Dopaminergic agonists and their influence on the oxygenation and function activity of underperfused brain tissue

The effect of two dopaminergic agonists (apomorphine and bromocriptine) on electrical activity and oxygen supply of the brain was investigated in cats submitted to hypovolemic oligemia (mean arterial blood pressure: 45 mmHg). While both drugs stimulated the brain by prolonging the oligemia-induced seizures in the caudate nucleus and in the cerebral cortex, only apomorphine improved the pO2 distribution in the cortical tissue after 120 min oligemia. Bromocriptine, in contrast, had a beneficial effect of shorter duration. These data show that under conditions of incomplete ischemia the brain can still be activated. Furthermore, these results provide additional support for the biochemically founded hypothesis of different dopamine receptors in the brain.     

Pregnancy in renal transplant patients: a review.

A questionnaire survey and review of the literature show that pregnancy can be well tolerated in most women with renal transplants. Fifty-two per cent of the renal transplant recipients who became pregnant had full-term infants with no serious complications. With therapeutic abortions, excluded, 71% of the 308 pregnancies permitted to continue resulted in full-term infants. Rejection episodes were occasionally a serious problem, occurring in 9% of the pregnancies. Mechanical interference with renal excretion or preventing vaginal delivery occurred in 5.6% of the cases. Hypertension and proteinuria, often existing prior to pregnancy, became frequently increased during pregnancy. Infections not associated with rejection were common but easily controlled in most cases. Prematurity was frequent but related to renal function and the time interval from transplant to conception. The most serious infant complications were related to prematurity. Unknown is the future of these infants and their progeny because of their intrauterine exposure to immunosuppressive drugs.     

A new concurrent chemotherapy with vinorelbine and mitomycin C in combination with radiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck

OBJECTIVE: The purpose of this pilot study was to evaluate the feasibility and toxicity of concurrent chemotherapy with vinorelbine and mitomycin C in combination with accelerated radiotherapy (RT) in patients with locally advanced cancer of the head and neck. PATIENTS AND METHODS: Between January 2003 and March 2004, 15 patients with T4/N2-3 squamous cell carcinoma (12/15) and with N3 cervical lymph node metastases of carcinoma of unknown primary (3/15) were treated with chemotherapy and simultaneous accelerated RT. RESULTS: 11 patients completed therapy without interruption or dose reduction. Grade 3-4 acute mucosal toxicity was observed in 9/15 patients, grade 4 hematologic toxicity in 6/15 patients. At a median follow-up of 7.5 months, 2 patients have died of intercurrent disease, 2 patients have experienced local relapse; 5 patients are alive with no evidence of disease at the primary tumor site. DISCUSSION: The described regimen is highly effective, but led to remarkable side effects.     

Hodgkin's lymphoma in elderly patients: a comprehensive retrospective analysis from the German Hodgkin's Study Group.

PURPOSE: With improved prognosis for patients with Hodgkin's lymphoma (HL), interest increasingly focuses on high-risk groups such as elderly patients. We thus performed a retrospective analysis using the German Hodgkin's Study Group (GHSG) database to determine clinical risk factors, course of treatment, and outcome in elderly HL patients in comparison with younger adults. PATIENTS AND METHODS: A total of 4,251 patients included in the GHSG studies HD5 to HD9 were analyzed, of whom 372 (8.8%) were 60 years or older and 3,879 (91.2%) were younger than 60 years. Patient characteristics, treatment results, toxicity, freedom from treatment failure (FFTF), and overall survival (OS) were compared. RESULTS: Elderly patients more often had mixed cellularity subtype, "B" symptoms, elevated erythrocyte sedimentation rate, and poorer performance status. Less frequently observed were nodular sclerosis subtype, large mediastinal mass, and bulky disease. Acute toxicity during chemotherapy was generally higher in elderly patients. This was most obvious for severe infections (grade 3 or 4; 15% v 6%) correlating with more severe leukopenia in elderly patients (grade 4; 38% v 23%). As a result, significantly fewer elderly patients received the intended full chemotherapy dose (75% v 91%). The survival analysis showed a significantly poorer treatment outcome for elderly patients in terms of 5-year OS (65% v 90%), FFTF (60% v 80%), and HL-specific FFTF (73% v 82%). CONCLUSION: Elderly patients have a poorer risk profile compared with younger HL patients and experience more severe treatment-associated toxicity. Higher mortality during treatment as well as lower dose-intensity are the major factors explaining the poorer overall outcome of elderly HL patients.     

