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Biomedical subjects

C Grau

Publications and source records attributed to C Grau.

At least 37 records · Page 2Linked to original sources
PubMed2000

Cervical lymph node metastases from unknown primary tumours. Results from a national survey by the Danish Society for Head and Neck Oncology.

BACKGROUND AND PURPOSE: The management of patients with cervical lymph node metastases from unknown primary tumours is a major challenge in oncology. This study presents data collected from all five oncology centres in Denmark. MATERIAL AND METHODS: Of the 352 consecutive patients with squamous cell or undifferentiated tumours seen from 1975 to 1995, a total of 277 (79%) were treated with radical intent. The general treatment policy at all centres during the entire study period has been to treat all suitable candidates with radiotherapy to both sides of the neck and include elective irradiation of the mucosal sites in nasopharynx, and larynx, hypopharynx and larynx (81%). Irradiation of the ipsilateral neck only was done in 26 patients (10%). Radical surgery was the only treatment in 23 N1-N2 patients (9%). RESULTS: The 5-year estimates of neck control, disease-specific survival and overall survival for radically treated patients were 51, 48 and 36%, respectively. The emergence of the occult primary was observed in 66 patients (19%). About half of the emerging primaries were within the head and neck region with oropharynx, hypopharynx and oral cavity being the most common sites. Emerging primaries outside the head and neck region were primarily located in the lung (19 patients) and oesophagus (five patients). The frequency of emerging primary in the head and neck was significantly higher in patients treated with surgery alone, the actuarial risks at 5-year being 54+/-1% (no RT) vs. 15+/-3% (with RT), P<0.0001. The most important factor for neck control was nodal stage (5-year estimates 69% (N1), 58% (N2) and 30% (N3)). Other important parameters for neck control and disease-specific survival included haemoglobin, gender and overall treatment time. Patients treated with ipsilateral radiotherapy had a relative risk of recurrence in the head and neck region of 1.9 compared with patients treated to both neck and mucosa. At 5 years, the estimated control rates were 27% (ipsilateral) and 51% (bilateral; P=0.05). The 5-year disease-specific survival estimates were 28 and 45%, respectively (P=0.10). CONCLUSIONS: This study has confirmed that patients with neck node metastases from occult head and neck cancer have clinical features and prognosis similar to other head and neck malignancies. Extensive irradiation to both sides of the neck and the mucosa in the entire pharyngeal axis and larynx resulted in significantly less loco-regional failures compared with patients treated with ipsilateral techniques, but only a trend towards better survival. A prospective randomized trial is required to determine the optimal strategy in terms of locoregional control, survival and morbidity.

Adolescent↗
PubMed2000

Has the outlook improved for amifostine as a clinical radioprotector?

UNLABELLED: Amifostine has recently been approved for clinical radiotherapy as a protector against irradiation-induced xerostomia. It is our aim to review the outlook for using amifostine as a general clinical radioprotector. Protection against X-rays is mainly obtained by the scavenging of free radicals. The degree of protection is therefore highly dependent on oxygen tension, with protection factors ranging from 1 to 3. Maximal protection is observed at physiological levels of oxygenation. A great variability in protection has also been observed between different normal tissues. Some tissue, like brain, is not protected while salivary glands and bone marrow may exhibit a three-fold increase in radiation tolerance. Amifostine is dephosphorylized to its active metabolite by a process involving alkaline phosphatase. Due to lower levels of alkaline phosphatase in tumor vessels, amifostine is marketed as a selective protector of normal tissue and not tumors. However, the preclinical investigations concerning the selectivity of amifostine are controversial and the clinical studies are sparse and do not have the power to evaluate the influence of amifostine on the therapeutic index. CONCLUSION: based on the present knowledge amifostine should only be used in experimental protocols and not in routine practice.

Amifostine↗
PubMed2000

The individual replicability of mismatch negativity at short and long inter-stimulus intervals.

OBJECTIVES: The individual replicability of the mismatch negativity (MMN) event-related brain potential (ERP) was studied at two different inter-stimulus intervals (ISIs), to establish its potential value for routine clinical evaluation of sound discrimination and auditory sensory memory. METHODS: Ten healthy young subjects were presented sequences of 3 stimulus trains, in two recording sessions approximately 1 month apart. The stimuli in the trains were delivered at an ISI of 300 ms, whereas the inter-train intervals (ITIs) were 0.4 s and 4.0 s in different blocks. ERPs were averaged to standard (75 ms) and deviant (25 ms) tones started equiprobably the stimulus trains. RESULTS: Significant Pearson product-moment correlations coefficients were found between sessions at all scalp locations for the short ITI, when the MMN was quantified as the mean amplitude in the 100-200 ms latency window around its peak. However, none of the correlations reached significance for the longer ITI. CONCLUSIONS: MMN appears to be a reliable measure for single-case assessment and follow-ups when obtained at short ISIs and quantified as an integrated window of neuroelectric activation over a temporal span.

