A method for comparing the peak intensity and duration of action of aerosolized bronchodilators using bronchoprovocation with methacholine

The effects of aerosolized metaproterenol (1.30 mg) and isoetharine (1.02 mg) on nonspecific airway responsiveness to inhaled methacholine were quantitated and compared in 6 asthmatic subjects for 4 h after dosing. Both metaproterenol and isoetharine demonstrated bronchodilatation and reduced airway responsiveness during the first hour. Isoetharine had lost its bronchodilator effects and its effects on airway responsiveness by 2.25 h. The effects of metaproterenol on airway responsiveness had decreased by half at 2.25 h, while its bronchodilator effect remained maximal. Metaproterenol had no effect on airway responsiveness by 4 h, despite persisting bronchodilatation. Thus, for metaproterenol, there is disparity between duration of bronchodilation and suppression of airway responsiveness. Because methacholine sensitivity is a measure of nonspecific airway responsiveness, which appears to correlate with the severity of asthma, this methodology may provide more relevant information for assessment of duration of effect and estimation of appropriate dosing intervals for maintenance therapy than do more traditional methods.     

Hepatitis and cholestasis in infancy: clinical and nutritional aspects

A major complication of cholestasis is fat malabsorption related to decreased intestinal bile acids, which leads to malnutrition and fat-soluble vitamin deficiency. The impaired excretion of bile acids leads to a low intraluminal micellar concentration that causes long-chain triglyceride lipolysis and absorption to be ineffective. Medium-chain triglycerides (MCTs) are more readily absorbed when there are low concentrations of bile acids and therefore are a good source of fat calories; MCTs can be administered as MCT-containing formulas. In those children who are unable to take sufficient calories by mouth, it is important to start nocturnal enteral feeding to improve nutritional status. In infants with cholestasis, the absorption of fat-soluble vitamins (A, D, E and K) that require bile acids is also impaired, and supplementation is mandatory. Vitamin K deficiency may be responsible for hypoprothrombinaemia, which may lead to bleeding diathesis, Vitamin K (phytomenadione) should therefore be promptly administered intravenously, at a dose of 1 mg. Chronic vitamin E (α-tocopherol) deficiency is associated with a progressive neuromuscular syndrome that can cause cerebellar ataxia, areflexia and peripheral neuropathy. Supplements are given orally in doses of 3–5 times the normal requirement if cholestasis is incomplete. In complete cholestasis, supplements must be given intramuscularly at monthly intervals. In infants who fail to thrive, dietary supplements of carbohydrate polymers and MCTs are required.     

Spontaneous discharge patterns in cochlear spiral ganglion cells before the onset of hearing in cats

Spontaneous neural activity has been recorded in the auditory nerve of cats as early as 2 days postnatal (P2), yet individual auditory neurons do not respond to ambient sound levels <90-100 dB SPL until about P10. Significant refinement of the central projections from the spiral ganglion to the cochlear nucleus occurs during this neonatal period. This refinement may be dependent on peripheral spontaneous discharge activity. We recorded from single spiral ganglion cells in kittens aged P3-P9. The spiral ganglion was accessed through the round window through the spiral lamina. A total of 112 ganglion cells were isolated for study in nine animals. Spike rates in neonates were very low, ranging from 0.06 to 56 spikes/s, with a mean of 3.09 +/- 8.24 spikes/s. Ganglion cells in neonatal kittens exhibited remarkable repetitive spontaneous bursting discharge patterns. The unusual patterns were evident in the large mean interval CV (CV(i) = 2.9 +/- 1.6) and burst index of 5.2 +/- 3.5 across ganglion cells. Spontaneous bursting patterns in these neonatal mammals were similar to those reported for cochlear ganglion cells of the embryonic chicken, suggesting this may be a general phenomenon that is common across animal classes. Rhythmic spontaneous discharge of retinal ganglion cells has been shown to be important in the development of central retinotopic projections and normal binocular vision. Bursting rhythms in cochlear ganglion cells may play a similar role in the auditory system during prehearing periods.     

Primary Care Physicians’ Attitudes Regarding Race-Based Therapies

Background  

There is little to no information on whether race should be considered in the exam room by those who care for and treat patients. How primary care physicians understand the relationship between genes, race and drugs has the potential to influence both individual care and racial and ethnic health disparities.     

