Long-term outcome of patients with acute non-specific abdominal pain compared to acute appendicitis: prospective symptom audit after two decades.

BACKGROUND: Non-specific abdominal pain (NSAP) and acute appendicitis (AA) are the two most frequent diagnoses of acute abdomen in the emergency wards. The long-term morbidity, mortality and quality of life of the patients with NSAP compared to AA are unknown. METHODS: The study group consisted of 186 patients with acute NSAP compared to 147 patients with AA initially treated during 1985-1986. Medical history, social background, quality of life and abdominal symptoms were assessed with standardized questionnaires in both groups during 2006-2009. The patients who continued to have abdominal symptoms were invited to a check-up visit. RESULTS: During 1985-6, the NSAP group had more previous abdominal symptoms and operations than the AA group. Some 29% of patients with NSAP and 11% of patients with AA had still abdominal symptoms at long-term check-up (p < 0.0001). Chronic abdominal pain (38 vs 17) and peptic ulcer disease (18 vs 2) occurred more often in the NSAP group than in the controls, respectively (p = 0.001). After five years of follow-up, 11 patients in the NSAP group and 6 patients in the AA group had died (ns). During the twenty years of follow-up, mortality was higher (46/22, 25/15%) in the patients with NSAP than in controls (p = 0.013). Ischaemic heart disease was the leading cause of death in both groups (18 NSAP vs 5 AA, p = 0.017). The quality of life scores were comparable in both study groups. CONCLUSION: Over 70% of NSAP- and almost 90% of AA-patients were free of symptoms after 20 years of follow-up. Mortality was higher and various alimentary track diseases were more frequent in patients with NSAP than in AA.

Regular-dose versus high-dose omeprazole in peptic ulcer bleeding: a prospective randomized double-blind study.

BACKGROUND: It has been suggested that profound acid inhibition along with endoscopic therapy might prevent rebleeding and reduce mortality in patients with peptic ulcer bleeding. The aim of the study was to test the possible equivalence of a high dose and the regular dose of omeprazole in peptic ulcer bleeding. METHODS: We performed a prospective randomized double-blind study involving 142 patients with acute peptic ulcer bleeding (Forrest classification I-II: spurting or oozing bleeding, non-bleeding visible vessel, clot and black base). One-hundred-and-two (71.8%) patients received endoscopic treatment (adrenaline injection and/or heater probe) in pre-entry. Patients were randomly assigned to receive the regular dose of omeprazole intravenously (20 mg once a day for 3 days, i.e. 60 mg/72 h) or a high dose of omeprazole (80 mg bolus + 8 mg/h for 3 days, i.e. 652 mg/72 h). Rebleeding, surgery and death were the outcome measures. RESULTS: Six (8.2%) of the 73 patients receiving the regular dose of omeprazole and 8 (11.6%) of the 69 patients receiving the high dose of omeprazole rebled (P = 0.002 for equivalence, equivalence limit 0.15). Three (4.1%) of the former patients and 5 (7.2%) of the latter group underwent surgery. Four (5.5%) patients in the regular-dose and 2 (2.9%) in the high-dose group died within 30 days. CONCLUSION: Under the defined tolerance limits, the regular dose of omeprazole is as successful as a high dose in preventing peptic ulcer rebleeding.

Laparoscopic or open cholecystectomy: a prospective randomised trial to compare postoperative pain, pulmonary function, and stress response.

