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Biomedical subjects

L F Martin

Publications and source records attributed to L F Martin.

At least 73 records · Page 4Linked to original sources

Effect of an altered glutathione content on renal ischemic injury.

Renal ischemia and reperfusion have been shown to be associated with an enhanced renal lipid peroxidation. Because glutathione (GSH) serves to protect cells from oxidative stress, the role of GSH in renal ischemia was investigated. The content of renal GSH in the rat declined to 40% of control values during 35 min of renal artery occlusion. Renal GSH levels only partially recovered after 120 min of blood reflow. To assess the significance of this effect, renal GSH levels were altered before occlusion of the renal artery. Rats were treated with either buthionine sulfoximine (BSO) or glutathione monoethylester (GSH-ester) to lower or elevate, respectively, renal GSH levels. The ischemia-induced changes in renal ATP, ADP, and AMP after 35 min of ischemia and 90 min of blood reflow were not affected by prior alteration of renal GSH levels. The ischemia-induced decrease in the respiratory control of isolated cortex mitochondria was also unaffected. In control animals, ischemia of 35 min increased urine flow rate 3.2-fold and decreased GFR to 29% of normal values during the reflow period. Similar changes occurred in kidneys with a depleted GSH level. In kidneys with an elevated GSH, however, both urine flow rate and GFR were decreased to values 50 and 3% of normal, respectively. Morphological analysis demonstrated that ischemia produced an enhanced degree of damage with an increase in cast formation in kidneys pretreated with GSH-ester; however, the ester also produced morphological changes in nonischemic kidneys. The severity of ischemic damage was similar in kidneys with a lower GSH content when compared with controls. We conclude that renal GSH is depleted by ischemia but depletion of renal GSH with BSO before ischemia has no effect on ischemic-induced damage to the kidney. However, ischemic-induced renal dysfunction is enhanced when GSH is elevated with glutathione monoethylester before ischemia.

Adenine Nucleotides↗

The effects of chronic bacteremia on the metabolic response to exercise in the conscious rat.

Cardiac function was indirectly assessed in a rat model of chronic sepsis by measuring maximal oxygen uptake (VO2max) during exercise. A subcutaneous abscess cavity was created in rats by implanting a gauze sponge in the hindquarter area. Animals with sterile abscesses were compared with rats that had the abscess cavity infected with Escherichia coli and Bacteroides fragilis (gram-negative group) or these two organisms plus Staphylococcus aureus (gram-positive/negative group). VO2max was measured during exercise before and after the abscess cavity was infected. After a carotid artery cannula was placed, heart rate, mean arterial pressure, arterial blood gases, and acid-base status were measured in three groups of rats (sterile abscess, gram-negative, gram-positive/negative) during submaximal and maximal exercise. Results demonstrated that the infected rats were febrile and had elevated white blood cell counts and intermittent bacteremia, while rats with sterile abscesses did not. VO2max was similar in all groups of rats both before and after the abscess cavity was infected. The metabolic and hemodynamic variables measured during submaximal and maximal exercise in the different groups of rats were similar. These results do not support the contention that gram-positive and/or-negative bacteremia produce cardiac dysfunction during early sepsis.

Acid-Base Equilibrium↗

3-Methylcholanthrene induction of enzymes in the vitamin K-dependent carboxylation system.

The effect of 3-methylcholanthrene on liver enzymes in the vitamin K-dependent carboxylation system has been investigated in normal rats and rats treated with the anticoagulant warfarin. It was found that 3-methylcholanthrene did not interfere with the anticoagulant function of the drug. Treatment of rats with 3-methylcholanthrene resulted in a 2.7-fold increase in liver cytosolic DT-diaphorase activity and a 1.5-fold increase in liver microsomal vitamin K-dependent carboxylase activity. A pathway for production of reduced vitamin K cofactor for the vitamin K-dependent carboxylase is catalyzed by DT-diaphorase and an as yet unidentified NADH-specific dehydrogenase(s). The data suggest that the unidentified enzyme(s) in the pathway is not induced by 3-methylcholanthrene.

