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Biomedical subjects

J L Seltzer

Publications and source records attributed to J L Seltzer.

At least 37 records · Page 2Linked to original sources

Nicardipine versus placebo for the treatment of postoperative hypertension.

Postoperative hypertension can cause serious complications, including bleeding from fresh anastomoses, cardiovascular accident, and myocardial ischemia. Therefore rapid control of blood pressure is essential to prevent poor outcome. In this study, 30 American Society of Anesthesiologists class I and II patients who did not have cardiac surgery and subsequently developed postoperative hypertension were randomly assigned to receive either nicardipine, a new dihydropyridine calcium channel blocker, or placebo. Intravenous nicardipine was given as a loading bolus of 10 mg/hr for 5 minutes and was titrated to 15 mg/hr if needed to achieve a therapeutic response. After therapeutic response, intravenous nicardipine was decreased to 3 mg/hr and subsequently titrated in increments of 1.0 to 2.5 mg/hr to maintain blood pressure control. Systolic and diastolic blood pressures during titration and maintenance did not differ significantly from preoperative levels in patients treated with nicardipine. The mean time to therapeutic response for the nicardipine-treated group was 8.67 +/- 1.46 minutes, and the median time to offset of action was 15 minutes. Eleven of the 12 patients who received placebo were crossed over to antihypertensive therapy, and of these, 10 received intravenous nicardipine. In this group all achieved therapeutic response in 7.3 +/- 1.18 minutes. The usefulness of intravenous nicardipine for postoperative hypertension was demonstrated in this study by: (1) the rapid control of blood pressure, (2) its continued efficacy during maintenance, and (3) little need to adjust dosage to control blood pressure.

Dose-Response Relationship, Drug↗

A comparison of labetalol and nitroprusside for inducing hypotension during major surgery.

The hemodynamic and intrapulmonary shunt effects of intravenous labetalol and nitroprusside were compared during induced hypotension for major spinal surgery. A randomized, double-blind protocol was used in which 20 patients, ASA physical status I or II, received either nitroprusside infusion (n = 10) or labetalol bolus injections of 10 mg every 10 min (n = 10) until mean arterial blood pressure was reduced to 55-60 mm Hg. Pulmonary artery pressures were measured and mixed venous samples obtained via a pulmonary artery catheter. Nitroprusside increased heart rate significantly more than labetalol during the period of hypotension. When compared with prehypotension baseline values, nitroprusside increased heart rate significantly with a concomitant significant decrease in systemic vascular resistance. Cardiac output increased significantly 60 min after hypotension was achieved in patients treated with nitroprusside. Systemic vascular resistance decreased significantly below baseline levels in patients treated with labetalol but without changes in cardiac output, heart rate, or mean pulmonary artery pressure. There was a 122% increase in intrapulmonary shunt with nitroprusside administration, compared with an 11% increase with labetalol. Labetalol was effective for inducing hypotension and was not associated with an increase in heart rate, intrapulmonary shunt, or cardiac output as seen with nitroprusside.

Adult↗

Cleavage specificity of type IV collagenase (gelatinase) from human skin. Use of synthetic peptides as model substrates.

Type IV collagenase (gelatinase) has a marked substrate specificity for denatured collagen (gelatin). Cleavage site specificity of type IV collagenase from human skin was determined using small collagenous peptides with varied sequences around Gly-Leu or Gly-Ile. Type IV collagenase showed essentially the same order of preference for the peptide substrates as did interstitial collagenase. Both required a peptide with a minimum of six amino acid residues to demonstrate significant gelatinolytic activity and were able to cleave uncharged molecules more rapidly than charged molecules. the repeating Gly-X-Y-Gly sequence of collagen is not an absolute requirement for either enzyme since both digested AcPro-Leu-Gly-Ile-Leu-Ala-Ala-OC2H5 at 70% of the rate of the best substrate peptide, AcPro-Leu-Gly-Leu-Leu-Gly-OC2H5. Km and kcat (Vmax) values were determined for several of the peptides and for the native substrate. Turnover numbers with type IV collagenase were similar to those with interstitial collagenase (Weingarten, H., Martin, R., and Feder, J. (1985) Biochemistry 24, 6730-6734). However, the Km for all peptides investigated was approximately 10-fold lower for type IV collagenase than for interstitial collagenase. Because type IV collagenase does not cleave helical interstitial collagens, the data support the conclusion that secondary structure determines whether the peptide bond can be hydrolyzed at any potential cleavage site.

