[Rare entity of a macroscopically visible tumor cone of squamous cell carcinoma in the greater veins of the head and neck]. / Seltene Entität eines makroskopisch sichtbaren Tumorzapfens eines Plattenepithelkarzinoms in den grossen Kopf-Hals-Venen.

Cones of malignant tumors are commonly known but only a few descriptions of cones in the head and neck area exist - as seen in a 91-year-old patient under our care. Cones of thymic and thyroid cancers are described in the literature. There are no descriptions of cones of head and neck squamous cell carcinomas. Metastases of squamous cell carcinoma in the head and neck area are very aggressive and have a high potential for vascular neogenesis. A vascular cone might be possible by vascular formation or by mechanical intrusion as described elsewhere.

Bone tissue ablation with sub-microS pulses of a Q-switch CO(2) laser: histological examination of thermal side effects.

. The goal of this study is an in vitro evaluation of thermal side-effects by the application of short sub- micro s CO(2) laser pulses in combination with an air-water spray on different types of bone tissue. A mechanically Q-switched CO(2) laser delivered 300 ns pulses at 9.6 micro m wavelength, which were focused down to a spot size of 440 micro m on the tissue (a corresponding energy density of 9 J/cm(2)). Bone samples (blocks from pig femur, rib, or cartilage) were moved through the beam repeatedly until 1-5 mm deep cuts were produced. An air driven water spray was applied to prevent the tissue dehydration. Subsequent visual and histological examinations revealed no carbonisation, melting traces or fissuring of the tissue. An extremely narrow, 2-6 micro m thick thermally altered layer was observed at the cut border in compacta and cartilage. No accumulation of the thermal damage occurred with increasing cut depth. Laser incisions in trabecular tissue were accompanied with a 100-200 micro m thick zone of thermal necrosis in bone marrow. The difference from compacta and cartilage can be explained considering the particular character of the spreading of the ablation products in the trabecular meshwork. Minor thermal side effects make the Q-switched and probably other short pulsed CO(2) laser systems interesting for hard tissue surgery.

Cyclandelate in the treatment of patients with mild to moderate primary degenerative dementia of the Alzheimer type or vascular dementia: experience from a placebo controlled multi-center study.

A 24-week, double-blind, multi-center, randomised parallel group study compared the efficacy and safety of 800 mg bid cyclandelate with placebo in patients with mild to moderate dementia of primary degenerative or vascular origin. A total of 196 patients entered the study, 147 patients completed treatment in adherence with the protocol. Primary outcome measures were the cognitive score of the Alzheimer's Disease Assessment Scale (ADAS-Cog), the subscale Instrumental Activities of Daily Living of the Nurses' Observation Scale for Geriatric Patients (NOSGER-IADL) and the Clinical Global Impressions of Change (CGI-C). Safety assessments included adverse events, vital signs, ECG and clinical laboratory parameters. The primary efficacy results based on a multi-level responder analysis including ADAS-Cog, NOSGER-IADL and CGI-C failed to demonstrate statistical superiority of cyclandelate in comparison to placebo. The direction of changes favored cyclandelate in each of the variables, but the differences to placebo were small and varied considerably between patients and centers. Retrospective exploratory analyses suggested that efficacy of cyclandelate might be dependent on the severity of the disease. The treatment effects in favor of cyclandelate were statistically significant in the subgroup of moderately impaired patients (MMSE at baseline <18) for ADAS-Cog (delta = -4.0 points, p = 0.015) and CGI-C (delta = -0.4 points, p = 0.043) but not for NOSGER-IADL (delta = -1.6 points, p = 0.059). When patients were stepwise selected for the severity of the disease according to ADAS-Cog at baseline (>15, >20, >25 points), statistical significance was reached for ADAS-Cog and NOSGER-IADL beginning with the step ADAS-Cog >20 points: delta ADAS-Cog = -3.9 points, p = 0.044; delta NOSGER-IADL = -1.0, p = 0.023. The treatment differences increased further with the step ADAS-Cog >25 points: delta ADAS-Cog = -7.0 points, p = 0.008; delta NOSGER-IADL = -1.7, p = 0.003. Treatment differences in CGI-C increased marginally with the stepwise selection but did not reach statistical significance. The drug was safe and well tolerated.

