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Biomedical subjects

E B Rypins

Publications and source records attributed to E B Rypins.

At least 19 recordsLinked to original sources

A computer model of the kidney.

We developed a computer model of renal function that factors perfusion pressure, serum sodium, potassium, antidiuretic hormone and aldosterone concentrations to derive urine output, urinary sodium and urinary potassium excretion. The model implements Uttamsingh's (Uttamsingh, R.J., et al. Mathematical model of the human renal system. Med. Biol. Eng. Comput. 23 (1985) 525-536) analytical equations as an electrical circuit suitable for network analysis. This model is useful for studying the effects of renal blood flow and the humoral milieu on renal function in normal kidneys either as a stand-alone unit or in combination with other physiological electrical models.

Computer Simulation

Cytologic detection of colorectal cancer after administration of oral lavage solution.

Whether malignant cells can be detected in the bowel movements induced by oral gut lavage solution administration was studied in patients with known colonic adenocarcinomas. The induced bowel movements were collected in 27 patients, nine of whom had cancer proven by anatomic pathologic examination. The cells present were recovered with a simple technique and stained by the Papanicolaou method. Malignant cells were identified in the stained preparations in all nine patients with cancer (100% sensitivity), and there were few false positives (94.5% specificity). The authors concluded that if additional studies with greater numbers of subjects confirm the reliability of this technique, a test may be developed that would be useful for either early detection or screening.

Adenocarcinoma

Blood vessel modeling.

We developed a computer program for calculating hemodynamic parameters in a segment of vessel or catheter using Poiseuille's Law. The program analyzes flow, pressure, flow velocity, total fluid volume, pulse pressure, resistance and Reynolds number in a segment of vessel. The user can dilate or constrict at any position along its length for modeling stenoses or aneurysms. Viscosity, fluid density, length, and intrinsic radius can be varied to simulate atherosclerotic vessels. Idealized linear hemodynamics of an abdominal aortic aneurysm or a coarcted aorta can be modeled from angiographic data. Interactive results are displayed graphically and can be printed for future reference. The program can estimate catheter, graft or vascular resistances, flow velocity in atherogenic arteries, and the likelihood of achieving laminar flow.

Arteries

Single-lumen vs double-lumen catheters for total parenteral nutrition. A randomized, prospective trial.

Multilumen catheters have been condemned for hyperalimentation based on reports of infection rates between 10% and 25% in uncontrolled studies. Because of the potential usefulness of multilumen catheters, we studied infection rates in a prospective, randomized trial. All patients requiring total parenteral nutrition were randomized to either single- or double-lumen catheters. Single-lumen catheters were used for dextrose-amino acids only. Medications or fat emulsions were given either by another central line or peripherally. Double-lumen catheters were used for dextrose-amino acid solutions, compatible medications, and fat emulsions. Catheters were cultured (48 single lumen and 53 double lumen) from 112 patients who successfully completed the study. No patients in either group developed catheter sepsis. We concluded that parenteral nutrition can be given as safely via double-lumen catheters as single-lumen catheters when strict protocols are established and followed.

Bacterial Infections

A computer model of the heart that obeys Starling's law.

We developed a computer model of the heart that accurately reproduces human left ventricular pressure wave morphology. The model factors beat-to-beat venous return in generating cardiac output and simulates congestive heart failure when the venous return exceeds the heart's pumping capacity. The blood pressure waveform produced by our model resembles experimental data with a greater than 98% correlation and the model incorporates Starling's transfer function. The model is useful for simulations of cardiovascular hemodynamics where accurate waveforms and venous return feedback or modeling failing hearts are important.

Blood Pressure

Three-phase study of phlebitis in patients receiving peripheral intravenous hyperalimentation.

We found clinical phlebitis in 57 of 88 patients with peripheral hyperalimentation (65%). To determine if this was a problem common to all intravenous fluid therapy at our hospital, we performed a point-prevalence study. The prevalence of phlebitis in nonhyperalimentation intravenous patients was 18% (84 of 456 patients). We then performed a randomized, prospective, double-blind trial of sham versus standard in-line filters to determine if bacteria or filterable particulate matter was responsible for phlebitis in the peripheral hyperalimentation group. The standard-filter group had a phlebitis rate of 74% compared with 64% in the sham-filter group. We then eliminated in-line filters and replaced the standard glucose-based solution with a glycerol-based peripheral hyperalimentation solution. The phlebitis rate decreased from 68% to 27% (p less than 0.001). In conclusion, phlebitis in peripheral hyperalimentation patients was probably due to chemical properties of the peripheral hyperalimentation solution rather than bacteria or particulates.