Autoantibodies against the platelet glycoprotein IIb/IIIa complex in patients with chronic ITP

Chronic idiopathic thrombocytopenic purpura (ITP) is caused by an antibody reactive with platelet-associated antigens. The present studies provide direct evidence that some patients with chronic ITP have autoantibodies against the platelet glycoprotein (GP) IIb/IIIa complex. Microtiter wells, coated with a monoclonal antibody (2G12) specific for GPIIb/GPIIIa were reacted with GPIIb/GPIIIa contained in a platelet extract. Control wells containing the same antibody were reacted with a cell extract containing no GPIIb/GPIIIa. After washing, the wells were reacted with patient or control plasma, and IgG binding was detected using 125I-Fab2-anti-human IgG. Assay values were expressed as binding ratios (cpm GPIIb/GPIIIa wells/cpm control wells). Plasma from 5 of 56 patients with chronic ITP had ratios (1.36-3.14) greater than 3 standard deviations above the mean (+/- SD) of control plasmas--0.93 +/- 0.12. Elevated values were also noted in two patients with anti-P1A1 antibody (ratios greater than 30) and in one patient with Hodgkin's disease and an ITP-like syndrome (ratio 1.53). Normal values were noted in 34 patients with a variety of immune and nonimmune diseases. Plasma from two of the positive ITP patients was reacted with 125I-surface-labeled platelets and, after solubilization, the IgG and bound antigen were precipitated with Staph-A. Autoradiographs from SDS- PAGE electrophoresis of the Staph-A-bound proteins shows two radioactive bands consistent in size with GPIIb and GPIIIa.     

A longitudinal study of incremental expansion using a mandibular lip bumper

A retrospective study using models was performed to evaluate the incremental expansion that occurred during mandibular lip bumper therapy in 44 adolescent patients. The purpose was to determine whether expansion occurs evenly between appointments or whether it attenuates with treatment time. Dental cast measurements were made for arch width and arch length. Treatment duration was broken into near-equal time segments and compared. Results showed that about 50% of the total expansion achieved occurred within about the first 100 days. Forty percent of the total amount of expansion occurred during the next 200 days, with only about 10% of the total expansion occurring after the first 300 days. It is unnecessary to have the appliance in place for longer than 300 days. The percentage of expansion that occurred at each time segment was not related to whether the patient had concomitant maxillary expansion.     

The immune system as a physiological indicator of marginal copper status?

Cu appears to have many important functional roles in the body that apparently relate, among others, to the maintenance of immune function, bone health and haemostasis. Some have suggested a role for long-term marginal Cu deficiency in the aetiology of a number of degenerative diseases. Accurate diagnosis of marginal Cu deficiency, however, has remained elusive despite an increased understanding of the biochemistry of Cu and its physiological roles in the body. Traditional markers of Cu status, such as serum Cu and caeruloplasmin protein concentrations are insensitive to subtle changes in Cu status. Cu-containing enzymes, such as Cu-Zn-superoxide dismutase, cytochrome c oxidase and diamine oxidase, may be more reliable but evidence to date is not conclusive. Development of markers sensitive to marginal Cu status is essential before conclusions can be drawn concerning the risks of long-term intake of suboptimal dietary Cu. As Cu appears to be essential for maintenance of immune function, activities of specific immunological markers, altered in Cu deficiency, offer alternatives. This review evaluates a selection of immunological markers that could be considered potentially sensitive markers of marginal Cu status. The indices of immune function reviewed are neutrophil function, interleukin 2 production, blastogenic response to mitogens and lymphocyte subset phenotyping.     

Education in Gynaecology and Obstetrics The Challenge

On March 24th, 1970 Her Majesty the Queen, Honorary Fellow of the College of Obstetricians and Gynaecologists, opened the first building of the Auckland School of Medicine which is now in its third year. Our Postgraduate School was established in 1948, the same year as the establishment of the New Zealand Regional Council. The growing school of medicine has come latterly under the influence of pre-clinical forces but with the advent of the clinical course in 1971 the clinical advisers are hard at work preparing a curriculum that must suit practitioners who will be still working in 2013, if the retiring age remains the same. "Upon the education of the people of this country the fate of this country depends" these words, spoken by Disraeli in the House of Commons in June 1874, are no less true in this or any other country today.