[Treatment of behavioral disorders in dementia with risperidone in psychogeriatric out-patients]. / Therapie demenzassoziierter Verhaltens- störungen mit Risperidon bei ambulanten gerontopsychiatrischen Patienten.

BACKGROUND: The atypical neuroleptic drug risperidone has been approved for the treatment of behavioural and psychological symptoms of dementia for more than three years in Germany. To assess the efficacy and tolerability of risperidone in general practice two open-label prospective studies were performed. PATIENTS AND METHOD: In 7142 patients with dementia the treatment course with risperidone was examined over 6 resp. 8 weeks. Efficacy was evaluated by assessing the target symptoms agitation, aggression, sleep-wake-cycle disturbances, social withdrawal, suspiciousness, and delusion. Furthermore, the global impression was rated by the physician and the caregiver at the end of the study. The tolerability of risperidone was documented by monitoring blood pressure, heart rate, bodyweight, and adverse events. RESULTS: 6170 patients complied with the inclusion criteria for analysis. Risperidone achieved statistically significant improvements of behavioural symptoms at an average dose of 1,5 mg/d (90% of patients received < or = 2 mg/d). 92% of the patients showed a favourable treatment response as defined by a > or = 30% improvement of the total score of the target symptoms. This improvement was already apparent 2 and 3 weeks after the start of treatment, respectively. A subgroup analysis demonstrated statistically significant improvements of target symptoms with risperidone also in patients who had been pre-treated with other neuroleptics. The global impression of physician and caregiver was positive in over 90% of patients. Adverse events were seen in 309 of 6170 patients (5,7%). CONCLUSION: Risperidone was highly effective and well tolerated in the treatment of behavioural disturbances in dementia under routine conditions of general practice.

Effect of blood transfusion on cardiorespiratory abnormalities in preterm infants.

The effects of red blood cell transfusion on the incidences of apnoea, bradycardia, tachycardia and oxygen desaturation over periods of 72 hours before and after transfusion were assessed in 25 infants with a gestational age of < or = 32 weeks (mean (SEM) 29.2 (0.4) weeks, birthweight 1170 (73) g; postnatal age at transfusion 39 (4) days). During transfusion haemoglobin rose from 78 (2) g/l to 117 (2) g/l. Significant decreases were observed in daily frequencies of apnoeas longer than 15 seconds (median from 2.7 to 0.9 events a day), tachycardias of more than 200 beats per minute (from 34 to 25 events per day), bradycardias below 100 beats per minute (from 65 to 12 events per day) and 80 beats per minute (from 8.4 to 3.3 events per day). Oxygen saturation improved in 20 of the infants. Transfusion improves cardiorespiration in preterm infants for several days.

Minimum spanning tree, integrated optical density and lymph node metastasis in bronchial carcinoma.

Surgical specimens comprising 80 primary lung carcinoma (lobes and lungs) were expanded by insufflation of air into the main bronchi, and fixed with buffered formalin for 24 h. After the usual tissue procedures, 3-4 microns thick histological sections of the tumour mass were Feulgen stained and various nuclear features such as integrated optical density (IOD), area, form factor, etc. were measured using an automated image analysing system (VISIAC). The geometrical centres of the nuclei were defined as vertices and the corresponding minimum spanning tree (MST) was calculated according to the distance between the vertices. The tumour mass was measured by serial sections of the surgical specimens; the lymph node stage was defined according to the rules of the UICC. Non-tumour infiltrated lymph nodes of the same case served as controls for the IOD and MST. The results revealed a DNA index of 1.1-3.0, a malignancy index (Böcking) 0.90-1.08 and a percentage of S-phases 10-23% (confidence limits). Only 19% of the bronchial carcinoma were found to be not aneuploid. Based upon the weighted MST, the distance of neighbouring cells, the IOD of the centre cells and IOD/area of neighbouring cells revealed statistically significant differences between tumours with and without lymph node metastases. The more advanced the lymph node stage, the 'closer' was the 'packing' of the tumour cells.

Combined morphometrical and syntactic structure analysis as tools for histomorphological insight into human lung carcinoma growth.

