Role of the pancreas in the control of interdigestive gastrointestinal motility

Our aim was to determine if the pancreas regulates the interdigestive motor patterns of the upper gut. Four dogs were prepared with gastric and intestinal manometry catheters and interdigestive (fasting) motility was measured before and after total surgical pancreatectomy. The characteristics of the gastric and intestinal migrating motor complex were very similar before and after pancreatectomy. The time intervals between successive migrating motor complexes in the antrum (145 +/- 11 vs. 135 +/- 15 min, mean +/- SE) or small intestine (133 + 10 vs. 137 +/- 16 min) were not significantly (p greater than 0.4) altered by pancreatectomy, but the antral motility index (the sum of the antral contractions in a 15-min period) was greater after pancreatectomy (53 +/- 6 vs. 27 +/- 4; p less than 0.05). Pancreatectomy led to undetectable plasma concentrations of pancreatic polypeptide, but had no effect on absolute concentrations of plasma motilin or on the cycling of plasma motilin in association with the duodenal migrating motor complex. We conclude that the pancreas and pancreatic polypeptide play little, if any, role in controlling canine interdigestive motility of the upper gut.     

A sudden increase in factor VIII inhibitor development in multitransfused hemophilia A patients in The Netherlands. Dutch Hemophilia Study Group

The development of antibodies to factor VIII (inhibitors) in response to clotting-factor concentrates administration in hemophilia is common during the first few years of treatment but rare in multitransfused patients. We have investigated the possible association of a recently introduced factor VIII concentrate (Factor VIII CPS-P) in The Netherlands with the occurrence of inhibitors. To this effect, we conducted two studies. First, we performed a national multicenter study in which clinical information and inhibitor test results were obtained for 447 hemophilia A patients over the period 1988 through 1991. Secondly, for a baseline comparison we estimated the frequency of inhibitor development in a closely followed cohort of 144 patients, from 1984 through 1989. Before the introduction of Factor VIII CPS-P, the incidence of new inhibitors was 4.4/1,000 patient-years in the national study from March 1988 through May 1990, and 3.9/1,000 patient- years in the cohort followed from 1984 through 1989. These figures are similar to the incidence of new inhibitors that was found in a large cohort of patients in the United States followed in the 1970s. In the period that the new concentrate Factor VIII CPS-P was on the market, from June 1990 through November 1991, 11 clinically relevant inhibitors were detected, which yielded an incidence over this interval of 20.1/1,000 patient-years, a 4.5-fold increase compared with the previous interval (C195: 1.4 to 14.3). Nine of these 11 patients had in their lifetime received over 250 infusions with factor VIII preparations. whereas all of the inhibitors detected in the previous time interval, and all of the 24 inhibitor patients described in the US study, had received less than 250 infusions in their lifetime. All patients who developed inhibitors after June 1990 had been exposed to Factor VIII CPS-P, whereas only 75% of the patients who did not develop an inhibitor had been exposed to this product. In a prospective extension of the study, with a second inhibitor measurement after 3 months, we found that one additional inhibitor had developed during 52.5 patient-years of Factor VIII CPS-P use. In conclusion, there has been a sudden increase in the frequency of inhibitor patients, for a large part among multitransfused patients. It seems more than likely that this increase is associated with the introduction of a new factor VIII concentrate in The Netherlands.(ABSTRACT TRUNCATED AT 400 WORDS)     

Human heart: tagging with MR imaging--a method for noninvasive assessment of myocardial motion

Specified regions of the myocardium can be labeled in magnetic resonance (MR) imaging to serve as markers during contraction. The technique is based on locally perturbing the magnetization of the myocardium with selective radio-frequency (RF) saturation of multiple, thin tag planes during diastole followed by conventional, orthogonal-plane imaging during systole. The technique was implemented on a 0.38-T imager and tested on phantoms and volunteers. In humans, tags could be seen 60-450 msec after RF saturation, thus permitting sampling of the entire contractile phase of the cardiac cycle. Tagged regions appear as hypointense stripes, and their patterns of displacement reflect intervening cardiac motion. In addition to simple translation and rotation, complex motions such as cardiac twist can be demonstrated. The effects of RF pulse angle, relaxation times, and heart rate on depiction of the tagged region are discussed.     

