Biomedical subjects

M B Brown

Publications and source records attributed to M B Brown.

At least 19 recordsLinked to original sources

PubMed1992

The reproducibility and sensitivity of sural nerve morphometry in the assessment of diabetic peripheral polyneuropathy.

The nerve fibre loss, atrophy and injury of diabetic peripheral polyneuropathy and their responses to metabolic intervention have been studied by morphometric analysis of sural nerve biopsies. The magnitudes and sources of intra- and inter-individual variation in these morphometric measures have not been investigated previously in a systematic manner. Morphometric parameters of nerve fibre damage were measured in four separate fascicles from bilateral sural nerve specimens obtained post-mortem from 13 diabetic and 13 non-diabetic subjects. Intra- and inter-individual coefficients of variation were computed and compared to the magnitude of the differences between normal and diabetic subjects. Several morphometric variables emerged as highly sensitive and reproducible measures of nerve fibre damage suitable for clinical studies of diabetic peripheral polyneuropathy. These observations provide a rational basis for the design of future clinical trials employing morphometric end-points.

Autopsy↗

PubMed1992

A test for the difference between two treatments in a continuous measure of outcome when there are dropouts.

Consider a randomized clinical trial that is designed to compare two treatments in which the treatment continues during the entire period of the study. Some subjects may refuse to complete the protocol and will not return for the final evaluation. Since the reason for dropping out may be related to the subject's self-assessed evaluation of the usefulness of the treatment or to undesirable side effects of the treatment, subjects who drop out cannot be treated as a random sample of those who entered the trial. We consider the situation where the measure of efficacy of the treatment is continuous. Under the assumption that the expected value of the measure for those who drop out is not better (the direction depends on the measure) than that for those who complete the study, we propose an adjustment to the usual test for a difference between treatments that allows for the inclusion of the probable effect of the dropouts; this provides a bound on the test for efficacy of the treatment. First, we estimate a predetermined percentile, such as the median score, of the control, or placebo, group and assign this score to all those who dropped out from both groups and to all subjects in both groups with scores that are worse than the assigned score. A Mann-Whitney statistic is then used to test the equality of the distributions of the two groups. We show by simulation that this modified test is equivalent to a test using the complete data and has greater power than that obtained when including the dropouts by assigning the worst observed score to them. This test will be less sensitive to bias that is induced by exclusion of dropouts from the final evaluation.

Bias↗

PubMed1992

The use of 3-D dose volume analysis to predict radiation hepatitis.

Although it is well known that the tolerance of the liver to external beam irradiation depends on the volume of liver irradiated, few data exist which quantify this dependence. Therefore, a review was carried out of our clinical trial for the treatment of intrahepatic malignancies in which the dose of radiation delivered depended on the volume of normal liver treated. Three dimensional treatment planning using dose-volume histogram analysis of the normal liver was used for all patients. Nine of the 79 patients treated developed clinical radiation hepatitis. None of the patient related variables assessed were associated with radiation hepatitis. All patients who developed radiation hepatitis received whole liver irradiation, as all or part of their treatment, which produced a mean dose greater than or equal to 37 Gy. Dose volume histograms were used to calculate normal tissue complication probabilities based on parameters derived from the literature. The risk of complication was greatly overestimated among patients receiving a high dose of radiation to part of the liver without whole liver treatment. An estimation of model parameters based on the clinical results indicated a larger magnitude for the "volume effect parameter" than the literature estimate (n = 0.69 +/- 0.05 vs 0.32; p less than 0.001). Computation of the normal tissue complication probabilities using the larger value of n produced a good description of the observed risk of radiation hepatitis. These findings suggest that dose volume histogram analysis can be used to quantify the tolerance of the liver to radiation. The predictive value of this parameterization of the normal tissue complication probability model will need to be tested with liver tolerance and dose volume histogram data from an independent clinical trial.

Adult↗

PubMed1992

Epidemiology of bladder emptying symptoms in elderly men.

We provide estimates of the prevalence, incidence and remission of difficult bladder emptying symptoms (prostatism) among noninstitutionalized men 60 years old and older living in a community in the United States. The prevalence of 1 or more symptoms of prostatism (hesitancy, straining, weak stream, intermittency or use of a catheter) among men who never had prostatic surgery is 35%. The annual incidence rates during years 1 and 2 of followup were 16.4% and 16.1%, respectively. Remission of symptoms of prostatism also was observed. Of the respondents with severe symptoms at baseline 22.9% were asymptomatic 1 year later. The prevalence of prostatic surgery in this population was 20%. The annual incidence rates during years 1 and 2 of followup were 2.6% and 3.3%, respectively. Urological and nonurological correlates of prostatism are identified. The irritative bladder symptoms are all significantly associated with moderate to severe bladder emptying symptoms (p < 0.0005). Nonurological conditions that also are associated with moderate to severe symptoms of prostatism include use of sedatives or tranquilizers, arthritis, poor health status and transient ischemic attacks. These observations are the initial step in documenting and understanding the various symptoms of prostatism, and its application in clinical practice.

