Oncogenesis in utero: fetal death due to acute myelogenous leukaemia with an MLL translocation

The incidence of translocations involving the 11q23 gene MLL is markedly increased in leukaemias that occur in infants < 1 year of age. Epidemiological and molecular data have demonstrated that at least some of these translocations occur in utero . In this report we describe a case of fetal death at 36 weeks of gestation. At autopsy the fetus was found to have widely disseminated acute myelogenous leukaemia (AML), FAB subtype M5. Molecular cytogenetic studies of nuclei recovered from paraffin-embedded tissue sections demonstrated that the leukaemic cells contained an MLL translocation. This is the first detailed report, to our knowledge, of fetal death due to acute leukaemia, and directly demonstrates oncogenesis in utero .     

Analogues of oxybutynin. Synthesis and antimuscarinic and bladder activity of some substituted 7-amino-1-hydroxy-5-heptyn-2-ones and related compounds

Oxybutynin chloride [4-(diethylamino)-2-butynyl alpha-cyclohexyl-alpha-hydroxybenzeneacetate hydrochloride, Ditropan] is widely used for the relief of symptoms in neurogenic bladder. This is a result of its combined anticholinergic, antispasmodic, and local anesthetic activities. In a study directed toward development of agents possessing the beneficial properties of oxybutynin, but having a longer duration of action, a series of metabolically more stable keto analogues of the parent ester, i.e. substituted 7-amino-1-hydroxy-5-heptyn-2-ones along with some analogues and derivatives, was prepared and evaluated for in vitro and in vivo antimuscarinic action in guinea pig preparations. Several members of the series were potent antimuscarinics having a longer duration of activity than that of oxybutynin in a guinea pig cystometrogram model. On the basis of its in vitro and in vivo antimuscarinic activity, coupled with a 5-fold greater duration of action than that of oxybutynin, 1-cyclobutyl-7-(dimethylamino)-1-hydroxy-1-phenyl-5-heptyn-2-one (14b) was selected for clinical evaluation.     

Effect of projective aspect variations on estimates of changes in bone mass using digital subtraction radiography

This study tests the hypothesis that estimates of changes in bone mass derived from subtraction data obtained in accord with published methods are independent of the spatial aspect of the lesion being evaluated when calibrations are performed independently. Nineteen sliver-shaped bone chips ranging in mass from approximately 1 to 35 mg were orientated with broad side parallel to the facial surface of a hemisectioned dry human mandible and radiographed using conventional exposure parameters on conventional E-speed dental X-ray film. Also attached to the film was a standardized aluminum calibration wedge that facilitated quantitative analysis of resulting subtraction data using established methodology. The effects of scatter were simulated by the addition of a 1-cm-thick slab of tissue-equivalent plastic. A second series of exposures then was produced using the same respective spatial chip locations and projection geometries but each chip was reorientated such that its broad side was now positioned perpendicular to the mandibular facial surface. Finally, a comparable series of control exposures was produced without any chips or calibration wedge to facilitate subtraction. When paired bone estimates derived from the two chip orientations were compared (paired comparisons) using Student's t-test, a statistically significant difference (p<0.05) was observed. These results also were tested for statistical significance using the non-parametric Wilcoxon test. As with the parametric analysis, the discrepancy between the parallel and perpendicular mass estimates was found to statistically significant (p<0.05). The methods employed in this investigation thus resulted in bone mass estimates that varied significantly depending upon lesion orientation.     

Ureteral obstruction secondary to indinavir in the pediatric HIV population

Indinavir sulfate is a protease inhibitor used in the treatment of the human immunodeficiency virus (HIV). This case report describes the radiographic and urologic manifestations of indinavir urolithiasis in two pediatric patients with acquired immunodeficiency syndrome (AIDS). Management involves aggressive hydration and surgical intervention when indicated. Received: 29 January 1998 Accepted: 16 March 1998     

Pulsed Radiofrequency Application in the Treatment of Chronic Pain

Abstract:   The efficacy of pulsed radiofrequency (PRF) in the treatment of painful lumbosacral spondylosis has been reported. This case series reviews 22 consecutive patients presenting to clinic who had been previously treated with PRF with good results. Patients being prescribed opioids were excluded. During the PRF application, tissue temperature was limited to 43°C. A minimum of 200 mA of current was delivered in each case. The minimum current (at 50 Hz) necessary to stimulate the involved nerve was recorded. The duration of time from PRF treatment until the patient requested a subsequent application was documented. The effective duration of PRF in patients treated for lumbosacral spondylosis ranged from 5 to 18 months (mean ± SD: 9 ± 3.7 months; n  = 16). PRF applications to dorsal root ganglia were effective from 2 to 12 months (7 ± 3.8 months; n  = 8). Similar results were observed when PRF was applied to cervical medial branch nerves, one suprascapular nerve, and one stellate ganglion. The mean (50 Hz) sensory stimulation thresholds obtained before treatment ranged from 0.08 V to 0.14 V. In this select population of patients not receiving controlled substances, who had a favorable response to a previous PRF application, the duration of pain relief supports the use of PRF as an effective pain treatment.     

Sleep disordered breathing in chronic stroke survivors. A study of the long term follow-up of the SCOPES cohort using home based polysomnography.

Prevalence of sleep-disordered breathing (SDB) (apnea-hypopnea index [AHI] > or = 5) in acute stroke patients ranges between 44% and 95%, compared to the community prevalence, 9 to 35% for women and 8 to 57% for men [age range 30-60 years]. Limited data exists beyond 3 months following stroke. We assessed the prevalence of SDB amongst stroke survivors at 3 years and compared results to data reported in normal and elderly populations. 90/143 eligible stroke survivors from an existing cohort underwent a home based sleep study. Mean age of the 78 subjects with a valid sleep study was 64 years (SD 15). Prevalence of SDB (AHI > or = 5) was 81% (95% CI 72% to 90%) and sleep apnoea syndrome (AHI > or = 5 plus ESS score > or =11) was 20% (95% CI 11% to 29%). Important predictors for AHI > or = 15 were haemorrhagic stroke (aOR12.06 [1.42-102.74]) and stroke severity at 1 month (aOR4.15 [1.05-16.38]). Large case-control studies are needed.     

Abrogation of the fibrotic effect of transforming growth factor-β in dermal wound healing

The growth factor, transforming growth factor-beta1, which under normal circumstances promotes wound healing by stimulating local fibroblasts to produce collagen and other extracellular matrix proteins, has also been implicated as the primary causative agent of fibrosis. Because transforming growth factor-beta1 is capable of stimulating its own production by fibroblasts, its normally beneficial effects may become amplified to the point where excess extracellular matrix accumulation occurs, thereby causing abnormal scarring. Therefore, strategies that block or counter the effects of transforming growth factor-beta1 may be useful in preventing or decreasing fibrosis. One such strategy is the use of glucocorticoid steroids such as dexamethasone, which normally have the opposite effect of transforming growth factor-beta1, namely the impairment of wound healing. When used in conjunction with transforming growth factor-beta1, glucocorticoid steroids may normalize the effect of transforming growth factor-beta1 on collagen synthesis, thereby reducing excessive collagen deposition and fibrosis.