[Functional disturbances of the cervical spine in tinnitus]. / Funktionsstörungen der Halswirbelsäule bei Tinnitus.

BACKGROUND: A total of 189 patients with tinnitus, Meniere's disease, and sudden hearing loss underwent manual therapeutic examination at the Department of Physical Medicine and Rehabilitation in the setting of an interdisciplinary program for the management of patients of the tinnitus daycare center and inpatients of the ENT department of the Charité Medical School. METHOD: In all patients, global and segmental joint mobility of the cervical spine, cervicothoracic junction, first rib, and craniomandibular system was assessed using standardized documentation. Muscle extensibility and trigger points were determined for the sternocleidomastoid muscle, the descending part of the trapezius muscle, the levator muscle of the scapula, and the masseter muscle. RESULTS: Results of the statistical analysis show that patients with tinnitus have characteristic and specific patterns of abnormalities in the joints and paravertebral muscles. The dominant finding is an overall impairment of cervical spine mobility, to which various factors contribute. These include disturbed function of segmental joints of the head and the cervicothoracic junction as well as muscular imbalances of the shoulder and neck muscles. CONCLUSION: Our results corroborate the clinical significance of manual therapeutic findings as part of the diagnostic workup for tinnitus. They show that a uniform and standardized examination protocol is needed, and that appropriate physical therapeutic measures should be incorporated into the interdisciplinary therapeutic management of patients with tinnitus.

Secondary insults in severe head injury--do multiply injured patients do worse?

OBJECTIVES: To study the occurrence of secondary insults and the influence of extracranial injuries on cerebral oxygenation and outcome in patients with closed severe head injury (Glasgow Coma Scale score < or =8). DESIGN: Two-year prospective, clinical study. SETTING: Two intensive care units in a level III trauma center. PATIENTS: We studied 119 patients. Eighty patients had severe head injury and were divided into two categories: "isolated" severe head injury patients (n = 36, Injury Severity Score <30), and severe head injury patients with associated extracranial injuries (n = 44, Injury Severity Score >29). Thirty-nine patients with extracranial injuries and no head injury served as the control group. INTERVENTIONS: After patients were admitted to the intensive care unit, we began continuous multimodal cerebral monitoring of intracranial pressure, mean arterial blood pressure, cerebral perfusion pressure, end-tidal Co2, brain tissue Po2 (Licox), jugular bulb oxyhemoglobin saturation in severe head injury patients, and mean arterial blood pressure in the control group. Targets of management included intracranial pressure <20 mm Hg, cerebral perfusion pressure >60 mm Hg, Paco2 > 30 mm Hg, control of cerebral oxygenation, and delayed surgery for non-life-threatening extracranial lesions. MEASUREMENTS AND MAIN RESULTS: Data were analyzed for critical thresholds. The occurrence of secondary insults (intracranial pressure >20 mm Hg, mean arterial blood pressure <70 mm Hg, cerebral perfusion pressure <60 mm Hg, end-tidal Co2 <30 torr, brain tissue Po2 <10 torr, jugular bulb oxyhemoglobin saturation <50%) was comparable in patients with isolated severe head injury and those with severe head injury with associated extracranial lesions (Abbreviated Injury Scale score < or =5). The duration of intracranial hypertension and arterial hypotension significantly correlated with an unfavorable outcome, independent of the Injury Severity Score. In patients with severe head injury, 1-yr outcome was 29% dead or vegetative, 17% severely disabled, and 54% moderate or good outcome. This was similar to patients with severe head injury and extracranial injuries (31% dead or vegetative, 14% severely disabled, and 56% moderate or good outcome) and was independent of the Injury Severity Score. Patients with no head injury had less secondary insults (mean arterial blood pressure <70 mm Hg, p <.01) and a better outcome compared with both severe head injury groups (p <.044). CONCLUSIONS: In patients with severe head injury who have targeted management including intracranial pressure- and cerebral perfusion pressure-guided therapy and delayed surgery for extracranial lesions, the occurrence of secondary insults in the intensive care unit and long-term neurological outcome were comparable and independent of the presence of extracranial lesions (Abbreviated Injury Severity level < or =5). A severe head injury is still a major contributor predicting an unfavorable outcome in multiply injured patients.

Human demineralised bone matrix as a bone substitute for reconstruction of cystic defects of the lower jaw.

