (N = 10), metoprolol (N = 11), quinidine (N = 2), and a combination of two antiarrhythmic agents (N = 7). Sixty-seven (88%) patients were successfully transferred to oral antiarrhythmic agents without loss of the therapeutic response obtained with esmolol. The most frequent adverse effect observed during the study was hypotension, which resolved quickly (16 +/- 14 min) either by decreasing the dose or by discontinuation of esmolol infusion. This study supports previous observations concerning the safety and efficacy of esmolol in the treatment of supraventricular tachyarrhythmias. Furthermore, it demonstrates that the majority of patients successfully treated with esmolol can be safely and effectively transferred to oral therapy with alternate antiarrhythmic agents.     

Progression and resolution of changes in pulmonary function and structure due to pulmonary microembolism and blood transfusion.

It was the purpose of this research to define the progression over several days of changes in pulmonary function and structure and to document the phases of recovery following transfusions to dogs of sublethal quantities of stored blood containing microaggregates. Ten dogs underwent partial exchange transfusions averaging 60% of blood volume through standard blood transfusion filters. Average screen filtration pressure (SFP) of the blood was 85 mm Hg. Pulmonary hypertension did not develop, but there were striking decreases in O2 consumption, increases in Qs/Qt and decreases in Do2. Changes became progressively more marked over the first 48 to 72 hours after the transfusions. Pulmonary function of surviving animals returned nearly to normal by the sixth day after transfusions. Pathologic examinations of the lungs of animals sequentially sacrificed over 6 days showed intravascular microemboli, alveolar cell hyperplasia and interstitial and alveolar pulmonary edema. Progressive recovery was associated with progressive resolution of all detrimental changes. In 6 animals exchange transfused 100% of their blood volumes through dacron wool (Swank) filters and in three control animals that were not transfused, there were no significant changes in pulmonary function or structure. These experiments define the progression of deterioration and recovery over 6 days of pulmonary function in dogs after sublethal pulmonary microembolism occurring during blood transfusion.     

High frequency and allele‐specific differences of BRCA1 founder mutations in breast cancer and ovarian cancer patients from Belarus

Bogdanova NV, Antonenkova NN, Rogov YI, Karstens JH, Hillemanns P, Dörk T. High frequency and allele‐specific differences of BRCA1 founder mutations in breast cancer and ovarian cancer patients from Belarus. Breast cancer and ovarian cancer are common malignancies in Belarus accounting for about 3500 and 800 new cases per year, respectively. For breast cancer, the rates and age of onset appear to vary significantly in regions differentially affected by the Chernobyl accident. We assessed the frequency and distribution of three BRCA1 founder mutations 5382insC, 4153delA and Cys61Gly in two hospital‐based series of 1945 unselected breast cancer patients and of 201 unselected ovarian cancer patients from Belarus as well as in 1019 healthy control females from the same population. Any of these mutations were identified in 4.4% of the breast cancer patients, 26.4% of the ovarian cancer patients and 0.5% of the controls. In the breast cancer patients, BRCA1 mutations were strongly associated with earlier age at diagnosis, with oestrogen receptor (ER) negative tumours and with a first‐degree family history of breast cancer, although only 35% of the identified BRCA1 mutation carriers had such a family history. There were no marked differences in the regional distribution of BRCA1 mutations, so that the significant differences in age at diagnosis and family history of breast cancer patients from areas afflicted by the Chernobyl accident could not be explained by BRCA1. We next observed a higher impact and a shifted mutational spectrum of BRCA1 in the series of Byelorussian ovarian cancer patients where the three founder mutations accounted for 26.4% (53/201). While the Cys61Gly mutation appeared underrepresented in ovarian cancer as compared with breast cancer cases from the same population (p = 0.01), the 4153delA mutation made a higher contribution to ovarian cancer than to breast cancer (p < 0.01). BRCA1 mutations were significantly enriched among ovarian cancer cases with a first‐degree family history of breast or ovarian cancer, whereas the median age at ovarian cancer diagnosis was not different between mutation carriers and non‐carriers. Taken together, these results identify three BRCA1 founder mutations as key components of inherited breast and ovarian cancer susceptibility in Belarus and might have implications for cancer prevention, treatment and genetic counselling in this population.     

