PubMed Health⌕ Search

Biomedical subjects

P A Jackson

Publications and source records attributed to P A Jackson.

At least 19 recordsLinked to original sources
PubMed2001

Effect of vagal cooling on the counterregulatory response to hypoglycemia induced by a low dose of insulin in the conscious dog.

We previously demonstrated, using a nerve-cooling technique, that the vagus nerves are not essential for the counterregulatory response to hypoglycemia caused by high levels of insulin. Because high insulin levels per se augment the central nervous system response to hypoglycemia, the question arises whether afferent nerve fibers traveling along the vagus nerves would play a role in the defense of hypoglycemia in the presence of a more moderate insulin level. To address this issue, we studied two groups of conscious 18-h-fasted dogs with cooling coils previously placed on both vagus nerves. Each study consisted of a 100-min equilibration period, a 40-min basal period, and a 150-min hypoglycemic period. Glucose was lowered using a glycogen phosphorylase inhibitor and a low dose of insulin infused into the portal vein (0.7 mU.kg(-1) min(-1)). The arterial plasma insulin level increased to 15 +/- 2 microU/ml and the plasma glucose level fell to a plateau of 57 +/- 3 mg/dl in both groups. The vagal cooling coils were perfused with a 37 degrees C (SHAM COOL; n = 7) or a -20 degrees C (COOL; n = 7) ethanol solution for the last 90 min of the study to block parasympathetic afferent fibers. Vagal cooling caused a marked increase in the heart rate and blocked the hypoglycemia-induced increase in the arterial pancreatic polypeptide level. The average increments in glucagon (pg/ml), epinephrine (pg/ml), norepinephrine (pg/ml), cortisol (microg/dl), glucose production (mg.kg(-1). min(-1)), and glycerol (micromol/l) in the SHAM COOL group were 53 +/- 9, 625 +/- 186, 131 +/- 48, 4.63 +/- 1.05, -0.79 +/- 0.24, and 101 +/- 18, respectively, and in the COOL group, the increments were 39 +/- 7, 837 +/- 235, 93 +/- 39, 6.28 +/- 1.03 (P < 0.05), -0.80 +/- 0.20, and 73 +/- 29, respectively. Based on these data, we conclude that, even in the absence of high insulin concentrations, afferent signaling via the vagus nerves is not required for a normal counterregulatory response to hypoglycemia.

Animals↗
PubMed2000

Pathologic features of uterine leiomyomas following uterine artery embolization.

Bilateral uterine artery embolization has recently been employed as an alternative to operational treatment of uterine leiomyomas. The pathologic features induced by uterine artery embolization have not been previously described in detail. Usually patients experience symptomatic improvement with a reduction in size of the leiomyomas. This report describes the pathologic features in a series of 10 uterine leiomyomas where tissue was available for histologic examination following uterine artery embolization. Characteristic histologic features within the leiomyomas included massive necrosis, sometimes with dystrophic calcification, vascular thrombosis, and intravascular foreign material that elicited a histiocytic and foreign-body giant cell reaction. In some cases, intravascular foreign material was present elsewhere in the myometrium, the cervix, or paraovarian region. In occasional cases, there were foci of myometrial necrosis and microabscess formation beyond the confines of the leiomyomas. Foci of extrauterine inflammation were also occasionally identified. Histopathologists should be aware of these findings because the use of uterine artery embolization will possibly become more widespread in the future.

Adult↗
PubMed2000

Effect of hepatic denervation on the counterregulatory response to insulin-induced hypoglycemia in the dog.

Our aim was to determine whether complete hepatic denervation would affect the hormonal response to insulin-induced hypoglycemia in dogs. Two weeks before study, dogs underwent either hepatic denervation (DN) or sham denervation (CONT). In addition, all dogs had hollow steel coils placed around their vagus nerves. The CONT dogs were used for a single study in which their coils were perfused with 37 degrees C ethanol. The DN dogs were used for two studies in a random manner, one in which their coils were perfused with -20 degrees C ethanol (DN + COOL) and one in which they were perfused with 37 degrees C ethanol (DN). Insulin was infused to create hypoglycemia (51 +/- 3 mg/dl). In response to hypoglycemia in CONT, glucagon, cortisol, epinephrine, norepinephrine, pancreatic polypeptide, glycerol, and hepatic glucose production increased significantly. DN alone had no inhibitory effect on any hormonal or metabolic counterregulatory response to hypoglycemia. Likewise, DN in combination with vagal cooling also had no inhibitory effect on any counterregulatory response except to reduce the arterial plasma pancreatic polypeptide response. These data suggest that afferent signaling from the liver is not required for the normal counterregulatory response to insulin-induced hypoglycemia.