[Radiation-induced submandibular extra-osseous osteogenic sarcoma]. / Strahleninduziertes submandibulares extraossäres osteogenes Sarkom.

Extraskeletal osteogenic sarcoma of the head and neck are extremely rare. This case report describes a 55-year-old patient who has suffered from four squamous cell carcinomas (SCC) of the mouth since 1985. Thirteen years after successful radical resection of the SCC of the planum buccale left and radiotherapy, the patient developed a radiation-induced extraskeletal submandibular sarcoma on the left [7, 8, 9, 12]. The primary sarcoma developed in the planum buccale, the area which had been repeatedly exposed to radiotherapy, and spread into the soft tissue. The difficulties of the clinical diagnosis, the morphology of the tumor and therapeutic procedure are described. This case demonstrates the problems of radiotherapy in SCC.

Pharmacokinetics of thymosin alpha1 after subcutaneous injection of three different formulations in healthy volunteers.

OBJECTIVE: Thymosin alpha1, an immunomodulatory endogenous peptide, has been shown to be effective in the treatment of chronic hepatitis B and C. In this study, single- and 5-day multiple-dose pharmacokinetics were characterized in nine Caucasian volunteers after subcutaneous administration of 900 microg/m2 thymosin alpha1. METHODS: Using a randomized, 3-way crossover design three available drug formulations were compared: Zadaxin (SciClone), Timosina (Sclavo), and Thymosin alpha1 (Tal-HLR; Hoffmann La Roche). AUC, Cmax, t(max), t(1/2), Cl/f, and the volume of distribution, V(Z)/f, were derived by model-independent methods. RESULTS: Endogenous serum concentrations were below the limit of quantification (0.10 microg/l) of the enzyme-linked immunosorbent assay method in most subjects. Thymosin alpha1 was well absorbed with a mean t(max) between 1-2 hours from all galenic formulations. Cmax concentrations of 30 to 80 microg/l and AUC(0-infinity) from 95 to 267 microg x h/l did not differ between single- and multiple-dose administration of all drugs. This apparent lack of accumulation was supported by the short elimination half-life of less than 3 hours. As indicated by a V(Z)/f in the range of 30-40 l, thymosin alpha1 appears to distribute within the extracellular volume. AUC and Cmax were similar for Zadaxin and T alpha1-HLR, but higher after administration of Timosina. CONCLUSION: Thymosin alpha1 kinetics from this study are comparable to those previously obtained in Japanese volunteers or cancer patients, but may be influenced by the drug formulation used.

[Antihypertensive action of various talinolol dosages after four week's treatment in comparison with placebo]. / Antihypertensive Wirksamkeit verschiedener Talinolol-Dosierungen nach vierwöchiger Behandlung im Vergleich zu Plazebo.

The dose dependence of the antihypertensive effect of the beta 1 selective blocker talinolol (CAS 57460-41-0, Cordanum) was investigated in 97 essential hypertensive patients (mild to moderate) using the ambulatory blood pressure monitoring (ABPM) in a single-centre, double-blind, randomized parallel-group study. After 4 weeks of treatment a comparison was made between the once daily administered doses of 50, 100 and 200 mg as well as with placebo. The primary parameter was the mean diastolic blood pressure between 8.00 and 22.00 (dTMW). Furthermore, the duration of action of the once daily administration of 200 mg talinolol was compared with the twice daily application of 100 mg each. With regard to dTMW an increasing antihypertensive effect was determined for the dosage step from 50 mg to 100 mg talinolol/d. No further increase in the blood pressure lowering effect was observed with 200 mg talinolol/d. The highest frequency of therapy responders was found in the 100 mg group with 72.2%. Moreover it could be demonstrated, that within the dosage range of 1 x 100-200 mg Talinolol/d a significant and 24 h lasting reduction of blood pressure and pulse rate was achieved, including the early morning period. There were no differences between the blood pressure profile of the 200 mg group and the 2 x 100 mg group at the end of the 4 weeks treatment. All talinolol dosages investigated in this study were proved to be safe and well tolerated. The observed complaints classified as adverse drug reactions represented typical side effects of beta-blockers of mild to moderate intensity. It can be concluded from the results that the once daily intake of talinolol in the dosage range of 100-200 mg/d shows a reliable efficacy in the treatment of essential hypertension accompanied by a noncritical safety profile.

