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Biomedical subjects

M L Brown

Publications and source records attributed to M L Brown.

At least 127 records · Page 7Linked to original sources
PubMed1991

Influence of left ventricular diastolic filling on symptoms and survival in patients with decreased left ventricular systolic function.

The relation between left ventricular (LV) filling variables measured by gated blood pool radionuclide ventriculography and clinical symptoms and survival was examined in 93 patients who had decreased LV systolic function. The diastolic data were not significantly associated with clinical symptoms. Time to peak filling rate, peak filling rate and ejection fraction were associated independently with survival free of cardiac death (chi-square = 7.74, 5.91 and 3.92, respectively, by stepwise Cox regression analysis). A short time to peak filling rate or increased peak filling rate was associated with decreased survival, whereas the opposite indicated a good prognosis. One-year Kaplan-Meier survival was 73 and 98% when time to peak filling rate was below or above the median value of 167 ms, respectively, 82 and 90% when peak filling rate was above or below the median value of 1.67 end-diastolic volumes per second, respectively, and 76 and 95% when LV ejection fraction was below or above the median value of 0.35, respectively. Thus, filling variables (time to peak filling rate and peak filling rate) measured by radionuclide ventriculography may be valuable in predicting survival in patients with decreased LV systolic function.

Cardiomyopathy, Dilated↗
PubMed1991

Structure-function studies of human cholesteryl ester transfer protein by linker insertion scanning mutagenesis.

Human plasma cholesteryl ester transfer protein (CETP) enhances transfer and exchange of cholesteryl ester (CE) and triglyceride (TG) between high-density lipoprotein and other lipoproteins. To define regions responsible for the neutral lipid transfer activities at the molecular level, a total of 27 linker insertion mutants at 18 different sites along the CETP molecule were prepared and transiently expressed in a mammalian cell line (COS). The inserted linkers were small (usually 6 bp) and did not interrupt the translational reading frame of the CETP cDNA. Although secretion of each mutant protein was less than that of wild-type CETP, the majority of the mutants had normal cholesteryl ester transfer activity (transfer activity per nanogram of CETP in media). However, insertional alterations in three regions severely impaired CE transfer activity: (1) in the region of amino acids 48-53; (2) at amino acid 165; and (3) in the region of amino acids 373-379. Although the impaired activities could also be a result of globally incorrect folding of these CETP mutants, hydrophobicity analysis and secondary structure predictions tended to exclude this possibility for most of the insertion sites at which insertions resulted in inactivation. The insertion at amino acid 379 occurs immediately after a triplet of lysine residues, suggesting that this region might be involved in an essential step in the mechanism of CE and TG transfer, such as the binding of CETP to phosphatidylcholine molecules in the lipoprotein surface. Effects on TG transfer activity were generally similar to those on CE transfer activity, suggesting a similar structural requirement for both neutral lipid transfer activities.

Amino Acid Sequence↗
PubMed1991

Comparison of exercise performance in left main and three-vessel coronary artery disease.

From a consecutive series of patients who underwent rest and exercise radionuclide angiography over several years, we retrospectively identified 34 patients with left main coronary artery disease and 103 patients with three-vessel coronary artery disease who did not have significant left main disease. The results of gated equilibrium radionuclide angiography were compared in these 2 groups. Multiple exercise hemodynamic, exercise electrocardiographic, and exercise radionuclide angiographic parameters were considered in an attempt to separate the 2 groups. The only parameter that was significantly different between the 2 groups was exercise heart rate. However, no value of the exercise heart rate could meaningfully separate the 2 groups. Despite their known difference in prognosis, patients with left main and three-vessel disease had very similar exercise performance and could not be distinguished from one another by exercise electrocardiography or exercise radionuclide angiography. The inability to distinguish these two groups is a clear limitation of noninvasive exercise modalities.

Coronary Angiography↗
PubMed1991

Towards a less costly but accurate test of gastric emptying and small bowel transit.

