Postoperative ileus-Establishing a porcine model.

BACKGROUND: Postoperative ileus (POI), characterized by absent gastrointestinal motility, is a frequent complication following major abdominal surgery, with no current effective treatment possibilities. For further research in the treatment of this condition, we aimed to establish a porcine model of POI. METHODS: A total of 12 Landrace pigs, weighing 60 kg, were included. Five animals were used as pilots to establish the surgical procedure, five animals received the same reproducible surgical procedure developed in the pilot experiments, while two animals were used as control. The primary endpoint was number of days to first stool. Intestinal motility was monitored using the SmartPill system. KEY RESULTS: Four of the five pigs who underwent the final surgical procedure passed first stool on the third postoperative day (POD), and one passed first stool on the fifth POD. SmartPill data showed retention of the capsule in the stomach in four of five pigs with usable traces. CONCLUSION AND INFERENCES: An experimental porcine model of POI was established, forming the basis for future studies in POI.

Molecular epidemiology of TTV-like mini virus in Norway.

TT virus (TTV), the first human circovirus to be discovered, appears to be present in most people; less is known about the prevalence of the related TTV-like mini virus (TLMV). A sensitive nested PCR, specific for TLMV, detected the virus in 48% of 201 sera (Norwegian blood donors) previously found to have a 90% prevalence of TTV. More samples were either positive for both or negative for both viruses than what would have been expected from a random distribution (p = 0.08). Sequence analysis revealed considerable heterogeneity of Norwegian TLMV as compared to international sequences, suggesting that TLMV is efficiently dispersed in human populations.

[Tick-borne encephalitis in Norway]. / Flåttbåren encefalitt i Norge.

BACKGROUND: Tick-borne encephalitis is caused by a virus that is transmitted to man by tick-bite. The virus is found in central and eastern parts of Europe and also in Sweden. MATERIAL AND METHODS: We report the first two cases of tick-borne encephalitis resulting from transmission of virus in Norway. RESULTS: Both patients had been to the island of Tromøy on the south coast of Norway. The course of the disease was very different in the two patients. One patient had significant neurological dysfunction. The other patient had intense headache, but no motor dysfunction. Both patients had reduced general health and fever, and leukocytosis and increased protein was found in the spinal fluid. The incubation period is most often 1 to 2 weeks. The disease may have a bi-phasic course with initial fever, headache and muscle pain. One week later symptoms of encephalitis follow. Subclinical infection is common, especially in children. One third of patients get permanent sequelae after encephalitis. Diagnosis is made by demonstration of antibodies in serum. Treatment is symptomatic. INTERPRETATION: These two patients indicate that there may be a reservoir of TBE virus in Norway.

Outpatient parenteral inotropic therapy for advanced heart failure.