Acute effect of infection by adipogenic human adenovirus Ad36

Human adenovirus Ad36 is causally and correlatively associated in animals and humans, respectively, with increased adiposity and altered metabolic profile. We inoculated rats with Ad36 or UV-inactivated Ad36, or mock-infected them. Four days later, Ad36-infected rats showed 23% greater epididymal fat pad weight and viral mRNA; the viral DNA could also be detected in tissues viz. the liver, brain, and adipose tissue. Intranasal or intra-peritoneal routes of viral inoculation showed similar tissue affinity. The serum cytokine response was markedly down-regulated. Ad36 acutely suppresses the systemic immune response and spreads widely. This information will help to determine Ad36 tissue tropism and its metabolic consequences.     

Functional ovarian tumors of stromal and sex cord origin.

Most functional ovarian tumors are of specific stromal or sex cord origin, capable of differentiating in either a female direction or, less commonly, a male direction. Tumors of stromal origin such as thecoma, stromal luteoma, and Leydig cell tumors are for all practical purposes benign, and evolve from mature ovarian stroma, recapitulating common non-neoplastic transformations such as stromal changes associated with follicle development and nodular stromal hyperplasia. Sex cord tumors of granulosa or Sertoli cell types are generally of a low order of malignancy, tending to late recurrence, occasional peritoneal seeding, and only rarely to distant metastasis. Nonfunctional tumors of the ovary may trigger hormone production from adjacent reactive stroma. Massive edema of the ovary due to partial torsion may simulate neoplasm and may produce hormonal syndromes by an unknown mechanism.     

Neurodevelopmental outcome in high-risk preterm infants treated with inhaled nitric oxide

Inhaled nitric oxide (iNO) is used to treat preterm infants with hypoxaemic respiratory failure. In this study we describe the long-term survival and neurodevelopmental status of high-risk preterm infants enrolled into a randomized controlled trial of iNO therapy. Information regarding long-term outcome was available for all 25 children enrolled in the original trial who survived until discharge from hospital. Formal, blinded, developmental assessment and neurological examinations were performed in 21 out of 22 children still alive at 30 mo of age, corrected for prematurity. No significant differences were found in long-term mortality (12/20 vs 8/22, RR 1.65, 95% CI 0.87-3.3), neurodevelopmental delay (4/7 vs 9/14, RR 0.89, 95% CI 0.37-1.75), severe neurodisability (0/7 vs 5/14, p = 0.12) or cerebral palsy (0/7 vs 2/14, p = 0.53) between iNO-treated and control infants. CONCLUSION: In this study there was no evidence of a significant effect on either survival or long-term neurodevelopmental status in infants treated with iNO.     

Special stains in cytology: a technique using one half of a previously stained slide

We describe a technique for performing special stains on one half of a slide previously stained by the Papanicolaou or Diff-Quick method. The technique varies depending on whether incubation is required during the staining procedure. For stains that do not require incubation, the portion of the slide to be preserved is covered with liquid paraffin. For stains that do require incubation, the area to be preserved is coverslipped with mounting medium and dried overnight prior to staining. The technique is easy, rapid, inexpensive, and enhances diagnostic accuracy.     

Insulin sparing action of Adenovirus 36 and its E4orf1 protein

Additional drugs are required to effectively manage diabetes and its complications. Recent studies have revealed protective effects of Ad36, a human adenovirus, and its E4orf1 protein on glucose disposal, which may be creatively harnessed to develop novel anti-diabetic agents. Experimental Ad36 infection improves hyperglycemia in animal models and natural Ad36 infection in humans is associated with better glycemic control. Available data indicate distinctive advantages for a drug that may mimic the action of Ad36 / E4orf1. The key features of such a potential drug include the ability to increase glucose uptake by adipose tissue and skeletal muscle, to reduce hepatic glucose output independent of proximal insulin signaling, and to up-regulate adiponectin and its hepatic action. The effect of Ad36/E4orf1 on hepatocyte metabolism suggests a role for treating hepatic steatosis. Despite these potential advantages, considerable research is required before such a drug is developed. The in vivo efficacy and safety of E4orf1 in improving hyperglycemia remain unknown, and an appropriate drug delivery system is required. Nonetheless, Ad36 E4orf1 offers a research opportunity to develop a new anti-diabetic agent with multiple potential advantages and conceptually advances the use of a rather unconventional source, microbial proteins, for anti-diabetic drug development.