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Biomedical subjects

B Kimmel

Publications and source records attributed to B Kimmel.

17 recordsLinked to original sources

An investigation on the use of data-driven scattering profiles in Monte Carlo simulations of ultraviolet light propagation in skin tissues.

Ultraviolet light can affect the appearance and medical condition of the human skin by triggering biophysical processes such as erythema, melanogenesis, photoaging and carcinogenesis. The evolution of these processes is related to the amount of ultraviolet light absorbed by skin pigments. This amount may vary with the wavelength and path length of the radiation that is propagated within the skin tissues. For many years, biomedical researchers have been investigating the propagation of ultraviolet light in skin tissues through Monte Carlo simulations. The scattering of the incident radiation by tissue internal structures, a key component in this process, is usually approximated by functions without a plausible connection with the underlying physical phenomena. In this paper, we examine the origins of such an approach, and question its generalized use with respect to wavelengths and biological materials for which there is no supporting data available. Furthermore, we perform comparisons to demonstrate that the accuracy and predictability of Monte Carlo simulations of ultraviolet propagation in skin tissues can be improved by using a data-driven approach to represent the scattering profile of these tissues.

Animals↗

Operational aspects of terminating the doxazosin arm of The Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).

The Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) is a randomized, practice-based trial sponsored by the National Heart, Lung, and Blood Institute (NHLBI). The double-blind, active-controlled component of ALLHAT was designed to determine whether the rate of the primary outcome-a composite of fatal coronary heart disease and nonfatal myocardial infarction-differs between diuretic (chlorthalidone) treatment and each of three other classes of antihypertensive drugs: a calcium antagonist (amlodipine), an angiotensin-converting enzyme inhibitor (lisinopril), and an alpha-adrenergic blocker (doxazosin) in high-risk hypertensive persons ages 55 years and older. In addition, 10,377 ALLHAT participants with mild to moderate hypercholesterolemia were also enrolled in a randomized, open-label trial designed to determine whether lowering serum LDL cholesterol with an HMG CoA reductase inhibitor (pravastatin) will reduce all-cause mortality as compared to a control group receiving "usual care." In January 2000, an independent data review committee recommended discontinuing the doxazosin treatment arm. The NHLBI director promptly accepted the recommendation. This article discusses the steps involved in the orderly closeout of one arm of ALLHAT and the dissemination of trial results. These steps included provisional preparations; the actual decision process; establishing a timetable; forming a transition committee; preparing materials and instructions; informing 65 trial officers and coordinators, 628 active clinics and satellite locations, 313 institutional review boards, over 42,000 patients, and the general public; reporting detailed trial results; and monitoring the closeout process. Control Clin Trials 2001;22:29-41

Adverse Drug Reaction Reporting Systems↗

Identification of immunodominant antigens from Helicobacter pylori and evaluation of their reactivities with sera from patients with different gastroduodenal pathologies.

Colonization of the gastric mucosa by Helicobacter pylori is the major cause of gastroduodenal pathologies in humans. Studying the outcome of the humoral immune response directed against this gastric pathogen may contribute substantially to vaccine development and to the improvement of diagnostic techniques based on serology. By using two-dimensional gel electrophoresis, 29 proteins from H. pylori G27 were identified which strongly react with sera derived from H. pylori-infected patients suffering from different gastroduodenal pathologies. These antigens were characterized by mass spectrometry and proved to correspond to products of open reading frames predicted by the H. pylori genome sequence. The comparison of the antigenic patterns recognized by these sera revealed no association of specific H. pylori antigens with antibodies in patients with particular gastroduodenal pathologies.

Antibodies, Bacterial↗

Specificity of the BvgAS and EvgAS phosphorelay is mediated by the C-terminal HPt domains of the sensor proteins.

Despite the presence of highly conserved signalling modules, significant cross-communication between different two-component systems has only rarely been observed. Domain swapping and the characterization of liberated signalling modules enabled us to characterize in vitro the protein domains that mediate specificity and are responsible for the high fidelity in the phosphorelay of the unorthodox Bvg and Evg two-component systems. Under equimolar conditions, significant in vitro phosphorylation of purified BvgA and EvgA proteins was only obtained by their histidine kinases, BvgS and EvgS respectively. One hybrid histidine kinase consisting of the BvgS transmitter and HPt domains and of the EvgS receiver domain (BvgS-TO-EvgS-R) was able to phosphorylate BvgA but not EvgA. In contrast, the hybrid protein consisting of the BvgS transmitter and the EvgS receiver and HPt domains (BvgS-T-EvgS-RO) was unable to phosphorylate BvgA but efficiently phosphorylated EvgA. These results demonstrate that the C-terminal HPt domains of the sensor proteins endow the unorthodox two-component systems with a high specificity for the corresponding regulator protein. In the case of the response regulators, the receiver but not the output domains contribute to the specific interaction with the histidine kinases, because a hybrid protein consisting of the EvgA receiver and the BvgA output domain could only be phosphorylated by the EvgS protein.

