Cost analysis of human islet transplantation for the treatment of type 1 diabetes in the Swiss-French Consortium GRAGIL

OBJECTIVE: To evaluate the cost of islet transplantation in type 1 diabetic patients with a functional renal graft in a multicenter network. RESEARCH DESIGN AND METHODS: The study involved nine diabetic patients transplanted in the Swiss-French Groupe Rh?ne-Alpes, Rhin et Geneve pour la transplantation d'Ilots Langerhans (GRAGIL) consortium between March 1999 and June 2000. The direct medical costs were estimated from Social Security's perspective from the inclusion of the patient to 1 year after transplantation. All cost components were computed separately and included evaluation, screening and candidacy, organ retrieval, islet processing, pancreas and islet transportation, hospitalization for transplantation, follow-up, medications (immunosuppressive, antidiabetic, and adjuvant drugs), and adverse events requiring hospitalization. RESULTS: During the study period, 56 pancreata were processed and 14 islet preparations were transplanted. The average cost of an islet transplantation (procedure and 1-year follow-up) was 77,745 euro (French rate, year 2000). The four main cost components were islet preparation (30% of the total cost), adverse events (24%), drugs (14%), and hospitalization (13%). CONCLUSIONS: Overall costs of islet transplantation are slightly higher than those of pancreas transplantation. The cell isolation process is a critical point; a reduction in overall cost will require more efficient ways of isolating high yields of viable islets. Costs generated by shipments within the GRAGIL network did not represent an economic burden. It can be expected that the costs will decrease with growing experience and improving technology.     

Specific alteration of the expression of selected hypothalamic neuropeptides during acute and late mouse brain infection using a morbillivirus: relevance to the late-onset obesity?

Neurotropic viruses are involved in pathologies of the central nervous system, triggering transient or irreversible disorders, such as neurological diseases or homeostasis imbalance. In experimental animals, viruses have been shown to cause obesity, a complex disease depending on multiple factors, including genetic susceptibility and environmental components. Using a mouse model of virally induced obesity following brain infection by the Canine Distemper Virus (CDV), a morbillivirus closely related to the human measles virus, we investigated the modulation of expression of several hypothalamic neuropeptides known to intervene in the regulation of body weight and energy expenditure, both during the acute and late stages of infection. During the acute stage, while viral replication occurs, we found a dramatic decrease of expressions of neuropeptides, in particular neuropeptide Y, melanin-concentrating hormone (MCH), hypocretin, vasopressin and tachykinins, the magnitude of which seemed to be linked to the viral burden and the individual susceptibility. The effect of the virus, however, varied with the hypothalamic nucleus and neuropeptide involved, suggesting that certain circuits were affected while others remained intact. During the late stage of infection, marked recovery to the initial hypothalamic levels of peptide expression was seen in a number of lean animals, suggesting recovery of homeostasis equilibrium. Interestingly, some neuropeptidergic systems remained disturbed in mice exhibiting obese phenotype, arguing for their involvement in triggering/maintaining obesity. Even though our data could not fully explain the viral-induced obesity, they may be helpful in understanding the molecular events associated with obesity and in investigating therapeutic alternatives.     

Glucose-receptor MR imaging of tumors: study in mice with PEGylated paramagnetic niosomes

PURPOSE: To evaluate a magnetic resonance (MR) imaging contrast agent for tumor detection based on paramagnetic nonionic vesicles (niosomes) bearing polyethylene glycol (PEG) and glucose conjugates for the targeting of overexpressed glucose receptors. MATERIALS AND METHODS: Four gadobenate dimeglumine-loaded niosome preparations including nonconjugated niosomes, niosomes bearing glucose conjugates (N-palmitoyl glucosamine [NPG]), niosomes bearing PEG 4400, and niosomes bearing both PEG and NPG were tested. In vitro cellular uptake was measured at electron paramagnetic resonance (EPR) after incubation with human prostate carcinoma, PC3, cells. In vivo distribution was studied at MR imaging 6, 12, and 24 hours after injection, with assessment of tumor, brain, liver, and muscle signal intensity (SI) in 49 mice bearing PC3 cells. Efficiency of targeted contrast agents was assessed with tumor-to-muscle contrast-to-noise ratio (CNR). Testing for differences was performed with analysis of variance followed by a posteriori Fisher test. RESULTS: In vitro, gadolinium could be detected at EPR only in cell pellets incubated with niosomes bearing glucose conjugates or niosomes bearing both glucose conjugates and PEG (4.9. 10(-15) and 4.5. 10(-15) mol gadolinium per PC3 cell). In vivo, marked predominant tumor enhancement was demonstrated 24 hours after injection of glycosylated PEG niosomes (P <.01); no significant differences were observed following injection of nonconjugated niosomes, glycosylated niosomes, or PEG 4400 niosomes. Twenty-four hours after injection, sole presence of NPG or PEG 4400 on the surface of the niosome led to higher tumor-to-muscle CNR than that observed after injection of nonconjugated niosomes (CNR of 3.3 +/- 0.7 [SD], 3.4 +/- 2.2, and 0 +/- 1.9). Combination of NPG and PEG led to even higher tumor-to-muscle CNR (6.3 +/- 2.2). CONCLUSION: Combination of PEG and glucose conjugates on the surface of niosomes significantly improved tumor targeting of an encapsulated paramagnetic agent assessed with MR imaging in a human carcinoma xenograft model.     