Our aim is to develop a less costly but accurate test of stomach emptying and small bowel transit by utilizing selected scintigraphic observations 1-6 hr after ingestion of a radiolabeled solid meal. These selected data were compared with more detailed analyses that require multiple scans and labor-intensive technical support. A logistic discriminant analysis was used to estimate the sensitivity and specificity of selected summaries of scintigraphic transit measurements. We studied 14 patients with motility disorders (eight neuropathic and six myopathic, confirmed by standard gastrointestinal manometry) and 37 healthy subjects. The patient group had abnormal gastric emptying (GE) and small bowel transit time (SBTT). The proportion of radiolabel retained in the stomach from 2 to 4 hr (GE 2 hr, GE 3 hr, GE 4 hr), as well as the proportion filling the colon at 4 and 6 hr (CF 4 hr, CF 6 hr) were individually able to differentiate health from disease (P less than 0.05 for each). From the logistic discriminant model, an estimated sensitivity of 93% resulted in similar specificities for detailed and selected transit parameters for gastric emptying (range: 62-70%). Similarly, combining selected observations, such as GE 4 hr with CF 6 hr, had a specificity of 76%, which was similar to the specificity of combinations of more detailed analyses. Based on the present studies and future confirmation in a larger number of patients, including those with less severe motility disorders, the 2-, 4-, and 6-hr scans with quantitation of proportions of counts in stomach and colon should provide a useful, relatively inexpensive strategy to identify and monitor motility disorders in clinical and epidemiologic studies.

Adult↗
PubMed1991

The effect of stool consistency on rectal and neorectal emptying.

Although stool consistency is considered to be an important component of anorectal continence, its effect on rectal emptying has never been quantitated. In 12 healthy volunteers and 12 patients after ileal pouch-anal anastomosis (IPAA) (46 +/- 5 months after the operation; mean +/- SEM), perfused anal manometry was performed; movements of the anorectal angle were quantitated scintigraphically; and rectal capacity and compliance were measured by air insufflation of an intrarectal balloon at three infusion rates. The efficiency of rectal evacuation of three consistencies (5 percent, liquid; 7.5 percent semisolid gel; 11.25 percent solid gel; w/w) of Tc99m labeled artificial stool (aluminum magnesium silicate gel) was quantitated by gamma camera imaging. No abnormalities of pelvic floor function were demonstrated in either controls or patients. The mean neorectal capacity and compliance of patients with IPAA did not differ from control, (capacity; IPAA: 215 +/- 22 ml vs. control; 245 +/- 29 ml; compliance; IPAA: 5.5 +/- 0.7 ml/cm H2O vs. control; 6.6 +/- 0.7 ml/cm H2O; P greater than 0.05). In controls, the percentage of the 7.5 percent consistency evacuated (81 +/- 5 percent, mean +/- SEM) was significantly more than the percentage evacuation of either the 5 percent consistency (67 +/- 7 percent) or the 11.25 percent consistency (77 +/- 2 percent) (P less than 0.05). After IPAA, the mean overall percent evacuation of the three stool consistencies was significantly less than control (52 +/- 6 percent after IPAA; 75 +/- 5 percent control, P less than 0.05). However, there was no significant difference in neorectal emptying between the liquid, the semisolid gel and the solid gel (56 +/- 6, 55 +/- 6, 51 +/- 9 percent, respectively, P greater than 0.1). We concluded that in healthy subjects but not in patients after IPAA, stool consistency affected the efficiency of evacuation of enteric content.

Adult↗
PubMed1991

Projections of the breast cancer burden to U.S. women: 1990-2000.

Although breast cancer incidence rates in the United States have been climbing for the last 40 years, recent trends have shown a more dramatic increase since 1982. This recent rise has been the subject of much study, and it is likely due in part to increased mammographic screening. A mathematical model incorporating the long-term incidence trend estimated from the Connecticut Tumor Registry and recent increases in availability of dedicated mammography machines is described and used to project incidence rates. Projections of breast cancer incidence rates among U.S. women ages 50 and over from 1990 to the year 2000 are developed. It appears that breast cancer incidence rates will continue to rise until about 1990 and then decline as screening rates stabilize.

Adult↗
PubMed1991

A technetium-labeled monoclonal antibody for imaging metastatic melanoma.

Twenty patients with histologically proven metastatic melanoma were scanned with a 99mtechnetium (99mTc)-labeled melanoma antibody to determine the detection rate of known malignant lesions and to evaluate the antibody's ability to discover occult metastases. Isotope localization in different organs was as follows: liver 100%, bone 100%, subcutaneous lesions 80%, lymph nodes 54%, and lung 33%. Four unsuspected bone lesions and 16 occult subcutaneous lesions were found. False positive lesions were noted in two instances--one benign thyroid adenoma, and one arthritic bone lesion. One patient developed an atypical serum sickness reaction with a rash and arthralgias that responded rapidly to treatment. The 99mTc antimelanoma antibody is a safe and effective method to detect metastatic melanoma. It has potential use for screening newly diagnosed melanomas that carry an increased risk of recurrence.

