Background. The efficacy of TCN-032, a human monoclonal antibody targeting a conserved epitope on M2e, was explored in experimental human influenza. Methods. Healthy volunteers were inoculated with ...influenza A/Wisconsin/67/2005 (H3N2) and received a single dose of the study drug, TCN-032, or placebo 24 hours later. Subjects were monitored for symptoms, viral shedding, and safety, including cytokine measurements. Oseltamivir was administered 7 days after inoculation. Results. Although the primary objective of reducing the proportion of subjects developing any grade ≥2 influenza symptom or pyrexia, was not achieved, TCN-032-treated subjects showed 35% reduction (P = .047) in median total symptom area under the curve (days 1-7) and 2.2 log reduction in median viral load area under the curve (days 2-7) by quantitative polymerase chain reaction (P = .09) compared with placebo-treated subjects. TCN-032 was safe and well tolerated with no additional safety signals after administration of oseltamivir. Serum cytokine levels (interferon γ, tumor necrosis factor α, and interleukin 8 and 10) were similar in both groups. Genotypic and phenotypic analyses showed no difference between virus derived from subjects after TCN-032 treatment and parental strain. Conclusions. These data indicate that TCN-032 may provide immediate immunity and therapeutic benefit in influenza A infection, with no apparent emergence of resistant virus. TCN-032 was safe with no evidence of immune exacerbation based on serum cytokine expression. Clinicaltrials.gov. registry number. NCT01719874
Peginterferon alfa (alfa) increases the risk of autoimmune disease. Peginterferon lambda-1a (Lambda) acts through a receptor with a more liver-specific distribution compared to the alfa receptor. In ...a phase-2b study, 525 treatment-naive patients with chronic hepatitis C virus (HCV) infection received ribavirin and Lambda interferon (120, 180, or 240 μg) or alfa interferon (180 μg) for 24 (genotypes 2 and 3) or 48 (genotypes 1 and 4) weeks. Retrospective analysis found that adverse events of MedDRA-coded thyroid dysfunction and abnormal levels of thyroid-stimulating hormone (TSH) were significantly more frequent with alfa versus Lambda (12% versus 2.6% and 15.2% versus 3.4%, respectively, both P<0.0001). Most Lambda recipients with abnormal TSH had levels below the lower limit of normal; the frequency of low and high TSH was similar in alfa recipients with abnormal TSH. Blinded review by an endocrinologist found that new-onset primary hypothyroidism or painless thyroiditis was less frequent with Lambda versus alfa (0.5% and 1.8% versus 5.3% and 7.5%, respectively, P<0.0001). Most TSH elevations reflected new-onset hypothyroidism requiring treatment, while most markedly suppressed TSH values reflected probable painless thyroiditis and resolved without sequelae. In conclusion, HCV-infected patients treated with Lambda/ribavirin experienced fewer adverse events of thyroid dysfunction compared with patients treated with alfa/ribavirin.
To determine the efficacy, safety, and treatment satisfaction of tadalafil 20 mg for erectile dysfunction (ED) in patients evaluated at tertiary-care academic centers.
In this randomized, ...double-blind, placebo-controlled trial, patients were randomly allocated to receive fixed-dose tadalafil 20 mg (n = 146) or placebo (n = 49) for 12 weeks. Efficacy was assessed by the International Index of Erectile Function (IIEF), Sexual Encounter Profile (SEP), and Global Assessment Question (GAQ); patient and partner treatment satisfaction by the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) and SEP; and safety by adverse events, laboratory values, and vital signs.
Mean baseline IIEF erectile function (EF) domain was 12.98. Fifty-one percent of enrolled patients had severe baseline ED, and 82% had organic ED. Pre-existing, ED-associated comorbid conditions were common. When compared with patients treated with placebo, those receiving tadalafil reported significant improvement from baseline in the IIEF EF domain (
P <0.001), successful penetration attempts (SEP question 2;
P <0.001), successful intercourse (SEP question 3;
P <0.001), and all secondary efficacy outcomes (
P <0.001). Patients and their sexual partners were also significantly more satisfied with tadalafil treatment (
P <0.001), including overall satisfaction (
P <0.001) and length of time the treatment worked (
P <0.001). Mild or moderate headache, dyspepsia, and myalgia were the most frequent treatment-emergent adverse events reported.
Tadalafil significantly improved erectile function and patient and partner satisfaction and was well tolerated. These results were observed in a tertiary-care, academic center population with a high incidence of severe, organic ED, and comorbid medical conditions, factors known to compromise erectile function and treatment outcome.
Abstract Background Previous studies of recombinant human thrombin (rThrombin) enrolled adult and adolescent patients. This phase 4, open-label, single-group study was conducted in pediatric patients ...undergoing synchronous burn wound excision and skin grafting to provide information regarding the safety and immunogenicity of rThrombin (primary and secondary endpoints) in this population. Methods Topical rThrombin was applied as a hemostatic aid during a surgical procedure (day 1). Adverse events and clinical laboratory abnormalities were recorded during the study. Immunogenicity samples were collected on days 1 and 29 (study end). Study results were summarized with descriptive statistics. Results Thirty patients enrolled and 28 completed the study. Mean age was 6.9 years (range, 0.9-17.8 years); 40.0% of patients were girls. Flame and scald were the most common burn types (33.3% each, n = 10/30). Mean graft size was 3.6% total body surface area. Procedural pain (50.0% patients), pruritus (43.3%), and anemia (30.0%) were the most commonly reported adverse events. All adverse events and clinical laboratory abnormalities were considered unrelated to treatment. No patients developed anti-rThrombin product antibodies at day 29. Conclusions In pediatric patients undergoing burn wound excision and skin grafting, rThrombin was well tolerated and did not lead to the formation of anti-rThrombin product antibodies.
