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Biomedical subjects

B S Lewis

Publications and source records attributed to B S Lewis.

At least 19 recordsLinked to original sources

Atrial natriuretic peptide in severe heart failure: response to controlled changes in atrial pressures during intravenous nitroglycerin therapy.

Atrial natriuretic peptide (ANP) levels were measured in 17 patients with severe congestive heart failure (New York Heart Association functional class IV), and the response of the peptide was studied during changes in cardiac filling pressures induced by a 24-hour infusion of nitroglycerin. In the control state plasma ANP levels (687 +/- 551 pg/ml) were 10-fold normal. During the administration of nitroglycerin, natriuretic peptide levels decreased (p less than 0.005) with changes matching very closely the decreases in pulmonary arterial wedge and right atrial pressures, a 1% mean decrease in the peptide level for every 1.5 to 2% mean change in atrial filling pressures. In patients with hemodynamic tolerance to constant-dose nitroglycerin infusion, the resulting increase in atrial pressures was accompanied by an appropriate secondary increase in the plasma ANP level. During the 24-hour study period there was a direct linear relationship between both wedge (r = 0.93, p = 0.007) and right atrial (r = 0.93, p = 0.008) pressures and the plasma ANP level, with a zero-pressure ANP intercept near normal (69 pg/ml for wedge, 174 pg/ml for right atrial pressure). The findings were no different in a subgroup of five patients receiving simultaneous treatment with captopril, except that plasma renin activity was higher and the aldosterone level lower than in the control group by a factor of approximately 2.5. The close relationship and tracking of atrial pressure and natriuretic peptide curves suggested that the sensitivity of the atrial stretch response to changes in atrial filling pressures was maintained in severe congestive heart failure.

Aged

Surgical approach to occult gastrointestinal bleeding.

In 5% of patients with gastrointestinal bleeding, standard evaluation fails to reveal the source of the bleeding. We describe the management of 71 patients treated for obscure gastrointestinal bleeding at the Mount Sinai Medical Center, New York, New York, from 1985 to 1991. There were 38 men (54%) and 33 women (46%). The mean age was 60 years. The patients had bleeding episodes for a mean period of 26 months and required an average of 20 units of blood prior to surgical treatment. All had undergone an extensive diagnostic workup including barium contrast studies, endoscopies, and angiographies. Some had multiple bleeding scans, Meckel scans, and surgical explorations. Three patients were found to have "watermelon stomach" on endoscopy and had an antrectomy. Sixty-eight (96%) patients underwent a preoperative small bowel enteroscopy, which revealed the precise diagnosis in 50 (70%) of the patients. All patients underwent surgery. In 30 (42%) patients in whom the bleeding site was not apparent at exploration, intraoperative enteroscopy was performed. Two actively bleeding patients had intraoperative enteroscopy, which failed to localize the bleeding site, and intraoperative scintigraphy was utilized. The bleeding was found to originate in small bowel arteriovenous malformation (AVM) (28 patients), leiomyoma (8 patients), primary small bowel malignancies (11 patients), and other causes (24 patients). Fifty-six patients (80%) had no further bleeding; 9 with multiple small bowel AVM have experienced rebleeding and are alive. Six patients died of recurrent bleeding, and six died of metastatic cancer. An aggressive approach should be applied in patients in whom standard evaluation fails to localize the source of gastrointestinal bleeding. Enteroscopy, surgical exploration with additional intraoperative enteroscopy, and occasional intraoperative scintigraphy can achieve an excellent yield and allow resection and potential cure.

Algorithms

Systemic diseases affecting the mesenteric circulation.

The mesenteric circulation is acutely sensitive to processes that affect the entire body. Such systemic diseases and syndromes are reviewed with particular emphasis on the mechanisms by which they influence the mesenteric vasculature and blood flow.

Connective Tissue Diseases

Usefulness of intracoronary isosorbide dinitrate in alleviating myocardial ischaemia during coronary balloon angioplasty.