3-Hydroxybutyric Acid↗
PubMed1999

A comparison of thoracic and lumbar epidural techniques for post-thoracoabdominal esophagectomy analgesia.

PURPOSE: To compare thoracic epidural analgesia (TEA) using a bupivacaine/fentanyl mixture and lumbar epidural analgesia (LEA) with morphine, in respect to the time to extubation and the quality of post-operative analgesia, in patients having thoracoabdominal esophagectomy. METHODS: Twenty two patients scheduled for elective thoracoabdominal esophagectomy were randomized to TEA or LEA. Postoperatively, the TEA group received Patient Controlled Epidural Analgesia (PCEA) with bupivacaine 0.125% and 5 microg x ml(BI) fentanyl, and the LEA group received PCEA with 0.2 microg x ml(BI) morphine. A blinded observer assessed criteria for tracheal extubation and the time of tracheal extubation was recorded. Early extubation was defined as tracheal extubation within four hours postoperatively. Visual analogue pain scores at rest (Static Visual Analogue Pain Scores, SVAPS) and with movement (Dynamic Visual Analogue Pain Scores, DVAPS) were recorded at 1, 6, 12, 18 and 24 hr post-extubation. Failure of the epidural protocol (FEP) was defined as a request for additional analgesia. RESULTS: Tracheal extubation was achieved in 70% of the LEA and 100% of the TEA at four hours postoperatively (P=NS). However, the TEA group achieved earlier extubation times when assessed with log rank testing (P = 0.01). By six hours post-extubation FEP had occurred in 50% of the LEA group but in none of the TEA group (P = 0.01). Mean SVAPS and DVAPS were lower in the TEA than in the LEA group at all measured times (P < 0.01). CONCLUSION: This study has demonstrated superior pain control in patients undergoing thoraco-abdominal esophagectomy treated with TEA than with LEA, particularly for pain with movement. Tracheal extubation occurred earlier in the TEA group, but this difference was not significant at four hours postoperatively.

Adult↗
PubMed1999

Portal glucose infusion increases hepatic glycogen deposition in conscious unrestrained rats.

It has been demonstrated in the conscious dog that portal glucose infusion creates a signal that increases net hepatic glucose uptake and hepatic glycogen deposition. Experiments leading to an understanding of the mechanism by which this change occurs will be facilitated if this finding can be reproduced in the rat. Rats weighing 275-300 g were implanted with four indwelling catheters (one in the portal vein, one in the left carotid artery, and two in the right jugular vein) that were externalized between the scapulae. The rats were studied in a conscious, unrestrained condition 7 days after surgery, following a 24-h fast. Each experiment consisted of a 30- to 60-min equilibration, a 30-min baseline, and a 120-min test period. In the test period, a pancreatic clamp was performed by using somatostatin, insulin, and glucagon. Glucose was given simultaneously either through the jugular vein to clamp the arterial blood level at 220 mg/dl (Pe low group) or at 250 mg/dl (Pe high group), or via the hepatic portal vein (Po group; 6 mg. kg(-1). min(-1)) and the jugular vein to clamp the arterial blood glucose level to 220 mg/dl. In the test period, the arterial plasma glucagon and insulin levels were not significantly different in the three groups (36 +/- 2, 33 +/- 2, and 30 +/- 2 pg/ml and 1.34 +/- 0.08, 1. 37 +/- 0.18, and 1.66 +/- 0.11 ng/ml in Po, Pe low, and Pe high groups, respectively). The arterial blood glucose levels during the test period were 224 +/- 4 mg/dl for Po, 220 +/- 3 for Pe low, and 255 +/- 2 for Pe high group. The liver glycogen content (micromol glucose/g liver) in the two Pe groups was not statistically different (51 +/- 7 and 65 +/- 8, respectively), whereas the glycogen level in the Po group was significantly greater (93 +/- 9, P < 0.05). Because portal glucose delivery also augments hepatic glycogen deposition in the rat, as it does in the dogs, mechanistic studies relating to its function can now be undertaken in this species.

