Biomedical subjects

D Franklin

Publications and source records attributed to D Franklin.

At least 37 records · Page 2Linked to original sources

PubMed1995

Problems encountered in meeting the Recommended Dietary Allowances for menus designed according to the Dietary Guidelines for Americans.

Forty-three menus that were to be used in a diet manual were designed to meet the requirements of a specific diet; provide 2,200 to 2,400 kcal, unless energy-restricted; meet the 1990 Dietary Guidelines for Americans; meet current recommendations for sodium (2g to 3 g/day), cholesterol (< or = 300 mg/day), and fiber (20g to 30 g/day); and meet or exceed the highest level for adults in the 1989 Recommended Dietary Allowances (RDAs). In addition, regular and low-fat, low-cholesterol menus for 1 week were collected from 11 hospitals throughout Arkansas. Menus were analyzed for energy, cholesterol, and 18 nutrients. Only 11% of the menus met the RDA for zinc. Half of the menus did not meet the RDA for vitamin B-6 and one third did not meet the RDA for iron. Zinc content of the menus was positively correlated (P < .001) with protein (r = .73) and with beef (r = .45). Vitamin B-6 was positively correlated with protein (r = .44, P < .001) and with all meat (r = .38, P < .01). Regular and low-fat, low-cholesterol hospital menus had the same nutrient inadequacies because they did not differ in total servings from any food group. These data indicate that the public may have difficulty choosing a diet that meets both the Dietary Guidelines and the RDAs.

Arkansas↗

PubMed1994

Determinants of collateral development in a canine model with repeated coronary occlusion.

It is now accepted that repetitive 2-min coronary occlusion can develop collateral vessels to the area perfused by the occluded coronary artery. However, which factors influence collateral development has yet to be fully elucidated. The goal of the present study was to identify the determinants of the rate of coronary collateral development in dogs undergoing repeated coronary occlusion. The study was conducted in 19 conscious dogs instrumented for measurements of a subendocardial segment length in the area perfused by the left circumflex coronary artery (LCCA), LCCA flow, and left ventricular pressure. An externally inflatable pneumatic occluder was placed around the LCCA. After the recovery from surgery, 2-min LCCA occlusions were conducted eight times daily. Following 141 +/- 61 (SD) LCCA occlusions (20 +/- 7 days), an LCCA occlusion produced no reduction in segment shortening and negligible reactive hyperemia. The total number of LCCA occlusions needed for adequate collateral development (the rate of collateralization) correlated well with the severity of myocardial ischemia during the first occlusion, which was determined mainly by the extent of postsurgical initial collateral circulation. On the other hand, the response to the ischemic stimulus in the later stage of collateral development was independent of the extent of development of the initial postsurgical collaterals. It is concluded that the overall rate of collateral development is slower in dogs with initially poorer collaterals; however, the response of each dog to the ischemic stimulus in the later stage of collateral development was similar among dogs regardless of the extent of the initial collaterals.

Animals↗

PubMed1994

Two loci for tuberous sclerosis: one on 9q34 and one on 16p13.

32 families informative for the segregation of Tuberous sclerosis (TSC) have been examined for genetic markers on chromosomes 9, 11, 12 and 16. In one large family there was clear evidence of linkage to markers on chromosome 16p13.3 (lodscore with D16S291 of 4.7 at theta = 0) but other families were too small to give individually convincing lodscores. Combined results for all families gave positive results with ABO/DBH on chromosome 9 (max lod 2.63) and with D16S291 on chromosome 16 (max lod 3.98) at values of theta of 0.2 in each case. Further analysis showed strong evidence for heterogeneity with approximately half the families linked to a locus TSC1 on chromosome 9 between ASS and D9S298 and half to TSC2 on chromosome 16 close to D16S291. There was no definite support for a third locus although in many families this could not be excluded. In three families the segregation pattern of TSC remains unexplained. In two of these the family apparently segregates for TSC1 but in each case a single affected individual appeared to exclude the whole of the candidate region. Preliminary analysis of clinical features did not reveal any definite differences in incidence of mental handicap between individuals in different linkage groups or with different sex of the parent of origin. The frequencies of periungual fibromas and facial angiofibromas were also similar in both linkage groups. The difficulties of detecting linkage in small families where there is locus heterogeneity are discussed. The program ZZ was found to be helpful in this respect.

