A clinical randomized study on the effects of invasive monitoring on burn shock resuscitation.

BACKGROUND: Ever since Charles Baxter's recommendations the standard regime for burn shock resuscitation remains crystalloid infusion at a rate of 4 ml/kg/% burn in the first 24h following the thermal injury. A growing number of studies on invasive monitoring in burn shock, however, have raised a debate regarding the adequacy of this regime. The purpose of this prospective, randomised study was to compare goal-directed therapy guided by invasive monitoring with standard care (Baxter formula) in patients with burn shock. PATIENTS AND METHODS: Fifty consecutive patients with burns involving more than 20% body surface area were randomly assigned to one of two treatment groups. The control group was resuscitated according to the Baxter formula (4 ml/kg BW/% BSA burn), the thermodilution (TDD) group was treated according to a volumetric preload endpoint (intrathoracic blood volume) obtained by invasive haemodynamic monitoring. RESULTS: The baseline characteristics of the two treatment groups were similar. Fluid administration in the initial 24h after burn was significantly higher in the TDD treatment group than in the control group (P = 0.0001). The results of haemodynamic monitoring showed no significant difference in preload or cardiac output parameters. Signs of significant intravasal hypovolemia as indicated by subnormal values of intrathoracic and total blood volumes were present in both treatment groups. Mortality and morbidity were independent on randomisation. CONCLUSION: Burn shock resuscitation due to the Baxter formula leads to significant hypovolemia during the first 48 h following burn. Haemodynamic monitoring results in more aggressive therapeutic strategies and is associated with a significant increase in fluid administration. Increased crystalloid infusion does not improve preload or cardiac output parameters. This may be due to the fact that a pure crystalloid resuscitation is incapable of restoring cardiac preload during the period of burn shock.

Is interval medication a successful treatment regimen for schizophrenic patients with critical attitudes towards treatment?

In neuroleptic long-term medication, only part of the patients accept regular intake of neuroleptic drugs. The question is whether an interval medication regimen as opposed to continuous medication can help to reduce drop outs in patients with critical attitudes towards long-term medication. In a 2-year prospective study, 122 patients were randomised to an interval and 164 to a continuous neuroleptic medication regimen. The drop out rates were 62.5% in the interval and 53.7% in the continuous medication group. Drop outs generally show more negative attitudes towards treatment. Patients with negative attitudes do not do better under interval medication. Moreover, this regimen even requires more cooperation and trust in terms of the necessity of medication on the part of the patient compared to the continuous medication regimen. Interval medication therefore is a strategy which can only be successful in highly cooperative, but not in treatment-reluctant patients.

Monitoring free flaps using laser-induced fluorescence of indocyanine green: a preliminary experience.

In a prospective, clinical study, the clinical utility of indocyanine green for intraoperative monitoring of free tissue transfer was evaluated. The study comprised 20 surgical patients undergoing elective microsurgical procedures. Indocyanine green angiography was performed intraoperatively, immediately after flap inset, and the operating team was blind to the fluoremetric findings. Thereafter, postoperative monitoring was done exclusively by clinical examination (color, temperature, time for recapillarization, and bleeding after puncture). Final outcome was compared with results of perioperative indocyanine (ICG)-imaging, and classified either as total flap loss, partial flap loss, or successful tissue transplantation. A total of 2 (10%) complications was recorded, and included one partial and one total flap loss. Both complications were detected by intraoperative ICG imaging. Another case of intraoperative subclinical arterial spasm at the place of microvascular anastomosis was revealed by dynamic ICG-videography. This flap did not develop postoperative complications. In conclusion, evaluation of perfusion by ICG imaging is feasible in all kinds of microsurgical flaps, irrespective of the type of tissue. Even though not meeting all the criteria of an ideal monitoring device, significant additional information can be obtained. In this study, cases with arterial spasm, venous congestion, and regional hypoperfusion were revealed by intraoperative ICG-videography. There was a strong correlation between intraoperative findings and clinical outcome.

A prospective study of factors influencing adherence to a continuous neuroleptic treatment program in schizophrenia patients during 2 years.