Amino Acids

Small-diameter portacaval H-graft for variceal hemorrhage.

This report describes the steps in the development of the concept of partial shunting from its earliest stages to the 8-mm-diameter portacaval H-graft. Sequentially decreasing the diameter of the graft from 20 mm did not seem to affect hepatic hemodynamics until the 10-mm-diameter graft was used. At this point, we began to see some patients maintain prograde portal flow. Further reduction in diameter gave a higher rate of patients with prograde flow. Postoperative flow patterns correlate with lower encephalopathy rates and better long-term survival. Important nuances of the operative technique as well as pre- and postoperative management are described.

Blood Vessel Prosthesis

Impaired oxygenation of gastric mucosa in portal hypertension. The basis for increased susceptibility to injury.

Increased susceptibility to mucosal damage is a prominent feature of portal hypertensive gastropathy. Since the portal hypertensive gastric mucosa has extensive microvascular changes, we postulated that the increased sensitivity to mucosal damage could have an ischemic basis. We measured distribution of gastric serosal and mucosal oxygenation in a group of portal hypertensive and sham-operated rats, and then studied the effects of intragastric aspirin. In the basal state, gastric mucosa of portal hypertensive rats had significantly reduced oxygenation compared to controls (24 +/- 5 vs 45 +/- 7 mm Hg PO2, P less than 0.02), while serosal oxygenation was similar between the two groups. Intragastric aspirin produced significantly greater mucosal damage to portal hypertensive rats and mucosal oxygenation was almost one third that of sham-operated controls. Systemic arterial pressures and oxygenation were similar between the two groups. We conclude that there is impairment of gastric mucosal oxygenation and increased mucosal damage by aspirin in portal hypertensive rats compared with sham-operated controls. These results support our hypothesis that the increased sensitivity of the portal hypertensive mucosa to damage is a consequence of impaired mucosal oxygenation.

Animals

Colonic mucosectomy using laser photodynamic therapy.

Photodynamic therapy (PDT) involves photosensitizing tissue and then activating it with monochromatic light, causing necrosis. Precise control of the extent of injury should be possible by varying the energy density of the light applied to the target tissue. We tested the sensitivity of colonic tissue to PDT by injecting 10 mg/kg Photofrin II intraperitoneally in 10 rats. After 24 hr the left colon was opened and cleansed. A 1.0-cm2 area of mucosa was exposed to 630 nm (red) light produced by an argon-pumped dye laser. Pairs of rats were treated with energy densities of either 10, 20, 40, 60, or 80 J/cm2, controlled by varying exposure times. After 48 hr, we sacrificed the rats and fixed, sectioned, and stained the left colons. The depth of injury was measured with an ocular micrometer and expressed as a percentage of normal bowel wall thickness. A curve was fit to the data points by computerized nonlinear regression. The relationship between depth of injury (Y) and energy density (X) was found to fit the equation Y = 1 - aebx, where constants a = 1.15 and b = -0.0353, (R2 = 0.93, P less than 0.001). The relationship between injury and energy density is biphasic, rising rapidly from 0 to 40 J/cm2 and more slowly after this point, suggesting that colonic mucosa is more sensitive to PDT than muscularis, providing a margin of safety against perforation. Bowel perforation did not occur in this study but is predicted by extrapolation for energy densities of 100 J/cm2 or greater. These data indicate that photodynamic colonic mucosectomy is possible.

Animals

Nonlinear SPICE models for physiologic systems.

