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Biomedical subjects

J Lessem

Publications and source records attributed to J Lessem.

At least 19 recordsLinked to original sources
PubMed2004

Clinical relevance of adjunctive minocycline microspheres in patients with chronic periodontitis: secondary analysis of a phase 3 trial.

BACKGROUND: A recent Phase 3 trial demonstrated that adjunctive treatment with minocycline microspheres resulted in significant reductions in patient mean probing depths as compared to scaling and root planing (SRP) alone. The objective of the present study was to evaluate clinical relevance of these changes within the trial using proposed site-based criteria. METHODS: A total of 499 patients with moderate to advanced chronic periodontitis were enrolled in a multi-center trial and randomized to either: 1) SRP alone or 2) SRP plus minocycline microspheres. Subjects received complete probing examinations including the measurement of probing depths at baseline, and 1 and 3 months. Probing depth reductions were tabulated by treatment, examination time, and baseline depths, and inter-group differences were evaluated with logistic regression models for correlated data. RESULTS: Significantly more sites treated with adjunctive minocycline microspheres exhibited probing depths < 5 mm at 1 (P = 0.0009) and 3 (P = 0.01) months as compared to sites treated with SRP alone, both in the overall population and in smokers. In addition, significantly more sites decreased by 1, 2, or 3 mm in the adjunctive minocycline group than in the SRP alone group at 1 and 3 months, both overall as well as in smokers (P < 0.05). CONCLUSION: This secondary analysis indicates that treatment with SRP plus minocycline microspheres is consistently more effective than SRP alone in providing clinically relevant site-based responses in patients with chronic periodontitis.

Anti-Bacterial Agents↗
PubMed2001

Treatment of periodontitis by local administration of minocycline microspheres: a controlled trial.

BACKGROUND: Periodontitis is an inflammatory condition of tooth-supporting tissues that is usually treated by mechanical removal of plaque and microorganisms that adhere to teeth. This treatment, known as scaling and root planing, is not optimally effective. Adjunctive therapy with locally delivered antimicrobials has resulted in improved clinical outcomes such as probing depth reduction. This article reports on the efficacy and safety of locally administered microencapsulated minocycline. METHODS: Seven hundred forty-eight (748) patients with moderate to advanced periodontitis were enrolled in a multi-center trial and randomized to 1 of 3 treatment arms: 1) scaling and root planing (SRP) alone; 2) SRP plus vehicle; or 3) SRP plus minocycline microspheres. The primary outcome measure was probing depth reduction at 9 months. Clinical assessments were performed at baseline and 1, 3, 6, and 9 months. RESULTS: Minocycline microspheres plus scaling and root planing provided substantially more probing depth reduction than either SRP alone or SRP plus vehicle. The difference reached statistical significance after the first month and was maintained throughout the trial. The improved outcome was observed to be independent of patients' smoking status, age, gender, or baseline disease level. There was no difference in the incidence of adverse effects among treatment groups. CONCLUSIONS: Scaling and root planing plus minocycline microspheres is more effective than scaling and root planing alone in reducing probing depths in periodontitis patients.

Administration, Topical↗
PubMed1997

Mechanisms and clinical effects of thiazolidinediones.

Studies of pioglitazone, troglitazone, BRL 49653 and other thiazolidinediones in preclinical animal models of non-insulin dependent diabetes mellitus (NIDDM) and obesity led to the observation that these compounds were effective in reducing hyperglycaemia and hyperlipidaemia. In these models, animals treated with thiazolidinediones had notable improvements in blood glucose levels, hepatic glucose output, peripheral insulin resistance, and serum lipid levels. Mechanistic studies indicate that thiazolidinediones act at many intracellular sites and can influence several processes to increase cell sensitivity to insulin. These include influence on insulin receptor kinase activity, control of insulin receptor phosphorylation, change in number of insulin receptors, quantity and activity of GLUT-4, modulation of tumour necrosis factor (TNF) activity, activation of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) and alteration of hepatic glucose metabolism. Available data on pioglitazone and troglitazone from clinical studies support the efficacy and safety of this class of compounds in reducing hyperglycaemia, hypertriglyceridaemia and insulin resistance associated with NIDDM. Currently, only troglitazone is approved for use in the United States and only in combination with insulin. This new pharmacological class of drugs has great promise for the treatment of NIDDM and also as a valuable research tool to further the understanding of the mechanisms that underlie NIDDM and insulin resistance syndrome.