Biomarkers↗

Warfarin poisoning and vitamin K antagonism in rat and human liver. Design of a system in vitro that mimics the situation in vivo.

The present paper describes a system in vitro that has been developed to mimic vitamin K metabolism and vitamin K function in liver. In this system the two pathways that are known to participate in vitamin K reduction are active and the vitamin K-dependent carboxylase accepts a synthetic pentapeptide as substrate. With this system in vitro the effect of warfarin on both pathways was examined under conditions which simulated a warfarin-poisoned liver. Identical experiments were completed with rat and human liver. All activities currently associated with vitamin K metabolism and vitamin K function were similar in the rat and human systems. Warfarin neutralized the ability of pathway I (the vitamin K epoxide reductase pathway) to produce reduced and active vitamin K cofactor for the carboxylase. In both the rat and the human system, however, when warfarin was present, reduced vitamin K cofactor was produced by pathway II (the dehydrogenase pathway). The data are consistent with observations in vivo on the effect of vitamin K1 when used as an antidote. This suggests that the system in vitro reflects the mechanism in vivo by which vitamin K1 overcomes warfarin poisoning.

Animals↗

Rat and human liver vitamin K epoxide reductase: inhibition by thiol blockers and vitamin K1.

1. Reduction of vitamin K1 2,3-epoxide by rat and human liver vitamin K epoxide reductase is inhibited by N-ethylmaleimide and iodoacetamide. 2. Both enzymes are protected from inhibition by N-ethylmaleimide by vitamin K1 or vitamin K1 2,3-epoxide. 3. Vitamin K1 inhibits reduction of vitamin K1 2,3-epoxide to vitamin K1 which suggests product inhibition of the enzyme.

Animals↗

DT-diaphorase in morbidly obese patients.

Dicumarol sensitive DT-diaphorase (EC 1.6.99.2) activity has been measured in human cytosol from liver and various extrahepatic tissues not containing tumors which were removed during elective operations. The specific activity was found to be highest in tissues of the gastrointestinal tract. In contrast to rodent liver, the human liver has extremely low DT-diaphorase activity. Tissue activity was found to be highly variable among the patients studied which suggests that nutritional and/or genetic factors may be involved. The variability ranged from undetectable levels in liver to 223 nmol/mg X min in stomach. The data question whether the current concept concerning the biological function of this enzyme is applicable to man.

Cytosol↗

An in vitro study of the properties influencing Staphylococcus epidermidis adhesion to prosthetic vascular graft materials.

This study examines the influence of the properties of various vascular graft materials on the bacterial adherence process of two different strains of Staphylococcus epidermidis (mucous and normucous producing). Dacron grafts (both knitted and woven), Teflon grafts, and Dacron grafts coated with one and two layers of silicone were studied because these materials differ significantly in porosity, hydrophobicity, and surface charge (zeta potential). Graft segments were immersed in 3H-labeled bacteria solution for periods ranging from 5 to 180 minutes and liquid scintillation techniques were used to quantify bacterial adherence. The porous knitted Dacron material had a significantly higher rate of bacterial adherence than either the woven Dacron or Teflon (p less than 0.05). Silicone coating (either one or two layers) reduced adherence by a factor of four for the knitted Dacron (p less than 0.05) and by a factor of two for woven Dacron (p less than 0.05). The mucous producing strain of S. epidermidis displayed significantly better adherence to woven and knitted Dacron than the normucous producing strain, but only when 0.25% dextrose was added to the bacteria solution. These findings indicate that the highly porous knitted Dacron grafts have the highest propensity for bacterial adhesion. Graft materials with the most negative zeta potentials are more resistant to bacterial adherence. Silicone coating of Dacron material significantly changed adherence characteristics, suggesting that this may be a viable strategy for protecting implantable medical devices containing materials to which bacteria readily adhere.

Adhesiveness↗

Renal lymphoma: an unusual example.