OBJECTIVE: Open cholecystectomy (OC) has been superseded by laparoscopic cholecystectomy (LC) for the treatment of cholelithiasis, although this fashion has not been validated by prospective studies. Our aim was to compare the two techniques. DESIGN: Prospective, randomised, open study. SETTING: University hospital, Finland. PATIENTS: 49 patients who required cholecystectomy for cholelithiasis confirmed by ultrasound. INTERVENTIONS: 49 patients were randomly allocated to LC (n = 27) or OC (n = 22): 25 and 22, respectively, eventually had the operation. LC was done using a four-trocar technique, and OC through a transverse right subcostal incision, as short as possible. MAIN OUTCOME MEASURES: Length of hospital stay and the duration of the sick leave were the primary outcome measures. Secondary outcome measures were: postoperative pain evaluated by visual analogue scale (VAS) and the need for opioids; pulmonary function measured by forced vital capacity (FVC), forced expiratory volume in one second (FEV1), peak flow velocity (PEFV), and arterial oxygen tension (PaO2), and endocrine stress measured by plasma catecholamines, cortisol and glucose concentrations. RESULTS: The median (range) hospital stay was significantly shorter after LC than OC, being 2.0 (1-15) compared with 4.5 (2-19) days p < 0.01. The duration of sick leave was also significantly shorter after LC than OC, being 14 (7-17) compared with 29 (4-34), p < 0.01. Patients had significantly less postoperative pain after LC than OC as reflected by the need for opioids. Pulmonary function and arterial oxygen tension deteriorated significantly less after LC than OC. The stress response was equal. There were three documented complications, one pneumonia after LC and two wound infections after OC. CONCLUSIONS: LC gives significantly better results in terms of less postoperative pain, better pulmonary function, better arterial oxygenation, and shorter hospital stay and duration of sick leave.

Enhanced plasma cholesterol lowering effect of retrovirus-mediated LDL receptor gene transfer to WHHL rabbit liver after improved surgical technique and stimulation of hepatocyte proliferation by combined partial liver resection and thymidine kinase--ganciclovir treatment.

In this study we report an improved method for in vivo gene transfer to liver. Repeated injections of Moloney murine leukemia virus-derived retroviruses containing LDL receptor cDNA were given to the portal vein in combination with a 10% partial liver resection and stimulation of hepatocyte proliferation by plasmid/liposome-mediated thymidine kinase gene transfer and ganciclovir treatment. The method was used for the treatment of LDL receptor deficiency in Watanabe heritable hyperlipidemic rabbits. We demonstrate an increase in hepatocyte proliferation index by thymidine kinase and ganciclovir treatment from 0.9 to 1.35% and a maximum of 35% decrease in total plasma cholesterol level 2-3 months after the gene transfer. A 20% decline was still present after a 52-week follow-up period. A 50% decrease was also observed in plasma triglycerides. Liver function tests indicated a transient increase in plasma alkaline phosphatase level up to 12 weeks after the gene transfer. In situ PCR and RT-PCR analyses indicated that the transgene was present in periportal areas and was transcribed to mRNA 1 week after the gene transfer. Because of the relatively simple and controllable technique we suggest that repeated retrovirus injections via a portal vein catheter together with the limited partial liver resection and plasmid/liposome-mediated thymidine kinase gene transfer-ganciclovir treatment may be used to improve the results of retrovirus-mediated liver gene therapy.

Clodronate increases bone mineral density in young growing oophorectomized beagles.

Nineteen beagles (8.8 +/- 0.1 months, 8.5 +/- 0.2 kg, mean +/- SEM) were oophorectomized (OX) at the beginning of the study. The dogs were randomly allocated into three groups: control group (OX, n = 5), OX+clodronate 20 mg/kg orally group (OX + 20, n = 7) and OX+clodronate 40 mg/kg orally group (OX + 40, n = 7). Clodronate administration began the day following oophorectomy and was continued for eight months. Bone mineral density (BMD) was evaluated by dual energy X-ray absorptiometry (DEXA) at baseline and at four and eight months and by quantitative computed tomography (QCT) at baseline and at eight months. Bone biopsies were taken at the beginning and at the end of the study. The change in BMD (g/cm2) during eight months was +2.0% (NS) in OX, +2.3% (NS) in OX + 20 and +10.0% (P < 0.01) in OX + 40 group when measured by DEXA, QCT revealed the same results but in a lesser extent. There were no differences in static and dynamic histomorphometric parameters between the groups at the end of the study. In conclusion, clodronate at a dose 40 mg/kg/day orally increases BMD in young oophorectomized dogs.

