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Biomedical subjects

D Johnston

Publications and source records attributed to D Johnston.

At least 199 records · Page 11Linked to original sources

Healthcare foodservice report 1993. Getting ready for reform. Interview by Mitchell Schechter.

Hospital foodservice directors & dietitians are facing the greatest challenge of their careers -- to prepare, along with their institutions, for the most thoroughgoing reform of America's healthcare system ever proposed. Healthcare institutions across the country are seeking the means to offer enhanced patient services & gain competitive advantages by forming new alliances, new patient-centered care systems & cost-reduction programs. To aid in these efforts, their foodservices are developing comprehensive cross-training schemes, inter-departmental teams with other service groups & new ways to cut operating subsidies. Here's how five hospital foodservice departments are using cost controls, revenue building, quality management processes & enhanced efficiencies to help their institutions prepare for the changes ahead.

Cost Control↗

Continence-preserving procedures for benign and malignant disease.

The musculature of the anal sphincter is not involved in ulcerative colitis and is seldom invaded directly by rectal carcinoma. Because the sphincter is capable of preserving a good degree of continence, even after removal of the entire rectum for rectal carcinoma, or even of the entire rectum and colon in ulcerative colitis, it should be preserved in most patients who require surgical treatment for these conditions. This review is primarily concerned with what type of enteric substitute should be used for the excised rectum. It addresses the issues of whether retention of a few centimeters of distal rectum above the anal high pressure zone (when permissible) is of value in patients with rectal carcinoma; whether the entire anal sphincter complex, including the so-called "sampling zone" of anal mucosa, should be preserved in the course of rectal excision for ulcerative colitis; or whether, alternatively, all mucosa above the dentate line should be removed and continuity restored by means of an endoanal, pouch-anal anastomosis. For the patient, the eventual clinical result depends on the quality of the anal sphincter, the physiologic characteristics of the "neorectum," the degree to which anal and rectal function are coordinated, and finally, the judgment and technical skill of the surgeon.

Fecal Incontinence↗

Early response gene signalling cascades activated by ionising radiation in primary human B cells.

We have used a panel of 13 protein kinase C-responsive immediate early gene probes to dissect the cellular signalling pathways activated by ionising gamma radiation in primary human B cells. Of these 13 genes, a delayed transient induction was observed for only 8: c-fos, c-jun, jun-B, jun-D, c-myc, ergI/krox 24 and two 'anonymous' genes, 3L3 and 19A. Expression of c-myc and c-fos mRNAs was paralleled by the appearance of their encoded proteins suggesting that these oncoproteins may couple radiation signalling to cellular responses. Of three protein kinase C-coupled transcription factors examined by gel retardation assay, (AP1, NF kappa B, EgrK/Krox24) only NF kappa B and, to a lesser extent, AP1 was stimulated in response to irradiation. These observations are not obviously compatible with a simple model invoking protein kinase C in radiation signalling in primary B cells and suggest that the pleiotropic effects of ionising radiation on this cell type are mediated through a distinct cellular signalling cascade.

B-Lymphocytes↗

Dendritic excitability in CNS neurons: insights from dynamic calcium and sodium imaging in single cells.

We measured changes in [Ca2+]i and [Na+]i in the dendrites of cerebellar Purkinje cells and hippocampal pyramidal cells using high speed imaging of the fluorescence changes of intracellularly injected fura-2 and SBFI. These transients were detected in synchrony with intracellular recordings of membrane potential. In this way rapid calcium or sodium transients could be associated with specific electrical events. Using this technique we could determine the spatial distribution and source of transients evoked either intrasomatically or synaptically and could relate them to electrically recorded sodium and calcium spikes.

Animals↗

An immediate early human gene encodes an Id-like helix-loop-helix protein and is regulated by protein kinase C activation in diverse cell types.

