Biomedical subjects

D H Miller

Publications and source records attributed to D H Miller.

At least 433 records · Page 24Linked to original sources

PubMed1986

Ovarian increase in kinin-generating capacity in PMSG/hCG-primed immature rat.

Ovarian kinin-generating capacity was determined during induced ovulation in immature Wistar rats. The onset of ovulation was monitored by counting the number of ova in the oviducts at 2-h intervals after the administration of human chorionic gonadotropin (hCG). Ova began to appear in significant numbers at 14 h after hCG, with an average of 7.6 +/- 2.3 ova/rat. By 16 h after hCG, the oviducts contained 32.7 +/- 4.1 ova/rat. The ovaries from each group of animals were homogenized in phosphate-buffered saline, and extracts of this tissue were incubated for 200 min to allow the generation of kinins from endogenous kininogen. The amount of kinin generated by this procedure was measured by radioimmunoassay. At 0 h (i.e., just before the administration of hCG), the ovaries contained 5.90 +/- 0.60 pg kinin/micrograms protein per 200 min in the ovarian extract. By 4 h after hCG, the kinins increased significantly (P less than 0.05) to 13.16 +/- 3.61 pg kinin/micrograms protein. The kinins progressively increased (P less than 0.001) to 67.88 +/- 23.26 pg kinin/micrograms protein by 16 h after hCG. Indomethacin and cycloheximide significantly inhibited both kinin-generating activity and ovulation. These data suggest that kinin-forming activity and kinins may have a role in the ovulatory process of mammals.

Animals↗

PubMed1985

Electrocardiographic detection of left ventricular hypertrophy: development and prospective validation of improved criteria.

To develop improved electrocardiographic criteria of left ventricular hypertrophy, individual electrocardiographic voltage measurements were compared with echocardiographic left ventricular mass in a "learning series" of 414 subjects. The strongest independent relations with left ventricular mass were exhibited by the S wave in lead V3, the R wave in lead a VL and the T wave in lead V1 (each p less than 0.001), and by age and sex. Better electrocardiographic detection of left ventricular hypertrophy was achieved by new criteria that stratified QRS voltage and repolarization findings in sex and age subsets. For men, at all ages, left ventricular hypertrophy is suggested by QRS voltage alone when the R wave in lead aVL and the S wave in lead V3 total more than 35 mm. When this voltage exceeds 22 mm, left ventricular hypertrophy is suggested in men under age 40 years when the T wave in lead V1 is positive (greater than or equal to 0 mm), and in men 40 years or older when the T wave in lead V1 is at least 2 mm. For women, at all ages, left ventricular hypertrophy is suggested when the R wave in lead a VL and the S wave in lead V3 total more than 25 mm. When this voltage exceeds 12 mm, left ventricular hypertrophy is suggested in women under 40 when the T wave in lead V1 is positive (greater than or equal to 0 mm), and in women over 40 when the T wave in lead V1 is 2 mm or greater.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1985

Predictive value and limitations of the ST/HR slope.

To assess the value and predictive limitations of the exercise ST/HR slope, exercise test results were compared in 50 patients with stable angina and in 17 normal subjects with those in two groups known to have a high prevalence of inaccurate electrocardiographic responses to exercise. The last two groups included 51 patients tested within three weeks of acute myocardial infarction and 17 with important aortic regurgitation but no coronary disease. Of the normal subjects, 16 (94%) had ST/HR values less than or equal to 1 X 1 microV/beat/min. Of those with stable angina pectoris, 42 of 46 (91%) patients with coronary artery disease had ST/HR slopes ranging from 1 X 2 to 20 X 0 microV/beat/min, with false negative findings (slopes less than or equal to 1 X 1 microV/beat/min) in only four (9%). In contrast, of those with recent myocardial infarction, 15 of 42 (36%) with coronary disease had false negative slopes, including 12 of 20 (60%) with anterior wall injury. Of those with aortic regurgitation, conversely, 14 of 16 (88%) patients with calculable ST/HR slopes had values greater than 1 X 1 microV/beat/min despite the absence of coronary disease. Despite the accuracy of the test in patients with stable angina, false negative results are common in those after recent myocardial infarction, and false positive results occur often in those with abnormal volume loading due to aortic regurgitation.

Adult↗

PubMed1985

Urinary and renal tissue kallikrein in the streptozocin-diabetic rat.

