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PubMed1998

Differential release of dopamine by nitric oxide in subregions of rat caudate putamen slices.

Fast cyclic voltammetry was used to measure NO and dopamine (DA) simultaneously in rat caudate putamen (CPu) slices. Analysis of electrochemical signals obtained from mixtures of DA and NO showed that subtraction of either the DA or the NO component revealed the contribution of the other component. Application of such data manipulation to signals obtained in CPu slices indicated that DA and NO components contributed to electrochemical signals. Following electrical stimulation (>1 s), site-dependent NO-like signals were observed. Pressure ejection of NMDA yielded a biphasic electrochemical signal. The first phase (lasting 10-20 s) had electrochemical characteristics of DA and was observed only during the first application of NMDA. The second phase developed more slowly, was of longer duration (1-3 min), and had electrochemical characteristics of a mixture of DA and NO. Generation of the NO-like signal by NMDA was antagonised by L-N-monomethylarginine. Pressure ejection of NO into CPu slices caused dose- and site-dependent DA release. More DA was released in the dorsolateral than in the dorsomedial CPu. Pressure ejection of DA did not generate NO. It is concluded that electrically stimulated DA release is not mediated by prior release of NO.

Animals↗
PubMed1984

Metabolic effects of intensified insulin therapy.

Intensified insulin therapy is usually carried out either with multiple subcutaneous insulin injections (ICT: intensified conventional therapy) or with continuous subcutaneous insulin infusion (CSII) by minipumps. For two years we have been studying two matched groups of type I diabetic patients, treated with 3 daily insulin injections (ICT) and with CSII ( Microjet , Miles), respectively. Blood glucose control, as assessed by integrated mean blood glucose (MBG), was similar in both groups, but a better metabolic stability ('M' index of Schlichtkrull ) was evident in the CSII group. From the 24-hour profiles of plasma 'free' IRI and metabolites (glucose, beta-OH-butyrate, lactate, pyruvate, alanine), both the hepatic and peripheral underinsulinization and related metabolic alterations were still evident in both groups of patients. The number of hypoglycaemic episodes, recorded by home blood glucose monitoring, was similar in both groups of patients, while the perception of symptomatic hypoglycaemia seemed to be reduced in the patients treated with CSII.

Alanine↗
PubMed2005

Complications of ultrasound guided percutaneous ethanol injection therapy of the thyroid and parathyroid glands.

OBJECTIVES: Since 1990 percutaneous ethanol injection therapy (PEIT) has been applied clinically as a treatment strategy for focal and diffuse autonomy of the thyroid, for cystic lesions and for ablation of parathyroid hyperplasia (PEA). There are some additional indications currently under consideration as for example inoperable advanced cancer of the thyroid. Since its inception PEIT and PEA have been regarded as an effective, inexpensive and low risk procedure. MATERIAL AND METHODS: We discuss mild and severe complications of these methods reported in literature and the first case so far of a severe ethyl toxic necrosis of the larynx and adjacent skin in a patient treated with PEIT by a radiologist. RESULTS: To date, no serious side effects have been reported in connection with these therapies. Some authors conclude that the side effects are in no way negligible and caution and routine should be exercised when using PEIT or PEA. Most complications have been transient in nature. The complication of ethyl toxic necrosis of the larynx was serious and the patient was admitted to hospital, treated conservatively and ten month later microsurgically. Voice thus could be restored to almost normal. CONCLUSIONS: PEIT for focal and diffuse autonomy, for cystic lesions of the thyroid, for thyroid hyperplasia and PEA for parathyroid hyperplasia are methods which are inexpensive and can be performed on an ambulatory base. These are the methods of choice if surgical intervention or radioiodine therapies are not practicable out of medical reasons or by refusal of the patient. The patient must be informed about possible severe complications. The examiner should have substantial experience in these methods. If complications an early opinion of a specialist is required.

Adenoma↗
PubMed2002

Potential use of autoinjector-packaged antidotes for treatment of pediatric nerve agent toxicity.

STUDY OBJECTIVE: We sought to determine the feasibility of discharging Mark 1 atropine and pralidoxime autoinjectors into small, sterile vials to facilitate the potential intramuscular injection of these antidotes, particularly pralidoxime, on a milligram per kilogram basis to small children. METHODS: Autoinjectors were swabbed with isopropyl alcohol and then discharged into emptied, sterile, plastic 10-mL vials. This was repeated with the investigator garbed in standard personal protective gloves and full face mask and hood. The autoinjector injection surfaces were cultured. RESULTS: The autoinjectors were easily discharged into the vials without need for practice or special dexterity, even when investigators were garbed in protective gear. A small core of rubber stopper might be injected into the vial, and thus, the vial contents need to be withdrawn through a filter needle before reinjection. The autoinjector injection surfaces were sterile after alcohol swabbing. CONCLUSION: Autoinjectors might be a readily available source of concentrated pralidoxime for potential intramuscular use in small children.

