Chronic childhood idiopathic thrombocytopenia purpura: long-term follow-up

An understanding of the natural history of childhood chronic idiopathic thrombocytopenia purpura (ITP) could contribute to a rational therapeutic approach to its treatment, which remains controversial. In our retrospective study of 92 children with ITP, 22 had a chronic course and were followed for 3–14 years (median 8.6 years). Treatment, when indicated, was individualized: 4 patients (18.2%) did not receive any treatment, 14 (63.6%) received steroids only, while 4 (18.2%) were treated with steroids and one of the following: high-dose gamma globulin (4 patients), splenectomy (2 patients) or immunosuppressive therapy (2 patients). During follow-up, 14 patients (63.6%) achieved complete remission, 5 (22.7%) partial remission and only 3 (13.5%) remained severely thrombocytopenic, with minimal bleeding tendency. Eleven patients (50%) responded to the initial prednisone course (1–5mg/kg/day), but showed a marked decrease in platelet count when steroids were tapered off. In view of the high rates of complete and partial remission and the mild course of the few non-responding patients, it is suggested that with adequate supportive therapy, follow-up problems and fatalities can be kept to a minimum. We believe that aggressive therapy, such as splenectomy, should be reserved for the rare symptomatic and severely thrombocytopenic patient.     

Achondrogenesis type I. A familial subvariant?

The clinical, pathological, and radiological features of 2 male sibs with a severe and lethal form of micromelic dwarfism are desribed. The family also includes 2 normal sibs. The histological and radiological appearances suggested a diagnosis of achondrogenesis type I, but the markedly deficient ossification of the skull and the presence of intrauterine rib fractures were atypical. These changes have been observed in two other families with 2 or more infants with suspected achondrogenesis, raising the possibility that these familial cases may be a subvariant of achondrogesis or even a distinct disease entity. The disease appears to be inherited as an autosomal recessive and death occurs shortly after birth because of severe pulmonary hypoplasia.     

Benzene and non-Hodgkin's lymphoma

Incidence rates for non-Hodgkin's lymphoma (NHL) have been rising throughout the world for several decades, and no convincing explanation exists for the majority of this increase. The commonest subtypes of NHL have no well-defined aetiological factors but lymphoma development has been linked with exposure to a variety of chemicals, including nitrates, pesticides, herbicides, and solvents. Benzene, a solvent and important constituent of petrochemical products, is a potent lymphomagen in experimental animals and high-dose exposure in humans is associated with both acute myeloid leukaemia and NHL. Much current interest centres on the possibility that environmental benzene exposure in the general public may underlie a proportion of the increase in NHL. Seventy per cent of benzene exposure in the environment is derived from vehicle exhaust emissions, whose increase has closely paralleled the rise in frequency of the disease. Mathematical modelling has been used to calculate an acceptable concentration of benzene in air based on risk estimates derived from industrial exposure, but the recommended target concentration in the U.K. of 1 ppb is regularly exceeded in urban locations. Detailed investigation of the health effects of low-level benzene exposure awaits an accurate assay for quantifying long-term human exposure. The (32)P post-labelling technique for the detection of toxin-specific DNA adducts is extremely sensitive and has been applied in the biomonitoring of exposure to a number of carcinogens, but benzene-DNA adducts have to date proved elusive of detection.     

Idiopathic avascular necrosis of the scaphoid: Preiser's disease

Preiser's disease, or idiopathic avascular necrosis of the scaphoid, is a rare, albeit often debilitating, condition. Although unknown, the etiology is probably multifactorial, with biomechanical or anatomical variations leading to an "at risk" scaphoid. Most commonly the diagnosis is made with the use of plain radiographs, but one should not hesitate to use MRI for both confirming the diagnosis and evaluating the stage of the disease. Current treatment algorithms are not standardized, and many scaphoids degenerate to a point that a salvage procedure is required. The authors attempt a revascularization procedure if the disease is caught early and the scaphoid has not yet gone on to collapse and degenerate. We save our salvage procedures for advanced cases with periscaphoid arthritis.     

