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Effect of gender and device mouthpiece shape on bolus insulin aerosol delivery using the AERx pulmonary delivery system.

PURPOSE: A study was designed to compare differences in insulin aerosol deposition profiles in healthy male and female subjects, as well as examine the effect of mouthpiece cross-sectional shape, volume, and taper on deposition profiles using a developmental AERx pulmonary delivery system. METHODS: Six mouthpieces were screened in the laboratory, and three were selected for clinical investigation: a cylindrical mouthpiece with constant-cross-sectional area, an elliptical mouthpiece with constant-cross-sectional area, and a tapered elliptical mouthpiece with an exit cross-sectional area equal to one half the entrance cross-sectional area. RESULTS: There was no significant difference in the lung dose or in the deposition pattern between males and females (p > 0.05, by ANOVA). The cross-sectional shape of the mouthpiece had no significant effect on the clinical lung dose or the deposition pattern (p > 0.05, by ANOVA), although in vitro testing showed lower emitted dose values with the tapered elliptical mouthpiece (by ANOVA and Duncan's multiple range test, alpha = 0.05). Using the tapered mouthpiece in the clinic resulted in significantly more deposition on the mouthpiece itself when compared to the nontapered mouthpieces. CONCLUSION: Inhalation of insulin using the AERx system was insensitive to differences in male and female respiratory tract geometry across all mouthpiece designs examined.

Adult↗

Delivery times for caesarean section at Queen Elizabeth Central Hospital, Blantyre, Malawi: is a 30-minute 'informed to start of operative delivery time' achievable?

A timesheet questionnaire was used to assess the time it took from informing the anaesthetist about a case to the start of operative delivery in 78 consecutive patients undergoing caesarean section. Median (IQR [range]) times for grade-1 cases (immediate threat to the life of the mother or fetus) and grade-2 cases (fetal or maternal compromise without immediate threat to life) were 20 (17-35 [6-75]) min and 41 (27-60 [17-136]) min, respectively. Delays occurred in all the component time intervals examined. The primary avoidable delay was the patient's late arrival in theatre. Many significant delays were apparently not perceived by the anaesthetist. In nine (69%) grade-1 cases, the 30-min target decreed by the Association of Anaesthetists of Great Britain & Ireland and the Obstetric Anaesthetists' Association was achieved.

Anesthesia, Obstetrical↗

Chronic intraperitoneal insulin delivery, as compared with subcutaneous delivery, improves hepatic glucose metabolism in streptozotocin diabetic rats.

We have previously shown that chronic insulin treatment by the intraperitoneal route normalizes the elevated glucose production (GP) in streptozotocin (STZ) diabetic rats, while insulin delivered by the subcutaneous route only partially normalizes GP. To investigate the biochemical mechanism of the effect of chronic insulin delivery by either route on hepatic glucose metabolism, we measured the hepatic activity of glucose 6-phosphatase (G6Pase) and glucokinase (GK). Four groups of rats were used: (1) nondiabetic rats (N, n = 7), (2) untreated STZ diabetic rats (D, n = 8), (3) diabetic rats treated intraperitoneally (IP, n = 6), or (4) subcutaneously (SC, n = 8) (both 3 U of insulin/d). Glucose levels, higher in D, were normalized by insulin treatment regardless of route. Peripheral insulin levels were lowest in D and highest in SC as expected (N, 162 +/- 18 pmol/L; D, 66 +/- 12; IP, 360 +/- 96; SC, 798 +/- 198). STZ diabetes resulted in a 10-fold decrease in GK (P < .001), and a 2-fold increase in G6Pase activity (P < .01). Both intraperitoneal and subcutaneous treatments normalized G6Pase activity. In contrast, with subcutaneous but not intraperitoneal treatment, GK activity was still 35% less than normal (SC v N, P < .05). Glucose 6-phosphate (G6P) levels did not differ among the groups. In summary: (1) the increase in GP in D reflected increased activity of G6Pase and reduced activity of GK, (2) the partial suppression of GP with subcutaneous insulin treatment reflected correction of increased G6Pase activity, but only partial correction of low GK activity, and (3) the normalization of GP with intraperitoneal insulin treatment reflected correction of both increased G6Pase activity and low GK activity. Our current studies indicate that chronic intraperitoneal insulin treatment is superior to subcutaneous treatment with regard to hepatic glucose metabolism.

Animals↗

Synthesis, characterization, biodegradation, and drug delivery application of biodegradable lactic/glycolic acid polymers: Part III. Drug delivery application.

