Minimized estradiol absorption with ultra-low-dose 10 microg 17beta-estradiol vaginal tablets.

OBJECTIVE: To investigate the pharmacokinetics of 10 microg and 25 microg 17beta-estradiol (E2) vaginal tablets in postmenopausal women with vaginal atrophy. METHODS: Fifty-eight women received either 10 microg or 25 microg estradiol vaginal tablets, administered once daily for 2 weeks, followed by twice-weekly dosing for 10 weeks. Blood samples were taken over 24 h at baseline (day -1) and days 1, 14, 82 and 83. Estradiol (E2), estrone (E1) and estrone sulfate (E1S) levels were quantified by gas chromatography-mass spectrometry (GCMS) and assessed by the average plasma concentration from time 0 to 24 h (C(ave)) derived from the area under the curve within 24 h (AUC((0-24))) divided by 24 h. RESULTS: Mean C(ave) values were 9.39 and 19.84 pg/ml on day 1, 6.56 and 18.29 pg/ml on day 14, and 4.64 and 9.41 pg/ml on day 83 for the 10 microg and 25 microg doses, respectively. After 12 weeks, E1 and E1S levels were slightly higher with the 25 microg dose and in the same range with the 10 microg dose, as compared to baseline. CONCLUSIONS: During 12 weeks' administration, 10 microg vaginal tablets resulted in at least 50% lower mean estradiol concentrations than with the 25 microg dose within 24 h after dosing. Administering the 25 microg dose, mean E2 levels during the first 2 weeks exceeded the published reference range for postmenopausal women using the GCMS method, while, with the 10 microg dose, mean E2 levels remained in that range from the beginning, indicating minimized estradiol absorption.

Acute pancreatitis: does gender matter?

In a number of gastrointestinal and nongastrointestinal diseases, gender has been proven to be an independent risk factor for severity. To determine whether this holds true for severity in acute pancreatitis is the aim of our study. This paper derives from a prospective study on the epidemiology of acute pancreatitis, which included 274 patients (172 male and 102 female) with a first attack of the disease. Severity parameters were: Atlanta criteria (arterial Po2 < or = 60 mm Hg, and serum creatinine on admission >2 mg/dl after rehydration); Ranson's and Imrie's prognostic factors; APACHE II score; Balthazar-scored contrast-enhanced computed tomography (CT) results obtained within 72 hr of admission; days spent in the intensive care unit and total hospital stay; the necessity for artificial ventilation, dialysis, or surgery; and mortality. As already known, there is a significant association between gender and etiology of pancreatitis in general. Not surprisingly, the men in our study had alcohol-induced acute pancreatitis more frequently than women, whereas biliary pancreatitis predominated among the women. As for severity, there was no significant association between gender and any of the severity parameters with a few minor exceptions: longer hospital stays, higher Imrie scores and more pseudocysts for women, and more necroses in women with idiopathic pancreatitis. Thus, gender is no independent risk factor for the severity and outcome of acute pancreatitis.

Do we need a computed tomography examination in all patients with acute pancreatitis within 72 h after admission to hospital for the detection of pancreatic necrosis?

BACKGROUND: The aim of this prospective study was to define the role of an initial contrast-enhanced computed tomography (CT) obtained within 72 h after admission to hospital for determining the prognosis of acute pancreatitis and to investigate whether CT scans can be replaced by conventional prognostic parameters. METHODS: The study involves 231 patients admitted to the Lüneburg clinic with a first attack of acute pancreatitis from 1988 to 1995. In all of them, a contrast-enhanced CT was performed within 72 h of admission and scored according to Balthazar. The results were compared with the Ranson and Imrie laboratory prognostic scores and with parameters of the severity of the disease: the initial organ failure according to the Atlanta classification; days spent on intensive care unit or altogether in hospital; indication for artificial ventilation, dialysis and surgical intervention (necrosectomy); development of pancreatic pseudocysts; and mortality. RESULTS: Although there was a good statistical correlation between Ranson, Imrie, and Balthazar scores with the severity of the disease (P < 0.001 to P = 0.03), low and moderately raised Ranson (0-2, 0-5 points) and Imrie scores (0-1.0-3 points) failed to identify all patients with pancreatic necrosis with sufficient sensitivity rates (31.7; 78.0 and 39.0; 78.0%), positive (32.6; 25.3 and 75.0; 45.0%) and negative (91.0; 87.9 and 85.4; 84.8%) predictive values. CONCLUSIONS: A contrast-enhanced CT on admission correlates significantly with the severity of the disease and cannot be replaced by conventional laboratory prognostic scores. The decision to use a CT cannot depend on the results of the Ranson/Imrie scores.

