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Biomedical subjects

D Johnston

Publications and source records attributed to D Johnston.

At least 181 records · Page 10Linked to original sources
PubMed1994

Secretory and absorptive activity of oesophageal epithelium: evidence of circulating mucosubstances.

The space between the oesophageal basal and prickle epithelial cells appears empty by standard ultrastructural preparative techniques. Fixation of human oesophageal biopsies with a variety of agents, including tannic acid, glutaraldehyde-lysine, cetylpyridinium chloride and Ruthenium Red shows that this space is filled with mucosubstances, some free, some attached to the cells as a glycocalyx. There is evidence that this material is secreted constitutively by the basal and prickle cells. This secretion may be changed or blocked by incubating oesophageal biopsies in the presence of colchicine or dinitrophenol. Incubation at 16 degrees C has the same effect. Absorption from the intercellular space may be followed using the fluid phase marker, horseradish peroxidase. Early endosomes may also be shown by their acid phosphatase activity. Incubation of biopsies at 20-22 degrees C allows early endosomes to accumulate material, but not pass it on the late endosomes.

Absorption↗
PubMed1994

Image analysis of the distribution of intraperitoneally administered fluids in patients with ovarian cancer.

Patients are selected for intraperitoneal chemotherapy based on the condition of the peritoneal cavity and the volume of residual disease, as determined by second-look surgery. Several techniques have been described to assess the distribution of intraperitoneal fluids. They rely on point, as opposed to area, measurements. We performed serial radionuclide scans of 15 patients undergoing intraperitoneal chemo for ovarian cancer. Scans were performed following intraperitoneal administration of 500-1000 ml of 99Tc-labeled human serum albumin in normal saline. Each patient underwent three scans at least 4 weeks apart. Radionuclide scans were digitized for computerized analysis. Area in picture elements (pixels) and optical density (mass) of the 99Tc-labeled regions were determined and analyzed for similarities in the pattern of distribution. Area analysis was used to divide the patients into two groups. Group 2 patients (n = 7) had more patients with < 0.5 cm of residual disease (P = .051) and no evidence of disease (P = 0.1) compared with group 1 patients (n = 8). No differences in overall survival were found (P = 0.21). No objective measurement of distribution of intraperitoneally administered fluids exists. Computer image analysis may be an improvement over static scoring techniques to assess non-invasive imaging studies.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Changes in paired-pulse facilitation suggest presynaptic involvement in long-term potentiation.

Long-term potentiation (LTP) is a use-dependent form of synaptic plasticity that is of great interest as a potential cellular substrate underlying memory. It is important to determine the pre- and/or postsynaptic locus of LTP expression in order to study its underlying mechanisms. Despite intensive investigation, however, its locus of expression remains uncertain. It has been hypothesized that if LTP expression includes a presynaptic locus then it may alter the expression of another presynaptically mediated form of potentiation like paired-pulse facilitation (PPF), which is an increase in a second population excitatory postsynaptic potential when it is elicited shortly after a first. Previous authors have found no change in PPF in association with LTP. We re-examined the hypothesis, however, to reconcile the negative PPF data with other data that have suggested presynaptic involvement in LTP. Extracellular recordings were made in area CA1 of the rat hippocampal slice preparation. Surprisingly, PPF both increased and decreased significantly in association with LTP. The changes in PPF occurred in a predictable way, however. They correlated inversely with initial PPF magnitude so that a larger initial PPF was associated with a decrease in PPF with LTP while a smaller initial PPF was associated with an increase. Because PPF increased or decreased in individual slices in association with LTP, the average PPF of all slices did not change, in agreement with previous studies. The changes in PPF were also specific to LTP; that is, they were input specific, were not due to changes in inhibition or nonspecific effects of high-frequency stimulation, were not due to active postsynaptic currents or their nonlinear summation, and PPF changed with the same time course as LTP. We conclude that the mechanism of early LTP expression includes at least the presynaptic locus. Two hypotheses regarding the presynaptic mechanism underlying LTP expression, which are consistent with finding both increases and decreases in PPF with LTP, are (1) that there is an increase in the number of release sites with LTP or (2) that there is an increase in both the number of release sites and the probability of neurotransmitter release. Increases in the probability of neurotransmitter release alone would not appear to account for our findings since such increases have been associated only with decreases in PPF. Our findings do not exclude additional postsynaptic involvement.(ABSTRACT TRUNCATED AT 400 WORDS)

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1993

Gastric cancer: a curable disease in Britain.

