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Biomedical subjects

T Henderson

Publications and source records attributed to T Henderson.

At least 19 recordsLinked to original sources
PubMed1995

Regions of evolutionary conservation between the rat and human prohibitin-encoding genes.

We have analyzed and compared the 5' promoter region, the intron structure and the exon-intron flanking sequences in the rat and human prohibitin-encoding genes (PHB). Comparative analysis of a 350-nt region immediately 5' to and including the first exon identifies eight highly conserved regions, four of which correspond to binding sites for known transcriptional control proteins (CCAAT box, 'SV40' site and two Sp1 sites). The promoter lacks a TATA box. Four transcription start points (tsp) clustered within a 35-bp region were identified by rapid amplification of cDNA ends (RACE). The exon-intron boundaries in rat and human are highly conserved, with identical positioning of splice junctions. PCR analysis with conserved exon primers was used to detect length variation between rat and human PHB, and length differences were observed in all of the introns.

Animals↗
PubMed1992

Angiotensin and adrenoceptors in the hemodynamic response to aortic cross-clamping.

This study was designed to test the hypothesis that activation of adrenoceptors and/or the renin-angiotensin system plays an important role in the overall hemodynamic response to aortic cross-clamping. The experiments were performed on anesthetized rats pretreated with either saline (control group), an angiotensin-converting enzyme inhibitor (enalapril maleate, 2 mg/kg), an alpha 1-adrenergic antagonist (prazosin hydrochloride, 0.5 mg/kg), a beta-adrenergic antagonist (propranolol hydrochloride, 5 mg/kg), or an alpha 2-adrenergic antagonist (atipamezole, 5 mg/kg). Cross-clamping of the thoracic aorta was associated with an expected increase in mean arterial pressure and systemic vascular resistance in all animals. During the period of cross-clamping, cardiac output gradually decreased in all groups. Animals pretreated with the alpha 1-adrenergic antagonist or the angiotensin-converting enzyme inhibitor developed hypertension of a lesser degree than the control animals, while rats pretreated with the beta-adrenergic or alpha 2-adrenergic antagonist demonstrated a greater arterial hypertension than the control animals. The possible mechanisms underlying the observed differences are discussed. In conclusion, the present study confirms the posed hypothesis that the reninangiotensin and sympathetic nervous systems play an important role in hemodynamic response to cross-clamping of the thoracic aorta.

Adrenergic alpha-Antagonists↗
PubMed1992

Haemodynamic changes and oxygen uptake during crossclamping of the thoracic aorta in dexmedetomidine pretreated dogs.

This study was designed to test the hypothesis that the alpha 2 adrenergic agonist, dexmedetomidine (DEX), decreases tissue oxygen demand thereby increasing tolerance to hypoxic insult. In 17 anaesthetized dogs, cardiac output was measured with thermodilution, blood flow through the inferior caval vein was determined using an electromagnetic flowmeter, and oxygen consumption was calculated by the Fick principle. The animals were divided into three groups: control group (n = 5), D3 and D30 groups (n = 6 for each group) treated with two doses of DEX (3 micrograms.kg-1 and 30 micrograms.kg-1, respectively) prior to aortic crossclamping. Upon crossclamping of the thoracic aorta, the cardiac index decreased in all three groups with the largest decrease in the D30 group, and the smallest decrease in the control group. Blood flow through the inferior vena cava decreased in all three groups of animals while blood flow through the superior caval vein increased in the control group, did not change in the D3 group, and decreased in the D30 group. Oxygen saturation in mixed venous blood increased in the control group, did not change in the D3 group and decreased in D30 group. Blood flow and oxygen uptake in the lower part of the body decreased in all groups. Oxygen consumption in the upper part of the body decreased equally in all three groups. Arterial lactate concentrations increased almost two-fold in the control group while it increased by only 30% in animals treated with DEX. A lesser increase in lactate concentrations and oxygen extraction in tissues below aortic crossclamping is consistent with the hypothesis that DEX decreases tissue oxygen requirement which might prove particularly useful in clinical situations where tissue hypoxia is expected.

Adrenergic alpha-Agonists↗
PubMed1991

Secular trends in nosocomial primary bloodstream infections in the United States, 1980-1989. National Nosocomial Infections Surveillance System.