Aged↗
PubMed1991

Unprepared human colon does not discriminate between solids and liquids.

In five healthy male volunteers, we compared solid and liquid transit though the unprepared colon. 99mTc-diethylenetriaminepentaacetic acid in 10 ml saline was injected into the cecum through an orocecal tube at 1 ml/min immediately after a methacrylate-coated medication capsule was seen to deliver 111In-labeled Amberlite IR-120PLUS pellets (avg diam, 1.0 mm) into the cecum. Segmental transits through the ascending, transverse, descending, and rectosigmoid regions were determined using a dual gamma camera system and a variable region of interest program. There was no difference between solid [half time, 247 +/- 60 (SE) min] and liquid (312 +/- 88 min) emptying from the ascending colon. Colonic transit of solids and liquids was further compared by regional counts and stool outputs at 12 and 24 h. There were no significant differences between solids and liquids (P greater than 0.05). Our data suggest that transit through the unprepared human colon is not different for solids and small volumes of liquids, when these are delivered together to the ascending colon.

Adult↗
PubMed1991

Abnormal gallbladder motility in irritable bowel syndrome: evidence for target-organ defect.

We have described previously that the gallbladder responds abnormally to infusions of cholecystokinin octapeptide (CCK-8) in patients with irritable bowel syndrome (IBS). To confirm these results and to examine the possible mechanisms, patients with IBS and predominant symptoms of diarrhea or constipation were compared with matched controls. During infusions of CCK-8 at one of three doses, the response of the gallbladder was measured ultrasonographically. The levels of CCK-8 reached in the peripheral circulation and degradation of the peptide in vitro and in vivo were used to evaluate metabolism of cholecystokinin. We confirmed that the gallbladders of patients with IBS responded abnormally to CCK-8; however, the differences were not due to any prereceptor event. Instead, this abnormality in IBS must be explained by an atypical response at the level of the target tissues.

Adult↗
PubMed1991

Elevated glucose impairs endothelium-dependent relaxation by activating protein kinase C.

A possible relationship between protein kinase C activation and impaired receptor-mediated endothelium-dependent relaxation in diabetes mellitus was examined in isolated aorta from normal rabbit exposed to elevated glucose. Aorta treated for 10 min with 4-phorbol 12-myristate 13-acetate (PMA), a protein kinase C activator, showed decreased relaxations to the endothelium-dependent vasodilator, acetylcholine, similar to normal aorta exposed to elevated glucose (22 and 44 mM) for 6 h. Relaxations to the receptor-independent endothelium-dependent vasodilator, A23187, and those caused by the direct smooth muscle vasodilator, sodium nitroprusside, were unaffected by treatment with PMA or exposure to elevated glucose. Indomethacin increased relaxations to acetylcholine of aorta treated with PMA indicating a role for vasoconstrictor prostanoids. PMA caused a significant increase in basal and acetylcholine-stimulated release of vasoconstrictor prostanoids including thromboxane A2 from aortic segments with, but not without endothelium. Protein kinase C inhibitors, H-7 or sphingosine, restored the abnormal acetylcholine-induced relaxations as well as suppressed the abnormal release of prostanoids in aorta exposed to elevated glucose. These findings suggest that the dysfunction of receptor-mediated endothelium-dependent relaxation associated with exposure to elevated glucose is due to increased production of vasoconstrictor prostanoids by the endothelium as a consequence of protein kinase C activation.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1991

Diagnosis of osteomyelitis of the foot in diabetic patients: value of 111In-leukocyte scintigraphy.

The noninvasive diagnosis of osteomyelitis of the foot in diabetic patients with currently available radiologic and radionuclide imaging techniques is often difficult. Recently, 111In-labeled leukocyte scintigraphy has been proposed as an attractive alternative. Accordingly, we retrospectively reviewed 51 111In-labeled leukocyte scans, 49 technetium-99m bone scans, and 49 plain radiographs obtained in 51 adults with diabetes in whom osteomyelitis of the foot was suspected. The sensitivity and specificity of these techniques were evaluated in all patients, as well as in a subgroup of 11 patients with neuroarthropathy. Results with 111In-labeled leukocyte scans were also examined in subsets of patients with soft-tissue ulcers (n = 35) and those receiving antibiotics during investigation (n = 20). Confirmation or exclusion of osteomyelitis was made surgically in 28 patients and clinically in 23. Fourteen patients had osteomyelitis. Bone scans were most sensitive (93%) but least specific (43%); plain radiographs were most specific (83%) but least sensitive (43%). 111In-labeled leukocyte scans were both sensitive (79%) and specific (78%), and remained useful in patients with neuroarthropathy, soft-tissue ulcers, and antibiotic treatment. Poor spatial resolution contributed to the false-negative and false-positive 111In-labeled leukocyte scans, suggesting that this technique should not be interpreted independent of other tests. 111In-labeled leukocyte scans are a valuable diagnostic tool for the diagnosis of pedal osteomyelitis in diabetic patients.

