Serum profiles of insulin-like growth factors and their binding proteins in adults with growth hormone receptor deficiency treated with insulin like growth factor I

Six adult patients with growth hormone receptor deficiency (GHRD) (2 men, 4 women) with an identical defect in the growth hormone receptor (GHR) gene, were treated with recombinant human insulin-like growth factor I (IGF-I), 40 μgikg S.C. twice daily, for 7 days. Serum concentrations of IGF peptide and IGF binding protein-3 (IGFBP-3) were measured by specific radioimmunoassays; serum IGFBPs were also measured by Western ligand blotting. The size distribution of both IGF-I and IGF-II was measured in serum following size-exclusion fast-performance liquid chromatography. IGF-I treatment resulted in a normalization of serum IGF-I levels on days 1–7 of treatment and a decrease in serum IGF-II levels. The fall in IGF-II levels and the simultaneous rise in IGF-I levels, however, resulted in an unchanged total serum IGF level. The low IGFBP-3 values did not significantly change during treatment, whereas there was a slight increase in IGFBP-2 levels. Preliminary analysis of size-fractionated sera suggested an increase in IGF-I levels in the 40 and 150 kDa regions at the expense of IGF-II levels. The results suggest that despite the failure of IGF-I treatment to increase IGFBPs significantly, serum IGFBP concentrations were sufficient to maintain normal levels of IGF-I. 0 Laron syndrome, growth hormone receptor deficiency, insulin-like growth factors, insulin-like growth factor binding protein     

Genetic reassortment indicates a new grouping for tick-borne orbiviruses

The Kemerovo (KEM) serogroup of tick-borne orbiviruses (Reoviridae family) is currently classified into four antigenic subgroups: KEM, Chenuda (CNU), Great Island (GI), and Wad Medani (WM) (B. M. Gorman, J. Taylor, and P. J. Walker, 1983, In "The Reoviridae," pp. 287-357). Reassortment assays were carried out to determine the potential for gene exchange both within and between subgroups. Genome segment reassortment was demonstrated between members of two subgroups: KEM virus (a human pathogen) and representatives of the GI subgroup (viruses associated with seabirds). Neither KEM nor GI subgroup viruses reassorted with three viruses currently assigned to the CNU subgroup [CNU, Essaouira (ESS), and Mono Lake (ML)]. Within the CNU subgroup, CNU and ESS viruses reassorted, but there was no evidence of genome segment exchange between either of these two viruses and ML virus. The genetic data, and previously published antigenic data, suggest the need for reassigning these viruses. Four new serogroups are proposed to replace the extant KEM serogroup: KEM serogroup (comprising KEM and GI subgroups), CNU serogroup (including CNU and ESS viruses), Mono Lake serogroup, and WM serogroup.     

Identification of degradome components associated with prostate cancer progression by expression analysis of human prostatic tissues

Extracellular proteases of the matrix metalloproteinase (MMP) and serine protease families participate in many aspects of tumour growth and metastasis. Using quantitative real-time RT-PCR analysis, we have undertaken a comprehensive survey of the expression of these enzymes and of their natural inhibitors in 44 cases of human prostate cancer and 23 benign prostate specimens. We found increased expression of MMP10, 15, 24, 25 and 26, urokinase plasminogen activator-receptor (uPAR) and plasminogen activator inhibitor-1 (PAI1), and the newly characterised serine proteases hepsin and matriptase-1 (MTSP1) in malignant tissue compared to benign prostate tissue. In contrast, there was significantly decreased expression of MMP2 and MMP23, maspin, and the protease inhibitors tissue inhibitor of metalloproteinase 3 (TIMP3), TIMP4 and RECK (reversion-inducing cysteine-rich protein with Kazal motifs) in the cancer specimens. The expression of MMP15 and MMP26 correlated positively with Gleason score, whereas TIMP3, TIMP4 and RECK expression correlated negatively with Gleason score. The cellular localisation of the expression of the deregulated genes was evaluated using primary malignant epithelial and stromal cell cultures derived from radical prostatectomy specimens. MMP10 and 25, hepsin, MTSP1 and maspin showed predominantly epithelial expression, whereas TIMP 3 and 4, RECK, MMP2 and 23, uPAR and PAI1 were produced primarily by stromal cells. These data provide the first comprehensive and quantitative analysis of the expression and localisation of MMPs and their inhibitors in human prostate cancer, leading to the identification of several genes involved in proteolysis as potential prognostic indicators, in particular hepsin, MTSP1, MMP26, PAI1, uPAR, MMP15, TIMP3, TIMP4, maspin and RECK.     

The effect of in vitro recombinant factor VIIA on coagulation parameters for blood taken during liver transplantation

Recombinant factor VIIa (rFVIIa) has been utilized in pilot studies in orthotopic liver transplantation (OLT) when administered to patients at doses of 68.37 microg/kg and 80 microg/kg. Although some effectiveness in normalizing measurements of coagulation has been demonstrated, the optimal dose for patients undergoing OLT has not been established. This study evaluated the effects of an in vitro equivalent dose of 120 microg/kg of rFVIIa on coagulation parameters when applied to the blood drawn from patients undergoing OLT. Coagulation function was assessed in 10 patients at four points during OLT. These time points were baseline, 5 minutes prior to reperfusion, 10 minutes after reperfusion, and 70 minutes after reperfusion. These patients did not receive rFVIIa perioperatively. At each of these four time points, a native sample was analyzed for prothrombin time (PT) and thromboelastogram. The rFVIIa (6.1 microg/kg or the approximate equivalent dose of 120 microg/kg for a 70 kg patient) was added to a second sample from the same patient. This second sample was also analyzed for PT and thromboelastogram. There was a statistically significant difference in baseline PT between native versus rFVIIa supplemented samples (15.8 +/- 3.21 vs 13.6 +/- 2.36 seconds, P < .02). The maximum amplitude of the thromboelastogram was larger in the native samples at 5 minutes prior to reperfusion (53.5 mm vs 39 mm, P < .02). No significant differences existed in the variables at any of the other sampling times. This study failed to demonstrate a consistent in vitro effect of rFVIIa on the blood taken from patients during OLT.     

