Noninvasive biomagnetic detection of intestinal slow wave dysrhythmias in chronic mesenteric ischemia.

Chronic mesenteric ischemia (CMI) is a challenging clinical problem that is difficult to diagnose noninvasively. Diagnosis early in the disease process would enable life-saving early surgical intervention. Previous studies established that superconducting quantum interference device (SQUID) magnetometers detect the slow wave changes in the magnetoenterogram (MENG) noninvasively following induction of mesenteric ischemia in animal models. The purpose of this study was to assess functional physiological changes in the intestinal slow wave MENG of patients with chronic mesenteric ischemia. Pre- and postoperative studies were conducted on CMI patients using MENG and intraoperative recordings using invasive serosal electromyograms (EMG). Our preoperative MENG recordings showed that patients with CMI exhibited a significant decrease in intestinal slow wave frequency from 8.9 ± 0.3 cpm preprandial to 7.4 ± 0.1 cpm postprandial (P < 0.01) that was not observed in postoperative recordings (9.3 ± 0.2 cpm preprandial and 9.4 ± 0.4 cpm postprandial, P = 0.86). Intraoperative recording detected multiple frequencies from the ischemic portion of jejunum before revascularization, whereas normal serosal intestinal slow wave frequencies were observed after revascularization. The preoperative MENG data also showed signals with multiple frequencies suggestive of uncoupling and intestinal ischemia similar to intraoperative serosal EMG. Our results showed that multichannel MENG can identify intestinal slow wave dysrhythmias in CMI patients.

A comparison of 399 open and 568 laparoscopic gastric bypasses performed during a 4-year period.

BACKGROUND: Laparoscopic Roux-en-Y gastric bypass surgery (RYGB) was introduced at the authors' institution 5 years ago. The authors analyzed the short- and long-term results of this procedure compared with those for the same procedure using the laparotomy approach over the same period. METHODS: Retrospective analysis of a prospectively collected bariatric database used the outcome end points used by the American Society of Bariatric Surgery (ASBS) and the American College of Surgeons (ACS) in their center of excellence programs. RESULTS: From January 2001 to July 2005, 568 laparoscopic and 399 open gastric bypasses were performed at Vanderbilt University. The patients were from the same bariatric surgery program and therefore received the same pre- and postoperative care. The hospital length of stay in the laparoscopic group was significantly shorter (2.5 +/- 2.4 days) than in the open group (3.7 +/- 3.7 days; p = 0.001). The procedure time was significantly shorter in the laparoscopic group (164 +/- 50 min) than in the open group (195 +/- 50 min; p = 0.0001). The follow-up assessment response at 2 years was 76.6%. At 2 years, the excess weight loss (EWL) was significantly greater in the laparoscopic group (71.3% +/- 18.4%) than in the open group (67.3% +/- 15.3%; p = 0.03). The wound infection rate was significantly higher in open group (9.2%) than in the laparoscopic group (1.7%; p = 0.001). There was no significant difference in 30-day mortality: open (0.50%) versus laparoscopic (0.17%; p = 0.371). There was no significant difference in the 30-day reoperation rate between the open (2.4%) and laparoscopic (2.6%; p = 0.705) groups. The 30-day readmission rate was similar in the open (5.0%) and laparoscopic (5.2%; p = 0.852) groups, as was the rate of leakage from the gastrojejunostomy in the open (0.50%) and laparoscopic (0.35%; p = 0.127) groups. The conversion rate from laparoscopic procedure to laparotomy was 1.7%. CONCLUSION: In the authors' institution, a laparoscopic bariatric surgery program with a very low rate of morbidity and mortality has been introduced. Operative time, hospital stay, and wound complications are reduced with the laparoscopic approach. The laparoscopic and open procedures are equally safe, with equivalent 30-day mortality, readmission, reoperation, and gastrojejunostomy leakage rates.

Risk of secondary hyperparathyroidism after laparoscopic gastric bypass surgery in obese women.

