Biomedical subjects
Publications and source records attributed to S Miller.
As Hillary Clinton worked on the reforms of the US health system, three University of Minnesota fellows, Meeta Pherwani, Craig Hostetler and Sarah Miller, offered her some advice based on their experience with the NHS.
The origins of "Shaker Extract of Roots" or "Mother Siegel's Curative Syrup". Its introduction into the market in 1876 by A.J. White in accordance with the Shaker community. Its expansion into twenty-four countries world-wide. Its distribution in France by O.-J. Fanyau and his successors. Its demise in 1957-1959.
PURPOSE: To determine whether fellow eyes with normal visual acuity of patients with unilateral neovascular age-related macular degeneration (AMD) have retinal malfunction. METHODS: Foveal cone electroretinograms (ERGs) were recorded from fellow eyes with visual acuities of 20/25 or better of 73 patients with unilateral neovascular AMD and from 28 normal volunteers of comparable age. Responses were elicited with a 4 degrees stimulus flickering at 42 Hz presented by a stimulator-ophthalmoscope. RESULTS: The study eyes of the patients were found to have foveal cone ERGs that, on average, were normal in amplitude but delayed in implicit (peak) time after adjustment of the data for age, sex, iris pigmentation, and refractive error by multiple linear regression. Based on all subjects, amplitude declined with increasing age and was smaller in eyes with darker irides; implicit time increased with increasing age. CONCLUSIONS: These findings suggest that fellow eyes with normal visual acuity of patients with unilateral neovascular AMD tend to have foveal cones that are normal in number but that function abnormally. In addition, foveal cone ERG amplitude should be adjusted for both age and iris pigmentation and implicit time should be adjusted for age when assessing retinal function of elderly patients.
This study has examined the abilities of (+/-)-CP96345 and (+/-)-SR48968, nonpeptide antagonists selective for the tachykinin NK1 and NK2 receptors, respectively, to block bronchoconstriction caused by intravenous administration of direct-acting receptor agonists and the indirect-acting mimetics capsaicin, serotonin and 2-methyl-serotonin in the anesthetized guinea pig. The NK1 antagonist (+/-)-CP96345 was found to cause, at a maximally tolerated dose of 9 mumol/kg, an approximate 10-fold rightward shift of the dose-response curves for selective NK1 agonists substance P (SP), [Sar9,Met(O2)11]SP and Ac-[Arg6,Sar9,Met(O2)11]SP6-11 without altering responses to selective NK2 agonists neurokinin A (NKA), [Nle10]NKA4-10 or [beta-Ala8]NKA4-10. The NK2 antagonist (+/-)-SR48968 caused dose-dependent rightward shifts of the dose-response curves for the NK2 but not the NK1 agonists. Results using combinations of the receptor antagonists indicate that the NK2 agonists could cause bronchoconstriction by acting on the NK1 receptors at large doses relative to those used without antagonists. Of the agonists used here, [beta-Ala8]NKA4-10 appeared to be the most selective for the NK2 receptors. When used alone, only (+/-)-SR48968 was found to block bronchoconstriction caused by capsaicin, serotonin (after blockade of 5-HT2 receptors by LY53857) and 2-methyl-serotonin. When (+/-)-CP96345 was also given, larger additional blockade was seen with capsaicin than with serotonin or 2-methyl-serotonin as mimetic substance. Atropine caused small and variable degrees of blockade of serotonin and 2-methyl-serotonin but not of capsaicin after combinations of the two antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)
The frequency of an abnormally anterior insertion of scalenus anterior to the scalene tubercle on the superior aspect of the 1st rib was examined as a possible contributory factor to venous compression syndromes and to difficulties in cannulation of the subclavian vein. The insertion of scalenus anterior was exposed bilaterally in 21 adult cadavers and its position determined. The position of the scalene tubercle was also determined in a sample of 50 dried 1st ribs. The results were normalised for height. Three of the cadavers had position values that were above or at the upper point of the 95% confidence limits for the sample, indicating an abnormally anterior insertion. Two dried 1st ribs had values just below the lower 95% confidence limits, implying an abnormally posterior position. In the 3 cadavers with an abnormally anterior position, the subclavian artery and vein followed an abnormally anterior and inferior course with respect to the clavicle, and in 1 the subclavian vein was stenosed bilaterally at the costoclavicular angle. An abnormally anterior insertion of scalenus anterior may be a cause of venous compression syndromes in the root of the neck and give rise to difficulties when undertaking cannulation of the subclavian vein.
The anatomical relationships between the fiber tracts and bone lining cells within the rat calvarial periosteum have been studied by electron microscopy. Classical Sharpey's fibers were not observed in this location. Rather, thin unmineralized fibers originating from the periosteum traversed the cambial layer and passed to the bone surface between individual osteoblasts or groups of osteoblasts. The organizational relationship suggests that the osteogenic calvarial cell populations are compartmentalized into domains that might be particularly sensitive and responsive to the biomechanical forces of masticatory muscles.