[Leiomyosarcoma of the mandibular canal. Possible differential diagnosis of cystic processes of the mandible]. / Leiomyosarkome im Canalis mandibularis. Mögliche Differentialdiagnose zystischer Prozesse im Unterkiefer.

Leiomyosarcomas in the mandible are extremely rare. The cases of a 40-year-old woman with a leiomyosarcoma in the mandible is reported. Diagnostic and therapeutic problems are discussed.

Proof of efficacy of the Ginkgo biloba special extract EGb 761 in outpatients suffering from mild to moderate primary degenerative dementia of the Alzheimer type or multi-infarct dementia.

The efficacy of the Ginkgo biloba special extract EGb 761 in outpatients with presenile and senile primary degenerative dementia of the Alzheimer type (DAT) and multi-infarct dementia (MID) according to DSM-III-R was investigated in a prospective, randomized, double-blind, placebo-controlled, multi-center study. After a 4-week run-in period, 216 patients were included in the randomized 24-week treatment period. These received either a daily oral dose of 240 mg EGb 761 or placebo. In accordance with the recommended multi-dimensional evaluation approach, three primary variables were chosen: the Clinical Global Impressions (CGI Item 2) for psychopathological assessment, the Syndrom-Kurztest (SKT)(1) for the assessment of the patient's attention and memory, and the Nürnberger Alters-Beobachtungsskala (NAB)(2) for behavioral assessment of activities of daily life. Clinical efficacy was assessed by means of a responder analysis, with therapy response being defined as response in at least two of the three primary variables. The data from the 156 patients who completed the study in accordance with the study protocol were taken into account in the confirmatory analysis of valid cases. The frequency of therapy responded in the two treatment groups differed significantly in favor of EGb 761, with p<0.005 in Fisher's Exact Test. The intent-to-treat analysis of 205 patients led to similar efficacy results. Thus, the clinical efficacy of the ginkgo biloba special extract EGb 761 in dementia of the Alzheimer type and multi-infarct dementia was confirmed. The investigational drug was found to be well tolerated.

Proof of efficacy of the ginkgo biloba special extract EGb 761 in outpatients suffering from mild to moderate primary degenerative dementia of the Alzheimer type or multi-infarct dementia.

The efficacy of the ginkgo biloba special extract EGb 761 in outpatients with presenile and senile primary degenerative dementia of the Alzheimer type (DAT) and multi-infarct dementia (MID) according to DSM-III-R was investigated in a prospective, randomized, double-blind, placebo-controlled, multi-center study. After a 4-week run-in period, 216 patients were included in the randomized 24-week treatment period. These received either a daily oral dose of 240 mg EGb 761 or placebo. In accordance with the recommended multi-dimensional evaluation approach, three primary variables were chosen: the Clinical Global Impressions (CGI Item 2) for psychopathological assessment, the Syndrom-Kurztest (SKT) for the assessment of the patient's attention and memory, and the Nürnberger Alters-Beobachtungsskala (NAB) for behavioral assessment of activities of daily life. Clinical efficacy was assessed by means of a responder analysis, with therapy response being defined as response in at least two of the three primary variables. The data from the 156 patients who completed the study in accordance with the study protocol were taken into account in the confirmatory analysis of valid cases. The frequency of therapy responders in the two treatment groups differed significantly in favor of EGb 761, with p < 0.005 in Fisher's Exact Test. The intent-to-treat analysis of 205 patients led to similar efficacy results. Thus, the clinical efficacy of the ginkgo biloba special extract EGb 761 in dementia of the Alzheimer type and multi-infarct dementia was confirmed. The investigational drug was found to be well tolerated.