The renal kallikrein-kinin system is thought to participate in blood pressure regulation and displays abnormalities in human hypertension, as well as in many animal models of hypertension. Urinary excretion and tissue levels of renal kallikrein were measured in streptozocin (STZ)-diabetic rats in relation to blood pressure, glycemia, and insulin treatment. In study 1, STZ-diabetic rats with marked hyperglycemia showed reduced kallikrein-like esterase excretion, compared with control rats, when first measured after 7 days of diabetes (9.9 +/- 2.5 versus 17.5 +/- 2.4 EU/24 h, P less than 0.05). This difference increased with time and, after 210 days, urinary esterase excretion in diabetic and control rats was 6.7 +/- 2.1 and 39.0 +/- 6.0 EU/24 h, respectively (P less than 0.001). Urine kallikrein, measured by radioimmunoassay, was similarly reduced in diabetic rats (40.4 +/- 8.0 versus 88.0 +/- 6.5 micrograms/24 h, at 30 days, P less than 0.001). At 120 days, systolic blood pressures were elevated in diabetic rats (P less than 0.05), and at 180 days over 60% of the diabetic rats had pressures above the highest pressures of control rats. In study 2, STZ-diabetic rats were treated with insulin for 2 wk (2 U NPH at 0800 h, or 2 U NPH at 0800 and 1600 h). In the single-dose group, with hyperglycemia similar to that of diabetic rats in study 1, kallikrein excretion was reduced as early as day 2, compared with nondiabetic rats (56.0 +/- 6.1 versus 109 +/- 9.4 micrograms/24 h, respectively, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1985

Tissue kallikrein levels and synthesis rates are not changed by an acute physiological dose of aldosterone.

Tissue kallikrein content and rate of synthesis have been measured in the kidney and submaxillary gland of the rat after a single physiological dose of aldosterone, and during the time in which the physiological effects of aldosterone are evident. No change in the renal cortical tissue content of immunoreactive kallikrein, in either adrenalectomized or sham-operated animals, was seen within 3 hr of the administration of aldosterone. The kininogenase activity of these samples also did not change. The rates of kallikrein synthesis in the submaxillary gland and the whole kidney were measured by specific immunoprecipitation of kallikrein after 20 min of [35S]methionine incorporation, and again no aldosterone effect was seen. We conclude that, under the conditions of these experiments, aldosterone does not induce the synthesis of tissue kallikrein in either the submaxillary gland or the kidney.

Adrenalectomy↗

PubMed1985

Renal kallikrein in human and experimental diabetes mellitus.

Urinary kallikrein excretion was studied in a group of insulin-dependent diabetic patients in relation to glycemic control, and both urinary and renal tissue levels of kallikrein were measured in untreated and insulin-treated streptozotocin-diabetic rats. While on a fixed normal sodium diet, diabetic patients in poor glycemic control (HbA1c greater than 11%) showed elevated urinary kallikrein, compared to patients with HbA1c less than 11% or normal subjects. Strict glycemic control lowered kallikrein excretion in diabetic patients. In contrast, severely hyperglycemic diabetic rats had reduced urinary and renal kallikrein levels, compared to nondiabetic control rats, and the reduction in urinary kallikrein preceded the development of systolic hypertension. Insulin treatment normalized urinary kallikrein in diabetic rats, but resulted in increased renal kallikrein levels compared to nondiabetic rats. The differences in kallikrein abnormalities observed in diabetic patients and a diabetic animal model may possibly be related to renal hemodynamic changes in clinical and experimental diabetic states.

Adult↗

PubMed1985

Studies of the kallikrein-kinin system and prostaglandins in epithelial ion transport.

Tissue kallikrein of colon mucosa is synthesized rapidly, and this synthetic process can now be examined in relation to hormonal or dietary manipulations or pathological circumstances that affect intestinal ion transport. Although the identical renal tissue enzyme is known to be enriched in membranes of distal convoluted tubular epithelial cells, the precise localization of the intestinal enzyme is uncertain. An understanding of the intestinal cellular locale of kallikrein will help in defining its local role. That tissue kallikreins can be inhibited by monovalent cations and some drugs (e.g., amiloride) and that kallikrein inhibitors affect cation transport across epithelial surfaces containing such enzymes must be reconciled with the new observations of kinin-induced chloride secretion. Extracellular calcium, eicosanoid synthesis, and cyclic nucleotide production are involved in the secretory response to kinins, although an absolute requirement for intact eicosanoid synthesis may not exist.

Amiloride↗

PubMed1984

Tissue kallikrein synthesis and its modification by testosterone or low dietary sodium.