The effect of intracoronary isosorbide dinitrate on provoked myocardial ischaemia during percutaneous transluminal coronary angioplasty (PTCA) was studied in 60 patients who had at least 1 mm electrocardiographic (ECG) ST segment deviation during a 70 s control balloon inflation period. Isosorbide dinitrate (dose 1 mg, 2 mg or 3 mg) or placebo (saline) was administered by slow intracoronary injection, and the ST segment changes recorded again during an identical dilatation period 2-4 min later. Following injection of isosorbide dinitrate, the severity of ST segment deviation decreased (1 mg -31 +/- 30%, P = 0.03; 2 mg -51 +/- 35%, P = 0.0001; 3 mg -36 +/- 32%, P = 0.002) during coronary balloon inflation, and the time until onset of 1 mm ST deviation was prolonged (1 mg +79 +/- 137%, P = 0.06; 2 mg +85 +/- 87%, P = 0.02; 3 mg +78 +/- 109%, P = 0.02). With the 3 mg dose, the time to maximum ECG change increased (+37 +/- 87%, P = 0.02). In the placebo group, there was a small decrease in the severity of ST segment deviation in patients receiving placebo (-23 +/- 32%, P = 0.03), but no change in the time to its onset or in the time to maximum ST deviation. Isosorbide dinitrate did not alter heart rate, systolic arterial pressure or the rate-pressure product at maximum ST segment change, implying that when isosorbide was administered by direct intracoronary injection, a direct cardiac effect was responsible for the major anti-ischaemic effect of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon, Coronary

Does hormonal therapy have any benefit for bleeding angiodysplasia?

Sixty-four patients took part in a cohort study measuring the efficacy of daily hormonal therapy in diminishing intestinal bleeding from small bowel angiodysplasia. Thirty patients received 5-10 mg norethynodrel either with mestranol, 0.075-0.15 mg (24 patients) or with conjugated estrogens, 0.625 mg (six patients). The cohort group consisted of 34 patients who either refused hormonal therapy (six patients) or were diagnosed early in our experience, before the resurgence of hormonal therapy (28 patients). Mean follow-up was 15.6 months (range 2-31 months) for the treated group and 13.4 months (range 1-23 months) for the untreated group. In addition, the change in monthly transfusion requirement with therapy was analyzed ("within group" analysis). Fifty percent (15 of 30) of the treated group required no further transfusion during therapy, while 44% (15 of 34) of the untreated group required no further therapy (not significant). During therapy, the mean monthly transfusion requirement of packed red blood cells in the treated group was not significantly different from that found before therapy (1.5 vs. 2.2 units, NS) or from that of the control group (1.5 vs. 1.6 units, NS). The findings do not support the use of hormonal therapy for bleeding from small intestinal angiodysplasia.

Adolescent

Colonoscopy: a prospective report of complications.

Patients (N = 2,097) undergoing ambulatory office colonoscopy were followed to determine the incidence of endoscopic complications. In this group, 1,320 patients had diagnostic colonoscopy with or without biopsy; 777 patients had 2,019 polyps removed. Three of 2,097 patients (0.1%) had transient hypotension requiring i.v. fluid resuscitation and oxygen administration. All patients went home without sequelae. Acute postpolypectomy bleeding occurred in 11 of 777 patients (1%) requiring acute management; bleeding was controlled during colonoscopy in all. Postpolypectomy syndrome occurred in 9 of 777 patients (1%). All patients were treated medically. Late postpolypectomy bleeding occurred in 15 of 777 patients (2%). Perforation occurred in two of 777 patients (0.3%), at 1 and 9 days postpolypectomy. Both patients underwent surgery with uneventful recoveries. We conclude that office colonoscopy including polypectomy is safe. The overall complication rate for therapeutic ambulatory colonoscopy was 5%, with major events requiring hospitalization in 2% of patients.

Adolescent

Small bowel tumours: yield of enteroscopy.

A total of 258 patients with obscure gastrointestinal bleeding were referred for small bowel enteroscopy, a procedure which allows endoscopic evaluation of most of the small intestine. A small bowel tumour was found in 5% of patients. In 50% of patients no diagnosis could be made, but when the cause of obscure bleeding was discovered small bowel tumours were the single most common lesion in patients younger than 50 years. Small bowel tumours causing gastrointestinal bleeding may remain undetected despite extensive diagnostic evaluation. We conclude that small bowel tumours are the most common cause of obscure gastrointestinal bleeding in patients less than 50 years of age. Small bowel enteroscopy is diagnostic of small bowel tumours even when all previous diagnostic studies, including enteroclysis and angiography, are negative.

