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Biomedical subjects

J L Ferguson

Publications and source records attributed to J L Ferguson.

At least 55 records · Page 3Linked to original sources

Spontaneous perseverative turning in rats with radiation-induced hippocampal damage.

This study found a new behavioral correlate of lesions specific to the dentate granule cell layer of the hippocampus: spontaneous perseverative turning. Irradiation of a portion of the neonatal rat cerebral hemispheres produced hypoplasia of the granule cell layer of the hippocampal dentate gyrus while sparing the rest of the brain. Radiation-induced damage to the hippocampal formation caused rats placed in bowls to spontaneously turn in long, slow bouts without reversals. Irradiated subjects also exhibited other behaviors characteristic of hippocampal damage (e.g., perseveration in spontaneous exploration of the arms of a T-maze, retarded acquisition of a passive avoidance task, and increased horizontal locomotion). These data extend previously reported behavioral correlates of fascia dentata lesions and suggest the usefulness of a bout analysis of spontaneous bowl turning as a measure of nondiscrete-trial spontaneous alternation and a sensitive additional indicator of radiation-induced hippocampal damage.

Animals↗

Choanal atresia: treatment trends in 47 patients over 33 years.

From 1977 through 1985, 11 patients underwent surgical correction of choanal atresia. This group brings the total number of patients corrected at our institution since 1951 to 47. This review compares treatment and outcome in the most recent group with the previous series of 36 patients. Eight patients were female and three were male; their ages at the time of surgical treatment ranged from 1 day to 19 years. The atresia was bilateral in five patients and unilateral in six. Six patients had other physical or mental developmental problems. Mean follow-up was 5.6 years (range, 2 to 10 years). All five patients who had transnasal puncture as primary treatment required reoperation; this is a higher incidence of failure than in the previous group. None of the three patients who had transpalatal procedures needed further operation. In two of the eight patients who had transseptal repair, restenosis developed.

Adolescent↗

Splanchnic blood flows in a rat model of antibiotic-controlled intra-abdominal abscess during normoxia and hyperoxia.

We have characterized splanchnic blood flows in a rat model of antibiotic-controlled, intra-abdominal abscess (ACIA) in normoxic and hyperoxic environments. Abscesses (1.5 ml average volume) were established by implanting a fecal-agar pellet containing known numbers and strains of live Escherichia coli and Bacteroides fragilis into the peritoneal cavity of rats via a midline incision. Sham-operated rats (SR) served as controls. Cannulas (PE-50) were placed into the left ventricle of both SR and ACIA rats for injection of tracer microspheres (MS) and into the tail artery for a reference withdrawal site. Blood flow measurements were made in conscious unrestrained rats before, during, and after hyperoxic exposure by using MS labelled with either 51Cr or 85Sr or 141Ce. No change in cardiac output (CO), heart rate (HR), or mean arterial pressure (MAP) was seen between ACIA and SR groups. The administration of hyperoxia diminished the fractional distribution of CO to the liver (portal), stomach, cecum, colon, and pancreas in both groups. The percent CO to the liver (arterial), small intestine, and spleen did not change in either group. The blood flow to all splanchnic organs, except liver (arterial), was diminished during hyperoxia in both groups and recovered after hyperoxia. In conclusion, central hemodynamics and splanchnic blood flows are not altered by the presence of a large intra-abdominal abscess controlled by antibiotics. Splanchnic blood flows are diminished by hyperoxia.

Abscess↗

Naloxone alters organ perfusion during endotoxin shock in conscious rats.

Antagonism of endogenous opioids has been shown to improve survival time, increase blood pressure, and attenuate acidosis during endotoxin shock. However, some of the most severe problems associated with this condition arise from the circulatory disturbances that occur. We investigated the circulatory effects of naloxone during endotoxin shock as they relate to hemodynamic parameters in conscious, unrestrained rats. Blood flow and hemodynamic variables were measured in male, Sprague-Dawley rats (300-400 g) 24 h after surgical preparation. Rats were challenged with either 10 mg/kg Escherichia coli endotoxin (100% lethal dose) or intravenous saline. Measurements were made at 0, 10, 30, and 60 min postchallenge. Naloxone (2 mg/kg) or saline was given as a treatment (intravenous bolus) at 25 min postchallenge. Cardiac output and blood distribution (%CO) and flow were measured with radiolabeled microspheres. Cardiac output was depressed and total peripheral resistance was elevated 10 min into endotoxin shock. Naloxone treatment improved blood pressure significantly during endotoxin shock, as would be expected with the observed increase in total peripheral vascular resistance and no significant change in cardiac output. Improved perfusion of skeletal muscle is a likely explanation for lower serum lactate levels that have been reported to occur in this model after naloxone administration. Our data also indicate that naloxone may improve cardiac efficiency and does not interfere with maintenance of global cerebral blood flow. Collectively, these effects would contribute to the observed improved survival time after naloxone treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗

The effects of sinus bacteria on human ciliated nasal epithelium in vitro.