Follow-Up Studies↗

PubMed1991

Evaluation of orthogonal mechanical properties and density of human trabecular bone from the major metaphyseal regions with materials testing and computed tomography.

We evaluated the orthogonal mechanical properties of human trabecular bone from the major metaphyseal regions with materials testing and quantitative computed tomography (CT). The proximal tibia, distal femur, proximal femur, distal radius, and proximal humerus from fresh cadaver specimens between the ages of 55 and 70 years were excised and prepared for experimentation. The bones were embedded and scanned at 1 or 1.5 mm intervals on a Technicare HPS 1440 and GE 9800 CT scanner. After scanning, the bones were sectioned, producing 8-mm cubes of trabecular bone which were mechanically tested in uniaxial compression at a strain rate of 1%. The testing sequence consisted of preyield tests in two of the three orthogonal directions and failure in the third. After testing, the cubes were evaluated for apparent density and ash weight. The results of the study show that the strength and stiffness of trabecular bone varies significantly within metaphyseal regions and from metaphysis to metaphysis. The power and significance of relationships between density and modulus varied as a function of metaphyseal location. Both linear and nonlinear models were significant, suggesting that trabecular deformation occurs in response to both axial and bending loads. Finally, the need for architectural measures of trabecular bone to predict mechanical properties is emphasized.

Aged↗

PubMed1991

A model for the identification of hormone pulses.

Several hormones are released into the blood in a pulsating manner, that is, in short bursts which cause a rapid increase in the circulating concentration. The concentration then declines due to excretion, chemical breakdown, and redistribution into other compartments. Based on a series of observations of the level of hormone in the blood, investigators desire to quantify characteristics of these pulses, that is, timing, amplitude and rate of decay. We describe a statistical model for hormone pulse data and introduce a new method for estimating the characteristics of the pulses.

Algorithms↗

PubMed1991

Relationship between use of diuretics and continence status in the elderly.

Although diuretics have been implicated as a cause of urinary incontinence, no evidence has been presented prior to this report to confirm such a relationship. Our epidemiologic survey of 1,956 respondents sixty years of age and older in Washtenaw County, Michigan, revealed 24.6 percent of men and 36.9 percent of women were current users of a diuretic medication. Comparisons between users and non-users of diuretics and continence and incontinence status revealed no significant difference in the prevalence of incontinence in either gender. However, when male respondents who had cystometric examinations were analyzed, it was found that diuretic users who have uninhibited detrusor contractions (UDC) had a significantly higher prevalence of urinary incontinence (85.7%) when compared with non-users with UDC (25%) (p = 0.009). Among men who did not have UDC, use or non-use of diuretics showed a similar relationship but did not reach statistical significance (p = 0.085). There were too few female respondents with UDC to make meaningful analysis in this group.

Aged↗

PubMed1991

Follicle-stimulating hormone signal transduction: role of carbohydrate in aromatase induction in immature rat Sertoli cells.

Receptor activated adenylate cyclase acts as a major transmembrane signalling system. It is widely accepted that upon binding to its receptor, follicle-stimulating hormone (FSH) activates the cAMP-dependent pathway which in turn mediates FSH-induced estradiol production in Sertoli cells. Studies utilizing several chemically derived variants of FSH have demonstrated that these variants bind to the FSH receptors with equal avidity but differ in their ability to activate cAMP-dependent pathways. Since cAMP is believed to be the second messenger responsible for FSH signal transduction, we tested two hypotheses: (1) that the effects of different oFSH variants on cAMP production and aromatase induction (as measured by estradiol production) would be in parallel; and (2) that deglycosylated ovine FSH (DG-oFSH) would antagonize the ability of intact oFSH to stimulate aromatase induction, similar to its reported antagonistic effect on cAMP production. Immature rat (7- to 10-day-old) Sertoli cells were cultured and the effects of several different oFSH variants on cAMP production and/or aromatase induction were tested. The variants tested were native oFSH, DG-oFSH, asialo oFSH (AS-oFSH), a recombinant of intact LH alpha and FSH beta (alpha + beta) and a recombinant of deglycosylated LH alpha and intact FSH beta (DG alpha + beta). Both native oFSH and alpha + beta recombinant at relatively large doses (10 ng) elicited a significant increase in extracellular cAMP accumulation as well as total cAMP production. In contrast, DG-oFSH did not produce an increase in cAMP even at 10-fold higher doses than native oFSH. Intracellular cAMP concentrations did not increase following stimulation with native oFSH, DG-oFSH or DG alpha + beta. In contrast to the divergent effects of oFSH and DG-oFSH on cAMP production all variants of oFSH stimulated estradiol production from Sertoli cells albeit with varying potencies. The sensitivity (minimal effective dose) and ED50 (dose at which half maximal response is achieved) of the estradiol (E2) response curve to increasing concentrations of native oFSH were 0.025 +/- 0.01 and 0.33 +/- 0.05 ng, respectively. Asialo-oFSH (AS-oFSH) increased E2 production with a potency (comparative dose required for effect) similar to that of native oFSH.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1991