Lactic/glycolic acid polymers (PLGA) are widely used for drug delivery systems. The microsphere formulation is the most interesting dosage form of the PLGA-based controlled release devices. In this study, the previously reported PLGA were used to prepare drug-containing microspheres. Progesterone was used as a model drug. The progesterone microspheres were prepared from PLGA having varied compositions and varied molecular weight. The microscopic characterization shows that the microspheres are spherical, nonaggregated particles. The progesterone-containing PLGA microspheres possess a Gaussian size distribution, having average size from 70-134 microm. A solvent extraction method was employed to prepare the microspheres. The microencapsulation method used in this study has high drug encapsulation efficiency. The progesterone release from the PLGA microspheres and the factors affecting the drug release were studied. The release of progesterone from the PLGA microspheres is affected by the properties of the polymer used. The drug release is more rapid from the microspheres prepared using the PLGA having higher fraction of glycolic acid moiety. The drug release from the microspheres composed of higher molecular weight PLGA is faster. The drug content in microspheres also has an effect on the drug release. Higher progesterone content in microspheres yields a quicker initial burst release of the drug.

Biocompatible Materials↗

Chemotherapeutic agent permeability to normal brain and delivery to avian sarcoma virus-induced brain tumors in the rodent: observations on problems of drug delivery.

Four chemotherapeutic agents (cyclophosphamide, 5-fluorouracil (5-FU), methotrexate (MTX), and bleomycin) were given intravenously to rats harboring the avian sarcoma virus-induced glioma. Drug content in brain, tumor, and systemic tissue was measured. The uptake of drug and the consistency of drug levels in normal brain and tumor varied widely among these agents. [14C]Cyclophosphamide and its metabolites penetrated normal brain and, to a greater extent, brain tumor. [14C]5-FU and its metabolites also entered normal brain and brain tumor, but to lesser extent than [14C] cyclophosphamide and its metabolites. Immunoreactive MTX entry into tumor was variable, ranging from 30 to 1080 ng/g of tissue, with only minimal concentrations in normal brain. After conventional doses, immunoreactive bleomycin levels in tumor were also variable, ranging from 24 to 164 mu units/g of tissue, and little if any drug entered surrounding brain. In addition, the cerebrovascular permeability of 5-FU and MTX in normal rats was measured. Utilizing the method of Rapoport, the PA (product of permeability and capillary surface area) of 5-FU was found to be 6- to 12-fold greater than that of MTX. The PA of both drugs was increased 4- to 7-fold after osmotic blood-brain barrier opening. The variable "leakiness" of glial tumors, both experimentally and clinically, as well as the varied permeabilities of different water-soluble chemotherapeutic agents, makes the drug delivery problem in brain tumors a very complex issue.

Animals↗

Let's reach all of the market for health administration education: design, development, and delivery issues in distance delivery.

Web-based distance learning is an up and coming form of education. Web-based education delivered via a Web browser through the Internet has been found to be less expensive, more efficient, and sometimes more effective than classroom training. In the distance learning environment, the traditional "lecture and chalkboard" classroom pedagogy is completely absent. The virtual classroom becomes an "active learning" environment in which students, while utilizing technology, are able to discuss health administration concepts, analyze cases, work exercises, and discuss and share these interactively with both the instructor and fellow classmates. This method of Health Administration Education encourages students to learn from each other and promotes the open exchange of ideas and experiences. It does not require working students to put their careers on hold while they continue their studies. In this paper, we explore the opportunities and challenges of delivering web-based Health Administration courses via the Internet. Included is a discussion of the design, development, and delivery of a distance learning, web-based Health Administration Education system.

Adult↗

A method for increasing jet nebulizer delivery efficiency for aerosol drug delivery in ventilated newborns: an in vitro study.

BACKGROUND: A substantial percentage of the aerosol produced by a nebulizer is lost down the expiratory limb of the ventilator circuit. We describe a method for the capture, return, and re-aerosolization of that undelivered aerosol. METHODS: We designed an expiratory-limb setup in which an "entraining jet" of gas accelerates unused aerosol and propels it toward an impaction surface. The deposited solution is then returned to the nebulizer reservoir via a feedback tube. As a result, more of the initial dose is delivered to the patient. The fraction of the dose delivered to a filter connected to a passive neonatal test lung was measured with and without the aerosol-recycling components activated. We used a deltaP (difference between the peak inspiratory pressure and the positive-end-expiratory pressure) of approximately 7.5 cm H2O, tidal volume of approximately 6 mL, respiratory rate of 40 breaths/min, and an inspiratory-expiratory ratio of 1:2.3. RESULTS: There was a statistically significant improvement with the feedback return to the reservoir, with up to nearly 60% more aerosol delivered. CONCLUSION: This improvement in aerosol delivery is encouraging, but more comprehensive studies are needed before such a device could be implemented clinically.

Administration, Inhalation↗

In vivo delivery of estradiol from ceramic drug delivery devices.