A patient with non-Hodgkin lymphoma presenting as unilateral soft-tissue encapsulation of a kidney is reported. The limited differential diagnosis is noted and lymphomatous involvement of the kidney is briefly reviewed.

Humans↗

Effect of hemorrhagic shock on oxidative phosphorylation and blood flow in rabbit gastrointestinal mucosa.

The pathophysiologic mechanism responsible for ulceration of gastric fundus and corpus mucosa following hemorrhagic shock is not well defined. We examined the effect of hemorrhagic shock (25 ml blood/kg) and resuscitation (reinfusion of shed blood) on oxidative phosphorylation in different tissues of the rabbit to determine if differences in mitochondrial response to hemorrhagic shock and resuscitation contribute to the propensity of gastric fundus and corpus to necrose before other tissues. Blood flow was measured by using radioisotope-labeled microspheres to determine if changes in regional blood flow could be correlated with this propensity to ulcerate. The respiratory control index (RCI), an index of the integrity of mitochondrial function, was significantly increased in gastric antrum, liver, and kidney from the animals subjected to hemorrhagic shock and successful resuscitation when compared to control animals. In liver and kidney, these differences were largely due to increases in state 3 respirations. Duodenal and gastric corpus and fundus mitochondria showed no differences in RCI between bled and control groups. Blood flow data did not implicate ischemia as the mechanism responsible for the differential rate of ulceration after hemorrhage. The inability of fundus, corpus, and small-bowel mucosal mitochondria to respond to the stress of hemorrhagic shock and resuscitation in a manner similar to liver, kidney, and gastric antral mitochondria may place these tissues at greater risk to ulcerate. Further work is necessary to define whether this difference in mitochondrial response patterns represents a real increase in the maximal respiratory capacity of liver, kidney, and antrum after shock and resuscitation.

Animals↗

The first 70 years experience managing cardiac disruption due to penetrating and blunt injuries at the University of Louisville.

Survival of patients with cardiac injuries requires prompt intervention and cardiography. Approximately 50 years ago, Dr. R. Arnold Griswold instituted a treatment plan for the management of cardiac injuries. Many of the tenets he espoused are still in use today. We have been able to collect data on 266 patients with heart wounds from 1913 to 1982 at Louisville General Hospital. Trends in the evolution of injury patterns and their treatment will be discussed.

Cardiac Surgical Procedures↗

Unifying concepts in treatment of esophageal leaks.

We treated 75 patients with esophageal trauma, perforation, or anastomotic leak. Several factors were shown to be associated with an increased mortality, including delayed treatment, presence of severe underlying esophageal disease, total parenteral nutrition catheter infection, the necessity for major extirpative procedures to treat the perforation, and the use of exclusion and diversion in the continuity procedure. The use of local muscle flaps to buttress suture line closure has led to excellent results in the 19 patients so treated. Delayed treatment of perforation or an anastomotic leak is a major problem, but the treatment protocol described herein has led to the survival of 12 of 16 patients treated. The use of primary muscle flap closure for extensive esophageal defects or delayed treatment of nonhealing leaks was evaluated in five patients. All five had healing of the defect, with one resultant esophageal stricture.

Dilatation↗

Telephone use by a multi-channel cochlear implant patient. An evaluation using open-set CID sentences.

A totally deaf person with a multiple-channel cochlear prosthesis obtained open-set speech discrimination using the telephone. CID Everyday Sentences were presented by telephone to the patient, who repeated an average of 21 per cent of key words correctly on the first presentation, and 47 per cent when a repeat of the sentences was permitted. This result is consistent with the patient's reports of telephone usage.

Adult↗

A comparison of three speech coding strategies using an acoustic model of a cochlear implant.

