Advice to a college student considering medicine as a career.
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Biomedical subjects
Publications and source records attributed to J M McGreevy.
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Gastric mucosal cells from guinea pigs were grown in cell culture. Acridine orange fluorescence at 624 nm was used as an qualitative indicator of intracellular pH. The cultured cells were exposed to Hank's solution at pH 7.4, 6.0, 5.0, 4.0, 3.0, and 1.8 for 30 min. After removal of the acid, the cells were loaded with acridine orange for qualitative pH assessment. The cells developed alkaline shifts in the cytoplasmic pH in direct proportion to the acid load. This alkaline overcorrection after exposure to acid was blocked by amiloride and blunted by taurocholic acid in a dose-dependent fashion. These results suggest that gastric surface cells may regulate their cytoplasmic pH with a sodium-hydrogen antiporter. These results also suggest that this antiport system may be adversely affected by bile salts.
Screening mammography provides a means of detecting clinically occult breast carcinoma, but the question of whether all abnormal mammograms require biopsy remains unanswered. We retrospectively reviewed records of 214 women referred over an 8-year period for abnormal mammograms. They were selectively assigned to biopsy or mammographic follow-up based on specific mammographic criteria. Of 114 women initially observed mammographically, 2 were later found by biopsy to have carcinoma. Initial assignment to mammographic observation delayed the recommendation for biopsy 3 and 12 months, respectively, in these patients, but no effect on outcome was documented. Because they have benign lesions by clinical and mammographic criteria, 102 women (53%) have been spared biopsy; they continue to be monitored closely. We believe these data support the use of a selective approach to biopsy based on specific mammographic criteria.
The charts of 38 patients managed with a period of intensive medical treatment (mean 7 days) prior to portosystemic shunting were examined. We found that the operative delay did not improve the Child's class or the indices of liver function. The operative mortality rates in these patients were 0 in Child's A patients, 13 percent in Child's B patients, and 50 percent in Child's C patients. Based on these findings, we began to operate on patients with bleeding esophageal varices as soon as they stabilized. The charts of 10 consecutive Child's C patients operated on without a period of intensive medical management (mean 3 days) were reviewed and compared with the charts of 8 Child's C patients with delayed operation. The two groups of patients were similar. We recommend that patients who need a shunt should be operated on as soon as possible after bleeding has ceased.
Screening mammography is a valuable tool in the detection of breast cancer at an early stage. Large numbers of patients are being referred to surgeons for biopsies on the basis of mammographic abnormalities alone. As mammograms are complex studies and the findings often subtle, variation in terms of interpretation and recommendations for biopsy can leave the surgeon in a difficult position. We have reported a systematic method for evaluating patients and mammograms. Eighty-eight patients were referred to a single surgeon solely for an abnormal mammographic finding. Physical examination was repeated and the mammogram reviewed with a single consulting radiologist using specific criteria to define a mammographic abnormality. Through this evaluation, biopsy was avoided in 42 of 88 patients, with follow-up mammograms and physical examinations finding no suspicion of malignancy. By becoming educated in regard to mammographic abnormalities, establishing specific criteria with a consistent radiologist, and following patients carefully who are not biopsied, the surgeon can deal effectively with screening mammography.
Omeprazole uncouples histamine-stimulated hydrogen and chloride secretion in the frog gastric mucosa. This uncoupling results in a large increase in PD and Isc due to the unmasking of an electrogenic Cl- flux. Using a selective anoxia technique, we have attempted to define the cellular origin of this electrogenic Cl- flux. Sixteen bullfrog gastric mucosae were mounted in Ussing chambers. Under short-circuit conditions, PD, Isc, R, and unidirectional 36Cl flux were determined every 15 min. Acid secretion (10(-5) M histamine) was measured by hand titration (0.1 N NaOH). With both sides of the mucosae oxygenated, the addition of omeprazole (10(-4) M) resulted in cessation of H+ secretion and the unveiling of an electrogenic Cl- flux. Subsequent serosal anoxia (5% CO2-95% N2 nutrient side/30% O2 secretory side) resulted in a drop in JClnet associated with an appropriate fall in Isc. These changes were reversible with reoxygenation: (Table: see text). Bullfrog gastric mucosae which are partially oxygenated on the secretory side only (serosal anoxia) do not secrete acid in response to histamine. Therefore, the JClnet which is inhibited in these experiments by serosal anoxia may originate in the gastric glands approximately equal to 3.0 mu eq/cm2 X hr). The JClnet which remains during serosal anoxia may originate in the surface epithelial cells (approximately equal to 1.0 mu eq/cm2 X hr).
Clinical data from two hundred consecutive patients undergoing surgical procedures at the Salt Lake City VA Hospital form the basis of this study. Results of nine commonly ordered preoperative tests (blood count, differential, electrolytes, chemistry panel, urinalysis, prothrombin time, partial thromboplastin time, electrocardiogram, and chest X-ray) were matched with the preoperative history and physical examination and the outcome of surgery in each patient. Each test was examined by the frequency with which it was ordered, the frequency with which it was abnormal, and the frequency with which the abnormal result affected preoperative care. A prevalence of medical illness was found in this population, with 47.5% having a major cardiovascular diagnosis, 35.5% a metabolic or endocrine disease, and 28% a major pulmonary diagnosis. A total of 1271 tests were performed, with 477 (35.5%) showing some abnormality. However, only 76 (5.9%) changed the patient's management before surgery. All but five of these abnormalities were predictable from the clinical evaluation and these five were minor. The overall postoperative complication rate was 9%. No complication was attributed to the omission of a preoperative test. No surgical cases were cancelled during the study period based solely on a preoperative test. We conclude that many preoperative tests can be safely eliminated by ordering only those based on a specific abnormality in the history or physical examination, resulting in more cost-effective surgical care.