OBJECTIVE: To determine whether more vigorous efforts aimed at earlier diagnosis allied to radical surgical resection lead to improved survival of patients with gastric cancer. DESIGN: Prospective audit of all cases of gastric cancer treated during 1970-89. SETTING: Department of surgery, general hospital. SUBJECTS: 493 consecutive patients with gastric adenocarcinoma. MAIN OUTCOME MEASURES: Operative mortality, postoperative morbidity, and five year survival after radical potentially curative resection. RESULTS: 207 (42%) patients underwent potentially curative resection. The proportion of all patients in whom this was possible increased significantly (p < 0.01) from 31% in the first five year period to 53% in the last five year period. The proportion of patients who had early gastric cancer rose from 1% to 15% (p < 0.01) and stage I disease rose from 4% to 26% (p < 0.001). After potentially curative resection, mortality 30 days after operation was 6%. Operative mortality decreased from 9% in the 1970s to 5% in the 1980s. Likewise, the incidence of serious postoperative complications decreased from 33% in the 1970s to 17% in the 1980s (p < 0.01). Five year survival was 60% in patients who underwent curative resection, 98% in patients with early gastric cancer, and 93%, 69%, and 28% in stage I, II, and III disease respectively. By the late 1980s five year survival after operation was about 70%. CONCLUSIONS: These findings suggest that an increasing proportion of patients with gastric cancer could be diagnosed at a relatively early pathological stage when about two thirds are curable by means of radical surgery.

Adenocarcinoma↗
PubMed1993

Serotonin inhibits induction of long-term potentiation at commissural synapses in hippocampus.

This study tests the effect of serotonin (5-HT) (1 microM) on the induction of long-term potentiation (LTP) at the commissural/associational (C/A)-CA3 synapse. The C/A input to CA3 was measured by field potentials in rat hippocampal slices. At the concentration used 5-HT had little or no effect on synaptic transmission, but suppressed the induction of LTP. Similar results were observed in normal saline and in saline containing picrotoxin (10 microM) and bicuculline (10 microM) to block GABAA inhibition. Perfusion with methysergide (1 microM), a 5-HT antagonist, had no effect on synaptic transmission, but partially blocked the effect of 5-HT on LTP. The block of LTP by 5-HT could be overcome by using a higher intensity of stimulation suggesting that 5-HT might hyperpolarize the postsynaptic neurons to inhibit LTP induction. We conclude that the activation of serotonergic receptors inhibits the induction of LTP at the C/A-CA3 synapse.

Animals↗
PubMed1993

Effect of anorectal eversion during restorative proctocolectomy on anal sphincter function.

Twenty-six patients underwent restorative proctocolectomy with end-to-end ileal pouch-anal anastomosis, without resection of the anal mucosa, by the eversion technique. Before surgery patients underwent tests of anorectal function. These were repeated a median of 8 (range 3-21) months after operation. The median (range) maximum resting anal pressure was 93 (36-149) cmH2O before and 71 (40-131) cmH2O after operation (P = 0.002). The median (range) maximum squeeze pressure before operation was 136 (73-280) cmH2O; it was 149 (69-290) cmH2O afterwards (P not significant). The median (range) length of the anal sphincter was 3.5 (2.5-4.5) cm before and 3.5 (2.0-4.5) cm after operation (P not significant). Thresholds for sensation in the upper, middle and lower thirds of the anal canal before and after operation were, respectively, 8.7 versus 8.7, 6.8 versus 7.4 and 4.2 versus 6.2 mA (P not significant). All 26 patients were continent, although one experienced minor leakage. Function of the anal sphincter is not significantly impaired by eversion of the rectum and anus during restorative proctocolectomy.

