Prognostic impact of meningeal dissemination in primary CNS lymphoma (PCNSL): experience from the G-PCNSL-SG1 trial.

BACKGROUND: We evaluated the frequency and prognostic impact of meningeal dissemination (MD) in immunocompetent adult patients with primary central nervous system lymphoma treated in a randomized phase III trial. PATIENTS AND METHODS: MD was evaluated at study entry and defined by lymphoma proof in the meningeal compartment detected by at least one of the following methods: cerebrospinal fluid (CSF) cytomorphology, detection of clonal B cells by IgH PCR in CSF or contrast enhancement of the leptomeninges on magnetic resonance imaging (MRI). RESULTS: Data on MD were available in 415 patients, of those, MD was detected in 65 (15.7%): in 44/361 (12.2%) by CSF cytomorphology, in 16/152 (10.5%) by PCR and in 17/415 (4.1%) by MRI. Major patients' characteristics and therapy did not significantly differ between patients with MD (MD+) versus those without MD (MD-). There was a significant correlation of MD with CSF pleocytosis (>5/µl; P < 0.0001), but no correlation with CSF protein elevation (>45 mg/dl). Median progression-free survival was 6.7 months [95% confidence interval (CI) 0-14.5] in MD+ and 8.3 months (5.7-10.8) in MD- patients (P = 0.95); median overall survival was 21.5 months (95% CI 16.8-26.1) and 24.9 months (17.5-32.3), respectively (P = 0.98). CONCLUSION: MD was detected infrequently and had no impact on outcome in this trial.

Meningeal dissemination in primary CNS lymphoma: prospective evaluation of 282 patients.

BACKGROUND: The impact of meningeal dissemination in primary CNS lymphoma (PCNSL) is debated, and the reported frequency varies. We prospectively evaluated the diagnostic value of PCR in comparison with CSF cytomorphology and MRI for diagnosing meningeal dissemination in PCNSL. METHODS: We evaluated 282 patients from a multicenter therapy study for PCNSL for the presence of meningeal dissemination: 205 with CSF cytomorphology, 171 with PCR of the rearranged immunoglobulin heavy-chain genes in CSF, and 217 with cranial MRI. RESULTS: Meningeal dissemination was found in 33 of 205 patients (16%) by cytomorphology, in 19 of 171 (11%) patients evaluated by PCR, and in 8 of 217 patients (4%) by MRI. Considering either of these methods, the relative frequency of meningeal dissemination was 17.4% (49 of 282 patients). PCR was monoclonal in 6 of 19 (32%) samples with positive cytomorphology, 1 of 13 samples (8%) with suspicious cytology, and in 10 of 105 (10%) cytologically negative samples. In 11 samples with positive and 12 with suspicious cytology, PCR showed only a polyclonal pattern. The probability of meningeal dissemination detection was higher in cases with CSF pleocytosis (>5/microL) with an OR of 2.48 (95% CI 1.15-5.34, p = 0.018). CSF protein had no predictive value for meningeal dissemination detection. CONCLUSIONS: We found a low rate of meningeal dissemination in primary CNS lymphoma in this large prospective study. The rate of discordant PCR and cytomorphologic results was high. Thus, the methods should be regarded as complementary. CSF pleocytosis had predictive value for meningeal dissemination detection.

Prospective trial on topotecan salvage therapy in primary CNS lymphoma.

BACKGROUND: Standard salvage therapy has not been established for recurrent primary central nervous system lymphoma (PCNSL). We report the final results of a prospective study on topotecan chemotherapy in relapsed or refractory PCNSL. PATIENTS AND METHODS: The study included 27 patients with a median age of 51 years and an ECOG performance status of 2. Fourteen patients were refractory to the last therapy, and 13 relapsed after a median period of 6.0 months. Pretreatment with up to four regimens included chemotherapy in 26 patients and whole brain irradiation in 14. A 30-min daily topotecan infusion of 1.5 mg/m(2) for 5 days was repeated every 3 weeks. RESULTS: The response rate was 33% with five complete (CR) and four partial remissions (PR). The median follow-up was 37.7 months. All complete responders had sustained remissions lasting for 9 to 28 months. The median event-free survival (EFS) was 2.0 months (9.1 months in responders), the overall survival (OAS) was 8.4 months. CTC grade 3-4 leukopenia occurred in 26% and thrombocytopenia in 11% of the patients. Eight of 12 patients alive without cerebral lymphoma > or = six months after topotecan exhibited deficits attributable to late neurotoxicity. CONCLUSION: Topotecan as monotherapy is active in relapsed and refractory PCNSL with tolerable toxicity.