Amino Acid Sequence↗

Cleavage of type VII collagen by interstitial collagenase and type IV collagenase (gelatinase) derived from human skin.

Type VII collagen is the major structural protein of anchoring fibrils, which are believed to be critical for epidermal-dermal adhesion in the basement membrane zone of the skin. To elucidate possible mechanisms for the turnover of this protein, we examined the capacities of two proteases, human skin collagenase, which degrades interstitial collagens, and a protease with gelatinolytic and type IV collagenase activities, to cleave type VII collagen. At temperatures below the denaturation temperature, pepsin cleaves type VII collagen into products of approximately 95 and approximately 75 kDa. Human skin collagenase cleaved type VII collagen into two stable fragments of approximately 83 and approximately 80 kDa, and the type IV collagenase (gelatinase) produced a broad band of approximately 80 kDa as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Cleavage of type VII collagen was linear with time and enzyme concentration for both enzymes. Although the Km values were similar for both enzymes, the catalytic rate of cleavage by type IV collagenase is much faster than by interstitial collagenase, and shows a greater rate of increase with increasing temperature. Sequence analysis of the cleavage products from both enzymes showed typical collagenous sequences, indicating a relaxation in the helical part of the type VII collagen molecule at physiological temperature which makes it susceptible to gelatinolytic degradation. Interstitial collagenase from both normal skin cells and cells from patients with recessive dystrophic epidermolysis bullosa, a severe hereditary blistering disease in which both an anchoring fibril defect and excessive production of collagenase can be observed, produced identical cleavage products from type VII collagen. These data suggest a pathophysiological link between increased enzyme levels and the observed decrease or absence of anchoring fibrils.

Amino Acid Sequence↗

A dose-response evaluation of pipecuronium bromide in elderly patients under balanced anesthesia.

Pipecuronium bromide is a new steroidal non-depolarizing muscle relaxant currently under investigation. It is similar to pancuronium with respect to the duration of action, but lacking its cardiovascular side effects. We examined the dose-response relation of pipecuronium in 27 patients, ages 66-79 years, utilizing the incremental dose method under balanced anesthesia. The ED50, ED90 and ED95 were 22.42 (5.2) mcg/kg, 31.81 (6.9) mcg/kg and 35.12 (7.8) mcg/kg, respectively (log probit method). Our recovery data also demonstrate that residual neuromuscular blockade due to pipecuronium can easily be antagonized with neostigmine as long as spontaneous recovery of T1- at the time of reversal administration is greater than 13%. The authors conclude that under balanced anesthesia the cumulative dose-response of pipecuronium in the elderly patients is consistent with those previously described for younger population. Therefore, no dose adjustment appears necessary for the elderly. However, as with all medications, careful administration is appropriate.

Aged↗

Intravenous labetalol for the treatment of hypertension after carotid endarterectomy.

