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The aim of the present study was to compare the efficacy of guided tissue regeneration (GTR) using two different biodegradable barriers (polylactide acetyltributyl citrate; polydioxanon) in three- and two-walled infrabony defects. The polydioxanon barrier is an experimental GTR membrane that consists of a continuous occlusive barrier with a layer of slings on the side that is meant to face the mucoperiosteal flap. Fifteen patients provided 15 pairs of similar contralateral periodontal defects: 12 predominantly two-walled and 18 predominantly three-walled infrabony defects. Each defect was randomly assigned to treatment with polylactide acetyltributyl citrate (control) or polydioxanon (test) devices. At baseline, 6, 12, 18, and 24 months after surgery, clinical measurements were performed and standardized radiographs obtained (not at 18 months). Both treatments revealed a significant Gingival Index reduction, probing depth reduction, and vertical probing attachment level gain 24 months after surgery. Both treatments showed slight resorption of the crestal alveolar ridge after 24 months, which failed to reach statistical significance. A statistically significant bone gain within the infrabony pockets was measured for both treatment options 24 months postsurgical. Regarding Gingival Index and probing depth reduction as well as vertical probing attachment level and bone gain, there were neither statistically significant nor clinically relevant differences between test and control barriers. The use of both biodegradable barriers in GTR therapy may be recommended.

We examined the interaction of various established risk factors for acute mountain sickness (AMS) in a setting relevant for mountaineering and trekking.Questionnaires were obtained from 827 mountaineers on the day of arrival at the Capanna Margherita (4559 m) and on the next morning. Susceptibility to AMS was assessed by type and frequency of symptoms during previous exposures. AMS was defined as an AMS-C score/= 0.7 (environmental symptom questionnaire) on the morning after arrival at 4559 m. Preexposure was defined as having spent more than 4 d above 3000 m during the 2 months preceding the climb to the Capanna Margherita. Slow ascent was defined as ascending in more than 3 d. A risk model was developed by multiple logistic regression and prospectively validated on independent data.In susceptible individuals, the prevalence of AMS was 58% with rapid ascent and no preexposure, 29% with preexposure only, 33% with slow ascent only, and 7% with both preexposure and slow ascent. The corresponding values for nonsusceptible individuals were 31%, 16%, 11%, and 4%. The overall odds ratio for developing AMS in susceptible versus nonsusceptible individuals was 2.9 (95% confidence interval, 2.1-4.1). Age, gender, training, body mass index, alcohol intake, and cigarette smoking had no significant effect in bivariate analyses or in multivariate logistic regressions.Individual susceptibility, rate of ascent, and preexposure are the major, independent determinants for prevalence of AMS.

To estimate the prevalence of undiagnosed diabetes mellitus, impaired glucose tolerance (IGT) and impaired fasting glucose (IFG), and their relations with cardiovascular risk factors in the general population aged 55 to 74 years in Southern Germany.Oral glucose tolerance tests were carried out in a random sample of 1353 subjects aged 55 to 74 years participating in the KORA (Cooperative Health Research in the Region of Augsburg) Survey 2000. Prevalences of glucose tolerance categories (1999 WHO criteria) were adjusted for sample probabilities. The numbers needed to screen (NNTS) to identify one person with undiagnosed diabetes were estimated from age-adjusted logistic regression models.Sample design-based prevalences of known and unknown diabetes, IGT, and IFG were 9.0%, 9.7%, 16.8%, 9.8% in men, and 7.9%, 6.9%, 16.0%, 4.5% in women, respectively. In both sexes, participants with undiagnosed diabetes had higher BMI, waist circumference, systolic blood pressure, triglycerides, uric acid, and lower HDL-cholesterol than normoglycaemic subjects. A combination of abdominal adiposity, hypertension, and parental diabetes in men resulted in a NNTS of 2.9 (95%CI: 2.0-4.6). In women, the combination of increased triglycerides, hypertension and parental diabetes history yielded a NNTS of 3.2 (95%CI: 2.2-5.1).About 40% of the population aged 55 to 74 years in the Augsburg region have disturbed glucose tolerance or diabetes. Half of the total cases with diabetes are undiagnosed. Cardiovascular risk factors worsen among glucose tolerance categories, indicating the need for screening and prevention. Screening for undiagnosed diabetes could be most efficient in individuals with abdominal adiposity (men), hypertriglyceridaemia (women), hypertension, and parental diabetes history.

Background: The aim of this 5-year follow-up case series was to clinically and radiographically evaluate the long-term results after guided tissue regeneration (GTR) therapy of infrabony defects using nonresorbable and bioabsorbable barriers. Methods: In 12 patients with advanced chronic periodontitis 12 pairs of contralateral infrabony defects were treated. Within each patient one defect received a non-resorbable (expanded polytetrafluoroethylene [ePTFE]; control: C) and the other a bioabsorbable (polyglactin 910; test: T) barrier by random assignment. At baseline and at 6 and 60 ±3 months after surgery clinical parameters and standardized radiographs were obtained. Gain of bone density within infrabony defects was assessed using subtraction radiography. Results: Eight of 12 patients were available for the 60-month reexaminations. Six and 60 ±3 months after GTR therapy statistically significant (P

Background: Teleconsultation services have the potential to improve the communication among different medical care providers and between them and the patient. Increasing effectiveness in the shape of a savings in time or cost is often the result of better communication. Methods: A study was performed in order to demonstrate the feasibility of teleconsultation services, using the perioperative management of cataract patients as an example, and to provide data on the quality, acceptance and effectiveness of these services in comparison with a control group experiencing normal treatment. Results: Over a period of 3 months 42 patients of the teleconsultation group and 20 controls were studied. There were two referring ophthalmologists and three surgeons. The teleconsultation group had one consultation fewer with the ophthalmic surgeon because of the teleconsultation service. Patient satisfaction was slightly higher using the new technology. Patients would like to see this technique used again should surgery on the second eye become necessary. Conclusions: Teleconsultation services are ready to support and improve perioperative cataract management. Patients' confidence in their medical treatment was increased by using teleconsultation services. Physicians will expand the use of teleconsultation.