We determined the frequency of acute complications associated with insulin pump therapy in 161 insulin-dependent patients followed up for a total of 2,978 patient-months. Diabetes control improved ...substantively with pump therapy, but 42% of the patients experienced one or more acute complications while using insulin pumps. Infected infusion sites, ketoacidosis, and hypoglycemic coma occurred once in every 27, 78, and 175 patient-months, respectively. More patients experienced ketoacidosis after the onset of pump therapy than in an equivalent interval immediately before the onset of pump therapy. Ketoacidosis also occurred in more patients using pump therapy than in a comparison group of 165 patients receiving conventional insulin injections surveyed during an equivalent period. The frequency of hypoglycemic coma was not significantly changed by pump therapy.
We investigated the efficacy of insulin-pump therapy in insulin-dependent diabetics, aged 18 to 69 years, by comparing the metabolic control achieved in 100 patients using this technique with that ...previously obtained by conventional insulin therapy. Patients were followed during pump therapy for as long as 15 months. Fasting and nonfasting blood glucose levels (mean +/- S.E.M.) decreased from 201 +/- 6 and 213 +/- 6 mg per deciliter (11.2 +/- 0.3 and 11.8 +/- 0.3 mmol per liter), respectively, to 158 +/- 5 and 145 +/- 3 mg per deciliter (8.77 +/- 0.3 and 8.05 +/- 0.2 mmol per liter) after one month of pump therapy (P less than 0.001). Ninety-three patients had improved blood sugar control; 71 per cent had a mean blood sugar concentration of 150 mg per deciliter (8.3 mmol per liter) or less after six months. Glycosylated hemoglobin values became normal in 44 per cent of 88 patients who had follow-up determinations. In over 500 patient-months there were four episodes of ketoacidosis and five episodes of serious hypoglycemia. Three patients abandoned pump therapy. We conclude that insulin-pump therapy is acceptable to patients and that it can be successfully applied to clinical practice and large-scale research studies.
To determine the long-term efficacy of insulin-pump therapy, we analyzed trends in glycosylated hemoglobin concentrations in 127 patients with Type I diabetes using insulin pumps for periods ranging ...from 13 to 47 months. In the first year of pump therapy the average glycosylated hemoglobin concentration improved in 83 per cent of the patients, as compared with the value before pump therapy. Although only 11 of the 127 subjects had normal glycosylated hemoglobin values before pump therapy, 33 had a normal average value during the first full year of pump use (P = 0.0001). This favorable trend persisted for the three-year duration of the study. Seventeen of the 19 patients who subsequently discontinued insulin-pump therapy had improved glycosylated hemoglobin values during the period of pump use. Eleven of the 19 patients remained available for follow-up study; the glycosylated hemoglobin concentration became worse in 7 when they returned to conventional treatment. We conclude that the improvement in metabolic control repeatedly demonstrated in short-term studies with the insulin pump can be maintained for a period of years.
Ectopically located parathyroid adenomas may be difficult to find during initial neck exploration. They account for over 70 percent of missed adenomas found at reexploration. Preoperative ...localization of parathyroid adenomas would reduce unnecessary dissection and possibly reduce the number of negative results of initial neck exploration. Before reoperative parathyroid surgery is performed, some means of localization is mandatory to detect ectopic adenomas in the neck and mediastinum. Computed tomography and ultrasonography cannot effectively evaluate the mediastinum. Angiography and venous parathyroid hormone sampling are invasive, costly, and tedious to perform. We have shown that thallium-201 will accurately localize ectopic parathyroid adenomas. All 10 adenomas found in positions not immediately adjacent to the thyroid gland were detected by thallium-201 scintigraphy. One was a mediastinal adenoma resected with a median sternotomy. Our results suggest that thallium-201 scintigraphy should be the initial localization procedure of choice before all reexplorations. Its use before initial explorations, as well, will enable the surgeon to immediately direct attention to the area of the localized adenoma. If mediastinal uptake is found to be present, then median sternotomy may be performed during initial surgery provided a thorough neck exploration is performed first.
Insulin-infusion pumps in type I diabetes Connell, F A; Mitchell, W H; Norman, J E ...
The New England journal of medicine,
01/1983, Letnik:
308, Številka:
2
Journal Article
"Autoimmune" hypoglycemia is a syndrome consisting of fasting hypoglycemia, hyperinsulinemia, and insulin-binding antibodies in a patient who has never been exposed to exogenous insulin. The stimulus ...for insulin-antibody formation and the mechanism of the hypoglycemia in this condition remain unknown. Three patients with this rare syndrome had severe hypoglycemia of limited duration. Two had received a drug containing a sulfhydryl group (methimazole and penicillamine) as treatment for an autoimmune disorder (Graves' disease and rheumatoid arthritis, respectively). A third patient who underwent surgery for a suspected insulinoma was found to have pancreatic beta cell hyperplasia. Drugs containing a sulfhydryl group may have a role in the etiology of the syndrome. Additionally, our findings suggest a relationship between circulating insulin antibodies and beta cell hyperplasia.
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