Predisposing factors and outcome of treatment of non-union of long-bone fractures in Ibadan, Nigeria.

AIMS AND OBJECTIVES: This study was done to find out factors that contribute to development of Non-union of long bone fractures in this environment and the outcome of operative intervention. This is a prospective hospital based study. PATIENTS AND METHODS: All patients with Non-union of long bone fracture that presented in the hospital since January 1997 were recruited into the study. The data included causative factors, treatment given before presenting in the hospital, type of surgical procedure and result of treatment. The study was completed in December, 2005. RESULTS: 78 patients presented with 87 Non-union of long bones. A male, female ratio of 1.6:1 was encountered while 69.2 per cent of the patients were below the age 55years. Road Traffic Accident accounted for 68 fractures (78.2 per cent) while duration of injury before presentation varies from 6 months to 22 months. Atrophic non-union occurred in 60 cases (69.0 per cent) and hypertrophic non-union in 21 cases. Non-union of the femur occurred in 33 cases (37.9 per cent) humerus in 24 cases (27.6 per cent), tibia in 16 cases (18.4 per cent), radius and ulna in 14 cases (16.1 per cent). The initial treatments of the fresh fracture in the 78 patients with nonunion were by the traditional bonesetters in 51 patients (65.4 per cent) while the remaining fractures were treated by plaster of paris in hospital. Open reduction and internal fixation using plate and screws with bone grafting was the most common procedure for treating the non-union in most cases. Union was achieved in the entire patients following surgical intervention. CONCLUSION: Important factor that appears to contribute to non-union of long bone in this environment is soft tissue interposition between the fracture ends of the bone, which is found in all fractures with more than one diameter displacement. Another factor is interference with periosteal blood supply from disruption of soft tissue envelope as a result of high energy injuries which is also responsible for the displacements that were observed in these fractures. The treatment by traditional bone setters which entails daily massage of the fracture creating a macro movement at the fracture site is also an important contributing factor.

[Paraneoplastic limbic encephalitis resulting from non-Hodgkin-lymphoma: two case reports]. / Paraneoplastische Limbische Enzephalitis als Erstmanifestation eines malignen Non Hodgkin Lymphoms.

Paraneoplastic limbic encephalitis (PLE) is a rare disease that is probably caused by an immunological reaction against CNS-structures. It may present with neurological, neuropsychological or psychiatric symptoms. Besides treatment of the underlying neoplastic disease, there is no generally applicable evidence-based treatment. PLE is most frequently associated with certain carcinomas, but its occurrence with Hodgkin lymphoma has also been recognized. Association with non-Hodgkin lymphoma has only been occasionally reported in single cases. We report two additional patients, in whom malignant non-Hodgkin lymphomas of the B- and T-cell lines were detected. Treatment with corticosteroids in one and chemotherapy in the other case were associated with clinical improvement.

Sex differences in length of survival with malignant astrocytoma, but not with glioblastoma.

In a retrospective analysis based on a malignant glioma databank, we describe effects of age, sex and diagnosis upon survival in patients with malignant cerebral glioma with a pre-treatment Karnofsky-index of 60 or more. All patients had been treated with 55-60Gy radiotherapy and nitrosurea-based adjuvant chemotherapy. We found an age-dependent sex effect upon survival in grade III astrocytoma patients, but not with glioblastoma.

[Coping in patients with malignant glioma in the course of radiation therapy]. / Krankheitsverarbeitung bei Hirntumorpatienten. Eine Untersuchung im Verlauf der Bestrahlung.

UNLABELLED: Twenty-one patients with malignant glioma were interviewed in the course of radiation therapy (before start, in the middle and at the end of treatment and six weeks later). We used the "Freiburger Fragebogen zur Krankheitsverarbeitung (FKV)", an assessment of coping strategies, the "State-Trait-Anxiety-Inventory (STAI)", the "Beck-Depression-Scale (BDI)", and the QLQ-C 30 questionnaire of the EORTC. RESULTS: The coping strategies of our patients are comparable with other cancer patients. They are mainly characterized by "self-encouragement", "compliance" and "trust in the treating physician". Anxiety was low and showed no significant changes. Depressivity was higher than in the normal population, however, it also showed no significant changes in the course of therapy. Quality of life scores remained constant, despite an increase of fatigue. In our patients with malignant glioma, the influence of radiation on coping, anxiety, depression and quality of life seems insignificant in comparison to that of the diagnosis of cancer.

TP53 gene mutations, nuclear p53 accumulation, expression of Waf/p21, Bcl-2, and CD95 (APO-1/Fas) proteins are not prognostic factors in de novo glioblastoma multiforme.

Glioblastoma multiforme (WHO grade IV; GBM) is the most common primary brain tumor with a median survival of less than one year despite multimodal treatment regimens. However, a small subgroup of GBM patients has a better clinical outcome, with a small number of patients surviving several years. Apoptosis, a genetically determined program of cell suicide, may be induced as a consequence of critical DNA damage. However, due to defects in the signaling pathways, cancer cells may escape apoptosis, despite carrying irreversible DNA damage. In the present study, we have analyzed tumors of two age-matched, equally treated groups of GBM patients with different postoperative time to tumor progression (TTP), defined as 'short-term' for TTP of less than 6 months (n = 54), and 'long-term' for TTP of more than 12 months (n = 39) for alterations in apoptosis regulatory pathways: Mutations of the TP53 tumor suppressor gene and/or nuclear accumulation of its gene product p53, expression of Waf/p21, CD95 (Apo1/Fas), and Bcl-2. TP53 mutations were found in 12 out of 54 (22%) GBMs of short-term survivors and 8 out of 35 (23%) tumors of long-term survivors; the respective numbers for nuclear p53 protein accumulation were 12/53 (23%) and 10/37 (27%). Waf1/p21 expression was found in 13/53 (25%) tumors of short-term survivors and 9/35 (26%) GBMs of long-term survivors. The respective numbers for Bcl-2 expression were 25/42 (60%) and 22/36 (61%) and for CD95 (Apo1/Fas) expression 20/49 (41%) and 14/36 (39%) GBMs. The percentage of alterations in genes/proteins involved in the apoptotic pathway investigated here was virtually identical in the two groups of clinically different GBM patients. Thus, our data imply that none of these alterations investigated per se has a strong impact on the overall survival of GBM patients.

