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Biomedical subjects

S M Hamilton

Publications and source records attributed to S M Hamilton.

At least 37 records · Page 2Linked to original sources
PubMed1989

Energy expenditure associated with CPAP and T-piece spontaneous ventilatory trials. Changes following prolonged mechanical ventilation.

The use of portable metabolic carts to assess energy expenditure (EE) by measuring oxygen consumption (VO2) and carbon dioxide production (VCO2) has recently been applied to patients undergoing weaning from mechanical ventilation. The VO2 and EE can be used to estimate changes in the work of breathing (WOB) associated with different weaning strategies. The purpose of this study was to use VO2 and EE to assess changes in the WOB when assisted mechanical ventilation (AMV) was replaced with two spontaneous ventilatory trial (SVT) techniques: continuous positive airway pressure (CPAP) and T-piece. Nine difficult-to-wean patients were studied during the initial weaning period following 26 +/- 18 days (mean +/- SD) of mechanical ventilatory support. The VO2 and EE during all AMV were 296 +/- 75 ml/min and 2069 +/- 519 kcal/day, respectively. Compared to the baseline AMV levels, during CPAP overall VO2 and EE increased 14 percent and 13 percent, respectively, and during T-piece overall VO2 and EE increased 20 percent and 19 percent, respectively. Respiration rate (f) increased and tidal volume (VT) decreased during both SVTs compared to AMV although no significant change in minute ventilation was seen. The WOB, as judged from changes in VO2, was only 5 percent higher during T-piece compared to CPAP; however, patients tolerated an average of only 141 +/- 45 min on T-piece vs 165 +/- 29 minutes on CPAP. We conclude that during the initial weaning stages in patients who have received prolonged mechanical ventilatory support, the WOB associated with SVTs is increased compared to AMV but that the WOB associated with T-piece is not significantly greater than that for CPAP.

Adult↗
PubMed1988

Mead Johnson Critical Care Symposium for the Practising Surgeon. 3. Monitoring and investigation of intra-abdominal sepsis.

Diagnosis and management of intra-abdominal sepsis continue to be major problems in critically ill patients. Multiple system organ failure secondary to intra-abdominal sepsis continues to cause serious morbidity and death. The first step in management is to recognize the infection, while providing careful supportive therapy. A number of radiologic investigations, including ultrasonography and computed tomography, will help to diagnose a potential source of infection, which can be positively identified by fine-needle aspiration and culture. The septic focus must be drained either percutaneously or, if this fails, surgically. Use of specific antibiotics is imperative. Delay in diagnosis and surgery increases the death rate, so all available diagnostic modalities should be utilized, but these should not replace careful ongoing clinical assessment.

Abdomen↗
PubMed1986

Relationship between increased vascular permeability and extravascular albumin clearance in rabbit inflammatory responses induced with Escherichia coli.

Intradermal injections of killed Escherichia coli are known to cause a variety of pathophysiological changes in the microcirculation that facilitate the extravasation of plasma constituents into the interstitium. In an attempt to learn more of the factors that regulate the magnitude and duration of inflammatory edema, we have focused on the relationship between the extravasation of protein into the interstitium and the removal of extravascular protein from the lesion sites. Vascular permeability changes have been assessed by the local accumulation of systemically administered [131I] or [125I]-albumin and extravascular protein clearance measured by monitoring the disappearance of [125I]-albumin from the same sites. Radioactivity was quantitated with an external gamma-scintillation probe or by punching out the lesion sites in sacrificed animals and counting in a gamma-spectrometer. Scintillation probe measurements of the net accumulation of intravenously administered [125I]-albumin in E. coli-induced skin lesions revealed that the extravasation of albumin was greater than the clearance of protein from the same sites. Comparisons of the removal rates of albumin injected directly into the E. coli sites revealed that, despite increases in vascular permeability amounting to 170 to 700% of control values, the mobilization of deposited albumin was no greater than that from control tissues that received saline; in fact with high concentrations of E. coli (10(8) injected/site) the mobilization of protein from the lesions was significantly reduced. The systemic administration of 055:B5 endotoxin (0.3, 1.6, or 3.3 micrograms/kg) also suppressed the clearance of albumin from skin. In contrast to these results, 300 to 1500% increases in vascular permeability induced with other inflammatory stimuli including thermal injury, high concentrations of bovine serum albumin, or bradykinin, resulted in enhanced clearance of extravascular protein from lesion or injection sites. These experiments suggest that an inability to effectively mobilize extravascular protein from the inflammatory focus could be a major contributing factor in regulating edema in inflammatory reactions induced with E. coli and may possibly contribute to the edema associated with septicemia.