Bacterial Proteins↗

Laparoscopic surgery and splanchnic vessel thrombosis.

We report a case of fatal mesenteric artery thrombosis following laparoscopic cholecystectomy in a 60-year-old hypertensive woman, whose preoperative complaints were not typical of calculous biliary disease. Two previous case reports have associated laparoscopic cholecystectomy and acute intestinal ischemia; one of these patients died. Experimental and clinical data indicate that carbon dioxide pneumoperitoneum reduces splanchnic blood flow through several mechanical and physiologic mechanisms. Consequently, we believe that, when laparoscopic surgery is contemplated, physicians and patients should be aware of the risk of splanchnic vessel thrombosis, especially when certain pre-existing conditions are present (e.g., impairment of splanchnic vessel flow, hypercoagulable states, etc.). For such high-risk patients, especially when the planned laparoscopic procedure may be lengthy, gasless or low-pressure laparoscopic surgery, or even reversion to traditional open surgery should be considered.

Carbon Dioxide↗

Providing equal access for deaf clients.

Fifteen years after the passage of a law by the Federal Government, many hospitals are still not providing hearing-impaired patients with equal access to their services in a consistent and effective way. Not only does this create frustrating situations for the patients and hospital staff, but it also puts the hospital in the position of noncompliance with the law. The author describes how one hospital addressed this issue at the level of service provision and found some workable solutions.

Aged↗

Diltiazem, nifedipine, and their combination in patients with stable angina pectoris: effects on angina, exercise tolerance, and the ambulatory electrocardiographic ST segment.

The efficacy and safety of oral nifedipine and diltiazem were compared in 20 patients with stable angina pectoris with use of a placebo run-in, randomized, double-blind titration to maximal effect crossover protocol. The effects of treatment withdrawal were also analyzed. All patients received placebo for 2 weeks and were then randomly assigned to receive either diltiazem or nifedipine. A 2 week drug titration phase in which patients received either diltiazem (180 to 360 mg/day) or nifedipine (30 to 120 mg/day) in three divided doses was followed by a 1 week maintenance phase. Patients then received placebo for 1 to 2 weeks, followed by crossover to the other treatment regimen and a second placebo washout period of 1 week. Patients (n = 13) who remained symptomatic on both diltiazem and nifedipine during the monotherapy periods entered a 3 week combination treatment phase, followed by a final 1 week placebo washout period. Frequency of angina, nitroglycerin consumption, exercise tolerance (Naughton protocol), and frequency of daily episodes of ST segment deviations on the electrocardiogram (1 mm of ST segment depression persisting for at least 1 min with and without chest pain) on an ambulatory electrocardiographic monitor were assessed during the baseline placebo, active monotherapy, placebo withdrawal, and combination treatment phases. Plasma drug levels were also measured. Compared with initial placebo values, the frequency of angina and the amount of nitroglycerin treatment were reduced by both diltiazem (p less than .001) and nifedipine (p less than .02). Diltiazem was more effective than nifedipine in reducing angina (p less than .02). Exercise duration increased with both drugs (p less than .0001). Diltiazem was significantly better than nifedipine in reducing the episodes of ST segment depression on the ambulatory monitor (p less than .01). Diltiazem reduced the resting heart rate (p less than .01); both drugs reduced the resting blood pressure and rate-pressure product. Overall, combination therapy was more effective in patients who did not maximally respond to diltiazem or nifedipine alone with respect to anginal and exercise variables and in reducing blood pressure at rest and during exercise. Plasma drug levels could not predict an individual patient's treatment response. Diltiazem may increase nifedipine drug levels when the drugs are combined. Fewer side effects were observed with diltiazem than nifedipine; the most side effects were seen with combination treatment. There were no apparent withdrawal effects observed with either treatment regimen.(ABSTRACT TRUNCATED AT 400 WORDS)

Angina Pectoris↗

Calcium-channel blockers for combined angina pectoris and systemic hypertension.