Evaluation of the clinical effect of topical application of doxycycline adjunctive to non-surgical periodontal therapy.A total of 111 patients suffering from untreated or recurrent moderate to severe periodontitis at 3 different centers (Heidelberg, Frankfurt, Nijmegen) were treated in this double-blind split-mouth study. In each patient, 3 different treatment modalities were assigned randomly to 3 test teeth: scaling and root planing alone (SRP), SRP with subgingival vehicle control (VEH), and SRP with subgingival application of a newly developed biodegradable 15% doxycycline gel (DOXI). At baseline, clinical parameters were measured at all single rooted teeth using a reference splint: PlI, PPD, relative attachment level (RAL-V), GI. 3 strata were generated according to baseline PPD: (i) 5-6 mm, (ii) 7-8 mm, (iii)or =9 mm. Not more than 50% active smokers were allowed to each stratum. 3 and 6 months after therapy re-examination was performed by examiners blinded to baseline data and test sites. The statistical comparison of RAL-V gain and PPD reduction between the treatments was based on a repeated measures ANOVA with correction according to HuynhFeldt. The comparison of SRP versus DOXI was considered as the main study question.110 patients finished the 3 months and 108 the 6 months examination. The study did not show adverse effects of VEH or DOXI except for one singular inflammation that occurred 2 months after application of the doxycycline gel. DOXI provided statistically significantly more favorable PPD reduction (SRP: -2.4+/-1.4 mm, VEH: -2.7+/-1.6 mm, DOXI: -3.1+/-1.2 mm; SRP versus DOXI p=0.0001, VEH versus DOXI p=0.0066) and RAL-V gain (SRP: 1.6+/-1.9 mm, VEH: 1.6+/-2.2 mm, DOXI: 2.0+/-1.7 mm; SRP versus DOXI p=0.027, VEH versus DOXI p=0.038) than SRP and VEH after 6 months.Adjunctive topical subgingival application of a biodegradable 15% doxycycline gel was safe and provided more favorable RAL-V gain and PPD reduction than SRP alone and VEH. Thus, by use of topical doxycycline the threshold for surgical periodontal therapy might be moved toward deeper pockets.

The aim of this 5-year follow-up study was to clinically and radiographically evaluate the long-term results after guided tissue regeneration (GTR) therapy of Class II furcation defects using non-resorbable and bioabsorbable barriers.Nine pairs of contralateral Class II furcation defects were treated in 9 patients with advanced periodontitis. Within each patient, one defect received a non-resorbable (expanded polytetrafluoroethylene [ePTFE]; control, C) barrier and the other a bioabsorbable (polyglactin 910; test, T) barrier by random assignment. At baseline, 6, and 60 +/- 3 months after surgery, clinical parameters and standardized radiographs were obtained. Gain of bone density within furcation areas was assessed using subtraction radiography.Six and 60 months after GTR therapy, statistically significant (P0.05) horizontal attachment (CAL-H) gain was observed in both groups (C6: 1.7 +/- 0.8 mm; C60: 1.6 +/- 1.2 mm; T6: 2.0 +/- 0.7 mm; T60: 2.2 +/- 0.9 mm). However, 1 furcation assessed as Class I six months after GTR therapy with a bioabsorbable barrier had progressed to Class III after 5 years, and in another patient, 5 years after placement of an ePTFE barrier, 1 furcation had lost all the CAL-H gain that had been observed at 6 months. Subtraction analysis revealed similar area gain in both groups 6 and 60 months postsurgically (C6: 0.3 +/- 0.5; C60 1.0 +/- 1.7; T6: 0.4 +/- 0.4; T60: 1.1 +/- 1.7).CAL-H gain achieved after GTR therapy in Class II furcations was stable after 5 years in 16 of 18 defects. The study failed to show a statistically significant difference in stability of CAL-H gain between control and test groups 5 years after GTR therapy.

Objectives: In this study we evaluate gender differences in affective adaptation and health perception in patients 6 months after stent implantation. Background: Assessment of gender-specific behavioral strategies to cope with serious cardiac disease conditions has not been given much attention until now. Preliminary data suggest greater impairments in female patients, which might be of clinical relevance. Methods: Three hundred seventeen patients were eligible for the 6-month follow-up investigation, 78 (24.6%) of whom were women. The women were significantly older but did not differ from men in their cardiac risk features and treatment procedures. There were no gender differences in prevalence of hypertension, hypercholesterolemia, and family history. Men had a significantly higher prevalence of smoking than women, whereas women had a significantly higher prevalence of diabetes than men. A structured interview and a standardized psychodiagnostic assessment was carried out, which covered domains of affective dysfunction (depression, anxiety, intrusion, and avoidance), vegetative symptoms (sleeping disorders), and parameters of negative health perception. Results: There were no significant gender differences in the prevalence of depressive symptoms. Women exhibited higher mean values of anxiety than men, which did not reach significance. Sleeping disorders were significantly more prevalent in women. The absolute level of being distressed by intrusive thoughts and avoidance behavior related to the severe underlying disease process was low in the total group of patients examined. Measurable gender differences did not emerge. Fifty-one (16.5%) patients exhibited pessimistic anticipation of dire consequences and severe signs of negative health perception (NHP group). There was a trend, although not statistically significant, toward more women being in the NHP group. The distribution of cardiac risk factors, however, was completely balanced in the NHP+ and NHP− patient groups. Objective somatic cardiac disease parameters did not account for the negative health perception. NHP was, however, associated with significantly more prestent angina pectoris (p < 0.040) and poststent angina pectoris (p < 0.0001). High levels of anxiety, depression, and of disturbed sleep also led to a sharp separation between patients with high degrees of an anticipated incapacitation due to the disease process. Univariate regression analysis suggested an effect of female gender on the occurrence of NHP (odds ratio 1.70; 95% CI 0.88 to 3.25), which was of borderline significance. Control for confounders in a multiple regression model, however, eliminated the gender effect (odds ratio 1.04, 95% CI 0.48 to 2.23). Poststent chest pain (odds ratio 7.75, 95% CI 3.28 to 18.32) and sleeping disorders (odds ratio 1.32, 95% CI 1.16 to 1.51) were identified as the most powerful confounders of the gender–NHP association. Conclusion: Contrary to expectation, women were not per se more distressed than men in all areas of adaptation of the midterm course after stent implantation, although the higher levels of anxiety and sleeping disorders in women deserve attention. A considerable proportion of patients exhibited a pessimistic disease perspective independent of their somatic status, which was associated with affective morbidity. The tendency toward more negative health perception in women may be due to their more frequent occurrence of chest pain and sleeping disorders.