BACKGROUND: Metabolic bone disease is a potential complication of bariatric surgery. The aims of our study were to evaluate the effects of laparoscopic gastric bypass on calcium and vitamin D metabolism, and to identify patients at high risk to develop secondary hyperparathyroidism (HPT). METHODS: Serum calcium, alkaline phosphatase, intact parathyroid hormone (PTH), and 25-hydroxy (OH) vitamin D were measured at 3, 6, 12, and 24 months after laparoscopic gastric bypass in a cohort of morbidly obese women. Logistic regression was used in both univariate and multivariate models to identify independent preoperative variables associated with secondary HPT. RESULTS: The study enrolled 193 morbidly obese women. During the 2-year follow-up period, the incidence of elevated PTH levels (>65 pg/ml) was 53.3%. The mean time elapsed between surgery and detection of secondary HPT was 9.1 months (range, 3-24 months). Vitamin D deficiency was observed in 39 patients (20.2%). On univariate analysis, the preoperative factors associated with secondary HPT were race (high PTH levels were detected in 70% of African Americans versus 50% of Caucasians; p < 0.05), preoperative body mass index (BMI; high PTH: 52.5 +/- 10.8 versus normal PTH: 48.9 +/- 7.5 kg/m2; p < 0.01), and age (high PTH: 44.9 +/- 9.2 versus normal PTH: 42.3 +/- 9 years, p < 0.05). Race and age remained independent risk factors for secondary HPT in the multivariate logistic regression model after adjusting for the covariate Roux-limb length. African Americans were at more than 2.5 times greater risk to develop secondary HPT as Caucasian (RR 2.5; 95% CI: 1.03-6.17, p < 0.05). Patients older than 45 years were at 1.8 times higher risk of developing secondary HPT as their younger counterparts (RR 1.8; 95% CI: 1.01-3.32, p < 0.05). CONCLUSIONS: Morbidly obese women have a high incidence of elevated PTH levels after gastric bypass surgery. Low vitamin D levels did not constitute the only reason behind this finding. African-American women and women older than 45 years of age were at significantly higher risk of developing secondary HPT. In these populations, aggressive supplementation with calcium citrate and vitamin D should be implemented.

The role of the surgeon in the evolution of flexible endoscopy.

Several cultures, including the Egyptians, Greeks, Romans, and Arabs, made attempts to view accessible human body cavities using a variety of instruments such as spatulas and specula. The first endoscope was created in 1806 when Phillip Bozzini, a German-born urologist, constructed the lichtleiter, which used concave mirrors to reflect candlelight through an open tube into the esophagus, bladder, or rectum. Maximilian Carl-Friedrich Nitze, another German urologist, produced the first usable cystoscope in 1877 by using series of lenses to increase magnification. He was also the first to place light inside the organ of interest to aid visualization. In 1880 Mikulicz made the first gastroscope using a system similar to Nitze's cystoscope. Modern endoscopy was born with the introduction of the fiberoptic endoscope in the late 1950s. Over the ensuing 50 years endoscopy revolutionized many aspects of the surgeon's practice. Endoscopy can now be used to diagnose and often treat gastrointestinal cancer, hemorrhage, obstruction, and inflammatory conditions. This review was initiated by the SAGES Flexible Endoscopy Committee to chronicle the role of the surgeon in the development and introduction of flexible endoscopy into clinical practice, historically and in contemporary surgery. Flexible endoscopy evolved out of surgeons' need to overcome diagnostic and therapeutic challenges. There have been many recent technological advances that facilitate endoluminal therapies, and flexible endoscopy is now traversing new ground. Surgeons have been major contributors in the development of all aspects of endoscopy. There is a continually expanding list of therapeutic options available to patients. The difficult questions of which procedure, on which patient, and when can be answered best by the surgeon versed in endoscopic, laparoscopic, and open surgical techniques.

A biomagnetic assessment of colonic electrical activity in pigs.