Animals↗
PubMed1998

Memory for duration: role of hippocampus and medial prefrontal cortex.

In this task rats had to learn that a three-dimensional object stimulus (a rectangle) that was visible for 2 s would result in a positive (go) reinforcement for one object (a ball) and no reinforcement (no go) for a different object (a bottle). However, if the rectangle stimulus was visible for 8 s then there would be no reinforcement for the ball (no go), but a reinforcement for the bottle (go). After rats learned this conditional discrimination by responding differentially in terms of latency to approach the object, they received large (dorsal and ventral) lesions of the hippocampus, lesions of the medial prefrontal cortex (anterior cingulate and precentral cortex), lesions of the cortex dorsal to the dorsal hippocampus, or served as sham-operated controls. Following recovery from surgery they were retested. The results indicate that there were major impairments following hippocampal lesions, in contrast to cortical control and medial prefrontal cortex lesions, as indicated by smaller latency differences between positive and negative trials on postsurgery tests. In order to ensure that the deficits observed with hippocampal lesions were not due to a discrimination problem, new rats were trained in an object (gray cylinder) duration discrimination task. In this go/no go procedure, the rats were reinforced for a 2-s exposure (duration) of the gray cylinder, but not a 10-s duration, or vice versa. The results indicate that after hippocampal lesions, there was an initial deficit followed by complete recovery. There were no significant changes for the medial prefrontal, cortical control, or sham-operated animals. It appears that the hippocampus, but not the medial prefrontal cortex, is actively involved in representing in short-term memory temporal attribute information based on the use of markers for the beginning and end of the presence (duration) of a stimulus (object).

Animals↗
PubMed1997

Inhibition of glycogenolysis enhances gluconeogenic precursor uptake by the liver of conscious dogs.

We investigated the effect of inhibiting glycogenolysis on gluconeogenesis in 18-h-fasted conscious dogs with the use of intragastric administration of BAY R 3401, a glycogen phosphorylase inhibitor. Isotopic ([3-3H]glucose and [U-14C]alanine) and arteriovenous difference methods were used to assess glucose metabolism. Each study consisted of a 100-min equilibration, a 40-min control, and two 90-min test periods. Endogenous insulin and glucagon secretions were inhibited with somatostatin (0.8 microgram.kg-1.min-1), and the two hormones were replaced intraportally (insulin: 0.25 mU.kg-1.min-1; glucagon: 0.6 ng.kg-1.min-1). Drug (10 mg/kg) or placebo was given after the control period. Insulin and glucagon were kept at basal levels in the first test period, after which glucagon infusion was increased to 2.4 ng.kg-1.min-1; BAY R 3401 decreased tracer-determined endogenous glucose production [rate of glucose production (Ra): 14 +/- 1 to 7 +/- 1 mumol.kg-1.min-1] and net hepatic glucose output (11 +/- 1 to 3 +/- 2 mumol.kg-1.min-1) during test 1. It increased the net hepatic uptake of gluconeogenic substrates from 9.0 +/- 2.0 to 11.6 +/- 0.6 mumol.kg-1.min-1. Basal glycogenolysis was decreased by drug (9.1 +/- 0.7 to 1.5 +/- 0.2 mumol glucosyl U.kg-1.min-1). Placebo had no effect on Ra or the uptake of gluconeogenic precursors by the liver. The rise in glucagon increased Ra by 22 +/- 3 and by 8 +/- 2 mumol.kg-1.min-1 (at 10 min) in placebo and drug, respectively. The rise in glucagon caused little change in the net hepatic uptake (mumol.kg-1.min-1) of gluconeogenic substrates in placebo (8.2 +/- 0.6 to 9.0 +/- 1.0) but increased it markedly (11.6 +/- 0.6 to 15.4 +/- 1.0) in drug. Glucagon increased glycogenolysis by 22.1 +/- 2.5 and by 7.8 +/- 1.6 mumol.kg-1.min-1 in placebo and drug, respectively. The amount of glycogen (mumol glucosyl U/kg) synthesized from gluconeogenic carbon was four times higher in drug (48.6 +/- 9.7) than in placebo (11.3 +/- 1.7). We conclude that BAY R 3401 caused a marked reduction in basal and glucagon-stimulated glycogenolysis. As a result of these changes, there was an increase in the net hepatic uptake of gluconeogenic precursors and in glycogen synthesis.