Adolescent↗
PubMed1993

Significance of circumferential resection margin involvement after oesophagectomy for cancer.

This study examined the influence of tumour involvement of the circumferential resection margin on subsequent local recurrence after oesophagectomy. Fifty patients were studied: 36 men and 14 women of median age 62 (range 44-83) years. Each patient had undergone oesophagectomy at which all macroscopic disease had been removed. Pathological specimens were sectioned tangentially at 0.5-1.0-cm intervals to permit microscopic examination of the circumferential resection margin. Patients were followed and investigated by endoscopy with biopsy and imaging techniques only if symptomatic. Twenty of the 50 specimens demonstrated involvement of the circumferential resection margin. At median follow-up of 36 (range 24-52) months, eleven of these 20 patients had developed histologically proven local recurrence compared with only four of the remaining 30 in whom the resection margin was clear of tumour (P < 0.01). Circumferential spread of oesophageal cancer appears to be a significant cause of local tumour recurrence.

Adult↗
PubMed1993

Quality of life after restorative proctocolectomy with a pelvic ileal reservoir compares favorably with that of patients with medically treated colitis.

There remains some reluctance among physicians to refer patients for restorative proctocolectomy (RP). They argue that their patients would be worse off with a pouch because of the attendant problems of urgency and frequent bowel actions. The aim of this study was to compare quality of life in patients who had undergone RP with that of patients with ulcerative colitis on long-term medical treatment. A detailed questionnaire and the Hospital Anxiety and Depression (HAD) test were completed by 103 patients who had undergone RP and by 95 patients with ulcerative colitis on medical treatment and in remission attending a gastroenterology clinic. Patients with a pouch had a greater frequency of bowel action [five times per 24 hours (range, 4-7) vs. two times per 24 hours (range, 1-3); P < 0.001] but less urgency of defecation [12/103 (11.7 percent) vs. 69/95 (72.6 percent); P < 0.001] than patients with medically treated colitis. Efficiency of evacuation, discrimination between flatus and feces, use of perianal pads, and perianal soreness were similar. Use of antidiarrheal medication was more common in the pouch group [53 of 103 patients (51.5 percent) vs. 3 of 95 patients (3.2 percent); P < 0.05], whereas use of topical steroids was more common in medically treated patients [40 of 95 patients (47.1 percent) vs. 9 of 103 patients (8.7 percent); P < 0.05]. Limitation of social activity and HAD scores were significantly higher in medically treated patients. Quality of life for patients with a pouch appears to be as good as that for patients with medically treated colitis.

Adolescent↗
PubMed1993

Vascular abnormalities in non-insulin-dependent diabetes mellitus identified by arterial waveform analysis.

PURPOSE: The arterial pressure waveform is derived from the complex interaction of the left ventricular stroke volume and the physical properties of the arterial circulation. Widespread abnormalities in the physical characteristics of the arterial vessels associated with diabetes mellitus can produce consistent changes in the shape of the pressure pulse waveform, providing information about arterial structure and tone that can be quantitated by pulse contour analysis. PATIENTS AND METHODS: We analyzed intraarterial brachial artery waveforms in 28 patients with non-insulin-dependent diabetes mellitus and 22 control subjects matched for age and sex. A computer-based assessment of the diastolic pressure decay and a modified Windkessel model of the circulation were employed to quantify changes in arterial waveform morphology in terms of the large-artery compliance (C1), the oscillatory diastolic waveform (C2), inertance, and systemic resistance. RESULTS: No differences were found in heart rate, mean arterial pressure, cardiac output, or stroke volume between groups. The mean oscillary arterial compliance estimate was significantly reduced in diabetic subjects versus controls: 0.02 (95% confidence interval [CI], 0.01 to 0.03) mL/mm Hg versus 0.08 (95% CI, 0.04 to 0.12) mL/mm Hg (p < 0.001). Oscillatory compliance values were uniformly reduced in the diabetic subjects regardless of the presence or absence of physical complications of the disease. No differences in large-artery compliance, inertance, or systemic resistance were found between groups. No positive correlations were found between indices of glycemic control, the known duration of diabetes, and any of the hemodynamic variables. CONCLUSIONS: Quantitative changes in the arterial pressure pulse waveform, reflected by a reduced oscillatory compliance estimate, were found in patients with non-insulin-dependent diabetes mellitus. This estimate appears to act as an early marker for the vascular abnormalities associated with diabetes before complications of the disease become clinically apparent. By contrast, no changes in large-artery compliance were found in this patient population free from clinically obvious macrovascular disease.

