Olanzapin in der Behandlung depressiver Störungen mit psychotischer Symptomatik

We report on the successful treatment of two female patients with psychotic depression with the new atypical neuroleptic drug olanzapine. A 75-year-old female inpatient suffering from recurrent endogenous depression with tactile hallucinations and coenesthesia was refractory to a systematic sequential antidepressant treatment strategy during a 39-week period. After addition of the new atypical neuroleptic olanzapine to the SSRI citalopram, she showed immediate and ongoing symptom relief. In the second case of a 57-year-old female inpatient suffering from delusional depression, we observed marked symptom relief and correction of the delusions of impoverishment. Olanzapine is discussed with regard to its receptor-binding profile (antagonism to 5-HT2A- and D1-D4 receptors) as a potential neuroleptic drug in the treatment of affective disorders with psychotic symptoms.     

Progression of burn wound depth by systemical application of a vasoconstrictor: an experimental study with a new rabbit model

The final depth of a necrosis resulting from burn trauma is determined within 3 days. The zone of stasis has the potential for complete regeneration or there may be ischemic influences that lead to necrosis. In our model, we examined the dermal influence of vasoconstrictors with reference to the development of burn necrosis. On the backs of New Zealand white rabbits (4.0–4.5 kg) standardized lesions were made with a heated aluminum stamp at 80°C, 14 s in duration.

The lesions were intradermal, whereby the border zone of the coagulated tissue was found in the middle two quarters of the dermis in 100% of untreated animals after 72 h. For dermal vasoconstriction epinephrine in a dose of 0.5 μg/kg/min was used.

There were two groups of seven animals each. One group received epinephrine and the dosage was dependent on the clinical state of the animal. Several cycles were administered within a 3-day period. The reduction of skin perfusion was documented by Laser–Doppler-flowmetry. After 3 days, the skin with the lesions was excised and using a hematoxylin dye, a histological examination followed. The parameter used to determine the efficacy was the thickness of the uncoagulated part of the excised dermis.

Over a period of 48 h, an average of 2.3 epinephrine cycles of average of 88 min per animal in duration resulted in an average reduction of skin diffusion of 41%. The uncoagulated part of the dermis in the epinephrine group was 28.6% average; in the control group, this was 43.5%. The statistical analysis revealed significant differences with a p-value of 0.0312 (significant, when value is less than 0.05). The test results indicate that temporary reduction of skin perfusion through external administration of vasocontrictors may lead to progression of burn necrosis in our animal model.

Clinically, this result indicates that for patients with burn injuries and systemic inflammatory response syndrome who have insufficient volume therapy, the administration of vasocontrictors may produce similar results in the injured area.     

Evaluation of reports of periconceptual occupational exposure: maternal-assessed versus industrial hygienist-assessed exposure.

BACKGROUND: While the number of women entering the work force has grown, so has the importance of investigating occupational reproductive hazards. The objective of this study was to examine the concordance between maternal-assessed and industrial hygienist-assessed exposure to four classes of occupational agents - video display terminals, paints, solvents, and agricultural chemicals. METHODS: Case (n=87) and control (n=102) mothers who participated in a population-based study of orofacial clefts provided occupational histories and exposure (yes/no) to selected classes of agents for the one-year period prior to their child's delivery. Two industrial hygienists reviewed the occupational histories and assigned mothers an exposure status for each class of agent. Using industrial hygienist-assessed exposure as the "gold standard", sensitivity and specificity of maternal reports were calculated for each class of agent. Kappa statistics were calculated for the study population to account for chance agreement between the two exposure assessment methods. RESULTS: Sensitivity estimates for cases were the highest for video display terminals (77%) and lowest for agricultural chemicals (14%). Respective estimates for controls were 74% and 14%. Specificity estimates tended to be high for both groups. Kappa values ranged from 0.16-0.45. CONCLUSIONS: With regard to the classes of agents examined, these data suggest screening questions alone may not be the preferred method of obtaining occupational exposure histories, even when the time period of interest is fairly short and recent.     

Activated protein C resistance and anticoagulant proteins in young adults with central retinal vein occlusion

BACKGROUND: Central retinal vein occlusion is a disease that is most common in old people, and often associated with atherosclerosis, hypertension, diabetes or glaucoma. Since these diseases are much less evident in young people, we wanted to investigate the prevalence of disorders in the most common anticoagulant proteins in a group of young patients with central retinal vein occlusion. METHODS: 37 consecutive patients younger than 50 years and with a history of central retinal vein occlusion, were analysed for deficiencies of natural inhibitors of coagulation (protein C, S, and antithrombin III), plasminogen, resistance to activated protein C, and the presence of anticardiolipin or lupus anticoagulants. RESULTS: Anticoagulant protein deficiencies were found in 4 patients (11%) and activated protein C resistance in 7 patients (19%). Anticardiolipin or lupus anticoagulants were not found in the patients. CONCLUSION: Activated protein C resistance and anticoagulant protein deficiencies seem to be important factors to the etiology to central retinal vein occlusion in young patients.     

Characterization of Echinacea species and detection of possible adulterations by RAPD analysis

In this report we describe the discrimination of all three pharmaceutically relevant Echinacea species by random amplified polymorphic DNA (RAPD) analysis. Genomic DNA prepared from either fresh root material or dried roots was probed in polymerase chain reactions (PCR) using several arbitrary primers. Distinct banding patterns were obtained for E. purpurea, E. angustifolia var. angustifolia, and E. pallida, respectively. Individual Echinacea drugs could be identified within mixtures containing variable amounts of individual drugs. We propose to use RAPD analysis as a rapid and reliable test for proving the identity of Echinacea root drugs.     

