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Biomedical subjects

W E Kemp

Publications and source records attributed to W E Kemp.

13 recordsLinked to original sources

Echocardiography in infective endocarditis.

BACKGROUND: Echocardiographic demonstration of valvular infection now ranks with positive blood cultures as one of the two major clinical criteria for diagnosis of infective endocarditis (IE), according to new, more accurate guidelines for diagnosis. Because early detection of IE and its complications is essential for determining whether to pursue medical therapy or to intervene surgically, transthoracic echocardiography (TTE) is an essential part of the initial examination of patients with suspected IE. METHODS: Using MEDLINE, we searched and reviewed all articles with the key words infective endocarditis and transesophageal echocardiography. RESULTS: With its superior imaging, transesophageal echocardiography (TEE) has proven to be more sensitive than TTE for the diagnosis of IE as well as in the detection of IE-associated complications. CONCLUSIONS: While superior in predicting which patients with IE have perivalvular abscess or prosthetic valve dysfunction and which are most susceptible to systemic embolism, TEE is more invasive and must be used selectively.

Abscess↗

Pulmonary vein stenosis after catheter ablation of atrial fibrillation.

BACKGROUND: This report describes the complication of pulmonary vein stenosis with resultant severe pulmonary hypertension that developed in 2 patients after successful catheter ablation of chronic atrial fibrillation. METHODS AND RESULTS: Three months after successful catheter ablation of atrial fibrillation, both patients developed progressive dyspnea and pulmonary hypertension. Both were found to have severe stenosis of all 4 pulmonary veins near the junction with the left atrium. Balloon dilation of the stenotic pulmonary veins was performed in these patients, with improvement in dyspnea and pulmonary hypertension. CONCLUSIONS: The complication of pulmonary vein stenosis is potentially life-threatening, and the application of radiofrequency current within the pulmonary veins with standard catheter technology should be avoided. This complication can be treated with balloon dilation, although the long-term course is unknown.

Adult↗

Echocardiographic and biochemical evaluation of the development and progression of carcinoid heart disease.

OBJECTIVES: To study the applicability of a newly developed echocardiographic scoring system in the assessment of carcinoid valvular heart disease. BACKGROUND: We investigated prospectively the development, progression and regression of carcinoid valvular heart disease in patients with carcinoid syndrome by serial echocardiography, correlating these features with urinary 5-HIAA levels and clinical data collected during therapy with somatostatin analog. METHODS: Twenty-three patients with carcinoid syndrome underwent serial echocardiographic examinations. An echocardiographic carcinoid valvular heart disease (CVHD) % score was determined from points assigned for tricuspid and pulmonary valve structure and function. RESULTS: Fifteen patients had no CVHD at study entry (group 1), while 8 patients had findings of CVHD (group 2). Five patients in group q developed new CVHD (1B), while one demonstrated progression of CVHD (2B). The remaining patients did not develop (1A) or had no progression of CVHD (2B). Despite major declines in 5-HIAA levels during therapy in most patients, CVHD did not regress. There were significantly lower levels of median baseline 5-HIAA (98.8 vs. 256 mg/24 h), posttreatment 5-HIAA (50.3 vs. 324 mg/24 h) and posttreatment 5-HIAA time integral (37.3 vs. 192 g/24 h* days) in group A vs. B (p < 0.05). However, only posttreatment 5-HIAA levels independently predicted the development or progression of CVHD by multiple step-wise regression analysis (p < 0.005), with a threshold observed in the 100 mg/24 h range. CONCLUSIONS: We designed a new echocardiographic scoring system to evaluate CVHD. Correlating echocardiographic scores with biochemical and clinical markers showed that only posttreatment 5-HIAA levels independently predicted the development or progression of CVHD. This study strengthens the association between serotonin secretion and CVHD, as well as introducing a new technique for serial follow-up of these patients.

Adult↗

Optimal Albunex dosing for enhancement of Doppler tricuspid regurgitation spectra.

Intravenous albunex was more effective than agitated saline in enhancing incomplete Doppler echocardiography spectra for tricuspid regurgitation without a significant alteration in the maximal detected velocity. The optimal dose was 1 to 4 ml in most patients, using an initial dose of 1 ml and titrating further dosing on the basis of the initial contrast effect.

Adult↗

Late generalized tuberculosis: unusual features of an often overlooked disease.

Late generalized tuberculosis--ie, disseminated tuberculosis occurring long after the primary infection-- is an often unrecognized cause of severe illness in patients with relative immunocompromise, such as the elderly, alcoholics, or those with chronic illnesses. It has become increasingly recognized in the elderly as a cause of a gradual debilitating illness, often with vague constitutional symptoms. We describe three cases of late generalized tuberculosis in patients seen on a single medical service over a 6-month period. Each case presents a unique features of extrapulmonary tuberculosis that escaped diagnosis for some time, and each of these elderly patients had a protracted and wasting illness. We present these cases and the ensuing discussion to reemphasize to clinicians that late generalized tuberculosis may be experiencing increased prevalence among the elderly and that diagnosis requires a heightened suspicion. A history of past tuberculosis infection is not always present, but the diagnosis should be entertained in any elderly patient with a chronic debilitating illness.

Aged↗

Effects of [(N-alkyl-1,3-dihydro-1-oxoisoindolin-5-yl)oxy]alkanoic acids on chloride transport in primary astroglial cultures.

