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Objective: The primary aim of this paper was to compare the effects of flupenthixol and risperidone on subjective quality of life and attitude towards medication in chronic schizophrenic patients with mainly negative symptoms. In a spectrum ranging from its typical end ‘haloperidol’ to its atypical end ‘clozapine’, flupenthixol has typical and atypical characteristics. Methods: The effects of flupenthixol versus risperidone were investigated in a multicenter, double-blind trial, whereas subjective quality of life was assessed by means of the EuroQuol-Visual Analogue Scale and the patient satisfaction questionnaire. The attitude towards medication was assessed by means of the Drug Attitude Inventory-30 (DAI-30). Results: Mean daily dose of study medication was 6.6 (SD 2.9) mg/day flupenthixol and 3.6 (SD 1.2) mg/day risperidone. Both groups showed a significant improvement regarding subjective quality of life and positive attitude towards medication. Especially the categories ‘control of their thoughts’, concentration and ‘feeling better in general’ ameliorated in both groups. In the flupenthixol group, the ‘ability to cope with stress’, ‘feel more relaxed’ and the ‘ability to achieve something’ improved significantly more than in the risperidone group. Conclusions: (1) The spectrum of schizophrenia can be treated effectively with different neuroleptic treatments. (2) Flupenthixol especially improves the ability to cope with stress, the ability to achieve something and feeling more relaxed. (3) Subjective quality of life significantly increased with no difference between the groups.

We investigated incremental cost of nosocomial pneumonia (NP) from the perspective of a hospital and health insurance funds.The incremental cost was determined by calculating total costs for pneumonia patients and controls using prospective and retrospective matched-pairs analysis with 29 and 37 matched pairs, respectively.Compared to controls, patients who developed pneumonia had to be on artificial ventilation 5 days longer, needed markedly more intensive care with 6.55 additional days in intensive care. Excess cost per pneumonia patient amounted to DM 14,606 (95% CI: DM 5,285-23,927) from the hospital's perspective and to DM 7,988 (95% CI: DM 5,281-10,894) according to statutory insurance charges. According to the retrospective anaLysis carried out on the neurosurgical and neurological intensive care wards, pneumonia patients were ventiLated 5 days longer than patients without pneumonia, needed more intensive care over 30 days and had an additional 14.03 days of intensive care and 10.14 more days in hospital. Excess cost per patient was DM 29,610 (95% CI: DM 23,054-36,174) from the hospitals perspective and DM 18,000 (95% CI: 14,885-21,020) according to the statutory insurance criteria.The study gives insight into the structure of incremental cost caused by NP and shows that based on a conservative cost calculation the incremental cost per NP patient is higher for the hospital than for health insurance funds which indicates a significant financial deficit for the hospital. Antibiotics and microbiology together only contribute 6.8% to incremental cost. Therefore in a cost saving initiative their close relationship to length of hospitalization must be considered.

Prospectively determined data on costs of chronic bronchitis were not yet available for the Federal Republic of Germany. The purpose of the burden-of-illness-study conducted in the Federal Republic of Germany from October 1996 to March 1998 was to calculate direct and indirect costs of chronic bronchitis as well as its acute exacerbations per patient and year. Furthermore, the health-related quality of life of the patients was determined.The burden-of-illness-study was conducted as an open, not randomised surveillance study. The evaluation based on 785 patients (55.4% male, 44.2% female, 0.4% unknown; mean age 60 years) who were treated by 147 general practitioners. 755 patients could be included into the cost analysis.Per patient and year direct costs of chronic bronchitis amounted to DM 1112.27, the calculation of indirect costs resulted in DM 959.09. 41.4% of direct costs were due to drug acquisition, hospitalisation costs shared 31.6% and costs for physicians' fee amounted to 20.6%. The severity of chronic bronchitis revealed significantly different results in cost analysis: per patient, mild disease lead to direct costs of DM 387.86, moderate disease to DM 802.62 and severe disease to DM 2224.40. This result was caused by higher costs for drug acquisition and hospitalisation costs due to chronic bronchitis in higher stages of severity. Indirect costs were calculated by applying the human-capital-approach: 45.8% of indirect costs were due to time-off-work, nursing costs amounted to 23.7%.The costs of chronic bronchitis have a considerable impact on the total costs of the health care system of Germany.