More than 25,000 primary bloodstream infections (BSIs) were identified by 124 National Nosocomial Infections Surveillance System hospitals performing hospital-wide surveillance during the 10-year period 1980-1989. These hospitals reported 6,729 hospital-months of data, during which time approximately 9 million patients were discharged. BSI rates by hospital stratum (based on bed size and teaching affiliation) and pathogen groups were calculated. In 1989, the overall BSI rates for small (less than 200 beds) nonteaching, large nonteaching, small (less than 500 beds) teaching, and large teaching hospitals were 1.3, 2.5, 3.8, and 6.5 BSIs per 1,000 discharges, respectively. Over the period 1980-1989, significant increases (p less than 0.0001) were observed within each hospital stratum, in the overall BSI rate and the BSI rate due to each of the following pathogen groups: coagulase-negative staphylococci, Staphylococcus aureus, enterococci, and Candida species. In contrast, the BSI rate due to gram-negative bacilli remained stable over the decade, in all strata. Except for small nonteaching hospitals, the greatest increase in BSI rates was observed in coagulase-negative staphylococci (the percentage increase ranged between 424% and 754%), followed by Candida species (219-487%). In small nonteaching hospitals, the greatest increase was for S. aureus (283%), followed by enterococci (169%) and coagulase-negative staphylococci (161%). Our analysis documents the emergence over the last decade of coagulase-negative staphylococci as one of the most frequently occurring pathogens in BSI.

Bacteremia↗
PubMed1991

Nosocomial infection rates in adult and pediatric intensive care units in the United States. National Nosocomial Infections Surveillance System.

To determine which intensive care unit (ICU) infection rate may be best for interhospital and intrahospital comparisons and to assess the influence of invasive devices and type of ICU on infection rates, we analyzed data from the National Nosocomial Infections Surveillance System. From October 1986 to December 1990, 79 hospitals reported 2,334 hospital-months of data from 196 hospital units. The median overall infection rate was 9.2 infections per 100 patients. However, this infection rate had a strong positive correlation with average length of ICU stay (r = 0.60, p less than 0.0001). When patient-days was used in the denominator, the median overall nosocomial infection rate was 23.7 infections per 1,000 patient-days. Although there was a marked reduction in the correlation with average length of stay, this rate had a strong positive correlation with device utilization (r = 0.59, p less than 0.0001). To attempt to control for average length of stay and device utilization, we examined device-associated nosocomial infection rates. Central line-associated bloodstream infection rates, catheter-associated urinary tract infection rates, and ventilator-associated pneumonia rates varied by ICU type. The distributions of device-associated infection rates were different between some ICU types and were not different between others (coronary and medical ICUs or medical-surgical and surgical ICUs). Comparison of device-associated infection rates and overall device utilization identified hospital units with outlier infection rates or device utilization. These data show that: (1) choice of denominator is critical when calculating ICU infection rates; (2) device-associated infection rates vary by ICU type; and (3) intrahospital and interhospital comparison of ICU infection rates may best be made by comparing ICU-type specific, device-associated infection rates.

Adult↗
PubMed1991

13C NMR study of hepatic pyruvate carboxylase activity in tumor rats.

Alanine and lactate, as major gluconeogenic substrates, must be converted into oxaloacetate by way of pyruvate carboxylase before their entry into gluconeogenesis. Although it is well known that hepatic gluconeogenesis from these substrates is increased in tumor hosts, the involvement of pyruvate carboxylase has not been demonstrated. In the present study, we examined pyruvate carboxylase activity in the perfused livers of tumor rats using 13C NMR spectroscopy with [3-13C]-alanine as the gluconeogenic substrate. A substantial increase in hepatic [3-13C]-aspartate production was found in the tumor rats. Since aspartate accumulation directly reflects fluxes of alanine through pyruvate carboxylase, the observed increase in hepatic production of [3-13C]-aspartate in tumor rats indicates that pyruvate carboxylase activity is significantly enhanced.

Alanine↗
PubMed1991

H1 and H2 receptor antagonists and hepatic oxygen supply-demand relationship in pigs.