Adult↗
PubMed1993

The effect of patient position and obesity on the spread of epidural analgesia.

The aim of this study is to assess the effect of patient positioning and obesity on the height of block achieved during routine labor epidural analgesia. Forty patients weighing <80 kg were allocated to a control group and a further 40 weighing >100 kg to a study group. Half the patients in each group received an epidural injection in the lateral position, the remainder were in the sitting position. After insertion of an epidural catheter and injection of 12 ml of 0.25% bupivacaine plain the patients remained in position for a further 5 min. The height of block achieved, as assessed by loss of cold sensation, showed no difference between any of the groups. The results indicate that, for routine labor epidural analgesia, using 12 ml of 0.25% plain bupivacaine, neither patient positioning nor obesity affects the height of block achieved.

Journal Article↗
PubMed1993

The administration of supplementary oxygen to prevent hypoxia during upper alimentary endoscopy.

A prospective, randomized, controlled trial was conducted in 200 consecutive patients undergoing endoscopy of the upper alimentary tract. One hundred patients received supplementary oxygen at 4 liters/minute through nasal cannulae, while 100 patients received no additional oxygen. Within each of these two groups, 50 patients were sedated with midazolam and 50 patients with diazepam suspension ("Diazemuls"). The patients' weights were recorded and correlated with their height to assess whether they were over or under their ideal weight. Oxygen saturation was recorded at baseline and throughout the endoscopic procedure. The principal finding of this study was that hypoxia (oxygen saturation less than 93%) was prevented in all cases by the administration of 4 liters/minute of oxygen, whereas 48 of the 100 patients who did not receive oxygen exhibited falls in oxygen saturation to less than 93% (p < 0.0001). Those with the highest risk were the obese patients (p < 0.01). There was no significant difference between the two sedative drug groups in either frequency or severity of associated hypoxia (p = 0.77, patients not given oxygen; p = 0.31, patients receiving oxygen). The cost of administering oxygen during upper gastrointestinal endoscopy would be an average of 95 pence ($1.60) per patient. In conclusion, the administration of oxygen during endoscopy is a worthwhile prophylactic measure to prevent hypoxia and its potential adverse effects.

Costs and Cost Analysis↗
PubMed1993

Cytokine production and immune cell activation in melanoma patients treated with liposomal muramyl tripeptide (CGP 19835A lipid).

We conducted a pilot study using liposome-encapsulated muramyl tripeptide phosphatidylethanolamine (L-MTP-PE) preoperatively in patients with stage III or IV resectable melanoma who were at high risk for recurrence. Patients received L-MTP-PE for 1 month before surgery and then 5 months postoperatively. Several immune parameters were monitored during preoperative therapy to search for correlations with clinical (tumor) response. The 18 patients were classified into three groups according to their responses and disease-free intervals: no evidence of disease (NED) at week 24 of therapy, relapse during therapy and progressive disease on therapy noted at the time of surgery. Six of nine patients in the NED group demonstrated increased monocyte tumoricidal activity (MTA) during week 1 of therapy. MTA increased in three of the six patients in the relapse group. MTA did not increase in the three patients who had progressive disease on therapy. Plasma neopterin levels were elevated by 72 h following the first L-MTP-PE dose in all 18 patients. Circulating levels of tumor necrosis factor were elevated in 15 of 16 patients tested, and IL-6 levels were elevated in all 18 patients. Melanoma cells from all three patients with progressive disease at the time of surgery proliferated well in vitro, whereas tumor cells from 10 of the 15 patients in the other two groups did not proliferate. There were no discernible differences among the three groups in the magnitude of IL-2-induced proliferation of tumor infiltrating lymphocytes. However, IL-2-activated TILs from the NED group exhibited cytotoxicity against autologous tumor cells in vitro. In summary, whereas L-MTP-PE stimulated several immunologic responses in all patients, the only two parameters that correlated with clinical status were MTA and the tumor proliferation assay. These two biologic assays could serve to distinguish potential responders from nonresponders early in the course of treatment.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1993