Normothermic retrograde continuous cardioplegia is a revolutionary development for myocardial preservation in cardiac surgery. Despite excellent reports regarding this technique, the surgical community has expressed concern over technical problems encountered. The method of normothermic retrograde continuous cardioplegia in current use requires both large total crystalloid volumes and large potassium loads to deliver adequate cardioplegia. We have developed a technique that eliminates these problems. The heart is stopped by an initial infusion of normothermic cardioplegic solution through a coronary sinus catheter. The infusate is then converted to normothermic pump blood. Small boluses of potassium chloride are added intermittently to maintain cardiac arrest. We applied this technique to 35 patients undergoing cardiac valve surgery. The average volume of crystalloid cardioplegia required was 125 mL (range, 40 to 155 mL), and the average total potassium load was 52 mEq (range, 2 to 100 mEq). Clinically significant sequelae were noted in 4 patients (11%), and 1 (3%) died of pneumonia on the 28th postoperative day. The method we describe is a safe and effective alternative to the current technique of normothermic retrograde continuous cardioplegia and offers both physiologic and technical advantages to patients undergoing cardiac valve procedures.
Small peptides, derived from endogenous proteins bind within the antigen binding groove created by the beta-pleated sheets and alpha helices of the alpha 1 and alpha 2 domains of the class I molecule of the major histocompatibility complex (MHC). However, the precise role of peptide in class I MHC conformation remains unclear. Here, we have shown that, in at least some instances, changes induced in the MHC molecule by the binding of distinct peptides can be identified as specific alterations in serological epitopes expressed on the class I protein. The nature of specific peptides expressed by class I-bearing cells may, therefore, have a dramatic influence on T cell development, self-tolerance, and alloreactivity.
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Mutation of the c-myc gene locus has occurred during in vitro culture of the Burkitt lymphoma cell line Namalwa. Gene cloning and sequencing of this c-myc gene locus has revealed the insertion of incomplete copies of the Squirrel Monkey Retrovirus-Human (SMRV-H) proviral genome. Insertions of the SMRV-H genome were seen in all Namalwa cell lines tested, with multiple insertions being seen in some sublines. Viral particles with the morphology of type-D retrovirus, budding from these cells, were seen by transmission EM. New insertions of the genome were produced spontaneously in these cells. The origins of the type-D retrovirus and its implications for workers in the field are discussed.
The potential roles of adrenergic and noradrenergic terminals in the hypothalamic paraventricular nucleus in the regulation of blood glucose and free fatty acids, the two major metabolic fuels, were examined. Corticosterone was also measured, both to assess the specificity of any effects for metabolic fuels, and because endogenous catecholamines in this site have previously been implicated in corticosterone regulation. In the first experiment adult male albino rats having chronically implanted guide cannulae aimed at the hypothalamic paraventricular nucleus or the caudate nucleus received microinjections of the agonists methoxamine (alpha 1), clonidine (alpha 2), and isoproterenol (beta) (0, 10, 30, 100 nmol/500 nl), and blood samples were taken from the tail tip. In the second experiment a different set of rats received 30 nmol clonidine or vehicle subcutaneously instead of brain microinjections. Intracranial clonidine and isoproterenol produced marked and moderate hyperglycemia, respectively; methoxamine did not alter glucose. For neither clonidine nor isoproterenol was there any difference in hyperglycemia as a function of microinjection site; also, subcutaneous clonidine injections produced the same peak glucose response as was found after both paraventricular and caudate nucleus microinjections of the same dose. Free fatty acid levels were increased by clonidine and isoproterenol, but slightly suppressed by methoxamine; the alpha agonist effects, but not the beta agonist effect, were greater after paraventricular microinjections than after caudate microinjections. Corticosterone was increased by both alpha agonists after paraventricular but not after caudate nucleus microinjections; beta agonist microinjections into the paraventricular and caudate nuclei produced equivalent corticosterone elevations. These results suggest that most, if not all, of the hyperglycemic effects of alpha and beta adrenergic agonist microinjection into the paraventricular nucleus can be ascribed to leakage of the material into the vasculature, with subsequent action at a distant site. In contrast, all 3 agonists seem capable of acting within the brain to alter free fatty acid levels. The effects on corticosterone of both the alpha 1 and alpha 2 agonists, but not the beta agonist, also appear due, at least in part, to actions within the brain. Previous suggestions that catecholamine terminals in the hypothalamic paraventricular nucleus are directly and strongly involved in metabolic fuel regulation may require reconsideration.