Antidotes↗
PubMedDate not supplied

Dermal and transdermal drug delivery systems: current and future prospects.

The protective function of human skin imposes physicochemical limitations to the type of permeant that can traverse the barrier. For a drug to be delivered passively via the skin it needs to have adequate lipophilicity and also a molecular weight <500 Da. These requirements have limited the number of commercially available products based on transdermal or dermal delivery. Various strategies have emerged over recent years to optimize delivery and these can be categorized into passive and active methods. The passive approach entails the optimization of formulation or drug carrying vehicle to increase skin permeability. Passive methods, however do not greatly improve the permeation of drugs with molecular weights >500 Da. In contrast active methods that normally involve physical or mechanical methods of enhancing delivery have been shown to be generally superior. Improved delivery has been shown for drugs of differing lipophilicity and molecular weight including proteins, peptides, and oligonucletides using electrical methods (iontophoresis, electroporation), mechanical (abrasion, ablation, perforation), and other energy-related techniques such as ultrasound and needless injection. However, for these novel delivery methods to succeed and compete with those already on the market, the prime issues that require consideration include device design and safety, efficacy, ease of handling, and cost-effectiveness. This article provides a detailed review of the next generation of active delivery technologies.

Administration, Cutaneous↗
PubMed1983

Insulin therapy: progress and prospects.

Approaches to better control of diabetes with more sophisticated insulin therapy are being tested in the hope that they will prevent the sequelae that incapacitate and kill. Some of the regimens and techniques are relatively simple and practicable; others are less easily implemented; still others are speculative. Collectively, they add up to an encouraging outlook for effective treatment.

Blood Glucose↗
PubMed1984

Calcium mediates the light-induced decrease in maintained K+ current in Limulus ventral photoreceptors.

In addition to increasing the conductance to sodium, light reduces the maintained voltage-dependent potassium current (iK) in Limulus ventral photoreceptors. We have investigated the mechanism underlying this long-lasting decrease in ik. Intracellular injection of calcium produced a similar reduction of the voltage-dependent outward current. This reduction was not due to an activation of the voltage-dependent inward current (iin) because calcium injection reduced the outward current even under conditions where iin was blocked with Ni2+, and because calcium injection produced a decrease in conductance, as measured from the slope of the instantaneous i-V curve. The effect of light on ik could be blocked by injection of the calcium buffer EGTA (pCa 7.1) to an intracellular concentration of 50-70 mM. Even larger injections of the pH buffer MOPS (100-200 mM) did not reduce the effect of light on ik. These experiments show that intracellular free calcium (Cai2+) can reduce ik. Furthermore, since Cai2+ is known to increase in light, our results are consistent with the hypothesis that calcium is the internal transmitter for the light-induced decrease in ik.

Animals↗
PubMed1984

Light reduces the voltage-dependent inward current in Limulus ventral photoreceptors.

In Limulus ventral photoreceptors, illumination not only increases a specialized light-activated sodium conductance but also modulates voltage-dependent conductances. Previous work has demonstrated that the delayed rectifier current is reduced by light; we report here that the early voltage-dependent inward current is also reduced by light. Furthermore, by maintained during continuous depolarization and that this maintained inward current can be reduced by light. EGTA injection was found to increase the maintained inward current.

Animals↗
PubMed2000

Local tolerance, pharmacokinetics, and dynamics of ganirelix (Orgalutran) administration by Medi-Jector compared to conventional needle injections.

The feasibility of administering a relatively high dose of the gonadotrophin-releasing hormone (GnRH) antagonist ganirelix by means of a needle-free injection device, which could be useful in the long-term treatment of sex-steroid-dependent disorders, was evaluated in a randomized, crossover study in 16 healthy females. Local tolerance and pharmacokinetics of ganirelix administered by MediJector versus conventional needle injections were compared. Additionally, the pharmacodynamic effect was evaluated. Two milligrams of ganirelix was administered s.c. once daily for 7 days by Medi-Jector or conventional needle in a randomized sequence, without a washout period. No apparent differences in local tolerance were observed. Most injections (87.5%) gave either no or only a mild reaction. Of the moderate reactions, swelling and redness were reported most frequently (overall 4.9 and 8.5% per injection, respectively). Administration by Medi-Jector was bioequivalent to conventional needle injection with respect to the peak concentration and area under the curve. A profound suppression of luteinizing hormone and follicle stimulating hormone was observed. Serum oestradiol and progesterone concentrations were relatively low prior to treatment and remained low during the entire study period. In conclusion, administration of a relatively high dose of ganirelix by Medi-Jector might be useful for long-term treatment of sex-steroid dependent disorders.