It has been demonstrated that agents which inhibit chloride influx and, therefore, lower intracellular chloride levels in the astrocyte, a major cell type in the cerebral gray matter, inhibit astrocytic swelling in vitro and in vivo. Herein, we report additional examples of a series of [(N-alkyl-1,3-dihydro-1-oxoisoindolin-5-yl)oxy]alkanoic acids and their effects upon ion transport in primary rat astrocyte cultures. The 4-chloro-substituted 1-oxoisoindolines demonstrated superior astrocytic chloride influx inhibitory activity as compared to the 6-chloro and non-chlorinated analogs. The four-carbon acid side chain derivatives were more active than the three- and two-carbon analogs. The pharmacological profile of these compounds was examined with respect to inhibition of the Cl(-)-Cl-/Cl(-)-HCO3- anion exchanger and Na(+)-K(+)-2Cl- cotransport mechanisms in glia, and the compounds were found to exhibit a similar profile to that of furosemide by inhibiting both transporters.

Animals↗

Conformational analysis, molecular modeling, and quantitative structure-activity relationship studies of agents for the inhibition of astrocytic chloride transport.

Molecular modeling studies were carried out on a series of 1-oxoisoindolines which are pharmacologically active as inhibitors of astrocytic chloride transport. Conformational analysis revealed that the halogen substituent exerted a pronounced steric directing effect on the acid side chain. The 4-substituted analogs apparently provided for the best spatial arrangement of pharamacophoric elements of the molecules. Conventional quantitative structure-activity relationship (QSAR) studies using lipophilic and dipole moment characteristics of the molecules as physical descriptor variables in the regression equation yielded a statistically significant model. Comparative molecular field analysis (CoMFA) was utilized as a three-dimensional QSAR technique to explore changes in the steric and electrostatic fields of the molecules that can account for differences in biological activity values. A highly predictive model was attained which supported the results from the qualitative and conventional quantitative structure-activity relationship analyses. These modeling techniques represent the evolutionary process by which structure-activity methods were employed to aid in the development of novel more potent inhibitors of astrocytic chloride transport.

Astrocytes↗

Effects of [(N-alkyl-1,3-dioxo-1H,3H-isoindolin-5-yl)oxy]alkanoic acids, [(N-alkyl-1-oxo-1H,3H-isoindolin-5-yl)oxy]butanoic acids, and related derivatives on chloride influx in primary astroglial cultures.

It has been shown that agents that inhibit chloride influx and therefore lower intracellular chloride levels in a major cell type in cerebral gray matter, the astrocyte, inhibit astrocytic swelling in vitro and in vivo. In our laboratories, 4-[(N-alkyl-1,3-dioxo-1H,3H-isoindolin-5-yl)oxy]alkanoic acids and related derivatives have been synthesized and tested for ability to lower intracellular astrocytic chloride levels in an established in vitro cultured rat astrocyte model. In general, derivatives with nitrogen substituents such as relatively small alkyl groups are active at 0.1 mM and/or 0.5 mM levels whereas larger substituents such as cyclopentyl and cyclohexyl are less active. Halogen substitution on the aromatic ring did not enhance activity. Derivatives with acid side chains of four carbons demonstrated superior activity to those of two carbons.

Animals↗

Sites of P element insertion and structures of P element deletions in the 5' region of Drosophila melanogaster RpII215.

Several P element insertion and deletion mutations near the 5' end of Drosophila melanogaster RpII215 have been examined by nucleotide sequencing. Two different sites of P element insertion, approximately 90 nucleotides apart, have been detected in this region of the gene. Therefore, including an additional site of P element insertion within the coding region, there are at least three distinct sites of P element insertion at RpII215. Both 5' sites are within a noncoding portion of transcribed sequences. The sequences of four revertants of one P element insertion mutation (D50) indicate that the P element is either precisely deleted or internally deleted to restore RpII215 activity. Partial internal deletions of the P element result in different RpII215 activity levels, which appear to depend on the specific sequences that remain after excision.

Animals↗

Homogeneous uridine kinase from Ehrlich ascites tumor: substrate specificity and inhibition by bisubstrate analogs.

Uridine kinase has been purified to homogeneity from Ehrlich ascites tumor cells. For the phosphate acceptor site, the enzyme shows substrate specificity only for ribopyrimidine nucleosides and is active with various analogs that have limited structural alterations; both endocyclic and exocyclic substituents can be acceptable. Of nucleosides that have been used in the chemotherapy of cancer, 5-fluorouridine, 6-azauridine, and 3-deazauridine are good substrates, whereas arabinosylcytosine is a poor substrate. No analogs are better substrates than the physiological substrates uridine and cytidine. 5', 5''' -P1, P4-Bisnucleoside oligophosphate bisubstrate analogs (e.g., Ap4U, Ap5U) were synthesized and tested as inhibitors. The most effective compound was Ap4U; with a Ki of 197 microM, it bound more tightly than ATP but no better than uridine. Ap3A, Ap4A, and Ap5A were also tested, with the result that both Ap4A and Ap4U were most effective, suggesting that this size of bisubstrate analog most closely approaches the spacing of the catalytic site.

Adenine Nucleotides↗

Acute inferior myocardial infarction complicated by rupture into the coronary sinus: diagnosis by two-dimensional echocardiography.

Ventricular rupture is a catastrophic, often fatal complication of myocardial infarction. We present a unique case of left ventricular rupture into the coronary sinus that was diagnosed by two-dimensional Doppler echocardiography in a patient with a recent inferior myocardial infarction. The echocardiographic findings essential to diagnosis were subsequently confirmed at autopsy and are reviewed in detail.

Aged↗