Therapy of leptomeningeal metastasis in solid tumors.

Leptomeningeal metastasis (LM), i.e. the seeding of tumor cells to the cerebrospinal fluid (CSF) and the leptomeninges, is a devastating and mostly late-stage complication of various solid tumors. Clinical signs and symptoms may include cranial nerve palsies, radicular symptoms, signs of increased intracranial pressure such as headache, nausea and vomiting, and cognitive dysfunction. In cases of suspected LM, the highest diagnostic sensitivity is provided by the combination of CSF cytology and contrast-enhanced MRI (cranial as well as complete spine). The therapeutic spectrum includes radiotherapy of the clinically involved region as well as systemic and intrathecal chemotherapy. The choice of treatment modalities depends on the type of LM (non-adherent tumor cells in the CSF vs. nodular contrast-enhancing tumor growth), additional systemic involvement (uncontrolled vs. controlled systemic disease) and additional involvement of the CNS parenchyma (LM as the only CNS involvement vs. LM+parenchymal CNS metastases). Larger contrast-enhancing nodular LM or symptomatic lesions of the spine may be treated with radiotherapy. In case of uncontrolled systemic disease, the treatment regimen should include systemic chemotherapy. The choice of systemic treatment should take into account the histology of the primary tumor. Intrathecal chemotherapy is most important in cases of LM of the non-adherent type. There are three substances for routine use for intrathecal chemotherapy: methotrexate, cytarabine, and thiotepa. Liposomal cytarabine shows advantages in terms of longer injection intervals, a sufficient distribution in the entire subarachnoid space after lumbar administration and improved quality-of-life. The role of new agents (e.g. rituximab and trastuzumab) for intrathecal therapy is still unclear.

Ifosfamide, carboplatin and etoposide in recurrent malignant glioma.

After failure of temozolomide, there is no established standard salvage chemotherapy for patients with recurrent glioblastoma (GBM). Two phase II trials combining ifosfamide, carboplatin and etoposide chemotherapy (ICE) showed favorable results. We therefore applied the ICE protocol to 13 patients (10 GBM, 3 anaplastic astrocytomas). Partial or complete remissions were not observed. None of the 13 patients survived progression-free for 6 months. Our retrospective analysis suggests that the ICE regimen is not effective in patients with recurrent high-grade glioma if applied at second or third relapse.

Incorporation of osteoblasts (MG63) into 3D nanofibre matrices by simultaneous electrospinning and spraying in bone tissue engineering.

Nanofibre scaffolds are suitable tools for bone tissue engineering. Mimicking the extracellular matrix, they allow for cell growth and differentiation. However, in large 3D scaffolds, uniform cell colonisation presents an unsolved problem. Our aim was to design and analyse a method of colonising nanofibre scaffolds, combining electrospinning of fibres and electrospraying of cells, to determine its impact on cell survival, growth, and gene expression. The osteoblast-like cell line MG63 was suspended in medium and electrosprayed into growing scaffolds of poly-(l-lactic acid) (PLLA) or PLLA/Col-I blend nanofibres. Fluorescein diacetate (FDA) staining was used to determine survival and growth over a 22 d culture period. Expression of osteocalcin (OC) and type I collagen (Col-I) genes was determined by real time PCR. Fluorescence microscopy was used to analyse Col-I and OC deposition, as well as cell densities. While spraying distance and cell density in the spraying solution influenced survival and cell density, the combination of electrospinning and electrospraying did not negatively influence the maintenance of the osteoblast phenotype. Furthermore, VEGF induction in response to hypoxia was not suppressed, but modulated by polymer composition. Therefore, simultaneous electrospinning and electrospraying is a suitable tool in producing nanofibre based 3D cell seeded scaffolds.

The factors associated with body mass index in adults from the study of health in Pomerania (SHIP-0), Germany.