Acoustic Stimulation↗
PubMed2000

Squamous cell carcinoma of the oropharynx--an analysis of treatment results in 289 consecutive patients.

In this retrospective study the results of primary and salvage treatment of oropharyngeal carcinoma were evaluated. A total of 289 consecutive patients (103 females and 186 males) were included in the study. Most tumours originated in the tonsil area (58%) and comprised stages I 8%, II 19%, III 46% and IV 28%. The primary treatment was delivered with curative intent in 276 cases (96%). Of these, 266 received primary radiotherapy. The median radiation dose was 62 Gy, given as laterally opposed fields to the primary tumour and bilateral neck. Eight patients were treated with primary surgery and two with chemotherapy as part of a curatively intended treatment programme including radiotherapy. Six patients received palliative treatment, and seven were not treated at all. Out of 276 tumours treated with curative intent, 173 reappeared; 72% recurred in T position, 38% in N position, and 12% at distant metastatic sites, some in combination. Salvage surgery was possible in 52 patients, and 24 treatments were successful. Salvage radiotherapy or cryotherapy was used in 22 patients and 4 were controlled. For the entire group, the 5-year locoregional tumour control, disease-specific survival and overall survival rates were 38%, 44% and 31%, respectively. For patients treated with curative intent, clinical T- and N-stage, stage, tumour size, gender, age, and pretreatment haemoglobin were significant prognostic parameters in a univariate analysis. The Cox multivariate analysis showed that T-stage, N-stage and gender were independent prognostic factors. It is concluded that T-stage, N-stage and gender are significant independent prognostic factors. The primary control of the carcinoma in the T-position is crucial for overall success, but salvage surgery is found to have a favourable success rate in patients suitable for relapse treatment.

Adult↗
PubMed2000

Hypopharyngeal squamous cell carcinoma--treatment results in 138 consecutively admitted patients.

The aim of this study was to evaluate the results of the initial and salvage treatment for hypopharyngeal carcinoma. The study was conducted in 1963 to 1991 and included 138 patients (38 females (28%) and 100 males (73%)). Most of the tumours originated in the piriform sinus (86%). Tumour stage distribution was T1: 20%, T2: 27%, T3: 37% and T4: 17% and nodal stage distribution was N0: 45%, N1: 25%, N2: 10%, and N3: 20%. Primary treatment was delivered with curative intent in 124 out of 138 cases (90%). Treatment failure was noted in 98 patients, with 55% recurrence in T-position, 39% in N-position, and 14% at distant metastases sites. Salvage surgery was successful in 9 out of 32 patients. The overall 5-year locoregional tumour control, cause-specific and overall survival rates were 20%, 25% and 19%, respectively. Univariate actuarial analysis showed that T- and N-stage, clinical stage, tumour size and well-differentiated tumours were significant prognostic parameters. A Cox multivariate analysis showed that only the T- and N-stages were independent prognostic factors. In conclusion, the prognosis for advanced hypopharyngeal carcinoma is extremely poor and the meagre results with conventional radiotherapy alone indicate that other treatment modalities should be introduced in the management of this disease.

Adult↗
PubMed1999

Follicular mycosis fungoides: presentation of a case and review of the literature.

Follicular mycosis fungoides is a rare variant of mycosis fungoides (MF). Structural-wise there are several acneiform lesions made up of comedones, cysts and hyperkeratosis. The main histological finding is atypical lymphocytic infiltration around follicular structures, without epidermotropism. The association with follicular mucinosis is widely discussed in the literature. We report a case of follicular (MF) and review the cases published to date.

Humans↗
PubMed1999

Mismatch negativity and auditory sensory memory in chronic alcoholics.

BACKGROUND & METHODS: Preattentive auditory processing and sensory memory were investigated by means of mismatch negativity (MMN) in a sample of 22 middle-aged abstinent chronic alcoholics and 25 age-matched healthy controls. Stimuli were presented at two inter-stimulus intervals (ISIs, 0.75 sec and 2.0 sec) in separate blocks. RESULTS: No significant differences in amplitude or latency of MMN were found between alcoholic and control subjects in either of the two ISI conditions. However, when age was included as a factor in the analysis, MMN amplitude was attenuated in chronic alcoholics who were older than 40 years of age. CONCLUSIONS: These results indicate that the automatic stimulus-change detector mechanism associated with MMN generation is impaired in chronic alcoholics over the age of 40, suggesting that the neurotoxic effects of chronic consumption of alcohol are more prone to appear after a critical age.

Adult↗
PubMed1998

Mismatch negativity and auditory sensory memory evaluation: a new faster paradigm.