A method has been developed to measure the relative rate of rat tissue kallikrein synthesis which employs a specific antiserum raised against a purified rat urinary kallikrein. Incorporation of [35S]methionine into kallikrein and protein 20 min after intraperitoneal injection was measured in submaxillary gland, pancreas, kidney and descending colon. Kallikrein content was measured with a direct radioimmunoassay, and kallikrein-specific incorporation of [35S]methionine measured after immunoprecipitation. Kallikrein specific radioactivity (c.p.m./mg of enzyme) was about 100-fold greater than that in total protein in both kidney and colon. In contrast, in pancreas the incorporation into the enzyme was only 5-fold higher than into protein, and in submaxillary gland the incorporation was equivalent. Measured as kallikrein-specific radioactivity relative to total protein radioactivity incorporated in 20 min, kallikrein represents 0.18% of total protein synthesis in the kidney, 0.34% in the pancreas, 0.41% in the colon, but 7.29% in the submaxillary gland. Dietary Na+ restriction increased the relative rate of kallikrein synthesis 1.8-fold in the kidney without a comparable effect in submaxillary gland. In contrast, testosterone increased the relative rate of synthesis 2.3-fold in submaxillary gland, but decreased it in kidney. The data show that endogenous kallikrein synthesis differs markedly in various tissues, and that interventions which are known to change kallikrein content or excretion also change the relative rate of enzyme synthesis.

Animals↗

PubMed1984

Standardization of M-mode echocardiographic left ventricular anatomic measurements.

To improve standardization of echocardiographic left ventricular anatomic measurements, echographic left ventricular dimensions and mass were related to body size indexes, sex, age and blood pressure. Independent normal populations comprised 92 hospital-based subjects (64 women, 28 men) and 133 subjects from a population sample (55 women, 78 men). All measurements of chamber size, wall thickness and mass differed between men and women in both series (p less than 0.01 to p less than 0.001). Left ventricular mass was related most closely to body surface area among measurements of body size (r = 0.37, p less than 0.01 to r = 0.57, p less than 0.001) in all four groups. Indexation by body surface area eliminated sex differences in wall thicknesses and internal dimension, but a significant sex difference in left ventricular mass index persisted (89 +/- 21 g/m2 in men versus 69 + 19 g/m2 in women in the entire series, p less than 0.0001). The 97th percentile of left ventricular mass index was identical in both groups of men (136 and 132 g/m2) and women (112 and 109 g/m2). A highly significant difference in lean body mass, estimated from 24 hour urine creatine excretion, was observed between men and women (58 +/- 15 versus 40 +/- 13 kg, p less than 0.001) and no sex difference existed in left ventricular mass indexed by lean body mass (3.4 +/- 1.3 versus 3.5 +/- 1.5 g/kg). Weak correlations were observed between left ventricular mass/lean body mass and systolic or diastolic blood pressure (r = 0.25, p less than 0.05 and r = 0.28, p less than 0.01, respectively) but not age (18 to 72 years).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1984

Electrocardiographic detection of left ventricular hypertrophy using echocardiographic determination of left ventricular mass as the reference standard. Comparison of standard criteria, computer diagnosis and physician interpretation.

Electrocardiographic findings of left ventricular hypertrophy were compared with echocardiographic left ventricular mass in 148 patients to assess performance of standard electrocardiographic criteria, the IBM Bonner program and physician interpretation. On echocardiography, 43% of the patients had left ventricular hypertrophy (left ventricular mass greater than 215 g). Sokolow-Lyon voltage-(S in V1 + R in V5 or V6) and Romhilt-Estes point score correlated modestly with left ventricular mass (r = 0.40, p less than 0.001 and r = 0.55, p less than 0.001, respectively). Sensitivity of Sokolow-Lyon voltage greater than 3.5 mV for left ventricular hypertrophy was only 22%, but specificity was 93%. Point score for probable left ventricular hypertrophy (greater than or equal to 4 points) had 48% sensitivity and 85% specificity, whereas definite hypertrophy (greater than or equal to 5 points) had 34% sensitivity and 98% specificity. Computer analysis resulted in 45% sensitivity and 83% specificity. Overall diagnostic accuracy of the IBM Bonner program (67%) was better than that of Sokolow-Lyon voltage (62%), but worse than the Romhilt-Estes point score (69% for greater than or equal to 4 points or 70% for greater than or equal to 5 points). Three cardiologists interpreted electrocardiograms independently and in a blinded fashion. Physician sensitivity was 56%, specificity 92% and accuracy 76%. Correlation with left ventricular hypertrophy was good (r = 0.70, p less than 0.001). It is concluded that: 1) computer diagnosis of left ventricular hypertrophy by the IBM Bonner program is no more accurate than diagnosis by Sokolow-Lyon or Romhilt-Estes criteria, and 2) physician recognition of left ventricular hypertrophy is more accurate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1984

Pneumonitis, pleural effusion and pericarditis following treatment with dantrolene.