OBJECTIVE: The importance of screening for diabetic retinopathy has been established, but the best method for screening has not yet been determined. We report on a trial of assessment of digital photographs by telemedicine compared with standard retinal photographs of the same fields and clinical examination by ophthalmologists. RESEARCH DESIGN AND METHODS: A total of 129 diabetic inpatients were screened for diabetic retinopathy by slit-lamp biomicroscopy performed by an ophthalmologist and by two-field 50 degrees non-stereo digital fundus photographs assessed by six screening centers that received the images by electronic mail. Conventional 35-mm transparencies of the same fields as the digital photographs were assessed by a retinal specialist and served as the reference method for detection of diabetic retinopathy. Slit-lamp biomicroscopy was the reference method for the detection of macular edema. RESULTS: The prevalence of any form of diabetic retinopathy was 30% (n = 35); of sight-threatening retinopathy including macular edema, the prevalence was 6% (n = 7). The assessment of digital images by the six screening centers resulted in a median sensitivity of 85% and a median specificity of 90% for the detection of moderate nonproliferative or sight-threatening diabetic retinopathy. Clinically significant macular edema (n = 4) was correctly identified in 15 of the 24 grading reports. An additional seven reports referred the patients for further investigation because of concurrent diabetic retinopathy. CONCLUSIONS: Telescreening for diabetic retinopathy by an assessment of two-field 50 degrees non-stereo digital images is a valid screening method. Although detection of clinically significant macular edema using biomicroscopy is superior to digital or standard non-stereo photographs, only few patients with sight-threatening diabetic retinopathy are missed.

There is increasing evidence of the efficacy and effectiveness of psychosocial interventions in schizophrenic patients. However, little research has been done on differential therapy effects. In a prospective, randomized clinical trial we carried out psychoeducational medication management training, cognitive psychotherapy, and key-person counseling. The patients of the control group participated in structured free-time activities for control of therapeutic commitment. Data from a total of 156 schizophrenic patients (DSM-III-R, no first-admissions) were available at 2-year follow-up. We analyzed in this study whether there are differential therapy effects of these interventions, depending on patient characteristics at baseline. There was a significant statistical interaction between treatment condition (specific/non-specific) and prognosis with respect to treatment outcome. Patients with a favorable prognosis and better social functioning had a better course under the specific treatment but a less favorable outcome in the non-specifically treated control group. These results suggest that more vulnerable patients are not sufficiently capable of learning and using coping strategies for relapse prevention. We need to learn more about differential indications for psychosocial treatment.

Angesichts der immer noch zunehmenden Flut an medizinischen Informationen ist es aus Zeit- und Effektivitatsgrunden notwendig, das Studium der veroffentlichten Beitrage so zu gestalten, das relevante Informationen als solche zuverlassig erkannt werden. In der folgenden Ubersicht soll versucht werden, Orientierungspunkte fur ein gleichzeitig kritisches und effektives Literaturstudium zu liefern. Die Darstellung wird sich auf das besonders wichtige Gebiet der klinischen (Therapie-)Studien konzentrieren. Viele Aussagen treffen auch fur Publikationen zur Evaluierung diagnostischer Tests zu, deren spezielle Anforderungen hier aber nicht behandelt werden (vergl. 4, 7, siehe auch den Artikel von Richter et al.). Andere grose Themenbereiche der medizinischen Literatur, z.B. epidemiologische Studien, konnen in diesem Zusammenhang nicht behandelt werden, da sie einerseits noch zu wenig strukturiert sind, als das man brauchbare Empfehlungen abgeben konnte, und andererseits individuell so voller Detailprobleme medizinischer, methodischer und statistischer Art stecken, das eine ubergreifende Darstellung kaum moglich ist. Ebenso werden Spezialgebiete der klinischen Therapieforschung, z. B. der Bereich der Meta-Analyse, nicht behandelt.

Conventional diagnostics fail to trace dysplasias and early cancers of the colon. By means of Laserlight Induced Fluorescence Diagnostics (LIFD) macroscopically not visible malignant tumors and dysplasias of the colon can be detected. The main side effect of systemically applicated photosensitizers is a general photosensibilization of the organism which provokes an increased photosensitivity of the body. Local application of (delta) -aminolevulinic acid (ALA) reduces systemic uptake without impairment of the quality of investigation. Colorectal cancer in male wistar rats was induced by weekly subcutaneous (s.c.) injections of 1,2- dimethylhydrazine (DMH) for 17 weeks. After s.c. DMH injection the wistar rats (n equals 25) developed in average 5.6 macroscopically visible colon carcinomas. 80% of these tumor were detected by LIFD after photosensibilization with Photofrin II intravenously (i.v.), 29% after application of mTHPC (i.v.), 13% after ALA (i.v.), 20% after intraperitoneal application of ALA (i.p.) and 57% after local application of ALA in the colon. LIFD is a capable method for the detection of macroscopically not visible dysplasias and colon carcinomas of the rat induced by DMH. The applied PS and the method of application influences the detection of carcinomas and dysplasias. Systemic photosensibilization of the whole organism can be avoided by the local application of ALA without limiting the quality of investigation.

The aim of the present study was to compare the effects of guided tissue regeneration (GTR) with non-resorbable (ePTFE [G]) and biodegradable barriers (Polyglactin 910 (V)). In 20 patients, providing 25 pairs of symmetrical periodontal defects (7 pairs of interproximal intrabony lesions, 12 pairs of degree II and 6 pairs of degree III furcation involvement), each defect was randomly assigned to treatment with either non-resorbable (control) or biodegradable (test) devices. At baseline and 6 months after surgery, clinical measurements (GI, PPD, PAL-V, PAL-H, P1I) and standardized radiographs were obtained. On the radiographs, the linear distances from the cemento-enamel junction (CEJ) to the alveolar crest (AC), and from the CEJ to bottom of the bony defect (BD) were measured using a computer-assisted analysing method (LMSRT). Both treatments revealed a significant (p < 0.05) PPD reduction (-2.90 +/- 1.33 mm (V), -2.71 +/- 1.41 mm (G)), PAL-V gain (1.78 +/- 1.27 mm (V), 1.46 +/- 1.35 mm (G)), PAL-H gain (2.00 +/- 0.82 mm (V), 1.60 +/- 0.59 mm (G)), and radiographic changes (CEJ-AC: 0.48 +/- 0.75 mm (V), 0.73 +/- 0.92 mm (G); CEJ-BD: -0.76 +/- 0.79 mm (V), -0.41 +/- 0.72 mm (G)) after 6 months. The mean differences between the changes for test and control were not significant for most clinical and radiographic parameters. Similar clinical and radiographic results were found 6 months after surgical treatment using either non-resorbable or biodegradable barriers. More favorable results concerning PAL-H gain could be observed with biodegradable barriers after 6 months. Therefore, based on these results, the use of biodegradable barriers in GTR may be recommended and, thereby, a surgical re-entry to remove non-resorbable barriers can be avoided.