Adolescent↗

PubMed1992

Optimization of non-isotopic in situ hybridization on formalin-fixed, paraffin-embedded material using digoxigenin-labelled probes and transgenic tissues.

The sensitivity of non-isotopic in situ hybridization (NISH), particularly on formalin-fixed, paraffin-embedded (FFPE) clinical tissues, has been the subject of controversy. Generally, NISH has been regarded as being less sensitive than radiolabelled procedures, although some reports have contradicted this. Accordingly, tissues from mice which were transgenic for variable amounts of the human alpha-1-antitrypsin gene were used to optimize the NISH procedure and to estimate the sensitivity. This approach showed that prolonged incubation of slides in final substrate resulted in high sensitivity--about 13 kb of target DNA. However, this prolonged incubation crucially depended on achieving minimal non-specific background staining. Many factors affected the degree of background staining, but five were particularly important. First, the method of mounting cut sections onto slides. Second, the length of the probe (ideally less than 400 bp). Third, the procedure for proteolytic digestion. Fourth, the denaturation technique, and fifth, the quality of the dextran sulphate used in the hybridization mix. The optimized protocol showed variable patterns of mRNA distribution in the transgenic mouse livers, while DNA distribution appeared uniform.

Animals↗

PubMed1992

Generation of digoxigenin-labelled double-stranded and single-stranded probes using the polymerase chain reaction.

As the polymerase chain reaction (PCR) can be used for the generation of vector-free probes, the optimum conditions for incorporation of digoxigenin-11-dUTP into hepatitis B virus (HBV) probes have been investigated. High yields of double-stranded or single-stranded probes can be obtained by utilizing a pair of primers or one primer alone. The probes were tested by dot-blot hybridization on HBV plasmid DNA, slot-blot hybridization on total cellular RNA of Alexander cells and Southern blot hybridization on cellular DNA of Alexander cells and HBV plasmid DNA. They were also tested by in situ hybridization (ISH) on HBV-positive biopsy liver tissue. A ratio of dig-dUTP:dTTP of 1:3 gave highest sensitivity in DNA hybridization. No loss of amplification efficiency and sensitivity was observed when the final concentration of dig-11-dUTP and dTTP was reduced to 20 microM and 60 microM respectively, compared to 200 microM each of dATP, dCTP, dGTP. Several different sizes of double-strand probes were compared by dot-blot hybridization. Longer probes were more sensitive. Strong signal could also be obtained by combination of two or three small probes, which have overlapping sequences. Single-stranded DNA probes had advantages of simplicity of use, high sensitivity and strand specificity.

Base Sequence↗

PubMed1991

Bidirectional function of coronary collateral channels in conscious dogs.

STUDY OBJECTIVE: The aim was to investigate the bidirectional functional adequacy of collateral perfusion in conscious dogs. DESIGN: Left circumflex coronary artery (LCCA) occlusions of 1 or 2 min duration were repeated to stimulate the development of collateral perfusion to the LCCA area, and the left anterior descending coronary artery (LAD) was occluded once daily to evaluate the development of retrograde LCCA-LAD flow. SUBJECTS: 7 male mongrel dogs were used, weight 25-28 kg. MEASUREMENTS AND MAIN RESULTS: Coronary collateral flow from the LCCA to the LAD perfusion area was measured as the abrupt decrease in the LCCA flow (implanted Doppler transducer) upon release of a brief LAD occlusion. Measurements were repeated daily during the development of collaterals induced by repeated, brief occlusions of the LCCA. After 35(SD17) days of such occlusions; there was no sustained reduction in LCCA regional myocardial function during an LCCA occlusion, and reactive hyperaemic repayment following the occlusion was negligible. Before and after collateral development, the LCCA to LAD collateral flow increased from 1.1(0.2) to 8.6(5.1) cm.s-1. LAD systolic segment shortening during the LAD occlusion increased from 2.1(2.0)% (first occlusion) to 19.3(8.6)% (last occlusion). CONCLUSIONS: LAD to LCCA collaterals serve as functionally significant bidirectional perfusion conduits, and monitoring of collateral perfusion development is practical by measuring the step reduction in LCCA flow upon abrupt release of an LAD occlusion.