[Value of Papanicolaou exfoliative cytology in diagnosis of cancers of the upper aerodigestive tract]. / Die Wertigkeit der Exfoliativzytologie nach Papanicolaou in der Diagnostik von Karzinomen des oberen Aerodigestivtraktes.

Exfoliative cytology of the pharynx and larynx is a valid tool in the diagnosis of tumours. It is useful in the follow-up of chronic epithelial lesions of these regions and after tumour therapy. Cytological findings in group "Pap III" demand careful follow-up possibly with biopsy. For all other groups a biopsy is only indicated if there is a strong clinical suspicion of a tumour in the individual case. The simple technique of exfoliative cytology makes it an important part of aftercare of patients with malignancy, especially squamous cell carcinoma of the pharynx and larynx. The validity of the method depends on the care with which the specimen is taken and on the experience of the investigator.

Resistance measurement in normal and obstructed excised human lungs by means of the interrupter method.

In 6 normal and 7 obstructed excised human lungs the interrupter resistance (APTA, Jaeger Company) with an airway occlusion period of 100 ms was determined, by measuring the equivalent of the alveolar pressure at the end of the occlusion period. To check the pressure equilibration between the tracheal pressure and the alveolar space, catheters were put in the most peripheral layer of the lung. The lungs were ventilated in an artificial thorax. The airway resistance determined from the transbronchial pressure difference by the catheters was taken as a reference. Compared with the reference method, an overestimation of the airways resistance by the interrupter technique in normal lungs was found which was caused by an overshoot of the pressure equilibration during the occlusion period. In contrast, in severely obstructed lungs the pressure equilibration was not complete which led to an underestimation of the airways resistance by the interrupter technique. The best approximation of the airways resistance by the interrupter method was found in lungs with a low degree of obstruction.

Measurements of total and intrabronchial resistances in normal and diseased isolated lungs.

Postmortem studies of the total lung airways resistance (Rt), the central airways resistance (Rc), and the peripheral airways resistance (Rp) had been performed on normal lungs, on lungs with emphysema and lungs from patients with chronic obstructive pulmonary disease (COPD). In the normal lung a significant relationship between age and Rt was found. A decrease between 20 and 40 yr of age resulted from a decrease of Rp whereas an increase of Rt above the age of 40 was related to an increase in Rp. In the lungs with emphysema and obstruction Rp was increased especially. By variations of the breathing frequency and the lung volume (% of vital capacity) it could be detected that a remarkable effect upon Rt was caused by Rp. In general we found that even in normal lungs Rp is much higher than previously thought.

[Ventilation mechanics in the newborn. II. Dynamical measurements of the isolated lungs (author's transl)]. / Untersuchungen zur Atemmechanik von Früh-und Neugeborenen. II. Dynamische Messungen an isolierten Lungen

On 31 pairs of lungs from still borns and newborns and new borns of differing stages of maturation and age (23rd week of gestation up to the 24th week after birth), dynamical measurements within an artificial thorax were performed including systematical changes of ventilation types, particularly breathing frequency. In 12 pairs of lungs, surfactant activity was diminished. In these cases, a marked heterogeneity of ventilation and partly excessive increases of work of breathing correlated with the life span following birth could be shown, and some pathogenetical ways of cardiorespiratory failure as well as mechanisms of damaging late effects of the lungs following respiratory distress syndrome could be demonstrated. Moreover, by measurements of airway resistance it could be shown that in diseased and normal lungs of unmature infants the range of laminar flow is low due to the lability of the bronchial walls. A new method of valuation of the experimental data using the laws of alternating current (Heusinger) has been proven to be useful in the analysis of pulmonary mechanics.