Adult↗
PubMed1991

Rapid preparation and quality control method for technetium-99m-2-methoxy isobutyl isonitrile (technetium-99m-sestamibi).

Technetium-99m-2-methoxy isobutyl isonitrile (99mTc-sestamibi) is a radiopharmaceutical that can be useful in the evaluation of patients with acute myocardial infarction. The current method for preparation requires a lengthy boiling water bath procedure and the recommended quality control procedure is cumbersome and time-consuming. Using a microwave oven, the heating time necessary to provide a labeling efficiency (averaging 97% for sestamibi-labeled with maximum allowable 99mTc activity and volume has been reduced to 10 sec. A new mini-paper chromatography (MPC) system has been developed to analyze the radiochemical purity of 99mTc-sestamibi involving a 1:1 chloroform/tetrahydrofuran developing solvent. The recommended thin-layer chromatography (TLC) system involving the use of an AI2O3-coated plate requires an average time for drying and development of 34.8 +/- 1.6 min (n = 58) to complete, whereas the new MPC system has an average developing time of 2.3 +/- 0.1 min (n = 26). For radiochemical purity values ranging from 71-99% (n = 31), the MPC and TLC methods correlated closely (r = 0.99) with a regression line of MPC% = 1.05 TLC%--5.75. The combined use of the microwave oven heating method and our quick quality control system will facilitate the rapid, emergency use of 99mTc-sestamibi and eliminate the need for advance preparation of multiple kits each day.

Chromatography, Paper↗
PubMed1991

Familial cholesteryl ester transfer protein deficiency is associated with triglyceride-rich low density lipoproteins containing cholesteryl esters of probable intracellular origin.

The net transfer of core lipids between lipoproteins is facilitated by cholesteryl ester transfer protein (CETP). We have recently documented CETP deficiency in a family with hyperalphalipoproteinemia, due to a CETP gene splicing defect. The purpose of the present study was to characterize the plasma lipoproteins within the low density lipoprotein (LDL) density range and also the cholesteryl ester fatty acid distribution amongst lipoproteins in CETP-deficient subjects. In CETP deficiency, the conventional LDL density range contained both an apoE-rich enlarged high density lipoprotein (HDL) (resembling HDLc), and also apoB-containing lipoproteins. Native gradient gel electrophoresis revealed clear speciation of LDL subclasses, including a distinct population larger in size than normal LDL. Anti-apoB affinity-purified LDL from the CETP-deficient subjects were shown to contain an elevated triglyceride to cholesteryl ester ratio, and also a high ratio of cholesteryl oleate to cholesteryl linoleate, compared to their own HDL or to LDL from normal subjects. Addition of purified CETP to CETP-deficient plasma results in equilibration of very low density lipoprotein (VLDL) cholesteryl esters with those of HDL. These data suggest that, in CETP-deficient humans, the cholesteryl esters of VLDL and its catabolic product, LDL, originate predominantly from intracellular acyl-CoA:cholesterol acyltransferase (ACAT). The CETP plays a role in the normal formation of LDL, removing triglyceride and transferring LCAT-derived cholesteryl esters into LDL precursors.

Animals↗
PubMed1991

Limitations of indium leukocyte imaging for the diagnosis of spine infections.

The usefulness of indium-111 white blood cell (WBC) scintigraphy in the detection of spine sepsis was studied in 22 patients who had open or percutaneous biopsies for microbiologic diagnosis. The indium images in 18 patients with vertebral infection were falsely negative in 15 (83%) and truly positive in 3 (17%). All four patients with negative cultures and histology had true-negative scans. The indium-111 WBC imaging results yielded a sensitivity of 17%, a specificity of 100%, and an accuracy rate of 31%. Prior antibiotic therapy was correlated with a high incidence of false-negative scans and photon-deficient indium-111 WBC uptake. The usefulness of indium-111 WBC scintigraphy for the diagnosis of vertebral infection may be limited to those patients who have not been treated with antibiotics previously.

Anti-Bacterial Agents↗