Three alternative speech coding strategies suitable for use with cochlear implants were compared in a study of three normally hearing subjects using an acoustic model of a multiple-channel cochlear implant. The first strategy (F2) presented the amplitude envelope of the speech and the second formant frequency. The second strategy (F0 F2) included the voice fundamental frequency, and the third strategy (F0 F1 F2) presented the first formant frequency as well. Discourse level testing with the speech tracking method showed a clear superiority of the F0 F1 F2 strategy when the auditory information was used to supplement lipreading. Tracking rates averaged over three subjects for nine 10-min sessions were 40 wpm for F2, 52 wpm for F0 F2, and 66 wpm for F0 F1 F2. Vowel and consonant confusion studies and a test of prosodic information were carried out with auditory information only. The vowel test showed a significant difference between the strategies, but no differences were found for the other tests. It was concluded that the amplitude and duration cues common to all three strategies accounted for the levels of consonant and prosodic information received by the subjects, while the different tracking rates were a consequence of the better vowel recognition and the more natural quality of the F0 F1 F2 strategy.

Adult↗

Vitamin K-dependent carboxylation and vitamin K metabolism in liver. Effects of warfarin.

The systems involved in vitamin K-dependent carboxylation and vitamin K metabolism have been extensively studied in rat liver. To determine how clinically applicable this information is, similar in vitro studies were completed using human liver. One major difference exists in the pathways that provide reduced vitamin K1 cofactor for the carboxylation reaction. The coumarin-sensitive DT-diaphorase (EC.1.6.99.2) in human liver appears to play a relatively minor role in the dehydrogenase pathway. However, similar to rat liver, the human liver contains a warfarin-insensitive enzyme in this dehydrogenase pathway. The data suggest that this enzyme is responsible for the antidotic effect of vitamin K1 in cases of coumarin intoxication. Human vitamin K epoxide reductase, which constitutes the other pathway for vitamin K1 reduction, has kinetic and enzymological characteristics that are very similar to the rat enzyme. This enzyme exhibited similar activity in rat and human microsomes. Initial velocities for vitamin K1 epoxide reduction in rat and human microsomes were 20 and 32 pmol/mg X min, respectively. The human enzyme is highly sensitive to warfarin inhibition. The mechanism for this inhibition appears to be similar to what has been proposed for the rat enzyme. Also, a vitamin K-dependent carboxylation system is described that allows both pathways to support the carboxylation reaction with reduced vitamin K1 cofactor. The effect of warfarin on this in vitro system is consistent with the current model for the mechanism of action of coumarin anticoagulant drugs in the rat.

Animals↗

Abdominal wall repair with polypropylene mesh in pregnancy.

A woman in her 34th week of gestation required emergency appendectomy for perforation, with postoperative wound dehiscence secondary to fasciitis and tension on the suture line. Polypropylene mesh was used to repair the abdominal wall. Fetal distress necessitated a cesarean section. The mother and child both survived without functional impairment. The indications, the disadvantages, and the unresolved issues concerning the use of polypropylene mesh during pregnancy are presented.

Abdominal Muscles↗

Bleeding from stress gastritis. Has prophylactic pH control made a difference?

Control of intragastric pH with antacids or H2-receptor antagonists is a standard prophylactic treatment routinely used to prevent or control bleeding from acute erosive gastritis (AEG) in critically ill patients on trauma and surgical services. The incidence of bleeding from AEG was documented on these services retrospectively before and after the institution of standard prophylaxis treatment to determine the relative morbidity, mortality, and risk factors of each era. During the preprophylaxis and postprophylaxis era, the incidence of bleeding was the same, 2.3 per cent (13 of approximately 550 patients in each study period). Prior to prophylaxis, three times as many patients required operation (1 versus 3 patients) although the average transfusion requirement was the same (4.4 units of blood). During both eras the majority of patients were septic and showed other signs of organ failure. Inadequate prophylaxis (failure to prescribe or early discontinuation) was documented in over half of the patients who bled and in the patient requiring operation in spite of a departmental interest in stress gastritis prophylaxis. If antacids and H2-receptor antagonists are used routinely, complications from AEG should be reduced. Even with improved methods of pH control, it appears unlikely that this problem will be eliminated.

Adult↗