Biomedical subjects

J R Fletcher

Publications and source records attributed to J R Fletcher.

At least 37 records · Page 2Linked to original sources

PubMed1987

Hormonal responses to graded surgical stress.

We tested the hypothesis that selected hormonal responses to surgery reflect the degree of surgical stress. Plasma norepinephrine, epinephrine, thromboxane B2, cortisol, serum angiotensin converting enzyme, thyroxine, triiodothyronine, free thyroxine, and free triiodothyronine levels were measured preoperatively, and then one hour, 24 hours, and five days postoperatively in three groups of patients. The groups were as follows: group 1, "minimal" stress, eg, inguinal hernia repair (n = 10); group 2, "moderate" stress, eg, cholecystectomy (n = 12); and group 3, "severe" stress, eg, subtotal colectomy (n = 9). Patients in group 1 showed no significant surgery-induced changes in hormonal values. The stress-induced changes in patients in groups 2 and 3 were seen at one and occasionally 24 hours; however, by five days postoperatively, circulating hormone values had returned to preoperative levels. Increases in plasma cortisol, norepinephrine, and epinephrine, and decreases in serum angiotensin converting enzyme levels characterized the surgery-induced hormonal changes. Conclusions are as follows: hormonal responses do reflect the degree of surgical stress; the hormonal changes are transient, lasting no longer than 24 hours in patients after uncomplicated surgery; hormonal responses to minimal surgical stress are negligible.

Adult↗

PubMed1986

Improved survival rates of patients with acral lentiginous melanoma treated with hyperthermic isolation perfusion, wide excision, and regional lymphadenectomy.

Twenty-three patients with extremity malignant melanoma who fit the clinical and pathologic criteria for acral lentiginous melanoma were treated in a prospective, nonrandomized trial of wide local excision, regional lymphadenectomy, and hyperthermic isolation perfusion. There were 17 patients (73.9 percent) pathologically judged to be in stage I and 6 (26.1 percent) in stage II. Three patients entered the study with regional recurrence. Delay in diagnosis of the lesions averaged almost 3 1/2 years. Increasing awareness about the occurrence of acral lentiginous melanoma may result in earlier diagnosis, increased survival rates, and cure. Life table survival analysis revealed 5 and 10 year survival rates of 75 percent and 58 percent, respectively. This supports the findings of Krementz et al and suggests not only that a marked improvement in survival can be achieved through the use of hyperthermic isolation perfusion, but that the survival of patients with acral lentiginous melanoma is comparable with that of patients with other extremity malignant melanomas treated with aggressive multimodality therapy.

Actuarial Analysis↗

PubMed1986

Species variability in the cardiovascular and hematologic effects of zymosan-activated plasma infusion.

The anaphylatoxins have been implicated in the pathogenesis of endotoxin shock and the adult respiratory distress syndrome. Both endotoxin and zymosan activate the complement pathway. Because there are marked species differences in the cardiovascular and hematologic effects of endotoxin infusion, the purpose of this study was to compare the effects of zymosan-activated plasma (ZAP) infusion in dogs, sheep, and baboons. ZAP was infused (0.11 ml/kg/min for 60 min) into dogs (n = 5), baboons (n = 5), and sheep (n = 3). The infusion of ZAP resulted in significant changes in heart rate (HR) (P less than 0.03), mean arterial pressure (MAP) (P less than 0.002), pulmonary artery pressure (PAP) (P less than 0.004), cardiac index (CI) (P less than 0.034), and extra vascular lung water (EVLW) (P less than 0.001). A specific difference between the species' response to ZAP infusion was present when evaluating the effect of ZAP on MAP (P less than 0.02), HR (P less than 0.003). EVLW (P less than 0.001), platelet count (P less than 0.01), and white blood cell count (P less than 0.01). The main species differences in the changes in MAP, HR, and platelet count were an increase in MAP, decrease in HR, and decrease in platelet count that occurred in dogs. The species difference in the WBC count was the result of ZAP-induced neutropenia in sheep versus a leukocytosis in dogs. Unlike dogs and baboons, sheep developed an increase in EVLW. Like endotoxin, the cardiovascular and hematologic effects of ZAP infusion are species dependent.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1986

Is ileoproctostomy a reasonable procedure after total abdominal colectomy?

A 17-year study has been made of 63 patients who had a variety of colonic disorders treated by total abdominal colectomy with ileorectal anastomosis in four hospitals affiliated with Vanderbilt University. Forty-three of these patients made an uneventful recovery, but 20 others sustained significant complications, nine of which proved to be fatal (hospital mortality rate, 14%). The study shows (and confirms the work of others) that ileorectal anastomosis after total abdominal colectomy is a reasonable procedure that provides satisfactory results on a long-term basis in a majority of patients when strict criteria in patient selection are followed in its application.