Effects of BCG Vaccination on Evolution of Leprosy

Background

BCG vaccine is considered to have immunoprophylactic potential in leprosy. However controversy exists about the extent of prophylaxis it provides. In view of this, a study was undertaken to see the evolution of disease in established cases of leprosy who were already vaccinated with BCG and to compare it with the cases of leprosy who were not vaccinated with BCG.

Methods

114 newly diagnosed cases of leprosy were studied. Patients were divided into two groups-BCG vaccinated and non-vaccinated. Clinical diagnosis of leprosy was confirmed by bacteriological and histopathological studies in each case. All patients were given standard anti leprosy treatment and were evaluated monthly for a minimum period of one year.

Results

All the cases were males in the age group of 20 to 50 years. 25.4% of cases had received BCG vaccine and 74.6% were not vaccinated for the same. No significant difference was observed in the incidence of different types of leprosy in vaccinated and non-vaccinated groups. 25.9% cases in non-vaccinated group developed lepra reaction as compared to 13.8% in vaccinated group. The incidence of deformities and disabilities in vaccinated group was only 10.3% as against 18.8% in non-vaccinated group. The rate of bacillary clearance appeared faster in vaccinated group.

Conclusions

Although there is no significant difference in the pattern of different types of leprosy in BCG vaccinated and non-vaccinated cases, there is reduction in the incidence of reactions as well as deformities and disabilities in BCG vaccinated cases as compared to non-vaccinated cases.Key Words: BCG Vaccine, Leprosy     

An analysis of the Research Fellowship Scheme of the Royal College of Surgeons of England

BACKGROUND: The Research Fellowship Scheme of the Royal College of Surgeons of England commenced in 1993 with the aim of exposing selected surgical trainees to research techniques and methodology, with the hope of having an impact on surgical research and increasing the cadre of young surgeons who might decide to pursue an academic career in surgery. Over 11 million pounds sterling (approximately US 20 million dollars) has been invested in 264 fellowships. The College wished to evaluate the impact of the Scheme on the careers of research fellows, surgical research, and patient care. As the 10th anniversary of the Scheme approached. STUDY DESIGN: Two-hundred and sixty research fellows whose current addresses were available were sent a questionnaire. Two-hundred and thirty-eight (91.5%) responded. RESULTS: Three-quarters of the research fellows conducted laboratory-based research, with most of the remainder conducting patient-based clinical research. One-third of the fellows who have reached consultant status have an academic component to their post. The total number of publications based on fellowship projects was 531, with a median impact factor of 3.5. Almost all fellows had been awarded a higher degree or were working toward this. Half of the fellows received subsequent funding for research, mostly awarded by national or international funding bodies. CONCLUSIONS: The Research Fellowship Scheme of the Royal College of Surgeons of England has successfully supported many trainee surgeons in the initial phase of their research career. It has helped surgical research by increasing the pool of surgeons willing to embark on an academic career. Indirectly, patient care has benefited by promoting an evidence-based culture among young surgeons. Such schemes are relevant to surgical training programs elsewhere if more young surgeons are to be attracted into academic surgery.     

A description of radical nephrectomy practice and outcomes in England: 1995-2002

OBJECTIVES: To describe national trends in the practice of radical nephrectomy (RN) in England between 1995 and 2002. METHODS: Data were extracted from the Hospital Episode Statistics database of the Department of Health in England between 1995/1996 and 2001/2002. Patients were included in the study if an International Classification of Diseases diagnosis code (ICD-10) for malignant neoplasm of the kidney, renal pelvis or ureter, and an operative procedure code (OPCS-4) describing total or partial excision of the kidney by either a laparoscopic or open approach, were present in any of the diagnosis or operative procedure fields. Overall, 17 308 patients were included. RESULTS: Patient age and the proportion who were men did not change over the study period. The proportion of patients admitted as an emergency decreased from 14.0% to 7.5% over this period (P < 0.001). The mean waiting duration increased by almost 6 days (P < 0.001) and length of stay by approximately 1 day, from 11.7 days in 1995 to 10.8 days in 2001 (P < 0.001). In-hospital mortality decreased from 2% to 1.5% (P = 0.134). In-hospital mortality and length of stay were higher in older patients and in those admitted as an emergency. Women had a longer stay than men (11.5 vs 11.1 days), but in-hospital mortality was higher in men (2.3% vs 1.6%). The national number of RNs per year increased by approximately 20%, from 2254 in 1995 to 2671 in 2001. Over the same period the mean annual hospital volume of RN increased by approximately 40%, from 17 in 1995 to 24 in 2001. The annual number of laparoscopic RNs nationally increased from seven in 1995 to 84 in 2002. CONCLUSIONS: The annual number of RNs in England increased by almost a fifth and this was accompanied by an increase in annual hospital volume of about two-fifths. There was a large proportional increase in the number of laparoscopic RNs. Emergency admission rates and length of stay decreased but this was not accompanied by a significant change in in-hospital mortality rate.