BACKGROUND: Transition from hospital to home is a critical period for older persons with acute myocardial infarction (AMI). Home-based secondary prevention programs led by nurses have been proposed to facilitate the patients' adjustment to AMI after discharge. The objective of this study was to evaluate the effects of a nurse-based case management for elderly patients discharged after an AMI from a tertiary care hospital. METHODS: In a single-centre randomized two-armed parallel group trial of patients aged 65 years and older hospitalized with an AMI between September 2008 and May 2010 in the Hospital of Augsburg, Germany, patients were randomly assigned to a case management or a control group receiving usual care. The case-management intervention consisted of a nurse-based follow-up for one year including home visits and telephone calls. Key elements of the intervention were to detect problems or risks and to give advice regarding a wide range of aspects of disease management (e.g. nutrition, medication). Primary study endpoint was time to first unplanned readmission or death. Block randomization per telephone call to a biostatistical center, where the randomization list was kept, was performed. Persons who assessed one-year outcomes and validated readmission data were blinded. Statistical analysis was based on the intention-to-treat approach and included Cox Proportional Hazards models. RESULTS: Three hundred forty patients were allocated to receive case-management (n=168) or usual care (n=172). The analysis is based on 329 patients (intervention group: n=161; control group: n=168). Of these, 62% were men, mean age was 75.4 years, and 47.1% had at least either diabetes or chronic heart failure as a major comorbidity. The mean follow-up time for the intervention group was 273.6 days, and for the control group it was 320.6 days. During one year, in the intervention group there were 57 firs unplanned readmissions and 5 deaths, while the control group had 75 first unplanned readmissions and 3 deaths. With respect to the endpoint there was no significant effect of the case management program after one year (Hazard Ratio 1.01, 95% confidence interval 0.72-1.41). This was also the case among subgroups according to sex, diabetes, living alone, and comorbidities. CONCLUSIONS: A nurse-based management among elderly patients with AMI had no significant influence on the rate of first unplanned readmissions or death during a one-year follow-up. A possible long-term influence should be investigated by further studies.Clinical trial registration: ISRCTN02893746. &nbsp

The 10-year follow-up of the Munich General Practitioner Project was designed as a long-term prospective study to evaluate factors predicting macrovascular and overall mortality in a random cohort of non-insulin-dependent diabetic (NIDDM) patients. Of the original 290 patients (103 males, 187 females, median age 65 years) 92.5 % could be assessed, 103 subjects had died, 58 from macrovascular causes. In an univariate analysis of baseline data, deceased patients, and especially those who died from macrovascular causes had significantly higher fasting blood glucose, HbA1c, von Willebrand-factor protein, urine albumin excretion, and serum β2-microglobulin, were significantly older, exhibited significantly more ischaemic heart disease (abnormal ECG Minnesota codes), carotid artery and peripheral vascular disease (both determined by ultrasound-Doppler), and had significantly inferior knowledge about diabetes and its treatment. No significant differences were seen for gender, blood pressure, smoking, total cholesterol, triglycerides, HDL-cholesterol, or the use of antidiabetic, antihypertensive or coronary drugs. In a multiple logistic regression analysis, the risk factors for macrovascular death were age, HbA1c and von Willebrand-factor protein. When baseline macrovascular disease was taken into account, carotid artery disease was also a determinant. The main variables from the metabolic syndrome (blood pressure, dyslipidaemia, body mass index) did not enter a multiple logistic regression analysis. The data suggest that age and haemoglobin A1c are major determinants, and that in addition von Willebrand-factor associated endothelial damage is a risk factor for macrovascular mortality in NIDDM patients. [Diabetologia (1996) 39: 1540–1545]

Background: Approximately 30% of the patients with primary breast cancer who have no axillary lymph node involvement (i.e., lymph node negative) at the time of surgery will relapse within 10 years; 10% -20% of the patients with distant metastases will be lymph node negative at surgery. Axillary lymph node dissection, as a surgical procedure, is associated with frequent complications. A possible alternative to nodal dissection in terms of prognosis may be the immunocytochemical detection of tumor cells in bone marrow. Purpose: In a prospective study, the value of tumor cell detection (TCD) in bone marrow was compared with axillary lymph node dissection in the prognosis of primary breast cancer after surgery. Methods: Data from 727 patients with primary, operable breast cancer were included in the analysis. All patients had surgery, including axillary lymph node dissection, from May 1985 through July 1994 at the Women's Hospital of the University of Heidelberg (Federal Republic of Germany). Bone marrow aspiration at two sites on each anterior iliac crest was performed immediately after surgery while the patients were under general anesthesia. Most patients received some type of systemic adjuvant therapy. The monoclonal antibody 2E11, directed against the polymorphic epithelial mucin TAG12, was used to detect tumor cells in bone marrow samples. The association of TCD with recognized prognostic indicators was evaluated by means of chi-squared tests. Survival without the development of distant metastases (i.e., distant diseasefree survival) and overall survival were estimated by use of the Kaplan-Meier method; the logrank test was used to compare survival curves. A multivariate Cox regression analysis with stratification according to adjuvant treatment type was used to assess the independent prognostic value of TCD in bone marrow in relation to other variables. Reported P values are two-sided. Results: Tumor cells were detected in the bone marrow of 203 (55%) of 367 lymph node-positive patients and in 112 (31%) of 360 lymph nodenegative patients. TCD was associated with larger tumors (P

Background and Purpose We sought to determine whether early ( Methods We prospectively studied 77 patients by combined Scandinavian Stroke Scale score at admission, repeated computed tomography and angiography before and after thrombolytic treatment at Results Recanalization rates at 8 and 24 hours after stroke correlated with sites of occlusion (middle cerebral artery branch, 73% and 73%; trunk, 27% and 38%, respectively; intracranial internal carotid artery bifurcation, 14% and 14%; P =.002), collaterals (good, 43% and 51%, respectively; scarce, 17% and 19%, respectively; P =.01), and Scandinavian Stroke Scale score at admission ( P =.002). Six of 7 patients with delayed recanalization had good outcomes. Recanalization at P =.69). Recanalization at 24 hours increased the proportion of good outcomes from 23% to 75% in a subgroup of patients. Recanalization did not independently affect mortality ( P >.15). Conclusions Even if delayed, arterial recanalization may improve clinical outcome in a subgroup of patients with middle cerebral artery occlusion.