Pharmacokinetics of cisplatin administered by continuous hyperthermic peritoneal perfusion (CHPP) to patients with peritoneal carcinomatosis

The pharmacokinetics of cisplatin administered by continuous hyperthermic peritoneal perfusion (CHPP) was characterized in patients with peritoneal carcinomatosis. Cisplatin was added into the perfusate with escalating doses from 100 mg/m2 to 400 mg/m2. The hyperthermic perfusion was maintained for 90 minutes with a flow rate of 1.5 L/min and a target peritoneal temperature of 42.5 degrees C after a tumor debulking procedure. Samples of both the perfusate and blood were obtained during the perfusion and 30 minutes after the perfusion. Cisplatin plasma and perfusate concentrations were determined by flameless atomic absorption spectrometry with a lower limit of detection of 2 ng/ml and a coefficient of variation (CV) < 10%. Fifty-six patients were enrolled in the study. The mean (+/- SD) percentage of cisplatin present in the perfusate at the completion of perfusion was 27.8% +/- 20% of the total dose. The maximum cisplatin concentrations in the perfusate were 10 times higher than those in plasma. The area under the concentration-time curve (AUC) of the perfusate was 13 times higher than the AUC of plasma. A two-compartment model with an additional peritoneal cavity compartment fits to the data best based on the Akaike information criterion. However, the interpatient variability was considerably high (CV < 100%). In conclusion, cisplatin administered by hyperthermic peritoneal perfusion resulted in a pharmacological advantage by obtaining higher and direct drug exposure to the tumor in the peritoneal cavity while limiting systemic absorption and toxicity. Using a complex two-compartment model, the authors were able to characterize the pharmacokinetics of cisplatin given intraperitoneally via this technique.     

Immunoassay and GC-MS procedures for the analysis of drugs of abuse in meconium.

The analysis of meconium specimens for metabolites of substances of abuse is a relatively accurate method for the detection of fetal exposure to drugs. Most of the methods reported in the literature before the early 1990s relied on radioimmunoassays. The purpose of this study was to develop and validate methods for meconium sample preparation for the screening and gas chromatography-mass spectrometry (GC-MS) confirmation of meconium extracts for cannabinoids, cocaine, opiates, amphetamines, and phencyclidine. EMIT and TDx immunoassays were evaluated as screening methods. The sample preparation method developed for screening included extraction and purification prior to analysis. Cutoff levels were administratively set at 20 ng/g for 11-nor-delta9-THC-9-COOH (THCCOOH) and phencyclidine and at 200 ng/g for benzoylecgonine, morphine, and amphetamines, although lower levels could be detected in meconium using the EMIT-ETS system. Ninety-five meconium specimens were subjected to the screening procedure with GC-MS confirmation of presumptive positives. In addition, 30 (40 for cocaine) meconium specimens were subjected to GC-MS analysis for all analytes regardless of the screening results to determine the false-negative rate, if any, of the immunoassay. Although there were no false negatives detected, the GC-MS confirmation rate for the immunoassay-positive specimens was generally low, ranging from 0% for amphetamines to 75% for opiates. The lowest rate of confirmed positives was found with the cannabinoids, suggesting that tetrahydrocannabinol (THC) metabolites other than free 11-nor-9-carboxy-delta9-THC may be major contributors to the immunoassay response in meconium.     

Inflammatory mechanisms in Alzheimer's disease

In recent years many studies have indicated an involvement of inflammatory mechanisms in Alzheimer's disease (AD). Acute-phase proteins such as 1-antichymotrypsin and c-reactive protein, elements of the complement system, and activated microglial and astroglial cells are consistently found in brains of AD patients. Most importantly, also cytokines such as interleukin-6 (IL-6) have been detected in the cortices of AD patients, indicating a local activation of components of the unspecific inflammatory system. Up to now it has remained unclear whether inflammatory mechanisms represent a primary event or only an unspecific reaction to brain tissue damage. Therefore, we investigated whether IL-6 immunoreactivity could be found in plaques prior to the onset of neuritic changes, or whether the presence of this cytokine is restricted to later stages of plaque pathology. we confirmed our previous observation that IL-6 is detectable in a significant proportion of plaques in the brains of demented patients. In AD patients IL-6 was found in diffuse plaques in a significant higher ratio as would have been expected from a random distribution of IL-6 among all plaque types. This observation suggests that IL-6 may precede neuritic changes, and that immunological mechanism may be involved both in the transformation from diffuse to neuritic plaques in AD and in the development of dementia.     

Antiapoptotic activity of bovine papilloma virus

Transformed fibroblasts have been recently shown to be sensitive for induction of apoptosis by TGF-beta-treated neighbouring untransformed cells. Cells transformed by a variety of different transformation principles were regularly sensitive for intercellular induction of apoptosis, but fibroblasts transformed by bovine papillomavirus (BPV) represented a striking exception. In contrast to chemically transformed C127 cells, BPV-transformed C127 cells showed resistance against intercellular induction of apoptosis. In addition, BPV-transformed cells were resistant against induction of apoptosis by ROS in glutathione depleted cells. The antiapoptotic function of papillomaviruses may be of central importance for papillomavirus-induced tumor formation as it can protect transformed cells from intercellular control of oncogenesis.     

Transformed cells trigger induction of their own apoptosis in coculture with normal cells

In vitro, transforming growth factor type betal triggers normal cells to induce apoptosis in transformed cells. We show that in the absence of exogenous transforming growth factor type betal, induction of apoptosis of transformed cells in coculture with normal cells is dependent on the number of transformed cells per assay and is abrogated by antibodies against TGF-beta 1. Therefore, transforming growth factor type betal produced by transformed cells seems to be responsible for triggering a mechanism that leads to the induction of their apoptosis. This mechanism may be crucial for the control of carcinogenesis in vivo.