The electrical control activity of the large intestine was recorded in six pigs using a SQUID magnetometer. The study was performed in pre- and post-colectomy/sham-colectomy conditions. The biomagnetic field associated with colonic ECA changed drastically in subjects that underwent the colectomy procedure, whereas the signal for the control animals was nearly unchanged. Power spectral analysis was used to determine the average changes of dominant frequency and amplitude between baseline versus colectomy and sham-colectomy conditions. The dominant frequency was increased by 68 +/- 24% (versus 2 +/- 3% in control). The amplitude was decreased by 69 +/- 24% (versus 13 +/- 17% in control). This is the first study of transabdominal magnetic fields associated with colonic ECA, suggests some of the side effects generated in colectomy surgery and shows the utility of the biomagnetic technique in studies of the large intestine.

Biomagnetic characterization of spatiotemporal parameters of the gastric slow wave.

Certain gastric disorders affect spatiotemporal parameters of the gastric slow wave. Whereas the electrogastrogram (EGG) evaluates electric potentials to determine primarily temporal parameters, fundamental physical limitations imposed by the volume conduction properties of the abdomen suggest the evaluation of gastric magnetic fields. We used a multichannel superconducting quantum interference device magnetometer to study the magnetogastrogram (MGG) in 20 normal human subjects before and after a test meal. We computed the frequency and amplitude parameters of the gastric slow wave from MGG. We identified normal gastric slow wave activity with a frequency of 2.6 +/- 0.5 cycles per minute (cpm) preprandial and 2.8 +/- 0.3 cpm postprandial. In addition to frequency and amplitude, the use of surface current density mapping applied to the multichannel MGG allowed us to visualize the propagating slow wave and compute its propagation velocity (6.6 +/- 1.0 mm s(-1) preprandial and 7.4 +/- 0.4 mm s(-1) postprandial). Whereas MGG and EGG signals exhibited strong correlation, there was very little correlation between the MGG and manometry. The MGG not only records frequency dynamics of the gastric slow wave, but also characterizes gastric propagation. The MGG primarily reflects the underlying gastric electrical activity, but not its mechanical activity.

Predictors of success after laparoscopic gastric bypass: a multivariate analysis of socioeconomic factors.

BACKGROUND: Laparoscopic gastric bypass (LGB) has proven efficacy in causing significant and durable weight loss. However, the degree of postoperative weight loss and metabolic improvement varies greatly among individuals. Our study is aimed to identify independent predictors of successful weight loss after LGB. METHODS: Socioeconomic demographics were prospectively collected on patients undergoing LGB. Primary endpoint was percent of excess weight loss (EWL) at 1-year follow-up. Insufficient weight loss was defined as EWL or=52.8%. According to this definition, 147 patients (81.7%) achieved successful weight loss 1 year after LGB. On univariate analysis, preoperative BMI had a significant effect on EWL, with patients with BMI <50 achieving a higher percentage of EWL (91.7% vs 61.6%; p = 0.001). Marriage status was also a significant predictor of successful outcome, with single patients achieving a higher percentage of EWL than married patients (89.8% vs 77.7%; p = 0.04). Race had a noticeable but not statistically significant effect, with Caucasian patients achieving a higher percentage of EWL than African Americans (82.9% vs 60%; p = 0.06). Marital status remained an independent predictor of success in the multivariate logistic regression model after adjusting for covariates. Married patients were at more than two times the risk of failure compared to those who were unmarried (OR 2.6; 95% CI: 1.1-6.5, p = 0.04). CONCLUSIONS: Weight loss achieved at 1 year after LGB is suboptimal in superobese patients. Single patients with BMI < 50 had the best chance of achieving greater weight loss.

Endoscopic evaluation of the gastrojejunostomy in laparoscopic gastric bypass. A series of 340 patients without postoperative leak.