Hypertension after carotid endarterectomy has a variable incidence ranging up to 56%. Blood pressure (BP) control is essential due to possible increased risk of morbidity from neurologic deficits or cardiovascular complications. This study evaluated intravenous labetalol for control of hypertension after carotid endarterectomy. Sixty ASA II-IV patients were studied; 20 developed BP high enough for treatment with labetalol. The anesthetic technique was standardized. Labetalol was administered at the conclusion of surgery as a 20-mg bolus over two minutes followed by 40 mg every 10 minutes until the desired BP was achieved (BP less than or equal to 10% above average preoperative BP or less than 150 mmHg, systolic) or 300 mg had been given. The mean total dose of labetalol was 42.0 +/- 33.0 mg (mean +/- SD) and mean time to reach the desired BP was 16.2 +/- 21.4 minutes. Systolic, diastolic, mean arterial pressure and heart rate significantly decreased after labetalol treatment and remained so for the remainder of the 180-minute study period. There was no hypotension, bradycardia, evidence of myocardial ischemia or central nervous system dysfunction present with labetalol treatment. Blood samples were obtained for determination of plasma renin activity, epinephrine, and norepinephrine in 10 patients who developed hypertension and received labetalol, and 10 patients who did not develop hypertension. In the patients developing hypertension, there was a significant elevation in epinephrine just before treatment, that decreased by 30 minutes after treatment. Norepinephrine levels became significantly elevated five minutes after labetalol treatment in the group with hypertension and remained elevated for 120 minutes. Concomitantly, there was a significantly lower plasma renin activity seen in this group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗

Comparison of tracheal intubating conditions and neuromuscular blocking profiles after intubating doses of mivacurium chloride or succinylcholine in surgical outpatients.

Thirty ASA physical status I or II outpatients scheduled to undergo short procedures (less than 1 hr in duration) requiring tracheal intubation received either 1.0 mg/kg succinylcholine or 0.20 mg/kg (2.5 x ED95) or 0.25 mg/kg (3 x ED95) mivacurium. A N2O/O2/narcotic anesthetic technique was utilized and the ulnar nerve was stimulated with subcutaneous electrodes placed at the wrist. Tracheal intubation was attempted in all patients either 2 min after mivacurium or 1 min after succinylcholine. Intubation conditions were not different between the succinylcholine and mivacurium groups or between the two mivacurium groups. The onset and duration of neuromuscular blockade were shorter with succinylcholine than with mivacurium. Suppression of the T1 response to 90% of baseline occurred in 0.9 min with 1.0 mg/kg succinylcholine and at 2.2 and 1.5 min respectively, with 0.20 mg/kg and 0.25 mg/kg mivacurium. Initial recovery of the T1 response occurred at 6.4 min after 1.0 mg/kg succinylcholine and 12.7 and 13.6 min respectively after 0.20 mg/kg and 0.25 mg/kg mivacurium. Subsequent to initial recovery from the intubating dose of relaxant, infusions of mivacurium or succinylcholine were administered to maintain approximately 95% block. The mean infusion rates were 6.6 micrograms.kg-1.min-1 mivacurium and 41.2 micrograms.kg-1.min-1 for succinylcholine. Spontaneous recovery from neuromuscular blockade occurred more quickly after succinylcholine than after mivacurium: the time from cessation of infusion to recovery of T1 to 95% of baseline was 6.5 min in patients given succinylcholine and 16.7 min in patients given mivacurium. When reversal was in order, residual mivacurium-induced blockade was readily antagonized by 0.045 mg/kg neostigmine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Clinical pharmacology of pipecuronium bromide.

The neuromuscular blocking and cardiovascular effects of pipecuronium, in doses ranging 2-3 times its ED95, were evaluated in 46 patients during thiopental, fentanyl, N2O/O2 anesthesia. The neuromuscular blocking effect of pipecuronium was evaluated by recording of the mechanical twitch of the adductor pollicis muscle in response to stimulation of the ulnar nerve at the wrist. Heart rate, systolic and diastolic blood pressures, and cardiac output were non-invasively measured during the onset of the neuromuscular blockade and compared to a saline control group to separate the effect of anesthesia from those of pipecuronium. The mean +/- SD time from administration of pipecuronium to 90% suppression of the first twitch (T1) of the train-of-four was 2.6 +/- 0.8, 2.0 +/- 0.6, and 2.1 +/- 0.6 min following the 70 micrograms/kg, 85 micrograms/kg, and 100 micrograms/kg dose, respectively. There was no significant difference between the different doses of pipecuronium in the time to 90% suppression of T1. In general, all three doses of pipecuronium provided good to excellent intubating conditions within 3 minutes after its administration. The time from the administration of pipecuronium to 5% recovery of T1 was 52.3 +/- 18.2 min in the group given 70 micrograms/kg. This was significantly longer in patients given 85 micrograms/kg (71.9 +/- 15.7 min) or 100 micrograms/kg (71.8 +/- 22.1 min). Times to the start of recovery of T1 and to 25% recovery of T1 showed a similar significant pattern.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

H-ras oncogene-transformed human bronchial epithelial cells (TBE-1) secrete a single metalloprotease capable of degrading basement membrane collagen.