Effect of a purified amylase inhibitor on carbohydrate metabolism after a mixed meal in healthy humans

In previous studies we found that in healthy subjects, 5 and 10 g of a partially purified amylase inhibitor delayed and decreased starch digestion and reduced postprandial plasma glucose after a starch meal but produced diarrhea in two of six and four of six subjects, respectively. Thus, we wondered whether lower doses of the inhibitor, when given with a meal that contained protein and fat as well as carbohydrate, would have the same effect on carbohydrate tolerance without causing diarrhea. Eight healthy subjects were randomized to receive 2.0 or 2.9 g of the inhibitor with a 650-calorie meal that contained carbohydrate, fat, and protein. In comparison with a placebo, ingestion of 2.9 g, but not 2.0 g, of the inhibitor significantly reduced postprandial increases in plasma glucose (P less than 0.05), C peptide (P less than 0.03), and gastric inhibitory polypeptide (P less than 0.008). Similarly, 2.9 g of the inhibitor in comparison with 2.0 g was associated with more carbohydrate malabsorption and more breath hydrogen excretion. Because the carbohydrate malabsorption observed with the 2.9-g dose was similar to that with the previously tested 5- and 10-g doses of the inhibitor but diarrhea was less frequent, impurities in the partially purified preparation may, in part, have been responsible for these adverse effects. We conclude that 2.9 g of the amylase inhibitor given with a meal that contains a mixture of nutrients is effective in increasing carbohydrate tolerance without causing diarrhea. Therefore, this dose is appropriate for use in studies to determine whether the inhibitor has a beneficial effect in patients with diabetes mellitus or obesity.     

Prognostic factors in pancreatic abscess

Pancreatic abscess is a highly lethal sequela of pancreatitis. The purpose of this study was to identify clinical and laboratory factors associated with the antecedent episode of pancreatitis or at the time of manifestation of a pancreatic abscess and factors related to its treatment that might have prognostic significance. The records of 66 consecutive patients with pancreatic abscess seen between 1966 and 1980 were reviewed. Factors adversely affecting survival included: severity of precipitating pancreatitis (p less than 0.03); sepsis and pulmonary dysfunction (p less than 0.05); and persistent postoperative sepsis (p less than 0.001). All four patients who were treated nonsurgically died. Of 62 patients treated surgically, 80% experienced serious complications, 31% required reoperations, and 40% died. No single surgical procedure, including marsupialization, proved to be superior. Surgical drainage offers the only possibility of survival for patients with pancreatic abscess. More thorough elimination of all focuses of infection is required, however, to reduce the high morbidity and mortality rates associated with persistent postoperative sepsis.     

Cooling effect of continuous renal replacement therapy in critically ill patients

Hypothermia is reported to increase intensive care unit (ICU) mortality. The heat loss that occurs during continuous renal replacement therapy (CRRT) favors the development of hypothermia. In an effort to assess the influence of CRRT on body temperature, we reviewed the records of 72 consecutive ICU patients treated with CRRT and further prospectively studied the temperature in the inlet and outlet lines for blood and dialysate of 27 other patients at various flow settings during continuous venovenous hemodialysis (CVVHD). Among the 72 retrospective cases, 36 episodes of hypothermia (core body temperature <35.5 degrees C) occurred and persisted for a mean of 2.6+/-1.8 days. It was more frequent during venovenous than arteriovenous modalities (31 of 67 v5 of 20, respectively); no patients developed hypothermia during arteriovenous slow continuous ultrafiltration (AVSCUS), whereas 48% of the patients undergoing CVVHD became hypothermic, occurring earlier in the therapy course (days 2 to 4). Mean arterial pressure (MAP) tended to increase after CRRT initiation, but absolute changes were not statistically significant. In the prospective arm, the CVVHD circuit temperatures were directly measured. Whereas no attempt was made to change body temperature, stepwise changes in blood (Qb) and dialysate flow rate (Qd) produced venous circuit temperature changes: the higher the Qb, the smaller the arteriovenous temperature differences independent of changes in Qd (P < 0.001). Also, venous circuit temperature varied directly with Qd at fixed Qb (P < 0.001). This relationship also held for temperature conversion to lost energy units per minute. Using room temperature dialysate, CRRT may significantly lower patients' core temperatures. Although the clinical significance of this effect is not clear at this point, energy loss during CVVHD may be important in hemodynamic stability or patient prognosis.     

Effect of a purified amylase inhibitor on carbohydrate tolerance in normal subjects and patients with diabetes mellitus

Slowing starch digestion by inhibiting amylase activity in the intestinal lumen should improve postprandial carbohydrate tolerance in patients with diabetes mellitus. Crude bean-derived amylase inhibitor ("starch blocker") that contains only minimal antiamylase activity, however, does not modify carbohydrate assimilation. To test the validity of the "starch blockade" concept, we assessed the effect of a partially purified bean-derived amylase inhibitor with increased antiamylase activity on carbohydrate tolerance in normal subjects and in patients with non-insulin-dependent diabetes mellitus. In comparison with a placebo, ingestion of this inhibitor with 50 g of starch substantially reduced postprandial increases in plasma concentrations of glucose and insulin in both normal subjects and those with diabetes. We conclude that a purified amylase inhibitor is effective and potentially beneficial in the treatment of diabetes mellitus.