Tenascin serum levels were evaluated in 118 patients with primary colorectal carcinoma and in a control group of 51 healthy persons in a double-sided sandwich ELISA. The data were correlated with post-operative TNM-staging. Patients with colorectal carcinomas had significantly higher serum levels of tenascin than the control group. At the 95% level of specificity, sensitivity was 25%. Tumor grading obviously had no influence on the level of tenascin in serum. With increasing pT-category, tenascin levels increased as well. In patients with distant metastatic disease, serum tenascin levels were significantly higher than in patients without distant metastases. These data suggest that, in colorectal carcinoma, the preoperative level of serum tenasin reflects the total tumor burden and correlates with metastatic disease. Our observation warrants a prospective study of the relevance of tenascin serum levels with regard to prognosis and as an indicator of relapse.

Purpose The population-based KORA (Cooperative Health Research in the Region of Augsburg [Germany]) study was used to evaluate the prevalence of eye diseases and potential interactions with general health status, laboratory data, medication, and genetic background. Methods In all, 2593 probands, ranging in age from 32 to 71 years (mean: 52 years), were asked in a standardized interview for the presence of cataracts, glaucoma, and corneal or retinal disorders; positive answers were validated and specified by treating ophthalmologists. Additional data came from a questionnaire or from laboratory data. Results We validated 10 probands with corneal diseases (validation rate: 32%), 26 with retinal diseases (validation rate: 60%), 40 with glaucoma (validation rate: 75%), and 100 participants with cataracts (validation rate: 88%). Glaucoma was significantly associated with increasing age, diabetes and its treatment, and the use of drugs in airway diseases. Cataracts were significantly associated with increasing age, female sex, hypertension, and diabetes. In females, cataracts were particularly associated with the use of ophthalmological corticosteroids, some antihypertensives, and antidiabetics. In contrast, cataracts in males were associated only with the use of angiotensin-converting enzyme inhibitors. We also tested some polymorphic markers; two (GJA8, CRYBB3) were significantly associated with cataracts. Conclusions Self-reported ocular diagnoses by questionnaire showed varying degrees of accuracy; this method of data collection is valid, providing confirmation is obtained from treating ophthalmologists. It revealed a similar profile of major risk factors for cataracts (age, female sex, and diabetes) in Germany like that of other international studies. The reported associations between medical treatment and genetic polymorphisms in early-onset cataract merit further functional study.

Introduction In Germany, regional data on the prevalence of type 2 diabetes mellitus (T2DM) are lacking for use in healthcare planning. We analysed regional differences in the prevalence of T2DM and treatment with antidiabetic agents. Methods Data from five regional population-based studies and the German National Health Interview and Examination Survey (GNHIES98) conducted between 1997 and 2006 were analysed. Estimates of self-reported diabetes, treatment, and onset of diabetes were compared. T2DM prevalence (95% CI) for the five regional studies was directly standardised to the German adult population (31 December 2007). Results From 11 688 participants aged 45–74 years, 1008 had prevalent T2DM, corresponding to a prevalence of 8.6% (8.1%–9.1%). For the GNHIES98 a prevalence of 8.2% (7.3%–9.2%) was estimated. Prevalence was higher in men (9.7%; 8.9%–10.4%) than in women (7.6%; 6.9%–8.3%). The age-standardised regional prevalence was highest in the East with 12.0% (10.3%–13.7%) and lowest in the South with 5.8% (4.9%–6.7%). The mean age of onset of T2DM was lower in Northeast (53+9SD) than in West-Germany (57+10SD). Treatment with oral antidiabetic agents was more frequently reported in the South (56.9%) than in the Northeast (46.0%), whereas treatment with insulin alone was more frequently reported in the Northeast (21.6%) than in the South (16.4%). Conclusion The prevalence of T2DM showed a Northeast and Southwest gradient within Germany with the highest standardised prevalence in the East, which is in accordance with regional differences in the distribution of risk factors for T2DM. Furthermore, the treatment with antidiabetic agents showed regional differences.

SummaryThis study considers the question of whether relapse rates among schizophrenic patients can be reduced by means of relatives' groups. In a randomized, controlled intervention study, two therapeutic strategies (therapeutic relatives' groups, initiated relatives' self-help groups) were compared with each other and with a control group. Interventions were confined to the relatives, with the patients continuing their standard treatment. The study involved 151 relatives of 99 chronic DSMIII schizophrenics. Data were collected before and after a 1-year intervention phase and in a 2-year follow-up. No difference existed between the groups with respect to rehospitalization data. However, numerous differences recorded in the psychopathological findings and in living and working circumstances suggest that therapeutic work with relatives is of clinically significant benefit.

Seen from societal perspective informal care is the major cost component in dementia care for community-living individuals. Values assigned to informal caregiving time are almost the three-fold of total health insurance’s expenditures. Hours family caregivers dedicate to a dementia patient strongly rise when diseases progresses, leading to jumping costs of informal care (€ 31,823 in mild vs. € 52,913 in moderate stage). This observation is in line with a review of 28 dementia related cost of illness studies conducted by Quentin et al. [see Acta Psychiatrica Scandinavica 2009, 1:17]. Community-based informal care is a non-cash item saving expenditures for professional care. The economic impact of such tasks is often disregarded, not to speak of the corresponding stress. Referring to a study on behalf of German “Ministry of Family Affairs, Senior Citizens, Women and Youth“ targeting at caregivers of geriatric population in general [see BMFSFJ, editor, 2005] we assumed that caregivers of demented people, too, wish to extend the patients’ time at home as long as feasible. Due to a change of traditional living arrangements within the past decades, a growing number of elderly people is now living on their own without support of any family member. This situation poses an enormous challenge regarding the future organization of dementia care and its financing via social security system. To maintain today’s care-setting concepts fostering community-based dementia care and support to family caregivers need to be further developed. Methods – study population The study observed over a two-years period 383 home-dwelling individuals with mild to moderate dementia in the German region „Middle-Franconia“. The Participants were recruited via general practitioners according to following inclusion criteria: • Member of AOK Bavaria Health Insurance Fund • aged 65 years or older • support of an informal caregiver • from 10 to 24 MMSE [For further details see BMC Health Services Research 2009, 9:91] MMSE values of 10-17 were defined as moderate stage of dementia (n = 135), MMSE values of 18-24 (n =248) as mild stage of dementia. RESULTS OF THE GERMAN IDA STUDY – ASSESSING THE FINANCIAL IMPACT OF INFORMAL CARE AMONGST COMMUNITY-LIVING DEMENTIA PATIENTS L. Schwarzkopf, S. Kunz, P. Menn, S. Wunder2, P. Marx3, J. Lauterberg4, E. Grasel5, R. Holle