Adult

Effect of nisoldipine on exercise performance in heart failure following myocardial infarction.

The effects of the second generation calcium channel blocking drug nisoldipine on subjective and objective measurements of exercise performance were studied in 19 patients with moderate to severe heart failure (9 New York Heart Association functional class 2, 9 class 3 and 1 class 4) due to fixed ventricular dysfunction following myocardial infarction. Nisoldipine (10 mg 3 times daily) or placebo were administered for 8 weeks in a double-blind parallel study, assessing exercise performance by symptom-limited treadmill exercise testing using a modified Naughton protocol. Nisoldipine was well-tolerated and produced a small increase in peak estimated workload performed (6.2 +/- 2.9 to 8.2 +/- 3.0 METs, p = 0.06). The rate of perceived exertion (Borg scale) increased from 17.5 +/- 2.2 to 18.8 +/- 1.2 (p less than 0.02). The higher workload was performed at a lower peak systolic blood pressure (p = 0.03), higher peak heart rate (p = 0.06) and identical double product (NS). There was no change in resting and peak heart rate and blood pressure or in exercise performance in patients receiving placebo. Resting left ventricular ejection fraction, measured by radionuclide ventriculography, was unchanged after 8 weeks both in the placebo (21 +/- 9 to 20 +/- 9%) and nisoldipine (34 +/- 17 to 36 +/- 19%) groups.

Aged

Small bowel enteroscopy and intraoperative enteroscopy for obscure gastrointestinal bleeding.

Intraoperative endoscopy (IOE) is accepted as the ultimate diagnostic procedure for completely evaluating the small bowel in patients with obscure gastrointestinal (GI) bleeding. Small bowel enteroscopy (SBE) has been reported useful in the nonsurgical evaluation of the small intestine in these patients, but findings may be limited because of incomplete small bowel intubation and a lack of tip deflection. Twenty-three patients underwent 25 SBE exams and subsequently had 25 IOE exams during surgical exploration for continued bleeding. Patients' bleeding histories averaged 2 yr, with an average transfusion requirement of 27 units. Findings on IOE were the same as with SBE in 17/22 (77%) of examinations. We conclude that SBE and IOE are comparable in depth of insertion and ability to detect small vascular ectasias. Both procedures missed pathology due to limited visibility and the evanescent nature of ectasias. Long-term success in abolishing bleeding with these combined techniques can be expected in 55% of these patients. SBE should precede surgery, since the finding of diffuse ectasias precludes any benefit from operative intervention.

Aged

Failure of captopril to prevent nitrate tolerance in congestive heart failure secondary to coronary artery disease.

The possible role of angiotensin-converting enzyme inhibition in preventing or minimizing tolerance to intravenous nitroglycerin in severe congestive heart failure (CHF) was studied by quantitating the degree of tolerance in 12 patients receiving nitroglycerin (group 1) and in 9 patients (group 2) receiving nitroglycerin and concurrent treatment with captopril (60 +/- 29 mg/day). At peak effect, nitroglycerin produced almost identical hemodynamic changes in both groups, with significant decreases in right atrial and pulmonary arterial wedge pressure, systolic blood pressure and systemic and pulmonary vascular resistances. Cardiac index increased. The extent of nitrate tolerance was calculated for each hemodynamic parameter as the percentage loss of the peak effect achieved by the drug. At 24 hours, 98 +/- 80% of the benefit achieved with respect to right atrial pressure was lost in group 1 and 61 +/- 74% in group 2 (group 1 vs 2, difference not significant). For pulmonary arterial wedge pressure, 51 +/- 31% (group 1) and 85 +/- 53% (group 2) (difference not significant) of the effect was lost, and for cardiac index, 53 +/- 58% (group 1) and 54 +/- 44% (group 2) (difference not significant). Tolerance was also almost identical regarding systolic blood pressure and systemic and pulmonary vascular resistance. Thus, the extent of tolerance to high-dose intravenous nitroglycerin in CHF was unaltered by administration of captopril, indicating that in clinical dosage, counter-regulatory neurohumoral mechanisms involving the renin-angiotensin system appear to be unimportant in its development.