Transcription factors characterized by the presence of a helix-loop-helix (HLH) domain play a central role in the regulation of cell growth/differentiation and tumorigenesis. We report here the cDNA sequence of a human early-response gene, designated HLH 1R21, encoding a 15-kDa HLH protein that lacks a basic, DNA-binding domain and which by a number of criteria appears to be the human homologue of mouse HLH 462. Like its murine counterpart, HLH 1R21 protein functions as an Id (inhibitor of DNA binding) transcription factor by inhibiting the binding of E2A-containing protein complexes to muscle creatine kinase E-box enhancer oligonucleotide in vitro. However HLH 1R21 does not inhibit the binding of HLH Max protein to a Max-binding oligonucleotide in vitro, indicating that it has limited promiscuity in its ability to antagonize the function of other HLH transcription factors. In addition, HLH 1R21 mRNA transcripts are regulated by phorbol ester treatment of a diverse range of human cell lines and, when overexpressed in mouse NIH3T3 cells, HLH 1R21 induces a morphologically transformed phenotype.

3T3 Cells↗

The prevalence of depression in a high school population.

This study examined the prevalence of depression in a nonclinical adolescent population (N = 2,698) in a major Canadian city. The Beck Depression Inventory was administered to students in three secondary schools. An analysis of variance revealed significant main effects of age and gender. The percentage of students categorized as experiencing none to mild depression was contrasted with those experiencing moderate to severe depression. Overall, the results showed relatively low rates of severe or moderate depression in this population. The findings are discussed in the context of previous investigations.

Adolescent↗

Drug-patient interactions and their relevance in the treatment of heart failure.

The effects of congestive heart failure (CHF) on drug disposition and elimination are many and varied. Indeed, the pharmacokinetics of many of the drugs used to treat CHF are significantly altered by the patient's underlying condition. Reduced gastric emptying in CHF delays absorption and decreases the peak plasma concentrations of furosemide, bumetanide, and digoxin. Moreover, drugs that have a high hepatic extraction ratio (organic nitrates, morphine, prazosin, and hydralazine) achieve higher than expected plasma concentrations in patients with CHF. In contrast, drugs requiring biotransformation to active forms, e.g., angiotensin-converting enzyme (ACE) inhibitors such as enalapril, perindopril, quinapril, and ramipril, generally have lower than expected plasma concentrations. Nevertheless, ACE inhibitors can impair renal function in CHF, leading to an actual increase in plasma concentrations. However, decreases in absorption and first-pass metabolism are often offset by reduced hepatic and renal clearance. The overall absorption of lisinopril may be reduced in some CHF patients; consequently, the onset of effect is delayed but is often more prolonged.

Angiotensin-Converting Enzyme Inhibitors↗

Reduction in factor VII, fibrinogen and plasminogen activator inhibitor-1 activity after surgical treatment of morbid obesity.

The aim of this study was to determine the effects of the surgical treatment of morbid obesity on some aspects of haemostatic and fibrinolytic function. Measurement of haemostatic and fibrinolytic factors was performed before and again 6 and 12 months after operation in 19 patients suffering from morbid obesity. Surgical treatment resulted in a mean decrease in body weight of 50 kg at 6 months and 64 kg at 12 months. Weight loss was accompanied at 12 months by significant reductions in median (interquartile range) concentrations of serum cholesterol from 5.3 (4.5-6.2) mmol/l to 3.6 (2.9-4.6) mmol/l; factor VII from 113 (92-145)% of normal to 99 (85-107)%; of fibrinogen from 3.5 (3-9.3) g/l to 2.8 (2.4-3.8) g/l; and of plasminogen activator inhibitor-1 (PAI-1) activity from 21 (11-30) IU/ml to 6.3 (5-10) IU/ml. The decrease in PAI-1 activity probably accounted for a significant reduction in euglobulin clot lysis time. Tissue plasminogen activator activity was undetectable in most patients pre-operatively but increased slightly after 1 year to 110 (100-204) mIU/ml. There were no significant changes in plasma levels of KCCT, factor VIII, von Willebrand factor antigen, alpha-2-antiplasmin, antithrombin III, protein C antigen, beta thromboglobulin, platelet factor 4, fibrinopeptide A or platelet count. These findings provide support for the hypothesis that the surgical treatment of morbid obesity may have a long-term beneficial effect on mortality from cardiovascular and thromboembolic disease.