Carriage of adhesive Escherichia coli after restorative proctocolectomy and pouch anal anastomosis: relation with functional outcome and inflammation.

Restorative proctocolectomy with pelvic ileal reservoir is a well accepted option for the surgical treatment of ulcerative colitis. Acute pouchitis is a common complication and resembles acute ulcerative colitis. Patients with ulcerative colitis carry Escherichia coli that adhere to epithelial cells and thus this study examined whether acute pouchitis is associated with the carriage of adhesive E coli. E coli isolated from stool samples from 24 patients (median age 34 years, range 16-64; 13 men, 11 women) who had had restorative proctocolectomy with pelvic ileal reservoir were examined by means of the buccal epithelial cell adhesion assay. Patients were studied at a median of 12 months (range 7-21) after operation. Eight of 24 patients had acute pouchitis at the time of study. Adhesive E coli were detected in nine of 24 patients with a pelvic ileal reservoir compared with none of 12 controls (p < 0.05). The buccal epithelial cell adhesion index was inversely related to the degree of acute pouchitis (rs = 0.46, p = 0.024) and to the functional outcome (rs = -0.49, p = 0.022). Carriage of adhesive E coli was not related to the design of the reservoir. By contrast with ulcerative colitis, acute pouchitis is not associated with the carriage of adhesive E coli.

Adolescent↗
PubMed1993

Restorative proctocolectomy with end to end pouch-anal anastomosis in patients over the age of fifty.

This study was to examine whether 'fit' patients over the age of 50 who require elective surgery for ulcerative colitis are suitable candidates for restorative proctocolectomy, providing that they are continent before operation and that the anal sphincter is preserved in its entirety without stripping of the mucosa or endoanal anastomosis. Between 1986 and 1991, 18 patients 50 to 66 years old (median 55 years: nine men) underwent restorative proctocolectomy with end to end ileoanal anastomosis without mucosal stripping (12 quadruplicated (W), four duplicated (J), two no reservoir). The results were compared 12 (range three to 24) months later with those of 18 matched patients who were less than 50 years of age (median 34 years). In patients over 50, median resting anal pressure was 88 (range 44-131) cm water before and 80 (47-138) cm water after the operation (NS). In patients under 50, median resting anal pressure was 76 (51-128) cm water before and 77 (36-137) cm water after operation (NS). Resting anal pressure in older patients did not differ significantly from that in younger patients either before or after the operation. Both sensory and reflex anal functions were preserved as well after operation in the older patients as in the younger ones. The clinical results in patients over 50 were slightly inferior to the results for the younger patients, but the difference was small and not significant. Hence age alone is not a contraindication to restorative surgery provided that the anal sphincter is preserved in its entirety.

Adolescent↗
PubMed1993

Voltage- and space-clamp errors associated with the measurement of electrotonically remote synaptic events.