Unintentional weight loss: diagnosis and prognosis. The first prospective follow-up study from a secondary referral centre.

OBJECTIVES: To establish the incidence and causes of unintentional weight loss and to compare prognoses. DESIGN: Prospective. SETTING: Secondary referral centre. SUBJECTS: 158 patients (89 female, 56%; 69 male, 44%) referred by general physicians for unexplained weight loss or for other reasons. In the latter case, weight loss was established after admission to hospital. Follow-up lasted for up to 3 years. MAIN OUTCOME MEASURE: Determining the course of weight loss in patients with diagnosed and undiagnosed causes. RESULTS: The cause of weight loss was established in 132 (84%) patients and remained unclear in 26 (16%). Reasons were non-malignant (60% of patients) and malignant (24%) diseases. Psychological disorders represented 11% of the non-malignant group. A gastrointestinal disease caused weight loss in 50 (30%) patients. Of malignant disorders, 53% (20 of 38 patients) were gastrointestinal. Amongst the non-malignant group, 39% (30 of 77 patients) had somatic disorders. The prognosis for unknown causes of weight loss was the same as for non-malignant causes. CONCLUSION: Contrary to common belief, weight loss is not usually due to a malignant disease. A gastrointestinal tract disorder accounts for weight loss in every third patient. If minimal diagnostic procedures cannot establish a diagnosis, then endoscopic investigation of the upper and lower gastrointestinal tract and function tests should be performed to exclude malabsorption.

Does gastroscopy induce myocardial ischemia in patients with coronary heart disease?

BACKGROUND AND STUDY AIMS: Gastroscopy has been reported to be dangerous for unstable patients with coronary heart disease (CHD). The aims of this study were to find out whether endoscopy is equally liable to cause myocardial ischemia in stable CHD patients, and whether this can be predicted prior to endoscopy, and to find out the frequency of abnormal findings in patients for whom a secondary prophylaxis with acetylsalicylic acid (ASA) is indicated. PATIENTS AND METHODS: Electrocardiograph recording using a Holter monitor was performed during gastroscopy in 71 patients with stable CHD, to check for silent ischemia. To predict potential ischemia during gastroscopy, the Holter monitoring ECG was applied prior to a treadmill test, and withdrawn after gastroscopy 16-22 hours later. RESULTS: During gastroscopy, 30 patients (42%) had silent ischemia, but only 1 patient (1%) became symptomatic. Ischemia was dependent on heart-rate (median heart rate with ischemia 124 beats/min, without 104 beats/min). Abnormal findings on gastroscopy were found in 53 patients (75%). They implied a potential bleeding risk in 30 patients (42%) and prevented the indication for ASA in 6 of them (8%). CONCLUSIONS: Gastroscopy is potentially a harmful procedure for CHD patients, but the incidence of ischemic periods may be reduced by conscious sedation and, if the patient is receiving beta-blocking agent therapy, by applying this medication prior to gastroscopy.

No strict correlation between necrosis and organ failure in acute pancreatitis.