Calcium-channel blockers have been successfully used in the treatment of angina of effort and systemic hypertension. Many patients present with concomitant angina pectoris and hypertension. Controlled clinical trials demonstrate that the calcium-channel blockers are safe and effective as monotherapy in the treatment of these patients, and that their use compares favorably with that of propranolol. The effectiveness of these agents in hypertension appears to be primarily due to their ability to induce systemic vasodilation. Calcium-channel blockers have several therapeutic effects in angina pectoris. Beneficial actions on the major determinants of oxygen consumption, i.e. heart rate, blood pressure and contractility, are generally seen. The potent coronary vasodilating actions of these agents allow for increased coronary blood flow. Improvements in ventricular compliance, regression of left ventricular hypertrophy and cardioprotection appear to be additional effects of the calcium-channel blockers; their contribution to the drugs' overall therapeutic efficacy is presently being evaluated. Calcium-channel blockers are a welcome addition to drug regimens available for the management of patients with coexisting angina pectoris and hypertension.

Adult↗

Twice-daily nicardipine in the treatment of essential hypertension.

The antihypertensive effect of twice-daily nicardipine, an investigational calcium-channel blocker, was evaluated in a placebo-controlled, single-blind trial in 18 adult patients with essential hypertension (supine diastolic blood pressure [BP] of greater than or equal to 95 and less than or equal to 120 mmHg). Following a 4-week run-in period in which patients received placebo for the final 2 weeks, nicardipine was administered for 12 weeks with a treatment goal of a supine diastolic BP of less than 90 mmHg at 12 hours postdosing or to a maximum dose of 60 mg twice daily. Supine and standing BPs and heart rates were determined at 1 hour and 12 hours postdosing. At all dose levels, supine and standing BPs were reduced at 1 hour after dosing, with partial loss of efficacy seen at 12 hours. Increases in heart rate seen at 1 hour were not significant at 12 hours. Eight patients withdrew from the study for minor, although troublesome, side effects, such as palpitations and headaches. These data suggest that nicardipine monotherapy given in a twice-daily dosing regimen has only a limited role to play in the chronic treatment of patients with essential hypertension.

Adult↗

Twice-daily administration of oral verapamil in the treatment of essential hypertension.

The antihypertensive effect of twice-daily administration of verapamil hydrochloride was evaluated in 21 adult patients with mild to moderate essential hypertension. Following four weeks of placebo therapy, verapamil was given for four weeks with a treatment goal of sitting diastolic blood pressure (BP) of less than 90 mm Hg, or to a maximum dose of 160 mg twice daily. Sitting and standing BPs, heart rate, and verapamil plasma levels were determined weekly, ten to 12 hours post dose. At the maximal dose (mean, 154 +/- 19.2 mg), heart rate was not affected, side effects were minimal, and sitting diastolic BP was significantly reduced from placebo baseline, with 12 of 21 patients having a fall in sitting diastolic BP of 10 mm Hg or more or less than 90 mm Hg. A trough verapamil plasma level of greater than 80 ng/mL was associated with a good hypotensive response. These data indicate the safety and utility of twice-daily verapamil administration for the treatment of essential hypertension and suggest the value of obtaining verapamil plasma levels as a guide to dosage determination.

Administration, Oral↗

Comparison of diltiazem and nifedipine for both angina pectoris and systemic hypertension.

In a randomized, double-blind, placebo-controlled crossover trial, diltiazem and nifedipine were compared in 10 patients with stable angina pectoris and mild to moderate hypertension (supine diastolic blood pressure greater than or equal to 90 mm Hg). Patients received placebo for 2 weeks, then increasing doses of diltiazem (90 to 360 mg/day) or nifedipine (30 to 120 mg/day) in 3 daily divided doses over 2 weeks, followed by 1 week of therapy at the maximal dose, a 1-week placebo "washout," then crossover to the other drug. Heart rate and blood pressure at rest and during exercise, anginal frequency, nitroglycerin consumption and treadmill exercise tolerance were assessed. Compared with placebo, anginal frequency and nitroglycerin consumption were reduced with both diltiazem and nifedipine (p less than 0.01) and exercise tolerance was increased with both drugs (p less than 0.01). Standing blood pressure at rest was reduced by diltiazem and nifedipine (146.6 +/- 11.4/97.7 +/- 5.3 mm Hg at placebo, baseline reduced to 129.6 +/- 15.2/79.5 +/- 13.7 mm Hg with diltiazem, and to 122.2 +/- 9.9/82.0 +/- 7.1 with nifedipine, p less than 0.01 for both). Compared with placebo, diltiazem and nifedipine also reduced exercise diastolic blood pressure (p less than 0.01), but not systolic blood pressure. Diltiazem lowered the heart rate at rest from 88.5 +/- 14.4 beats/min at placebo baseline to 79.7 +/- 17.9 beats/min (p less than 0.01); the heart rate with diltiazem was 11 beats/min lower than that with nifedipine (p less than 0.05). Both diltiazem and nifedipine had similar effects on the heart rate-blood pressure product at rest and during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Lidoflazine and propranolol combination treatment in chronic stable angina.