Journal Article↗
PubMed1993

Primary and secondary prevention of myocardial infarction and strokes: an update of randomly allocated, controlled trials.

AIM: To summarize the risk factors associated with coronary heart disease and strokes and to evaluate measures used in the prevention and treatment of these diseases. METHOD: A review of the results of randomly allocated clinical trials of treatment for both primary and secondary prevention of coronary heart disease and strokes. RESULTS: Reductions in elevated blood pressure and cholesterol and cessation of cigarette smoking have clearly been shown to reduce the incidence of coronary heart disease. A reduction in blood pressure has also been shown to reduce the risk of strokes. In addition to other classical risk factors, such as abnormal serum lipids, diabetes and a genetic predisposition, recent studies have shown that elevated levels of fibrinogen and other clotting factors, elevated levels of renin and decreased levels of anti-oxidant vitamins such as E, C and beta-carotene can predict coronary heart disease and strokes. Thrombolytic therapy, aspirin and beta-blockers have been shown to reduce mortality in patients with myocardial infarction, and the latter two agents reduce mortality, re-infarction and strokes with long-term use. Treatment with intravenous magnesium and nitrates has shown promise but larger trials are required to confirm the results. Both aspirin and heparin have proven value in reducing the incidence of myocardial infarction and death in unstable angina. Following an acute myocardial infarction, long-term therapy with aspirin, beta-blockers, lipid-lowering agents and oral anticoagulants has been shown to reduce mortality and re-infarction. In patients with large infarcts associated with a low ejection fraction or heart failure, the use of angiotensin converting enzyme (ACE) inhibitors reduces mortality, hospitalization for heart failure and re-infarction. The use of diuretics to lower blood pressure reduces strokes. In contrast, calcium antagonists do not appear to consistently reduce mortality or prevent vascular events when used for primary or secondary prevention of either myocardial infarction or strokes. CONCLUSIONS: Myocardial infarction and strokes can be prevented by refraining from smoking and maintaining appropriate blood pressure levels and a favourable balance of lipids. Following a myocardial infarction, further drug treatment should include aspirin, thrombolytic therapy (in acute myocardial infarction), beta-blockers, ACE inhibitors (in patients with a low ejection fraction) and perhaps anticoagulants.

Adrenergic beta-Antagonists↗
PubMed1989

Nicardipine and hydrochlorothiazide in essential hypertension.

Nicardipine is an investigational dihydropyridine calcium channel blocking agent. One hundred fifty-one patients with hypertension received either 30 mg nicardipine t.i.d. or 25 mg hydrochlorothiazide b.i.d. in a double-blind, randomized, multicenter trial. After 4 weeks of therapy and at the end of the dosing interval, nicardipine reduced arterial pressure by 10/6 mm Hg and 12/6 mm Hg in the supine and standing positions, respectively (all p less than 0.01). In the hydrochlorothiazide group, the reductions were 12/6 mm Hg and 14/6 mm Hg, respectively (all p less than 0.01). The maximum reduction in blood pressure of 16/14 mm Hg supine and 20/15 mm Hg standing occurred within 1 hour after administration of nicardipine. The mean reduction in the hydrochlorothiazide group after 1 hour was 14/11 mm Hg supine and 16/12 mm Hg standing. Neither drug affected autonomic reflexes associated with maximum exercise. Nicardipine increased urinary sodium excretion during the 4-hour period after the first dose. Adverse effects of nicardipine were primarily extensions of its vasodilator effect and included flushing, headache, and edema.

Adult↗
PubMed1984

In vivo labelling of RBC with 99mTc for blood pool imaging using different stannous radiopharmaceuticals.