The mechanisms by which bacteria colonize and damage ciliated epithelium are important in understanding the pathophysiology of rhinitis, sinusitis, and otitis. Bacteria that have the ability to impair mucociliary clearance would be at an advantage in establishing infection of ciliated surfaces. This study investigates the effect of Hemophilus Influenzae, Streptococcus pneumoniae, Branhamella catarrhalis, and Staphylococcus epidermidis on the ciliary activity of normal ciliated nasal epithelium in human beings. Ciliary activity of the nasal epithelium in the presence of each pathogen was assessed for more than 240 minutes with a photometric method of ciliary beat frequency (CBF) measurement. H. influenzae exerted significant effects on ciliary activity, with a 46% decrease in the CBF by 4 hours (with bacteria-containing broth) and a 32% decrease with bacteria-free filtrate. S. epidermidis decreased CBF by 44% with the bacterial broth. A sterile cell-free filtrate had no significant effect. S. pneumoniae and B. catarrhalis had no significant effect on CBF within a 240-minute period. H. influenzae and S. epidermidis disrupted normal synchronous ciliary motion, causing adjacent cilia to beat at different rates.

Bacterial Physiological Phenomena↗

Total pharyngolaryngectomy and cervical esophagectomy with jejunal autotransplant reconstruction: complications and results.

Eighteen patients underwent pharyngoesophageal reconstruction with a free jejunal autotransplant in a one-stage procedure after circumferential resection for cancer of the pharynx and cervical esophagus. Of these, six had minor complications (fistulas) and six had major complications including abdominal bleeding, cervical bleeding, graft failure, and one surgical death. The mean survival was 427 days after resection and reconstruction (range, 120 to 866 days). Ten patients died of their disease, and four died of other causes. The site of failure was local in five and distant in five. In view of this high complication rate and unimpressive survival rate, the use of other lower-morbidity reconstructive options or staged procedures may need to be considered in poor surgical candidates.

Adult↗

Effect of naloxone on regional cerebral blood flow during endotoxin shock in conscious rats.

Maintenance of cerebral blood flow (CBF) is vital during cardiovascular shock. Since opioids have been implicated in the pathophysiology of endotoxin shock and have been shown to alter cerebral perfusion patterns, we determined whether opioids were responsible for any of the changes in regional CBF observed during endotoxin shock and whether the use of naloxone might impair or aid in the maintenance of CBF. When blood flow (BF) is studied with microspheres in rats, the left ventricle of the heart is often cannulated via the right carotid artery. Questions have arisen concerning the potential adverse effects of this method on CBF in the hemisphere ipsilateral to the ligated artery. We measured right and left regional CBF by use of this route of cannulation. Twenty-four hours after cannulations were performed, flow measurements were made using radiolabeled microspheres in conscious unrestrained male Sprague-Dawley rats (300-400 g) before and 10, 30 and 60 min after challenging with 10 mg/kg Escherichia coli endotoxin (etx) or saline. Naloxone (2 mg/kg) or saline was given as a treatment 25 min post-etx. We found no significant differences between right and left cortical, midbrain, or cerebellar BF at any time in any treatment group. After etx, the whole brain received a large share of the depressed cardiac output. Thus global CBF was not significantly reduced below its pre-etx value, an effect unaltered by naloxone. Regionally, BF was reduced to cerebellum and midbrain by 30 min post-etx. Naloxone prevented this depression. No region was affected to a greater or lesser degree than others.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Measurement of myocardial blood flow by ultrafast computed tomography.

Myocardial blood flow was analyzed by radioisotope-labeled microspheres and ultrafast computed tomography (CT) in 16 closed-chest, anesthetized dogs. The first set of 10 dogs had CT and microsphere measurements before and after chromonar-induced increases in myocardial blood flow. A second set of six dogs had flows measured at control and during temporary reductions in regional flow produced by balloon cuff occlusion of the left anterior descending coronary artery. All dogs had four-slice, 20-instance CT scans after injection of a medium bolus (0.35 ml/kg) of contrast medium into a femoral vein simultaneous with injection of microspheres into the left atrium. CT myocardial flow was calculated as the change in myocardial CT numbers divided by the area from a blood pool time-density curve. A wide range of myocardial blood flows was produced as determined by microspheres (0 to 6.7 ml/min/g). Global flow of the first set of dogs was shown to have excellent correlation (r = .95, n = 17) for a limited range (.4 less than X less than 1.4 ml/min/g) of flows. Regional flows of these measurements demonstrated less correlation (r = .63, n = 110) but extended the range of flow to 1.7 ml/min/g. At higher flows (greater than 2.5 ml/min/g) the correlation for global and regional flows was not significantly different than zero. Regional ischemic flow correlation extended the linear range of flow to 0 ml/min/g (r = .62, n = 17). These results show that CT can measure myocardial blood flow over a limited but clinically relevant range of flows defined as slightly above normal to ischemic. These results indicate that another preparation of CT flow measurement must be sought for quantification of myocardial perfusion values significantly above normal.

