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Biomedical subjects

J L Seltzer

Publications and source records attributed to J L Seltzer.

At least 19 recordsLinked to original sources
PubMed1992

Time-course of respiratory depression after an alfentanil infusion-based anesthetic.

Postoperative respiratory depression after alfentanil administration has been described in several case reports. The effects of a prolonged alfentanil infusion on the CO2 response curve or cognitive function have not been studied. Twenty-one ASA physical status I or II patients were studied after a prolonged alfentanil infusion (> 90 min) to determine the incidence of postoperative respiratory depression, arterial O2 desaturation, and impairment of cognitive function. Each patient's recovery was observed at 30-min intervals for evidence of respiratory depression (utilizing the Read CO2 rebreathing method), desaturation by pulse oximetry (severe desaturation defined as arterial O2 saturation < 90%), and cognitive function (utilizing Trieger dot and digit substitution tests). Plasma samples were also examined for secondary elevations in alfentanil plasma concentrations. Significant depression of the CO2 response curve and cognitive function was found up to 1 h postoperatively. Arterial O2 desaturation was seen in 11 of 21 patients (52%). No correlation was found between arterial O2 desaturation and cognitive function scores or CO2 rebreathing results. Increased depression of the CO2 response curve was not necessarily associated with severe desaturation episodes. A secondary increase in plasma alfentanil concentration was detected in 5 of the 21 patients (24%), but these patients did not experience further depression of the CO2 response curve. We conclude that prolonged alfentanil administration may result in severe arterial O2 desaturation with significant depression of the hypercapnic respiratory drive during the first hour in the postanesthesia care unit, even though the majority of our patients were easily aroused in response to verbal stimuli.

Adult↗
PubMed1992

Laterality and modality-specific effects of chronic pain.

Previous investigations indicated that thresholds to nonpainful tactile stimuli were elevated in chronic-pain patients when compared with pain-free individuals (Seltzer & Seltzer, 1986; Seltzer et al., 1988). The present study attempted to determine whether thresholds to tactual and visual stimuli also were elevated by chronic pain. Furthermore, lateralization of the pain effect on tactile thresholds was assessed by obtaining thresholds from both left and right arms. A decrease in tactile sensitivity to nonpainful stimuli in chronic-pain patients was confirmed, but laterality of the effect was not demonstrated. Visual thresholds were not significantly affected by chronic pain. The data in the present study, taken together with other data, support the proposition that pain does not affect right hemispheric processes more than left hemispheric processes.

Arousal↗
PubMed1991

Investigating stress levels of residents: a pilot study.

A pilot study of the levels of stress among residents was conducted in three departments in a university hospital prior to initiating a programme in stress management for residents. The Beck Depression Inventory, which is a brief, standardized self-report measure of depression, was given to residents in anaesthesiology, paediatrics and psychiatry. Six additional questions were asked about the functioning of peers and services residents would like to have available. Of the 113 residents surveyed, 16% were experiencing a mild mood disturbance. The researchers feel this is probably under-reported. Residents felt that about 15% of their colleagues were emotionally impaired; 10% may have a drug and/or alcohol problem; 12% were having marital problems. Eighty per cent of all residents studied said that they would attend support groups if they existed. Approximately 60% thought coping skills/stress management seminars would be useful, and 30% of the paediatric and anaesthesiology residents (60% of the psychiatry residents) said they would use confidential individual psychotherapy if it were available.

Anesthesiology↗
PubMed1990

Cleavage specificity of human skin type IV collagenase (gelatinase). Identification of cleavage sites in type I gelatin, with confirmation using synthetic peptides.

Type IV collagenase (gelatinase) readily cleaves denatured collagen into very small peptides. Large cyanogen bromide fragments (25 kDa) of type I collagen are degraded at the same rate as the complete alpha-chain. A number of the gelatinolytic cleavage sites of alpha 1(I)CB7 and alpha 1(I)CB8, representing 50% of the collagen alpha-chain, were determined by sequence analysis of product peptides. In addition to the expected cleavage between glycine and hydrophobic residues, several other cleavage sites were identified. These sites were Gly-Glu, Gly-Asn, and Gly-Ser. Basic residues were found adjacent to the cleavage site in several cases. Hexapeptides containing these unexpected cleavage sites were synthesized, and Km and kcat values were determined. All but one of the Km values were in the submillimolar range, and turnover numbers for the peptides uncharged at the carboxyl terminus were on the order of 10,000/h. Of particular significance was the finding that hydroxyproline occurs 5 residues from the cleavage site in all carboxyl-terminal product peptides and also occurs 5 residues from the cleavage site in seven of nine amino-terminal product peptides. A requirement for hydroxyproline may be of importance in determining the specificity of this enzyme for denatured collagenous substrates.