The aim of this study was to determine the relationship between pancreatic necrosis and organ failure in acute pancreatitis. Two hundred seventeen patients with acute pancreatitis were prospectively included. All of them had been examined by computed tomography (CT) within 72 hours of admission. Initial organ failure was defined according to the Atlanta classification (arterial pO2 <60 mm Hg, serum creatinine >2 mg/dL after rehydration). Organ failure during the total hospital stay was defined as necessity for artificial ventilation and/or dialysis treatment, independent of initial organ failure. One hundred seventy-five (81%) patients had interstitial and 52 (19%) necrotizing pancreatitis. Forty-two (19%) had initial organ failure and 54 (25%) organ failure during the total hospital stay. There was a significant correlation between the incidence of initial pancreatic necrosis and initial organ failure as well as initial pancreatic necrosis and organ failure during hospital stay (p < 0.001). However, 24 (57%) of the 42 patients with pancreatic necrosis had no initial organ failure, and 19 (45%) no organ failure during hospital stay, and vice versa, 24 (14%) patients had initial and 31 (18%) organ failure during the total hospital stay in the absence of pancreatic necrosis. Initial organ failure and organ failure during the total hospital stay were independent of the extent of pancreatic necrosis. The incidence of initial organ failure and organ failure during the total hospital stay increased significantly with the CT score (p < 0.001). However, 24 (15%) and 31 (18%) of the patients with interstitial pancreatitis had initial organ failure and organ failure during the total hospital stay, respectively. Patients with pancreatic necrosis are not necessarily at risk of having initial organ failure or organ failure during the total hospital stay and vice versa. Thus, these groups should be considered separately in therapy studies.

Which etiology causes the most severe acute pancreatitis?

BACKGROUND: The aim of the study was to define the prognostic role of etiology in the course of acute pancreatitis. METHODS: The study involved 208 consecutive patients with a first attack of acute pancreatitis. Etiology was biliary in 81 (39%) patients and alcohol abuse in 69 (33%); other etiologies were present in 16 (8%), and etiology remained unknown in 42 (20%). Etiology was correlated with the following parameters of severity of the disease: days in an intensive care unit (ICU); total hospital stay (THS); Ranson, Imrie, and Balthazar scores (contrast-enhanced computed tomography [CT] within 72 h of admission); indication of artificial ventilation, dialysis, or surgery; development of pancreatic pseudocysts; mortality. RESULTS: Alcoholic etiology correlated significantly more frequently than other subgroups with necrotizing pancreatitis, need for artificial ventilation, and development of pancreatic pseudocysts. For the other parameters, there were no significant differences between the etiologies. CONCLUSION: Patients with alcohol-induced acute pancreatitis should be given special attention because of the higher incidence of necrotizing pancreatitis and necessity for artificial ventilation. Whether the pronounced frequency of pseudocysts in alcoholics suggests progression to chronic pancreatitis has to be clarified in follow-up studies.

Acute pancreatitis: which patient is most at risk?

This prospective study aimed to pinpoint acute pancreatic patients who are at a higher risk of clinical deterioration. Once identified, they can be given more costly intensive-care therapy or transferred promptly to hospitals with specialized equipment. Our study included 217 patients with acute pancreatitis. All of them underwent computed tomography within 72 h of admission. Initial organ failure was defined according to the Atlanta classification (arterial pO2, < or = 60 mm Hg; serum creatinine, > 2 mg/dl after rehydration). Forty-two (19%) of the 217 patients had initial organ failure, and 13 (31%) of these deteriorated (i.e., 10 of them needed artificial ventilation, and three, dialysis treatment). Deterioration of initial organ failure was significantly more frequent in alcohol- than in non-alcohol-induced acute pancreatitis (p = 0.005). One hundred seventy-five (81%) patients had no initial organ failure, and 12 (7%) of these deteriorated. All needed artificial ventilation, and two of them dialysis treatment also. There was no significant correlation between etiology and deterioration in these patients. Patients with alcohol-induced acute pancreatitis and initial organ failure represented a major group at risk and should be closely monitored or transferred to specialized units, whereas patients without initial organ failure have a lower risk of later developing organ failure and usually do not need intensive care.

Underestimation of acute pancreatitis: patients with only a small increase in amylase/lipase levels can also have or develop severe acute pancreatitis.