Histological sections of formalin-fixed, paraffin-embedded tissue comprising 60 surgical specimens of human lung carcinoma were Feulgen stained. The histomorphological images were transferred to an automated image analysing system (VISIAC) and analysed as follows. The geometrical centers of tumor cell nuclei were defined as vertices, and the minimum spanning tree (MST) was calculated based on the two-dimensional distance between the vertices. Segmentation of the images was performed semiautomatically by interactive definition of nuclei of interest and automated detection of nuclear boundaries. Several morphometric features of tumor cell nuclei were measured including size, DNA-content (extinction), and form factor, and were set in relation to parameters of the MST. The following results were obtained: DNA-content and tumor cell nucleus size ('center cell') of different microscopic tumor growth patterns are related to the number of nearest neighboring cells. No relation was found in the neighboring (surrounding) cells. The different cell types of lung carcinoma, i.e., the different microscopic tumor textures expressed the relation of center cell features to the parameters of MST. A high amount of DNA content in branching points of the MST for epidermoid carcinoma may be interpreted as carcinoma growing in epidermoid textures tend to proliferate from tumor cell nuclei related to at least one neighboring cell. The opposite was found for large cell anaplastic carcinoma (no perceptible microscopic textures of the tumors) which showed the highest DNA content in tumor cell nuclei but which was not related to any neighboring cells. This technique allows analysis of growth centers and microenvironment conditions in human lung cancer in relation to tumor texture at the light microscopy level.

DNA-content, inflammatory tissue response and tumour size in human lung carcinoma.

Tumour imprints of 75 resection specimens with human lung carcinoma (lobe and lungs) were fixed with alcohol and Feulgen-stained. Resection specimens were cut into serial sections 6 mm thick and tumour mass, tumour involvement into intrapulmonary and extrapulmonary lymph nodes, detailed pTN-stage were determined. DNA-content, DNA-index, percentage of diploid/hyperploid tumour cells, and morphometric nuclear features were measured using an automated image analyzing system (VISIAC). Only 10% of the measured carcinomas were diploid. The DNA-index showed the broadest variance in large cell anaplastic carcinoma (1.2-3.3). Carcinomas growing predominantly within the alveolar space, i.e. without destroying the interstitial tissue showed a lower DNA-content above 3c and above 5c compared to carcinomas destroying the interstitial tissue. Carcinomas with severe stroma reaction were found to have 33%-48% of DNA above the 3c value whereas carcinomas without stromal reaction had a percentage above 3c ranging 46%-64% (confidence limits, p less than 0.05). DNA-index increases with increasing tumour volume and decreases for large tumours (greater than 100 ccm). Hyperploid and polyploid tumours were found more frequently in case of pT2 and pT3-stages compared to pT1-stages. No relation of DNA-content or ploidy was found to lymph node involvement and inflammatory response of host tissue.

Minimum spanning tree, Voronoi's tesselation and Johnson-Mehl diagrams in human lung carcinoma.

A program written in Amba was developed for the automated construction of minimum spanning trees, Voronoi's tesselation and Johnson-Mehl diagrams, combined with quantitative measurements of nuclear parameters in histopathological specimens. Sections, 4 microns thick obtained from paraffin-embedded surgical lung specimens, were Feulgen-stained. The boundaries of the nuclei were calculated automatically after interactive identification of the relevant cells. The geometric centres of the nuclei were computed. They were used for constructing the minimum spanning tree, Voronoi's tesselation and the Diriclet cells. The direction of the main axis to the best fitting ellipsis according to the nuclear size was used for construction of the Johnson-Mehl diagrams. The following textural parameters were measured: 1) Minimum spanning tree: Distribution of neighbouring cells; minimum distance between neighbouring cells according to number of neighbours. 2) Voronoi's tesselation: Area and surface of obtained cells; Ratio of nuclear area/cell area. 3) Johnson-Mehl diagram: Area and surface of obtained cells; Ratio of nuclear area/cell area. The following nuclear parameters were measured: 1) Area, surface, absolute extinction (DNA-content); Similarity of quantitative nuclear parameters between neighbouring cells and in relation to number of neighbouring cells was analyzed. Twenty cases of primary lung carcinoma (five cases of each of epidermoid, adeno, large cell anaplastic, and small cell anaplastic carcinoma) were measured. Analysis of texture parameters in combination with morphometric nuclear parameters offers new possibilities in quantitative histopathology.

[Forensic medicine roentgen studies in gunshot wounds of the skull]. / Rechtsmedizinische Röntgenuntersuchungen bei Schädelschüssen.

14 X-ray examined deaths caused by cranial bullet injuries are described. Three of them are demonstrated. In all cases with bullet injuries X-ray examination should be done prior to the post mortem. With radiographs bullets can be localised quickly. An antero-posterior and a lateral view are necessary. Little parts of the bullet and bone meal particles may be visible in radiographs along the path of the bullet; using normal technique of autopsy those details may not be visible.

[The simulation of histopathological diagnosis with the help of an automated image analysis system (VISIAC)]. / Simulation der histopathologischen Diagnostik mit Hilfe eines automatischen Bildanalysesystems (VISIAC).