In the present study the costs of schizophrenia in Germany were studied using the "bottom up" prevalence-based method. In a random sample of 180 schizophrenic patients stratified according to the most important care institutions, direct and indirect costs were retrospectively documented for a 12-month period. Depending on the place of recruitment and the extent of care provided, total yearly costs result between about DM 33,000 for a patient treated predominantly on an outpatient basis and about DM 126,000 for a patient requiring hospital care and about DM 135,000 for a patient in job rehabilitation. The direct yearly treatment costs were, as expected, lowest for patients recruited in the private practice of a psychiatrist and predominantly treated on an outpatient basis (DM 5,788), and were the highest in the psychiatric hospital (DM 64,661) and in job rehabilitation (DM 79,996). In the patients recruited in the outpatient domain, doctors' fees and medication together were responsible for only 4.5% of the total costs, whereas the indirect costs (e.g., through work incapacity) were responsible for 87% of the total yearly costs. For methodological reasons the total costs caused by schizophrenic psychoses in Germany per year can at present be estimated only roughly. A conservative estimate is between 8.5 and 18 billion DM per year. The study shows that schizophrenia is a very expensive illness, the direct and indirect costs of which are on the whole comparable to those of the common somatic illnesses. Therefore, also for economical reasons, sufficient financial means should be invested in the research and treatment of this severe illness.

OBJECTIVES: Health economic assessment of cost-effectiveness parameters for the comparison of typical (Haloperidol), partially atypical depot (Flupentixol) and atypical neuroleptics (Olanzapin, Risperidon) in the treatment of schizophrenia from the perspective of German health insurance. METHODS: A published markov model was rebuilt and calibrated with DATA®, taking into consideration relapse rates, extrapyramidal symptoms (EPS) and other prognostic symptoms. All data were derived from published sources where available. Besides the comparison of monotherapy, a stepwise treatment scenario was simulated, starting with three months Olanzapin treatment followed by Flupentixol. Over the 5-year simulation period cumulated complication rates (percentage of relapse, positive and negative symptoms), patient related outcomes (Brief Psychiatric Rating Score “BPRS”) and cost parameters (medication, EPS-cost and total costs) were assessed. A cost-effectiveness analysis was performed. RESULTS: Olanzapin/Flupentixol in combination had the lowest relapse rate (42.9 %), followed by Flupentixol (44.4%), Olanzapin (44.8%), Risperidon (48.0 %) and Haloperidol (57.6%). Olanzapin treatment showed the highest BPRS score (3.13), followed by Risperidon (3.07), Olanzapin/Flupentixol (2.52), Flupentixol (2.42) and Haloperidol (2.37). The most cost-effective treatment measured by cost in DEM per relapse free patient was Olanzapin/Flupentixol (200,000), followed by Olanzapin (211,000), Flupentixol (212,000), Risperidon (231,000) and Haloperidol (287,000). The best cost-effectiveness (expressed in DEM/BPRS) was observed in Olanzapin (37,100), followed by Risperidon (39,100), Olanzapin/Flupentixol (45,500), Flupentixol (48,600) and Haloperidol (51,400). Total 5-year drug cost (DEM) were 24,600, 26,800, 3,800, 2,700 and 3,210 respectively. CONCLUSIONS: In terms of relapse rates Olanzapin and Flupentixol lead to better clinical outcome and better cost-effectiveness results as compared to alternative typical or atypical neuroleptic therapy. With Olanzapin and Risperidon most favorable BPRS scores were achieved. Flupentixol depot as monotherapy or following initial Olanzapin treatment is a cost-effective alternative to atypical neuroleptics at low drug cost and low relapse rates.

OBJECTIVES: German hospitals receive the same reimbursement by the statutory health insurance for CABG surgery irrespective of whether or not a rethoracotomy, which involves higher in-hospital costs, has to be performed following hemorrhage. In order to evaluate the in-hospital costs for CABG with and without rethoracotomy from the hospital perspective, a cost-analysis of CABG surgery was performed. Furthermore, the cost-effectiveness of prophylactic administration of the antihemorrhagic agent aprotinin was investigated. METHODS: The detailed resource utilization of 138 CABG patients, 68 with rethoracotomy and 70 without, was analysed based on sample of patient medical records from 7 German hospitals. Resource costs were provided by hospital administrations and supplemented by literature. The overall costs for both groups were then combined with rethoracotomy rates in patients with and without prophylactic administration of aprotinin derived from a published meta-analysis of all relevant clinical trials in open heart surgery. RESULTS: The total in-hospital costs per patient with CABG were on average DM 21,241 and increased to DM 31,326 for a CABG patient requiring rethoracotomy. Besides the costs of the rethoracotomy, the costs of intensive care were the main cost driver in patients with rethoracotomy. The meta-analysis showed with statistical significance that aprotinin can reduce the rethoracotomy rate from 5.0% to 1.8% in patients undergoing heart surgery. When combining the cost data with the results of the meta-analysis, the expected average costs per patient treated with aprotinin (including drug costs) were DM 21,432 compared to DM 21,655 per patient without aprotinin treatment. A cost-effectiveness analysis (costs per patient without rethoracotomy) resulted in a difference of DM 970 in favour of the prophylactic antihemorrhagic treatment. CONCLUSION: The analysis showed that CABG patients requiring an additional rethoracotomy generated about 47% higher costs than patients with CABG surgery only. The administration of the antihemorrhagic agent aprotinin can be recommended in the light of the reduced complication rate and improved cost-effectiveness of CABG-surgery.

