Stimulation of human fibroblast protein, ribonucleic acid, and deoxyribonucleic acid synthesis by bovine growth hormone fragments

Bovine GH and two fragments which were obtained by dissociation of a limited tryptic digest of the hormone stimulated protein, RNA, and DNA synthesis of contact-inhibited human fibroblasts. The stimulation of protein, RNA, and DNA synthesis was similar for the test substances. Maximal stimulation was noted at 10 nM. At that concentration, protein, RNA, and DNA synthesis were respectively increased 1.80, 1.42, and 1.37 times by GH; 1.93, 1.27, and 1.46 times by A-I (the larger fragment); and 1.99, 1.26, and 1.33 times by A-II (the smaller fragment). The action of GH, A-I, and A-II was similar to that of fetal calf serum, but was distinguished by the time course of stimulation and by the magnitude of the response. For example, GH, A-I, and A-II produced their earliest detectable effect at 10 h for protein synthesis, 22 h for RNA synthesis, and 26 h for DNA synthesis. On the other hand, serum stimulated protein, RNA, and DNA synthesis at 6, 10, and 16 h, respectively. These data show that human fibroblasts respond equally to GH, A-I, and A-II and suggest that there may be more than one "active site" in the GH molecule. Lastly, human fibroblasts may represent a useful system to study the actions of GH in vitro.     

Ciprofloxacin versus chloramphenicol in the treatment of salmonella infection

Strains of Salmonella typhi resistant to chloramphenicol and ampicillin have been isolated in several countries. This study compares treatment of Salmonella infection using ciprofloxacin (500 mg twice daily) for 10 days with chloramphenicol (50 mg/kg per day divided into four doses) for 14 days. The pathogen eradication rates for patients receiving ciprofloxacin was 18/20 (90%), compared with 25/28 (89%) for those who received chloramphenicol. Signs and symptoms in patients receiving chloramphenicol lasted longer and sometimes twice as long as patients treated with ciprofloxacin. In this study, ciprofloxacin was superior to cloramphenicol in the treatment of S. typhi infection and also had fewer side-effects and the convenience of a twice-a-day dosing     

A model system illustrating the isolation and enrichment of a rare population of tumour cells in bone marrow

A model system employing a modified nylon matrix is described for the separation of rare cells titrated into either a leukaemic cell line or normal bone marrow. A 75- to 125-fold enrichment and recovery of the rare cell population was achieved, starting from an initial level of 0.014 to 0.2% of the total population. The rare cell population was identified by pre-labelling with Hoechst 33342, which intercalates into the DNA, and renders cells highly fluorescent. Separation and recovery of cells was totally dependent on the use of a panel of monoclonal antibodies binding to the labelled population. The nylon matrix, precoated with an anti-mouse immunoglobulin, traps the cells coated with monoclonal antibodies, and these can be released simply by gentle manipulation of the matrix. The matrix employed has been shown to not specifically trap committed bone marrow progenitors as determined by CFU-GM, BFU-E and CFU-GEMM assays. The use of this technique should simplify the isolation of rare tumour cells metastasizing to bone marrow.     

Age shift in patterns of injection drug use among the HIV/AIDS population in Miami-Dade County, Florida

Analysis of HIV exposure category for 20,034 persons in three age groups (13-29, 30-49, 50 and over) who were alive through 2003 and had been reported to the Florida Department of Health with HIV or AIDS in Miami-Dade County, Florida, found that having a history of injection drug use increases with increasing age (p < .001). Consideration of age-specific HIV risk profiles has implications for primary and secondary HIV prevention interventions, planning, and policy.     

Morphological and quantitative study of ganglionated plexus of Calomys callosus trachea

Calomys callosus is a wild, native forest rodent found in South America. In Brazil, this species has been reported to harbour the parasitic protozoan Trypanosoma cruzi. The ganglionated plexus of this species was studied using whole-mount preparations of trachea that were stained using histological and histochemical methods. The histological methods were used to determine the position of the ganglia with respect to the trachea muscle and to determine the presence of elastic and collagen fibers. The histochemical method of NADH-diaphorase was used for morphometric evaluations of the plexus. The tracheal plexus lies exclusively over the muscular part of the organ, dorsal to the muscle itself. It varies in pattern and extent between animals. The average number of neurons was 279 and the cellular profile area ranged from 38.37 microm2 to 805.89 microm2. Acetylcholinesterase (AChE) histochemistry verified that both ganglia and single neurons lie along nerve trunks and are reciprocally interconnected with the plexus. Intensely AChE-reactive neurons were found to be intermingled with poorly reactive ones. Two longitudinal AChE-positive nerve trunks were also observed and there was a diverse number of ganglia along the intricate network of nerves interconnecting the trunks. A ganglion capsule of collagen and elastic fibers surrounding the neurons was observed. Under polarized light, the capsule appeared to be formed by Type I collagen fibers.     