BACKGROUND: Patients with advanced heart failure generally have hemodynamic perturbation characterized by low cardiac output and high ventricular filling pressures. This creates a clinical milieu with profound symptomatology that includes weakness, fatigue, and fluid-retention states causing peripheral edema, mesenteric congestion, and dyspnea syndromes. Great morbidity including hospital admissions and readmissions as well as high mortality rates ensue. Though medication and/or surgical intervention often attenuate heart failure symptomatology, morbidity, and mortality, some patients reach more advanced stages despite aggressive maneuvers. Indeed, patients presenting with acute decompensation of chronic congestive heart failure frequently receive parenteral inotropic drugs during their hospitalization with clinical improvement. Because these agents generally increase cardiac output and reduce pre-load and afterload, they can be lifesaving. Some patients, however, have symptomatic and hemodynamic rebound to worsened heart failure states during or shortly after inotrope weaning. METHODS: It was, then, a logical step to segue from acute inpatient inotrope infusion to long-term administration of these drugs in the outpatient setting when patients were dependent on these agents. Dopamine, dobutamine, and milrinone are all generally available inotropes that have been used singly or in combination in a chronic outpatient infusion setting. CONCLUSIONS: Data from a few small clinical trials and anecdotal case experience suggest that these drugs result in both hemodynamic and clinical improvement that is generally sustained during chronic administration, and even noted long after discontinuation of infusions in some patients. Some reports have suggested that intermittent infusion therapy in outpatients (so-called pulsed therapy) is effective in attenuating congestive heart failure symptoms long term, with more data supporting chronic infusion of these agents. Though questions regarding safety of these agents have been raised, a reasonable compendium of data published to date supports the contention that inotropic drugs used in this fashion ameliorate symptoms. Legitimate concern may be raised regarding exacerbation of arrhythmias with subsequent sudden cardiac death syndrome; however, in severely symptomatic heart failure patients, the trade-off between symptomatic amelioration and the chance of sudden cardiac death may be worthwhile. Unfortunately, precise guidance regarding the best drug, dose, optimal administration technique, weaning protocol, and actual risk/benefit ratio are not well characterized. Practice as been guided, in large part, by anecdotal experience. However, it appears that chronic or pulsed outpatient parenteral inotropic infusion therapy is frequently prescribed and that this treatment option is an effective alternative for carefully selected patients with severely symptomatic and advanced heart failure. Formulating optimal protocols for home inotropic drug infusion therapy by conducting properly designed clinical trials will be an essential endeavor.

Pricing and reimbursement of pharmaceuticals. A new culture for the community pharmacist.

Pricing and reimbursement of pharmaceuticals are of concern for pharmacists. Different countries have different ways of organising their health care systems. The place for pharmaceuticals within these systems also differ. This article looks into the price- and reimbursement systems for medicinal products in Germany, Sweden, the UK and Norway. Various ways of organising the pharmaceutical market emerge. Some existing measures have been in place for a long time while others have been introduced more recently. A common goal for the four countries seems to be the drive to cut costs, and attempts to do this can be directed through various reimbursement systems, by focusing on prices or by influencing the physicians' prescribing behaviour, either through the use of advice or through the use of budgets. It is important for the pharmacists to have in-depth knowledge of the price- and reimbursement system they have to work within in order to be of full service to their customers.

[Changes among residents in homes for the aged in Bergen between 1985-96]. / Endringer i aldershjemsklientellet i Bergen 1985-96.

Homes for the aged are intended for elderly people who, by and large, are able to perform basic activities of daily living (ADL) on their own, but who, in spite of this, need or wish to live in an institutional setting, where only minor nursing facilities are available. The present study focuses on the changes in mental capacity and in the altered need for nursing assistance with ADL functions which developed among residents at 13 homes for the aged in the city of Bergen, between 1985 and 1996. In 1985, the average age for residents was 84 years; and in 1996 it was 87 years. The average duration of stay was 30 and 38 months, respectively. There was a significant increase in the proportion of mentally impaired residents (28% and 35%). There was also an increase in the percentage in need of intensive nursing care (34% and 41%). The changes in residents living in the homes were not caused by dementia. It is concluded that homes for the aged are used increasingly for elderly in need of nursing care. There is an obvious mismatch between tasks and resources.

Long-term follow-up of gender-specific outcomes after thrombolytic therapy for acute myocardial infarction from the GUSTO-I trial. Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries.