OBJECTIVE: To investigate the relation between dental status, BMI and systemic diseases and to evaluate the risk factors for having a higher BMI. MATERIALS AND METHODS: Apopulation based cross sectional study of 6248 subjects aged 18-80 years (response of 68.8%, n=4310) was conducted in the Study of Health in Pomerania (SHIP-0). Socio-demographic, medical and oral health information was recorded by 5 dentists at two similarly equipped medical/dental services in the cities of Greifswald and Stralsund. Bivariate statistics, multivariate statistics, linear and logistic regression models were performed to assess the relationship between following covariates: gender, educational level, family status, social activities, income, quality of life (SF-12), smoking, alcohol abuse, diabetes, renal disease, high blood pressure, dental status and high physical activity. RESULTS: Significant risk factors for subjects having a higher BMI were: high blood pressure (OR=2.28), diabetes (OR=2.10), educational level (low: OR=1.49; medium OR=1.27), male (OR=1.32) and former smoker (OR=1.20). whereas young age, being single and being dentate (natural teeth, replaced teeth or fixed teeth) was shown to be protective for having a "high" BMI. CONCLUSION: The most important predictors of BMI were shown to be social and medical factors. Dental factors are most significantly influenced by social factors and also exhibit an important impact on BMI.

Evaluation of shape and size changes of bone and remodelled bone substitute after different fixation methods.

Suitable tissue fixation is indispensable to histological analysis. This investigation, therefore, sought to evaluate changes of shape and size of bone specimens and remodelled bone substitute material following different fixation methods. Mandibular bones of 9 pigs (Sus scrofa domesticus) served as specimens. Two mandibular premolars were extracted respectively and the extraction alveoli were filled with synthetic bone substitute material. The samples were collected after 70 days. Fixation of 6 specimens respectively was done for 7 days in 4% formalin (formaldehyde), 70% ethanol and glycerol at 18 degrees C room temperature. The samples were radiographically examined before and after fixation using a reference specimen and subsequently underwent histological analysis. After fixation in formalin, the samples showed no size changes. After fixation in glycerol, morphological analysis revealed minor shape changes. Fixation in ethanol causes shrinking of the tissue specimens. Histological inspection of the tissues shows no morphological changes except slight shrinking. In conclusion there is no universal fixative that could met all requirements and permited proper examination without affecting tissues or bone specimens.

A novel post-and-core restoration system--results of three years of clinical application of the "Wuerzburg Post".

The Wuerzburg Post is a new post-and-core restoration system designed to eliminate the weak parts of post-and-core restorations and the associated problems, respectively. In contrast to conventional posts, the Wuerzburg Post is a short and thick post, which no longer relies on cementation or luting for retention in the root, but on stress-free positive locking, which it achieves by means of a post which can be spread into a predefined and form-congruent undercut cavity. The second key feature is an annular groove which runs in the dentin, girded by a corresponding structure, ensuring regular force transmission and stress dissipation, as opposed to the classic ferrule design. There are two versions: one with a machined core which can be prepared like a classic build-up to support crowns and bridges, and another one with a 2.25 mm ball end to connect to common dies which can be integrated into removable prostheses. As the system utilizes prefabricated parts made from Titanium, a precise fit is ensured, enabling the user to restore teeth quickly and easily. Over the course of the past three years, 129 posts were inserted, most commonly on upper and lower incisors and canines. The main application was restoration of fractured telescopes. During the observation period, five failures were observed. Two of the failiures did not cause significant damage to the tooth, and were subsequently immediately repairable. The survival rate amounts to over 95% after three years under risk.

Adaptation of myosin heavy chain mRNA expression after implantation of poly(3)hydroxybutyrate scaffolds in rat m. latissimus dorsi.

The aim of this study is to identify the synergistic effect between an ectopic bone substitute and surrounding tissues, in this case muscle tissue, which is known to have a considerable potential for adaptation. To describe this effect, changes of myosin heavy chain (MyHC) isoform mRNA content of 12 Wistar-King rats m. latissimus dorsi with implanted poly(3)hydroxybutyrate (PHB) scaffolds were examined after six and 12 weeks. At each time interval six rats were killed and implants and surrounding tissues prepared for genetic evaluation. Eight rats without any implants served as controls. After homogenisation of muscle tissue, RNA was extracted and reverse transcribed. Changes in mRNA content were measured by Real-Time PCR using specific primers for type I MyHC, IIa, IIb and IIx isoforms. The mRNA level of myosin isoform type I of the muscles surrounding the implant was significantly increased (p<0.02) compared to the control group. Further, the studied muscle tissue showed a significant decrease in MyHC isoform IIx mRNA compared to the controls (p<0.02). Implantation of PHB scaffolds into rat m. latissimus dorsi causes an increase of its' content of slow myosin isoforms indicating a synergistic effect between the PHB scaffold and the surrounding muscle tissue.