H-ras-transformed human bronchial epithelial cells (TBE-1) secrete a single major extracellular matrix metalloprotease which is not found in the normal parental cells. The enzyme is secreted in a latent form of 72 kDa, which can be activated to catalyze the cleavage of the basement membrane macromolecule type IV collagen. The substrates in their order of preference are: gelatin, type IV collagen, type V collagen, fibronectin, and type VII collagen; but the enzyme does not cleave the interstitial collagens or laminin. This protease is identical to gelatinase isolated from normal human skin explants, normal human skin fibroblasts, and SV40-transformed human lung fibroblasts. Based on its ability to initiate the degradation of type IV collagen in a pepsin-resistant portion of the molecule, it will be referred to as type IV collagenase. This enzyme is most likely the human analog of type IV collagenase detected in several rodent tumors, which has the same molecular mass and has been linked to their metastatic potential. Type IV collagenase consists of three domains. Two of them, the amino-terminal domain and the carboxyl-terminal domain, are homologous to interstitial collagenase and human and rat stromelysin. The middle domain, of 175 residues, is organized into three 58-residue head-to-tail repeats which are homologous to the type II motif of the collagen-binding domain of fibronectin. Type IV collagenase represents the third member of a newly recognized gene family coding for secreted extracellular matrix metalloproteases, which includes interstitial fibroblast collagenase and stromelysin.

Amino Acid Sequence↗

Effect of myocardial revascularization and vein graft blood flow on pacing function.

The effect of myocardial revascularization and vein graft blood flow on pacing function was determined in nine patients undergoing aortocoronary bypass. Pacing variables including threshold, current, and resistance were measured with a pacing system analyzer during intermittent pacing with a transluminal bipolar ventricular pacing probe. Pacing function was analyzed immediately before cardiopulmonary bypass (CPB) and compared with measurements taken eight minutes after full flow through the vein grafts had been established. Comparison of these two times showed a significant decrease in resistance, P < 0.003, and threshold, P < 0.03. After the second measurement, left anterior descending (n = 8), or right coronary (n = 1) vein graft blood flow was interrupted. Pacing variables were analyzed at one minute, two minutes, and four minutes following vein graft clamping; and a final set of measurements was obtained one minute following release of the vein graft clamp. Threshold increased but did not reach statistical significance. Resistance increased significantly: P < 0.03. All values returned to baseline following release of the vein graft clamp and full return of blood flow. The results of this study suggest that pacing function measurements are sensitive to changes in vein graft blood flow and may provide useful information about the condition of the myocardium, especially immediately prior to weaning from CPB.

Cardiac Pacing, Artificial↗

Evaluation of a new design pulmonary artery catheter for intraoperative ventricular pacing.

A new design pulmonary artery catheter and pacing probe were evaluated in 30 patients undergoing cardiac surgery. Ventricular pacing was attempted before, during, and after cardiopulmonary bypass. Ventricular current threshold, output, resistance, and R wave sensitivity were measured during all three periods. Successful pacing was achieved in 69 of 72 attempts, the vast majority completed in less than four minutes. Pacing thresholds and R wave sensitivities were within acceptable ranges and compatible with commercial pulse generators. Ventricular pacing can be quickly and reliably established with this type of pacing pulmonary artery catheter. The results suggest this system can be used to effect cardiac pacing in the patient requiring emergency extrinsic pacemaker support.

Adult↗

Prostacyclin mediation of vasodilation following mesenteric traction.