Albumins↗
PubMed1984

Cushing's disease with 'normal suppression' due to decreased dexamethasone clearance.

Suppression of urinary corticosteroids during low-dose dexamethasone testing (0.5 mg every six hours eight times) has commonly been recognized as a response that excludes the diagnosis of Cushing's syndrome. Although "normal suppression" has been reported previously in Cushing's disease, rarely has an explanation been provided for this aberrant response. We report a case of proven Cushing's disease in which normal suppression was observed with low-dose dexamethasone testing. Further study suggested that this phenomenon, which is not widely recognized, was related to an abnormally decreased clearance of dexamethasone. We therefore suggest that whenever responses to testing appear discordant with the clinical index of suspicion, simultaneous plasma dexamethasone and cortisol levels should be obtained to exclude abnormalities in dexamethasone clearance.

Adrenocorticotropic Hormone↗
PubMed1983

Synthesis and release of Hageman factor (Factor XII) by the isolated perfused rat liver.

The site of synthesis of Hageman factor (HF, Factor XII) has not been previously demonstrated with certainty. We have studied the production and release of HF in the isolated perfused rat liver and have compared rates of synthesis in this system with absolute rates of degradation measured in vivo. Rat livers, perfused for 5 h with a recycling fluid consisting of a perfluorochemical emulsion (Fluosol 43), were used to demonstrate a cumulative increase of HF in the perfusate as measured by a specific and sensitive radioimmunoassay. The rate of increase in the perfusate pool of HF during the final 4 h of perfusion yielded a mean synthetic rate of 3.5 micrograms/h per 100 g body wt, which was approximately 0.2% of the synthetic rate of albumin in the same system. The cumulative appearance of albumin and transferrin was linear after 1 h and calculated rates of synthesis were 2,012 micrograms/h per 100 g and 263 micrograms/h per 100 g body wt, respectively. De novo synthesis of HF was confirmed by demonstrating incorporation of [14C]lysine into specific immunoprecipitates of HF, and by the observations that both specific incorporation of labeled amino acid and net release of immunoassayable HF were inhibited by the administration of cycloheximide. Finally, it was evident that the rates of synthesis observed in the isolated perfused liver agreed closely with absolute rates of degradation of HF measured in vivo with 125I-rat HF (4.0 micrograms/h per 100 g). From these data we conclude that the liver is the principal site of synthesis of HF.

Animals↗
PubMed1982

Incorporation of molecular oxygen into pyrimidine cofactors by phenylalanine hydroxylase.