Adult↗

CI-973, a new platinum derivative with potential antileukemic activity.

We examined the effects of CI-973 (supplied by Parke-Davis) on several human leukemia cell lines and a Chinese hamster ovary (CHO) line and their drug-resistant counterparts. The cell lines used were HL-60, HL-60/mAMSA, HL-60/DOX, KBM3, KBM3/mAMSA 6, KBM3/mAMSA 6(85), CHO, and CHO/AC-7. DOX, mAMSA, and AC-7 indicate resistance to doxorubicin, amsacrine, or 1-beta-D-arabinofuranosylcytosine, respectively. Cells were incubated with CI-973, and the effect was evaluated by two methods: growth inhibition assay and inhibition of colony formation. All cell lines examined were inhibited by CI-973; two of three amsacrine-resistant lines and the one cytarabine-resistant line demonstrated collateral sensitivity. At equivalent dosages, a 4-day exposure provided much greater cell kill than a 1-h exposure. Clonogenic assay showed exponential killing over 3 log units. Maximum CI-973 levels required to kill 50% of cells were 10-fold lower than the peak plasma levels achieved in a phase I solid tumor study. A continuous infusion phase I study in acute leukemia has been initiated.

Animals↗

The spread of Na+ spikes determines the pattern of dendritic Ca2+ entry into hippocampal neurons.

The dendrites of many types of neurons contain voltage-dependent Na+ and Ca2+ conductances that generate action potentials (see ref. 1 for review). The function of these spikes is not well understood, but the Ca2+ entry stimulated by spikes probably affects Ca(2+)-dependent processes in dendrites. These include synaptic plasticity, cytotoxicity and exocytosis. Several lines of evidence suggest that dendritic spikes occur within subregions of the dendrites. To study the mechanism that govern the spread of spikes in the dendrites of hippocampal pyramidal cells, we imaged Ca2+ entry with Fura-2 (ref. 9) and Na+ entry with a newly developed Na(+)-sensitive dye. Our results indicate that Ca2+ entry into dendrites is triggered by Na+ spikes that actively invade the dendrites. The restricted spatial distribution of Ca2+ entry seems to depend on the spread of Na+ spikes in the dendrites, rather than on a limited distribution of Ca2+ channels. In addition, we have observed an activity-dependent process that modulates the invasion of spikes into the dendrites and progressively restricts Ca2+ entry to more proximal dendritic regions.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

Prognostic value of proliferating cell nuclear antigen expression in chronic lymphoid leukemia.

Chronic lymphocytic leukemia (CLL) is a usually indolent disease that can assume an aggressive clinical course in some patients. To develop assays that would be predictive of how a particular patient's disease would evolve, we studied the expression of proliferating cell nuclear antigen (PCNA) by Western blotting in 40 patients with CLL. The concentration of PCNA, a cofactor for delta DNA-dependent DNA polymerase, is indicative of the proliferative state of the cell. Significantly lower PCNA levels were observed in earlier stage CLL when compared with more advanced disease. The leukemic cell proliferative rate, assessed by lymphocyte doubling time and flow cytometry, also correlated significantly with the level of PCNA expression. These results suggest that a high level of PCNA in the cells of CLL patients at presentation identifies a subgroup of patients whose CLL cells have a higher proliferative activity and who may, therefore, have a potentially shorter survival.

Actins↗

Laparoscopic cholecystectomy as a routine procedure for gallstones: results of an 'all-comers' policy.

A total of 165 consecutive patients with gallstones were considered for laparoscopic cholecystectomy. Three were excluded. The median age was 52 years and 76 per cent were women. Eighteen patients underwent urgent operation. Laparoscopic cholecystectomy was successful in 160 of the 162 patients (99 per cent). The two failures were the result of dense adhesions and stones in the bile duct. There were no deaths but major complications occurred in three patients: fenestration of the colon sutured laparoscopically; bleeding from a cannulation site and subsequent laparotomy for a strangulated hernia; and subphrenic abscess. There were 13 minor complications, but no bile duct injuries or peritonitis. The median postoperative hospital stay was 1 day. Bile duct stones were present in 14 patients (9 per cent) and were removed by endoscopic sphincterotomy (11 patients), by laparoscopic exploration of the common duct (two) and by conversion to laparotomy (one). These results suggest that laparoscopic cholecystectomy is applicable to the large majority of patients who require elective or urgent cholecystectomy, if appropriate radiological and endoscopic support is available.