[Better health care for children and adolescents with attention deficit hyperactivity disorder]. / Betere gezondheidszorg mogelijk voor kinderen en adolescenten met aandachtstekort-hyperactiviteitstoornis.

Recently Donker et al. reported a massive rise in the prescription of methylphenidate by general practitioners in the northeast of The Netherlands. On comparing their results with national and international guidelines on the management of attention deficit hyperactivity disorder (ADHD) it would appear that medication is not always being prescribed to the correct group of children i.e. those with the core problems of ADHD. Girls are under-diagnosed, while boys frequently receive medication for oppositional or conduct problems, which are usually better treated by parent management training. Many children are never given the full multidisciplinary assessment recommended by the guidelines and it is unclear whether other evidence-based treatments such as school liaison or parent management training were offered. Overall it seems children with ADHD do not always receive the treatment they require. Improvement might be achieved if the European and Dutch recommendations are followed.

Response of relapsed or refractory primary central nervous system lymphoma (PCNSL) to topotecan.

The authors treated 16 immunocompetent patients with refractory or relapsed primary CNS lymphoma with topotecan. Fifteen patients had been pretreated with up to three chemotherapy regimens, three of them additionally with whole brain irradiation (WBI), and one with WBI alone. Four complete remissions and two partial remissions were achieved. Progression-free survival was 20% at 6 months and 13% at 12 months.

[Normal values and evaluation of the German parents' version of Strengths and DIfficulties Questionnaire (SDQ): Results of a representative field study]. / Normierung und Evaluation der deutschen Elternversion des Strengths and Difficulties Questionnaire (SDQ): Ergebnisse einer repräsentativen Felderhebung.

OBJECTIVE: The (SDQ) is a short questionnaire which addresses positive and negative behavioural attributes of children or adolescents. Being rated by parents or teachers, or as an equivalent self-report version, the 25 SDQ items were designed to include both strengths and difficulties. Although several reports have demonstrated the validity of the German SDQ, normative data have not yet been established. METHODS: In a nationwide representative field study, parent ratings were completed for 930 children and adolescents aged between 6 and 16 years. Following verification of the scale structure by factor analysis, the observed distributions of scores were used to define normal, borderline, and abnormal score ranges. Possible effects of gender, age, and social class were also investigated. RESULTS: Factor analysis yielded an exact replication of the original scales. Several associations with gender, age, and social status attained statistical significance, but cut-off scores for the five subscales remained stable in different subgroups. Age- and sex-specific bandings for the total problem score reflected small differences between homogeneous subgroups. CONCLUSIONS: After replication and confirming the original scale factors, the availability of normative data further enhances the diagnostic value of the SDQ and facilitates future validation studies. Present evidence suggests that the SDQ may serve as a useful and economical screening measure, and in many other clinical and research settings.

Interrater reliability for the basic categories of the AO/ASIF's system as a frame of reference for classifying distal radial fractures.

This study is about agreement on the assignment into the three basic classes or categories (A, B, C) of the Arbeitsgemeinschaft für Osteosynthesefragen/Association for the Study of Internal Fixation's (AO/ASIF) classification system for distal radial fractures. A random sample of 124 distal radial fractures was classified by two experienced observers. Their agreement was calculated according to Cohen's kappa statistic. To investigate the possible bases for disagreement, all conflicting X-ray assessments were discussed in a consensus meeting. It appeared that the kappa value was .65 (good agreement) before the meeting; kappa rose to .86 (excellent agreement) after the consensus meeting. It appeared that the undisplaced fractures were a major source of disagreement. Further, the presence of articular involvement was an important issue. It was frequently noted that one observer classified the fracture as extraarticular (basic Class A), while the other observer chose classification as an intra-articular fracture (basic Class C) or vice versa. This phenomenon has been called the A/C reversal shift. It is concluded that radiological innovations might enhance agreement on articular involvement, and a separate category for undisplaced fractures should be defined in the Arbeitsgemeinschaft für Osteosynthesefragen (AO) system. However, agreement on relevant distinctive features and discussion of conflicting assessments may also be important in achieving excellent agreement.

