Does histology influence outcome in childhood Hodgkin's disease? Results from the United Kingdom Children's Cancer Study Group

PURPOSE: Histology has been identified as an important prognostic factor in Hodgkin's disease (HD) in adults. Information regarding the impact of histology on outcome in childhood HD is scarce. This study determines the effect of histology on the overall survival (OS) or progression-free survival (PFS) in a national series of children treated in a standardized manner. PATIENTS AND METHODS: The results of treatment of 331 assessable patients, treated between January 1, 1982 and June 30, 1992, in the United Kingdom Children's Cancer Study Group (UKCCSG) Hodgkin's study I were reviewed to evaluate OS, PFS, and deaths according to stage and histology. Treatment was either involved-field radiation alone (stage IA) or chlorambucil, vinblastine, procarbazine, and prednisolone (ChlVPP) chemotherapy with or without mediastinal radiation. All were clinically staged at diagnosis. RESULTS: Nodular sclerosing (NS) HD was the most common histologic subtype (155 of 331 patients [47%]) and was uniformly distributed through all stages. Lymphocyte-depletion (LD) HD was extremely uncommon (< 1%). Mixed-cellularity (MC) HD had the highest relapse rate, but this was only significant (P < .05) in stage I patients who received local irradiation alone. There was no other statistically significant difference in OS and PFS between the various histologic subtypes. Multivariate analysis for PFS and OS confirmed that stage was the most important prognostic factor and that histology did not have an effect after stratification by stage. CONCLUSION: This study demonstrates that with effective multiagent chemotherapy, histologic subtype does not influence outcome. The high relapse rates in stage I MC subtype indicates that MC HD is biologically aggressive and systemic treatment with or without local irradiation may be indicated. The high relapse rate in stage IV patients appeared to be independent of histology.     

Specific dietary interventions. Diabetes, osteoporosis, renal disease

A dietary treatment plan that considers both quality-of-care and quality-of-life issues is most beneficial for elderly patients. Diabetes can be successfully managed in most elderly patients with a liberalized diet that is low in simple sugars and includes variety and moderation in food choices. Although dietary management in osteoporosis may be most compelling in its preventive capacity, clinicians treating elderly patients with osteoporosis are well advised to consider supplementation of the diet with calcium and vitamin D in amounts equal to the RDAs if patients are unable to consume adequate calcium and vitamin D and if exposure to sunlight is minimal. Encouraging calcium intake, moderate exercise, maintenance of desirable body weight, and avoidance of laxative and antacid abuse with patients throughout the life cycle is appropriate preventive advice. The elderly renal failure patient may benefit from dietary modification of protein, potassium, sodium, fluid, vitamins, and minerals when complications associated with these nutrients are present. Because clinicians treat significant numbers of elderly diabetic, osteoporotic, and renal failure patients, and because many skilled nursing facilities are developing specialty and rehabilitation units for such high-acuity level patients, the clinician is well advised to know how to maximize quality of care and quality of life for these patients through appropriate dietary intervention.     

Oxygen mass transfer calculations in large arteries

Parkinsonism is characterised by overactive glutamatergic transmission in the cortico-striatal and subthalamo-medial pallidal pathways. Local blockade of glutamatergic transmission in these pathways can alleviate parkinsonian symptoms. The effectiveness of the treatment, however, is often limited by the simultaneous appearance of unwanted side-effects. These side-effects, including ataxia and dissociative anaesthesia, are particularly problematic when N-methyl-D-aspartate (NMDA) antagonists are used. In an attempt to overcome these problems we have attempted to manipulate excitatory amino acid (EAA)-mediated neurotransmission indirectly by targeting the NMDA receptor associated modulatory sites. We review evidence which demonstrates that antagonists for both the NMDA associated glycine and polyamine sites can reverse parkinsonian symptoms when injected intra-cerebrally in both MPTP-treated and bilateral 6-OHDA lesioned marmosets without eliciting unwanted side-effects. We further review preliminary data which suggest that ifenprodil, a polyamine site antagonist, has striking anti-parkinsonian actions in the marmoset. Potential mechanisms of action underlying these effects are discussed in terms of NMDA receptor subtypes and the neuroanatomical locus of action. The anti-parkinsonian efficacy of intra-striatally administered EAA antagonists leads us to question the view of dopamine acting in the striatum as a simple neuromodulator.     

Isolation of a non-sedimenting membrane fraction from the water soluble fraction of bovine lens

A membrane fraction was isolated from the water soluble fraction of bovine lens by increasing the density of the water soluble fraction with KBr and subjecting it to overnight centrifugation at 100000 g. We have called this fraction, which floats to the top of the mixture upon centrifugation, the non-sedimenting membrane fraction (NSMF). Electron microscopy of the NSMF revealed that it is composed of the expected membrane structures of unit membrane, fiber junction and cytoskeleton. Significantly less of the total membrane of the NSMF was devoted to fiber junction (22.8%) than in the sedimenting membrane fraction (SMF) (41.1%) prepared by sucrose density centrifugation of the water insoluble fraction. The NSMF accounted for about 7-12% of the total bovine lens membrane, and preliminary experiments demonstrated that a similar fraction could be isolated from the water soluble fraction of lenses from rats, rabbits, chickens and humans. The NSMF contained about 0.9 mg total lipid per mg total membrane protein, which was significantly greater than the value obtained for the SMF (0.5 mg total lipid per mg total membrane protein). The greater relative amount of total lipid in the NSMF was due to a significantly greater relative amount of phospholipid in the NSMF which was further reflected by the observation that the cholesterol: phospholipid molar ration of the NSMF (0.58) was significantly less than that of the SMF (0.88). Thus the relative lipid composition of the NSMF was significantly different than that of the SMF. Although the phospholipid content of the NSMF was greater than that of the SMF, the compositions of the phospholipids in the two membrane fractions were similar. The NSMF possessed essentially the same polypeptides (both extrinsic and intrinsic) which were found in the SMF. The NSMF was found to be distributed throughout the lens in a proportionate manner. We conclude that the NSMF may account for most of the lipid which remains in the water soluble fraction of the normal bovine lens after sedimentation of the water insoluble fraction. This membrane fraction substantially differs from the SMF in terms of structure and relative lipid composition. We speculate that the NSMF may represent a specialised domain of the fiber cell plasma membrane which has been previously unrecognized.     

Tuberculous meningitis: a 30-year review

Tuberculous meningitis remains an important illness that can be difficult to diagnose in a timely fashion and carries significant morbidity. We present a retrospective review of the cases of tuberculous meningitis diagnosed and treated at a single institution. Fifty-eight cases were identified and stratified according to stage of disease at presentation. Four patients (7%) died; three (5%) developed severe neurological sequelae. Poor outcomes were largely confined to cases presenting in an advanced stage and at the extremes of age. Corticosteroids were administered to 56 patients and may have contributed to the comparatively good outcome in these cases.