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1. The contractile vacuole in Amoeba proteus contains at the surface a well differentiated membrane about 0.5µ thick. Adjoining this membrane on the outside there is usually a layer of substance in which numerous beta granules (Metcalf's "excretory granules") are imbedded. This layer is more viscous and heavier than the adjoining cytoplasm. It is usually about 3µ thick when the vacuole is maximum in size and it becomes thicker during contraction.2. The beta granules around the contractile vacuole vary greatly in number and the layer of substance in which they are imbedded varies greatly in thickness, without any apparent variation in the function of the vacuole. These facts indicate that neither the granules nor the layer of substance is involved in the function of the contractile vacuole, at least not directly.3. The differentiation of a layer of substance on the surface of the contractile vacuole is probably due to the action of the fluid in the vacuole on the adjoining cytoplasm.4. There is much confus...

1. If a colpidium which contains numerous globules of fat is ingested by an amoeba which contains no fat, the food vacuole and its content soon divide several times forming a number of vacuoles, each containing a fragment of the colpidium.2. The globules of fat in these fragments gradually disappear and as they disappear, small droplets of fat appear in the cytoplasm of the amoeba, which gradually increase in size and number until in 24 hours all the fat in the fragments has disappeared and the cytoplasm of the amoeba is well filled with globules of it.3. Treatment with Nile blue sulfate shows that the fat in the intact colpidia and that in the cytoplasm of the amoebae is neutral, but that the fragments of colpidia in the food vacuoles contain fatty acid as well as neutral fat.4. The fact that the globules of fat in the fragments of colpidia in the food vacuoles are much smaller than those in the cytoplasm of the amoebae when first observed, shows that they do not pass out into the cytoplasm and it indica...

Amoeba proteus contains a central elongated fluid portion (plasmasol), a rigid layer surrounding this (plasmagel), a thin elastic surface layer (plasmalemma), and a hyaline layer between the plasmagel and the plasmalemma which is fluid at the tip of active pseudopods and in certain other regions. The plasmasol is an emulsion. It consists of a fluid in which various vacuoles and granuoles are suspended. The plasmagel is probably alveolar in structure. It contains the same kinds of substances as the plasmasol, but some of the fluid appears to be gelated so as to form alveoli. The plasmalemma probably consists of interwoven protein fibers and a lipoid which fills the interstices. The plasmasol is probably hypertonic; the plasmagel and the plasmalemma are probably semipermeable. This and other factors result in an excess inflow of water, stretching the plasmagel and the plasmalemma. When a pseudopod is formed, the inner portion of the plasmagel liquefies locally. This produces a local decrease in elastic strength resulting in the formation of a protuberance, a pseudopod. As this is formed there is contraction at the posterior end, resulting in forward flow of the plasmasol and extension of the pseudopod. If the pseudopod is attached, the plasmalemma, being attached to the substratum and to the adjoining plasmagel, slides over the plasmagel above and remains stationary below, rolling movement results. If it is free, the plasmalemma is stretched out with movement in it equal on all sides. If the free pseudopods become attached to the substratum at the tip after they are thus formed, walking movement results. During locomotion of either type, the plasmasol continuously gelates at the tip of the extending pseudopods forming plasmagel, and the plasmagel continuously solates at the posterior end forming plasmasol. Response is due largely to changes in the elastic strength of the plasmagel in the adhesiveness of the plasmalemma and in turgidity. Locomotion in Amoeba verrucosa is in principle the same as it is in Amoeba proteus.

1. The direction of locomotion of Euglena in a field of light consisting of two horizontal beams crossing at right angles is in close accord with that demanded by the “Resultantengesetz”, that is, the tangent of the angle between the direction of locomotion and the rays in the stronger beam is approximately equal to the intensity of the weaker divided by that of the stronger beam. 2. This can be explained on the assumption that the eyespot is a photoreceptor, that the photosensitive substance in it is a layer in the concavity of the pigmented portion, that this layer is practically parallel with the direction of locomotion and that the light absorbed by it varies from a maximum when the incident rays are perpendicular to it, to zero when they are parallel with it, for if all this obtains and the “Resultan-tengesetz” holds the amount of light absorbed in all symmetrically opposite positions assumed in the process of rotation is equal when the organism is oriented, no matter what the ratio of intensities in the two beams may be. 3. The fact that the direction of locomotion in Euglena is in accord with the “Resultantengesetz” merely indicates that if the organism goes in any other direction it is unequally stimulated in different positions assumed in the process of rotation and that this results in responses which change its direction of locomotion until it is no longer unequally stimulated. It has no bearing on the problem concerning the quantitative relation between the stimulus and the response. 4. In Volvox and Gonium the direction of locomotion in light from two sources is not in accord with the “Resultantengesetz”. 5. In these forms the light is brought to a focus in the eyespots. The position of the focal point varies with the direction of the incident light and the stimulating effect of a given amount of light absorbed at this point varies with its location. 6. In Gonium the stimulating effect of a given amount of light absorbed by the photosensitive substance in the central part of the eyespot is about 9 times as great as that of the same amount of light absorbed by this substance in the posterior part. The photosensitive substance in the central part of the eyespot is therefore about 9 times as sensitive as that in the posterior part.