Adult↗
PubMed1995

Insertional sequence primers for Bordetella pertussis diagnostic polymerase chain reaction differentiate strains of Pseudomonas cepacia.

Insertion sequence primers originally intended to amplify a singular specific product for the rapid diagnosis of Bordetella pertussis respiratory infection were used to differentiate strains of Pseudomonas (Burkholderia) cepacia. A modified sample preparation of proteinase K treatment and boiling was used in lieu of DNA extraction. The method was simple, rapid, and reproducible. This scheme identified 10 variations among 35 strains. Repeat strains from patients with cystic fibrosis and epidemiologically linked strains from an infection associated with a jet gun injection device were homologous in each setting.

Bacteremia↗
PubMed1975

Comparison of two steroid preparations used to treat tennis elbow, using the hypospray.

Methyl prednisolone acetate and hydrocortisone acetate were compared in a trial using the Hypospray to treat tennis elbow. There was little difference between the two preparations as far as side-effects and short-term suppression of symptoms were concerned, both being successful. However, late recurrence was very common in both groups, suggesting that a reappraisal of local steroid in this condition is needed.

Acetates↗
PubMedDate not supplied

A proposed mechanism for transient increases in arterial pressure and flow during angiographic injections.

In a series of animal experiments, we have confirmed the observation that arterial pressure and flow increase distal to the injection site during power injections through non-obstructing catheters. Our data suggest that the phenomenon is secondary to the transient production of turbulence. Thus, for a given injection rate, catheters with smaller end holes create more fluid velocity, which increases the Reynolds number and causes augmentation of downstream pressure and flow. The addition of side holes decreases the fluid velocity of the injectate and minimizes the hemodynamic effects. The discussion deals with factors contributing to the generation of local turbulence, the magnitude of pressure and flow changes caused by the injections, and the clinical implications of these artifacts.

Angiography↗
PubMed1988

No pulmonary edema or congestion after central venous injection of conventional and newer contrast media in dogs.

Our aim was to determine whether large central venous doses of ionic diatrizoate, nonionic iopromide, or nonionic iotrolane produce pulmonary edema or pulmonary congestion in dogs. Eighteen dogs (six per group) anesthetized with piritramide and N2O received three sequential doses (1.5 mL/kg body weight) of one contrast medium in less than 20 seconds. Before the first injection, and again 1, 5, 10, 20, and 30 minutes after each contrast injection, extravascular lung water, pulmonary blood volume, and cardiac output were determined by thermal-dye dilution. Neither extravascular lung water nor pulmonary blood volume increased after any contrast medium. Pulmonary blood volume and cardiac output decreased slightly but not significantly after all contrast media during the course of the study. We conclude that diatrizoate, iopromide, or iotrolane do not produce pulmonary edema or congestion in dogs.

Animals↗
PubMed2006

Enfuvirtide plasma levels and injection site reactions using a needle-free gas-powered injection system (Biojector).

OBJECTIVES: To assess the use of the Biojector B2000 needle-free gas-powered injection system for subcutaneous administration of enfuvirtide in HIV-infected patients and to compare this system with standard needles and syringes with respect to ease of use, severity of injection site reactions (ISR), and enfuvirtide plasma levels. DESIGN: An observational study among 32 treatment-experienced HIV clinic patients receiving enfuvirtide. METHODS: Adult patients were assessed before and after switching from standard needles to the Biojector for enfuvirtide administration. Patients used the Biojector for up to 24 weeks and rated ease of use from 0 (easy) to 3 (difficult). ISR were graded from 0 to 31 for signs and symptoms (erythema, induration, pruritus, nodules/cysts, ecchymosis), duration of individual lesions, and number of lesions. Plasma was collected pre-dose and 1 h post-dose for enfuvirtide measurement. The high-pressure liquid chromatography with tandem mass spectrometry method used was specific for enfuvirtide over its known plasma metabolite. Wilcoxon rank sum tests were used to compare needle-based and Biojector outcomes. RESULTS: The Biojector was rated as being significantly easier to use (P < 0.001) and reduced the occurrence of ISR compared with standard needles (P < 0.001). Enfuvirtide plasma levels were not statistically different between the two administration methods at either pre-dose trough (P = 0.41) or 1 h post-dose (P = 0.74). CONCLUSIONS: The Biojector needle-free injection system was easy to use for enfuvirtide administration and was associated with a decreased severity of ISR. Plasma enfuvirtide levels pre-dose and 1 h post-dose were comparable when injecting with standard needles or the Biojector.

Adult↗