A 6-month, open-label clinical trial of pancrelipase delayed-release capsules (Creon) in patients with exocrine pancreatic insufficiency due to chronic pancreatitis or pancreatic surgery.

BACKGROUND: Pancreatic enzyme replacement therapy (PERT) is necessary to prevent severe maldigestion and unwanted weight loss associated with exocrine pancreatic insufficiency (EPI) due to chronic pancreatitis (CP) or pancreatic surgery (PS). AIM: To assess the long-term safety and efficacy of pancrelipase (pancreatin) delayed-release capsules (Creon) in this population. METHODS: This was a 6-month, open-label extension of a 7-day, double-blind, placebo-controlled study enrolling patients ≥18 years old with confirmed EPI due to CP or PS who were previously receiving PERT. Patients received individualised pancrelipase doses as directed by investigators (administered as Creon 24 000-lipase unit capsules). RESULTS: Overall, 48 of 51 patients completed the open-label phase; one withdrew due to the unrelated treatment-emergent adverse event (TEAE) of cutaneous burns and two were lost to follow-up. The mean age was 50.9 years, 70.6% of patients were male, 76.5% had CP and 23.5% had undergone PS. The mean±s.d. pancrelipase dose was 186960±74640 lipase units/day. TEAEs were reported by 22 patients (43.1%) overall. Only four patients (7.8%) had TEAEs that were considered treatment related. From double-blind phase baseline to end of the open-label period, subjects achieved a mean±s.d. body weight increase of 2.7±3.4 kg (P<0.0001) and change in daily stool frequency of -1.0±1.3 (P<0.001). Improvements in abdominal pain, flatulence and stool consistency were observed. CONCLUSIONS: Pancrelipase was well tolerated over 6 months and resulted in statistically significant weight gain and reduced stool frequency in patients with EPI due to CP or PS previously managed with standard PERT.

A randomized trial of daily and thrice-weekly trimethoprim-sulfamethoxazole for the prevention of Pneumocystis carinii pneumonia in human immunodeficiency virus-infected persons. Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA)

We enrolled 2,625 human immunodeficiency virus-infected patients into a randomized trial to assess the efficacy and tolerability of daily vs. thrice-weekly trimethoprim-sulfamethoxazole (160 mg/800 mg) for prophylaxis of Pneumocystis carinii pneumonia (PCP). The rate of PCP was 3.5 and 4.1 per 100 person-years in the daily and thrice-weekly groups, respectively, with a relative risk (RR) of 0.82 (95% confidence interval [CI], 0.61-1.09; P = .16) (RR of <1.0 favors daily trimethoprim-sulfamethoxazole). The RR for PCP determined by on-treatment analysis was 0.59 (P = .03). The RR for death was 0.91 (P = .12); for bacterial pneumonia, 0.82 (P = .06); and for combined PCP and bacterial pneumonia, 0.84 (P = .04). Discontinuation due to adverse events occurred more commonly in the daily trimethoprim-sulfamethoxazole group (RR, 2.14; 95% CI, 1.73-2.66; P < .001). Overall estimates for efficacy end points favored daily trimethoprim-sulfamethoxazole, although rates of intolerance were higher among patients receiving that dose. Daily trimethoprim-sulfamethoxazole may offer advantages as a first choice for PCP prophylaxis; thrice-weekly dosing is an appropriate option for patients intolerant of the daily dose.

Gastric myoelectric activity in patients with end-stage liver disease.

BACKGROUND: Abnormalities of gastrointestinal motility and transit time have been reported in association with end-stage liver disease. Motility abnormalities could be routinely studied if a simple noninvasive test were available. The electrogastrogram is a cutaneous measure of gastric myoelectric activity and correlates well with serosal recordings of gastric myoelectric activity. The aim of this study was to evaluate gastric myoelectric activity in patients with end-stage liver disease. METHODS: Fourteen patients with end-stage liver disease had gastric myoelectric activity measured with the electrogastrogram. An electrogastrogram was considered abnormal when normal gastric slow waves were seen less than 70% of the time or there was no increase in the electrogastrogram amplitude after a meal. RESULTS: Abnormal electrogastrograms were present in 8 of 14 (57%) end-stage liver disease patients. CONCLUSIONS: Abnormal gastric myoelectric activity is common in end-stage liver disease.

The effect of intravenous vasopressin on gastric myoelectrical activity in human subjects.

UNLABELLED: Vasopressin's role in the sensation of nausea is incompletely understood. In this study, our goals were to investigate whether high intravenous vasopressin levels in normal subjects would induce nausea and vomiting and to determine the electrogastrographic (EGG) pattern which would develop at these concentrations. METHODS: EGG recordings were made on five fasting healthy subjects (three females, mean age: 27 years). Vasopressin was infused (0.15 or 0.3 U kg-1 h-1) for 1 h after a 30-min baseline recording. Serum vasopressin levels were measured every 15 min. Symptoms of nausea, cramping, retching, vomiting and bloating were graded from 0 to 5 (0 = none, 5 = most severe). Normal saline at the same rate was then infused for 1 h, with recording of symptoms and measuring blood levels of vasopressin as done previously. RESULTS: EGG data showed a 43% reduction in the percentage of normal slow waves (96-53%) at a vasopressin rate of 0.3 U kg-1 h-1. A 29% reduction (88-59%) occurred at 0.15 U kg-1 h-1. The EGG dominant frequency decreased by 0.8 cpm (3.07-2.25) for the high dose, while only 0.2 cpm reduction (2.9-2.7) occurred at the lower dose. Bradygastria (< 2.4 cpm) rather than tachygastria (> 3.7 cpm) was the predominant abnormality with the high dose. Symptoms of nausea correlated with the infusion of vasopressin and significantly increased with the higher dose. CONCLUSIONS: (i) At supraphysiological vasopressin levels, nausea was present in 80% of subjects but there was no retching or vomiting, (ii) bradygastria was the predominant dysrhythmia at these high vasopressin concentrations, (iii) increasing vasopressin levels correlated symptomatically with increases in nausea.

Case report: pancreatic cancer presenting with paraneoplastic gastroparesis.

Delayed gastric emptying has been observed in some patients with histologically proved pancreatic cancer without evidence of obstruction. The case of a 73-year-old women who had signs and symptoms of delayed gastric emptying is described. Workup included a gastric emptying study that showed 95% retention of the radiolabeled test meal after 2 hours (normal result, <70%). Abdominal computed tomography showed findings consistent with a pancreatic mass. Indirect immunofluorescence study of the patient's serum showed staining of Purkinje cell nuclei and prompted further evaluation for malignant masses. No other cause for the patient's gastroparesis was found, including obstruction. This case illustrates how gastroparesis with no other apparent cause, particularly in elderly patients, may represent a paraneoplastic syndrome. Pancreatic cancer should be included in the list of occult carcinomas that can manifest in this manner.