Simulation of the diagnostic algorithm in histopathology at 2 different light microscopical magnifications (x4, x40) for separating 7 diagnostic groups in lung pathology (healthy lung, healthy bronchus, lymphocytic inflammation, epidermoid-, adeno-, small cell, and large cell carcinoma) is presented. 140 cases were tested as a teaching set, 105 cases as learning set. Gray value distribution discriminates between healthy parenchyma and the diseases in all cases tested; minimum spanning tree discriminates between inflammation and carcinoma in all cases, and in between the carcinoma with 70% to 80% accuracy. The measurements may be used as additional aid in difficult diagnostic cases.

Rapid microwave fixation--a comparative morphometric study.

Tissue blocks taken from healthy human lung tissues, from primary bronchial carcinoma and from mediastinal and hilar lymph nodes were placed in the following solutions: Tris buffer; buffered formalin (0.5%, 1%, 7%); 0.1 mol NaCl; distilled water; DMSO (1%, 10%, 20%); acetone (10%); methanol (50%, 80%, 100%); glutaraldehyde (2.5%), and fixed by use of a commercial microwave oven. Tissue blocks obtained from the same surgical specimens were fixed in 7% buffered formalin for 24 h for comparison. Conventional and microwave-fixed tissue was embedded in paraffin, and stained with haematoxylin and eosin. Fifteen specimens of each group and each solution were examined by light microscopy. Minimum diameter and area of 100 nuclei of each specimen were measured interactively. Histomorphological sections fixed with Tris buffer in a microwave oven revealed best morphological results showing more contrast in chromatin distribution of nuclei and 'opening' of interstitial lung capillaries in comparison to conventional formalin-fixed specimens. No statistically significant differences in area and minimum diameter of nuclei between the different groups were found. Microwave fixation using Tris buffer is a time-saving fixation method at least comparable to conventional formalin fixation. It is not accompanied by hazards to the environment that are unavoidable by formalin fixation.

Invasion of human lung carcinoma into cartilage of the bronchus.

In vivo invasion of human carcinoma of the lung into the cartilage of the bronchus was studied by light microscopy. Tumor spread into the cartilage was found in 26% (60/229). It occurred in 38/128 epidermoid carcinoma (30%) and in 14/55 adenocarcinoma (25%), but was observed in only 1/17 large cell anaplastic carcinoma (6%). Degradation of cartilage matrix was found to be limited. Destroyed area measured 9.9 +/- 1.8 mm2 on average. Tumors able to destroy bronchus cartilage were similar in size compared to tumors without detectable invasion into cartilage. Analysis of pTN stages revealed no differences between both groups. Tumor volume in extrapulmonary lymph nodes was significantly larger in case of cartilage degradation. Patients with tumors degrading bronchus cartilage showed poorer survival (median survival 360 vs. 780 days, p less than 0.10). Immunohistology differentiating inflammatory cells (B lymphocytes, T lymphocytes, monocytes, granulocytes, macrophages) revealed no participation of inflammatory cells in tumorous degradation of cartilage. The findings suggest that hyalin cartilage is highly resistant to invasion of human lung carcinoma although evidence exists for proteolytic activity of human lung carcinoma.

Diffuse pulmonary ossification associated with metastatic melanoma of the lung.

A case with advanced diffuse pulmonary ossification is described. The patient underwent surgical treatment of a malignant nodular melanoma of the right shoulder followed by postoperative cytostatic therapy for 6 months. He developed renal insufficiency and pulmonary infiltrates 3 years after the operation. Two metastases into the lung were operated 4 years after extirpation of the melanoma. Histopathological findings revealed two major metastases of a malignant amelanotic melanoma and multiple tumour thromboses in lymphatic and venous vessels. Severe interstitial lung damage including diffuse pulmonary ossification and focal interstitial fibrosis was noted. Morphometric measurements of ossified nodules revealed increased ossification in fibrotic lung areas. Immunohistology for differentiating immunoglobulins and lymphocytic subpopulations was insuspicious. The findings suggest that diffuse intraalveolar ossification is probably not related to pulmonary congestion.

[Antimicrobial chemoprevention in colorectal interventions: a single parenteral dose at the start of surgery is adequate]. / Antimikrobielle Chemoprophylaxe bei colorectalen Eingriffen: Parenterale Einmalgabe bei Operationsbeginn ausreichend.

The effectivity in reducing septic complications after colorectal operations of oral 1 g Neomycin plus 0.25 g Metronidazol t.i.d. on the last preoperative day vs. intravenous single dose 5 g Mezlocillin plus 0.5 g Metronidazole was tested by sequential medical plan. There was no statistically significant difference between both chemoprophylaxis groups (p = 0.10). It is concluded that the intravenous chemoprophylaxis should be preferred because of the lowest dosage and therefore the fewest side-effects.