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.     

Die Bedeutung der Kerntemperatur für die chemische Temperaturregulation beim Hund in leichter Narkose

Zusammenfassung 1. Bei zwölf Hunden wurde in leichter Pernoctonnarkose der Kopf der Tiere durch Unterbindung der Vertebralgefäße und durch die Beeinflussung der Temperatur des Carotiden- und Jugularvenenblutes mittels eingebundener Wärmeaustauscher vom Rumpf thermisch isoliert. Durch Kühlung des Carotidenblutes wurde die Hirntemperatur gesenkt, während die Hauttemperatur durch eine hohe Umgebungstemperatur von 29–30° C und die Temperatur des Rumpfkernes durch Erwärmung des Jugularvenenblutes auf einem normalen oder erhöhten Wert gehalten wurden. Alle untersuchten Tiere waren in der Lage, auf einen extracerebralen Kaltreiz mit Kältezittern zu reagieren.2. In vier Versuchen wurde durch die Hirnkühlung Kältezittern und eine Steigerung des Sauerstoffverbrauches ausgelöst. In acht Fällen, in denen unter der Hirnkühlung kein Kältezittern auftrat, hatte die Senkung der Hirntemperatur keinen eindeutigen Einfluß auf den Sauerstoffverbrauch. Ein Unterschied im Verhalten der Kern- und Hauttemperaturen zwischen den positiven und den negativen Versuchen war nicht feststellbar.3. Die möglichen Ursachen des bei gleichen Untersuchungsbedingungen unterschiedlichen Verhaltens der Wärmeproduktion unter der Hirnkühlung und der Auslösungsmechanismus des Kältezitterns werden diskutiert.

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Summary 1. In dogs, lightly anesthetized with Pernocton, the ventral muscles of the neck and the vertebral arteries and veins were ligated. The carotid arteries and the jugular veins were cannulated and connected with heat exchangers. At an high ambient air temperature of 29–30° C, the brain temperature was reduced by perfusing the heat exchanger, connected with the carotid arteries, with water of 36–30° C, whereas the trunk was kept warm by heating the blood of the jugular veins. In all cases shivering could be produced by cooling the deep body tissues before and after the brain cooling.2. In 4 out of 12 dogs shivering and an increase in oxygen consumption could be elicited by cooling the brain only. In 8 dogs shivering did not occur, and no significant change in oxygen consumption could be observed.3. The factors, responsible for the different reactions of the thermoregulatory system under the same experimental conditions, are discussed.

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A hybrid approach to measuring electrical activity in genetically specified neurons

The development of genetically encoded fluorescent voltage probes is essential to image electrical activity from neuronal populations. Previous green fluorescent protein (GFP)-based probes have had limited success in recording electrical activity of neurons because of their low sensitivity and poor temporal resolution. Here we describe a hybrid approach that combines a genetically encoded fluorescent probe (membrane-anchored enhanced GFP) with dipicrylamine, a synthetic voltage-sensing molecule that partitions into the plasma membrane. The movement of the synthetic voltage sensor is translated via fluorescence resonance energy transfer (FRET) into a large fluorescence signal (up to 34% change per 100 mV) with a fast response and recovery time (0.5 ms). Using this two-component approach, we were able to optically record action potentials from neuronal cell lines and trains of action potentials from primary cultured neurons. This hybrid approach may form the basis for a new generation of protein-based voltage probes.     

Glycinergic neurons expressing enhanced green fluorescent protein in bacterial artificial chromosome transgenic mice

Although glycine is a major inhibitory transmitter in the mammalian CNS, the role of glycinergic neurons in defined neuronal circuits remains ill defined. This is due in part to difficulties in identifying these cells in living slice preparations for electrophysiological recordings and visualizing their axonal projections. To facilitate the morphological and functional analysis of glycinergic neurons, we generated bacterial artificial chromosome (BAC) transgenic mice, which specifically express enhanced green fluorescent protein (EGFP) under the control of the promotor of the glycine transporter (GlyT) 2 gene, which is a reliable marker for glycinergic neurons. Neurons expressing GlyT2-EGFP were intensely fluorescent, and their dendrites and axons could be visualized in great detail. Numerous positive neurons were detected in the spinal cord, brainstem, and cerebellum. The hypothalamus, intralaminar nuclei of the thalamus, and basal forebrain also received a dense GlyT2-EGFP innervation, whereas in the olfactory bulb, striatum, neocortex, hippocampus, and amygdala positive fibers were much less abundant. No GlyT2-EGFP-positive cell bodies were seen in the forebrain. On the subcellular level, GlyT2-EGFP fluorescence was colocalized extensively with glycine immunoreactivity in somata and dendrites and with both glycine and GlyT2 immunoreactivity in axon terminals, as shown by triple staining at all levels of the neuraxis, confirming the selective expression of the transgene in glycinergic neurons. In slice preparations of the spinal cord, no difference between the functional properties of EGFP-positive and negative neurons could be detected, confirming the utility of visually identifying glycinergic neurons to investigate their functional role in electrophysiological studies.     

Coeliac disease in The Netherlands

BACKGROUND: The prevalence of adult coeliac disease in The Netherlands was studied in the Dutch Coeliac Disease Society and in blood donors but not in the general population. We therefore studied the prevalence of recognized and unrecognized coeliac disease in a large cohort, representative of the adult Dutch general population. Blood samples were available for anonymous research, as well as data on dietary habits, self-reported physical characteristics, health problems, quality of life and socio-economic circumstances. METHODS: Subjects included 50,760 individuals who had previously participated in two large population-based studies on health status in relation to lifestyle factors. Recognized coeliac disease was studied in all subjects by identification of self-reported adherence to a gluten-free diet and subsequent confirmation of the diagnosis of coeliac disease. Unrecognized coeliac disease was studied in a random sample of 1440 out of the 50,760 subjects through serologic screening and human lymphocyte antigen (HLA) typing. RESULTS: The prevalence of recognized coeliac disease was 0.016% (95% confidence interval 0.008-0.031) and of unrecognized coeliac disease 0.35% (95% confidence interval 0.15-0.81). Menarcheal age was higher in women with recognized coeliac disease than in women without coeliac disease. CONCLUSIONS: The prevalence of adult recognized coeliac disease in The Netherlands is one of the lowest in Europe, while the prevalence of unrecognized coeliac disease is comparable with that in other European countries. Adult coeliac disease is strongly under diagnosed in The Netherlands. The higher menarcheal age in women with recognized coeliac disease may be explained by diagnostic delay.