Tetracycline resistance determinants in streptococcal species isolated from the bovine mammary gland.

Seventy-one streptococci isolated from dairy cows with clinical mastitis were tested for tetracycline resistance. Twenty-one (30%) isolates were tetracycline resistant (Tcr), and eight hybridized with the Tet O, one hybridized with the Tet L, and one hybridized with both the Tet L and Tet K determinants. The remaining Tcr isolates did not hybridize with any of the 5 Gram-positive Tet determinants tested. The Tet O determinants were plasmid-mediated, and four selected strains transferred the Tet O determinant at frequencies of 10(-6) to 10(-8). Strains which did not hybridize with known probes were tested for resistance to minocycline. All of the Streptococcus dysgalactiae had low minimum inhibitory concentrations (MICs) for minocycline, while the S. agalactiae and the one S. uberis showed high MICs to minocycline. This suggests that at least two different uncharacterized Tet determinants exist in these isolates, one conferring high resistance to both tetracycline and minocycline and one conferring only tetracycline resistance.

Animals↗

PubMed1991

Immunoglobulin class- and subclass-specific responses to Mycoplasma pulmonis in sera and secretions of naturally infected Sprague-Dawley female rats.

Mycoplasma pulmonis causes chronic murine respiratory mycoplasmosis and genital disease in rats. Specific immunoglobulin M (IgM), IgA, and IgG and its subclasses present in sera and tracheal and uterine lavage samples from 36 naturally infected Sprague-Dawley female rats were tested for reactivity with M. pulmonis in an enzyme-linked immunosorbent assay. Ten specific-pathogen-free Sprague-Dawley female rats served as the negative controls. Tracheal and uterine lavage samples were cultured quantitatively for M. pulmonis. M. pulmonis was isolated from the trachea (35 of 36) and uterus (17 of 36) of naturally infected rats; all rats were infected in at least one of the two sites cultured. M. pulmonis was not isolated from any control rat. There was a significant difference in levels of specific antibody of all classes except IgG2c between control and naturally infected animals (P less than 0.001 for IgM, IgG, IgG1, and IgG2a; P less than 0.002 for IgG2b; and P less than 0.02 for IgA). There was no correlation between numbers of M. pulmonis cells isolated and the amount or class of antibody measured in serum or tracheal lavage specimens. The predominant antibodies to M. pulmonis found in the sera of naturally infected rats were IgG and IgM. The IgG2a subclass was responsible for the majority of IgG-positive animals. There were no differences between rats which were positive by culture for M. pulmonis in the uterus (U+) and rats which were negative by culture for M. pulmonis in the uterus (U-) with respect to distribution or amount of antibody classes and subclasses in the serum. However, tracheal wash samples from U+ rats had significantly higher (P less than 0.03) levels of specific IgG1 and IgG2a than those from U- rats. Conversely, IgG2a was present in higher levels in pooled uterine lavage specimens from U- rats than in those from U+ rats.

Animals↗

PubMed1991

Detection of antibodies to Mycoplasma gallisepticum in egg yolk versus serum samples.

Serum (n = 1,636) and egg yolk (n = 802) samples collected from hens on four commercial egg farms in Florida were tested for the presence of specific antibodies to Mycoplasma gallisepticum in a commercially available enzyme-linked immunosorbent assay. No significant differences were noted between serum and egg yolk samples with respect to distribution of positive, suspect, and negative test results or for the mean sample/positive control ratio values of positive, suspect, and negative test results. A linear relationship between the distribution of positive and negative results and the age of the birds was observed for results obtained with both serum and egg yolk samples. On the basis of the results of this study, egg yolk samples can be used in lieu of serum samples to screen flocks for antibodies to Mycoplasma gallisepticum.

Aging↗

PubMed1991

Survival of feline mycoplasmas in urine.