Although electrophysiologic studies are often used to assess antiarrhythmic drug efficacy in patients with ventricular tachycardia (VT), the reproducibility of these studies during therapy has not been definitively established. Confirmation studies were performed during drug therapy in 64 patients (51 men, mean age 63 years) with sustained ventricular arrhythmias induced during initial study to assess the reproducibility of drug effect. All patients had coronary artery disease. The stimulation protocol used included the serial introduction of up to 3 premature ventricular stimuli during sinus rhythm and with ventricular pacing at 2 pacing rates. Rapid ventricular pacing techniques were also used. Antiarrhythmic drug efficacy was confirmed in 77% of patients. Sustained VT was induced at repeat electrophysiologic study in 19% of patients during antiarrhythmic therapy that was previously thought to be effective. In summary, electrophysiologic study results during antiarrhythmic therapy exhibit significant day-to-day variability. Sustained VT can be induced during antiarrhythmic therapy that was previously defined as effective by programmed stimulation in a substantial number of patients.
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Unscheduled DNA synthesis (UDS) induced by two exposure levels of ultraviolet light (UV) or two concentrations of methyl methane sulfonate (MMS) was evaluated in secondary cultures of lung fibroblasts established from weanling, 11-month-old and 31-month-old female Fischer 344 rats fed ad libitum (AL) or calorically restricted (CR) diets. [3H]Thymidine incorporation as a function of UDS was highest for weanling-derived cells treated with either UV or MMS, declining consistently with increased age between cells from weanling, 11-month-old and 31-month-old animals. [3H]Thymidine incorporation as a function of UDS in cells from 11-month-old AL vs. CR rats differed only at the highest UV exposure level. In contrast, cells derived from 31-month-old CR rats exhibited UDS levels which were at least twice as high at each UV treatment level as UDS levels of cells derived from the same age AL rats. Cells from both old AL and old CR rats were shown to initiate DNA excision repair at about the same rate. Cells from CR rats, however, repaired DNA damage at an accelerated rate and completed excision repair while repair in cells from AL animals was slower and apparently did not proceed to completion. Data from this study indicate that cells from young and old AL and CR animals initiate excision repair, but demonstrate an age-related loss of UV- or MMS-stimulated [3H]thymidine incorporation in cells derived from AL animals. Cells derived from CR animals did not exhibit that age-related loss of UDS activity; rather, they showed an enhanced UDS response to DNA damage and appeared to complete ligation as the final step in excision repair. The data suggest that caloric restriction of a cell donor animal not only delays the age-associated decrease in in vitro DNA excision repair capacity in cells from that animal, but may actually enhance repair capacity.
Human serum contains an inhibitor of leukotriene D4 (LTD4) dipeptidase which was separated from the enzyme by ultrafiltration (Amicon, YM-10). Removal of the inhibitor resulted in a 3- to 5-fold increase in total LTD4-dipeptidase activity in the material retained by the filter. Inhibitor activity (which was assayed with a partially purified LTD4-dipeptidase) was recovered in the filtrate. Ultrafiltration of serum using YM-3, YM-1, and YC-05 membranes suggested an inhibitor molecular weight of less than 500. Elution of inhibitor activity from a Bio Gel P2 gel filtration column was identical to the elution pattern of pure carbonate. The inhibitor was heat stable (95 degrees C, 30 min), stable in 0.1 N NaOH, but rapidly inactivated by 0.1 N HCl at both 4 degrees C and 30 degrees C. Partially purified LTD4-dipeptidase was inhibited by carbonate and phosphate but not by nitrate, sulfate, or chloride. Based on these observations it was concluded that the inhibitor of LTD4-dipeptidase in human serum either was carbonate or required carbonate. The relative concentrations of LTC4, LTD4, and LTE4 appear to be important parameters in determining the duration and intensity of LT mediated reactions. The relative concentration of carbonate in serum or extracellular fluids might, therefore, be a factor in modulating localized LT mediated responses.
People who stutter are frequently viewed as more anxious than nonstutterers and as being depressed. Further, a strong and pervasive stereotype is held by nonstutterers that people who stutter are guarded, nervous, and tense. This study examined self-perceptions of general state and trait anxiety, depression, and communication attitude in matched groups of stutterers and nonstutterers. Results refute the assertion that people who stutter are more anxious or depressed than those who do not. Anxiety and depression are not related to self-ratings of stuttering severity. Communication attitude is negative for this group of people who stutter and becomes increasingly negative as self-ratings of stuttering become more severe. People who stutter, grouped by severity rating, differed in the strength of the relation between measures of communication attitude, anxiety, and depression. Findings suggest that the anxiety of people who stutter is restricted to their attitude towards communication situations and that it is a rational response to negative communication experiences.
Cephalometric radiographs of 42 growth study subjects (21 males, 21 females) were the basis of an investigation into the longitudinal growth of the mandible from 5 to 20 years using a digitizer program capable of generating curved outlines through groups of four points. In this presentation mean plots for all subjects at 5, 10, 15, and 20 years of age, variously superimposed, confirmed the previous theories of Björk and Skieller (1983) with regard to mandibular rotation and provide a visual representation of the processes of mandibular growth.