Most biological systems are nonlinear but investigators interested in modeling them often make linear approximations to avoid performing tedious manual calculations. SPICE (Simulation Program with Integrated Circuit Emphasis, developed at the University of California, Berkeley, CA), an electrical circuit simulation program, is frequently used for creating and analyzing linear network models of physiologic and pathophysiologic processes. However, few investigators use the full capabilities of the program by modeling nonlinear elements. We developed six nonlinear SPICE elements, allowing simplified modeling of most commonly encountered physiologic processes. These are provided as subcircuits that can be easily incorporated into existing SPICE models. Included are voltage and current controlled nonlinear resistors, capacitors and inductors. In addition, we describe adders, multipliers, powers, inverse, and derivative functions.

Computer Simulation

Misoprostol versus antacid titration for preventing stress ulcers in postoperative surgical ICU patients.

Bleeding from gastroduodenal lesions is a potentially life-threatening complication in patients subjected to overwhelming physiologic stress. Titration of gastric contents with antacid was the first prophylactic treatment regimen proved to decrease the incidence of bleeding and remains the standard by which other methods are compared. We designed a prospective double-blind, double-placebo study comparing the effectiveness of antacid titration with fixed doses of a synthetic prostaglandin E1 analog (misoprostol) for preventing stress gastritis and bleeding. To assess the success of each treatment regimen, we did endoscopic examinations before operation, 72 hours after operation, and after the patient had completed the study. A total of 281 patients entered the study (140 misoprostol, 141 antacid). The two groups were comparable with respect to preoperative parameters and type of operation. We found no statistically significant differences between the two treatment groups concerning upper gastrointestinal tract lesions or serious adverse effects. No clinically evident upper gastrointestinal hemorrhage occurred in either group. Mean gastric pH, measured at two-hour intervals during the initial 72 hours, was maintained at 4.0 or higher in both groups. We conclude that fixed-dose misoprostol is as effective as intensive antacid titration in preventing stress ulcers and bleeding in surgical ICU patients.

Adult

Repair of incisional hernia.

Because wound infection is a major cause of incisional hernia, the question posed is whether or not repairs of incisional hernias are at a higher risk for wound infection also. To answer this, we analyzed the incidence of wound infection after repair of incisional hernias during a 30 month period and compared it with the infection rate in all other clean procedures performed during the same period. All repairs of incisional hernias were performed upon patients with completely healed incisions without clinical signs of infection. Patients undergoing concomitant procedures upon the gastrointestinal tract were excluded. During the 30 month period, 995 clean operations were performed. In the 80 repairs of incisional hernias, there were 13 infections proved by culture, yielding an over-all infection rate of 16 per cent. In the remaining 915 clean procedures, there were 14 wound infections (1.5 per cent, p less than 0.0001). Of these 915 clean operations, 241 were repairs of inguinal hernias. Two infections occurred in this subgroup (0.8 per cent, p less than 0.0001, compared with repairs of incisional hernias). In patients undergoing repairs of incisional hernias with previously documented wound infections, 41 per cent had infected repairs. By comparison, only 12 per cent of patients without a prior infection had infections develop in the hernial repair (p less than 0.05). The infection rate for patients not receiving prophylactic antibiotics (21 per cent) was almost twice the rate for those receiving antibiotics (11 per cent), p = 0.07. We concluded that repair of incisional hernias has a significantly higher rate of infection than do other clean general surgical procedures. Herniorrhaphy of a wound that was previously infected is at a higher risk for reinfection, despite complete healing of the skin and absence of clinical signs of infection. Perioperative antibiotic prophylaxis may be indicated, but randomized studies are needed. For reporting and surveillance purposes, repairs of incisional hernias should not be classified as clean surgical procedures.

Abdominal Muscles

Modeling splanchnic hemodynamics after distal splenorenal shunt: a computer simulation and sensitivity analysis.

The distal splenorenal shunt operation was specifically designed to preserve portal flow and maintain elevated portal pressure. However, although this goal is met in the immediate postoperative period, flow decreases over time, and in as many as 75% of alcoholic patients, portal flow is lost in the first year. Various explanations have been offered for this observation, and modifications of the original operation have been proposed (splenopancreatic disconnection). Although other portacaval shunts have been successfully modeled as electrical circuits, this approach has never been described for the distal splenorenal shunt. In this study we developed a computer program that modeled the distal splenorenal shunt as an electrical circuit. We performed an analysis to determine the sensitivity of portal flow to changes in each resistance element and then performed a series of simulation experiments to critically examine the various explanations offered for the gradual changes in hepatic hemodynamics. We found that portal flow was most sensitive to resistance in the renal vein followed by resistance in the anastomosis. The simulation experiments suggested a new alternative to splenopancreatic disconnection--restricting the ability of the splenic vein, anastomosis, or renal vein to dilate. Additional clinical studies will be needed to test these predictions.