BACKGROUND: In most treatment studies on acute pancreatitis, pancreatologists base their diagnosis on amylase/lipase levels more than three times above the upper limit of normal (>3n) and thus exclude patients with smaller enzyme level increases. The recommendations derived from the results of treatment studies do not take into account such patients. Non-pancreatologists frequently believe that only patients with high enzyme levels have a serious prognosis. AIMS: To question the assumption that high enzyme levels indicate severe, and conversely low enzyme levels indicate mild, acute pancreatitis. PATIENTS/METHODS: This retrospective study includes 284 consecutive patients with a first attack of acute pancreatitis. The cause was biliary in 114 (40%) patients, alcoholism in 83 (29%), other in 21 (7%), and unknown in 66 (23%). Patients were divided into two groups according to their serum enzyme levels (amylase: 3n, n = 196; lipase: 3n, n = 233). Renal impairment, indication for dialysis and artificial ventilation, development of pseudocysts, necessity for surgery, and mortality were taken as parameters of severity. RESULTS: The incidence of severity was the same for both the 3n groups. CONCLUSIONS: The severity of acute pancreatitis is independent of the elevation in serum amylase/lipase level (3n) on admission. Patients with only a slight increase can also have or develop severe acute pancreatitis. Patients with

Presence and extent of extrapancreatic fluid collections are indicators of severe acute pancreatitis.

BACKGROUND: It has been suggested that early localization of both necrosis and extrapancreatic fluid collections by contrast-enhanced computed tomography (CT) can predict the outcome in severe acute pancreatitis. These two assumptions were evaluated. PATIENTS AND METHODS: This study comprises 228 patients with a first attack of acute pancreatitis admitted to our clinic from 1987 to 1995 and for whom the prognostic value of a contrast-enhanced CT obtained within 72 h of admission was prospectively evaluated. These CTs were retrospectively re-evaluated for the localization of pancreatic necrosis and extrapancreatic fluid collections. The indication for dialysis and artificial ventilation, the development of pancreatic pseudocysts, the necessity for surgery (necrosectomy), and mortality were used as clinical parameters. RESULTS: There was a significant correlation between the presence of pancreatic necrosis and extrapancreatic fluid collections versus the clinical parameters. The localization of pancreatic necrosis was of no importance for the outcome of the disease, whereas the increasing amount of extrapancreatic fluid collections paralleled the severity of acute pancreatitis. CONCLUSION: Pancreatic necrosis and extrapancreatic fluid collections are indicators for severe acute pancreatitis. Whereas the localization of pancreatic necrosis is not important for the outcome of the disease, the extent of extrapancreatic fluid collections is significantly correlated with a severe course.

Faecal elastase 1: not helpful in diagnosing chronic pancreatitis associated with mild to moderate exocrine pancreatic insufficiency.

BACKGROUND/AIM: The suggestion that estimation of faecal elastase 1 is a valuable new tubeless pancreatic function test was evaluated by comparing it with faecal chymotrypsin estimation in patients categorised according to grades of exocrine pancreatic insufficiency (EPI) based on the gold standard tests, the secretin-pancreozymin test (SPT) and faecal fat analysis. METHODS: In 64 patients in whom EPI was suspected, the following tests were performed: SPT, faecal fat analysis, faecal chymotrypsin estimation, faecal elastase 1 estimation. EPI was graded according to the results of the SPT and faecal fat analysis as absent, mild, moderate, or severe. The upper limit of normal for faecal elastase 1 was taken as 200 micrograms/g, and for faecal chymotrypsin 3 U/g stool. Levels between 3 and 6 U/g stool for faecal chymotrypsin are usually considered to be suspicious for EPI. In this study, both 3 and 6 U/g stool were evaluated as the upper limit of normal. RESULTS: Exocrine pancreatic function was normal in 34 patients, of whom 94, 91, and 79% had normal faecal elastase 1 and faecal chymotrypsin levels (< 3 U/g and < 6 U/g) respectively. Thirty patients had EPI, of whom 53, 37, and 57% had abnormal faecal enzyme levels (differences not significant). When EPI was graded as mild, moderate, or severe, 63% of patients had mild to moderate EPI, and 37% had severe EPI. In the latter group, between 73 and 91% of patients had abnormal faecal enzymes. In the group with mild to moderate EPI, abnormal test results were obtained for both faecal enzymes in less than 50% of the patients (differences not significant). Some 40% of the patients had pancreatic calcifications. There were no significant differences for either faecal enzyme between the two groups with and without pancreatic calcifications. In 62% of the patients who underwent an endoscopic retrograde cholangiopancreatography (ERCP), abnormal duct changes were found. Again, there were no significant differences for either faecal enzyme between the two groups with abnormal and normal ERCP. CONCLUSION: Estimation of faecal elastase 1 is not distinctly superior to the traditional faecal chymotrypsin estimation. The former is particularly helpful only in detecting severe EPI, but not the mild to moderate form, which poses the more frequent and difficult clinical problem and does not correlate significantly with the severe morphological changes seen in chronic pancreatitis.