Clodronate prevents immobilization osteopenia in rats.

We investigated the effect of clodronate on immobilization osteopenia (IO) induced by sciatic neurectomy in rats. 100 Wistar female rats were divided into 5 groups of 20 animals each: 1) sham-operated, control group, 2) IO+saline control group, 3) IO+clodronate 3 mg/kg/day, 4) IO+clodronate 10 mg/kg/day, and 5) IO+clodronate 30 mg/kg/day. Clodronate was administered subcutaneously beginning on the day after nerve sectioning. After 7 weeks, the animals were killed and both tibiae were removed. Bone mineral density, ash weight and calcium, phosphorus and magnesium contents of the ash of the tibiae were analyzed. The weight of the rats did not differ between the groups during the experiment. The ash weight of the tibiae decreased by 6.6 percent and the mineral density decreased by 5.1 percent after neurectomy. Clodronate reduced IO in a dose-dependent manner and the highest dose neutralized the effect of neurectomy. The calcium content of the ash decreased after neurectomy as compared to the sham-operated group, and clodronate increased it to the sham-operated level. The bone Ca/P ratio remained normal.

Effect of clodronate on fracture healing in denervated rats.

The effect of clodronate on healing of the fracture of osteopenic bone was studied in rats. A total of 165 female rats (14 +/- 1 weeks, 216 +/- 2 g) were divided into five fracture groups (n = 30), and a neurectomized group (n = 15). Osteopenia (op) was induced by right sciatic neurectomy 4 weeks before the fracture. Nonosteopenic (nop) rats were not operated. A closed prepinned diaphyseal fracture of the right femur was done by three-point bending method both to op and nop rats, and the left femur served as an unoperated control. All the fracture groups were divided into treatment (clodronate 10 mg/kg/day sc) and control (saline sc) groups, and the administration was continued throughout the study. The op rats were killed 2, 4, 8, and 12 weeks and nop rats 8 weeks after the fracture. Fracture healing was examined by x-ray and bone-bending strength. Neurectomy reduced bone strength (p < 0.01) at 4 weeks. Clodronate did not affect the bending strength of healing callus of op rats at 2, 4, 8, or 12 weeks after fracture, but reduced the strength of healing callus in nop rats (p < 0.05) at 8 weeks. Radiologic callus width increased in clodronate-treated groups both in op (8 and 12 weeks, p < 0.001) and nop rats (8 weeks, p < 0.05) when compared with saline-treated groups. Clodronate did not affect normal bone strength. In conclusion, clodronate did not affect the bending strength of op fracture nor the strength of the control bones. The remodeling of the fracture was delayed with clodronate.

Clinical evaluation of serum tumour markers CEA, CA 50 and CA 242 in colorectal cancer.

The aim of the present prospective study was to evaluate the clinical value ol serum tumour markers CEA, CA 50 and CA 242 in patients with colorectal cancer (n = 138) and patients with benign gastrointestinal disease (n = 104). The cutoff levels (90% specificity) determined for each test were 2.5 ng/ml for CEA, 17 U/ml for CA 50 and 17 U/ml for CA 242. The diagnostic sensitivity of the CEA test was 0.63, that of the CA 50 test was 0.30 and 0.30 for the CA 242 test in detecting colorectal cancer. CEA, CA 50 and CA 242 tests were tested in a multivariate analysis to find the best combination of independent predictors of colorectal cancer. The most important predictor of colorectal cancer was CEA followed by CA 242. In order to calculate the contributions of tumour marker tests, a diagnostic score (DS) was developed. The sensitivity of the DS in detecting colorectal cancer was 0.47 with a specificity of 0.88 and an efficiency of 0.67. On the basis of this study, serum CEA and CA 242 seem to possess diagnostic value in preoperative evaluation of patients with colorectal cancer.