Animals↗

Respiratory compensation and acidosis in endotoxin shock: effects of naloxone in conscious rats.

Naloxone treatment of endotoxin shock has been shown to alter many cardiovascular parameters. However, since opioids can affect ventilatory function we thought it important to assess the effects of naloxone on some respiratory variables during endotoxin shock. Male Sprague-Dawley rats (300-400 g) were surgically prepared with carotid artery and jugular vein cannulas 24 hours before experiments were begun. Conscious, unrestrained rats were challenged with 10 mg/kg E. coli endotoxin or saline. Measurements of blood gases, pH, respiratory rate, serum lactate, and medullary/pontine blood flow (radio labelled microsphere method) were made 0, 10, 30, and 60 minutes postchallenge. Rats were treated with either 2 mg/kg naloxone or saline at 25 minutes postchallenge. Arterial PO2 rose and PCO2 fell in a stepwise fashion in saline-treated endotoxic rats. These changes were unrelated to medullary/pontine perfusion or to arterial pH (up to 30 minutes postchallenge). In naloxone-treated endotoxic rats the increased ventilatory drive at 60 minutes was attenuated, apparently as a result of prevention of acidosis at this time. These data further support uncoupling of ventilatory drive and arterial pH reported earlier and also indicate that naloxone's ability to prevent acidosis in these animals is not mediated through respiratory compensation.

Acid-Base Equilibrium↗

Characterization of plasmids conferring resistance to gentamicin and apramycin in strains of Salmonella typhimurium phage type 204c isolated in Britain.

In Salmonella typhimurium phage type 204c isolated in Britain, gentamicin resistance is specified by plasmids of the I1 compatibility group which also confer resistance to apramycin. These plasmids have been subdivided into three types within the I1 group on the basis of their antibiotic resistance specificity, their ability to produce colicin Ib and their restriction enzyme digest fragmentation patterns. All three have been identified in strains from cattle, but as yet only two types have been found in strains from humans. It is suggested that the use of apramycin in animal husbandry is responsible for the appearance of gentamicin resistance in multiresistant strains of phage type 204c, a phage type already epidemic in bovine animals and with an increasing incidence in humans.

Acetyltransferases↗

Effect of chemical sympathectomy with oxidopamine on systemic blood flow in rats with acute pancreatitis.

In response to previous demonstrations that either surgical or chemical sympathectomy can ameliorate the severity of acute experimental pancreatitis, and suggestions that the benefits of sympathectomy are related to alterations in the absolute blood flow or the pattern of blood flow within the pancreas or splanchnic organs, we studied blood flow in rats with acute deoxycholate pancreatitis. The animals had preliminary chemical sympathectomy with a false neurotransmitter (oxidopamine) prior to the experiment and were studied for 120 min after the onset of pancreatitis. All animals with pancreatitis had a fall in cardiac output by 120 min but maintained blood flow to the heart and brain by increasing the percent of cardiac output to these organs. Despite a 61% decrease in cardiac output, at 120 min the chemical sympathectomy group showed an increase in the percentage of flow within the pancreas. However, there was no change in the absolute organ blood flow in any group except at the 10 min measurement, when the pancreata showed an absolute increase in all groups. This study does not support the concept that chemical sympathectomy is beneficial in acute pancreatitis but does indicate a specific and possibly beneficial effect on the distribution of pancreatic blood flow. The decreased cardiac output after chemical sympathectomy is a clear disadvantage of this mode of treatment and probably disqualifies systemic chemical sympathectomy as a treatment consideration.

Acute Disease↗

The cerebral circulatory response during canine anaphylactic shock.

Radiolabeled microspheres were employed to measure the cerebrovascular response to severe anaphylactic-induced hypotension in pentobarbital-anesthetized dogs. A rapid drop in mean arterial pressure (MAP, 140 to below 50 mm Hg) coincided with total and regional cerebral blood flows (CBF) that were not significantly different from prechallenge values. While blood flow to the occipital region (highest measured region of the brain) was significantly greater than that of brainstem regions prior to and during the shock regimen, no major redistributional phenomena occurred to any cerebral region. These findings were in contrast with other reports that demonstrated a loss in CBF and a redistribution of regional CBF as perfusion pressures declined below 55 to 60 mm Hg. To investigate whether the maintenance of CBF during severe anaphylactic hypotension was associated with cerebral hypoxia or hypercapnia, we employed in a second group of dogs the technique of venous drainage from the confluens sinus, so that the cerebral arterial-venous difference for blood gases and other blood components could be determined. Similar to our previous findings, CBF was maintained to perfusion pressures of 39 +/- 4 mm Hg. The drop in cerebral vascular resistance during the severe hypotensive period was not associated with a significant decline in arterial PO2, or a significant increase in arterial PCO2, A-V PO2, or V-A PCO2. Our results suggest that the fall in cerebral vascular resistance during anaphylactic-induced hypotension would not be associated with a severely altered cerebral metabolism.