Dropout from prophylactic neuroleptic treatment is one major reason for relapse in schizophrenia patients. There is a lack of prospective studies on factors that predict medication adherence. We investigated factors suspected to predict dropout from continuous neuroleptic treatment in a 2-year prospective study involving 122 outpatients with a DSM-III-R diagnosis of schizophrenia. Forty-two (34.4%) were classified as patient-related dropouts. No significant difference between compliant patients and dropouts was found with regard to sociodemographic variables, except that compliant patients were significantly older. Also, no differences in psychopathology were seen at the beginning of treatment, but compliant patients had a longer duration of illness. Compliant patients had higher doses of neuroleptics in the initial stabilization phase and correspondingly showed more extrapyramidal signs. Physicians rated compliant patients from the beginning as more cooperative. These patients also showed significantly higher scores in positive treatment expectations. In a stepwise regression analysis, positive illness concepts, the global assessment of functioning (GAF), and the physicians' view of patients' cooperation predicted 19 percent of the variance. We concluded that the prediction of dropouts is insufficient and remains largely an unsolved problem. Future research should focus more on context factors in the search for clinically meaningful explanations of patient dropout from treatment.

Prodromal states in schizophrenia.

The vulnerability-stress-coping (VSC) model is the most influential heuristic concept in understanding the course of schizophrenia, whose prodromal status still offers unsolved conceptual and methodological issues. Improved knowledge about the prodromal phase would provide a better understanding of the developing psychopathology and psychophysiology of schizophrenia and could also be of predictive value to attune therapeutic actions to the course of the illness more precisely. To shed more light on the characteristics of prodromal states, data from a German multicenter study on intermittent versus maintenance neuroleptic long-term treatment in schizophrenia (ANI study) were reanalyzed with respect to the prevalence and profile, nature, time course, and predictive value of prodromal symptoms in impending relapse. The results demonstrate that prodromes are a category of symptoms on their own, but they share variance with other symptom domains. Treatment side effects, psychotic symptoms, dysphoric mood, and social dysfunction are all associated with prodromal states--the direction of this association, however, is still to be clarified. Prodromal symptoms are also related to the neuroleptic treatment strategy and its relapse-preventive efficacy--findings that underscore neuroleptic maintenance medication in preventing both overt and subthreshold psychotic morbidity in schizophrenia.

[Positive and negative symptoms in chronic schizophrenic patients under maintenance therapy with flupenthixol decanoate for a twelve month perioid]. / Positiv- und Negativsymptomatik bei chronisch schizophrenen Patienten unter Erhaltungstherapie mit Flupentixol-Decanoat im 12-Monats-Verlauf.

62 chronic schizophrenics, who after a psychotic exacerbation were stabilized again, were randomized on 3 different maintenance dosages of flupentixol-decanoate and observed for 12 months. 15 (24.2%) patients had a relapse independently of the dose. 34 of the 47 patients without relapse had complete documentations of the follow-up. After 3 to 6 months there was an obvious and constant clinical improvement as assessed by various test inventories. The BPRS-scores for psychopathology, negative and positive symptoms improved significantly between 14 to 18%. There was also significant reduction of negative symptoms assessed by SANS (22%) as well in the severity of illness (CGI) and an amelioration of psychosocial functioning (GAS, Strauss-Carpenter). At the end of trial 26.4% of the patients had mild involuntary movements (AIMS), 23.5% were on antiparkinson-medication. It is concluded that there could be an indication for flupentixol-decanoate in the long term maintenance therapy especially of chronic schizophrenics with negative symptoms and problems of compliance under oral medication.

Cartilage tissue engineering with novel nonwoven structured biomaterial based on hyaluronic acid benzyl ester.

The aim of this study was to investigate the possibility of using the benzyl ester of hyaluronic acid (HYAFF 11), a recently developed semisynthetic resorbable material, as a scaffold for the culture of human nasoseptal chondrocytes in tissue-engineering procedures of cartilage reconstruction. Different techniques such as immunohistochemistry, scanning electron microscopy, and confocal laser scanning microscopy were used to study the behavior, morphology, and phenotype expression of the chondrocytes, which were initially expanded and then seeded on the material. The nonwoven cell carrier allowed good viability and adhesivity of the cells without any surface treatment with additional substances. Furthermore, the cultured cells expressed cartilage-specific collagen type II, indicating that they were able to redifferentiate within the scaffold of HYAFF 11 and were able to retain a chondrocyte phenotype even after a long period of in vitro conditions. Nevertheless, the expression of collagen type I, which was produced by dedifferentiated or incompletely redifferentiated chondrocytes, was noticeable. Additional data were obtained by subcutaneous implantation of samples seeded with human cells in the in vivo model of the athymic nude mouse. The results after 1 month revealed the development of tissue similar to hyaline cartilage. This study is promising for the use of this scaffold for tissue engineering of cartilage replacements.