Adult

Nitrate tolerance in heart failure: differential venous, pulmonary and systemic arterial effects.

The hemodynamic profile of tolerance to intravenous nitroglycerin was studied in 9 patients with New York Heart Association Class III to IV congestive heart failure. After rapid dosage build-up to the maximal tolerated dose (decrease in pulmonary wedge pressure to 10 mm Hg or systolic blood pressure to 90 mm Hg), nitroglycerin (525 +/- 548 micrograms/min) was administered at a constant continuous intravenous infusion for a total of 24 hours. The extent of nitrate tolerance at 24 hours was calculated as the percentage loss of the benefit achieved at time of peak effect of nitroglycerin. Tolerance had a different time course and magnitude in the venous, arterial and pulmonary circulations. At 24 hours, right atrial pressure and pulmonary vascular resistance returned to control values in most patients, while 40 to 50% of the effect on systemic vascular resistance, cardiac index and pulmonary wedge pressure was maintained. These findings emphasize the importance of precise definitions in studies relating to nitrate tolerance.

Adult

The effects of aminoguanidine on the glycation (non-enzymic glycosylation) of lens proteins.

Aminoguanidine is being studied as a possible drug to prevent diabetic complications, by blocking the reactive carbonyl group of the Amadori product formed by glycation (non-enzymic glycosylation) of proteins. Thus it prevents the later browning and cross-linking steps. In the present work we show that labelled aminoguanidine becomes bound to glycated lens proteins. We also show that aminoguanidine inhibits the first steps of glycation of lens proteins but has no effect on carbamylation, the reaction with cyanate. It appears, therefore, that aminoguanidine can prevent glycation as well as the browning reactions, and may do so not by acting on the proteins, as other putative anti-cataract drugs do, but by decreasing the concentration of the active aldehyde form of the sugars.

Animals

Predicting late restenosis after coronary angioplasty by very early (12 to 24 h) thallium-201 scintigraphy: implications with regard to mechanisms of late coronary restenosis.

To examine whether late coronary restenosis may be predicted by abnormalities of myocardial perfusion in the early hours after successful percutaneous transluminal coronary angioplasty and to study in greater detail the mechanisms involved in the development of late coronary restenosis after angioplasty, a prospective study was undertaken in 90 consecutive patients. Thallium-201 scintigrams were recorded at rest and during the stress of atrial pacing, 12 to 24 h after angioplasty, and the results were related to the findings at angiography in 70 patients undergoing late cardiac catheterization. A reversible thallium-201 perfusion defect was found in 39 (38%) of 104 myocardial regions supplied by the dilated coronary vessel and identified a subset of patients at high risk of late (6 to 12 months) angiographic restenosis (sensitivity 77%, specificity 67%). In contrast, late coronary restenosis developed in only 7 (11%) of 65 vessels and in 5 (14%) of 37 patients with a nonischemic thallium-201 scintigram on day 1 (p less than 0.005). Multivariate logistic regression analysis of 14 possible preangioplasty and periangioplasty clinical and angiographic variables selected reversible perfusion defect on the thallium-201 scintigram on day 1 (p = 0.016) and immediate postangioplasty residual coronary narrowing (p = 0.004) as significant independent predictors of late restenosis, with younger patient age as an additional less powerful predictor (p less than 0.05). The findings have important implications regarding the pathogenesis of late coronary restenosis in patients undergoing successful angioplasty and they imply that in the majority of these patients pathophysiologic events in the early minutes and hours after angioplasty may determine the development of late restenosis.

Adult

Intraoperative scintigraphy for active small intestinal bleeding.

Localizing active sites of bleeding within the small intestine remains a difficult task. Endoscopic, angiographic or scintigraphic studies may point to the small intestine as the site of blood loss, but at operation, without a palpable lesion, the exact site of bleeding remains elusive. Patients are managed at laparotomy with intraoperative endoscopy, angiography, multiple enterotomies, "blind" resections, or placement of an enterostomy. We describe two patients in whom intraoperative scintigraphy accurately identified active sites of bleeding in the small intestine when other modalities failed. Intraoperative scintigraphy is rapid, easy to perform and is an effective means of identifying active sites of bleeding within the small intestine.

Aged