Human biodistribution of an ultrasound contrast agent (Quantison) by radiolabelling and gamma scintigraphy

The biodistribution and kinetics of an air filled human serum albumin microcapsule formulation (Quantison) intended for use as an intravenous ultrasound contrast agent have been examined. 12 healthy subjects were administered with approximately 50 million microcapsules per kilogram body weight, radiolabelled with 50 MBq 123I. Imaging was performed over a period of 58 h using a large field-of-view gamma camera and the amount of labelled material present in the blood, urine and faeces measured. Imaging demonstrated that the liver was the organ with the highest uptake, with a mean uptake of 41.8% (SD 10.4%) of the administered dose 1 h following administration. The maximum uptake of the agent in the lungs was low, mean 4.0% (SD 3.4%). A small amount of uptake was visible in the bone marrow; however, this was not quantifiable. There was also evidence of minimal myocardial activity within 5 min of administration. No adverse events were observed and there were no changes in any of the individual post-study indices. The present study demonstrates the safety of Quantison. Gamma scintigraphy played a useful role in confirming the biodistribution of the agent with little lung uptake, high liver uptake and evidence of myocardial uptake.     

Partnering with physicians to achieve quality improvement

BACKGROUND: The Maine Medical Assessment Foundation (MMAF) has successfully involved hundreds of Maine physicians in study groups to analyze data on small-area variation and assess physician decision-making patterns. In 1991 the MMAF model was replicated across a tri-state area (Maine, New Hampshire, Vermont) in an effort called the Outcomes Dissemination Project, which is funded by a five-year grant from the U.S. Agency for Health Care Policy and Research. THE OUTCOMES DISSEMINATION PROJECT: Five specialty study groups, each meeting three times a year, examine local and national utilization data, examine guidelines and research findings, participate in outcomes studies and patient education, and disseminate their findings through specialty society presentations and other feedback efforts. The MMAF study group process is based on the beliefs that medicine is a subculture with a complex set of professional values, beliefs, socialization processes, and norms, and that quality improvement efforts work best when they are nonpunitive and educational. ISSUES IN OBTAINING PHYSICIAN INVOLVEMENT: (1) Physicians are willing to change their practices if they are brought into a culturally appropriate improvement program. (2) Related specialties (for example, internists and family practitioners) can often work together effectively on issues of common interest. (3) Involving respected clinical leaders has helped establish the legitimacy of MMAF methods among physicians. (4) Area- and physician-specific data are not made public, so as to build a sense of confidentiality among participants. CONCLUSIONS: The project continues to function as a powerful education process and serves as a model for replication elsewhere.     

Sj?gren's syndrome. New diagnostic aspects

European criteria for classification of Sj?gren's syndrome have recently been developed and evaluated. We report the clinical and laboratory findings in 96 patients with primary Sj?gren's syndrome who have been classified according to these new criteria. In our patient population the latency from appearance of the first symptom to diagnosis was 11 years. In addition to sicca symptoms in mucous membranes, the dominant symptoms were periodic fatigue (92%), arthralgia (82%), hoarse voice (71%), dry cough (54%) and diarrhoea (51%). Antibodies to the nuclear antigens SSA and SSB were found in respectively 22.2% and 15.6% of the patients. Two out of ten patients with both anti-SSA and anti-SSB antibodies gave birth to a child with heart block.     

Sexual abuse within the marital relationship

OBJECTIVE: The pathophysiology of pulmonary fibrosis in patients with systemic sclerosis (SSc) is poorly understood, but a number of recent studies have demonstrated an inflammatory process involving the lower respiratory tract. The objective of the present study was to determine the concentrations of several cytokines in the bronchoalveolar lavage (BAL) fluid of patients with SSc and to assess whether the enhanced expression of certain cytokines is associated with the presence of alveolitis. METHODS: BAL was performed on patients with SSc (with or without alveolitis) and on normal control subjects. Lyophilized BAL fluid samples were assayed by enzyme-linked immunosorbent assay for tumor necrosis factor alpha (TNF alpha), interleukin-1alpha (IL-1alpha), IL-4, IL-6, IL-8, macrophage inflammatory protein 1alpha (MIP-1alpha), and RANTES. RESULTS: There were significant differences between groups in the BAL fluid concentrations of TNF alpha (P = 0.0005, with levels in SSc patients with alveolitis higher than those in normal controls), IL-8 (P = 0.006, with levels in both SSc groups higher than those in normal controls), MIP-1alpha (P = 0.009, with levels in SSc patients with alveolitis higher than those in SSc patients without alveolitis and than those in normal controls), and RANTES (P = 0.03, with levels in SSc patients without alveolitis higher than those in normal controls). With the exception of RANTES, the highest levels were detected in SSc patients with alveolitis. CONCLUSION: Each of these cytokines, either alone or in combination, may play an important role in the pathogenesis of pulmonary fibrosis in SSc.     

The inducible and cytochrome P450-containing dehydroepiandrosterone 7alpha-hydroxylating enzyme system of Fusarium moniliforme

7Alpha-hydroxylation of DHEA by Fusarium moniliforme was investigated with regard to inducibility and characterization of the responsible enzyme system. Using GC/MS, the 7-hydroxylated metabolites of DHEA produced after biotransformation by Fusarium moniliforme mycelia were identified. The strain of Fusarium moniliforme hydroxylated DHEA predominantly at the 7alpha-position, with minor hydroxylation occurring at the 7beta-position. Constitutive 7alpha-hydroxylation activity was low, but DHEA induced the enzyme complex responsible for 7alpha-hydroxylation via an increase in protein synthesis. DHEA 7alpha-hydroxylase was found to be mainly microsomal, and the best production yields of 7alpha-hydroxy-DHEA (28.5 +/- 3.51 pmol/min/mg protein) were obtained with microsomes prepared from 18-h-induced mycelia. Kinetic parameters (KM=1.18 +/- 0.035 microM and Vmax=909 +/- 27 pmol/min/mg protein) were determined. Carbon monoxide inhibited 7alpha-hydroxylation of DHEA by microsomes of Fusarium moniliforme. Also, exposure of mycelia to DHEA increased microsomal P450 content. These results demonstrated that: (i) DHEA is 7alpha-hydroxylated by microsomes of Fusarium moniliforme; (ii) DHEA induces Fusarium moniliforme 7alpha-hydroxylase; (iii) this enzyme complex contains a cytochrome P450.     

Hexon-only binding of VP26 reflects differences between the hexon and penton conformations of VP5, the major capsid protein of herpes simplex virus

VP26 is a 12-kDa capsid protein of herpes simplex virus 1. Although VP26 is dispensable for assembly, the native capsid (a T=16 icosahedron) contains 900 copies: six on each of the 150 hexons of VP5 (149 kDa) but none on the 12 VP5 pentons at its vertices. We have investigated this interaction by expressing VP26 in Escherichia coli and studying the properties of the purified protein in solution and its binding to capsids. Circular dichroism spectroscopy reveals that the conformation of purified VP26 consists mainly of beta-sheets (approximately 80%), with a small alpha-helical component (approximately 15%). Its state of association was determined by analytical ultracentrifugation to be a reversible monomer-dimer equilibrium, with a dissociation constant of approximately 2 x 10(-5) M. Bacterially expressed VP26 binds to capsids in the normal amount, as determined by quantitative sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Cryoelectron microscopy shows that the protein occupies its usual sites on hexons but does not bind to pentons, even when available in 100-fold molar excess. Quasi-equivalence requires that penton VP5 must differ in conformation from hexon VP5: our data show that in mature capsids, this difference is sufficiently pronounced to abrogate its ability to bind VP26.