Bone graft substitutes in periodontal and peri-implant bone regeneration.

Regenerative medicine provides different therapy alternatives alongside gold standard autogenous grafts for the treatment of periodontal or peri-implant osseous defects. Continuing progress in the field of alloplastic bone substitutes has yielded promising solutions to the appropriate indications with the membrane technique either alone or in combination with enamel matrix derivatives. Their clinical outcomes, however, still require critical discussion.

The morphological and clinical relevance of mandibular and maxillary bone structures for implantation.

Tooth loss, which interrupts the biocybernetic feedback circuit of the masticatory system, changes the structures of the jaw bone: such changes are termed "inactivity atrophy". The mandible is subject to vertical atrophy and the maxilla is primarily subject to horizontal atrophy. The mandible possesses more compact bone, the maxilla more spongy; the resorption directions also differ (mandible: towards the oral aspect; maxilla: towards the vestibular). An implant helps to restore the biocybernetic feedback system. The amount of available bone, bone structure, and topographic conditions are crucial factors influencing implant success. Osseointegration is performed at an early stage (which includes bleeding, granulation tissue, foreign-body recognition, interactions) and at a late stage (so-called osseous bridging, development of fibrous and lamellar bone).

Epidemiological evaluation of the multifactorial aetiology of abfractions.

The purpose of this study was to determine risk indicators for the aetiology of abfractions (cervical wedge-shaped defects) on teeth using dental and medical variables obtained in a population-based sample of the cross-sectional epidemiological 'Study of Health in Pomerania' (SHIP). Medical history, dental, and sociodemographic parameters of 2707 representatively selected subjects 20-59 years of age with more than four natural teeth were checked for associations with the occurrence of abfractions using a two-level logistic regression model on a tooth and a subject level. The estimated prevalence of developing abfractions generally increased with age. The following independent variables were associated with the occurrence of abfractions: buccal recession of the gingiva, odds ratio (OR) = 6.7; occlusal wear facets of scores 1, 2 and 3, OR = 1.5, 1.9, 1.9; tilted teeth, OR = 1.4; inlays, OR = 1.6; toothbrushing behaviour, OR = 1.9 to 2.0 (two and three times a day versus once a day). First premolars had the highest estimated risk for developing abfractions, followed by the second premolars. Maxillary and mandibular teeth behaved similarly in terms of abfractions, with the exception of mandibular canines, which had a much lower estimated risk of incurring abfractions than did maxillary canines. The results of this analysis indicated that abfractions are associated with occlusal factors, like occlusal wear, inlay restorations, altered tooth position and tooth brushing behaviour. This study delivers further evidence for a multifactorial aetiology of abfractions.

Signs of temporomandibular disorders in tinnitus patients and in a population-based group of volunteers: results of the Study of Health in Pomerania.