1. The voltage- and space-clamp errors associated with the use of a somatic electrode to measure current from dendritic synapses are evaluated using both equivalent-cylinder and morphologically realistic models of neuronal dendritic trees. 2. As a first step toward understanding the properties of synaptic current distortion under voltage-clamp conditions, the attenuation of step and sinusoidal voltage changes are evaluated in equivalent cylinder models. Demonstration of the frequency-dependent attenuation of voltage in the cable is then used as a framework for understanding the distortion of synaptic currents generated at sites remote from the somatic recording electrode and measured in the voltage-clamp recording configuration. 3. Increases in specific membrane resistivity (Rm) are shown to reduce steady-state voltage attenuation, while producing only minimal reduction in attenuation of transient voltage changes. Experimental manipulations that increase Rm therefore improve the accuracy of estimates of reversal potential for electrotonically remote synapses, but do not significantly reduce the attenuation of peak current. In addition, increases in Rm have the effect of slowing the kinetics of poorly clamped synaptic currents. 4. The effects of the magnitude of the synaptic conductance and its kinetics on the measured synaptic currents are also examined and discussed. The error in estimating parameters from measured synaptic currents is greatest for synapses with fast kinetics and large conductances. 5. A morphologically realistic model of a CA3 pyramidal neuron is used to demonstrate the generality of the conclusions derived from equivalent cylinder models. The realistic model is also used to fit synaptic currents generated by stimulation of mossy fiber (MF) and commissural/associational (C/A) inputs to CA3 neurons and to estimate the amount of distortion of these measured currents. 6. Anatomic data from the CA3 pyramidal neuron model are used to construct a simplified two-cylinder CA3 model. This model is used to estimate the electrotonic distances of MF synapses (which are located proximal to the soma) and perforant path (PP) synapses (which are located at the distal ends of the apical dendrites) and the distortion of synaptic current parameters measured for these synapses. 7. Results from the equivalent-cylinder models, the morphological CA3 model, and the simplified CA3 model all indicate that the amount of distortion of synaptic currents increases steeply as a function of distance from the soma. MF synapses close to the soma are likely to be subject only to small space-clamp errors, whereas MF synapses farther from the soma are likely to be substantially attenuated.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

The long-term prevention of tobacco use among junior high school students: classroom and telephone interventions.

OBJECTIVES: The purpose of this study was to implement and evaluate the effectiveness of a long-term tobacco use prevention program for junior high school students that used college undergraduate change agents and telephone boosters. METHODS: A psychosocial intervention combining refusal skills training, contingency management, and other tobacco use prevention methodologies such as telephone and mail boosters was implemented in 11 junior high schools in San Diego County, California. Eleven other junior high schools served as controls. Of the 2668 participants, 57% were White/non-Hispanic, 24% were Hispanic, and 19% were of other racial/ethnic groups. College undergraduates served as change agents for both the classroom and booster interventions, the latter of which was delivered in the third (ninth-grade) year of the program. RESULTS: At the end of the third year, the prevalence of tobacco use within the past month was 14.2% among the intervention students and 22.5% among the controls, yielding an odds ratio of 0.71 for analysis at the school level. CONCLUSIONS: Both college undergraduate change agents and direct one-to-one telephone interventions appear to provide cost-effective tobacco-related behavior modification.

Adolescent↗
PubMed1993

Proliferating cell nuclear antigen (PCNA) expression in chronic lymphocytic leukemia (CLL).

Chronic Lymphocytic Leukemia (CLL) is usually an indolent disorder which in some patients assumes an aggressive clinical course. In order to assess at presentation the prognosis of a given patient, several staging systems and prognostic variables have been proposed including the expression of the Proliferating Cell Nuclear Antigen (PCNA). PCNA is a 36 kd nuclear protein, the regulation of which is cell cycle-dependent. In CLL, PCNA levels correlate with cell proliferation, clinical stage and the lymphocyte doubling time (LDT). Furthermore, preliminary data suggests that PCNA expression may also predict response to Fludarabine-based chemotherapy. Since PCNA is a cofactor for Delta DNA polymerase, PCNA overexpression in CLL may also reflect the intrinsic DNA repair activity of the leukemic cells and thus their resistance to chemotherapy. Further studies aiming at modulation of PCNA expression in CLL cells may clarify this issue and may offer a future new therapeutic strategy with which to treat this disorder.

Antigens, Neoplasm↗