Our objective was to assess gender differences in mortality 1 year after acute myocardial infarction (MI). The Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-I) trial database of 41,021 patients with suspected acute MI was used to generate 1-year Kaplan-Meier survival plots. Risk quartiles and mortality of women and men were compared. The unadjusted 1-year mortality rate for the initial GUSTO-I population and 30-day survivors demonstrates a large gender gap [odds ratio for all patients = 2.2, 95% confidence interval (CI), 2.0-2.3, p < 0.001]. For the initial population, when adjusted for age, the gender gap is still apparent (odds ratio = 1.4, 95%, CI = 1.3-1.5, p < 0.001) although no longer significant when adjusted using the 30-day survival model (odds ratio = 1.06, 95% CI = 0.97-1.15, p < 0.001). For the 30-day survivors, adjustment based on age alone explained the 1-year mortality difference (risk ratio = 0.96, 95% CI 0.85-1.07, p = 0.441). When the population was divided into expected risk quartiles, women were more likely to fall into the higher expected risk quartiles, even after adjusting for age. A gender gap after acute MI is apparent, nearly all of which occurs within the first 30 days. A substantial portion of the gender gap is explained by the increased age of women, and the rest of the gap may be attributed to differences in variables predictive of 30-day mortality. During 1-year follow-up, the late mortality of women is no greater than that of age-matched men.

Intestinal morphology and cytokinetics in pancreatic insufficiency. An experimental study in the rat.

Intraluminal pancreatic enzymes influence intestinal function, adaptation, and susceptibility to injury. These effects may be mediated partly through changes in the rate of epithelial cell turnover. We assessed intestinal morphology and cytokinetics in a rat model of exocrine pancreatic insufficiency that does not alter anatomic relationships or animal growth. Pancreatic duct occlusion was performed by applying metal clips on both sides along the common bile duct. Control animals underwent sham-operation with exposure and manipulation of the pancreas without duct occlusion. Twelve days later, pulse labeling with tritiated thymidine was performed, and mitotic arrest was induced with colcemid. Groups of animals were sacrificed at 0 and 2 hr after colcemid injection. Specimens for histopathology, morphometry, and autoradiography were obtained from duodenum, proximal jejunum, distal jejunum, and ileum. Labeling index, grain counts, mitoses per crypt, cells per crypt, cells per villus, crypt depth, villus height, and number of goblet cells per villus were used as end points. Pancreatic duct occlusion resulted in increased labeling index across intestinal segments relative to sham-operated controls (P < 0.01) and increased labeling index and mitotic rate in distal compared to proximal intestine (P < 0.05). Grain-count histograms were similar in the two experimental groups. There were no significant morphologic differences between pancreatic duct-occluded animals and controls. Exocrine pancreatic insufficiency increases crypt cell proliferation in distal small intestine but does not alter the duration of S phase. These changes are most likely due to an increase in the size of the proliferative compartment and may be partly responsible for changes in small bowel function and response to injury.

Microdistribution and microdosimetry of thorium deposited in the liver.

The distribution of thorium in the liver of a patient 36 y after injection with Thorotrast was examined with autoradiographic and scanning electron microscope backscatter image techniques. Autoradiographic examination of randomly selected histologic sections of the liver showed a total alpha activity calculated at 33.7 Bq g-1, with the highest concentration of alpha activity sequestered in subcapsular scare tissue. Subcapsular scare tissue received 4.8 cGy d-1 of alpha radiation, periportal areas were accumulating 1.4 cGy d-1, and the hepatic cord areas 0.09 cGy d-1 of alpha radiation at the time of death. The concentration of dose in periportal areas correlates with higher incidence of bile duct tumors (than hepatocellular carcinomas) found in patients exposed to Thorotrast. The backscatter technique was demonstrated as useful for identifying thorium in liver specimens.

Chitosan cross-linked with Mo(VI) polyoxyanions: a new gelling system.

A procedure for preparing homogeneous chitosan gels by in situ molybdate cross-linking is described. The gels are obtained by dispersing solid MoO3 in a buffered chitosan solution and the polymer is cross-linked by formation of heavily negatively charged molybdate polyoxyanions. The resulting ionic gels are very transparent, thermoirreversible and can be made at low polymer concentrations. Depending on the ionic strength, these gels are able to swell several times their original size in aqueous solutions. Estimates of the degree of cross-linking reveal a very open pore structure which is confirmed by electron micrographs of the gel.

Evidence of mouse epidermal subpopulations with different cell cycle times.