Animals↗

PubMed1991

Effects of coronary occlusion duration on reactive hyperemia in conscious dogs and ponies.

Coronary reactive hyperemia duration (RHD) and coronary blood flow debt repayment (BFDR) were compared in conscious dogs and ponies instrumented with coronary artery Doppler flow probes and pneumatic occluders. Additional ponies were instrumented with pacing electrodes. With the use of a Latin square design, eight animals of each species were subjected to a randomized series of nine coronary occlusions ranging from 5 s to 2 min in duration. In both species, postocclusion blood flow velocity rose rapidly and plateaued at similar peak levels relative to control, but in ponies this plateau lasted significantly longer. The interspecies difference in plateau duration increased as a function of coronary occlusion duration (COD). RHD ranged from 19.5 +/- 5.9 to 139.7 +/- 5.9 s in dogs and from 26.6 +/- 9.0 to 395.0 +/- 9.0 s in ponies. The slope of the RHD vs. COD curve was steeper in ponies. BFDR was similar in dogs and ponies at the shortest COD (418.1 +/- 26 vs. 451.4 +/- 58%) but declined in dogs as a function of COD to 232.3 +/- 26%. In ponies, BFDR increased as a function of COD to a maximum of 945.4 +/- 58% with a 60-s occlusion and then declined to 614.3 +/- 58%. RHD was not significantly altered in ponies when heart rate was changed to match that in dogs. Although the underlying basis for these interspecies differences in RHD and BFDR was not determined, the differences were considered to be too large to be explained by animal model differences in coronary conductance, collateral blood flow, or myocardial oxygen consumption.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Effects of nitroglycerin and diltiazem on well-developed coronary collateral circulation in conscious dogs.

The purpose of the present study was to compare the effects of nitroglycerin and diltiazem on coronary collateral circulation. Studies were conducted in 8 conscious dogs instrumented for the measurement of left circumflex coronary artery (LCCA) flow, subendocardial segment lengths in areas perfused by the LCCA, and left anterior descending coronary artery (LAD). Brief, repeated LCCA occlusions sufficiently developed collateral vessels for the resting metabolic requirement in the LCCA region. One week following the cessation of repeated LCCA occlusions, two-minute coronary occlusions with and without drug pretreatment were performed on separate days. The ischemic responses to coronary occlusions were not altered by diltiazem (50 micrograms/kg, IV), but nitroglycerin (5 micrograms/kg, IV) attenuated myocardial ischemia definitely. The authors conclude that nitroglycerin produces greater effects than diltiazem in attenuating myocardial ischemia in the collateral dependent zone when effects of each drug on systemic and coronary circulation were minimized by pretreatment with small doses.

Animals↗

PubMed1990

Importance of myocardial ischemia for coronary collateral development in conscious dogs.