Collateral Circulation

Computer-derived equations for predicting survival postoperatively. Their usefulness and limitations.

We used multivariate analysis to determine whether survival following perforations of the gastrointestinal tract could be accurately predicted from preoperative data. Of 12 variables tested, four were found to have predictive value. These were age, pulmonary disease, preoperative shock, and the attending surgeon. When these four variables were employed in a logistic regression equation on 42 patients, it correctly predicted which 21 patients died before leaving the hospital. To produce an equation useful for other hospitals, we recalculated it without the attending surgeon variable. Again, the equation was used to predict survival. The correlation of predicted vs observed outcome remained high, and, using a 2 x 2 chi 2 test, the correlation was significant. We then cross validated the three-variable model on data from a second hospital. The model accurately predicted the new data equally well. We believe that predictive models can identify risk factors in a variety of patient populations and can determine who is likely to benefit from specific treatment modalities.

Age Factors

A prospective, randomized clinical investigation of cholecystoenterostomy and choledochoenterostomy.

A prospective, randomized clinical trial was conducted to assess the efficacy of bilioenteric bypass in noncalculous distal biliary obstruction. Thirty-one patients required bypass for either malignant obstruction or chronic pancreatitis and were randomized into two groups: cholecystoenterostomy or choledochoenterostomy with cholecystectomy. Nine bypasses failed after cholecystoenterostomy and two after choledochoenterostomy (p less than 0.04). Eight of the 9 failures occurred in the subgroup of 22 patients with malignant biliary obstruction. In this subgroup, five bypasses failed within 90 days of operation, all after cholecystoenterostomy (p = 0.03 compared with choledochoenterostomy). The results indicate that choledochoenterostomy is the superior operation for malignant distal biliary obstruction. Additional studies will be necessary to identify the procedure of choice for benign noncalculous obstructions.

Aged

Influence of portal hemodynamics on long-term survival of alcoholic cirrhotic patients after small-diameter portacaval H grafts.

Estimating postoperative survival rates after portasystemic shunt procedures has concerned surgeons during the last 40 years. The relationship between survival and Child's classification has clearly demonstrated the importance of preoperative hepatic functional reserve. Maintaining hepatic portal perfusion has been proposed as an additional protective factor but has never been proved clinically. Our analysis of survival after partial shunting with small-diameter portacaval H grafts has shown that both hepatic functional reserve and postoperative portal perfusion correlate with postoperative survival in alcoholic patients, but the latter was a stronger correlate of long-term survival. A predictive model based on both factors has been described for estimating the overall survival rate of alcoholics after partial shunting with small-diameter portacaval H grafts.

Actuarial Analysis

Asymptomatic peptic disease in patients undergoing major elective operations: a prospective endoscopic study.

Postoperative bleeding is usually attributed to stress ulcers; however, occult preoperative lesions could also be responsible. To determine their frequency and nature, we prospectively examined 72 patients endoscopically prior to major elective operations. Entry criteria included a planned stay in the Surgical Intensive Care Unit, greater than 2 days, and a negative history, physical examination, and stool guaiac. Gastric and duodenal mucosae were scored separately, using a 0- to 7-point scale. Scores were graded negative (0), hyperemia (1), gastroduodenitis (2-5), mucosal erosions (6), and ulcers (7). Erosions or ulcers were found in 14% of patients and gastroduodenitis is an additional 10%. We found that none of the 27 risk factors or any combination of factors tested correlated with ulcers, erosions, or gastroduodenitis. Thus, patients with asymptomatic gastroduodenal erosions or ulcerations could not be identified preoperatively, except by endoscopy. Until the significance of these lesions as cause of postoperative bleeding is determined, we recommend routine postoperative gastric pH titration with antacids for patients undergoing major elective operations.

Gastrointestinal Hemorrhage