Management of intracranial tuberculoma in children

Thirty-one patients were studied during a period of 3 years in order to identify features helpful for the diagnosis of tuberculoma. Sixteen had a history of pyrexia, 4 had had contact with cases of tuberculosis, the tuberculin test was positive in 15, the erythrocyte sedimentation rate (ESR) was elevated in 23, and 5 had concomitant tuberculous infections. Three had multiple lesions and 10 showed CT scan features suggestive of tuberculoma. Nineteen patients were successfully treated with drugs alone; seven needed surgery because they failed to respond to drugs clinically or because CT indicated no improvement. One patient proved to have a tumor, having shown an absence of response to drugs; four were operated on without drug trial because they were thought to have a tumor, and 1 needed surgery because of the mass effect of a very large tuberculoma. Infratentorial lesions associated with hydrocephalus were treated with ventriculoperitoneal shunts.     

Chemotherapy-induced scleroderma: a pleiomorphic syndrome

A scleroderma-like disease has recently been described in association with taxanes. We present the first case of diffuse scleroderma occurring in a woman treated with doxorubicin and cyclophosphamide for breast cancer. The clinical pattern of skin involvement and histological alterations were identical to those found in the classical form of scleroderma. Skin involvement progressed to affect 80% of total body area, and subsequently remained unchanged despite progression of the underlying cancer, making a paraneoplastic aetiology of the scleroderma unlikely. Specific chemotherapeutic agents might be directly responsible for the clinical manifestations and the parameters of progression. Analysis of all similar case reports defines the particular features and clinical course of this phenomenon.     

Usefulness of various MRI sequences in the diagnosis of viral encephalitis

There is paucity of studies regarding the utility of various conventional MRI sequences in the diagnosis of viral encephalitis. The present study evaluates the usefulness of various MRI sequences in acute viral encephalitis. 88 consecutive viral encephalitis patients, aged 2-72 years were subjected to clinical evaluation. Consciousness was assessed by Glasgow Coma Scale (GCS). Serum or cerebrospinal fluid (CSF) was analyzed for dengue, Japanese encephalitis (JE), herpes, measles, echo, coxsackie and polio viruses using ELISA or PCR. Cranial MRI was done and T1, T2, FLAIR and DW images were obtained. The MRI changes were correlated with type of encephalitis and duration of illness. All the patients had altered sensorium and 37 had seizures. 22 patients had JE, 9 had dengue, 8 had herpes simplex encephalitis (HSE), 2 had Epstein-Barr virus encephalitis (EBVE) and 47 had non-specific encephalitis. The median duration of MRI study from onset was 10 days. In JE (20/22), HSE (8/8), and EBVE (2/2), MRI abnormalities were more common compared to dengue (2/9) and non-specific (20/47) encephalitis. The MRI abnormalities were more common in FLAIR (57.1%) compared to T2 (52.9%), DWI (38.1%) and T1 (19.3%) sequences. The mean ADC value in JE patients was lower (974.0 ± 110.85 ×10⁻⁶ mm²/s) than HSE (1024.33 ± 485.76 × 10⁻⁶ mm²/s). Additional MRI lesions were seen in 12.6% cases on FLAIR sequence. FLAIR and T2 sequences were more sensitive in revealing abnormalities in viral encephalitis.     

Ocular distribution, bactericidal activity and settling characteristics of TobraDex® ST ophthalmic suspension compared with TobraDex® ophthalmic suspension

Introduction

TobraDex® ophthalmic suspension (tobramycin 0.3%, dexamethasone 0.1%; Alcon Laboratories Inc, Fort Worth, Tex) is frequently used for inflammatory ocular conditions where a risk of bacterial ocular infection exists. A new formulation, TobraDex® ST ophthalmic suspension (tobramycin 0.3%, dexamethasone 0.05%, Alcon), utilises a novel suspension technology to reduce viscosity and help prevent settling in the container.

Methods

A rabbit model that closely mimics the human eye and a clinical study with cataract patients was used to compare the pharmacokinetics and tissue permeability of TobraDex ST and TobraDex. An in-vitro model was used to assess the bactericidal activity using the rabbit tear concentrations of tobramycin 10 minutes after a single topical dose.