Acetabular fractures in children and adolescents.

A retrospective study of 29 acetabular fractures in children 2 to 16 years of age with an average followup of 14 years is presented. Nineteen patients had an additional dislocation of the femoral head and 14 patients had an associated neurologic injury. Surgical treatment was performed in 16 patients and consisted of open reduction and internal fixation in 14 patients and a simple arthrotomy in two patients. Thirteen patients were treated nonoperatively with traction or bedrest. The outcome was satisfactory in all patients with undisplaced fractures and fractures with disruption of a small fragment. Eight patients with linear fractures with instability all were treated surgically. All but one of the patients had a satisfactory functional outcome; one patient had early degenerative changes develop after an open pelvic and acetabular fracture. Patients with central fractures and dislocations had a relatively poor outcome, and congruency was achieved in only one of the four patients who were treated surgically. Results may deteriorate with time, as was seen when the results of the current study were compared with those published 10 years previously.

Parents and GPs at cross-purposes over hyperactivity: a qualitative study of possible barriers to treatment.

BACKGROUND: Although childhood hyperactivity is a common, serious, and treatable disorder, most affected children in Britain do not receive effective treatment. AIM: To investigate the views that parents and GPs hold about hyperactivity, and to explore how far these views, and clashes between these views, influence access to services. METHOD: Qualitative study making use of semi-structured interviews with 10 general practitioners (GPs) and 29 parents of hyperactive children drawn from parents' groups, community services, and specialist clinics. RESULTS: The views of parents and GPs differed markedly. Parents generally saw severe hyperactivity as a long-lasting, biologically-based problem that needed treatment in its own right and that benefited from diagnosis. Most of the GPs were unsure whether hyperactivity was a medical disorder warranting a label and specific treatment, and often saw it as a passing phase related to family stresses. Parents worried that professionals would blame them for their child's problem, whereas many GPs saw the parent's tendency to medicalise as a way to avoid thinking about their own shortcomings in parenting. CONCLUSION: Access to treatment was influenced by the views of parents and GPs, by the clashes between these views, and by each group's perceptions of the other group's beliefs. Clashes between the views of parents and GPs were particularly likely to lead to misunderstandings, dissatisfaction, and lack of access to effective help.

A name, what's in a name? The medicalization of hyperactivity, revisited.

Although attention-deficit hyperactivity disorder has in recent years become one of the most common psychiatric problems diagnosed in children, its status as a medical disorder remains controversial, especially in Britain. This study examines the experience of parents and doctors dealing with hyperactive children, focusing in particular on the process of medicalization. It alms at understanding what is at stake for families and doctors and asks about the role of a medical label in the therapeutic process. It uses an anthropologically informed methodology, in which qualitative semistructured interviews of 1-2 hours duration were held with 29 parents of hyperactive children and 10 general practitioners. Interviews were audiotaped; the content was transcribed and analyzed according to grounded hermeneutic theory. It was found that raising a hyperactive child can provoke a profound sense of alienation in parents. Family and social roles are affected, as are parents' views of themselves in their parental and social roles. Parents tended to experience medicalization and labeling as important aspects of validation and legitimation of their experience, which gave them a sense of control and led to improved parent-child relationships. Doctors felt more reluctant about such medicalization, fearing that it could lead to scape-goating the child and to self-fulfilling prophecies. It may be concluded that the medical framework, especially the medical diagnosis, can provide a powerful tool that has both advantages and disadvantages in the therapeutic process. In trying to avoid stigmatization, doctors can delegitimate parents' experience, thus increasing their suffering.

A historical review of the use of silver in the treatment of burns. II. Renewed interest for silver.