A new faster paradigm to measure the duration of auditory sensory memory, as indexed by mismatch negativity (MMN) suppression to stimuli presented at increasing inter-stimulus intervals (ISI), is proposed. Trains of three stimuli were delivered at very short ISI (300 ms). The inter-train interval varied according to the memory probe interval (MPI) tested. Trains started randomly with a deviant or standard stimulus (50% each), with their event-related brain potentials subtracted to obtain the MMN. The new paradigm provided MMNs identical to the conventional one at MPIs of 0.4 and 4.0 s in young subjects, and revealed MMN suppression when the MPI was increased to 5.0 s in older subjects. The new paradigm estimates auditory sensory memory duration in one-third the time of conventional MMN.

Acoustic Stimulation↗
PubMed1997

[Centralized follow-up of patients treated for head and neck cancer].

In a prospective study, the value of the clinical follow-up after treatment for head and neck cancer has been assessed. A total of 407 visits in 377 patients were recorded during a three month period in 1993 at the two major radiotherapy departments in Denmark. The results showed that 61% of follow-up visits included one or more problems either related to treatment morbidity or tumour recurrence. About 50% of all visits included treatment related normal tissue problems, and 30% had problems that required intervention. Although the majority of problems occurred within a few years after treatment, 47% of patients at three to four years observation time still had one or more problems. A total of 34 new tumour recurrences were found in the period, and of these 11 (32%) were asymptomatic. It is concluded that head and neck cancer patients have both tumour and normal tissue problems several years after the end of treatment. Since effective salvage treatment improves local control significantly, early detection of possible recurrence is important. A follow-up period of four to five years is recommended-preferably by qualified experts in the management of both recurrent disease and treatment morbidity.

Centralized Hospital Services↗
PubMed1997

Detection of hypoxic cells in a C3H mouse mammary carcinoma using the comet assay.

The comet assay was used to estimate radiobiological hypoxic fraction across a full range of tumour oxygenations in C3H mammary tumours implanted into the feet of female CDF1 mice. Tumours were either clamped before irradiation or mice were allowed to breath air, 100% oxygen, carbogen or carbon monoxide for 5-35 min before and during exposure to 15 Gy. For the alkaline comet assay, tumours were excised after irradiation and individual tumour cells were analysed for DNA single-strand breaks. Hypoxic cells were defined as those cells with approximately three times fewer single-strand breaks than aerobic cells. Radiobiological hypoxic fraction was calculated by fitting DNA damage histograms to two normal distributions, representing the response of the aerobic and hypoxic populations. The percentage of hypoxic cells estimated using the comet assay was then compared with hypoxic fraction measured using a clamped tumour control assay. Carbogen and oxygen breathing reduced the normal hypoxic fraction from 14% to 2-3% in this tumour, whereas 75-660 p.p.m. carbon monoxide progressively increased the hypoxic fraction from 18% to 82%. The slope of the line comparing the two methods was 1.23 with 95% confidence limits of 1.12-1.33 (r2 = 0.994). In the SCCVII squamous cell carcinoma growing subcutaneously in C3H mice, a similar correlation was observed between hypoxic fraction measured using the comet assay and hypoxic fraction measured in the same tumour cells using the paired survival curve assay (slope = 1.20 with 95% confidence limits of 1.03-1.37). These results confirm the ability of the comet assay to provide an accurate estimate of radiobiological hypoxic fraction over a wide range of tumour oxygenations and between two tumour types.

Animals↗
PubMed1997

Cancer of the nasal cavity and paranasal sinuses. A clinico-pathological study of 277 patients.

In the period 1963-1991, a total of 277 consecutive patients with malignant tumours of the nasal cavity and paranasal sinuses were treated at Aarhus University Hospital. The major histological types included squamous cell carcinoma (46%), lymphoma (14%), adenocarcinoma (13%), and malignant melanoma (9%). Kaplan-Meier estimates of 5-year corrected survival (death from cancer) showed the best prognosis for adenoid cystic carcinoma (87%), adenocarcinoma (65%) and lymphoma (56%), and the poorest prognosis for undifferentiated carcinoma (17%) and malignant melanoma (24%). The 5-year corrected survival for squamous cell carcinoma was 35%. Of the 180 patients with treatment failure, the vast majority occurred locally (n = 166); a minor proportion was regional (n = 23) or distant (n = 30). For the 195 patients with carcinoma, the following parameters were of statistical prognostic significance (5-year corrected survival): histological differentiation (moderate-well 65% vs. poor 22%), primary T-site (nasal cavity 56% vs. maxillary antrum 39% vs. other sinuses 24%), tumour stage (T2 68% vs. T3 37% vs. T4 29%), nodal stage (N0 48% vs. N1-3 21%), treatment (radiotherapy + surgery 56% vs. radiation alone 35%).

Aged↗
PubMed1996

The H1-receptor antagonist chlorpheniramine decreases the ending phase of the mismatch negativity of the human auditory event-related potentials.