[The social status of schizophrenic patients]. / Zur sozialen Situation schizophrener Patienten.

In the German multicenter ANI study comparing continuous prophylactic treatment with intermittent medication, the social situation of a large sample of 364 schizophrenic patients was investigated and followed up over a 2-year period of outpatient aftercare. Effective therapy and prophylaxis substantially reduced relapses and rehospitalization. On the other hand, the psychosocial situation still showed considerable disadvantages. Of the patients (35 years old on average), 60% were still unmarried. Almost one-half of the patients still lived alone or with their parents, and one-third lived a very solitary life. At the end of the 2-year aftercare period, one-third was able to earn their own living. Almost one-half retired early from their occupations. Predictors and intervening variables are presented in order to stimulate early rehabilitation approaches. Schizophrenics are particularly placed at a disadvantage by tighter competition in the employment market, even though the course of illness can be improve. Social psychiatry must to be involved in helping to improve social contacts, accommodation and employment in order to prevent major distress.

Predictors of relapse and rehospitalization in schizophrenia and schizoaffective disorder.

In a German multicenter treatment study, 354 patients with schizophrenia and schizoaffective disorder were followed for 2 years. The data collected were taken as a basis for the present predictor study. For the first time, the technique of classification and regression tree (CART) analysis has been employed for this purpose. CART yielded informative data and appeared to be a useful instrument in predictor research. On the outcome variables "relapse" and "rehospitalization," significant predictor variables were found in several areas: neuroleptic treatment, onset and previous course (precipitating factors, first manifestation, hospitalization in the preceding year, suicide attempts), psychopathology (residual type, schizoaffective disorder), social adjustment (marital status, employment, intensity of life, Phillips score), previous life experiences (traumatic experiences and psychiatric or developmental disturbances in childhood), and biology (gender, age). Our investigation confirmed the generally prevalent views regarding the value of neuroleptic treatment, the multifactorial etiology, and the vulnerability stress model of schizophrenia.

Lithium versus carbamazepine in the maintenance treatment of bipolar disorders--a randomised study.

In a randomised multicentre study, the prophylactic efficacy of lithium and carbamazepine was compared in 144 patients with bipolar disorder (74 vs. 70 patients; observation period: 2.5 years; lithium serum level: 0.63 +/- 0.12 mmol/l, carbamazepine dose: 621 +/- 186 mg/day). Hospitalisations, recurrences, need of psychotropic comedication and adverse effects prompting discontinuation were defined as treatment failures. Survival analyses regarding hospitalisations and recurrences showed no statistically significant differences between both drugs. Results were distinctly in favour of lithium, considering recurrences combined with comedication (P = 0.041) and/or adverse effects (P = 0.007). Whereas adverse effects prompting discontinuation were more frequent under carbamazepine (9 vs. 4, ns), lithium patients reported more often slight/moderate side effects (61% vs. 21% after 2.5 years; P = 0.0006). In completers, recurrences occurred in 28% (lithium) vs. 47% (carbamazepine) of the patients (P = 0.06). Lithium seems to be superior to carbamazepine in maintenance treatment of bipolar disorder, in particular when applying broader outcome criteria including psychotropic comedication and severe side effects.

Lithium vs carbamazepine in the maintenance treatment of schizoaffective disorder: a randomised study.