The short-term (1 month) and long-term (6 months) safety of combination lidoflazine-propranolol therapy was investigated in an open trial of 15 patients with stable angina of effort. The possible advantages of adding lidoflazine (titrated to 360 mg daily) to patients having a therapeutic response to propranolol (80-400 mg daily) was also evaluated. Effects on non-invasive indexes of left ventricular function (echocardiography, systolic time intervals, radionuclide ventriculography) and exercise tolerance (treadmill exercise testing) were determined. There was no change in mean resting heart rate with the combination therapy, although one patient developed sinus bradycardia at a rate of 44 and had to have his propranolol dose reduced. Electrocardiographic analysis showed significant prolongation of the QTc intervals on lidoflazine-propranolol therapy compared to propranolol alone, with 3 patients having QTc interval prolongation to above .53 seconds, but there was no evidence of increased arrhythmogenesis with the combination therapy compared to propranolol alone. Left ventricular end-diastolic volume index tended to rise with combination therapy. However, lidoflazine-propranolol therapy did not produce any significant effects on resting ejection fraction determined by M-mode echocardiography or by radionuclide ventriculography. Radionuclide ventriculography determined peak exercise ejection fractions were also not significantly changed with combination therapy compared to propranolol alone. There were only small, insignificant improvements in exercise tolerance with the lidoflazine-propranolol combination treatment compared to propranolol alone. It is concluded that lidoflazine-propranolol combination therapy is generally safe but has the potential of causing serious adverse effects in certain patients, i.e. those with sick sinus disease, prolonged QTc intervals, and severe baseline left ventricular dysfunction, and that caution must be exercised in its use. Furthermore, it would appear that combination therapy provides only slight, if any, improvements in exercise tolerance in patients with chronic stable angina having a therapeutic response to oral propranolol.

Adult↗

Calcium entry blockers for the treatment of severe hypertension and hypertensive crisis.

Calcium entry blockers (diltiazem, nifedipine, and verapamil) are currently indicated for the treatment of patients with vasospastic and chronic stable angina pectoris. The calcium entry blocking actions of these drugs cause potent peripheral vasodilatory and antihypertensive effects in human subjects. The drugs have proved beneficial in the treatment of patients with severe hypertension and hypertensive emergencies. Single oral, sublingual, and intravenous doses of these drugs have been shown to rapidly and smoothly reduce blood pressure in adults and children, without significant untoward effects. The absolute reduction in blood pressure with treatment appears to be inversely correlated with the pretreatment blood pressure level, and few episodes of hypotension have been reported. Combinations of calcium entry blockers with other antihypertensive regimens have also proved effective. Some patients experience a mild increase in heart rate with nifedipine, an effect that appears to be inversely related to age. Side effects are minimal and not life-threatening. Continuous hemodynamic monitoring of patients does not seem necessary in most cases. The role of calcium entry blockade in the treatment of hypertensive emergencies still needs to be established in relation to other available approved drug regimens for this condition.

Antihypertensive Agents↗

Sedation for pediatric patients undergoing CT and MRI.

Adequate sedation remains one of the most important parts of performing high quality cross-sectional imaging in children. This is a noncomparative retrospective analysis of existing sedation protocols used in 1,158 children between the ages of 1 day and 18 years, checking for safety and efficacy. The most commonly used drugs were chloral hydrate (60-120 mg/kg) by mouth for infants less than 18 months and intravenous Nembutal (2-6 mg/kg) for older children. Sedation was successful in 97% of patients.

Administration, Oral↗