Auditory event-related potentials (ERPs) were recorded in 20 healthy male humans, who received either a single 4 mg dose of d-chlorpheniramine or a placebo, according to a double-blind design. Subjects were instructed to read a book and to ignore random sequences of 90% standard (1000 Hz) and 10% deviant (1100 Hz) tones, presented with stimulus-onset asynchrony (SOA) of 480 ms. Deviant tones elicited the mismatch negativity (MMN) response, which was smaller at its ending phase in the chlorpheniramine group. The auditory exogenous components (N1 and P2) were similar in both groups. Results demonstrate that the antihistamine chlorpheniramine selectively affects the automatic stimulus-change detector associated with MMN, and suggest an involvement of the histamine H1-receptor in the genesis of the MMN.

Acoustic Stimulation↗
PubMed1996

Repopulation in the SCCVII squamous cell carcinoma assessed by an in vivo-in vitro excision assay.

An in vivo-in vitro excision assay was used to study repopulation after a single dose of clamped irradiation (40 Gy) in the SCCVII tumour implanted in the foot of C3H/Km mice. The growth pattern of clonogenic cells was analysed by two different mathematical models: the logistic model and the Gompertz model. The logistic model described the data better than the Gompertz model. Accelerated repopulation was found when the regrowth rate after irradiation was compared to the growth rate at the time of treatment, and when it was compared to the growth rate in untreated tumours with a number of cells equivalent to the number that was found after irradiation. The clonogenic doubling time (cDT) was estimated at 15.1 h (95% c.i.: 14.2; 16.0) after irradiation, and 27.8 h (95% c.i.: 16.7; 43.5) in untreated controls of matching size. However, the estimate relies on the mathematical model chosen and on extrapolation below actually measured data. A small cDT points to shortening of the cell cycle time and recruitment of non-cycling clonogenic tumour cells to be the main mechanism behind the accelerated repopulation.

Animals↗
PubMed1996

Short-term replicability of the mismatch negativity.

The short-term replicability of the mismatch negativity (MMN) between two recording sessions spaced 2 h apart was evaluated at individual and group levels in a sample of 11 healthy adults. Subjects were presented with a random sequence of 1000 Hz standard (92%) and 1100 Hz deviant (8%) tones while they were reading a book. The N1 and P2 exogenous components to standard tones showed a fairly good individual and group replicability. There were no significant differences in the MMN amplitude and latency between the two sessions in the group of subjects as a whole. The individual replicability of the MMN was not as good as for the N1 to standards, reaching significance in only some of the electrodes. This result was, however, similar to that obtained for the N1 after deviant tones. The results indicate that the MMN has good replicability at the group level, and further that at the individual level, MMN replicability is similar to that of the N1 to deviants. This suggests that the number of summations should be increased in order to improve the clinical usefulness of the MMN.

Acoustic Stimulation↗
PubMed1996

A double-blind trial of haloperidol, chlorpromazine, and lorazepam in the treatment of delirium in hospitalized AIDS patients.

OBJECTIVE: The purpose of this study was to examine the efficacy and side effects of haloperidol, chlorpromazine, and lorazepam for the treatment of the symptoms of delirium in adult AIDS patients in a randomized, double-blind, comparison trial. METHOD: Nondelirious, medically hospitalized AIDS patients (N = 244) consented to participate in the study and were monitored prospectively for the development of delirium. Patients entered the treatment phase of the study if they met DSM-III-R criteria for delirium and scored 13 or greater on the Delirium Rating Scale. Thirty patients were randomly assigned to treatment with haloperidol (N = 11), chlorpromazine (N = 13), or lorazepam (N = 6). Efficacy and side effects associated with the treatment were measured with repeated assessments using the Delirium Rating Scale, the Mini-Mental State, and the Extrapyramidal Symptom Rating Scale. RESULTS: Treatment with either haloperidol or chlorpromazine in relatively low doses resulted in significant improvement in the symptoms of delirium as measured by the Delirium Rating Scale. No improvement in the symptoms of delirium was found in the lorazepam group. Cognitive function, as measured by the Mini-Mental State, improved significantly from baseline to day 2 for patients receiving chlorpromazine. Treatment with haloperidol or chlorpromazine was associated with an extremely low prevalence of extrapyramidal side effects. All patients receiving lorazepam, however, developed treatment-limiting adverse effects. Although only a small number of patients had been treated with lorazepam, the authors became sufficiently concerned with the adverse effects to terminate that arm of the protocol early. CONCLUSIONS: Symptoms of delirium in medically hospitalized AIDS patients may be treated efficaciously with few side effects by using low-dose neuroleptics (haloperidol or chlorpromazine). Lorazepam alone appears to be ineffective and associated with treatment-limiting adverse effects.

AIDS Dementia Complex↗