In a randomised multicentre study, the prophylactic efficacy of lithium and carbamazepine was compared in schizoaffective disorder. A total of 90 ICD-9 schizoaffective patients were included in the maintenance phase (2.5 years). They were also diagnosed according to RDC and DSM-III-R and classified into subgroups. Mean serum levels were 0.58 +/- 0.12 mmol/l for lithium and 6.4 +/- 1.5 micrograms/ml for carbamazepine (mean dose 643 +/- 179 mg/d). Outcome criteria were hospitalisation, recurrence, concomitant psychotropic medication and adverse effects leading to discontinuation. There were more non-completers under carbamazepine than under lithium (p = 0.02). Survival analyses demonstrated no significant differences between lithium and carbamazepine in treatment outcome. Patient's ratings of side effects (p = 0.003) and treatment satisfaction (p = 0.02) favoured carbamazepine. Following the RDC criteria, patients of the schizodepressive and non-classifiable type did better under carbamazepine (p = 0.055 for recurrence), whereas in the schizomanic patients equipotency of both drugs was found. Applying DSM-III-R, carbamazepine demonstrated a superiority in the patient group with more schizophrenia-like or depressive disorders (p = 0.040 for recurrence), but not in patients fulfilling the DSM-III-R criteria of bipolar disorder. Lithium and carbamazepine seem to be equipotent alternatives in the maintenance treatment of broadly defined schizoaffective disorders. However, in subgroups with depressive or schizophrenia-like features and regarding its long-term tolerability carbamazepine seems to be superior.

Comparative efficacy of lithium and amitriptyline in the maintenance treatment of recurrent unipolar depression: a randomised study.

The present study, including 81 depressive patients, compares the prophylactic efficacy of lithium and amitriptyline in recurrent unipolar depression over a treatment period of 2.5 years in a randomised multicentre design. Hospitalisation, re-emergence of depressive or subdepressive recurrences, unwanted side-effects and need of concomitant psychotropic medication were considered to indicate treatment failures. Average dosage for amitriptyline was 98 +/- 37 mg/day, average lithium blood level was 0.59 +/- 0.12 mmol/l. Survival analyses demonstrated a significant superiority of lithium (P = 0.015) regarding the outcome criteria 'recurrences and/or subclinical recurrences' and non-significantly better results of lithium compared to amitriptyline concerning 'recurrence' (P = 0.059) or 'recurrence and/or concomitant medication' (P = 0.066).

[Non-compliance and lack of indications for depot treatment as reasons for exclusion from adequate prevention of recurrence]. / Non-Compliance und fehlende Indikation zur Depotbehandlung als Ausschlussgründe für eine adäquate Rezidivprophylaxe.

OBJECTIVE: The paper reports on the recruitment of a multicenter study on ambulant prophylactic treatment of schizophrenic disorders. METHODS: For a study of the relapse-preventative effect of different dose patterns of Flupentixol, a screening phase was carried out among of 1129 schizophrenic patients. The aim of the screening phase was to establish the criteria for exclusion or inclusion in the treatment phase of the study. RESULTS: Only 62 patients could be included. The reason for 54 patients not being included was a lack of compliance from either the patient or the clinician. The meaning of patient- and therapist-compliance in carrying out a multicenter study is also discussed.

Dibenzoxepinone hydroxylamines and hydroxamic acids: dual inhibitors of cyclooxygenase and 5-lipoxygenase with potent topical antiinflammatory activity.

Hydroxylamine and hydroxamic acid derivatives of a known nonsteroidal antiinflammatory dibenzoxepine series display both cyclooxygenase (CO) and 5-lipoxygenase (5-LO) inhibitory properties. Many of these new dual CO/5-LO inhibitors also exhibit potent topical antiinflammatory activity in the arachidonic acid-induced murine ear edema model. On the basis of their promising profile of in vitro and in vivo activities, hydroxamic acids 24h, 3-(6,11-dihydro-11-oxodibenz[b,e]oxepin-2-yl)-N-hydroxy-N-++ +methylpropanamide (HP 977), and 25, 3-(6,11-dihydrodibenz[b,e]oxepin-2-yl)-N-hydroxy-N- methylpropanamide (P10294), were selected as developmental candidates for the topical treatment of inflammatory skin disorders.

Early neuroleptic intervention in schizophrenia: are prodromal symptoms valid predictors of relapse?

All recently completed controlled two-year studies on intermittent, early neuroleptic intervention treatment have failed to compare favourably with studies on maintenance treatment concerning relapse prevention. The reason for this failure is still unclear. Therefore the implicit, but as yet unproven, hypothesis that a relapse can be predicted from prodromal symptoms was tested from the perspective of our German multicentre study. Results demonstrate that this is not the case. Possible reasons for and clinical implications of this negative finding are discussed.