In 1965, Moyer revived interest in silver nitrate solution. He concluded on the basis on in vitro and in vivo studies that a 0.5% solution represented the lowest concentration at which antibacterial action (against Staphylococcus aureus, haemolytic streptococci and generally against Pseudomonas aeruginosa and E. coli) was obtained. Mafenide acetate was introduced a short time after the reintroduction of silver nitrate, followed a few years later by silver sulphadiazine. Thus, in a short period of time three medicaments appeared on the market which represented a radical change in the topical treatment of burns. The action of silver sulphadiazine has been intensively studied. Since silver sulphadiazine does not offer sufficient protection to prevent or retard the growth of gram-negative bacteria in patients with burns covering more than 50% of body surface, Monafo introduced the combined preparation silver sulphadiazine and cerium nitrate. Although various attempts have been made to develop more effective silver compounds, so far silver sulphadiazine still remains the most widely used substance of this type.

A review on the nonoperative removal of necrotic tissue from burn wounds.

The study of nonoperative debridement of burns got underway during the Second World War. A large number of substances such as enzymes of plant origin, acids and proteolytic enzymes of bacterial origin were examined since. The proteolytic enzymes derived from filtrates of C. histolyticum and B. subtilis have attracted the greatest interest. Although enzymatic debridement would seem at first sight to be an attractive form of treatment, unfortunately the results are highly variable.

Clinicians' recognition of 10 different types of distal radial fractures.

This study concerned baseline performance in recognition of 10 different types of distal radial fractures. Verbal tasks of admitting knowing about fractures and Visual tasks were designed for each fracture type. The Verbal task of admitting knowing consisted of a description with the relevant distinctive features of the fracture. The surgical resident was asked whether he admitted knowing the particular fracture described. The Visual task consisted of X-rays for which the subject had to label the fracture or identify its distinctive features. The test was presented to 30 surgical trainees working in five teaching hospitals. On the Verbal task of admitting knowing, scores were statistically significantly higher (68% "yes") than on the Visual task (33% correct). Responses met our criterion of 80% correct for the following fracture types: Colles's, distal forearm, and Smith's fracture. For seven other fracture types (combination radius and scaphoid, radial styloid process, dorsal Barton's, volar Barton's, pilon, chauffeur's, and lunate load fracture), the 80% criterion was not met. Analysis of the incorrect answers on the Visual task indicated that the surgical residents tended to label unknown fracture types as Colles's or Smith's fractures. Furthermore, the residents tended to overestimate their own diagnostic competence (overconfidence bias) for several fracture types. It was concluded that to improve diagnosis, the relevant distinctive features of distal radial fractures should be taught.

Comparing the German versions of the Strengths and Difficulties Questionnaire (SDQ-Deu) and the Child Behavior Checklist.

The Strengths and Difficulties Questionnaire (SDQ) is a brief behavioural screening questionnaire that can be completed in about 5 minutes by the parents and teachers of 4-16 year olds. The scores of the English version correlate well with those of the considerably longer Child Behavior Checklist (CBCL). The present study compares the German versions of the questionnaires. Both SDQ and CBCL were completed by the parents of 273 children drawn from psychiatric clinics (N = 163) and from a community sample (N = 110). The children from the community sample also filled in the SDQ self-report and the Youth Self Report (YSR). The children from the clinic sample received an ICD-10 diagnosis if applicable. Scores from the parent and self-rated SDQ and CBCL/YSR were highly correlated and equally able to distinguish between the community and clinic samples, with the SDQ showing significantly better results regarding the total scores. They were also equally able to distinguish between disorders within the clinic sample, the only significant difference being that the SDQ was better able to differentiate between children with and without hyperactivity-inattention. The study shows that like the English originals, the SDQ-Deu and the German CBCL are equally valid for most clinical and research purposes.

Moyamoya disease in a 12-year-old Caucasian boy presenting with acute transient psychosis.

This paper reports the case of a 12-year-old boy who presented with an acute transient psychosis. Investigations revealed Moyamoya disease with occlusion of the left middle cerebral artery. There was no previous history of transient ischaemic attacks, no history of psychiatric disease, no family history of psychosis and no history of illicit drug use. Although no previous cases of Moyamoya disease with psychosis as the sole presenting feature have been described, we suggest the possibility of a causal link.

Immune response capacity after human splenic autotransplantation: restoration of response to individual pneumococcal vaccine subtypes.