The literature has documented a controversial discussion on the possible relationship of otogenous symptoms and craniomandibular dysfunction since the 1920s. Therefore, an investigation was conducted which consisted of two parts: a case study with population-based controls and a cross-sectional study. The aim of the first study was to screen a group of patients suffering from acute or chronic tinnitus for temporomandibular disorders (TMD) in comparison with a population-based group of volunteers without tinnitus. To this end, 30 patients (13 females and 17 males, age 18-71 years) suffering from acute hearing loss associated with tinnitus, isolated acute tinnitus, and chronically transient tinnitus were examined for symptoms of craniomandibular dysfunction. The results were compared with those of clinical functional analysis from 1907 subjects selected representatively and according to age distribution from the epidemiological 'Study of Health in Pomerania' (SHIP); the occurrence of tinnitus was ruled out in these control subjects. Statistical analysis was performed with Chi-square and Mann-Whitney U-tests. Sixty per cent of the tinnitus patients and 36.5% of the control subjects exhibited more than two symptoms of TMD (P = 0.004). Tinnitus patients had significantly more muscle palpation pain (P < 0.001), temporomandibular joint (TMJ) palpation pain (P < 0.001), and pain upon mouth opening (P < 0.001) than the general population group. No statistical differences were found in TMJ sounds, limitation of mandibular movement, or hypermobility of the TMJ. Furthermore, 4228 subjects of the population group examined in the epidemiological study were screened for co-factors of tinnitus with the help of a multivariate logistic regression model which was adjusted for gender, age, and a variety of anamnestic and examined data. Increased odds ratios (OR) were found for tenderness of the masticatory muscles (OR = 1.6 for one to three painful muscles and OR = 2.53 for four or more painful muscles), TMJ tenderness to dorsal cranial compression (OR = 2.99), listlessness (OR = 2.0) and frequent headache (OR = 1.84) A relationship between tinnitus and TMD was established in both examinations. Tinnitus patients seem to suffer especially from myofascial and TMJ pain. A screening for TMD should be included in the diagnostic survey for tinnitus patients.

Analysis of imaging modalities, staging systems, and prognostic indicators for renal cell carcinoma.

A retrospective analysis of 314 patients with renal cell carcinoma was done focusing mainly on imaging modalities and prognostic significance of tumor stage using both the Robson and TNM systems. Computerized tomography (CT) scan proved to be the most effective modality for staging. Overall staging accuracy was 62 and 68 percent for TNM and Robson staging, respectively, and understaging was more frequent than overstaging. The actuarial five-year survival using the Robson system was 73 percent for Stage A, 68 percent Stage B, 51 percent Stage C, and 20 percent Stage D. The main limitation of the Robson system is the heterogeneity of the Stage C group which includes patients with renal vein and those with nodal involvement with a significant difference in survival. The survival by the TNM system showed no difference in those with T1, T2, T3a and T3b disease but a significant difference in those with T3c or T4a. One hundred sixteen patients (37%) presented with metastatic disease with a median survival of seventeen months (range 2-204) for those with solitary metastasis and six months (range 1-132) for those with multiple metastases (the difference was not statistically significant). Except for anecdotal cases, nephrectomy with or without treatment of the metastases did not seem to affect survival significantly. The presence of spindle cell, alone or in association with clear or granular cell, affected the prognosis adversely. Thirty-one patients had their tumors identified incidentally. Their stage at diagnosis was earlier than the symptomatic group (Stage T1-T2: 77% vs 34%), and there was a significant difference in the disease-free survival at fifty-four months between the two groups (79% vs 57%, respectively).

Conservative management of renal lacerations in blunt trauma.

Controversy in the treatment of blunt renal trauma is largely focused on immediate surgery versus conservative management for parenchymal lacerations. A retrospective analysis of 133 cases of blunt renal trauma at the Victoria General Hospital in Halifax over a 10-year period revealed 26 cases of renal laceration. The conservative approach to radiologic diagnosis and treatment options is discussed. Our experience confirms a low rate of both nephrectomy and secondary complications using conservative management.

Growth and development of broiler breeders. 1. Effect of early plane of nutrition and growth rate.

In two experiments, male and female broiler breeders were reared on two different planes of growth as a result of early nutritional treatment. The starter treatment(s) consisted of a 19.5% crude protein, (CP), 2970 kcal diet from 0 to 14 days and 15.5% CP, 2750 kcal ration from 2 to 10 weeks. The birds in the grower treatment were fed the latter diet from 0 to 10 weeks. Both treatments were ad libitum fed from 0 to 3 weeks and then restricted to meet the breeder's recommended body weight targets. In Experiment 1, the starter treatment resulted in significantly heavier body weights at 3 weeks of age but not at later ages. The initiation of feed restriction was necessarily more severe for those chicks fed the starter diet. This restriction resulted in a significantly smaller liver at 10 weeks of age in breeder cockerels and dwarf breeder females. Vaccination titers [Newcastle, Infectious Bursal Disease (IBD),] and response to sheep red blood cells (SRBC) brachial vein injection were not affected by treatment. In a second experiment, there were no differences in bursa, spleen, or thymus weights between starter and grower treatments at 10 weeks of age, and the liver weights were again significantly larger in the grower treatment. One treatment of dwarf and normal pullets was overly restricted from 3 to 10 weeks (Grower-R), and lighter body weights were obtained at all ages. Only the spleen in the normal breeders was significantly smaller at 10 weeks of age in this treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Rectal obstruction by prostatic carcinoma: diagnosis by computerized tomography scan.