The recruitment process for a multicenter study on the long-term prophylactic treatment of affective disorders.

The paper reports on the process of patient recruitment for a controlled clinical multicenter study on the treatment of affective disorders. Two thirds of the patients screened did not participate because prophylactic treatment was either unnecessary or not justified for medical reasons. Further, a number of patients equal to that eventually allocated to the trial refused to participate for personal, idiosyncratic reasons. In spite of this, the patients in the trial were very similar to those not participating with respect to relevant variables such as age, sex, number of and intervals between previous episodes or severity of the present episode.

Nuclear roundness factor and local failure from definitive radiation therapy for prostatic carcinoma.

Of 375 patients with prostatic carcinoma treated definitively with radiation therapy at this institution with at least a 5 year follow-up, 23 patients failed locally only, 72 failed with distant metastasis only, 60 had both local and distant failure, while 220 showed no evidence of disease. In search for a possible marker for local failure following radiation therapy, we examined several nuclear morphometric parameters which have been shown to correlate with the biologic aggressiveness of this disease. The 23 locally failed only patients were matched with 23 no evidence of disease patients for stage, grade, treatment modality, prior surgery, age at diagnosis and race. Archival hematoxylin and eosin slides were obtained for 22 of the 23 matched pairs, and morphometric features, including nuclear roundness factor and nuclear area, as well as numbers of nucleoli were assessed using computer-assisted image analysis in both tumor cells and normal prostatic epithelium. Tumor nuclei from the locally failed only patients had significantly higher nuclear roundness factor values (p = 0.0089) compared with tumor cells from no evidence of disease patients. Analysis of these data by clinical stage demonstrated no significant differences between the locally failed only and no evidence of disease patients. Likewise, there were no significant differences in nuclear roundness factor values of locally failed only and no evidence of disease patients with poorly or moderately well-differentiated tumors. However, there was a highly significant difference (p = 0.0012) in the nuclear roundness factor values of locally failed only and no evidence of disease patients with well-differentiated tumors. Thus, there appears to be a subset of patients with well-differentiated adenocarcinoma of the prostate who have significantly more irregular tumor nuclei and who fail locally only following definitive radiation therapy.

Depressive syndromes in schizophrenic patients under neuroleptic therapy. ANI Study Group Berlin, Düsseldorf, Göttingen, Munich, Federal Republic of Germany.

Schizophrenic outpatients (= 364) were assigned at random to three different treatment strategies: (1) continuous medication with neuroleptic drugs, (2) intermittent medication with crisis intervention and (3) intermittent medication with early intervention. Depressive syndromes were rated according to three different scales for depressive syndromes (Brief Psychiatric Rating Scale anxious depression factor, Arbeitsgemeinschaft für Methodik und Dokumentation in der Psychiatrie/depression, and the self-rating Paranoid Depression Scale) after 1 and 2 years of treatment. No differences in depression scores were found between the three treatment strategies. Comparisons between patients treated with neuroleptic drugs at the time and patients without neuroleptics revealed significantly higher depression scores in the neuroleptics group in most comparisons. No differences were found between patients treated with low versus high potency neuroleptics and between oral versus depot neuroleptics. However, depression correlated with extrapyramidal symptoms.

[Double-blind comparison of 3 x 75 mg zotepine und 3 x 4 mg haloperidol in acute schizophrenic patients]. / Doppelblindvergleich von 3 x 75 mg Zotepin und 3 x 4 mg Haloperidol bei akut schizophrenen Patienten.

To assess the efficiency/risk ratio, fixed doses of zotepine and haloperidol were compared by means of a double-blind study in acute schizophrenics over a 4-week period. The assessment tools were BPRS, CGI, and the Simpson-Angus scale for the extrapyramidal disturbances, and a free report on side effects. No differences between the groups were found in respect of efficacy. According to the Simpson-Angus scale, the patients who had been treated with zotepine achieved better values, this being a general trend. There were significant differences according to the free report on side effects. Especially at onset of treatment, the patients treated with zotepine complained of tiredness. Partly marked extrapyramidal disturbances were seen in the patients who had been treated with haloperidol.