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Biomedical subjects

S Greenberg

Publications and source records attributed to S Greenberg.

At least 109 records · Page 6Linked to original sources

Angiotensin converting enzyme inhibitors as initial monotherapy in severe hypertension. Quinapril and captopril.

This 6-week, double-blind, parallel-group study compared the efficacy and safety of the angiotensin converting enzyme (ACE) inhibitors quinapril and captopril as initial monotherapies in patients with severe hypertension (diastolic blood pressure [DBP] greater than or equal to 115 and less than or equal to 130 mm Hg). A total of 97 patients, aged between 18 and 70 years, were randomized to 5 mg oral quinapril twice daily or 25 mg captopril twice daily with maximum titration to 20 mg quinapril twice daily or 100 mg captopril twice daily. With the morning dose 25 mg hydrochlorothiazide (HCTZ) could be added at week 4 of the double-blind phase or earlier if required for safety considerations. For the monotherapy phase, mean reductions in DBP of 12.1 mm Hg were achieved with both treatments. Clinical response rates (reduction in DBP greater than or equal to 10 mm Hg) were 58% for quinapril and 44% for captopril. At the end of therapy, with optional HCTZ, mean reductions in DBP were 19.0 mm Hg for the quinapril-treated group and 16.2 mm Hg for the captopril-treated group. None of the differences achieved statistical significance. Headache was the most frequently reported adverse event in both treatment groups with 8 reports each. No clinically significant changes in laboratory data were observed in any parameter for either treatment group. Quinapril and captopril provide comparable efficacy and safety in treatment of severe hypertension when used as initial monotherapy and with the addition of optional HCTZ.

Administration, Oral↗

Hemodynamic and myocardial energetic effects of CK-3197, a selective positive inotropic agent.

CK-3197 was developed as a selective positive inotropic agent for the treatment of congestive heart failure. We compared the hemodynamic and myocardial energetic effects of CK-3197 to ouabain in the pentobarbital-anesthetized dog. Fifteen minutes after intravenous (i.v.) administration of CK-3197 (0.1, 0.3, and 1.0 mg/kg) to five dogs, mean left ventricular (LV) dP/dt increased by 24, 68, and 109% and mean arterial pressure (MAP) decreased by 4, 9, and 18%, respectively, from basal values. CK-3197 was 11 times more potent as a positive inotropic agent than as a vasodilator. Heart rate (HR) increased by 5, 14, and 24% after these doses of CK-3197, whereas LV end diastolic pressure (LVEDP) decreased by 4 mm Hg after the highest dose of compound. LV oxygen consumption (MVO2) and stroke MVO2 increased by 9, 25, and 102% and 1, 8, and 58%, respectively, at the peak of the increases in LV dP/dt. Ouabain (0.02 and 0.03 mg/kg, i.v.) increased MAP (12 and 22%), HR (2 and 20%), and LV dP/dt (19 and 36%), with a 14 and 16% increase in LV MVO2 and a 12 and -6% change in stroke MVO2. Thus, CK-3197 is a selective, positive inotropic agent with preload reducing activity in the dog. CK-3197, similar to ouabain, produced energy-efficient positive inotropic responses with either no increase in MVO2 or increases in myocardial oxygen consumption that were less than the expected 1:1 ratio with LV dP/dt. Therefore, CK-3197 may have significant utility in the clinical treatment of congestive heart failure.

Animals↗

A composite model of the auditory periphery for the processing of speech based on the filter response functions of single auditory-nerve fibers.

A composite model of the auditory periphery, based upon a unique analysis technique for deriving filter response characteristics from cat auditory-nerve fibers, is presented. The model is distinctive in its ability to capture a significant broadening of auditory-nerve fiber frequency selectivity as a function of increasing sound-pressure level within a computationally tractable time-invariant structure. The output of the model shows the tonotopic distribution of synchrony activity of single fibers in response to the steady-state vowel [e] presented over a 40-dB range of sound-pressure levels and is compared with the population-response data of Young and Sachs (1979). The model, while limited by its time invariance, accurately captures most of the place-synchrony response patterns reported by the Johns Hopkins group. In both the physiology and in the model, auditory-nerve fibers spanning a broad tonotopic range synchronize to the first formant (F1), with the proportion of units phase-locked to F1 increasing appreciably at moderate to high sound-pressure levels. A smaller proportion of fibers maintain phase locking to the second and third formants across the same intensity range. At sound-pressure levels of 60 dB and above, the vast majority of fibers with characteristic frequencies greater than 3 kHz synchronize to F1 (512 Hz), rather than to frequencies in the most sensitive portion of their response range. On the basis of these response patterns it is suggested that neural synchrony is the dominant auditory-nerve representation of formant information under "normal" listening conditions in which speech signals occur across a wide range of intensities and against a background of unpredictable and frequently intense acoustic interference.

