Reversible Albumin-Binding GH Possesses a Potential Once-Weekly Treatment Profile in Adult Growth Hormone Deficiency.

CONTEXT: NNC0195-0092 is a reversible, albumin-binding GH derivative, developed for once-weekly administration. OBJECTIVES: The objective of the study was to evaluate safety, local tolerability, pharmacodynamics, and pharmacokinetics of multiple, once-weekly doses of NNC0195-0092, compared with daily GH. DESIGN AND SETTING: This was a phase 1, randomized, open-label, active-controlled, multiple-dose, dose-escalation trial. PATIENTS: Thirty-four GH-treated adult subjects (male, n = 25) with GH deficiency participated in the study. INTERVENTIONS AND MAIN OUTCOME MEASURES: Subjects were sequentially assigned into four cohorts of eight subjects, randomized within each cohort (3:1) to once-weekly NNC0195-0092 (n = 6) for 4 weeks (0.02, 0.04, 0.08, and 0.12 mg/kg) or daily injections of Norditropin NordiFlex (n = 2) for 4 weeks with a dose replicating the pretrial dose of somatropin. A safety assessment was performed prior to initiating treatment at the next dose level of NNC0195-0092. Daily GH treatment was discontinued 14 days before the trial start. Blood samples were drawn for assessment of safety, pharmacokinetics, pharmacodynamics (IGF-1 and IGF-binding protein-3) profiles, and immunogenicity studies. RESULTS: Numbers of adverse events were similar at the dose levels of 0.02, 0.04, and 0.08 mg/kg NNC0195-0092 vs daily injections of Norditropin NordiFlex, whereas the number of adverse events was greater at the highest dose level of NNC0195-0092 (0.12 mg/kg). NNC0195-0092 (area under the curve[0-168h]) and peak plasma concentration) increased in a dose-dependent manner, and a dose-dependent increase in IGF-1 levels was observed. IGF-1 profiles were elevated for at least 1 week, and for the 0.02-mg/kg and 0.04-mg/kg NNC0195-0092 doses, the observed IGF-1 levels were similar to the levels for the active control group. CONCLUSION: Four once-weekly doses of NNC0195-0092 (dose range 0.02-0.12 mg/kg) administered to adult patients with GH deficiency were well tolerated, and IGF-1 profiles were consistent with a once-weekly treatment profile. No clinically significant safety and tolerability signals causally related to NNC0195-0092 were identified, nor were any immunogenicity concerns revealed.

Fresh muscle fiber fragments on a scaffold in rats-a new concept in urogynecology?

OBJECTIVE: To investigate if a synthetic, biodegradable scaffold with either autologous in vitro cultured muscle-derived cells or autologous fresh muscle fiber fragments could be used for tissue repair. STUDY DESIGN: Twenty scaffolds with muscle-derived cells and 20 scaffolds with muscle fiber fragments were implanted subcutaneously on the abdomen of rats, 2 in each rat, and examined after 3 weeks (10 of each preparation) and 8 weeks (10 of each preparation). Immonohistochemistry and histopathology was undertaken for assessment of growth pattern and biocompatibility, respectively. RESULTS: At 3 weeks, both muscle-derived cells and muscle fiber fragments could be identified. At 8 weeks, the muscle fiber fragments generated fragmented, striated muscle tissue in 6 of 10 explants, whereas the muscle-derived cells and all scaffolds had vanished. CONCLUSION: Autologous fresh muscle fiber fragments on a biodegradable scaffold seem useful for tissue repair. This study introduces a promising new concept with possible implications for the surgical reconstruction of pelvic organ prolapse.

Cerebral palsy among children born after in vitro fertilization: the role of preterm delivery--a population-based, cohort study.

OBJECTIVE: Our aim was to assess the incidence of cerebral palsy among children conceived with in vitro fertilization and children conceived without in vitro fertilization. METHODS: A population-based, cohort study, including all live-born singletons and twins born in Denmark between January 1, 1995, and December 31, 2000, was performed. Children conceived with in vitro fertilization (9255 children) were identified through the In Vitro Fertilization Register; children conceived without in vitro fertilization (394,713) were identified through the Danish Medical Birth Register. Cerebral palsy diagnoses were obtained from the National Register of Hospital Discharges. The main outcome measure was the incidence of cerebral palsy in the in vitro fertilization and non-in vitro fertilization groups. RESULTS: Children born after in vitro fertilization had an increased risk of cerebral palsy; these results were largely unchanged after adjustment for maternal age, gender, parity, small-for-gestational age status, and educational level. The independent effect of in vitro fertilization vanished after additional adjustment for multiplicity or preterm delivery. When both multiplicity and preterm delivery were included in the multivariate models, preterm delivery remained associated strongly with the risk of cerebral palsy. CONCLUSIONS: The large proportions of preterm deliveries with in vitro fertilization, primarily for twins but also for singletons, pose an increased risk of cerebral palsy.

Psychic vulnerability and the associated risk for cancer.

BACKGROUND: Psychic vulnerability has been associated with a number of physical symptoms and diseases. This study was designed to estimate the incidence of cancer in a random sample of persons in the general Danish population in relation to a personality characteristic measured by the Test of Psychic Vulnerability. METHODS: The authors examined the cancer incidence in a cohort of 5136 randomly sampled persons age > 25 years living in Copenhagen County, Denmark. The responses to questionnaires and the results of examinations, including the Test of Psychic Vulnerability, were collected during 1982-1984 and during 1991-1992. The observed numbers of cancers were compared with the numbers that would have been expected if the cohort members had experienced the same risk of cancer as the population of Copenhagen County. Regression analyses were performed with the Cox proportional hazards model to adjust for well-known risk factors for cancer. RESULTS: A total of 403 cancers were observed, and 412.02 were expected, yielding a standardized incidence ratio of 0.98 (95% confidence interval [95% CI], 0.88-1.19). The authors did not observe a significant increase in the risk of site specific cancers. The risk for cancer was not influenced by the type of vulnerability in a multivariate analysis (hazards ratio, 1.16; 95% CI, 0.85-1.57). CONCLUSIONS: The authors found no increased risk for cancer among psychically vulnerable persons compared with nonvulnerable persons; however, the results indicate that behavior and certain life-style factors may be determined by personality, which, in turn, may determine the risk for cancer.