The purpose of this study was to evaluate the effects of myocardial ischemia on the development of collateral circulation. Thirteen conscious dogs were instrumented for serial measurements of subendocardial segment length in the area perfused by the left circumflex coronary artery, left circumflex coronary artery flow and left ventricular pressure. In 6 dogs (group A), 1 min left circumflex coronary artery occlusions were carried out at 30 min intervals. When the 442nd 1 min left circumflex coronary artery occlusion produced a reduction in segment shortening and a significant reactive hyperemia, the occlusion time was increased to 2 min. In the remaining 7 dogs (group B), 2 min left circumflex coronary artery occlusions were conducted hourly. In group A, following 451 +/- 201 (SD) min of total occlusion time with the mixture of 1 and 2 min left circumflex coronary artery occlusions (43 +/- 18 days) a left circumflex coronary artery occlusion produced no reduction in segment shortening and negligible reactive hyperemia. By contrast, in group B, 218 +/- 99 min of total occlusion time (18 +/- 8 days) was required to develop adequate collateral circulation. The relative contribution of the first and second 1 min of left circumflex coronary artery occlusion to the collateral development was mathematically evaluated. This analysis indicated that the second 1 min of left circumflex coronary artery occlusion is 4.43-fold more effective than the first 1 min of occlusion in terms of the collateral induction. We concluded that severe myocardial ischemia plays an important role in the development of collateral circulation.

Animals↗

PubMed1990

Coronary collateral regression in conscious dogs.

To study the effect of long-term coronary reperfusion on regression of newly developed collateral vessels, the authors reoccluded the coronary artery for ten minutes following one to fifteen weeks of reperfusion. They repeated one- or two-minute occlusions of the left circumflex coronary artery (LCCA) in 8 conscious dogs. After 401 +/- 202 (SD) minutes of total LCCA occlusion time (35 +/- 19 days), The LCCA occlusion produced no sustained reduction in regional myocardial shortening and negligible reactive hyperemia. Upon reocclusion following a long-term reperfusion, the subendocardial segment shortening in the region at risk deteriorated markedly. At two minutes of occlusion, percent systolic shortening showed minimal values and thereafter gradually returned to the preocclusion resting levels within six to eight minutes of occlusion. In the presence of a resting heart rate similar to that at the time of functional recovery during the LCCA occlusion, long-term reperfusion did not modify the time course of regional functional response to the prolonged coronary occlusion. It is concluded that the newly developed collateral vessels still serve as significant blood-conveying conduits following a considerable period of reperfusion, and it requires approximately six to eight minutes to restore regional myocardial function in the collateral dependent zone following coronary reocclusion.

Animals↗

PubMed1989

Changes in regional myocardial cross-sectional area during brief coronary occlusion and reperfusion in conscious dogs.

The effect of a brief period of coronary occlusion on a regional myocardial cross-sectional area was studied in 6 conscious dogs. Subendocardial segment length and wall thickness were continuously measured with a sonomicrometer in the central ischemic area perfused by the left circumflex coronary artery during a 2-min circumflex occlusion and subsequent reperfusion. Measurements were repeated before and after collateral development induced by 180 +/- 30 (SEM) 2-min circumflex occlusions (20 +/- 3 days). In order to evaluate the changes in regional myocardial volume, end-diastolic regional cross-sectional area was calculated as a product of end-diastolic segment length and wall thickness. Before collateral development, end-diastolic regional cross-sectional area transiently decreased 1.4 +/- 0.6% (NS) at 10 sec following sudden coronary occlusion, thereafter gradually increased to 3.7 +/- 1.0% (P less than 0.05) at the end of a 2-min occlusion. At 10 sec of reperfusion, end-diastolic regional cross-sectional area further increased to 7.0 +/- 1.1% (P less than 0.05) probably due to increased intravascular volume. Increase in end-diastolic regional cross-sectional area was still 2.5 +/- 0.6% (NS) at 3 min after the release of occlusion. After collateral development, the changes in end-diastolic regional cross-sectional area were 0.1 +/- 0.1% (NS), 0.4 +/- 0.3% (NS), 1.0 +/- 0.6% (NS) and 0.2 +/- 0.4% (NS), respectively. Thus, a significant increase in the regional myocardial cross-sectional area occurs during a brief period of coronary occlusion and reperfusion.