In a retrospective study validated by a standardized clinical and radiological examination, the bone regeneration in 90 patients with cystic mandibular defects was examined. In 50 patients bony defect reconstructions with human demineralised bone matrix (HDBM) were carried out, while in a comparable group of 40 patients the hollow pockets were left to regenerate bone spontaneously. The bone regeneration after the implantation of human demineralised bone matrix (HDBM) was subjected to a comparative validation. Osteoinductive proteins present in HDBM (bone morphogenetic proteins) can diffuse into the implant seat and induce new bone formation (osteoinduction). A markedly faster and more thorough bone regeneration was demonstrated after the surgical therapy of cystic mandibular lesions with HDBM than without. HDBM also proved to be exceptionally biocompatible.

[Improved prognostic assessment of head-neck carcinomas by new genetic markers]. / Verbesserte Prognoseeinschätzung bei Kopf-Hals-Karzinomen durch neue genetische Marker.

In individual patients with head and neck squamous cell carcinomas (HNSCC), established prognostic factors do not satisfactorily predict clinical outcome. For the first time we investigated a total of 100 HNSCC by Comparative Genomic Hybridization (CGH) to define chromosomal alterations that are associated with the patients prognosis. Patients were followed for at latest 4 but at least 2 years after surgery or until death. During this observation period twenty-nine of them died because of cancer disease. The Kaplan-Meier method was used plotting survival curves for every single chromosomal alteration as well as every clinico-pathological parameter. The curves were tested for significance by the log rank as well as the Breslow test. Significance of particular prognostic parameters was then evaluated by the Cox regression model. The overall survival time as well as the recurrence free survival time were significantly lower in patients who's tumors showed amplifications of the chromosomal region 11q13 (p = 0.0008 for LR and p = 0.0024 for B). The survival time of the patients was also lower if the carcinomas carried over-representations of chromosome 3q (p = 0.0299 for LR and p = 0.0546 for B). Multivariate analysis (Cox's proportional hazards model) revealed both alterations as most important independent prognostic factors in HNSCC. None of the conventional clinicopathological parameters (pT-, pN-status, UICC stage, grading) achieved statistical significance in the multivariate model. These results suggest that in HNSCC the occurrence of 11q13 amplification and 3q overrepresentation are highly significant independent prognostic markers and of better value than the established TNM and grading criteria.

Genetic imbalances with impact on survival in head and neck cancer patients.

Chromosomal imbalances in 113 primary head and neck squamous cell carcinomas (HNSCCs) determined by comparative genomic hybridization were correlated with patients survival using custom-made computer software which enabled the assessment of individual chromosomal loci. The Kaplan-Meier analysis revealed that overrepresentations of 2q12, 3q21-29, 6p21.1, 11q13, 14q23, 14q24, 14q31, 14q32, 15q24, 16q22, and deletions of 8p21-22 and 18q11.2 were significantly associated with both shorter disease-free interval and disease-specific survival in this tumor collective. Multivariate Cox proportional hazards regression models consistently identified the gains of 3q21-29, 11q13, and the loss of 8p21-22 as independent prognostic markers carrying a higher significance than the nodal status as the only clinicopathological parameter with statistical importance. In addition, these three markers allowed a molecular dissection of the patients with low clinical risk (pN0 and pT2 tumors). Thus, the genomic data being derived from the evaluation of primary HNSCC enabled a stratification of the patients into subgroups with different survival highlighting the necessity of a genetically based tumor classification for refining diagnosis and treatment of HNSCC patients.

Colour Doppler assessment of ascendent uterine artery perfusion in an in-vitro fertilization-embryo transfer programme after pituitary desensitization and ovarian stimulation with human recombinant follicle stimulating hormone.