Doxorubicin and streptozotocin after failed biotherapy of neuroendocrine tumors

Background: Well-differentiated neuroendocrine tumors are treated primarily with somatostatin analogs and interferon-α. It is not clear what therapy should be applied after failed biotherapy. Our aim was to establish whether patients whose tumors rapidly progress under biotherapy may benefit from chemotherapy. Patients and Methods: In 10 patients with metastatic neuroendocrine tumors (4 foregut, 3 midgut, 1 retroperitoneal, and 2 of unknown origin) streptozotocin and doxorubicin were used as second-line or third-line therapy. Tumor response was assessed by computed tomography of the abdomen and thorax and measurement of tumor secretion products (serum chromogranin A, urinary 5-hydroxyindoleacetic acid). Results: Three patients showed a radiological response over a mean time of 30 mo (range: 7–67 mo). Median survival after initiation of chemotherapy was 50 mo in patients with a response and 8 mo in non-responders. Three patients developed major side effects (nephrotoxicity, diabetes, and encephalopathy). Conclusion: Streptozotocin and doxorubicin produce poor response rates in patients with progressive neuroendocrine tumors after failed biotherapy, but may prolong life in those patients who show a tumor response.     

Arcuate ligament vascular compression syndrome in infants and children

Background

Arcuate ligament vascular compression syndrome has not been described previously in the pediatric or pediatric surgical literature. However, it is mentioned in the literature of vascular and general surgery and in journals of radiology and orthopedics. In this review, the intraoperative pathological anatomy and the principles of treatment for 8 children will be presented.

Methods

The chart records and the anatomical sketches that were documented by the surgeon immediately after each procedure were analyzed retrospectively. In addition, preoperative courses and long-term follow-up (range, 3-18 years) were evaluated by a defined program.

Results

The diagnosis of celiac artery compression by an arcuate ligament was suspected in children presenting with a history of several years of recurrent acute abdominal pain associated with a typical arterial bruit in the midline of the epigastric region.

Conclusions

Other diseases with recurrent abdominal pain and an arterial bruit must be excluded before making the decision for an operative intervention. Duplex ultrasound and angiography are possibly helpful tools to establish the respective diagnosis, but in the patients of the present series, these techniques neither confirmed compression of the celiac axis nor demonstrated decreased perfusion of the superior mesenteric artery. However, as the clinical symptoms clearly announce the disease, these diagnostic measures are not mandatory.     

Lack of toxicity of therapy-induced T cell responses against the universal tumour antigen survivin

Prognosis of disseminated melanoma remains gloomy as neither chemotherapeutic nor unspecific immune modulatory approaches were able to improve the overall survival of these patients. Hence, specific immunotherapy has received increasing attention. Disappointing clinical results, however, indicate that the choice of suitable antigens is of special importance. To this end, the inhibitor of apoptosis (IAP) protein survivin, which is over-expressed in several tumours but is largely undetectable in adult tissues, appears to be a promising target for vaccination purposes, since down-regulation or loss of expression is associated with impaired tumour progression. Consequently, five heavily pretreated stage IV melanoma patients were vaccinated with the HLA-A2 restricted survivin(96-104) epitope presented by autologous dendritic cells (DCs) in a compassionate use setting. Four of these patients mounted strong T cell responses to this epitope as measured by ELISPOT assay. Furthermore, in situ peptide/HLA-A2 multimer staining confirmed that these survivin reactive cells infiltrated both visceral and soft tissue metastases.