Adolescent↗

Role of the rectum in the physiological and clinical results of coloanal and colorectal anastomosis after anterior resection for rectal carcinoma.

This study investigated the relationships between length of residual anorectum, anorectal physiological function and clinical outcome after anterior resection for rectal carcinoma. Thirty-four patients were studied a median of 13 (range 4-100) months after anterior resection. They were compared with a control group of ten patients who had undergone sigmoid colectomy for carcinoma without rectal excision. Resting anal pressure was found to be lower after coloanal than after colorectal anastomosis, and the capacity of the (neo)rectum was less after coloanal than after colorectal anastomosis. The (neo)rectoanal inhibitory reflex was found to be present in each patient, but maximum anal pressure during this 'sampling' reflex was significantly lower (P < 0.01) after coloanal than after colorectal anastomosis, and the volume required for maximal inhibition of the sphincter was also less (P < 0.01). At 1 year after operation, median bowel frequency was greater after coloanal (4 per day) than after colorectal (2 per day) anastomosis and the degree of urgency of defaecation was also greater (P < 0.01). Quality of life in terms of anorectal function after anterior resection is thus significantly influenced by the length of rectum that is left. This, in turn, influences the functional capacity of the neorectum and the degree of inhibition of the anal sphincter during the neorectoanal inhibitory reflex.

Adult↗

Morphometry of gastric carcinoma: its association with patient survival, tumour stage, and DNA ploidy.

Morphometric image analysis of nuclear features was performed on tissue from 46 patients who had had curative resections for gastric cancer. Clinical, pathological, flow cytometric, and follow-up data were available for these patients, which were drawn from a larger, previously reported series. The morphometric data were compared with patient survival, clinico-pathological status, and DNA ploidy. Univariate survival analysis revealed that morphometric parameters were not significantly related to survival, but examination of clinico-pathological data showed lymph node involvement, involvement of the resection margin, and lymphatic invasion to be significantly associated (P < 0.01) with patient prognosis. Multivariate survival analysis using the Cox model found only lymph node and resection margin involvement to be independently related to survival. Comparison of morphometric results with the clinico-pathological parameters showed various features, relating to nuclear size, and its variation to be significantly associated (P < 0.01) with the presence of lymphatic invasion, resection margin involvement, and tumour pattern (intestinal/diffuse). A comparison of morphometry with flow cytometric analysis in these cases showed that nuclear size was not significantly related to either DNA aneuploidy or the DNA proliferative index.

Aged↗

One-stage restorative proctocolectomy without temporary defunctioning ileostomy.

A temporary ileostomy has been employed routinely by most medical centers to defunction the ileal reservoir after restorative proctocolectomy. The aim of this study was to compare the clinical outcome in patients who underwent restorative proctocolectomy with and without the use of a temporary, defunctioning ileostomy. A consecutive series of 58 patients was studied. Each patient underwent restorative proctocolectomy with quadruplicated ileal reservoir and stapled pouch-anal anastomosis, without mucosectomy; 28 had a temporary, defunctioning ileostomy and 30 did not. The decision for or against an ileostomy was taken at the end of the operation. The two groups of patients were similar in age and sex distribution. There was no postoperative mortality. There were no significant differences in the incidence of pelvic sepsis, anastomotic stricture, and intestinal obstruction in patients without an ileostomy compared with patients with an ileostomy. The total length of stay in hospital after the operation was significantly reduced in the group of patients without an ileostomy (P less than 0.01). The avoidance of a temporary ileostomy did not lead to an increase in postoperative complications and was associated with a shorter length of stay in hospital after restorative proctocolectomy.

Adult↗