The hypothesis that histamine receptor (H1 and H2) blockade beneficially affects the hepatic oxygen supply-demand relationship was tested during experiments performed on 13 miniature pigs. Hepatic arterial and portal blood flows were measured with electromagnetic flowmeters. Cardiac output was determined by thermodilution. H1 and H2 receptor blockade was achieved with promethazine, 5 mg.kg-1 and cimetidine 30 mg.kg-1 IV, respectively. The study demonstrated no significant effect of H1 and H2 receptor blockade on hepatic oxygen uptake and no noticeable effects of cimetidine on hepatic circulation. However, promethazine decreased total hepatic blood flow, primarily by decreasing portal blood flow; this resulted in an increase in oxygen extraction as reflected in a decreased oxygen content in hepatic venous blood. The results reject the posed hypothesis: H1 receptor antagonist promethazine decreased, while H2 receptor antagonist cimetidine did not affect hepatic blood flow and oxygen supply; hepatic oxygen demand remained unaffected during H1 and H2 receptor blockade.

Animals↗
PubMed1991

Humoral factors and hemodynamics during cross-clamping of the thoracic aorta.

The present study was designed to test the hypothesis that vasoactive compounds produced in the ischemic part of the body below an occluded aorta are responsible for the hemodynamic changes observed during cross-clamping of the thoracic aorta. The experiments were performed on 32 rabbits anesthetized with halothane that underwent experiments with cross-circulation; the blood from the inferior caval veins of rabbits A was pumped into the inferior caval veins of rabbits B. Simultaneously, exactly the same amount of blood was pumped from the jugular vein of rabbits B into the jugular vein of rabbits A. The aorta and inferior vena cava were exposed and then simultaneously cross-clamped directly below the diaphragm. The cross-clamping of the aorta and inferior vena cava in rabbits A was associated with a 29% to 44% increase in mean arterial pressure in rabbits B. The experiments support the hypothesis and suggest that endogenously produced humoral factors are responsible for at least one third to one half of the arterial hypertension that usually develops during aortic cross-clamping.

Anesthesia, Inhalation↗
PubMed1991

Efficacy and duration of antistaphylococcal activity comparing three antibiotics bonded to Dacron vascular grafts with a collagen release system.

Type 1 collagen, minimally cross-linked, was used to bind one of three antibiotics (amikacin, chloramphenicol, or rifampin) to double-velour Dacron grafts to develop a prosthesis resistant to infection. Six millimeter disks of graft were placed in separate flasks (specific for each antibiotic) containing albumin in saline and continuously agitated. At daily intervals the solution was changed, and paired graft samples were removed and placed on a blood agar plate confluently streaked with bacteria. The initial zone of inhibition (centimeters squared), the time to 50% reduction of initial inhibition zone, and the overall duration of antibacterial activity were recorded on an exponential model. Grafts bonded with amikacin and chloramphenicol had an overall duration of activity of only 2 and 1 day, respectively, against Staphylococcus aureus. The collagen bonded rifampin grafts had an initial zone of 14.76 cm,2 took 3.92 days to reach 50% of initial inhibition, and had an overall duration of activity of 22.4 days. This was significantly better than grafts preclotted with 1.0 ml of rifampin (60 mg/ml) and 9 ml of blood (10.92 cm,2 1.06 days, and 5.6 days). When tested against a slime-producing Staphylococcus epidermidis (American Type Culture Collection No. 35983), the graft bonded with rifampin had inhibitory activity of up to 27.77 days with a 50% of activity eluted at 4.78 days, significantly better than the preclotted rifampin graft without collagen bonding. These data suggest that rifampin bonded by collagen can protect a vascular graft against infection from S. aureus and S. epidermidis for up to 3 weeks after implantation.

Amikacin↗
PubMed1990

Dopamine and hepatic oxygen supply-demand relationship.

The present study examined the effect of small, vasodilating doses of dopamine on the hepatic oxygen supply--uptake ratio. Thirteen miniature pigs weighing 18-27 kg were studied under sodium pentobarbital anesthesia. Hepatic arterial and portal blood flows were measured. Oxygen content in arterial, portal, and hepatic venous blood was determined. Dopamine was infused in doses of 5, 10, and 15 micrograms.kg-1.min-1. Dopamine infusion was associated with a dose-related increase in hepatic oxygen uptake and a dose-independent increase in hepatic oxygen delivery with a maximal increase (30%) in the hepatic oxygen delivery at 10 micrograms.kg-1.min-1. The hepatic oxygen delivery--uptake ratio remained unchanged during dopamine infusion in doses of 5 and 10 micrograms.kg-1.min-1 and significantly decreased during the dose of 15 micrograms.kg-1.min-1. The study demonstrated that an increase in cardiac output and hepatic oxygen delivery during dopamine administration was not associated with an improvement in hepatic oxygen supply--demand relationship since hepatic oxygen uptake also increased.