Background The aim of this study was to measure HrQoL during acute exacerbations of COPD using generic and disease-specific instruments, and to assess completeness, proportion with best or worst health state, sensitivity to change and discriminative ability for each instrument. Methods EQ-5D, SF-12 and SGRQ were obtained from COPD patients with GOLD stage III and IV hospitalized for an acute exacerbation both at admission and discharge. To assess the instruments' properties, utility values were calculated for EQ-5D and SF-12, and a total score was derived from the SGRQ. Results Mean utilities ranged from 0.54 (SF-12, stage IV) to 0.62 (EQ-5D, stage III) at admission, and from 0.58 (SF-12, stage IV) to 0.84 (EQ-5D, stage III) at discharge. Completeness was best for EQ-5D and SGRQ, while no utility value for the SF-12 could be calculated for more than 30%. For SGRQ subscales, the minimal score occurred in up to 11% at admission, while full health was observed for the EQ-5D at discharge in 13%. Sensitivity to change was generally good, whereas discrimination between COPD stages was low for the EQ-5D. Conclusions Acute exacerbations seriously impair health status and quality of life. The EQ-5D is generally suitable to measure HrQoL in exacerbations of severe COPD, although the high proportion of patients reporting full health at discharge poses a problem. The main issue with the SF-12 is the high proportion of missing values in a self-assessed setting. Properties of the SGRQ were satisfactory. However, since no utility values can be derived from this disease-specific instrument, it is not suitable for cost-utility analyses in health-economic evaluations.

The objective of this study was to identify clinically relevant predictors of short-term (2 years) outcome in schizophrenic patients and to gather these predictors into one simple prognosis model for the course of the disease. Ninety-nine schizophrenic outpatients classified according to DSM-III criteria were observed for 3 years with regard to their relapse (rehospitalization) frequency. Predictors of both a high and a low relapse risk permitting a prognostic assessment of the individual case were based on various sources: case history data, especially those relating to the previous course of the disease; cocial and therapeutic situation; psychopathological findings; emotional family atmosphere; and prognosis scales.

Patients with relapsed Hodgkin's disease who respond to salvage therapy are successfully treated with cyclophosphamide, carmustine (BCNU), and etoposide (VP-16) (CBV) followed by autologus bone marrow transplantation (ABMT). Because of heavy pretreatment including radiation to the pelvic site, marrow harvest was not feasible in those patients. We therefore used blood-derived hemopoietic precursor cells as an alternative stem-cell source to rescue them after superdose chemotherapy. Hemopoietic precursor cells were mobilized into the peripheral blood either by chemotherapeutic induction of transient myelosuppression followed by an overshooting of blood stem-cell concentration, or by continuous intravenous (IV) granulocyte-macrophage colony-stimulating factor (GM-CSF) administration. The median time to reach 1,000 WBC per microliter, 500 polymorphonuclear cells (PMN) per microliter, or 20,000 platelets per microliter was 10, 20.5, and 38 days, respectively, for 50% of all patients. The platelet counts of two patients never dropped below 20,000/microL following autologous blood stem-cell transplantation (ABSCT), whereas two other patients had to be supported with platelets for 75 and 86 days posttransplant until a stable peripheral platelet count of 20,000/microL was attained. Among the 11 assessable patients, seven are in unmaintained complete remission (CR) at a median follow-up of 318 days. This is a first report on a series of ABSCTs in patients with advanced Hodgkin's disease proving that, despite prior damage to the marrow site, the circulating stem-cell pool is still a sufficient source of hemopoietic precursor cells for stem-cell rescue.

Recently, the International Diabetes Federation (IDF) has formulated a new worldwide definition for the metabolic syndrome (1). In contrast to the previous World Health Organization (WHO) and National Cholesterol Education Program (NCEP) criteria, abdominal obesity was considered as a prerequisite (2, 3). Population-based epidemiological data on the metabolic syndrome in Europe are rare, and the prevalence in Germany is unknown. Thus, we estimated sex-specific prevalences of the metabolic syndrome according to the IDF, WHO, and NCEP definitions in the population-based KORA Survey 2000 (Augsburg, …

Histopathologic specimens from 249 patients with small cell lung cancer (SCLC) were reviewed and classified into oat cell-type, pure intermediate cell-type (excluding specimens with mixed small cell/large cell features), and small cell/large cell-type. One hundred seventy (68%) specimens displayed oat cell features (including 30 with mixed oat cell/intermediate cell features), 66 (27%) displayed intermediate cell features, and 13 (5%) displayed mixed small cell/large cell features. No differences among these subtypes were found with respect to stage of disease, sex, age, performance status, and number and distribution of metastases. Complete and partial remission rates for the oat cell-type were, respectively, 31% and 38%, for the intermediate cell-type 20% and 45%, and for the small cell/large cell-type 38% and 31%. Two-year survival rates were 7%, 11%, and 15%, respectively. These data were all statistically insignificant, and comparisons of log-rank analyses of survival curves for these SCLC subtypes also showed no statistically significant differences. We thus conclude that histologic subtypes of SCLC are not distinct entities of clinical relevance, and that prognostic as well as therapeutic decisions cannot be based on histologic subtyping.

Von Juli 1981 bis November 1983 vvurden insgesamt 282 Patienten mit einem kleinzelligen Bronchialkarzinom erstmals in der Thoraxklinik Rohrbach behandelt. Hiervon erfullten nur 85 die Selektionskriter

Analyses of relapse in small cell lung cancer (SCLC) were performed in 443 evaluable patients included in two multicenter trials. The time to first progression mainly depended on best response to therapy. Nearly all patients with no change (NC) suffered from progression within 6 months. In patients with partial remission (PR), progression occurred within 12 months in nearly all cases. If complete remission (CR) was achieved, no relapse was seen within the first 6 months after the onset of treatment. Between the 6th and 8th month a slowly increase and after the 8th month a rapid increase of relapse was noticed. In the majority of patients with limited disease relapse was localized in the area of the primary tumor, whereas in patients with extensive disease relapse mostly was due to the development of distant metastases. Of the 443 patients, 35 achieved 2-year survival (8%). Main prognostic factors for the achievement of 2-year survival were extent of disease and sex. Patients with distant metastases and CR had a poor chance of achieving a 2-year survival, while patients without distant metastases and CR had a 30% chance. Females with limited disease and a Karnofsky score of 70% or more had a 40% chance of achieving 2-year survival, the corresponding probability for males was less than 10%. Because of the high frequency of relapse in SCLC, the stabilization of best response has to be considered as a main objective in therapy. In our opinion, two different strategies may be useful in order to achieve higher 2-year survival rates: a) periodic controls and renewal of therapy as soon as possible after relapse has occurred or b) reinduction therapy in intervals of about 8 weeks or more in order to delay or prevent the development of relapse. To find out if one of these strategies is superior to the other, is one of the objectives of our new randomized trial in SCLC.