Low Vitamin B(12) level as a risk factor for very early recurrent abortion

OBJECTIVE: To examine the relationship between Vitamin B(12) deficiency and early recurrent abortion (ERA) or very early recurrent abortion (VERA) abortion around 5 weeks of amenorrhea. STUDY DESIGN: Serum B(12), folate and homocysteine levels were carried out in 110 consecutive women with unexplained ERA or VERA and in 96 women with one or more children and no abortion history. RESULTS: Ten women were found to have low serum B(12) levels versus one in the control group. A total of 50% of these had raised homocysteine. No difference was noticed between cases and controls for folate. Among women with low serum B(12) level and ERA, 87.5% of the abortions were VERA. Vitamin B(12) supplementation led to four normal pregnancies in five women who became pregnant again. In a statistical analysis performed on five studies in which serum B(12) was assayed in ERA, including ours, a significant relationship was found between ERA and Vitamin B(12) deficiency. CONCLUSION: Vitamin B(12) deficiency may be involved in ERA. Vitamin B(12) assay should be done in ERA women whether or not hematological abnormalities are present.     

Etiologic diagnosis of 204 pericardial effusions

The etiologic evaluation of pericardial effusion is frequently unsuccessful when noninvasive methods are used. To determine the cause of the current episode, all patients with echographically identified pericardial effusion from May 1998 to December 2002 underwent noninvasive diagnostic testing of blood, throat, and stool samples. Patients with postpericardiotomy syndrome were excluded. To analyze the value of our tests, we tested randomly selected blood donors as negative controls. Among 204 included patients, 107 (52.4%) had a final etiologic diagnosis: the etiology of 52 was highly suspected at first examination and later confirmed (thyroid deficiency, 5 cases; systemic lupus erythematous, 7; rheumatoid arthritis, 7; scleroderma, 3; cancer, 25; and renal insufficiency, 5). A definite etiologic diagnosis was made in 11 patients from pericardial fluid analysis (cancer, 5 cases; tuberculosis, 3; Streptococcus pneumoniae, Citrobacter freundii, and Actinomyces, 1 case each). Among 141 patients considered to have idiopathic pericarditis, 44 (32.1%) gained an etiologic diagnosis by our systematic testing strategy. This included serologic evaluation of serum (Coxiella burnetii, 10 cases; Bartonella quintana, 1; Legionella pneumophila, 1; Mycoplasma pneumoniae, 4; influenza virus, 1), viral culture of throat swabs (enterovirus, 8 cases; and adenovirus, 1), high-level antinuclear antibodies (>1/400, 3 cases), and thyroid-stimulating hormone (15 abnormal results). Antibodies to Toxoplasma and cytomegalovirus, enterovirus recovered from rectal swabs, and low-level antinuclear antibodies were seen with equal frequency in patients and controls.Using our evaluation strategy, the number of pericardial effusions classified as idiopathic was less than in other series. Systematic testing for Q fever, Mycoplasma pneumoniae, thyroid abnormalities, and antinuclear antibodies, accompanied by viral throat cultures, frequently enabled us to diagnose diseases not initially suspected in patients with pericardial effusion.     

Nine-year surveillance of methicillin-resistant Staphylococcus aureus in a hospital suggests instability of mecA DNA region in an epidemic strain

The distributions of the antibiotic resistance patterns in a population of Staphylococcus aureus isolates from a teaching hospital were studied over a 9-year period. The results indicate the existence of successive major epidemic methicillin-resistant strains and the emergence of a methicillin-susceptible strain with an unusual resistance pattern. Our findings suggest that this methicillin-susceptible S. aureus strain could be derived from the dominant gentamicin-susceptible methicillin-resistant S. aureus strain with the loss of a 40-kb DNA fragment.