Animals↗
PubMed1990

Hemodynamics and oxygen uptake below and above aortic occlusion during crossclamping of the thoracic aorta and sodium nitroprusside infusion.

The effects of controlled vasodilation on blood flow and oxygen consumption above and below the aortic occlusion during crossclamping of the thoracic aorta were examined in 16 mongrel dogs anesthetized with halothane. Blood flow in the inferior vena cava was measured with an electromagnetic cannulating flow probe, and cardiac output was measured by thermodilution. The animals were divided into two groups. In the control group the thoracic aorta was crossclamped at the diaphragmatic level for 30 minutes. In the sodium nitroprusside group the aorta was also crossclamped for 30 minutes, but an infusion of sodium nitroprusside was initiated after 10 minutes of occlusion to decrease systemic blood pressure. Measurements were made before and at 10, 20, and 30 minutes after aortic crossclamping, and at 10 minutes after aortic unclamping. Crossclamping of the thoracic aorta was associated with marked decreases in blood flow and oxygen consumption in organs and tissues below the aortic occlusion in both groups. Above the occlusion, blood flow increased but oxygen uptake decreased. Sodium nitroprusside increased cardiac output and blood flow above the aortic occlusion even more than crossclamping alone while it decreased blood flow and oxygen consumption below the crossclamp.

Animals↗
PubMed1989

Efficacy of corticosteroids in suppression of intimal hyperplasia.

The effect of steroids and immunosuppression on the development of intimal hyperplasia was studied in 24 New Zealand white rabbits. Staged bilateral arteriotomy and stripping of intima of the common carotid artery was performed by means of a 2F balloon catheter under 700 mm Hg of pressure. At 3 months, after the control side artery was harvested (N = 24), the rabbits were assigned to three groups of eight animals each: (1) dexamethasone 0.1 mg/kg, (2) cyclophosphamide (Cytoxan) 1 mg/kg, or (3) azathioprine 1 mg/kg intramuscularly. The animals were treated on the day before the contralateral intimal stripping and then were treated six times a week for 8 weeks; the vessels were harvested at 3 months. Twelve-week patency rates were 62.5% in the control group, 83.3% in the dexamethasone group, 100% in the Cytoxan group, and only 33.3% in the azathioprine group. The ratio of the luminal area to the area enclosed by the internal elastic lamina was used as an index of intimal hyperplasia, with a higher ratio indicating less intimal thickening. This ratio of the patient vessels was 0.74 +/- 0.14 (N = 15) for the controls, 0.79 +/- 0.11 (N = 6) for the Cytoxan group, and 0.91 +/- 0.06 (N = 5, p less than 0.05) for the dexamethasone group, which is statistically significant by means of analysis of variance. Occluded vessels had evidence of organized thrombus without any intimal hyperplasia. The decrease in intimal hyperplasia seen in the steroid group suggests a potential role for steroids in small vessel revascularization, but further studies are required.

Animals↗
PubMed1989

Topical metronidazole for severe and recalcitrant rosacea: a prospective open trial.

Nineteen patients with severe or recalcitrant rosacea were treated twice daily with 0.75 percent metronidazole topical gel in an open label study. Sixteen of the patients (84 percent) showed 50 percent or greater reduction in inflammatory lesions, while fifteen (79 percent) demonstrated a reduction in erythema severity and an improvement when evaluated by the investigator global assessment. No positive response was recorded for any patient prior to topical medication, whereas six of nine patients previously treated with tetracycline/minocycline demonstrated improvement. Seven of these nine patients responded to topical metronidazole treatment. One additional patient who did not respond to minocycline or desonide treatment showed a good response to topical metronidazole. Only one patient reported local irritation after using metronidazole. These results demonstrate that topical metronidazole gel is safe and effective for the treatment of severe or recalcitrant rosacea.

Administration, Topical↗
PubMed1988

Isolation and partial characterisation of a 26 kilodalton antigen from Plasmodium falciparum recognised by an inhibitory monoclonal antibody.

A 26 kDa protein, present in trophozoites and schizonts of Plasmodium falciparum, has been identified as the target of a monoclonal antibody that weakly inhibits parasite growth in vitro. The antigen has been purified to homogeneity by immuno-affinity chromatography and electrophoresis. The sequence of 19 amino acids at the N-terminus of the protein has been determined.