The purpose of the present study was to evaluate the use of colour Doppler sonography of ascendent uterine artery perfusion in 91 patients undergoing in-vitro fertilization (IVF)-embryo transfer treatment after ovarian stimulation with a depot formulation of goserelin and recombinant human follicle stimulating hormone according to the long protocol. Resistance index (RI), pulsatility index (PI), maximum peak velocity (Vmax) and minimum diastolic velocity (Vmin) were assessed for the left and right ascending uterine artery on day 1 of ovarian stimulation, on day -2 [the day of human chorionic gonadotrophin (HCG) application] and on day +14 (12 days after embryo transfer). The data of 75 patients who had at least two cleaved preimplantation embryos available for transfer were analysed: 21 patients became pregnant resulting in a pregnancy rate of 28% (21/75). After exclusion of biochemical, ectopic and abortive pregnancies (n = 5), the data from 54 non-pregnant patients and 16 pregnant patients were analysed. No differences with respect to patient age, current cycle number, indication for IVF treatment, endometrial thickness at day -2 and serum oestradiol and serum progesterone concentrations at day -2 were found between the pregnant and non-pregnant groups. Compared to the non-pregnant patients the ascendent uterine artery flow of the pregnant patients showed significantly lower RI (P < 0.009) and PI (P < 0.03) values at the beginning of ovarian stimulation. Vmax and Vmin did not differ between the two groups. On day -2 no differences in RI, PI, Vmax and Vmin were found between pregnant and non-pregnant patients. On day +14 the flow in the ascendent uterine arteries of the pregnant patients showed significantly lower RI (P < 0.008) and PI (P < 0.03) values and significantly higher Vmax (P < 0.003) and Vmin (P < 0.0001) values. RI (P < 0.009) and PI (P < 0.003) values had decreased significantly and Vmax (P < 0.0002) and Vmin (P < 0.0001) had increased significantly on day +14 compared to the previous observation times in both the pregnant and non-pregnant groups. A significant correlation between the increase of serum progesterone concentrations and the decrease of RI (r = 0.68, P < 0.009), and the increase of Vmin (r = 0.67, P < 0.01) was only detected in the pregnant group. In conclusion, the differences found in RI and PI values at the beginning of ovarian stimulation were not clinically helpful as there was a wide overlap between non-pregnant and pregnant patients. The parameters currently used in colour Doppler assessment of uterine artery perfusion are not clinically helpful in discriminating prospectively which patients will and will not become pregnant in an IVF programme. In pregnant patients, increasing progesterone concentration is correlated with a significant decrease in impedance to uterine perfusion in the late luteal phase.

[Value of lymphatic outflow directed continuity dissection in melanoma surgery]. / Die Bedeutung der lymphabstromgerechten Kontinuitätsdissektion in der Melanomchirurgie.

Radicality of the surgical procedure in patients with intermediate and high risk melanomas is enhanced by the additional removal of the transit tract between tumor and regional lymph node (continuity dissection). After introduction of the lymphatic out flow scintigraphy in 1984, the accurate removal of the transit tract is easily possible in tumors located on the trunk, the upper arm and the thigh as well as of the head/neck region. The main reasons for the improved survival rates are the exact removal of the transit tract together with potentially existing occult tumor cells or in transit metastases, respectively, as well as ectope lymph node metastases and the consequent elective lymph node dissection.

Regional lymph node morphology in malignant melanomas and their prognostic value.

The occurrence of granulomatous epithelioid cell reaction, hyperplasia of lymphatic paracortex and existence of histiocytosis of the intermediary-medullary sinuses observed on sections of lymph nodes of 582 patients suffering from high-risk melanomas, examined during a ten-year period, have been established as reliable indicators of survival. On the other hand, lymphocytic infiltrative processes of the lymph node capsule, medullar plasmocytosis, and hyperplasia of germinal centres have been seen as indicators of a bad prognosis. Lymphocytic paracortical depletion and a predominance of postcapillary venules within the T zone were found to be less important in patients with a low chance of survival. We were able to establish a connection between lymphonodular parameters and the survival rate of the patients. In a multivariate test we found that there were four factors for statistical ascertainment of the prognosis of melanoma patients with lymphadenectomy: mitotic rate of primary tumour, lymphocytic infiltration of the lymph node capsule, existence of paracortical hyperplasia, and sex of the patient.

[Clinical experience with different modes of preoperative radiotherapy in advanced carcinomas of the tongue and the floor of the mouth]. / Klinische Erfahrungen mit untershciedlichen Vorbestrahlungsmodi bei fortgeschrittenen Zungen-Mundbodenkarzinomen.

In a controlled prospective study of 90 patients with locally advanced but operable epidermoid carcinomas (T2/T3N0-3M0) of the tongue and the floor of the mouth underwent 3 types of preoperative radiation: 1.5 x 5 Gy; 2.15 x 2 Gy and 3.5 x 2.5 Gy. The preoperative radiation led to a marked decrease of local recidives and to a lengthening of the recidive-free interval respectively. The type of preoperative radiation 5 x 5 Gy seemed to have the most favourable results. Otherwise the preoperative radiation had no advantages in regard to a better prevention of regional metastases and because of that there is no indication for it.