Animals↗

PubMed1989

Changes in isovolumic segment shortening following acute coronary occlusion: disproportionate effects of anterior versus posterior ischemia.

We evaluated the changes in left ventricular pressure and isovolumic segment shortening in both the ischemic and nonischemic areas following acute coronary occlusion in 12 conscious dogs instrumented for the measurement of subendocardial segment lengths perfused by the left circumflex coronary artery and left anterior descending coronary artery, and left ventricular pressure. An externally inflatable pneumatic occluder was placed around the left circumflex coronary artery. In 6 dogs, another occluder was installed around the proximal left anterior descending coronary artery. Under the resting conditions, the isovolumic segment shortening in the areas supplied by the left anterior descending coronary artery and the left circumflex coronary artery were 2.1 +/- 0.5% (SE) and -0.1 +/- 0.5% (P less than 0.01; versus values in the area of the left anterior descending coronary artery), respectively. During a 1-min occlusion of the left circumflex coronary artery, the isovolumic shortening in the anterior segment increased to 3.8 +/- 0.5% (P less than 0.001; versus values in the basal state), while the posterior segment produced isovolumic elongation (-2.2 +/- 0.5%, P less than 0.001; versus values in the basal state). By contrast, during a 1-min occlusion of the left anterior descending coronary artery, the extent of isovolumic bulge in the anterior segment and the augmentation in the isovolumic shortening in the posterior segment was less prominent compared with the occlusion of the left circumflex coronary artery.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

An automatic syringe for coronary occlusion in long-term collateralization studies.

A portable apparatus for performing repeated, brief coronary artery occlusions automatically in long-term chronic studies involving dogs and larger animals is described. The battery-operated, back-pack-carried device uses a motorized syringe driven by a digital-programmable timing circuit to inflate a coronary artery occluder for durations of 10 s to 3 min at intervals from 14 s to 16 h. A single battery charge produces 450 occlusions. The generated pressure is adjustable to 1,000 mmHg maximum. A separate fail-safe circuit monitors system operation to open a pressure-relief valve if occlusions exceed a preset duration.

Animals↗

PubMed1988

Cadmium fume inhalation and emphysema.

Lung function and chest radiographs of 101 men who had worked for 1 or more years manufacturing copper-cadmium alloy were compared with those of a referent group matched for age, sex, and employment status. Cigarette consumption was similar in the two groups. The cadmium workers had an excess of abnormalities of lung function and of radiographic changes consistent with emphysema. Classification of the cadmium workers by exposure categories based on either estimated cumulative cadmium exposure or liver cadmium measured by neutron activation analysis showed that abnormalities of lung function were greatest in those with the highest cumulative cadmium exposure or liver cadmium. The difference in the transfer coefficient (KCO) between cadmium workers and referents increased linearly with increasing cumulative exposure without evidence for a threshold. The estimated mean decrement in KCO for a cadmium worker employed 5 or more years with a cumulative exposure of 2000 yr.microgram.m-3 (exposure to the current UK control limit of 50 micrograms.m-3 for a working lifetime of 40 yr) lies between 0.05 and 0.3 mmol.min-1.kPa-1.l-1 (95% confidence interval). This decrement is consistent with the functional and radiological changes of emphysema observed in this group of workers.

Aged↗

PubMed1988

Regional myocardial volume alterations induced by brief repeated coronary occlusion in conscious dogs.

