Clinical immunogenicity of measles, mumps and rubella vaccine delivered by the Injex jet injector: comparison with standard syringe injection.

BACKGROUND: The measles, mumps and rubella (MMR) vaccine confers trivalent immunity in >90% of subjects immunized. Alternatives to the use of needles for vaccine administration have recently been made available. We report the safety and efficacy of MMR vaccine delivered by a new needle-free jet injector (Injex) compared with needle syringe administration. METHODS: Forty adolescent subjects were injected bilaterally via needle syringe and jet injector with MMR vaccine and reconstitution buffer. Subjects were blinded as to which device contained the vaccine. Subjects were followed longitudinally for 12 weeks postimmunization, and titers to measles, mumps and rubella immunogens were determined by enzyme immunoassays. Injection pain was quantified using the visual analog pain scale. RESULTS: Adverse events were mild and included injection site soreness (jet injector, 2.5% of subjects; needle, 12.5%), injection site bleeding (jet injector, 0%; needle, 7.5%), malaise (jet injector, 0%; needle, 5%) and fever (jet injector, 0%; needle, 2.5%). All subjects displayed measles titers significantly above baseline during the follow-up. Ninety-five percent of subjects displayed titers above baseline for the mumps antigen vs. 97.5% for rubella. No significant differences in immunogenicity were found between groups receiving the vaccine via the jet injector or the needle syringe at any time during the follow-up (P > 0.05). Injection pain scores were not significantly different between injector types (P > 0.05). CONCLUSIONS: We conclude that the measles, mumps and rubella vaccine can be safely and effectively delivered by the Injex jet injector. This device therefore provides an alternative to standard needle injection and a methodology that might reduce the risk of needle stick accidents.

Croatian Medical Journal at the turn of the millennium.

The turn of the millennium coincided with the inclusion of the Croatian Medical Journal into the bibliographic databases MEDLINE (1998), and Current Contents/Clinical Medicine (1999), which greatly increased the number of submitted manuscripts. The increased pressure on the editorial office prompted us to modify the editorial procedure and sharpen our acceptance criteria. At the same time, we extended our author-friendly policy to all for global medicine and (2) medicine in translational and emerging countries. The Editorial Board and the Advisory Board were critical in developing and improving the Journal and setting the highest standards in all aspects of publication, especially in manuscript selection by high-quality peer review. In this editorial, we finally meet the members of the two Boards in person, or rather, in photographs and short biographies.

Plasma amylin concentrations in fasted and fed rats quantified by a monoclonal immunoenzymometric assay.

Amylin is a 37-amino acid peptide co-secreted from the pancreatic beta-cell with insulin in response to nutrient stimuli. Plasma amylin concentrations in the rat are reported to vary widely. We have employed a recently-developed immunoenzymometric assay to quantify plasma amylin concentrations in fasted, fed and glucose-administered rats. Fasted amylin concentrations ranged between 1.02+/-0.09 and 1.63+/-0.15pM among three different common rat strains, and increased up to 7.70+/-0.80 pM after feeding. The differences among strains and between fasted and fed rats were all significant at P<0.01 or less. Intravenous glucose administration (5.2 mmol/kg) also significantly increased plasma amylin concentrations in fasted rats from 1.5+/-0.3pM to 3.4+/-0.5pM, and in fed rats from 4.6+/-1.1 pM to 9.1+/-1.7 pM. Plasma amylin/insulin molar ratios ranged between 2.3+/-0.2% and 3.6+/-0.5% (mean 3.0%), but did not differ among strains, or between the fasted vs fed state in any strain. In conclusion, a new sensitive immunoenzymometric assay revealed fasting plasma concentrations which are lower than previously reported, and which are significantly increased by stimulation with feeding or glucose administration.

Nephrectomy decreases amylin and pramlintide clearance in rats.

Amylin is a 37 amino acid hormone, co-secreted with insulin from the pancreatic beta-cell in response to nutrient stimuli. Because the human amylin analog, pramlintide, is being tested in patients with diabetes mellitus, a known risk factor for nephropathy, we examined the role of the kidney on amylin and pramlintide metabolism and action in functionally nephrectomized rats. Nephrectomy markedly altered amylin metabolism: it increased incremental area under the plasma amylin concentration curve 3.6-fold (P<0.001) and increased the elimination half-life from 17+/-1 to 26+/-2 minutes (P < 0.01) after subcutaneous injection of 100 microg amylin. Nephrectomy decreased plasma amylin clearance from 20.3+/-1.1 to 7.9+/-0.4 mL/min (P < 0.0001). Thus, at these doses in the rat, the kidney is important for metabolizing amylin and pramlintide.

Effects of rat amylin on renal function in the rat.

Amylin is a peptide secreted from the pancreatic beta-cell along with insulin in response to nutrient stimuli. Amylin has been reported to delay gastric emptying, inhibit glucagon secretion and gastric acid secretion, increase plasma lactate, plasma glucose and plasma renin activity, and decrease plasma calcium. Receptors for amylin have been found in the rat nucleus accumbens and the kidney. In the present experiments, amylin was administered to anesthetized rats by continuous intravenous infusions at varied rates. Amylin significantly increased urine flow at an infusion rate resulting in a plasma concentration of approximately 52 pM, and at a concentration of approximately 193 pM, it increased sodium excretion, glomerular filtration rate and renal plasma flow. Renal calcium and potassium excretion were significantly elevated at plasma amylin concentrations of approximately 52 pM and 193 pM, respectively. Higher concentrations of plasma amylin decreased plasma calcium and potassium and blunted urinary excretion of these electrolytes. Thus, of the renal responses tested, diuresis and natriuresis appeared to be the most sensitive to infused amylin. These renal effects occurred only at plasma concentrations above the normal range, but within the range of concentrations reported in insulin resistant rats.

Development and characterization of monoclonal antibodies specific for amylin.

Highly selective monoclonal antibodies to the peptide hormone human amylin have been produced and characterized. These antibodies are produced by hybridomas resulting from the fusions of BALB/c-derived myelomas and splenocytes from either inbred or outbred mouse strains. Certain of these antibodies recognize epitopes at the amino-terminus or the amidated carboxy-terminus, as well as conformational epitopes within the central region of the 37 amino acid peptide. Several of these antibodies show less than 0.1% cross-reactivity with related peptide hormones such as calcitonin and calcitonin gene-related peptide (CGRP) and have apparent affinities in the low nanomolar range. Antibody pairs were selected for use in two-site assays for the direct measurement of endogenous amylin and the synthetic human amylin analogue, pramlintide (25, 28, 29 tripro-human amylin), which is presently under clinical investigation for improving glucose control in patients with both Type I and Type II diabetes treated with insulin.