Effect of incremental exercise on initiation and movement times in a choice response, whole body psychomotor task

Objectives: To examine how exercise at moderate and maximal intensities affects performance on a choice response time, whole body psychomotor task. Methods: Subjects (n = 12) were tested on a three-choice response time task, after rest and after exercise at 70% and 100% maximum power output (W^·_max). The dependent variables were time to begin forward momentum (initiation time) and time to complete the movement (movement time). Stride time for the first and second strides and number of strides to cover first 1.1 m were also measured. Blood lactate concentrations and heart rate were recorded before and after completion of each psychomotor test. The subjects subjectively assessed the amount of effort that they used to complete the task. Results: Repeated measures analysis of variance showed a significant effect for initiation (F_2,22 = 11.47, p<0.001) and movement times (F_2,22 = 14.61, p<0.001). Post hoc least significant difference (LSD) tests showed that initiation time after exercise at 70% W^·_max was significantly faster than that in the other two conditions. Speed of initiation after rest was significantly quicker than that after exercise at W^·_max. For movement time, LSD tests showed that time after maximal exercise was significantly slower than that in the other two conditions. Stride time for the second stride showed a significant effect (F_2,22 = 6.20, p<0.01). LSD tests found that time after exercise at W^·_max was significantly slower in the other two conditions. Stepwise multiple regression analyses found that the increment of change, from rest, of lactate concentrations could significantly predict the increment of change in initiation (R² = 0.40) and movement (R² = 0.50) times. Conclusions: Exercise affects a whole body task differently from purely cognitive tasks. Central factors are probably more important than peripheral factors.     

Phase I trial of high-dose tamoxifen in combination with cisplatin in patients with lung cancer and other advanced malignancies

BACKGROUND: Tamoxifen has been reported to enhance the antitumor activity of cisplatin in preclinical models by modulation of protein kinase C signal transduction and apoptosis-related pathways. METHODS: We conducted a phase I study of high-dose oral tamoxifen in combination with intravenous cisplatin, with two objectives: 1) to determine tolerability, and 2) to determine the daily tamoxifen dose required to achieve serum levels equivalent to in vitro concentrations reported to enhance cisplatin cytotoxicity in preclinical models. Tamoxifen was administered days one through seven at escalating daily doses of 160 mg/m2 (n = 5), 200 mg/m2 (n = 6), and 250 mg/m2 (n = 4) by patient cohort, followed by cisplatin at 100 mg/m2 on day eight. Serum concentrations of tamoxifen and its hydroxylated metabolite N-desmethyltamoxifen were determined by high-performance liquid chromatography (HPLC) on day eight of the first treatment cycle in seven patients. RESULTS: Fifteen patients with advanced malignancies received treatment with tamoxifen at 160 mg/m2, 200 mg/m2, and 250 mg/m2 per cycle, respectively. Serum concentrations of tamoxifen and N-desmethyltamoxifen on day eight of the first cycle ranged from 1.75-8.22 microM (mean 4.72 microM) and 3.62-10.85 microM (mean 3.87 microM), respectively. Toxicity analysis demonstrated that grade 3/4 nonhematological toxicity occurred in 0/5 at a tamoxifen dose of 160 mg/m2, 1/6 at a tamoxifen dose of 200 mg/m2, and in 1/4 patients at the 250 mg/m2 dose level. No grade 4 hematological toxicity occurred. Classic dose-limiting toxicity was not observed; the trial was closed to further accrual after documentation that targeted tamoxifen levels (around 5 microM) were achieved with daily tamoxifen doses > or = 160 mg/m2 in combination with cisplatin. CONCLUSIONS: This regimen of high-dose tamoxifen in combination with cisplatin can be safely administered. Serum tamoxifen levels comparable to concentrations required for enhancement of cisplatin sensitivity in vitro are clinically achievable with acceptable toxicity. The level of antitumor activity in nonsmall cell lung cancer NSCLC is encouraging (partial response in 4/10 patients). Based on these data, a Phase II study of high-dose tamoxifen in combination with cisplatin in patients with metastatic NSCLC is being conducted through the Southwest Oncology Group.     

An unusual case of pyrexia of unknown origin with cervical lymphadenopathy

Kikuchi's disease is usually a self limiting illness characterised by pyrexia, neutropenia, and cervical lymphadenopathy particularly in young women of Asian descent. This often leads to an initial misdiagnosis of lymphoma. A case of a young Asian woman who presented with pyrexia of unknown origin is described.