Adult↗

PubMed1986

Hemorrhagic hypotension increases plasma beta-endorphin concentrations in the nonhuman primate.

The role which beta-endorphin plays in the pathogenesis of hemorrhagic hypotension is controversial. In the present experiment, 20 ml/kg of blood was bled from ten healthy male baboons (Papio anubis) over 60 min and then retransfused over the next 30 min. We found that the mean plasma beta-endorphin level increased 109% above baseline (p less than .05) within 15 min after starting hemorrhage, and rapidly returned to a baseline concentration with retransfusion. We conclude that in a primate species, circulating endogenous opioid peptide concentrations increase rapidly in response to sublethal hemorrhagic hypotension and normalize with restoration of the baseline intravascular volume. These findings support the concept that endogenous opioid peptides may mediate the hypotension of shock states.

Animals↗

PubMed1986

Nitrate in vegetables: estimation by HPLC.

Over the past fifty years the development of high-tech farming has led to excessive amounts of fertiliser being applied to soil. Some research aspects of this abuse are described in relation to the uptake of nitrate into vegetables. In order to monitor this problem a high precision HPLC method capable of rapid throughput has been evolved. Using this HPLC method the results over a twelve month period are presented and compared with the existing standards now legally enforced in Switzerland and Holland.

Chromatography, High Pressure Liquid↗

PubMed1986

Positive end-expiratory pressure increases plasma catecholamine levels in non-volume loaded dogs.

UNLABELLED: Positive end-expiratory pressure (PEEP) is commonly used in the treatment of critically ill patients whose sympathetic nervous system is stressed; however, PEEP's actions on sympathetic nervous system activity are unknown. We therefore measured the plasma noradrenaline response (an index of sympathetic nervous system activity) to graded doses of PEEP in nine mongrel dogs. After 30 minutes at each level of PEEP, plasma noradrenaline concentrations increased from baseline mean values of 300 (SD 108) pg/ml to 388 (SD 225) pg/ml (P less than 0.05) at 5 cm, 433 (SD 255) pg/ml (P less than 0.01) at 10 cm and 1194 (SD 882) pg/ml (P less than 0.01) at 20 cm water pressure of PEEP. The increases in plasma noradrenaline concentrations correlated inversely (r = -0.43, P less than 0.01) with PEEP-induced changes in cardiac output. Plasma adrenaline levels did not change significantly in response to 5 or 10 cm of PEEP; however, plasma adrenaline increased, while heart rate and mean arterial blood pressure fell, at 20 cm water pressure of PEEP (P less than 0.05). Within 15 minutes after discontinuation of PEEP, the plasma catecholamine concentrations returned to baseline levels. CONCLUSIONS: 1. PEEP significantly increases sympathetic nervous system activity in a rapid, dose-dependent, reversible manner; 2. the PEEP-induced increases in sympathetic activity may explain the reductions in organ blood flow which others have observed following the initiation of PEEP; 3. PEEP-related changes in sympathetic nervous system activity are a consequence of PEEP-induced reductions in cardiac output.

Animals↗

PubMed1986

The Beirut terrorist bombing.

The Beirut terrorist bombing on October 23, 1983, caused 234 immediate deaths and injured at least 112 survivors. Military medical records were available for each casualty; postmortem examination reports were available for each immediate fatality. This represented a unique opportunity to assess type, incidence, treatment, and outcome of neurological injuries suffered in a mass casualty terrorist bombing situation. Three categories of neurological injuries are described: head injuries, spine and spinal cord injuries, and peripheral nerve injuries. The following types and numbers of injuries occurred among the 112 immediate survivors of the explosion: 37 head injuries--28 concussions, 20 scalp lacerations, 13 skull fractures, 6 facial bone fractures, 4 cerebral contusions, 5 dural lacerations, 2 cerebrospinal fluid fistulas, and 2 intracerebral hematomas; 2 spine or spinal cord injuries--1 cervical and 1 thoracolumbar spine fracture associated with neurological deficit; and 9 peripheral nerve injuries--1 facial nerve palsy, 2 brachial plexus palsies, 1 median and 1 radial nerve palsy, and 4 peroneal nerve palsies. Among 234 immediate fatalities, the types and numbers of neurological injuries were: 167 head injuries--93 scalp lacerations, 85 skull fractures, and 24 facial bone fractures; and 22 spine and spinal cord injuries--15 cervical and 7 thoracolumbar fractures. Seven of the 112 immediate survivors died; 4 of these deaths were related to severe head injuries. The treatment and outcome of survivors with neurological injuries is briefly described. One-third of the immediate survivors who suffered either a scalp laceration or a concussion had a concomitant skull fracture.(ABSTRACT TRUNCATED AT 250 WORDS)

Blast Injuries↗

PubMed1985

Percutaneous subclavian catheterization for prolonged systemic chemotherapy.