Animals↗

Resolution of ventricular tachycardia and endocardial tuberculoma following antituberculosis therapy.

A 23-year-old woman presented with sustained ventricular tachycardia and was found to have an endocardial mass by echocardiography and by magnetic resonance imaging. The diagnosis of cardiac endocardial tuberculoma was made, and she was treated with antituberculous therapy and an antiarrhythmic drug for one year. After a year, the mass was no longer present, and with all antiarrhythmic medications stopped, ventricular tachycardia could no longer be induced by electrophysiologic study. There has been no clinical recurrence.

Adult↗

Treatment of superior vena cava thrombosis with recombinant tissue type plasminogen activator.

Thrombotic occlusion of the superior vena cava is an uncommon but serious complication of chronic indwelling venous catheters. Several reports have shown thrombolytic therapy with intravenous streptokinase or urokinase to be effective in the treatment of this condition. We report a case of superior vena cava thrombosis in a 53-year-old woman receiving chemotherapy for breast carcinoma through a subcutaneously implanted venous access catheter who was successfully treated with peripheral infusion of recombinant tissue type plasminogen activator (rtPA).

Antineoplastic Combined Chemotherapy Protocols↗

Visual function after optic neuritis: a preliminary study.

We assessed visual function after recovery from optic neuritis in 15 consecutive patients using five objective tests: colour vision testing with Ishihara colour plates and with D15 colour desaturated spots, Humphrey automated perimetry, contrast acuity testing with Regan letter charts and testing of visual evoked response (VER). Recovery of visual function was not found to be dependent on presenting Snellen visual acuity or treatment with oral steroids. The most sensitive measures of residual visual deficit were mean defect on automated perimetry, low-contrast acuity and VER.

Adult↗

Colocalization of F-actin and talin during Fc receptor-mediated phagocytosis in mouse macrophages.

We have studied the distribution of talin in J774 cells and mouse peritoneal macrophages undergoing Fc receptor-mediated phagocytosis. At early stages of phagocytosis, talin accumulates in the cells' cortical cytoplasm adjacent to the forming phagosome and extends into pseudopods that are encircling the particle. Talin colocalizes with F-actin at these sites. After particle ingestion is completed, F-actin and talin are no longer concentrated adjacent to phagosomes. Thus, talin and F-actin undergo dynamic and coordinate changes in their cytoplasmic location during Fc receptor-mediated phagocytosis.

Actins↗

Prevalence, incidence and prognosis of recognized and unrecognized myocardial infarction in persons aged 75 years or older: The Bronx Aging Study.

The prevalence, incidence and prognosis of recognized and unrecognized Q-wave myocardial infarction (MI) was assessed in an 8-year prospective study of 390 community-based subjects (age 75 to 85 years at entry, mean 79 years). Subjects were studied at baseline and with annual follow-up electrocardiographic (ECG) exams. At baseline, 7.9% had a history of MI without ECG evidence, 6.4% had ECG evidence of Q-wave MI without clinical history, 4.1% had both clinical history and ECG evidence and 81.5% had neither history nor ECG evidence (control subjects). After an average follow-up period of 76.2 months, the total mortality rate was 5.9/100 person-years for subjects with some evidence of MI at baseline versus 3.9 in the control group (p = 0.059). The incidence of cardiovascular disease in subjects with evidence of MI was 8.8/100 person-years versus 4.7 among control subjects (p = 0.002). During the follow-up period, 115 new Q-wave MIs occurred (50 unrecognized, rate 2.4/100; 65 recognized, rate 3.2/100). There was no difference in mortality and morbidity outcome between subjects with recognized and unrecognized MIs. Those with only a history of MI at baseline had a threefold greater risk of a new MI (recognized and unrecognized) than the control group (p = 0.003). Unrecognized Q-wave MI is a common occurrence in the "old old" with subsequent morbidity and mortality prognosis comparable to that of recognized MI. History of MI alone in this age group is also associated with an increased risk of MI, suggesting the need for better diagnostic markers of myocardial ischemia in the old.