The effects of length of incubation and urine osmolality on the survival of feline mycoplasmas and ureaplasmas and representative gram-positive and gram-negative bacteria in synthetic urine which approximated the osmolality of normal cat urine were investigated. Both Escherichia coli and Staphylococcus aureus withstood the effects of increasing osmotic pressure. In the most concentrated urine, significant decreases (P less than 0.001) in CFU were observed for E. coli at exposure times of 30 min and longer. S. aureus was not affected by longer exposure or increased osmotic strength. Both Mycoplasma felis and Mycoplasma gateae were affected adversely by longer exposure times and high osmotic strength (P less than 0.001). A Ureaplasma sp. was not adversely affected except at very high (greater than or equal to 2,980 mosM) osmotic strengths or after prolonged incubation (120 min) at relatively high (1,976 mosM) osmotic strengths (P less than 0.001). The failure of both M. felis and M. gateae to survive under osmotic conditions present in normal feline urine suggests that it is unlikely that these mycoplasmas are involved in urinary disorders in cats.

Animals↗

PubMed1991

Naloxone does not reverse the suppressive effects of testosterone infusion on luteinizing hormone secretion in pubertal boys.

In this study we wished to test whether, and if so when, the suppressive effects of testosterone on LH and, by inference, GnRH secretion are mediated via endogenous opioid pathways during male pubertal maturation. As a preliminary study, we evaluated the acute effects of a 24-h infusion of testosterone (T) in eight pubertal boys with constitutional delay of growth in order to determine the optimal time for administration of naloxone. Eight additional pubertal boys received a saline infusion, followed 1 week later by a similar T infusion starting at 1000 h and lasting for 33 h. After 2 h of infusion (both saline and T), four iv boluses of saline were given hourly, and after 26 h of infusion, four hourly iv boluses of naloxone were given. Blood was obtained every 15 min for LH and every 30 min for T measurements. T infusion increased the mean T concentration by 3.8-fold (P less than 0.001). Mean LH and LH pulse frequency were suppressed (P less than 0.01), and the sleep-associated increase in LH secretion was abolished. Naloxone administration during the infusion of T did not reverse the suppression of LH secretion. Compared to the saline control period, mean LH was significantly lower during T infusion during the time naloxone boluses were given (4.5 +/- 0.9 vs. 5.9 +/- 1.1 IU/L, T infusion and naloxone boluses vs. saline respectively, P less than 0.01). Although the suppression of LH pulse frequency remained significantly lower than that during the saline control period (0.23 +/- 0.04 pulses/boy.h during T infusion and saline boluses; 0.33 +/- 0.04 pulses/boy.h during T infusion plus naloxone boluses; 0.44 +/- 0.06 pulses/boy.h during saline infusion and saline boluses). Naloxone increased mean LH and LH pulse frequency only in the four older, more mature boys during the infusion of saline. Pituitary responsiveness to exogenous GnRH was not altered by infusion of T. We conclude that acute administration of T suppresses LH secretion and, by inference, GnRH secretion at all stages of pubertal maturation in boys. These negative feedback effects, however, cannot be reversed by coadministration of naloxone, even in mid- to late pubertal boys who respond to naloxone with increased pulsatile secretion of LH. These studies suggest that during pubertal maturation in boys, endogenous opioid pathways do not play a major role in the regulation of the negative feedback effects of T.

Adolescent↗

PubMed1991

Chronic upper respiratory tract disease of free-ranging desert tortoises (Xerobates agassizii).

Seventeen desert tortoises, Xerobates agassizii, with upper respiratory tract disease were examined; thirteen were euthanatized for necropsy. Four normal control desert tortoises from a clinically healthy population were similarly evaluated. Hemoglobin and phosphorus values were significantly (P less than or equal to 0.05) lower and serum sodium, urea, SGOT, and cholesterol values were significantly higher in ill tortoises compared to controls. No significant differences in concentrations of serum or liver vitamins A and E were found between the two groups. While no significant differences were found for concentrations of lead, copper, cadmium, and selenium, the livers of ill tortoises had higher concentrations of mercury and iron. Lesions were found consistently in the upper respiratory tract (URT) of ill tortoises. In all ill tortoises dense infiltrates of lymphocytes and histiocytes obscured the mucosal epithelium and underlying glands. The mucosal epithelium was variably dysplastic, hyperplastic, and occasionally ulcerated. Electron microscopic studies revealed small (350 to 900 nm), pleomorphic organisms resembling Mycoplasma sp., in close association with the surface epithelium of the URT of ill tortoises. Pasteurella testudinis was cultured from the nasal cavity of all ill tortoises and one of four control tortoises. A Mycoplasma sp. was cultured from the nasal passageways of four ill tortoises and was ultrastructurally similar to the pleomorphic organism present on the mucosa in tissue section.