In order to obtain information on the distribution of total cell cycle times in hairless mouse epidermis, basal cells were isolated and prepared for DNA flow cytometry at intervals after a pulse labeling with 50 microCi of thymidine. The DNA distributions were recorded, and cells were sorted from windows in the S, G2, and G1 phases of the cell cycle, collected on glass slides, and subjected to autoradiography. The proportions of labeled cells were scored in each fraction, and the percentage of labeled mitoses was determined in histologic sections from the same animals. Grain count distributions were recorded at selected time points over labeled cells in sorted fractions and over labeled mitoses. The movement of the labeled S-phase cohort was thus followed through all cell cycle phases. Peaks in labeled cells were observed at about 36 h in S phase, G2 phase, and mitosis, and high levels of labeled G2 cells and mitoses were seen at about 80 h. These results indicate the existence of one rapidly cycling subpopulation of keratinocytes with a cell cycle time slightly less than 30 h, in addition to keratinocytes with considerably longer cell cycle times. The first peak of labeled G2 cells reached only about 30%. This is consistent with earlier findings of about 30% G2 cells with a rapid traverse, and 70% with a considerably delayed traverse through G2 phase. The proportion of labeled G1 cells reached a value corresponding to twice the initial labeling index at 8 h after pulse labeling. This is consistent with previously obtained phase durations, indicating an unperturbed cell cycle traverse of labeled cells from S phase through G2 and mitosis.

The relative importance of family planning and development for fertility reduction: critique of research and development of theory.

PIP: 3 recent studies about the relative effects of family planning and development are reviewed in an effort to point out their limitations and to augment them. A tentative theoretical framework is presented from which the problem of fertility reduction may be viewed. Also presented is an analysis of the "outliers" in 1 of the 3 studies. This analysis involves consideration of macrosocial and contextual aspects of different nations as a supplement to other analyses. Mauldin and Berelson (1978) and Tsui and Bogue (1978) used indicators of social setting and family planning effort to explain declines in, respectively, crude birthrate between 1965 and 1975, and total fertility rates between 1968 and 1975. The 2 studies used nearly identical sets of explanatory variables. With both studies using the same indicators, except for "labor force," it is not surprising that the results were the same. The results were previously obtained by Freedman and Berelson (1976), who also used the Lapham Mauldin index of planning effort along with similar indicators of social setting. Freedman and Berelson found that birthrate declines could be explained better by program effort (which independently explained 17% of the variance in crude birthrate (CBR) declines) than by social setting (which independently accounted for 7% of that variance), and that the 1972 birthrate itself was similarly explained (15% of the variance attributed to program effort alone, 5% to social setting alone). Mauldin and Berelson obtained nearly identical results. In the Tsui and Bogue study, the contribution of the 1968 level of fertility was the dominant influence on the 1975 total fertility rate. The standardized regression coefficient indicated that previous fertility explained 50-60% of subsequent fertility by direct relationship, a figure comparable to the social setting family planning interaction effects (44-58%) in the 2 other studies. Much of this discussion is devoted to an analysis of the "outliers" in the exploratory data analysis done by Sykes for Mauldin and Berelson (1978). The outliers in Sykes' exploratory data analysis were divided along 2 dimensions. The first involves the relationship between predicted and actual reductions in fertility. The 2nd dimension refers to the independent variables used to predict the fertility declines. This analysis involves analysis of contextual variables and an analysis of distributional variables. It is limited by missing data, but the analysis of Freedman and Berelson (1976), Mauldin and Berelson (1978), and Tsui and Bogue (1978) is plagued by missing variables: contextual variables; distributional variables; and unique national, regional, or local circumstances. These can only be adequately revealed by case studies and may be important influences on fertility behavior. Effects of family planning and social setting may be conditioned by contextual variables (e.g., island status as in Taiwan), or unique circumstances (e.g., coercion as in India), and distribution appears to have an effect of its own.^ieng