Anaphylaxis↗

Determination of cardiac output by ultrafast computed tomography.

Three methods of determining cardiac output were compared in six anesthetized dogs (23-28 kg) for the purpose of evaluating the ability of ultrafast computed tomography to measure cardiac output at three points of the circulation: pulmonary artery, left ventricle, and descending aorta. Computed tomography cardiac output is calculated by indicator dilution analysis of an iodinated contrast bolus time-density curve. Computed tomography cardiac output was compared to thermodilution and radioactive microsphere cardiac output methods. The results show very good agreement between thermodilution and computed tomography methods (r = .90) and good agreement between microsphere and computed tomography (r = .88). Comparison of computed tomography cardiac output measurements from the left ventricle and pulmonary artery was excellent (r = .99), as were measurements from the left ventricle and descending aorta (r = .97). This study also showed minimal interlevel scan-density response variability (3%) and minimal variability between experiments (7%). Therefore, it is concluded that cardiac output can be accurately measured at many points in the blood pool by ultrafast computed tomography.

Animals↗

Increasing incidence of resistance to gentamicin and related aminoglycosides in Salmonella typhimurium phage type 204c in England, Wales and Scotland.

Phage type 204c of Salmonella typhimurium (DT 204c) appeared in bovine animals in 1979. It is now the predominant type in cattle in England, Wales and Scotland and ranks in the 10 most common phage types in humans. All strains of DT 204c have been resistant to at least four antimicrobial drugs. In 1979 and 1980 the most common resistance pattern was that of chloramphenicol, streptomycin, sulphonamides, tetracyclines and trimethoprim (CSSuTTm) but since 1981 strains with additional resistance to ampicillin and neomycin-kanamycin (AK) have predominated. Strains resistant to furazolidone (Fu) have caused sporadic outbreaks. Gentamicin resistance (G) appeared in DT 204c in 1983 and gentamicin-resistant strains are increasing in incidence. With the exception of resistance to furazolidone, drug resistance in DT 204c has been plasmid-mediated. Characterisation of gentamicin resistance plasmids in DT 204c of R-type ACGKSSuTTm has demonstrated the existence of three distinct lines, two of which have been found exclusively in cattle and one in cattle and humans. The misguided and often inappropriate use of antimicrobial drugs in calves has contributed to the appearance of multiresistant strains of DT 204c and positive measures to limit range and levels of antimicrobials available to feed manufacturers may be necessary.

Aminoglycosides↗

The effects of acute and chronic morphine on regional distribution of cardiac output in brain.

Both acute and chronic administration of morphine resulted in an increase in the percent cardiac output received by brain. However, various brain regions were affected differently by the drug treatments. The greatest increases in percent cardiac output received after chronic administration of morphine occurred in pons and cerebellum, while the greatest increases after acute administration occurred in cortex and midbrain. The changes found are in contrast with earlier studies which suggest that morphine has no effect on cerebral blood flow.

Animals↗

Hemodynamic and regional circulatory alterations in dog during anaphylactic challenge.

Microspheres were employed to measure the cardiac output (CO), percent distribution of CO (%CO), and blood flow (BF) to various tissues in the dog during anaphylactic shock. Five minutes after challenge there was a 66 and 83% drop from control for mean arterial pressure and CO, respectively. Arterial glucose and lactic acid rose 62 and 537%, respectively. Furthermore, there was a narrowing of the systemic arteriovenous difference for PO2 and a widening of the venoarterial difference for PCO2. Pressure compensation toward control values began 5 min postchallenge and continued through 180 min. Circulatory perturbations during severe hypotension (less than mmHg) included depressed %CO and BF to the pancreas and spleen and elevated %CO to the brain and adrenals. Cerebral and adrenal BF remained unchanged at this period. BF to the kidneys, liver (hepatic artery), and gastrointestinal tract dropped markedly as a function of increased peripheral resistance and decreased CO. As cardiac performance improved, blood flow to the pancreas, spleen, liver, diaphragm, and gastrointestinal tissues returned toward control but was elevated to the adrenals and decreased to the brain.

Acid-Base Equilibrium↗