A patient developed pulmonary infiltration, pleural effusions and pericarditis three months after starting dantrolene sodium. Peripheral blood eosinophilia and a raised ESR were present. Symptoms and signs resolved after the drug was discontinued. Dantrolene toxicity should be considered in the differential diagnosis of pneumonitis and pleuro-pericarditis.

Adult↗

PubMed1984

Small vessel vasculitis presenting as neurological disorder.

Three patients with skin or muscle biopsy evidence of small vessel vasculitis presented with neurological symptoms: (1) frequent transient ischaemic attacks, (2) myalgia with encephalopathy, and (3) myalgia with marked weakness. The diagnosis of small vessel vasculitis needs consideration especially if presentation with polyneuropathy or cutaneous involvement is associated with elevation of ESR or serum immunoglobulins. Neurological illness may be a more common presentation of small vessel vasculitis than previously recognised.

Adolescent↗

PubMed1983

The cardiomyopathies. A pathophysiologic approach to therapeutic management.

"Cardiomyopathies" are a disparate group of myocardial disorders, usually of unknown or obscure origin, characterized by systolic or diastolic myocardial dysfunction but involving conditions of widely divergent pathophysiology. For purposes of devising appropriate clinical management, a useful classification scheme can be created with reference to the type of pathophysiologic abnormality exhibited. On this basis, three major types can be identified: (1) congestive (poor systolic function, normal diastolic function, left ventricular dilatation without the expected degree of compensatory hypertrophy), (2) hypertrophic (supernormal systolic function, subnormal diastolic function, and pronounced left ventricular hypertrophy, usually asymmetric, without dilatation), and (3) restrictive (normal or near-normal systolic function and subnormal diastolic function, usually mild symmetrical left ventricular, without dilatation). Noninvasive identification of these pathophysiologic features can be useful in optimizing management programs.

Cardiomyopathy, Dilated↗

PubMed1983

Electrocardiographic recognition of left atrial enlargement.

The ECG is widely used as a screening test for left atrial enlargement (LAE). Surprisingly, the most widely used criterion of LAE, the P-terminal force in lead V1 (PTF-V1) has not been systematically evaluated to determine the optimal level of PTF-V1 for detection of LAE in clinical populations. Accordingly, we examined the relationship between PTF-V1 and left atrial size by echocardiogram in 361 patients and performed a Bayesian analysis of test performance in populations with a varying prevalence of LAE. As PTF-V1 increased from greater than or equal to 0.03 to greater than or equal to 0.08, sensitivity in the 82 patients with LAE (LA dimension greater than 40 mm) fell from 51% to 23%, and specificity rose from 70% to 93%. In our study population (LAE prevalence = 23%), diagnostic performance of criteria was: PTF-V1 greater than or equal to 0.03 greater than or equal to 0.04 greater than or equal to 0.05 greater than or equal to 0.06 greater than or equal to 0.08 Positive Predictive Accuracy 33 46 52 58 50 Negative Predictive Accuracy 83 83 84 83 80 Per Cent Correct Diagnosis 66 76 78 80 77 Positive predictive accuracy and per cent correct diagnosis improved progressively as PTF-V1 rose from greater than or equal to 0.03 to greater than or equal to 0.06, but fell at greater than or equal to 0.08. Applying our sensitivity and specificity data to Bayesian analysis, PTF-V1 greater than or equal to 0.06 performed best in all populations with prevalence of LAE less than or equal to 50%. We conclude that use of PTF-V1 greater than or equal to 0.06 is superior to the standard criterion of PTF-V1 greater than or equal to 0.04 for all purposes ranging from screening of a general population to evaluation of diseased individuals whose likelihood of LAE ranges up to 50%.

Adolescent↗

PubMed1982

Prostaglandin-mediated inhibition of lymphokine secretion in normal individuals and patients with progressive systemic sclerosis (scleroderma, PSS).