Eight untreated patients (group I) and four patients who received ibuprofen preoperatively (group II) scheduled for elective abdominal aortic aneurysm repair were studied. Heart rate (HR); systolic, diastolic, and mean arterial pressure (MAP); systolic and diastolic pulmonary artery pressure; pulmonary capillary wedge pressure (PCWP); cardiac output (CO); and central venous pressure (CVP) were recorded pre-induction, before mesenteric traction, and 5, 15, and 30 min post-mesenteric traction. Plasma samples were obtained at these times for analysis of six-keto-prostaglandin F1 alpha (PGF1 alpha) concentration by radioimmunoassay. Group II patients received ibuprofen 12 mg/kg orally 1 1/2 h before surgery. Plasma samples from six group I patients and all group II patients taken 5 min after mesenteric traction were added to isolated helical strips of cat superior mesenteric arteries precontracted with norepinephrine (200 ng/ml) for analysis of reduction in developed force. In group I, abdominal mesenteric traction resulted in a significant decrease in MAP (P less than 0.03) and SVR (P less than 0.005) with an increase in CO (P less than 0.05) at 5 min post-mesenteric traction, which returned to mean pre-mesenteric traction values by 30 min and a significant increase in PGF1 alpha concentrations. There was a significant positive correlation between PGF1 alpha and CO (P less than 0.001) and a significant negative correlation between PGF1 alpha and SVR (P less than 0.01) at 5 min post-mesenteric traction.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Eriochrome black T inhibition of human skin collagenase, but not gelatinase, using both protein and synthetic substrates.

The intracellular degradation of interstitial collagen is accomplished by two neutral metalloproteases, collagenase and gelatinase. Both enzymes are inhibited by metal chelating agents, by certain sulfhydryl reagents, and by similar protein inhibitors. Here, we demonstrate that the dye eriochrome black T (EBT) appears to be unique in its capacity to inhibit collagenase but not gelatinase. Using native reconstituted helical collagen in gel form at 37 degrees C, half-maximal inhibition of collagenase activity by EBT occurs at approximately 45 microM. EBT more effectively inhibits the breakdown of native collagen in solution, with a KI of approximately 8 microM. Using a newly-developed spectrophotometric substrate, AcProLeuGly-S-LeuLeuGly-OC2H5, a KI of 1.4 microM was calculated for EBT on collagenase. Although this same thiopeptolide serves as a substrate for gelatinase with kinetics similar to those of collagenase, no inhibition by EBT was observed. EBT also did not inhibit the gelatinase-mediated breakdown of the natural substrate, gelatin. The data suggest that EBT may have significant potential for allowing the differentiation in biological fluids of two metalloproteases with similar cleavage site specificities.

Azo Compounds↗

The lack of response to suggestion under controlled surgical anesthesia.

Thirty-two ASA I or II women undergoing abdominal hysterectomy were randomly allocated to four groups to determine what type, if any, of recorded intraoperative message they would receive. Groups I and II heard a neutral recording with no verbal content. Group III heard an experimental recording with a positive suggestion for a rapid recovery. Group IV had a self-prepared message. The tapes were played during general anesthesia when anesthetic depth was judged to be stable and adequate by vital signs, end-tidal anesthetic concentration and EEG compressed spectral array. No patient reported any recall of intraoperative messages when interviewed on the day after surgery. Chart review showed no difference in days of hospitalization, dose of analgesics required, time to beginning oral intake, or the amount of wound drainage (P greater than 0.05). We conclude that no awareness can be observed directly by recall or indirectly by response to suggestion given under stable and adequate general anesthesia.

Adult↗

Pain control for the urologist.

Pain states can be divided into three categories: acute, chronic not resulting from malignancy, and chronic malignant pain. A Pain Clinic can provide in-depth evaluation and treatment of difficult pain problems. A variety of oral and parenteral medications, ranging from nonsteroidal analgesics to narcotics, are available to control pain. Local anesthetics can be used for local infiltration, and peripheral and central nerve blocks can also be used as indications warrant.

Acupuncture Therapy↗