BACKGROUND: A significant and potentially deadly complication of the Roux-en-Y gastric bypass is leakage from the gastrojejunostomy (GJ). The aim of our study was to evaluate the efficacy of intraoperative endoscopy in preventing postoperative anastomotic leakage. METHODS: The study enrolled 340 consecutive patients undergoing laparoscopic gastric bypass procedures performed from January 2001 to July 2004. In all cases, an endoscopist performed video gastroscopy to evaluate the integrity of the GJ using air insufflation of the pouch after distal clamping of the Roux limb. Intraoperative leaks were repaired and the anastomosis was retested. Demographic, operative, and endoscopic data were collected and analyzed. Logistic regression was used in both univariate and multivariate modeling to identify independent preoperative variables associated with the presence of intraoperative leak. Model parameters were estimated by the maximum likelihood method. From these estimates, odds ratios (ORs) with 95% confidence intervals (CIs) were computed. RESULTS: There were no postoperative anastomotic leaks or mortalities in our series. Overall, endoscopic evaluation of the GJ resulted in the detection of 56 intraoperative leaks (16.4%). There was a significant difference in the incidence of intraoperative leakage for patients older than 40 years (21%) vs those younger than 40 years (10.5%; p = 0.01). In the initial 91 cases, the GJ was performed by the end-to-end anastomosis (EEA) technique; the subsequent 249 were performed with a combination of linear stapling and handsewn technique. There was a trend toward more leakage in the GIA group (18%) versus EEA (12%); however, the difference was not significant (p = 0.188). Age remained an independent risk factor for leak detected intraoperatively in the multivariate logistic regression model after adjusting for covariates. Age >40 years increased the risk of intraoperative leakage by 2.3 times (OR, 2.3; 95% CI, 1.2-4.6; p = 0.01). The rate of postoperative anastomotic stricture was the same among patients detected with an intraoperative leak (5.4%) and those without (5.6%; p = 0.934). CONCLUSIONS: Endoscopic evaluation of the GJ is a sensitive and reliable technique for demonstrating anastomotic integrity and preventing postoperative morbidity after gastric bypass. Age >40 years was identified as an independent risk factor for intraoperative leak in this series.

Long-term evaluation of patient satisfaction and reflux symptoms after laparoscopic fundoplication with Collis gastroplasty.

BACKGROUND: Esophageal shortening is a complication of advanced gastroesophageal reflux disease (GERD). For patients with short esophagus, Collis gastroplasty combined with fundoplication provides excellent symptomatic relief from GERD disease. The literature lacks studies comparing satisfaction and reflux symptoms between patients who underwent Nissen fundoplication with Collis gastroplasty and those who had primary fundoplication alone. This study aimed to assess long-term satisfaction and GERD-related quality of life after laparoscopic Collis-Nissen fundoplication, and to compare them with those for Nissen fundoplication alone. METHODS: A nested case-control study was conducted. In this study, 14 cases of laparoscopic Collis-Nissen fundoplications were matched for age, gender, and length of the follow-up period to a cohort of 120 control subjects who underwent laparoscopic Nissen fundoplication. All the patients were mailed a follow-up survey which included a Short Form-12 (SF-12) health status (quality-of-life) questionnaire (a validated quality-of-life instrument), a Quality of Life in Reflux and Dyspepsia (QOLRAD) questionnaire (a GERD-specific quality-of-life instrument), and queries regarding long-term satisfaction and medication use. RESULTS: Both groups showed a significant postoperative increase in QOLRAD mean scores (p = 0.01). However, the difference in the delta (postoperative-preoperative) score between the two groups was not significant (Fig. 1). There were no differences in mental (MCS) or physical (PCS) SF-12 scores between the two groups. The rate of satisfaction with the surgery was similar in the Nissen-Collis fundoplication (87.5%) and Nissen fundoplication (87%) groups. CONCLUSIONS: Collis gastroplasty combined with Nissen fundoplication is an effective procedure for patients with a shortened esophagus diagnosed intraoperatively during antireflux surgery. Patient satisfaction, postoperative quality of life, and QOLRAD score improvement after this procedure are comparable with those observed in patients treated with Nissen fundoplication alone.

Heller myotomy vs Heller myotomy plus Dor fundoplication: cost-utility analysis of a randomized trial.