Amino Acid Sequence↗
PubMed1988

Patency and intimal hyperplasia: the effect of aspirin on small arterial anastomosis.

This experiment evaluated the effect of aspirin (ASA) on the patency and development of intimal hyperplasia in autologous, small caliber, arterial end-to-side anastomosis. Twenty-eight adult female rabbits had their distal left external iliac artery transposed and anastomosed to the right proximal external iliac artery. Fourteen rabbits received ASA 40 mg by gavage twice in the 24 hours preceding the operation and 5 times a week postoperatively (experimental) and 14 rabbits received no ASA therapy (control). Plasma salicylate levels range from 25 to 36 micrograms per milliliter in experimental animals. Patency of the reconstruction was assessed by Doppler examination each month, confirmed by autopsy and calculated by life table analysis. Five cross sections of each patent anastomosis harvested at six and nine months were examined by light microscopy. A total of seven thromboses occurred in the control group versus two occlusions in the experimental group. Four of the thromboses in the control group occurred less than seven days after the reconstruction, whereas no such events occurred in the experimental group. Patency by actuarial methods at nine months was 45.5% versus 81.8% (p less than .05) in control and experimental groups, respectively. This improvement occurred in spite of similar values for intimal thickness and lumen-to-basement membrane ratios in both control and experimental groups. We conclude that aspirin significantly improves the nine month patency rate of small autologous end-to-side anastomosis, and its effect is most noticeable in the early postoperative period.(ABSTRACT TRUNCATED AT 250 WORDS)

Anastomosis, Surgical↗
PubMed1987

Fetal metabolism and placental transfer of vasoactive intestinal peptide in sheep.

Vasoactive Intestinal Peptide (VIP) is a 28-amino-acid putative neurotransmitter that may have a role in the regulation of myometrial blood flow and uterine contractility. The chronically cannulated fetal sheep preparation was used to examine the fetal clearance and placental transfer of VIP. Metabolic Clearance Rate (MCR) and placental transfer of VIP were measured by alternate steady-state infusion of VIP into the mother and fetus. Plasma concentrations of VIP were measured by radioimmunoassay. MCR was similar in the pregnant (45 +/- 10 ml/kg/min) and nonpregnant ewes (35 +/- 5 ml/kg/min). However, compared to both pregnant and nonpregnant ewes, fetal MCR was significantly increased at 77 +/- 15 ml/kg/min, indicating highly developed clearance mechanisms in the fetus. VIP did not cross the placenta in either direction. Both the placenta and fetal liver metabolized VIP and contributed to the elevated fetal clearance of VIP. The results show that VIP in fetal tissue is unlikely to influence maternal uterine activity with any VIP-mediated effects emanating from maternal and/or placental sources.

Animals↗
PubMed1987

Primary anastomotic bonding in polytetrafluoroethylene grafts?

Previous studies have demonstrated that standard knitted and woven fabric grafts are forever dependent on the suture material for anastomotic tensile strength. Clinical experience with polytetrafluoroethylene (PTFE) and double velour knitted grafts have shown that there is extensive fibrous capsular bonding between the graft and the surrounding tissues. This would lead to increased anastomotic tensile strength. To test this theory, 34 mongrel dogs underwent replacement of their infrarenal aortas with grafts made of PTFE (10 dogs), of double velour knitted Dacron (DVD, 11 dogs), of single velour knitted Dacron (SVD, 5 dogs), and of woven Dacron (WD, 8 dogs). One anastomosis was constructed with 5-0 Prolene and the opposite anastomosis was constructed with 5-0 Dexon (average absorption time, 21 days). In five grafts each of PTFE and DVD, as well as in all eight WD grafts, the midgraft was divided and resutured with 5-0 Dexon. All grafts were harvested together with adjacent proximal and distal aorta between 3 and 10 months from the time of implantation. The tensile strength of each anastomosis was measured with a tensiometer. The mean graft-to-artery (absorbable suture) anastomotic tensile strength, in pounds, for PTFE (14.3) and DVD (12.6) was significantly higher than that for SVD (6.9) or WD (7.2) (p less than 0.003). Graft-to-graft anastomotic tensile strength for PTFE (mean 17.3) was significantly better than that for DVD (mean 9.0; p less than 0.03) or WD (mean 7.9; p less than 0.001). Analysis of anastomotic tensile strength as a function of time revealed continued increase in PTFE in contrast to a slow decline with time in DVD.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