Recent experience with 108 Broviac catheters was reviewed. Sixty-eight were percutaneously placed in the subclavian veins of adults receiving systemic chemotherapy. For subclavian catheters perioperative and late complications were unusual. There was no pneumothorax or serious bleeding associated with insertion, even in severely thrombocytopenic patients. Mean catheter life was 93 days. Infection occurred in only five cases (7%). We conclude that percutaneous placement of right atrial catheters is a safe procedure which provides reliable access for prolonged chemotherapy in cancer patients.

Adolescent↗

PubMed1985

Lidocaine inhibition of esophageal peristalsis and lower esophageal sphincter pressure in baboons.

Intravenous lidocaine was infused at 0.82 ml/min in a concentration of 1.2 mg/ml (2.3 mg/kg) for 120 min in awake chair-restrained baboons (Papio anubis), and measurements of esophageal peristalsis and LES pressure were compared before and after lidocaine or control infusions. Lidocaine produced a progressive and significant (P less than 0.05) decrease in amplitude in the peristaltic wave in the smooth muscle portion of the distal esophagus during the 120-min infusion. Lower esophageal sphincter pressure was similarly significantly lower than control after the infusion of lidocaine (P less than 0.05). Velocity and duration of the peristaltic wave were unchanged during the infusion. The decreased amplitude occurred during therapeutic and stable serum concentrations of lidocaine. It did not appear that the inhibitory effect of lidocaine was due to an induction of prostaglandin synthesis, because pretreatment of animals with indomethacin did not change the inhibitory effect of lidocaine, and serum metabolites of prostacyclin decreased during the infusion. Furthermore, the inhibitory effect of lidocaine was not topical. The response to the muscarinic agonist, bethanechol was similar in lidocaine-treated animals and control animals. The preservation of a bethanechol response after lidocaine inhibition of LES pressure and distal esophageal amplitude suggests that lidocaine acts proximal to the muscarinic receptor in the esophageal body and smooth muscle portion of the lower esophageal sphincter. This study suggests that lidocaine produces an inhibitory effect on the peristaltic wave and lower esophageal sphincter pressure that is similar to inhibitory effects described after anticholinergic agents and calcium channel blocking drugs, but intravenous lidocaine infusion requires a longer period of time to produce inhibition of muscle function.

Animals↗

PubMed1985

Diminished pressor response to exogenous norepinephrine and angiotensin II in septic, unanesthetized rats: evidence for a prostaglandin-mediated effect.

Despite elevated plasma concentrations of norepinephrine (NE), septic patients generally have normal or low mean arterial pressure (MAP) and systemic vascular resistance. We tested the hypothesis that sustained sepsis in rats results in relative hyporesponsiveness to the pressor actions of NE and angiotensin II (AII). Sprague-Dawley rats were studied 48 hr after sepsis was induced by cecal ligation. Sham-operated rats served as controls. Carotid artery and jugular venous catheters were placed under halothane anesthesia and the rats were allowed to waken fully in restraining cages. Peak increments in MAP were measured after bolus iv doses of NE (0.125-8.0 micrograms/kg) or AII (0.0125-0.5 microgram/kg). Some rats were pretreated with indomethacin (5 mg/kg, iv) 30 min prior to the dose-response study. Data were fitted to a two-parameter hyperbolic function and the resulting curves were compared by analysis of variance. Compared with controls, sepsis decreased the pressor response to both NE (P less than 0.0001) and AII (P less than 0.0001). Indomethacin restored responsiveness toward normal for both pressor agents (P less than 0.0001). It is concluded that sepsis is associated with hyporesponsiveness to two chemically dissimilar vasopressors and that this phenomenon may be mediated by prostaglandins.

Analysis of Variance↗

PubMed1985

The role of thromboxane in primate endotoxin shock.