The 5-amino substituents of two pyrimidine cofactors of rat liver phenylalanine hydroxylase, 2,5,6-triamino-4-pyrimidinone (TP) and 5-benzylamino-2,6-diamino-4-pyrimidinone (BDP), have been shown to be cleaved quantitatively by enzyme (Bailey, S. W., and Ayling, J. E. (1980) J. Biol. Chem. 255, 7774-7781). That the pyrimidine product of this process (when carried out in the presence of 2-mercaptoethanol) is 2,6-diamino-5-hydroxy-4-pyrimidinone (divicine) is further confirmed by mass spectrometry of an isolated t-butyldimethylsilyl derivative. The origin of the oxygens in this divicine was studied with enzyme reactions containing 18O2. Corrected for the loss in the controls, the divicine generated by phenylalanine hydroxylase from TP and BDP incorporated one atom of 18O with an efficiency of 98 +/- 5% and 100 +/- 3%, respectively, even though these reactions are partially uncoupled. The position of the isotope was unambiguously assigned to the 5-hydroxyl group by the simultaneous use of [18O] TP and 18O2, the divicine from which was found to be doubly labeled. o-Methylphenylalanine stimulates a rate of cofactor oxidation at least 10-fold greater than its own rate of hydroxylation. The majority of divicine isolated from phenylalanine hydroxylase incubations with o-methyl substrate analog was labeled with oxygen from 18O2. The demonstration, with phenylalanine hydroxylase, that one atom of molecular oxygen remains attached to position 5 of pyrimidine cofactor, provides the first strong evidence for activation of oxygen by aromatic amino acid monooxygenases via covalent addition to C4a of tetrahydrobiopterin.

Animals↗
PubMed1980

Production and release of plasminogen by isolated perfused rat liver.

In view of conflicting evidence for a major hepatic role in the synthesis of circulating plasminogen, the precursor of the fibrinolytic enzyme plasmin, we carried out the present study with a sensitive assay in order to measure the accumulation of small quantities of plasminogen in a recycling rat liver perfusion system. We have purified plasminogen from Sprague-Dawley rat plasma and have raised a monospecific antiserum against it in rabbits. Isolated rat liver perfusions were performed with an oxygenated recycling perfusate consisting of a perfluorotributylamine/Pluronic F-68 emulsion (Fluosol 43) free of plasma proteins and blood cells. The system was shown to be capable of synthesizing albumin and transferrin. The cumulative appearance of plasminogen in the perfusate was measured by a sensitive, specific radioimmunoassay. Plasminogen concentration increased progressively during the first 2 hr of perfusion; the observed average net synthesis in five separate experiments was approximately 35 microgram/hr per 100 g of body weight. Exposure of the perfused liver to 18 microM cycloheximide inhibited additional increase in the titer of plasminogen. Evidence for de novo synthesis was provided by the incorporation of 14C-labeled leucine into specific immunoprecipitates of plasminogen and the inhibition of this incorporation by cycloheximide. Analysis of the immunoprecipitates by sodium dodecyl sulfate/polyacrylamide gel electrophoresis revealed a single peak of radioactivity corresponding to Mr of 82,000. These data indicate that the liver is a major site of plasminogen production.

Animals↗
PubMed1977

Metabolic clearance and plasma half disappearance time of exogenous gonadotropin releasing hormone in normal subjects and in patients with liver disease and chronic renal failure.

The metabolic clearance rate (MCR) and half disappearance time (t 1/2) of gonadotropin releasing hormone (GnRH) has been measured during and after cessation of constant infusion of exogenous GnRH. Studies were performed on normal subjects and patients with severe renal and liver disease. GnRH was quantified by a sensitive and specific radioimmunoassay which does not measure GnRH fragments. The MCR of GnRH in normal subjects was 1640+/-59.7 ml/min (23.7+/-1.8 ml/min/kg), similar to values found in 4 patients with liver disease. However in chronic renal failure an MCR of only 631+/-62 ml/min (9.1+/-0.7 ml/min/kg) was obtained. The t1/2 of GnRH after infusion was linear for 8-10 min, after which a much slower component was observed. The t1/2 of the first component ranged from 5.5 to 8 min in normal subjects, 6.5-8 min in patients with liver disease but prolonged (12-16.5 min) in patients with renal failure. It would appear that GnRH is cleared rapidly in normal subjects, that moderate liver dysfunction does not alter this, but that impaired renal function significantly prolongs the t1/2 and lowers the MCR. The kidney might be an important catabolic organ for infused GnRH; alternatively, uremia might impair catabolism non-specifically.

Adult↗
PubMed1977

Virilization with diffuse involvement of ovarian androgen secreting cells.