Aged↗

Co-enzyme Q10: a new drug for cardiovascular disease.

Co-enzyme Q10 (ubiquinone) is a naturally occurring substance which has properties potentially beneficial for preventing cellular damage during myocardial ischemia and reperfusion. It plays a role in oxidative phosphorylation and has membrane stabilizing activity. The substance has been used in oral form to treat various cardiovascular disorders including angina pectoris, hypertension, and congestive heart failure. Its clinical importance is now being established in clinical trails worldwide.

Administration, Oral↗

Lymphokine receptor-directed therapy: a model of immune intervention.

We have proposed a multichain model for the high-affinity interleukin-2 (IL-2) receptor involving two IL-2-binding peptides, a 70/75 kilodalton (kD) and a 55 kD, reactive with the anti-Tac monoclonal antibody, which are associated in a receptor complex. With the use of coprecipitation analysis, radiolabeled interleukin-2 cross-linking procedures, and flow cytometric resonance energy transfer measurements, a series of additional peptides of molecular weight 22,000, 35,000, 40,000, 75,000 (non-IL-2 binding), 95,000-105,000, and 180,000 has been associated with the two interleukin-2-binding peptides. In contrast to resting T cells, the abnormal T cells of patients with human T-cell lymphotropic virus I-associated adult T-cell leukemia, patients with select autoimmune disorders, and individuals rejecting allografts express the Tac peptide (p55) of the IL-2 receptor. To exploit this difference in Tac antigen expression, we have initiated therapeutic trials using unmodified anti-Tac, conjugates of anti-Tac with truncated Pseudomonas exotoxin PE-40, interleukin-2-truncated toxin fusion proteins, and alpha- and beta-emitting isotopic chelates of anti-Tac. Furthermore, by genetic engineering humanized hyperchimeric anti-Tac molecules have been prepared in which the molecule is entirely human IgG1, except for the small complementarity-determining regions that are retained from the mouse antibody. This "humanized" antibody manifested the ability to perform antibody-dependent cellular cytotoxicity absent in the original mouse monoclonal. The clinical application of anti-interleukin-2 receptor-directed therapy represents a new perspective for the treatment of certain neoplastic diseases and autoimmune disorders and for the prevention of allograft rejection.

Animals↗

Interstitial radiotherapy for the treatment of advanced or recurrent vulvar and distal vaginal malignancy.

From March 1, 1985 to April 30, 1988 10 patients with locally advanced primary or recurrent vulvar or distal vaginal malignancy were managed with interstitial radiotherapy with or without teletherapy. One patient died of complications of a total pelvic exenteration for radionecrosis 8 months after completion of radiotherapy. The remaining nine patients were alive at a mean follow-up of 28 months (14 to 50 months). Recurrent disease developed within a bed of severe radionecrosis in two patients at 13 and 47 months after completion of radiotherapy. The remaining seven patients have remained without evidence of recurrent disease. Of the 10 total patients severe radionecrosis developed in six at a median of 8.5 months (6 to 26 months) after radiotherapy. We conclude from our data that the use of interstitial needles, mainly combined with external radiotherapy, for the treatment of locally advanced primary or recurrent vulvar and introital malignancy is highly effective but also highly morbid.

Adult↗

Effect of flosequinan (BTS 49465) on myocardial oxygen consumption.