Analysis of Variance↗
PubMed1997

Effects of vagal blockade on the counterregulatory response to insulin-induced hypoglycemia in the dog.

Our aim was to determine whether vagal transmission is required for the hormonal response to insulin-induced hypoglycemia in 18-h-fasted conscious dogs. Hollow coils were placed around the vagus nerves, with animals under general anesthesia, 2 wk before an experiment. On the day of the study they were perfused with -15 degrees C ethanol for the purpose of blocking vagal transmission, either coincident with the onset of insulin-induced hypoglycemia or after 2 h of established hypoglycemia. In a separate study the coils were perfused with 37 degrees C ethanol in a sham cooling experiment. The following parameters were measured: heart rate, arterial plasma glucose, insulin, pancreatic polypeptide, glucagon, cortisol, epinephrine, norepinephrine, glycerol, free fatty acids, and endogenous glucose production. In response to insulin-induced hypoglycemia (42 mg/dl), plasma glucagon peaked at a level that was double the basal level, and plasma cortisol levels quadrupled. Plasma epinephrine and norepinephrine levels both rose considerably to 2,135 +/- 314 and 537 +/- 122 pg/ml, respectively, as did plasma glycerol (330 +/- 60%) and endogenous glucose production (150 +/- 20%). Plasma free fatty acids peaked at 150 +/- 20% and then returned to basal levels by the end of the study. The hypoglycemia-induced changes were not different when vagal cooling was initiated after the prior establishment of hypoglycemia. Similarly, when vagal cooling occurred concurrently with the initiation of insulin-induced hypoglycemia (46 mg/dl), there were no significant differences in any of the parameters measured compared with the control. Thus vagal blockade did not prevent the effect on either the hormonal or metabolic responses to low blood sugar. Functioning vagal afferent nerves are not required for a normal response to insulin-induced hypoglycemia.

Animals↗
PubMed1996

Efficacy of arthroscopic surgery and midlaser treatments for chronic temporomandibular joint articular disc derangement following motor vehicle accident.

As a result of motor vehicle accident soft-tissue injury, temporomandibular joint articular disc derangement may develop and persist despite symptomatic treatment and medication. This study reports the effectiveness of management directed at controlling the TMJ and masticatory neuromuscular pain dysfunction with a TMJ/interocclusal stabilization appliance, specific biofeedback and ultrasound therapy. Following these conservative measures residual articular disc derangement was present in some subjects who were offered arthroscopic surgery and infrared midlaser with TMJ/occlusal stabilization. Twenty subjects with residual disc derangement were randomly selected into two groups with and without arthroscopic surgery, and analyses of variance made before treatment, 12 months after conservative procedures, 3 months following arthroscopic surgery and midlaser therapy and 3 years since commencement of management. Dependent variables compared were pain-discomfort, Clinical Dysfunction Index, articular disc derangement and maximal voluntary jaw opening. Conservative management alone provided significant reduction of pain-discomfort and clinical dysfunction, while arthroscopic surgery resulted in significant reduction in articular disc derangement. The midlaser with TMJ/occlusal stabilization maintained significant improvement in the variables (p < 0.01) for both groups. The common articular deviations in form found at arthroscopy were soft tissue alteration with hyperaemia, synovitis, synovial membrane and posterior attachment folding with connective tissue hyperplasia, and disc displacement with fibrous adhesions. The Global Status Score of pain behaviour compared with residual function, confirmed the presence of greater pain before treatment commenced.

Accidents, Traffic↗
PubMed1996

Lymphocyte subset infiltration patterns and HLA antigen status in colorectal carcinomas and adenomas.