Rabbit fundic mucosa mounted in Ussing chambers for 4 h developed morphological deterioration of the gastric glands (GG), while the surface epithelial cell layer (SEC) remained intact. Since the tissues maintained a steady-state potential difference (PD) and resistance (R), it seemed that the surface cells might be responsible for both the PD and the R. To test this hypothesis, segments of fundic mucosa were exposed to selective anoxia by bubbling the mucosal (anoxic SEC) or serosal (anoxic GG) nutrient solutions with N2 instead of O2. Control tissues received O2 into both nutrient solutions. SEC anoxia resulted in a PD and short-circuit current (Isc) of zero within 10 min; R fell by 60% within 2 h. GG anoxia caused no change in PD or R over 2 h. Unidirectional fluxes (J) of 36Cl did not diminish as expected in tissues with no PD or Isc. This persistent JCl in tissues with a PD of zero was investigated in tissues with anoxic SEC. Simultaneous unidirectional fluxes of 36Cl and [3H]mannitol were determined to identify the transcellular (JClcell) and paracellular (JClleak) components of JCl during SEC anoxia. Similar flux measurements were made in control tissues (no anoxia). In control tissues, the calculated JClcell correlated with Isc (r = 0.72, n = 44). In tissues with anoxic SEC, the JClcell was 0.05 +/- 0.4 (mean +/- SD, n = 44). This series of experiments suggests that the PD and mucosal barrier characteristics of rabbit gastric mucosa in Ussing chambers are functions of a healthy surface cell layer.
Ischemia of the gastric epithelium has emerged as one of the more likely mechanisms for gastric ulceration. Radiolabeled microspheres (15 mu) were used to measure blood flow to exteriorized, chambered stomach segments in eight dogs during the development of aspirin erosions. Flow determinations were made before aspirin (20 mM in 140 mM HCl) exposure and at 2, 10, and 20 minutes after the initiation of the chemical insult. Lesions formed at 30 minutes of acetylsalicylic acid exposure. The epithelium was separated into normal and injured, based on gross discoloration caused by intramucosal hemorrhage. The calculated blood flows to the abnormal and normal mucosa were identical at 2 minutes (0.22 +/- 0.04 versus 0.15 +/- 0.03, NS) and at 10 minutes (0.39 +/- 20 versus 0.17 +/- 0.04, NS) after initiation of aspirin injury (all values in ml/gram-wet weight/min, mean +/- SEM). By 20 minutes of aspirin exposure, mucosal blood flow to areas that eventually became injured was greater than the blood flow to areas that remained normal (0.45 +/- 0.12 versus 0.13 +/- 0.05 P less than 0.05). The data suggest that ischemia does not play a role in chemical erosive gastritis.
Topical 16,16-dimethyl (dm) prostaglandin E2 produces an alkaline secretion from the canine stomach. This study attempts to assess whether this prostaglandin-induced secretion might have a cytoprotective role. Chambered ex vivo perfused wedges of canine stomach were divided into equal halves: a control and test side. The mucosa of each half was sequentially exposed to isosmotic hydrochloric acid, 20 microgram of 16,16 dm PGE2 in acid, 20 mmol aspirin + 20 microgram of dm PGE2 in acid then isosmotic acid. The test side received 40 mmHg pneumatic counterpressure to reduce the prostaglandin-induced fluid movement before, during and after the aspirin exposure. The mucosal lesions produced on each side were graded 0 to 14. If prostaglandin exerts its cytoprotective effect by stimulating an alkaline secretion, elimination of that secretion with counterpressure should prevent a cytoprotective action. Nine dogs were studied. Topical prostaglandin increased transmucosal fluid movement from 10 microliter/min to 65 microliter/min. Counterpressure decreased this volume flow by 50 per cent (P < 0.01); it also decreased mucosal blood flow on the test side by 20 per cent (P < 0.05). The lesions on the counterpressure side were worse 2.0 +/- 0.6 v. 0.8 +/- 0.3 (P < 0.01). Thus the greater damage in the counterpressure group could have been caused by diminished fluid movement or by reduced blood flow or a combination of both factors. Although this study cannot distinguish between these possibilities, it seems like that the prostaglandin-induced alkaline secretion has a cytoprotective role.
A primate model for the study of biliary pancreatic reflux under relatively physiological conditions is described. Cannulas were inserted into the gallbladder and the common bile duct of rhesus monkeys, and a pedicled segment of small bowel was used to create a pancreaticocutaneous fistula after resection of the spleen and pancreatic tail. Following recovery, Hypaque was instilled into the gallbladder with maintenance of common duct pressure within a normal range. The pancreatic duct was visualized in 21 of 34 radiographic studies (19 monkeys). Small amounts of iodine were detected in the fistula effluent of nine of 11 animals that refluxed radiologically. Radioactive polyethylene glycol (PEG-C14) was instilled into the gallbladder and pancreatic fistula drainage sampled by aspiration (26 studies, four monkeys). When compared to controls without PEG instillation (six studies, four monkeys), there was a significant rise in fistula counts beginning 50 minutes after injection and peaking at 180 minutes. In a second series of studies, pancreatic fistula aspiration was replaced by a flush technique using a triple-lumen cannula which allowed constant monitoring and control of fistula pressure. A statistically significant rise and fall of radioactivity after PEG introduction again was demonstrated. These data demonstrate taht biliary pancreatic reflux can occur and be quantitated under these experimental conditions.
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