Animals↗

PubMed1990

Mycoplasmal mastitis in a dairy herd.

In October 1985, mycoplasmas were isolated from bulk tank milk samples in a large Florida dairy (greater than 1,400 lactating cows). At that time, measures to isolate and control the spread of infection were instituted. In an initial screening test, Mycoplasma bovis was isolated from 21 of 153 milking string samples (milk from all quarters of 10 cows/string). Composite quarter milk samples from all quarters of every individual lactating cow in the herd were obtained for culture in November 1985 and December 1985. In October, 88 of 1,535 (5.7%) cows were identified as Mycoplasma-positive. An additional 31 Mycoplasma-infected cows were identified in December. The dairy elected to maintain the infected cows in a separate Mycoplasma-positive subherd, which would be milked at the end of each milking session. Seven additional Mycoplasma-positive cows were identified at initiation of lactation. All newly identified infected cows were transferred to the Mycoplasma-positive subherd. After segregation of Mycoplasma-positive cows, bulk tank milk samples obtained routinely from the main herd remained culture negative throughout the study. From February 1986 to October 1986, quarter milk samples were obtained monthly from cows in the Mycoplasma-positive subherd. Any cow that developed clinical mastitis or substantial decrease in milk production was, at the discretion of the herdsman, culled. Of the 126 cows in the subherd, 22 (17.5%) were culled for mastitis, 35 (27.8%) were culled for low production, and 9 (7.1%) were culled for other reasons. Of the remaining 60 cows, 16 (12.7% of the 126 cows) were Mycoplasma-positive on the basis of results from one or more samples obtained after February 1986.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Urodynamic tests for female geriatric urinary incontinence.

Most urodynamic tests currently in use in the evaluation of female urinary incontinence have not been applied to a community-based sample to determine their specificity. In this study of a random sample of noninstitutionalized elderly, 258 self-reported continent and 198 self-reported incontinent women sixty years and older, who participated in a household survey, underwent a clinic evaluation (history, physical examination, and urinalysis); of these 67 continent and 100 incontinent female respondents underwent urodynamic testing. The uroflowmetry, cystometry, and supine static urethral pressure profilometry (UPP) findings did not differ significantly between continent and incontinent subjects (whether based on a self-report or a clinician's diagnosis of urinary continence status). Standing static and dynamic UPP and lateral cystography showed significant differences between self-reported continent and incontinent respondents. The provocative stress test significantly distinguishes continence from incontinence, and stress incontinence from other types. The sensitivity of the provocative stress test was 39.5 percent, whereas its specificity is 98.5 percent. Urodynamic testing including uroflow study, static UPP, and lateral cystography should not be used as a screening test but rather selectively as a confirmatory test, and to determine the therapeutic approach, and to assess the outcome of therapy.

Aged↗

PubMed1990

Two-year incidence, remission, and change patterns of urinary incontinence in noninstitutionalized older adults.

In this study, patterns of urinary incontinence, its severity and types were studied by three sequential data collections at annual intervals. The data are from a panel survey of a probability sample of 1,956 noninstitutionalized persons aged 60 and over residing in Washtenaw County, Michigan, who were interviewed in their homes about urine loss. Based on these self-reports, the prevalence of urinary incontinence was 18.9% in men and 37.7% in women. One-year incidence rates of about 20% among women and about 10% among men were found. One-year remission rates were about 12% for women and about 30% for men. When becoming incontinent, respondents were most likely to develop mild incontinence. Those who changed their severity level were most likely to progress from mild to moderate.

Aged↗

PubMed1990

Identification of Mycoplasma felis and Mycoplasma gateae by an immunobinding assay.

An immunobinding assay capable of distinguishing between Mycoplasma felis and Mycoplasma gateae was developed. Nitrocellulose was used as the solid support. Polyclonal rabbit antiserum against M. felis or M. gateae was used in the assay. Binding of the specific rabbit antiserum was detected by alkaline phosphatase-conjugated goat anti-rabbit immunoglobulin and an alkaline phosphatase substrate (Nitro Blue Tetrazolium-5-bromo-4-chloro-3-indolyl phosphate). The immunobinding assay was effective in the detection of feline mycoplasmas on agar plates, on primary isolation plates, in broth cultures, and in mixed cultures. No cross-reactions were observed with other related mycoplasmal species. The assay was cheap to perform and easy to interpret, and it required little technical time.

Alkaline Phosphatase↗