BACKGROUND: The addition of a Dor antireflux procedure reduces the risk of pathologic gastroesophageal reflux (GER) by ninefold following laparoscopic Heller myotomy for achalasia. It is not clear, however, how these benefits compare with the increased cost of the fundoplication. The objective of this study was to estimate the cost-effectiveness of Heller myotomy plus Dor fundoplication compared with Heller alone in patients with achalasia. METHODS: We conducted a cost-utility analysis using the Markov simulation model to examine the two treatment alternatives. The model estimated the total expected costs of each strategy over a 10-year time horizon. Data for the model were derived from our randomized clinical trial. The strategies were compared using the method of incremental cost-effectiveness analysis. RESULTS: The incidence of pathologic GER was 47.6% (10 of 21 patients) in the Heller group and 9.1% (2 of 22 patients) in the Heller plus Dor group using an intention-to-treat analysis (p = 0.005). Heller plus Dor was associated with a significant reduction in the risk of GERD (relative risk 0.11; 95% confidence interval 0.02-0.59; p = 0.01). The cost of surgery was significantly higher for Heller plus Dor than for Heller alone (mean difference $942; p = 0.04), secondary to a longer operating room time (mean difference 40 min; p = 0.01). At a time horizon of 10 years, when proton pump inhibitor (PPI) therapy costs are considered, the cost-utility analysis demonstrates that Heller plus Dor surgery is associated with a total cost of $6,861 per patient and a quality-adjusted life expectancy of 9.9 years, whereas Heller-alone surgery is associated with a cost of $9,541 per patient and a quality-adjusted life expectancy of 9.5 years. CONCLUSIONS: In achalasia patients, Heller myotomy plus Dor fundoplication is preferred to Heller alone because it is both more effective in preventing postoperative GERD and more cost-effective at a time horizon of 10 years.

Diabetic gastroparesis alters the biomagnetic signature of the gastric slow wave.

BACKGROUND: Gastroparesis is characterized by delayed gastric emptying without mechanical obstruction, but remains difficult to diagnose and distinguish from other gastrointestinal (GI) disorders. Gastroparesis affects the gastric slow wave, but non-invasive assessment has been limited to the electrogastrogram (EGG), which reliably characterizes temporal dynamics but does not provide spatial information. METHODS: We measured gastric slow wave parameters from the EGG and magnetogastrogram (MGG) in patients with gastroparesis and in healthy controls. In addition to dominant frequency (DF) and percentage power distribution (PPD), we measured the propagation velocity from MGG spatiotemporal patterns and the percentage of slow wave coupling (%SWC) from EGG. KEY RESULTS: No significant difference in DF was found between patients and controls. Gastroparesis patients had lower percentages of normogastric frequencies (60 ± 6% vs 78 ± 4%, p < 0.05), and higher brady (9 ± 2% vs 2 ± 1%, p < 0.05) and tachygastric (31 ± 2% vs 19 ± 1%, p < 0.05) frequency content postprandial, indicative of uncoupling. Propagation patterns were substantially different in patients and longitudinal propagation velocity was retrograde at 4.3 ± 2.9 mm/s vs anterograde at 7.4 ± 1.0 mm/s for controls (p < 0.01). No difference was found in %SWC from EGG. CONCLUSIONS & INFERENCES: Gastric slow wave parameters obtained from MGG recordings distinguish gastroparesis patients from controls. Assessment of slow wave propagation may prove critical to characterization of underlying disease processes. Future studies should determine pathologic indicators from MGG associated with other functional gastric disorders, and whether multichannel EGG with appropriate signal processing also reveals pathology.

Three year's experience with the Stretta procedure: did it really make a difference?