Etiology and age have only a limited influence on the course of acute pancreatitis.

In a retrospective study of 602 patients with a first attack of acute pancreatitis, it was investigated whether the etiology of the disease and age of the patient are negative factors. There was no significant difference concerning hospital stay, respiratory and renal insufficiency, indication for surgery, or mortality rate among the different etiological groups. However, pancreatic pseudocysts developed significantly more frequently in alcoholics than in patients with other etiologies (p < 0.001 to p = 0.007). There was also no difference concerning hospital stay and respiratory insufficiency among the age groups. The increased incidence of renal insufficiency probably is related to physiological alteration with age, but the indication for dialysis did not increase. Pancreatic pseudocysts were more frequent in patients between 31 and 40 years of age, which was also the peak age group of alcoholics. Indication for surgery was the same for all age subgroups. The increase in mortality rate with age was weakly significant (p = 0.049). For the etiological subgroups, an increase in mortality with age was found only for biliary pancreatitis patients (p = 0.003). It is concluded that etiology and age of the patient have only limited influences on the course of acute pancreatitis.

Diagnostic intervals for recognizing celiac disease.

The aim of this retrospective study was to determine the time intervals between the onset of symptoms and diagnosis of celiac disease on the basis of a questionnaire that was published in the journal of the German Celiac Society (Verbandszeitschrift der Deutschen Zöliakie-Gesellschaft). 408 adult patients in whom the diagnosis of celiac disease was made after the age of 15 responded to the questionnaire. The time interval between the onset of symptoms and diagnosis (total diagnostic interval) was 5.4 (median) and 10.1 +/- 12.3 (mean +/- SD) years, interval-1 (time interval between the onset of symptoms and the first visit to a doctor) was 0.4 (median) and 2.2 +/- 6.6 (mean +/- SD) years, and interval-2 (time interval between the first visit to a doctor and the diagnosis) was 3.9 (median) and 8.0 +/- 10.4 (mean +/- SD) years. The time intervals shortened only a little over the years. At all times, interval-2 was significantly longer than interval-1. There were no differences between female (n = 328) and male (n = 80) patients and between the age groups. Furthermore, none of the gastrointestinal and non-gastrointestinal symptoms had had a distinct influence on all diagnostic intervals and also the fact that other family members having the disease did not shorten any of the intervals. In summary, the diagnostic intervals for recognizing celiac disease are still unacceptably long. More public awareness work has to be done so that patients can recognize their symptoms and doctors especially can suspect celiac disease sooner and perform the necessary diagnostic procedures when patients present with suggestive symptoms.

Morbidity and mortality in 602 patients with acute pancreatitis seen between the years 1980-1994.

The course of a first attack of acute pancreatitis was evaluated in a retrospective study of 602 patients, who were admitted between 01.01.1980 and 30.09.1993 to the Centers of Internal Medicine and Surgery of the University of Göttingen (n = 417) and from 16.11.1986 to 30.06.1994 to the Municipal Hospital of Lüneburg (n = 185). Etiology was biliary tract disease in 227 (37.7%), alcohol abuse in 177 (29.4%), unknown in 133 (22.1%), and other causes in 65 (10.8%) patients. Mean hospital stay was 27.9 +/- 24 days (x +/- SD), median 23 days. Pancreatic pseudocysts developed in 14.3% of the patients, and surgical treatment was necessary in 11.1%. Within the first 48 hours, respiratory insufficiency was observed in 63.2% of the 204 patients undergoing arterial blood gas analysis while renal impairment occurred in 32.6% of 602 patients. Artificial ventilation was indicated in 12.5%, and dialysis in 7% of the patients. Mortality rate was 6.1%, correlating significantly with respiratory and renal impairment and procedures in connection with these complications and also with transfers from other hospitals.