OBJECTIVE: To evaluate features of general immune function, in particular the restoration of the humoral immune response to pneumococcal capsular polysaccharides, in humans undergoing a spleen autotransplantation after splenectomy because of trauma. SUMMARY BACKGROUND DATA: After splenectomy, patients have an increased risk of overwhelming infection or sepsis involving encapsulated bacteria such as pneumococci. The value of human spleen autotransplantation after splenectomy because of trauma has long been questioned. Mononuclear phagocyte system function appeared to be similar to that in splenectomized persons. The presence of specific antipneumococcal antibodies would allow other parts of the mononuclear phagocyte system, such as those in the liver, to phagocytose opsonized bacteria. METHODS: Ten consecutive patients undergoing splenectomy followed by autotransplantation were compared with the next 14 consecutive patients undergoing splenectomy alone. After a minimum of 6 months, the patients were vaccinated with 23-valent pneumococcal vaccine. Blood samples were taken at the time of vaccination and after 3 and 6 weeks for antipneumococcal capsular polysaccharides IgM and IgG enzyme-linked immunosorbent assay against types 3, 4, 6, 9, 14, and 23. Splenic regrowth was evaluated by scintigraphy. RESULTS: Surprisingly, several of the nonautotransplanted patients showed scintigraphic activity, indicating the presence of either accessory spleens or traumatic seeding (splenosis). Significant antibody titer increases (more than twofold) were found for both IgM and IgG in the autotransplanted patients. Splenectomized-only patients showed no significant increase in Ig levels in patients without splenic regrowth and partial improvement in patients with splenosis/accessory spleens. CONCLUSIONS: Considering this significant antipneumococcal antibody increase, spleen autotransplants can be expected to permit an adequate humoral response to pneumococcal infections and presumably also to other TI-2 antigens, and to protect against overwhelming postsplenectomy infection or sepsis.

Fracture of the distal forearm: epidemiological developments in the period 1971-1995.

This study describes longterm epidemiological trends of 8361 distal forearm fractures out of 256,431 trauma patients (3 per cent) treated in a Dutch university hospital. The mean incidence rate across the whole lifespan was 42 per 10,000 inhabitants. The general picture was that the incidence rate decreased from 47 in 1971 to 38 per 10,000 in 1995. The highest age-specific incidence rate was found in the age group above 79 years (90 per 10,000), followed by the age group of 0-9 years (80 per 10,000). The pattern of aetiology did not change: the distribution was accidental fall (62 per cent), sports and leisure (19 per cent) and traffic (14 per cent). The rate of hospital admission increased from 6 per cent in 1971 to 14 per cent of patients in 1995. It appeared that the longterm increase of hospital admission can largely be attributed to patients younger than 50 years of age. It has been discussed that the rise in operative treatment may be explained by a growing population and a change in surgical policy leading to more indications to operate on distal forearm fractures.

External fixation for phalangeal and metacarpal fractures.

From 1987 to 1993 we treated 33 patients with 29 phalangeal and seven metacarpal fractures by external fixation using a mini-Hoffmann device. There were 27 open and 25 comminuted fractures. In 12 patients one or more tendons was involved. The mean follow-up was 4.4 years. Complications occurred in ten fractures; two required repositioning of the fixator. All the fractures healed. The functional results after metacarpal fractures were better than those after phalangeal fractures and fractures of the middle phalanx had better recovery than those of the proximal phalanx. Twenty-eight of the 33 patients were satisfied with their result. External fixation proved to be a suitable technique for stabilising unstable, open fractures with severe soft-tissue injuries.

Open reduction and internal fixation of combined fourth and fifth carpometacarpal (fracture) dislocations.

BACKGROUND: Traditionally, combined fourth and fifth carpometacarpal fracture dislocations are treated conservatively or by means of Kirschner wire after closed reduction. Since 1983, unstable dislocations have been treated with open reduction and screw fixation or with a temporary plate that bridges the fourth carpometacarpal (CMC) joint to maintain anatomical reduction. METHODS: In a retrospective study, we evaluated the results of this surgical approach in a group of 11 patients and another group of 4 conservatively treated patients. RESULTS: Eleven patients were treated by means of open reduction and rigid screw fixation (n = 6) or plate bridging of the fourth CMC joint (n = 5). Reduction and fixation of the fourth CMC joint always led to spontaneous anatomical reduction of the fifth CMC joint. At long-term follow-up, nine of these patients had full recovery of their hand function without any complaints. CONCLUSION: Open reduction and internal fixation of unstable ulnar CMC dislocations produced excellent results.