Nonspecific excitatory effects of morphine: Reverse-order precipitated withdrawal and dose-dose interactions

We recently reported that, in naive mice pretreated with naloxone, morphine can cause withdrawal-like signs that seemingly are not mediated by opiate receptors. Such results were confirmed and extended here with another mouse strain. Repetitive vertical jumping could occur irrespective of injection sequence and depended on dose and dose ratio of the two drugs.     

Should patients with asymmetrical noise‐induced hearing loss be screened for vestibular schwannomas?

Should patients with asymmetrical noise‐induced hearing loss be screened for vestibular schwannomas? The Peterborough ENT department receives many referrals for MoD personnel who have suffered hearing loss from occupational noise exposure. Those patients with asymmetrical sensorineural hearing loss are routinely screened for vestibular schwannomas by MRI scanning. Scan reports from the past 5 years have been reviewed and out of 152 scans, four revealed vestibular schwannomas giving a pick‐up rate of 2.5%, which compares favourably with other published pick‐up rates. Review of the audiograms in these cases suggests that they can be misleading in this context. The conclusion is that patients with noise‐induced asymmetrical hearing loss should be screened for acoustic neuromas.     

Intramedullary nailing of femoral fractures in adolescents

Fifty femoral shaft fractures were treated with reamed, interlocking, intramedullary nails utilizing a greater trochanteric starting point from 1991 through 1998. The 17 girls and 31 boys ranged in age from 10 to 16 years (mean, 13.2 years) at the time of injury. Average follow-up after fracture was 16 months. All fractures united, and the average leg-length discrepancy was 1 mm (range, -10 mm to +11 mm). No patient had angular or rotational deformities. No patients developed osseous necrosis of the femoral head. Despite intramedullary nailing through the greater trochanteric apophysis, articulotrochanteric distance measurements increased only 4.5 mm at the time of last follow-up. No patient developed significant proximal femoral deformity with some follow-up as far as 60 months from the time of surgery. Intramedullary nailing through a trochanteric starting point is a safe, effective method for treating femur fractures in this adolescent age group.     

Incidence of apnoea and bradycardia in preterm infants following DTPw and Hib immunization: A prospective study

Objective: To evaluate the incidence and severity of apnoea and bradycardia in hospitalized preterm infants following immunization at 2 months of age, and identify risk factors.
Methodology: A prospective study of 98 preterm infants, of gestational age 24–31 weeks, immunized at approximately 2 months post natal age with diphtheria-tetanus-whole cell pertussis vaccine (DTP_w) in the neonatal intensive care unit (NICU) at King George V Hospital Sydney. Half the infants also received Haemophilus influenzae type b conjugate vaccine (Hib) simultaneously. All infants were monitored for apnoea and bradycardia in the 24 h periods pre- and post immunization.
Results: Only one infant had apnoea and/or bradycardia pre-immunization compared with 17 post immunization. For 12 infants these events were brief, self-limiting and not associated with desaturations (oxygen saturation <90%). However, for five infants (30%) these events were associated with oxygen desaturation and two of these infants required supplemental oxygen. The group that had apnoea and/or bradycardia and the group that did not were not significantly different in terms of gestational age, birth weight and other variables. Infants who received Hib together with DTP_w were less likely to have apnoea and/or bradycardia than those given DTP_w alone.
Conclusion: When considering immunization for preterm infants, the benefits of early immunization must be balanced against the risk of apnoea and bradycardia. We recommend that the cardio-respiratory function of hospitalized infants born at less than 31 weeks gestation be monitored for 48 h post immunization.     

Phase I study of temozolomide in paediatric patients with advanced cancer. United Kingdom Children's Cancer Study Group.

A phase I study of temozolomide administered orally once a day, on 5 consecutive days, between 500 and 1200 mg m(-2) per 28-day cycle was performed. Children were stratified according to prior craniospinal irradiation or nitrosourea therapy. Sixteen of 20 patients who had not received prior craniospinal irradiation or nitrosourea therapy were evaluable. Myelosuppression was dose limiting, with Common Toxicity Criteria (CTC) grade 4 thrombocytopenia occurring in one of six patients receiving 1000 mg m(-2) per cycle, and two of four patients treated at 1200 mg m(-2) per cycle. Therefore, the maximum-tolerated dose (MTD) was 1000 mg m(-2) per cycle. The MTD was not defined for children with prior craniospinal irradiation because of poor recruitment. Plasma pharmacokinetic analyses showed temozolomide to be rapidly absorbed and eliminated, with linear increases in peak plasma concentrations and systemic exposure with increasing dose. Responses (CR and PR) were seen in two out of five patients with high-grade astrocytomas, and one patient had stable disease. One of ten patients with diffuse intrinsic brain stem glioma achieved a long-term partial response, and a further two patients had stable disease. Therefore, the dose recommended for phase II studies in patients who have not received prior craniospinal irradiation or nitrosoureas is 1000 mg m(-2) per cycle. Further evaluation in diffuse intrinsic brain stem gliomas and other high-grade astrocytomas is warranted.     

Chronic cerebral hypoperfusion: loss of pupillary reflex, visual impairment and retinal neurodegeneration

Adult rats underwent permanent bilateral occlusion of the common carotid arteries (2VO) to determine the effect of chronic cerebral ischemia on vision and retina. They were monitored post-surgically for the presence of the pupillary reflex to light. Some rats were tested for 6 months post-surgically on a radial arm maze task and then tested in another water-escape task which explicitly tested visual function. Another group of rats were tested post-surgically for 3 months on a task which simultaneously assessed visual and tactile discrimination ability. The thicknesses of the retinal sub-layers were then measured for some rats. Fourteen of the 25 rats that underwent 2VO lost the pupillary reflex. This seemed to occur within 5 days. Rats that lost the pupillary reflex but not rats whose reflex was intact, were impaired on all visually guided mazes. Tactile discrimination ability was unaffected. Only rats that lost the pupillary reflex showed reduced thickness of the retinal outer nuclear and plexiform layers, reduced cell density in the retinal ganglion cell layer and astrocytosis and degeneration of the optic tract. We conclude that 2VO can eliminate the pupillary reflex. Photoreceptors and retinal ganglion cells degenerate, but it is unclear if these are the cause(s) or result(s) of the loss of the pupillary reflex. These effects are accompanied by impairment of visually guided behavior. The possibility that visual system damage may also occur in acute ischemia merits further investigation.