BTS 49465 (flosequinan), a putative selective, balanced arterial and venous vasodilator, displays positive inotropic effects in doses lower than those producing vasodilation. Thus rather than unloading the myocardium, flosequinan may increase myocardial work and oxygen consumption (MVO2), and may adversely affect the patient with myocardial ischemia or compromised coronary blood flow. This study compared the effects of flosequinan with milrinone, a mixed positive inotropic agent and vasodilator, and with nitroprusside (SNP), a standard direct-acting vasodilator, on myocardial dP/dT, MVO2, and myocardial energetics in the normal pentobartital-anesthetized dog. The effect of flosequinan on myocardial work was also evaluated in the dog with propranolol-induced heart failure (PIHF). Fifteen minutes after intraduodenal (id) administration of flosequinan (0.3, 1.0, and 3.0 mg/kg) to seven dogs, mean myocardial dP/dT was increased by 11%, 27%, and 54%, respectively, whereas stroke MVO2 was increased by 10%, 24%, and 47%, respectively. Doses of flosequinan greater than 0.3 mg/kg decreased left ventricular (LV) work but LV efficiency decreased in a dose-related manner. Milrinone (0.1, 0.3, and 1.0 mg/kg, id) increased LV dp/dt by 34%, 68%, and 104% above basal values, while increasing stroke MVO2 by 24%, 106%, and 249%, respectively (n = 7). LV work and LV efficiency decreased after each dose of milrinone. SNP (0.001, 0.003, and 0.01 mg/kg/min, intravenously) did not increase dP/dT but decreased LV work by 28%, 42%, and 46% (n = 5). In animals with PIHF, flosequinan (1 and 3 mg/kg, id) increased LV dP/dT 58% and 87% and increased LV work by 58% and 76% above control values. It was concluded that (1) flosequinan is a positive inotropic agent as well as a vasodilator; (2) in the normal animal the energy cost of positive inotropic activity is less with flosequinan than with milrinone, despite the lesser vasodilating action of the former; and (3) in the animal with a depressed myocardium, flosequinan may adversely affect myocardial work and wall tension.

Animals↗

Atomic veterans and their families: responses to radiation exposure.

In-depth interviews with seven atomic veterans and their families indicated powerful psychological effects on all family members from exposure to low-level ionizing radiation. Four themes emerged: the invalidation of their experiences by government and other authority figures; family concerns about genetic effects on future generations; family members' desire to protect each other from fears of physical consequences; and desire to leave a record of their experiences to help prevent future suffering.

Abnormalities, Radiation-Induced↗

Positive inotropy contributes to the hemodynamic mechanism of action of flosequinan (BTS 49465) in the intact dog.

Flosequinan (BTS 49465) is a putative, selective direct-acting balanced vasodilator currently undergoing evaluation for the treatment of congestive heart failure (CHF) and hypertension. We examined the pharmacologic action of flosequinan and compared it to milrinone and nitroprusside (SNP). In ferret papillary muscle, in vitro, flosequinan (1-100 microM) increased the rate of force development up to 116%. The effect was not blocked by nadolol (10 microM). Flosequinan was less effective than milrinone and SNP as a relaxant of canine renal and coronary arteries, in vitro, since 100 microM of flosequinan produced less than 50% relaxation of the arteries, whereas milrinone or SNP (100 microM) produced between 85 and 125% relaxation of the precontracted arteries. Flosequinan, SNP, and milrinone (100 microM) completely relaxed precontracted canine mesenteric veins. Fifteen minutes after intraduodenal administration (i.d.) of flosequinan (0.3, 1.0, and 3.0 mg/kg) to anesthetized dogs (n = 7), mean left ventricular (LV) dP/dT increased by 11, 27, and 54%, respectively, whereas total peripheral resistance (TPR) decreased by 4, 4, and 13%, and mean arterial pressure (MAP) decreased by 7, 14, and 23%, respectively. flosequinan was 4.6 times more potent as a positive inotrope than as a vasodilator. The hemodynamic profile of milrinone was similar to that of flosequinan, except milrinone produced greater increases in LV dP/dT and decreases in MAP and TPR. In contrast, SNP (1, 3, and 10 micrograms/kg/min i.v.) decreased TPR (7, 18, and 34%, respectively) and MAP (14, 32, and 41%, respectively) without any increase in LV dP/dT. In dogs with propranolol-induced heart failure (PIHF), flosequinan (1.0 and 3.0 mg/kg, i.d.) increased mean myocardial dP/dT by 54 and 84% (n = 5) and MAP, but decreased TPR. The data show that (a) the hemodynamic effects of flosequinan in the normal and PIHF dogs were primarily due to positive inotropy rather than to arterial vasodilation and (b) the positive inotropic effect of flosequinan is independent of catecholamines, since it occurred in dogs with PIHF. The beneficial effect of flosequinan in patients with CHF may not be mediated by balanced vasodilation.

Animals↗

Magnetic resonance imaging of pathologic conditions of the Achilles tendon.

The advent of magnetic resonance imaging (MRI) has improved imaging of the Achilles tendon. Various pathologic conditions of the Achilles tendon and their MRI characteristics are described. The superior resolution of the tendon provided by MRI can aid in the diagnosis of Achilles tendon disorders, which include complete or partial rupture of the tendon as well as postoperative assessment of tendinous healing, tendinitis and tenosynovitis, and various tumors of the Achilles tendon.

Achilles Tendon↗