The purpose of this study was to evaluate whether brief repeated coronary occlusions induce changes in regional myocardial geometry at rest. Five conscious dogs were instrumented for the measurement of subendocardial segment length and transmural wall thickness in the ischemic area, subendocardial segment length in the normally perfused area, coronary flow and left ventricular pressure. After recovery from surgery, 180 (mean) 2 min coronary occlusions were given over a period of 20 days. The heart rate at rest, left ventricular peak systolic and end-diastolic pressures and peak positive first derivative of left ventricular pressure (dP/dt) remained unchanged throughout the experiment. In the normal area, the end-diastolic segment length at rest did not change significantly. By contrast, in the ischemic area, at 14 days after the initiation of repeated coronary occlusion, the end-diastolic regional cross-sectional area (product of segment length and wall thickness) at rest had increased by 9.7% (p less than 0.05); thereafter it decreased to 6.5% (p less than 0.05) above the value at rest before repeated occlusion despite an additional 6 days of coronary occlusions. At 10 days after the interruption of repeated occlusion, this value had regressed to 4.3% (p = NS) above control. These findings suggest the occurrence of regional myocardial hypertrophy confined to the ischemic area in response to the periodic ischemic stimulus.

Animals↗

PubMed1988

Electrocardiographic evaluation of collateral development in conscious dogs.

In seven conscious dogs, endocardial ST-segment changes within the central ischemic area at 2 min after coronary occlusion were compared with the amount of reactive hyperemia and collateral blood flow. With the use of ultrasonic dimension gauges implanted in the subendocardium perfused by the left anterior descending coronary artery (LAD) and left circumflex coronary artery (LCCA), endocardial electrocardiograms and regional myocardial dimensions were simultaneously measured. Collateral vessels were developed by repeated 2 min LCCA occlusions during three weeks. Blood flow debt repayment following the release of LCCA occlusion was measured using a Doppler flowmeter. The collateral blood flow from LCCA to the area supplied by the occluded LAD was measured as a stepwise reduction in LCCA flow upon the release of LAD occlusion. With the attenuation of myocardial ischemia due to the collateral development, endocardial ST-segment shift revealed earlier restoration compared with subendocardial function. In the presence of mild ischemia, the ST-segment was still elevated. Thus, endocardial ST-segment changes serve as an indirect functional index of collateral development as well as regional myocardial function and blood flow debt repayment.

Animals↗

PubMed1988

Effects of glyceryl trinitrate on functionally regressed newly developed collateral vessels in conscious dogs.

The effects of glyceryl trinitrate on collateral blood flow and regional myocardial function during a 2 min coronary occlusion were evaluated in 10 conscious dogs with well developed collateral vessels. Collateral growth was promoted by brief, repeated, reversible coronary occlusions. After partial regression in collateral function a small dose of glyceryl trinitrate (5 micrograms.kg-1) was injected intravenously 1 min before coronary occlusion. After pretreatment with glyceryl trinitrate the collateral blood flow velocity (mean[SD]) increased from 3.0(0.9) to 4.4(1.4) cm.s-1 (p less than 0.05). After 2 min of occlusion the percentage systolic subendocardial segment shortening in the collateral dependent zone increased from 7.8(6.1) to 12.6(6.7)% (p less than 0.05). The blood flow debt repayment after release of the occlusion decreased from 122(41) to 68(34%) (p less than 0.05). Thus in conscious dogs with regressed newly developed collaterals a major component of the beneficial effects of glyceryl trinitrate on collateral circulation is dilatation of collateral vessels, as evidenced by a pronounced increase in collateral blood flow and myocardial function during a transient period of coronary occlusion.

Animals↗

PubMed1988

Opening of coronary collaterals by repeated brief coronary occlusions in conscious dogs.

The collateral blood flow and regional myocardial function during a one-minute coronary occlusion were compared before and after multiple one-minute coronary occlusions. After repeated coronary occlusions, the collateral blood flow velocity increased significantly from 0.7 +/- 0.1 (SE) to 2.0 +/- 0.2 cm/sec (p less than 0.05), and the blood flow debt repayment decreased from 326 +/- 26% to 189 +/- 12% (p less than 0.05). The systolic segment shortening in the collateral dependent zone improved slightly. Thus, the native coronary collateral vessels open in response to a repeated ischemic stimulus.

Animals↗