We report 3 cases of rectal obstruction from locally invasive prostatic carcinoma. The importance and difficulty of differentiating primary prostatic cancer from rectal cancer in this circumstance are stressed, and the usefulness of computerized tomography is discussed.

Carcinoma of the penis: an 11-year review.

Management of primary carcinoma of the penis in 37 men by local excision or radiotherapy was associated with a high risk of recurrence. The authors in this review recommend partial penectomy as the minimum surgical procedure for the primary lesion. Clinical assessment of the inguinal lymph nodes was often inaccurate and the value of early sentinel node biopsy is discussed. All patients who underwent ilioinguinal node dissection had complications and only one of six men with histologic stage III disease was cured. The overall 2-year survival rate was 51%.

Acute renal failure secondary to bilateral ureteric obstruction: review of 50 cases.

The records of 50 patients with acute renal failure secondary to bilateral ureteric obstruction were reviewed. An underlying malignant disorder was the cause of the obstruction in 38 of the patients and had not previously been diagnosed in almost half of them. Carcinomas of the cervix and prostate were the most frequent malignant disorders, and aggressive management resulted in good survival rates. Similarly, the outcome for patients with benign bilateral ureteric obstruction, usually caused by retroperitoneal fibrosis, was good with proper management.

Clinical and hemodynamic criteria for use of the intra-aortic balloon pump in patients requiring cardiac surgery.

In order to establish criteria for elective use of the intra-aortic balloon pump (IABP) in patients having cardiac surgery, we conducted a retrospective study of 43 patients who required counterpulsation, because of inability to be weaned from cardiopulmonary bypass, between May, 1972, and June, 1974. Patients in cardiogenic shock preoperatively were excluded. The 43 patients included 23 (Group A) who had severe preoperative left ventricular dysfunction with a mean cardiac index less than 1.8 L. per minute per square meter, ejection fraction less than 30 per cent, and end-diastolic pressure greater than 22 mm. Hg; 20 patients (Group B) had a combination of moderate cardiac dysfunction (cardiac index less than 2.2, ejection fraction less than 40, end-diastolic pressure less than 18) in the presence of acute infarction or severe aortic stenosis (gradient greater than 80 mm. Hg) with or without coronary disease. An inverse relationship was noted between survival and delay from completion of operation to the use of 1ABP. Thirty-two of 43 patients were weaned off bypass and were balloon assisted for 12 to 96 hours postoperatively; 25 patients were discharged (58 per cent). In Subgroup A, 14 of 23 (60 per cent) and, in Subgroup B, 9 of 20 (45 per cent) were long-term survivors. Based on these findings, 45 patients were operated upon between June, 1974, and December, 1975, with elective use of 1ABP and were assessed by serial hemodynamic studies. Sixteen had severe preoperative left ventricular dysfunction similar to Subgroup A and 29 had moderate dysfunction in combination with pathology similar to Subgroup B. Fifteen of these patients were hemodynamically unstable at time of arrival in the operating room; 1ABP was inserted under local anesthesia. Thirty-nine patients (87 per cent) were weaned off bypass and were hospital survivors. In Subgroup A, 13 of 16 (81 per cent) and, in Group B, 21 of 29 (72 per cent) were long-term survivors. Criteria for elective use of 1ABP in cardiac surgery should include severe preoperative left ventricular dysfunction or a combination of moderate dysfunction with coronary or valvular pathology. Elective 1ABP improves the survival with trivial iatrogenic morbidity.