Amino Acid Sequence↗
PubMed1990

Differential susceptibility of type X collagen to cleavage by two mammalian interstitial collagenases and 72-kDa type IV collagenase.

We have studied the degradation of type X collagen by human skin fibroblast and rat uterus interstitial collagenases and human 72-kDa type IV collagenase. The interstitial collagenases attacked the native type X helix at two loci, cleaving residues Gly92-Leu93 and Gly420-Ile421, both scissions involving Gly-X bonds of Gly-X-Y-Z-A sequences. However, the human and rat interstitial enzymes displayed an opposite and substantial selectivity for each of these potential sites, with the uterine enzyme catalyzing the Gly420-Ile421 cleavage almost 20-fold faster than the Gly92-Leu93 locus. Values for enzyme-substrate affinity were approximately 1 microM indistinguishable from the corresponding Km values against type I collagen. Interestingly, in attacking type X collagen, both enzymes manifested kinetic properties intermediate between those characterizing the degradation of native and denatured collagen substrates. Thus, energy dependence of reaction velocity revealed a value of EA of 45 kcal, typical of native interstitial collagen substrates. However, the substitution of D2O for H2O in solvent buffer failed to slow type X collagenolysis significantly (kH/kD = 1.1), in contrast to the 50-70% slowing (kH/kD = 2-3) observed with native interstitial collagens. Since this lack of deuterium isotope effect is characteristic of interstitial collagenase cleavage of denatured collagens, we investigated the capacity of another metalloproteinase with substantial gelatinolytic activity, 72-kDa type IV collagenase, to degrade type X collagen. The 72-kDa type IV collagenase cleaved type X collagen at both 25 and 37 degrees C, and at loci in close proximity to those attacked by the interstitial enzymes. No further cleavages were observed at either temperature with type IV collagenase, and although values for kcat were not determined (due to associated tissue inhibitor of metalloproteinases-2), catalytic rates appeared to be substantial in comparison to the interstitial enzymes. In contrast, type X collagen was completely resistant to proteolysis by stromelysin. Type X collagen thus appears to be highly unusual in its susceptibility to degradation by both interstitial collagenase and another member of the metalloproteinase gene family.

Amino Acid Sequence↗
PubMed1990

Relationship between arterial carbon dioxide and end-tidal carbon dioxide when a nasal sampling port is used.

End-tidal carbon dioxide (ETCO2) values obtained from awake nonintubated patients may prove to be useful in estimating a patient's ventilatory status. This study examined the relationship between arterial carbon dioxide tension (PaCO2) and ETCO2 during the preoperative period in 20 premedicated patients undergoing various surgical procedures. ETCO2 was sampled from a 16-gauge intravenous catheter pierced through one of the two nasal oxygen prongs and measured at various oxygen flow rates (2, 4, and 6 L/min) by an on-line ETCO2 monitor with analog display. Both peak and time-averaged values for ETCO2 were recorded. The results showed that the peak ETCO2 values (mean = 38.8 mm Hg) correlated more closely with the PaCO2 values (mean = 38.8 mm Hg; correlation coefficient r = 0.76) than did the average ETCO2 values irrespective of the oxygen flow rates. The time-averaged PaCO2-ETCO2 difference was significantly greater than the PaCO2-peak ETCO2 difference (P less than 0.001). Values for subgroups within the patient population were also analyzed, and it was shown that patients with minute respiratory rates greater than 20 but less than 30 and patients age 65 years or older did not differ from the overall studied patient population with regard to PaCO2-ETCO2 difference. A small subset of patients with respiratory rates of 30/min or greater (n = 30) did show a significant increase in the PaCO2-ETCO2 difference (P less than 0.001). It was concluded that under the conditions of this study, peak ETCO2 values did correlate with PaCO2 values and were not significantly affected by oxygen flow rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Arteries↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1988

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↗