Fifty eight large bowel adenocarcinomas and 20 adenomas were studied immunohistochemically, using fresh frozen tissue sections, with regard to lymphocyte subpopulations (CD3, CD4, CD8, CD19, and CD20) in the inflammatory infiltrate and to expression of human leucocyte antigens (HLA-ABC, HLA-A2, and HLA-DR). The findings were related to differentiation and Duke's stage of carcinoma. The inflammatory infiltrate was found to have a phenotype that remained constant irrespective of the intensity of the inflammation. CD4 and CD3 positive cells predominated with fewer CD8 positive cells and a scanty diffuse CD19/20 positive cell population. CD19/20 follicular aggregates were common at the advancing margin of the carcinomas. There was no significant association with Duke's stage, differentiation or HLA status. HLA changes (ABC loss, A2 loss, and DR gain) were associated with differentiation, being more common and more extensive in poorly differentiated carcinomas. HLA-A2 loss was also associated with stage of progression of carcinoma. Inflammation associated with adenomas was found to have a similar phenotype to that associated with carcinomas. HLA changes in adenomas were uncommon, being seen in only one of our 20 cases.

Adenocarcinoma↗
PubMed1995

Lobular carcinoma of the breast: cytological features supporting the diagnosis of lobular cancer.

Lobular carcinomas have a distinct natural history with a better response to endocrine therapy and a higher incidence of local recurrence and are more often bilateral. The cytological diagnosis of lobular carcinoma permits a discriminating therapeutic approach with pre-operative Tamoxifen, more generous resection margins, and assessment of the contralateral breast. The cytological features of lobular cancer however are not well defined and the low cell yield from such neoplasms can result in a high false negative rate. To determine whether we could improve the pre-operative diagnosis, we reviewed the cytological features of 112 lobular carcinomas. They had small uniform sized nuclei with irregular outlines and inconspicuous nucleoli. The degree of dissociation was similar to duct carcinomas and the incidence of inadequate aspirates was no higher. We found no features that confidently diagnosed lobular cancer or its sub-types. However, using a combination of features, typing of lobular cancer on aspirated material is possible and should be attempted.

Biopsy, Needle↗
PubMed1995

Relation between stage, grade, proliferation, and expression of p53 and CD44 in adenomas and carcinomas of the colorectum.

AIMS: To investigate the changes in and relations among p53, CD44 and MIB-1 expression in adenocarcinomas of the colorectum and to determine whether these changes are progressive across the adenoma-carcinoma sequence. METHODS: Expression of p53 protein, CD44 adhesion molecule and MIB-1 proliferation antigen was detected using immunohistochemistry in 68 colorectal carcinomas and 32 colorectal adenoma. The staining characteristics were compared with degree of dysplasia in adenomas, and differentiation and Dukes' stage in carcinomas. Results were analysed and assessed using Spearman's rank correlation and independent t tests. RESULTS: p53 staining was present in som adenomas and correlated with the degree of dysplasia. There was significantly more staining in carcinomas than adenomas and significant correlation between staining and Dukes' stage. CD44 staining was maximal in adenomas, diminished in carcinomas and was minimal in metastasising carcinomas. There was inverse correlation between p53 and CD44 expression across the adenoma-carcinoma-metastasising carcinoma sequence. MIB-1 expression was highest in carcinomas but did not correlate with either p53 or CD44 expression. CONCLUSIONS: There are progressive changes in p53, CD44 and MIB-1 expression in adenomas and carcinomas. A combination of these tests may prove useful in assessing which patients with adenomas are at greatest risk of progressing to carcinoma.

Adenocarcinoma↗
PubMed1994

Prognostic value of cytological grading of fine-needle aspirates from breast carcinomas.

Because neoadjuvant therapy, including preoperative chemotherapy and tamoxifen, is becoming increasingly common for early breast cancer, it is desirable to grade tumours before surgery so that the most appropriate medical regimen can be selected. We have used a cytological grading system for ductal carcinoma of type not otherwise specified (NOS). Wet-fixed Papanicolaou-stained breast aspirates are examined for the extent of cell dissociation, cell size and uniformity, and the appearance of nucleoli, the nuclear margin, and chromatin. 377 invasive breast carcinomas were removed after preoperative diagnostic fine-needle aspiration cytology (FNAC) during the 25 months of the study. 286 tumours were ductal carcinomas NOS on histology. We established three cytological grades and found that cytological grade corresponded well with the established histological grades (Elston's modified Bloom and Richardson method). All cytological features included in the score were equally important on regression analysis. This study shows that grading of breast cancer on FNAC is feasible and reproducible. Cytological grade may substitute for histological grade, so a combination of FNAC and mammography can provide information on tumour type, grade, and size before surgery. We recommend this grading system to centres that use FNAC for the diagnosis of breast cancers.

Biopsy, Needle↗