UNLABELLED: Previous studies have suggested an important role of thromboxane (Tx) in the pathogenesis of endotoxin shock in the rat. The present study evaluated the role of thromboxane in an LD70 primate model of endotoxin shock by administering 6 mg/kg of endotoxin to three groups of animals that were pretreated with either saline (5 ml), OKY 1581 (2 mg/kg, 10 min prior), or imidazole (25 mg/kg/hr starting 30 min prior), groups I, II, and III, respectively. There were significant differences between the groups with respect to changes in MAP, PAP, and CO. OKY 1581 effectively blocked endotoxin-induced increase in plasma Tx. However, as a result of shunting of the endoperoxides into the prostacyclin pathway, there was a greater increase in plasma 6-keto PGF1 alpha, the stable hydrolysis product of prostacyclin. Imidazole augmented the formation of both prostacyclin and Tx. Despite the differences in plasma prostanoids, there was no difference between the groups with respect to changes in platelet or WBC counts, nor in survival: I (4/10); II (4/10); III (2/6). CONCLUSIONS: (i) endotoxin-induced neutropenia and decrease in the platelet count are not Tx mediated; (ii) Tx is not solely responsible for the decrease in CO during endotoxin shock; (iii) it is possible to prevent endotoxin-induced increase in the PAP by either blocking Tx formation or by increasing endogenous PGI2 production; and (iv) Tx may not be a major contributing factor in the mortality of endotoxin shock in baboons.

6-Ketoprostaglandin F1 alpha↗

PubMed1985

Synergistic effects of cyclic AMP and nerve growth factor on neurite outgrowth and microtubule stability of PC12 cells.

The outgrowth of neurites from rat PC12 cells stimulated by combined treatment of nerve growth factor (NGF) with cAMP is significantly more rapid and extensive than the outgrowth induced by either factor alone. We have compared the responses of PC12 cells under three different growth conditions, NGF alone, cAMP alone, and combined treatment, with respect to surface morphology, rapidity of neurite outgrowth, and stability of neurite microtubules, to understand the synergistic action of NGF and cAMP on PC12. Surface events at early times in these growth conditions varied, suggesting divergent pathways of action of NGF and cAMP. This suggestion is strongly supported by the finding that cells exposed to saturating levels of dibutyryl cAMP without substantial neurite outgrowth initiated neurites within 5 min of NGF. This response has been adopted as a convenient assay for NGF. Neurites that regenerated in the three growth conditions showed marked differences in stability to treatments that depolymerize microtubules. The results indicate that microtubules in cells treated with both NGF and cAMP are significantly more stable than in either growth factor alone. We suggest that a shift of the assembly equilibrium favoring tubulin assembly is a necessary prerequisite for the initiation of neurites by PC12.

Animals↗

PubMed1985

Plasma levels of 6-keto PGF1 alpha but not TxB2 increase in rats with peritonitis due to cecal ligation.

Acute, overwhelming sepsis or endotoxemia in experimental animals is associated with increased circulating levels of thromboxane (Tx)B2 (stable metabolite of TxA2) and 6-keto PGF1 alpha (stable metabolite of prostacyclin). The purpose of the present investigation was to determine the plasma prostanoid response to sepsis using an animal paradigm in which the septic process evolved more slowly than in previous similar studies. Bacterial peritonitis was induced in rats by cecal ligation (group B) or cecal ligation plus puncture with a 22-gauge needle (group C). Compared to sham-operated controls (group A), levels of immunoreactive 6-keto PGF1 alpha were significantly (p less than .05) elevated in group C rats at 6, 12, and 24 hr after surgery. At 48 hr after surgery, levels of this prostanoid were significantly (p less than .05) elevated in group B animals. In contrast, TxB2 levels were never significantly increased in septic (groups B and C) as compared to control (group A) rats. These data are consistent with results from several clinical studies and emphasize an important difference between the cecal ligation model and other experimental sepsis paradigms.

6-Ketoprostaglandin F1 alpha↗

PubMed1985

Hemodynamic and plasma catecholamine responses to epinephrine-containing perianal lidocaine anesthesia.

Despite the frequent use of large volumes (30-40 ml) of epinephrine-containing local anesthetic solutions for ano-rectal surgery, little is known about the anesthetic-induced hemodynamic consequences. Therefore, we measured the heart rate, blood pressure, and plasma catecholamine (norepinephrine and epinephrine) responses to the perianal injection of 40 ml of 0.5% lidocaine alone (n = 8) or 0.5% lidocaine with 1:200,000 epinephrine (n = 10) in 18 healthy adults undergoing outpatient ano-rectal surgery. The mean +/- SEM plasma epinephrine concentration increased from a baseline of 42 +/- 7 pg/ml to a peak of 622 +/- 94 pg/ml 4 min after injection of epinephrine-containing anesthetic (P less than 0.001), whereas lidocaine alone increased the mean plasma value from 36 +/- 9 pg/ml (baseline) to only 69 +/- 16 pg/ml (not significantly different) at its peak. Despite the increases in plasma epinephrine levels in the group receiving epinephrine-containing anesthesia, no changes in blood pressure, heart rate, or plasma norepinephrine levels were observed. Given the advantages (including prolongation of the duration of anesthesia) of adding epinephrine to perianal local anesthetics, our data support its safe use in healthy adults.