BACKGROUND: Endoscopic treatment is merging as a new option for GERD treatment. Many modalities have been used with modest short-term success, but no long-term follow-ups have been published. We present our 3-yr experience at Vanderbilt University using endoscopic radiofrequency energy (Stretta procedure) for GERD treatment. METHODS: Patients with follow-up >6 months were prospectively studied under IRB protocol. All were mailed SF-12 health status questionnaire and GERD specific quality-of-life (QOLRAD) questionnaires, queries about satisfaction with Stretta, and medication use. All were invited for 24-hour pH study. RESULTS: Eighty-six Stretta procedures were performed between 8/2000 and 7/2003 on 85 patients; all were outpatients, 89% under conscious sedation. Seventy-seven patients qualified for the study; 61 completed the survey, 24 returned for pH study. Follow-up was 26.2 +/- 7.5 months (6-36). All were on daily PPIs, with proven GERD by pH study or endoscopy. Mean preoperative acid exposure time was 7.8+/-2.6%, mean DeMeester score was 40.2+/-17.6. Postoperative mean acid exposure time was 5.1+/-3.3 (p=0.001), DeMeester score was 29.5+/-20.5 (p=0.041). Normal postoperative acid exposure time (pH<4 in <4.2%) was achieved in 42% of patients tested. Patients were then divided according to medication use at the end of f/u in 2 groups: Responders (off or >50% decrease in PPI dose), and nonresponders (on >50% of original PPI dose, or had fundoplication). Response rate was 60% (39 patients), 8 nonresponders underwent fundoplication (12%). Satisfaction rate was 73%. Statistically significant difference was found between the 2 groups in all measurements; SF-12 physical and mental score for responders were 45.5+/-10.2, and 52.6+/-7.8; and for nonresponders were 37.8+/-11.2 and 40.9+/-11.3 (p=0.012, p=0.0001), respectively. Statistically significant difference was also found between responders and nonresponders in postoperative acid exposure (4.5+/-3.34 vs 7.2+/-2.3, p=0.034), and DeMeester score (26.3+/-20.4 vs 39.7+/-20.2, p=0.05). Paired T test was used to compare pre- and postoperative acid exposure in each group; statistically significant difference was found only among responders: total reflux time was 7.50+/-2.3 preop and 4.5+/-3.34 postop (p=0.0001), whereas for nonresponders it was 8.6+/-3.7 and 7.2+/-2.3 (p=0.8), DeMeester scores pre- and postop among responders were 40.0+/-19.7 and 26.3+/-20.4, respectively (p=0.016), whereas for nonresponders it was 40.5+/-14.3 and 39.7+/-20.2 (p=0.79). CONCLUSIONS: Stretta is a safe modestly effective, totally endoscopic treatment for GERD. Symptomatic improvement when achieved is often associated with correlating improvement in distal acid exposure. This exposure normalizes in nearly half the treated patients.

The impact of a laparoscopic colorectal surgeon on the laparoscopic colectomy experience of a single academic center.

BACKGROUND: The objective of this study was to evaluate the impact of a laparoscopic colorectal surgeon (LCRS) on the laparoscopic colectomy experience of a single academic center. METHODS: We performed a retrospective review of case complexity, patient characteristics, operative and preparation time, and trends over time for the LCRS compared to two veteran laparoscopic surgeons (VLS). RESULTS: The LCRS performed 48 of the procedures (83%) and the VLS 10 (17%) for a total of 58 laparoscopic colon cases. The LCRS handled a greater number of complex cases (p = 0.07). For less complex cases, overall operative time differed for the two groups (LCRS = 220 +/- 11 vs VLS = 152 +/- 15 min, p = 0.004). Overall hospital stay was 4.8 +/- 0.6 days (range, 2-33). Minor complications occurred in 12 cases (21%); major complications in occurred in seven cases (12%). Among procedures performed by the LCRS, comparison of the first 24 cases to the second 24 demonstrated that operative and preparation time decreased in the second cohort (all p < 0.05). CONCLUSION: The addition of an LCRS had a significant impact on this center's experience with laparoscopic colectomies in terms of both volume and case complexity.

Vector projection of biomagnetic fields.

Biomagnetic measurements are increasingly popular as functional imaging techniques for the non-invasive assessment of electrically active tissue. Although most currently available magnetometers utilise only one component of the vector magnetic field, some studies have suggested the possibility of obtaining additional information from recordings of the full magnetic field vector. Three projection techniques were applied to different biomagnetic signals for analysis of the three orthogonal components of the vector magnetic field. Vector magnetic fields obtained from fetal cardiac activity were projected into evenly spaced directions around a unit sphere. The vector magnetic field recorded from multiple intestinal current sources with independent temporal frequencies was then projected. Finally, an external reference signal from an invasive electrode was used to project the recorded vector magnetic fields due to gastric electrical activity. In each case, it was found that the information obtained by examination of the projected magnetic field vectors gave superior clinical insight to that obtained by analysis of any single magnetic field component.