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1. Under certain conditions Volvox is photopositive, under others, photonegative, and under still others it is neutral. If it is positive, a shadow on the photosensitive substance in the eyespots in the zooids causes change in the direction of the stroke of the flagella of the zooids from diagonal to backward and a flash of light on this substance causes change from diagonal to sidewise. If it is negative the reverse obtains and if it is neutral there is no response unless the changes in luminous intensity are great. 2. The nature of the response to light in Volvox depends upon the state of adaptation and the intensity of the illumination. If it is fully adapted it becomes positive if the intensity is increased and negative if it is decreased. If it is not fully adapted, it becomes negative if the intensity is increased and positive if it is decreased. 3. The time required for colonies of Volvox to become photopositive (reaction time) in illumination of a given intensity, after having been in strong light 1 to 2 hr., followed by darkness, increases to a maximum and then decreases as the time in darkness increases. If the colonies are kept longer in strong light and then subjected to darkness the reaction time decreases to a minimum and then increases as the time in darkness increases. The time required for dark adaptation depends upon preceding illumination. 4. The reaction time of dark adapted colonies is closely correlated with luminous intensity. As the intensity increases it decreases from 29 min. in 5/24 m. c. to a minimum of .098 min. in 7.5 m. c., and then increases to .358 min. in 62222 m. c. The energy required to make the colonies positive varies directly with the luminous intensity over the whole range tested and over most of the range the variation is nearly proportional to the variation in intensity. 5. If colonies are kept in a given intensity or in darkness they become adapted, i. e. they lose the ability to respond to light and if the intensity is now changed they regain it. If dark adapted colonies are exposed to light of 22400 m. c. for .05 min., then returned to darkness, it takes about 20 min. in darkness to eliminate the effect of the light. If they are left in the light .15 min. it takes about 30 min. The processes associated with adaptation and those induced by change in illumination are antagonistic. 6. To account for the responses to light in Volvox, it is necessary to postulate at least three groups of interacting substances.

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ItAmoeba proteus, A. dubia, A. dofleini, orA. radiosa is put into a solution of albumin or into a hypertonic balanced salt solution or a hypertonic solution of calcium gluconate, it rapidly decreases in volume, then numerous tubes filled with fluid are formed. These tubes disintegrate releasing their fluid content inside of the organism. There are frequently more than 50 at a time. Considerable quantities of fluid are consequently ingested in this way. The ingestion of fluid by means of these tubes is a biological adaptation which serves to compensate for the rapid loss of water. It is probable that the process of ingestion of fluid observed byLewis in macrophages is similar to that inAmoeba, and that it occurs in many other cells.

1. In Amoeba new food vacuoles which contain chilomonads or colpidia decrease greatly in size and the organisms in them die soon after they have decreased to minimum; then the size increases rapidly and digestion begins, after which the size decreases very gradually.2. If the culture fluid contains neutral red, the organisms in the vacuoles become purple (like buffer solution, pH 3.5, containing neutral red) immediately after they die, but the fluid around them remains colorless until after the vacuoles have increased in size, then it becomes yellow like buffer, pH 8, but the organisms in it remain purple for some time after this, then become brownish yellow.3. The color of the organisms immediately after death in the food vacuoles is the same as that of organisms which have died in a solution of neutral red outside. This and the fact that the fluid in the food vacuole does not, at this time, become colored indicates that the acid originates in the vacuole, not in the cytoplasm around it. The fact that th...

When Amœba repeatedly comes in contact with a band of intense light the number of attempts to continue in the original direction decreases as the number of trials increases.This indicates that there is some change in Amœba that is analogous to what is called "learning" in the higher animals.

1. Didinia encyst most readily at a temperature of 25°-30°, which is also the optimum temperature for growth and fission.2. They do not encyst in temperature so low or so high that it is injurious. They do not encyst at all below 16° and rarely above 39°.3. They encyst more freely in cultures supplied with food than in those without food, but this is probably due to greater increase in numbers, resulting in greater accumulation of waste material in the one than in the other.4. They encyst most readily in culture media, which are probably most favorable for growth and reproduction of the paramecia on which they feed.5. Encystment serves as protection against unfavorable conditions in reference to food and temperature, but such conditions do not facilitate encystment.6. Encystment is probably induced by the accumulation of excretory waste material.