Patients with small cell carcinoma of the lung (SCCL) were treated in two multicenter trials with different cytostatic drug regimens including ifosfamide. In the first randomized study, including 306 patients, alternating chemotherapy with VP 16, ifosfamide, vindesine (VPIV), adriamycin, cisplatinum, vincristine (APO), and cyclophosphamide, methotrexate, CCNU (CMCC) was compared against standard treatment with ACO (adriamycin, cyclophosphamide, vincristine). It was shown that the alternating therapy resulted in a higher response rate (88% vs 78%) and a longer median survival time (11 months vs 10 months). Regarding toxicity, VPIV was similar to ACO, whereas APO and CMCC had more side-effects, leading to an increase in the number of drop-outs. In the second randomized study 144 patients were treated either with ifosfamide/VP 16 (IVP) or with cisplatinum/VP 16 (PVP). In the case of no further response, no change, or progression the induction therapy was changed to ACO. Interim analyses show that both regimens have similar therapeutic effects; but higher toxicity was observed in patients treated with cis-platinum/VP 16 than in patients treated with ifosfamide/VP 16. According to the response rate in patients treated with ACO after first-line therapy there was less cross-resistance of IVP than of PVP to ACO.

Elective radical groin dissection was performed on 297 consecutive patients with high-risk melanoma of the leg, Anderson Stages I, IIA, IIIA. By separate histologic examination of the so-called "Rosenmuller's node," the other inguinal, and the external iliac lymph nodes, the diagnostic excision of the Rosenmuller's node was tested as a suitable mode of screening for metastases before a planned elective regional lymph node dissection. Eighty patients (27%) presented with what was histologically determined to be occult groin metastases. Rosenmuller's node was involved in 30 of these cases; in the remaining 50, however, it was not affected; that is, 63% of the cases were false-negative. Thus, the involvement of Rosenmuller's node is not representative of metastases in the other ilioinguinal lymph nodes, but is rather a matter of chance. In women with superficial spreading melanoma the rate of occult lymph node metastases was significantly lower than that in men with melanomas of the other type. Iliac lymph node involvement was observed in 18 patients (22%) depending on clinical stage and depth of invasion of the primary tumor.

A total of 144 patients with small-cell lung cancer (SCLC) were randomized to receive cisplatin/etoposide (PE) or ifosfamide/etoposide (IE) combination chemotherapy. PE consisted of cisplatin, 80 mg/m2, intravenously (IV) on day 1, and etoposide, 150 mg/m2, IV on days 3 through 5. IE consisted of ifosfamide, 1,500 mg/m2, IV on days 1 through 5, and etoposide, 120 mg/m2, IV on days 3 through 5. Six cycles were administered in 3-week intervals. Nonresponders were switched immediately to CAV, consisting of cyclophosphamide, 600 mg/m2, IV on days 1 and 2, Adriamycin (Adria Laboratories, Columbus, OH), 50 mg/m2, IV on day 1, and vincristine, 2 mg, IV on day 1. Patients obtaining complete remission (CR) received prophylactic cranial irradiation with 30 Gy. After completion of chemotherapy, patients with limited disease received chest irradiation with 45 Gy. No maintenance therapy was given to patients in CR. Minimum follow-up was 2 years. Of the 141 patients evaluable, the overall response rate was 65% in PE therapy and 68% in IE therapy. The CR rate was 32% v 20% for all patients, 50% v 24% for limited disease, and 22% v 18% for extensive disease, all in favor of PE therapy. Median survival for all patients was 11.6 months v 9.4 months, for limited disease 14.8 months v 11.0 months, and for extensive disease 8.9 months v 7.5 months, all preferring PE therapy. The 2-year survival rate was higher in PE therapy than in IE therapy for all patients (12% v 9%) and for limited disease (23% v 10%), but not for extensive disease (5% v 9%). Median progression-free survival was 7.5 months v 6.0 months for all patients, 12.2 months v 8.8 months for limited disease, and 5.9 months v 4.4 months for extensive disease, all in favor of PE. Relapse in the area of the primary tumor was found less often after PE than after IE therapy (25% v 38%). Response to second-line CAV was seen in 30% of patients with prior PE and 43% with prior IE therapy, but was usually short lasting, and only one patient achieved CR. Toxicity included three lethal complications. Nausea, vomiting, diarrhea, and skin lesions occurred more often after PE than after IE therapy. These results suggest that PE is superior to IE chemotherapy in limited-stage, but not in extensive-stage SCLC, and that CAV is cross-resistant to PE, as well as to IE in the majority of patients.

Carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), and the BB isoenzyme of creatine kinase (CK-BB) were evaluated before therapy in the sera of 195 patients with histologically confirmed small cell lung cancer (SCLC) in a prospective multicenter trial. Forty-four percent (84 of 193) of all patients had CEA levels higher than 5 ng/ml, 66% (111 of 168) had NSE levels higher than 12.5 ng/ml, and 32% (40 of 123) had CK-BB levels higher than 10 ng/ml. Clear pathologic levels were less frequently observed. Significantly higher pretreatment titers for CEA, NSE, and CK-BB were found in patients with bone marrow and/or liver metastases. The most elevated marker levels were observed in the group of nonresponding patients with bone marrow and/or liver metastases. Only a slight correlation between the pretreatment CEA level and survival time could be observed. Patients with pathologic NSE (greater than or equal to 30 ng/ml) levels and, in particular, those with pathologic CK-BB (greater than or equal to 25 ng/ml) levels had a significantly shorter median survival than those with normal or elevated levels. In addition, a positive linear correlation between pretreatment NSE and CK-BB (n = 116, r = 0.54) levels was found, but CEA levels did not correlate with other marker levels. From these data it is concluded that pretreatment CEA, NSE, and CK-BB levels are helpful in the clinical management of a subset of patients with SCLC, i.e., those with bone marrow and/or liver metastases.