The in vivo 99mTc-RBC labelling efficiency and stability of labelling was assessed after pretinning with a high-stannous content DTPA kit (Sn DTPA) in comparison with Sn-pyrophosphate (Sn PPi) and a low-stannous DTPA kit (DTPA). The distribution in Sprague Dawley rats showed that similar fractions of administered 99mTc remained within the blood pool after pretinning with Sn DTPA and Sn PPi when equal quantities of stannous ions (15 micrograms/kg) and equal time intervals (30 min) between successive IV injections of pretinning agent and 99mTc-pertechnetate were used. Significantly lower fractions were found when DTPA (1.9 micrograms Sn2+/kg) was used for pretinning. The rate of 99mTc elution emphasises the importance of the Sn2+ concentration used, not only for labelling efficiency but also for stability of the labelling. Satisfactory intravascular activity, exceeding 80% during the first hour post-injection, was demonstrated in three volunteers after 99mTc injection, when Sn DTPA was used for pretinning. Left ventricular ejection fractions (LVEF) measured by equilibrium radionuclide angiography after pretinning with Sn DTPA in 24 patients correlated well (r = 0.98) with those obtained by contrast angiographies over a broad spectrum of values (0.14-0.72). Four repeated LVEF measurements at 45-min intervals in six additional patients at rest showed excellent reproducibility in each patient: maximum variation was less than 6%.

Animals↗
PubMed1984

Combined therapy with Ca-antagonists and beta-adrenergic receptor blocking agents in chronic stable angina.

There have been conflicting reports on the safety of combining beta-adrenergic receptor blockers and Ca++-antagonists, especially verapamil, in the treatment of cardiovascular diseases. Warnings have been raised against additive negative chronotropic and inotropic effects. This study was designed to compare the efficacy and safety of simultaneous administration of verapamil, 360 mg daily, and atenolol, 100 mg daily, with that of either drug alone. Eighteen patients (mean age 58 years) with chronic stable angina were included in the study. After a two-week run-in period, the patients received either drug alone for six weeks and were then given the combination for another six weeks. Frequent ECG and blood pressure measurements were performed. Radionuclide evaluation of left ventricular ejection fraction was done before and at the end of the combined therapy. Exercise testing using a bicycle ergometer was performed during each treatment period. Only one patient developed sinus bradycardia when on combined therapy (48 bpm). The P-Q time increased with single drug therapy as well as with the combination (p less than 0.01). Maximal exercise time increased more with the combination than with single drug therapy. No serious adverse hemodynamic effects were recorded. LVEF increased by 4.6% (p less than 0.01) with the combined therapy. A decrease in nitroglycerine consumption occurred, beeing most pronounced with the combined therapy and corresponding to a subjective improvement. It is concluded that an additive negative chronotropism occurred but that the combination is safe and offers an effective therapeutic alternative in chronic stable angina.

Adult↗
PubMed1983

Interaction between digoxin and the calcium antagonists nicardipine and tiapamil.

The investigation was designed to test whether nicardipine and tiapamil interact with digoxin, resulting in increased plasma digoxin levels. Ten patients mean age, 67 years) taking 0.13 mg to 0.25 mg of digoxin daily were given nicardipine (20 mg TID), and eight patients (mean age, 77 years) taking 0.13 mg to 0.25 of digoxin daily were given tiapamil (200 mg TID). Plasma levels of digoxin and nicardipine, heart rate, blood pressure, weight, serum electrolytes, and serum enzymes were measured and the electrocardiogram was monitored twice before, four times during, and once after the intervention with a calcium antagonist. No measurements of plasma levels of tiapamil were made. A chest roentgenogram was taken before, during, and after use of nicardipine or tiapamil. Mean plasma digoxin levels increased significantly in patients receiving tiapamil (P less than 0.01), but the values returned to normal after treatment with the experimental drug was discontinued. A wide variation of plasma nicardipine levels was observed, but there was no proportionate correlation between these levels and changes in digoxin levels. Blood pressure decreased significantly (P less than 0.01) and heart rate increased significantly (P less than 0.05) in patients receiving nicardipine. Similar changes in blood pressure and heart rate were not seen in patients receiving tiapamil. Although the use of each calcium antagonist led to an increase in plasma digoxin levels, the effect of tiapamil was greater than that of nicardipine.

Aged↗
PubMed1982

New design for clinical trial of antihypertensive drugs applied to pindolol, clopamide, and combinations thereof.

A beta-blocker (pindolol) and a diuretic (clopamide) were given in different dosages, singly and in two different combinations, to 71 patients with mild to moderate essential hypertension. The trial design was such that patients took both drugs singly and in combination, and in different doses, according to a set plan. The best regimen for each patient was determined by taking into account not only blood pressure but also resting heart-rate, body-weight, serum potassium, and serum urate. For 19 patients (27%) monotherapy was best--pindolol for 16 and clopamide for 3. For the remaining patients, a combination of pindolol 10 mg and clopamide 5 mg was best for 39, and in 35 of these one tablet daily was sufficient. All patients reached the preset target blood-pressure. The differences in proportions responding best to the following pairs of regimens compared--monotherapy vs combination, and combination of clopamide 5 mg and pindolol 5 mg vs combination of clopamide 5 mg and pindolol 10 mg--were significant (2p less than 0.01). The process by which the best treatment is chosen according to this study design resembles much more closely that followed in general medical practice, than does the process in the conventional hypertension trial, in which only average effects are reported and compared.