The sensitivity of peripheral blood lymphocytes to E-type prostaglandin-mediated inhibition of lymphokine secretion was examined in 3 groups of individuals; normal controls, hospitalized patients, and patients with progressive systemic sclerosis (PSS, scleroderma). Leukocytes were stimulated by a polyclonal T-cell activator, phytohemagglutinin, and the release of the lymphokine, leukocyte migration inhibitory factor (LIF), was measured in the presence or absence of exogenous PGE2 using a direct agarose droplet migration inhibition technique. Leukocytes of scleroderma patients were found to be hyporesponsive to E-type prostaglandin (i.e., lymphokine secretion by these cells was not inhibited at concentrations of PGE2 between 2.8 X 10(-8) and 2.8 X 10(-5) M). In addition, a marked sex difference in PGE responsiveness was found to exist among normal controls, whereby females were hyporesponsive during the latter half of the menstrual cycle. It is possible that this deficit may facilitate, in part, the development of connective tissue diseases in women of childbearing age. The inability to suppress lymphokine production and arrest persistent immune reactivity, coupled with the known ability of lymphokines to augment fibroblast collagen production, offers a a reasonable explanation for the accumulation of tissue collagen in scleroderma.

Adult↗

PubMed1982

Exercise testing early after myocardial infarction. Risks and benefits.

Submaximal exercise testing in the early weeks following myocardial infarction appears to be safe in selected patient groups. Potential benefits of such testing includes: (1) promotion of patient self-confidence, (2) determination of post-hospital exercise prescription, (3) detection of arrhythmias, and (4) determination of post-hospital prognosis. However, the practical value of the apparent psychologic benefits and of the exercise prescription information in a patient not participating in formal exercise rehabilitation therapy is unclear. Detection of potentially important arrhythmias appears to be more adequately effected with 24-hour ambulatory electrocardiography, and detection of such arrhythmias appears to add relatively little prognostic information to that available from exercise electrocardiographic S-T analysis, or from resting radionuclide ejection fraction. Nonetheless, exercise-induced S-T segment depression can provide potentially useful prognostic information regarding morbid or fatal events during the year after infarction. Moreover, recent data suggest that exercise-induced angina and/or S-T segment depression can aid importantly in the noninvasive determination of the anatomic extent of coronary artery disease. The additional benefit or radionuclide cineangiographic determination of left ventricular function during exercise and of thallium 201 scintigraphic determination of myocardial perfusion during stress remain to be defined, although both approaches appear to provide important prognostic information. However, despite the potential benefits of exercise testing, in the absence of clinical trials of available therapy in the "high risk" patient defined by exercise testing, there remains an ill-defined relationship between the information available from exercise testing and the results of management decisions based on this information.

Angina Pectoris↗

PubMed1980

Father psychological absence and heterosexual behavior, personal adjustment and sex-typing in adolescent girls.

Until recently, research efforts have neglected the father as a significant influence on female personality development. This study proposed that the psychological absence of the father is related to a greater frequency and extent of heterosexual behaviors, increased anxiety as a personality trait and increased anxiety in a dating situation. A positive psychological presence of the father was hypothesized to correlate with androgyny in adolescent females. Measures of perceived parental behavior, extent and frequency of heterosexual behaviors, manifest anxiety and sex-role identification were obtained from 160 single female college students. Results indicated a significant relationship between father psychological absence and a greater extent and frequency of heterosexual behaviors. Father psychologically absent girls also exhibited greater manifest anxiety as a personality trait and in a dating situation. Significant correlations between androgyny and a positive father-daughter relationship were not found. Also reported were additional findings relating several variables to self-rating of attractiveness.

Adolescent↗

PubMed1979

Regulatory interactions between mitochondrial genes. I. Genetic and biochemical characterization of some mutant types affecting apocytochrome b and cytochrome oxidase.

The region of the mtDNA containing the structural gene for apocytochrome b is called the cob or box region. There is evidence that the same region is also involved in the regulation of cytochrome oxidase. We have isolated eight mit- mutants in this region and have ordered them using petite deletion mapping. Four of these mutants appear to map outside the boxII region on the oli2-proximal end. Analysis of restriction endonuclease fragments of the mtDNA from peptides used in the deletion mapping suggests a minimum size of 3.1 x 10(3) base pairs for the whole cob region. Although none of our mutants contained any cytochrome b or cytochrome b-linked activities, polypeptides apparently related to apocytochrome b were present in some but not all mutants. Additional regulatory effects (both positive and negative) on cytochrome oxidase by virtue of control of its subunit I were also observed. In addition to these phenotypic traits, some of the mutants accumulated novel, mitochondrially translated polypeptides not seen in wild type.

Apoproteins↗