To the Editor: Variation in the calpain-10 gene (CAPN10 [MIM 605286]) was recently linked and associated with type 2 diabetes mellitus (T2DM) susceptibility (Horikawa et al. 2000). The initial linkage of T2DM to chromosome 2 was found in a population of Mexican Americans from Starr County, Texas (Hanis et al. 1996). Specific combinations of three intronic variants, designated “SNP-43,” “SNP-19,” and “SNP-63,” that capture most of the haplotype diversity at CAPN10 were associated with a three-fold increased risk of T2DM in this population and could account for the observed linkage (Horikawa et al. 2000). Subsequent association and linkage studies of these three polymorphisms in other populations have produced conflicting results, with association being observed in some populations (Baier et al. 2000 [Pima Indian]; Cassell et al. 2002 [South Indian]; Garant et al. 2002 [African American]; Malecki et al. 2002 [Polish]; Orho-Melander et al. 2002 [Finnish/Botnia]), but not others (Evans et al. 2001 [British]; Hegele et al. 2001 [Oji-Cree Indians]; Tsai et al. 2001 [Samoan]; Xiang et al. 2001 [Chinese]; Daimon et al. 2002 [Japanese]; Elbein et al. 2002 [whites from Utah]; Fingerlin et al. 2002 [Finnish]; Rasmussen et al. 2002 [Danish and Swedish]; Horikawa et al. 2003 [Japanese]). We previously reported that another variant, SNP-44 (designated “CAPN10-g4841T→C”; minor allele frequency 16%), located in intron 3 and 11 bp from SNP-43, was independently associated with T2DM in whites from the United Kingdom (Evans et al. 2001). Further studies have provided tentative support for a role of SNP-44 in T2DM and related traits: associations with polycystic ovary syndrome (Gonzalez et al. 2002) and with measures of oral glucose tolerance (Wang et al. 2002; Tschritter et al. 2003) have been reported. Functional studies suggest that SNP-44 is located in an enhancer element and might affect CAPN10 expression (Horikawa et al. 2000). Also, in the U.K., German, Japanese, and South Indian populations, SNP-44 is in perfect linkage disequilibrium (r2=1) with a missense mutation Thr504Ala (SNP-110) and two polymorphisms in the 5′-UTR (SNP-134 and SNP-135) (Evans et al. 2001; Cassell et al. 2002; Y. Horikawa and P. E. Schwarz, unpublished data). To assess the association of SNP-44 with T2DM more comprehensively, we performed a meta-analysis of all published SNP-44/T2DM association study data. To identify all relevant published studies, we searched PubMed using the keywords “calpain 10,” “diabetes,” “44,” “SNP 44,” “CAPN10,” and “type 2,” in different combinations. When necessary, authors were contacted to obtain exact genotype numbers, so that precise odds ratios (ORs) from each study could be calculated. Our search identified 10 published case/control studies, consisting of 3,303 subjects. The studies were spread across a number of ethnic groups: British (three studies, Evans et al. 2001); Chinese (Wang et al. 2002); Japanese (Daimon et al. 2002; Horikawa et al. 2003); Finnish/Botnia (two studies, Orho-Melander et al. 2002); South Indian (Cassell et al. 2002); and Mexican American (Horikawa et al. 2000). The frequency of the T2DM-associated SNP-44 C allele (allele 2) ranged from 6% in Mexican Americans to 25% in the Botnia I control population. There was no evidence for OR heterogeneity (Q test P=.27), and, although these studies are only a small sample from the many existing T2DM genetic resources, a funnel-plot analysis (Egger et al. 1997) suggested an absence of publication bias (P=.44). A Mantel-Haenszel meta-analysis of these studies showed that the C allele was associated with increased risk of T2DM (OR 1.17 [1.02–1.34], P=.02). Three transmission/disequilibrium tests (TDT) had been performed (Evans et al. 2001; Cassell et al. 2002; Orho-Melander et al. 2002). The combined TDT results demonstrated that the C allele was significantly overtransmitted (117 transmitted vs. 77 not transmitted, P=.004) from heterozygous parents to diabetic offspring. Although this result cannot be considered independent replication, as proband data was included in the case/control meta-analysis from two of the TDT studies (Evans et al. 2001; Cassell et al. 2002), it provides evidence that the association is not due to population stratification. Of the 10 studies in the meta-analysis, only 1 reported a significant (P

Das kleinzellige Bronchialkarzinom, ein Tumor vermutlich neuroendokrinen Ursprungs, ist haufig mit der Bildung von Peptidhormonen vergesellschaftet. Da es sich in der Regel bei den gebildeten Hormonen um hochmolekulare Hormonvorlaufer mit geringer oder fehlender biologischer Aktivitat handelt, sind paraneoplastische Syndrome selten. Wie in Tabelle 1 wiedergegeben, finden sich in Patientenseren zum Zeitpunkt der Diagnose Hormone und andere Tumormarker bis zu 70% erhoht, wobei nicht selten mehrere Marker gleichzeitig erhoht gefunden werden.

The prognostic significance of evaluation of response according to chest X-ray after only one cycle of treatment was investigated in patients with small cell lung cancer (SCLC). Three hundred and six patients entered a multicenter randomized German trial testing alternating vs. sequential chemotherapy. Decrease of tumor size after the first cycle was seen to be 78% in the alternating group and 70% in the sequential group. Stable disease occurred in 25% of the sequentially treated and 19% of the alternatingly treated patients. No substantial differences in pretreatment characteristics were noticed between patients with stable disease in sequential and alternating treatment. In sequential therapy, median survival was 323 days for patients with decrease of tumor size after the first cycle and 219 days for patients with no change. Only five out of 21 patients with no change after one cycle responded to continuous administration of this regimen including one complete remission. In alternating therapy, median survival was 347 days for patients with decrease in tumor size after the first cycle and 378 days for patients with no change indicating no difference in prognosis. Twelve out of 18 patients with no change responded to continuous administration of alternating treatment including six complete remissions. We concluded that response to the first cycle according to chest X-ray is a reliable and prognostically valid response criterion if sequential therapy is used. In this treatment modality no change in tumor size after the first cycle indicates poor prognosis, and improvement of the patients' outcome may be achieved by a switch to a second non-cross resistant drug combination.

Changes in hemodynamic variables and plasma renin activity (PRA) induced by short-term alteration of blood pressure and sympathetic nervous system activity were studied in normotensive and hypertensive men on high-sodium and low-sodium intake. Blood pressure and heart rate alterations caused by standard cold pressor tests, amyl nitrite inhalation, phentolamine infusion, and phenylephrine infusion were recorded. PRA was measured at time 0, 5, 15, and 30 min. No change in PRA occurred in either group following cold pressore test and amyl nitrite inhalation. Phenylephrine suppressed PRA in normal but not hypertensive subjects, and phentolamine elevated PRA in normotensive and hypertensive subjects regardless of diet. Short-term stimulation of the sympathetic nervous system does not appear to elevate PRA in man. Suppression of PRA by an alpha agonist was not observed in hypertensives and may reflect barorecptor insensitivity in this group of subjects.