Selective effect of liver disease on the activities of specific metabolizing enzymes: investigation of cytochromes P450 2C19 and 2D6.

BACKGROUND AND OBJECTIVES: Drug metabolism is influenced by liver disease because of the central role that the liver plays in metabolic activities in the body. However, it is still unclear how activities of specific drug-metabolizing enzymes are influenced by the presence and severity of liver disease. As a consequence, alteration in metabolism of specific drugs cannot be easily predicted or appropriate dosage adjustment recommendations made. METHODS: The activities of cytochromes P450 (CYP) 2C19 and 2D6 were investigated in a group of patients with mild or moderate liver disease (n = 18) and a group of healthy control subjects (n = 10). The disposition of racemic mephenytoin for CYP2C19 and debrisoquin for CYP2D6 were characterized in plasma and urine samples collected over 192 hours. RESULTS: The elimination of S-mephenytoin was severely reduced among patients with liver disease, resulting in a 79% decrease in plasma clearance for all patients combined. This reduction was related to the severity of disease, patients with moderate disease being affected more severely than patients with mild disease. Similar differences were observed in the urinary excretion of 4'-hydroxymephenytoin metabolite. By contrast, there was no effect on the disposition of R-mephenytoin or debrisoquin. CONCLUSION: These results show selectivity in the effect of liver disease on activities of specific metabolizing enzymes, CYP2C19 being more sensitive than CYP2D6. They suggest that recommendations for modification in drug dosage in the presence of liver disease should be based on knowledge of the particular enzyme involved in metabolism of the drug. The results emphasize the need for further studies of each specific drug-metabolizing enzyme in the presence of liver disease.

The disposition of dapsone in cirrhosis.

Acetylation and N-hydroxylation of dapsone were evaluated in drug-free, non-smoking, normal subjects and subjects with cirrhosis (n = 7 for each group) after oral administration of 100 mg dapsone. Acetylation was not correlated with oral dapsone clearance or reduced in cirrhosis (0.37 +/- 0.43 versus 0.52 +/- 0.32). Fractional metabolic clearance of dapsone to its hydroxylamine was associated with dapsone oral clearance (r = 0.96, p less than 0.001, n = 14). In patients with cirrhosis, liver disease was associated with a trend to reduction in oral clearance (22%) and metabolic clearance of dapsone (48%). Protein binding was minimally reduced by cirrhosis (73% +/- 1% versus 69% +/- 3% in patients with cirrhosis (p less than 0.02). The dapsone recovery ratio was validated as a phenotypic index of the metabolic clearance of dapsone (r = 0.74, p less than 0.05). In an extended comparison of 14 patients with cirrhosis to 70 control subjects, cirrhosis was associated with reductions of 28% in dapsone recovery ratio (p less than 0.001), and 37% in acetylation ratio (p less than 0.01). Neither dapsone recovery ratio nor acetylation ratio correlated with Pugh Score, conventional liver function tests, indocyanine green clearance, or phenotypic measures of S-mephenytoin hydroxylase or debrisoquin hydroxylase activity. We conclude that cirrhosis is associated with minor changes in dapsone disposition and that dosage modification is not required. In addition, there is evidence that cirrhosis has a selective influence on activity of individual isozymes of cytochrome P450.

Opsonic fibronectin deficiency in patients with intra-abdominal infection.