Non-surgical rhinoplasty technique: An innovative approach for nasal reshaping with hyaluronic acid fillers

Objective

Nonsurgical rhinoplasty has become increasingly popular among patients who want to improve the aesthetic aspects of their nose and do not accept the risks and/ or cost of surgical rhinoplasty. The main goal of the current paper was to present the preliminary aesthetic and clinical outcomes of an innovative injection technique for nose sculpturing with hyaluronic acid (HA) filler.

Methods

Retrospective analysis of a prospective clinical registry of patients who attended one of the study centers and were candidates for non-surgical nose reshaping between October 2019 and November 2020. A 25 mg/mL HA filler was administered, in all the cases, by using a syringe with a fixed microneedle (30G/8mm). All patients were injected at three key nose points with the following order: (1) Tip (maximum HA injected 0.2 mL); (2) columella (maximum HA injected 0.3 mL); and (3) Radix and Dorsum (maximum HA injected 0.3 mL). Degree of patient satisfaction with the treatment was assessed by using a five-points Likert scale. The primary endpoint was the degree of patients' satisfaction 12 months after treatment.

Results

One-hundred-and-one patients (91 women) were included in the study. Fifty-six (56%) patients underwent a unique treatment-session and 44 (44%) subjects needed an additional touch-up. Eighty-five (84.2%) patients were very satisfied with the treatment results. Six (5.9%) patients reported moderate adverse events, which were successfully controlled with medical therapy.

Conclusions

Our nose sculpturing technique, by using hyaluronic acid filler, was an effective, predictable, and relatively safe procedure, that obtained a high degree of patient satisfaction.     

Use of local hyperthermia as prophylaxis of fibrosis and modification in penile length following radical retropubic prostatectomy.

OBJECTIVE: The aim of the study was to evaluate the effectiveness of local hyperthermia in reducing possible penile shortening following radical retropubic prostatectomy. PATIENTS AND METHODS: The study population comprised 40 patients, aged 52-74 years, submitted to radical retropubic prostatectomy. Patients were divided into two groups of 20. In Group A, patients were submitted to local hyperthermia 3 weeks after surgery, three times a week, with treatment lasting 30 min. Patients received a total of 10 applications, which reached a local temperature of 39-40 degrees C. A second cycle was repeated after 1 month. In Group B, patients were submitted only to post-operative follow-up once a month. Penile length was measured in all patients both before and 3 months after surgery in the 'stretching phase' from the pubo-penile junction to the tip of the glans. RESULTS: In Group A patients (hyperthermia treatment), no variation in penile length was observed in 16 cases (80%), while the reduction ranged from 0.5-1.5 cm in four cases (20%). In Group B, 12 patients (60%) showed a reduction in penile length ranging from 0.5-2.5 cm, while penile length remained unchanged in eight patients (40%). CONCLUSIONS: Results of this study demonstrate a mild but statistically relevant reduction in penile shortening following low-grade, externally delivered penile hyperthermia, thus confirming the efficacy of this approach in preventing penile shortening caused by post-ischaemic fibrosis.     

Observations on Three Endpoint Properties and Their Relationship to Regulatory Outcomes of European Oncology Marketing Applications

Background.

Guidance and exploratory evidence indicate that the type of endpoints and the magnitude of their outcome can define a therapy’s clinical activity; however, little empirical evidence relates specific endpoint properties with regulatory outcomes.

Materials and Methods.

We explored the relationship of 3 endpoint properties to regulatory outcomes by assessing 50 oncology marketing authorization applications (MAAs; reviewed from 2009 to 2013).

Results.

Overall, 16 (32%) had a negative outcome. The most commonly used hard endpoints were overall survival (OS) and the duration of response or stable disease. OS was a component of 91% approved and 63% failed MAAs. The most commonly used surrogate endpoints were progression-free survival (PFS), response rate, and health-related quality of life assessments. There was no difference (p = .3801) between the approved and failed MAA cohorts in the proportion of hard endpoints used. A mean of slightly more than four surrogate endpoints were used per approved MAA compared with slightly more than two for failed MAAs. Longer OS and PFS duration outcomes were generally associated with approvals, often when not statistically significant. The approved cohort was associated with a preponderance of statistically significant (p < .05) improvements in primary endpoints (p < .0001 difference between the approved and failed groups).

Conclusion.

Three key endpoint properties (type of endpoint [hard/surrogate], magnitude of an endpoint outcome, and its statistical significance) are consistent with the European Medicines Agency guidance and, notwithstanding the contribution of unique disease-specific circumstances, are associated with a predictable positive outcome for oncology MAAs.

Implications for Practice:

Regulatory decisions made by the European Medicines Agency determine which new medicines will be available to European prescribers and for which therapeutic indications. Regulatory success or failure can be influenced by many factors. This study assessed three key properties of endpoints used in preauthorization trials (type of endpoint [hard/surrogate], magnitude of endpoint outcome, and its statistical significance) and whether they are associated with a positive regulatory outcome. Clinicians can use these properties, which are described in the publicly available European public assessment reports, to help guide their understanding of the clinical effect of new oncologic therapies.