Adult↗
PubMed1982

Beta-blocker therapy evaluated by radionuclide angiography: a study in chronic stable angina.

In order to evaluate the negative inotropic effects of sotalol, metoprolol, and propranolol in patients with chronic stable angina pectoris, left ventricular ejection fraction (LVEF) was measured with radionuclide angiography and echocardiography. Fifteen patients entered the study, which was designed as a randomized crossover trial. The patients served as their own control at all times. Surprisingly, LVEF increased when measured by echocardiography in all three treatment periods, and decreased in the propranolol period when measured by radionuclide methods. The changes were not significant. There was no negative inotropic effect registered during any of the three drug treatments.

Adrenergic beta-Antagonists↗
PubMed1982

Predictive use of routine 24-hour electrocardiography in suspected Adams-Stokes syndrome. Comparison with cardiac rhythm during symptoms.

Using strictly defined criteria of significant arrhythmias, long term electrocardiographic recording has been evaluated for confirmation of arrhythmias as the cause of cerebral symptoms in 81 patients with suspected Adams-Stokes syndrome. Extension of long term electrocardiographic recording for more than 24 hours gives marginal additional information at a high cost. Among 43 patients monitored until symptoms appeared, non cardiogenic causes were confirmed in 20 of 22 patients because the recording showed normal rhythm during symptoms. Fifteen of 21 patients with a significant arrhythmia during an asymptomatic 24 hour recording later had the same arrhythmia during symptoms. Of 38 patients who failed to develop symptoms, 21 had a significant arrhythmia detectable within 24 hours and 23 when 48 hours of recording were analysed.

Adams-Stokes Syndrome↗
PubMed1982

Tiapamil in the treatment of lidocaine-resistant ventricular arrhythmias complicating acute myocardial infarction.

The antiarrhythmic effects of tiapamil were investigated in 48 patients, mean age 54, with acute myocardial infarction and ventricular arrhythmias. 9 had ventricular tachycardia, 6 ventricular fibrillation, and 33 multifocal premature ventricular contractions. Before and after therapy, ECG parameters, left ventricular ejection fraction (measured using 99mTc-labelled blood cells), and serum enzymes were recorded. Tiapamil was administered in a dose of 1 mg/kg i.v. (injection) followed by 25 micrograms/kg/min i.v. (infusion) until a 70% reduction in premature ventricular contractions was achieved. Thereafter, tiapamil was given in oral administration of 200 mg three times daily for 3 months. 13 patients did not respond to treatment. Of these, 5 had ventricular tachycardia and 4 ventricular fibrillation. 6 patients died and showed massive necrosis at autopsy. Premature ventricular contractions decreased by 70-90% in the remaining 35 patients (73%). Mean arterial pressure and heart rate decreased significantly, the left ventricular ejection fraction improved, and the P-R interval increased significantly. No side effects were observed. It is concluded that tiapamil has the propensity to control premature ventricular contractions in patients with acute myocardial infarction.

Anti-Arrhythmia Agents↗
PubMed1980

Accumulation of technetium-99m pyrophosphate in experimental infarctions in the rat.

Cardiac accumulation patterns of pyrophosphate labelled with techetium-99m (TcPyP) in rats one hour to 7 days after coronary artery ligation were studied by light microscopy, myocardial scintigraphy, imaging the isolated heart and by direct measurement of tissue activity. Results suggest that myocardial cells taking up TcPyP are irreversibly damaged and that the disappearance of TcPyP uptake coincides with the removal of necrotic cells by phagocytes.

Animals↗
PubMed1980

Epilepsy and myopathy in a patient with Rothmund-Thomson's syndrome.

A report of a 21-year-old female, who has had Rothmund-Thomson's syndrome since early childhood, is given. In addition to the original disease with skin and tendon manifestations, she has also developed myopathy and epilepsy. It is discussed whether these two recent manifestations are part of her original syndrome or of different pathogenesis.

Adult↗