The reticuloendothelial system provides host defense functions by the intravascular phagocytosis of bacteria and nonbacterial particulates. Fibronectin is opsonic for reticuloendothelial phagocytosis. Plasma fibronectin was measured before and after operation in patients with intra-abdominal infection. Preoperatively opsonic fibronectin was reduced by 39% of normal control levels in 16 patients with intra-abdominal infection. There was an even greater reduction of opsonic fibronectin after operation that was first observed in the recovery room. This deficiency persisted for the first 4 days with a tendency toward recovery of normal circulating levels by the fifth postoperative day. In contrast, patients who underwent elective major abdominal operation without infection manifested a transient opsonic fibronectin deficiency with recovery by the second and third postoperative days. Eight of 16 patients with intra-abdominal infection developed multiple organ failure. The opsonic fibronectin levels in those patients were lower than the levels in eight patients who did not develop multiple organ failure. Furthermore, there was no tendency toward recovery of normal circulating opsonic fibronectin in those patients. On all days when multiple organ failure occurred there was a marked deficiency of circulating opsonic fibronectin. We conclude that transient opsonic fibronectin deficiency occurs after major elective abdominal operation. Patients with intra-abdominal infection manifest opsonic fibronectin deficiency before operation, and further depletion of opsonic fibronectin occurs after operation. Postoperative multiple organ failure occurs only in association with severe opsonic fibronectin deficiency.

Pancreatoduodenectomy with pyloric preservation for carcinoma of the pancreas: a cautionary note.

Radical pancreatoduodenectomy for treatment of pancreatic carcinoma has been the surgical standard of care for the past four decades. The recent popularization of pylorus-sparing pancreatoduodenectomy to treat benign pancreatic disease, because of its decreased morbidity and long-term nutritional consequences, has led to the use of this procedure in cases of pancreatic carcinoma. We report recent experience with three patients with pancreatic carcinoma in whom pyloric preservation would have compromised the potential chance for curative resection or compromised palliation because of occult spread of tumor to a region not resected with this new operative approach. Two patients had proximal, microscopic intramural spread of pancreatic adenocarcinoma within the duodenum or antrum--a mode of spread not previously reported with pancreatic carcinoma. Both patients had no other evidence of metastatic involvement, and both would have had positive surgical margins in a pylorus-sparing pancreatoduodenectomy. A third case demonstrates a true submucosal recurrence of pancreatic carcinoma after a pylorus-sparing pancreatoduodenectomy. It is debatable that any case demonstrating intramural spread within the duodenum could be cured with a standard Whipple resection as this may well represent another sign of incurability, like lymphatic or perineural spread, but it is clearly a major potential obstacle to palliation if submucosal recurrences occur as a result of the use of the pylorus-sparing pancreatoduodenectomy in cases of pancreatic cancer. The use of pylorus-sparing pancreatoduodenectomy in resectable pancreatic cancers must be viewed skeptically at this time.

Simplification of cryoprecipitate coagulum choledocholithotomy by deletion of thrombin. Prevention of retained biliary duct stones.

Conventional removal of stones from the biliary ducts can be difficult and may result in retained stones. We developed a modified tenacious coagulum that entraps biliary duct stones, resulting in a more complete extraction. Coagulum choledocholithotomy was simplified by mixing 20 parts of cryoprecipitate with one part of 10% calcium chloride solution without thrombin. Tenacious coagula were generated that had a tensile strength of 106 to 140 g/sq cm within three to six minutes and were 106% to 300% stronger than coagula with thrombin. This technique was performed on six patients. In each case, an intact coagulum that entrapped more calculi than were seen on the cholangiogram was extracted. This modified technique is simple, safe, nontraumatic, and achieves a more complete extraction of stones.

Biomagnetic detection of gastric electrical activity in normal and vagotomized rabbits.

We recorded the vector magnetogastrogram (MGG) due to gastric electrical activity (GEA) in normal rabbits using a Superconducting QUantum Interference Device (SQUID) magnetometer and measured the degree of correlation of the MGG with 24 channels of serosal electrodes. The vector magnetometer allows us to non-invasively record three orthogonal magnetic field components and project the recorded magnetic field vector into arbitrary directions. We optimized the magnetic field vector direction to obtain the highest possible correlation with each serosal electrode recording. We performed a vagotomy and examined spatial and temporal changes in the serosal potential and in the transabdominal magnetic field. We obtained spatial information by mapping the recorded signals to the electrode positions in the gastric musculature. Temporal evidence of uncoupling was observed in spectral analyses of both serosal electrode and SQUID magnetometer recordings. We conclude that non-invasive recordings of the vector magnetogastrogram reflect underlying serosal potentials as well as pathophysiological changes following vagotomy.