A case is reported in which virilization of long duration and gradual progression was found in association with ovarian hyperthecosis and bilateral hilar cell lesions. The frequency occurrence of both masculinizing and nonmasculinizing ovarian tumors in association with ovarian hyperthecosis and polycystic ovaries is discussed.

Adult↗
PubMedDate not supplied

A cluster of patients with inferior rectus restriction following local anesthesia for cataract surgery.

During a 5-month period, four patients developed contracture of the inferior rectus muscle following local anesthesia for cataract surgery in the practice of one ophthalmologist. Two anesthesiologists administered retrobulbar anesthesia. All patients had persistent vertical diplopia caused by a large hypotropia of the operated eye. Forced duction testing revealed marked restriction to elevation of the eye. In two patients, MRI demonstrated segmental thickening of the inferior rectus muscle, just posterior to the globe. All patients had normal thyroid function tests. No patient had a previous history of strabismus. Three of the four have had strabismus surgery consisting of recession of the markedly restricted inferior rectus muscle on an adjustable suture. These three patients have regained fusion and are now asymptomatic.

Aged↗
PubMedDate not supplied

Effects of isothiocyanates on the metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and benzo[a]pyrene by hamster and rat liver microsomes.

Benzyl isothiocyanate (BITC) and phenethyl isothiocyanate (PEITC) strongly inhibited the N-pyridine oxidation and alpha-carbon hydroxylation pathways of the in vitro metabolism of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) by Syrian golden hamster liver microsomes from saline-injected (noninduced) animals. PEITC was more potent than BITC. NNK-reduction was enhanced by both isothiocyanates. Both N-oxidation and alpha-hydroxylation activities were several-fold greater in hamster liver microsomes compared with F344 rat liver microsomes. Consequently, the inhibitory effect of BITC and PEITC on rat liver microsomes (noninduced) was not as pronounced. NNK-reduction in rat liver microsomes was not significantly different from hamster and was not enhanced by BITC and PEITC. Neither BITC nor PEITC had a strong inhibitory effect on the in vitro metabolism of benzo[a]pyrene (BaP) by either hamster or F344 rat liver microsomes from beta-naphthoflavone treated animals. The extent of BaP metabolism was similar for the two microsome groups. Since the metabolism of NNK and BaP depends upon cytochrome P450-mediated reactions that may utilize different isozymes of cytochrome P450, our data suggest that BITC and PEITC may inhibit the activity of some isozymes and not others. Our results also indicate that the inhibition of the metabolism of NNK by isothiocyanates as previously described for the mouse and rat can now be extended to include the hamster as well.

Animals↗
PubMedDate not supplied

Inhibition of liver microsomal cytochrome P450 activity and metabolism of the tobacco-specific nitrosamine NNK by capsaicin and ellagic acid.

The tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3- pyridyl)-1-butanone (NNK), present in tobacco and tobacco smoke, is metabolically activated by microsomal enzymes. In this study, we examined the effect of capsaicin and ellagic acid on the in vitro metabolism of NNK by hamster and rat liver microsomes. Capsaicin is the principal component of Capsicum fruits used widely throughout the world as a food additive. Ellagic acid, with reported anticarcinogenic properties, is found in various soft fruits and nuts. Both capsaicin and ellagic acid inhibited the major pathways of NNK-reduction, N-pyridine oxidation and a-hydroxylation by hamster liver microsomes. Capsaicin inhibited NNK-reduction and a-hydroxylation and ellagic acid inhibited N-oxidation and a-hydroxylation by rat liver microsomes. The effects of capsaicin and ellagic acid on isozymes of cytochrome P450 were observed in the hydroxylation reactions of the metabolism of the steroid hormone testosterone. Results of these experiments indicated that both capsaicin and ellagic acid strongly inhibited the constitutive enzymes CYP 2A2, 3A1, 2C11, 2B1, 2B2 and 2C6. This study suggests that capsaicin and ellagic acid, as naturally occurring dietary constituents, possess antimutagenic and anticarcinogenic properties through the inhibition of xenobiotic metabolizing enzymes.

Animals↗