Adult↗

PubMed1984

Increased circulating plasma norepinephrine concentrations in noncardiac causes of pulmonary hypertension.

Sympathetic nervous system (SNS) activity and circulating norepinephrine (NE) levels may play roles in the elevated pulmonary vascular resistance (PVR) found in patients with pulmonary hypertension. To study the relationship between plasma NE levels, pulmonary NE metabolism, and pulmonary hypertension, we studied 9 patients, suspected of having noncardiac causes of pulmonary hypertension, before and after vasodilator therapy with phentolamine, nitroglycerin, isoproterenol, or hydralazine. Patients were admitted to the ICU and studied using pulmonary artery thermodilution catheters. Seven of 9 patients had noncardiogenic pulmonary hypertension whereas 2 patients did not have hemodynamic evidence of pulmonary hypertension. Simultaneous pulmonary and radial artery samples were analyzed for plasma NE and epinephrine (EPI) content before and after various vasodilator agents. Baseline pulmonary artery (PA) and radial artery NE concentrations correlated (r = .72) with PVR, PA pressures, and PA minus pulmonary capillary wedge (WP) pressures and were increased compared to the 2 patients with normal pulmonary pressures (p less than .01). The normal pulmonary extraction of circulating NE was absent in the 7 patients with pulmonary hypertension. PVR decreased significantly in all 7 patients with each vasodilator (p less than .05); however, the decrease was independent of any change in plasma NE concentration and therapy had no effect on the pulmonary extraction of circulating NE. These data indicate that elevations in plasma NE are coincident with the presence of noncardiogenic pulmonary hypertension and that acute pharmacologic reduction of PVR does not normalize the loss of pulmonary NE metabolism.

Adult↗

PubMed1984

Dexamethasone causes less steroid-induced alkalemia than methylprednisolone or hydrocortisone.

Corticosteroid-induced metabolic alkalemia is an important ICU problem because many of these patients may compensate by alveolar hypoventilation. The effects of 3 commonly used steroids on arterial pH, PaCO2, and serum bicarbonate concentrations were studied in 24 healthy male baboons randomly divided into 3 groups. Each group of 8 animals received 7-day dose-equivalent courses of either hydrocortisone (300 mg daily), methylprednisolone (60 mg daily), or dexamethasone (15 mg daily). Treatment with either hydrocortisone or methylprednisolone increased arterial pH (p less than .05) and serum bicarbonate levels (p less than .01) and the animals receiving hydrocortisone showed significant (p less than .05) compensatory alveolar hypoventilation. Dexamethasone therapy did not cause any of these steroid-induced changes.

Acid-Base Imbalance↗

PubMed1984

Sympathetic nervous system sensitivity to hemorrhagic hypotension in the subhuman primate.

The endogenous catecholamine response to hemorrhagic hypotension is poorly defined since most data have been derived from experiments in lower animal species. To clarify this situation we studied the plasma norepinephrine (NE) and epinephrine (Epi) responses to hemorrhagic hypotension in ten healthy male baboons (Papio anubis). After an overnight fast, animals were tranquilized with 100 mg of ketamine hydrochloride after which femoral artery and vein catheters were inserted. The animals then underwent phlebotomy of 20 ml/kg over 60 minutes with retransfusion of the autologous blood over the next 30 minutes. Plasma specimens for catecholamines were collected at 5, 15, 30, and 60 minutes during phlebotomy and again at 15 and 30 minutes during retransfusion. Plasma NE and Epi concentrations were measured by a radioenzymatic technique. Mean arterial blood pressure (MAP) decreased (p less than 0.01) and heart rate (HR) increased (p less than 0.01) within 15 minutes of phlebotomy, and these variables returned to baseline with retransfusion. Plasma NE and Epi levels increased (p less than 0.025) within 5 minutes of the onset of 'hemorrhage' and within 15 minutes plasma NE concentrations were 56% above baseline, whereas plasma Epi levels were six times greater than baseline. With retransfusion, plasma NE and Epi levels returned to baseline concentrations. We conclude: 1) in a primate species, the sympathetic nervous system responds rapidly to hemorrhage; 2) contrary to prior studies in rats, plasma NE increases as rapidly as Epi but not to the same degree; 3) plasma NE and Epi concentrations rapidly return to baseline levels with fluid resuscitation; and 4) there is little justification for the use of exogenous synthetic catecholamines in hemorrhagic hypotension where fluid resuscitation remains the treatment of choice.

Animals↗