Long-term survival of glioblastoma multiforme: importance of histopathological reevaluation.

The overall prognosis for patients with glioblastoma multiforme is extremely poor. However, a small proportion of patients enjoy prolonged survival. This study investigated retrospectively the extent to which erroneous histopathological classification may contribute to long-term survival of patients initially diagnosed with "glioblastoma multiforme." We compared two age- and gender-matched patient groups with different postoperative time to tumor progression (TTP), defined as "short-term" for TTP of less than 6 months (n = 54), and "long-term" for TTP of more than 12 months (n = 52). Histological specimens of the corresponding tumors, all primarily diagnosed as glioblastoma multiforme, were reevaluated according to the current World Health Organization (WHO) classification of central nervous system tumors, with the investigators being blinded to clinical outcome. Among the tumors from short-term TTP patients, one tumor (2%) was reclassified as anaplastic oligoastrocytoma (WHO grade III) while the remaining 53 were confirmed as glioblastoma multiforme. In contrast, 13 tumors (25%) from the long-term TTP patients were reclassified, mostly as anaplastic oligodendroglioma (WHO grade III; n = 7) or anaplastic oligoastrocytoma (WHO grade III, n = 2), respectively. In addition, three were reclassified as anaplastic astrocytoma (WHO grade III), and one was identified as anaplastic pilocytic astrocytoma (WHO grade III). Our data indicate that a sizable proportion of glioblastoma patients with long-term survival actually carry malignant gliomas with oligodendroglial features. The correct histopathological recognition of these tumors has not only prognostic but also therapeutic implications, since oligodendroglial tumors are more likely to respond favorably to chemotherapy.

Mdr1 mRNA expression differs between grade III astrocytomas and glioblastomas.

104 N2-frozen samples from 33 astrocytic tumors previously untreated with cytotoxic drugs have been analyzed for the expression of p-glycoprotein transcripts (mdrl) by RT-PCR using beta2-microglobulin as an internal control. A remarkable variation was observed even within a single tumor in 50% of the cases. Nevertheless, a difference became visible between the groups of anaplastic astrocytomas and glioblastomas. While 78% of the grade 3 astrocytomas contained at least a minimum of 1 sample with a very low mdr1 expression, this was the case only in 23% of the glioblastomas. This supports an earlier observation revealing a positive correlation between tumor grading and the tumor cell fraction stained with the monoclonal antibody JSB1. On the other hand, no major differences were found between the histological groups when the samples with the highest mdr1 expression were selected to represent the individual tumors. Those samples are less informative. They might be derived from tumor regions in which capillaries deliver a larger fraction of the total mRNA pool. No induction of mdr1 was observed in some early astrocytoma or glioblastoma cell cultures even after administration of high concentrations of the drugs ACNU and VM26, often used in glioma therapy.

Immunohistochemical expression of P-glycoprotein and glutathione S-transferases in cerebral gliomas and response to chemotherapy.

The expression of the drug resistance-related proteins glutathione S-transferases (GST) and P-glycoprotein (Pgp) was analyzed quantitatively in samples of 53 astrocytic gliomas (eight WHO grade 1, 11 WHO grade 2, 9 WHO grade 3 and 25 glioblastomas, WHO grade 4). Sections of these tumors were immunohistochemically stained with antibodies to Pgp (MDR1-gene product) and to GST subclasses alpha, mu and pi. Pgp expression was not detected in tumor cells of the majority of low-grade astrocytomas (69%) and the percentage of Pgp stained cells generally increased with tumor grade. However, 4 of the 34 malignant gliomas were negative. Many neoplastic cells of most tumors were dominantly stained for GST-pi. The other two subclasses were expressed in a less consistent fashion with no linear correlation to grading. Grade 2 astrocytomas exhibited the highest percentage of cells with GST expression. GST-alpha was absent in 9 tumors, GST-mu in 8 and GST-pi in 4. Four tumors showed no expression of any GST subclass or Pgp in neoplastic cells. Of 13 patients 5 with a more favorable clinical course after radiation and chemotherapy had a lower percentage of neoplastic cells immunostained for Pgp and the three GST subclasses than 8 patients with a worse clinical course. These results suggest a relationship between expression of drug resistance-related proteins in gliomas and response to chemotherapy with ACNU/VM26.

[Malignant angioendotheliomatosis as a rare cause of cerebrovascular insufficiency]. / Die maligene Angioendotheliomatose als seltene Ursache der zerebrovaskulären Insuffizienz.

Malignant angioendotheliomatosis, so called intravascular malignant lymphomatosis or angiotropic lymphoma, was found in cerebral hemispheres, spinal cord and nerve roots of a 50-year-old woman who died 4 months after onset of neurological symptoms. The pathological findings were characterised by neoplastic cells within the lumina and wall of small vessels as well as by multiple infarcts in the CNS. Vascular occlusions were caused by tumor cells and secondary changes of the wall. Positive reactions of Common Leucocyte Antigen and B-cell-markers support the idea of a lymphoid origin for the tumor cells. The differentiation to the angiocentric lymphoma as a T-cell tumor and the obscure pathogenesis of this neoplastic process must be clarified in the future.