Results

Concentrations of both tobramycin and dexamethasone were greater in the tear film and ocular tissues of rabbits treated with TobraDex ST. There was an 8.3-fold increase in tobramycin concentration in the rabbit tear film 10 minutes after dosing with TobraDex ST compared with TobraDex. Concentrations of tobramycin and dexamethasone in ocular tissues from rabbits exposed to TobraDex ST were up to 12.5-fold greater relative to TobraDex. The in-vitro bactericidal activity (>99.9% kill, 3-log reduction) of TobraDex ST toward tobramycin-resistant and methicillin-resistant Staphylococcus aureus occurred in 90 minutes. TobraDex ST killed Streptococcus pneumoniae 3-log in 5 minutes. TobraDex had no activity toward tobramycin-resistant, methicillin-resistant S. aureus and required approximately 120 minutes for 3-log reduction of S. pneumoniae. In humans, the mean ratio of dexamethasone levels in the aqueous humour at 1 hour was 1.17 in favour of TobraDex ST.

Conclusion

TobraDex ST demonstrated improved suspension formulation characteristics, enhanced pharmacokinetic distribution and improved bactericidal characteristics, and may provide a useful alternative as compared to TobraDex.     

Acute lymphoblastic leukaemia-type intensive chemotherapy to eliminate minimal residual disease after high-dose melphalan and autologous transplantation in multiple myeloma - a phase I/II feasibility and tolerance study of 17 patients

Aiming to target the minimal residual disease in patients with multiple myeloma, a phase I/II single centre study was undertaken for feasibility and tolerance of intensive acute lymphoblastic leukaemia consolidation chemotherapy (ALL-IC) as part of a strategy for post-transplant consolidation targeted at pre-B cells. Seventeen newly diagnosed patients with myeloma (median age 55 years; 30-65) were initially treated with courses of infused cyclophosphamide, vincristine, adriamycin and methylprednisolone (C-VAMP) followed by melphalan 200 mg/m2(HDM) and peripheral blood stem cell rescue (PBSC). Forty-seven percent were in CR and the rest in PR after HDM. ALL-IC consisted of vincristine, daunorubicin, etoposide, cytarabine, 6-thioguanine and prednisolone given over 5 days. All patients became neutropenic (<0.5 x 109/l) at a median of 10 days (4-18) and one of the 17 patients (5.8%) died 15 days post ALL-IC of sepsis. A further four have died of relapse with an overall survival (OS) of 67% at 4 years. Two of nine patients in PR at the time of ALL-IC achieved CR. Matched-pair analysis of 34 control patients shows no difference for OS and event-free survival between ALL-IC and controls. We conclude that ALL-IC given to myeloma patients after HDM/PBSC is as safe as when used in ALL and warrants further assessment in randomised trials for myeloma.     

The role of autologous transplantation in patients with multiple myeloma aged 65 years and over

Autologous stem cell transplantation after high-dose melphalan for the treatment with multiple myeloma has resulted in prolonged progression-free survival and overall survival in patients under 65 years. We have examined the role of autologous transplantation in 17 patients with multiple myeloma over 65 years at our centre using a matched pair analysis with younger patients. The median age of this cohort of patients over 65 years was 67 years (65-74) and their outcome and transplant-related morbidity was compared with 17 younger pair mates with a median age of 55 years (31-64). Sixteen patients received high-dose melphalan, and one received busulphan with autologous stem cell rescue. The high-dose therapy was well tolerated in both elderly patients and the matched pairs, with comparable time to recover neutrophils and platelets. Treatment-related mortality also did not differ significantly in both the groups. Median overall survival of the elderly patients was 3.59 years similar to 3.01 years of the pair mates (P = 0.92). Autologous stem cell transplantation after high-dose melphalan conditioning was equally well tolerated in groups of patients above and below 65 years. There was no difference in relapse rate, OS and myelotoxicity in both the groups. These findings suggest that advanced age should not be an exclusion criterion from autologous transplant programmes. Bone Marrow Transplantation (2000) 25, 533-539.