Ceramic drug delivery systems (CDS) are capable of delivering a wide variety of chemicals and/or biologicals directly into the systemic circulation in a continuous manner over long intervals with minimum risk to the recipient. The objectives of the present study were: (i) to determine the capability of tricalcium phosphate (TCP) capsules to deliver estradiol (E) in a sustained manner into the circulation of intact adult male rats, and (ii) to investigate the physiological responses associated with the presence of constant levels of estradiol in adult male rats. Microcrystals, particle size of less than 38 um, of TCP powder were prepared using standard procedures. TCP capsules with an outer diameter of 0.8 cm and an inner diameter of 0.4 cm were prepared by compressing calcined materials in a cylindrical dye at a compression load of 700 Kg. The ceramic capsules had a final density of 1.82 +/- 0.03 gm/cm3. A total of 54 adult male rats were divided into three groups of 18. Each rat in group I was implanted intraperitoneally with 2 CDS, one TCP capsule impregnated with polylactic acid (PLA) and the second nonimpregnated TCP capsule. Each capsule contained 40 mg of E. Animals in group II were implanted with two similar capsules without E (shams) and group III animals which served as intact controls were not fitted with CDS. Eight rats from each group were euthanized 2, 4, or 6 months following CDS implantation. Ceramic capsules were retrieved from the euthanized animals and the amount of E left within the ceramic was determined.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Levodopa delivery from controlled-release polymer matrix: delivery of more than 600 days in vitro and 225 days of elevated plasma levels after subcutaneous implantation in rats.

Parkinson's disease is commonly treated with orally applied levodopa (l-dopa). However, because this treatment modality is associated with a number of undesirable side effects, some due to plasma fluctuations, we have developed a slow-release polymer system that can be used to deliver l-dopa continuously for extended periods of time in vitro (greater than 600 days) and in vivo (at least 225 days) in rats. In vitro l-dopa release was evaluated using polymer matrices with appropriately selected parameters (loading and geometry), and zero-order (linear) release of l-dopa was observed for more than 600 days (in highly loaded, noncoated material first-order kinetics), in some instances in mg quantities per day. This was achieved even in polymer matrices, which did not possess a dissolution limiting barrier. Scanning electron-microscopic analysis suggests that the mechanism of release is dissolution through channels and pores within the polymer matrix. To assess in vivo release, l-dopa was quantified in plasma from rats given s.c. implants of l-dopa polymer matrices using high-performance liquid chromatography. We observed release of l-dopa for a period of at least 225 days after an initial burst of release. Continuous release of l-dopa from s.c. implanted slow-release polymer matrices has several advantages over oral delivery: 1) l-dopa plasma fluctuations are eliminated, 2) patient compliance issues are reduced and 3) the gastrointestinal tract is circumvented, thus requiring a lower dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Delivery of antifibroblast agents as adjuncts to filtration surgery--Part II: Delivery of 5-fluorouracil and bleomycin in a collagen implant: pilot study in the rabbit.

A pilot study was performed in order to determine if filtration bleb longevity could be enhanced in rabbits by delivery of 5-fluorouracil or bleomycin in a collagen sponge implant. Results showed that both agents prolonged bleb longevity and lowered intraocular pressure when compared to controls. Bleomycin treated animals had the best bleb appearance and function at the longest postoperative intervals.

Animals↗

[Induction of lung maturation in pending premature delivery and scheduled premature delivery].

At the Women's Hospital of the Medical Academy of Erfurt we have examined the efficiency of dexamethasone on fetal lungs maturation at imminent premature birth and planned untimely delivery. Dexamethasone was given in a randomized series at a dosage of 12-mg per day orally on three successive days. The effectiveness of induction was measured at the percentage of the total phospholipid fraction in the amniotic fluid and at the mortality of RDS in both groups. A successful induction with dexamethasone we can only reach after the 32nd week of pregnancy.--Because this effect is not always continuous, we recommend to make the induction of fetal lungs maturation with dexamethasone and--if it necessary--its repetition after one week conditional upon the content of total phospholipids in amniotic fluid.

Adult↗

[Injury hazards in deliveries using the Shute forceps (analysis of 1016 forceps deliveries)].

Report about 1016 deliveries by means of the parallel forceps (W. B. Shute). This group contains pathologic-anatomical results of 30 stillbirthes or died newborns. Accordingly to the classification in subarachnoidal, subependymal or subdural hämorrhage there are only in two cases signs of obstetrical brain damage. The hypoxia is the most important reason of intracraniale haemorrhage. In order to an objektive indication, without progredient signs of fetal hypoxia the extraction by means of parallel forceps is not dangerous. We have used the instrument for extraction as well term as preterm infants with good results.

Adult↗