Shortage of paediatric radiologists acting as an expert witness: position statement from the British Society of Paediatric Radiology (BSPR) National Working Group on Imaging in Suspected Physical Abuse (SPA).

One of the most challenging areas of radiological imaging in children is the diagnosis of physical abuse. There is a dearth of paediatric radiologists willing to act as expert witnesses, particularly in the family courts. There are a number of reasons why radiologists may not be interested or willing to put themselves forward to work as expert witnesses in this field. A group of imaging experts recently formed the "British Society of Paediatric Radiology (BSPR) Working Group on Imaging in Suspected Physical Abuse (SPA)". The group comprises radiologists and neuroradiologists with current or previous experience of providing expert witness reports to the court in cases of SPA. The group met in January 2019 to explore pragmatic solutions to the chronic inefficiencies in both medical and legal practices and the challenges that arise from working in a legal arena with different structures, goals, and assessment criteria. Key issues concerned organisational inefficiencies, variable support from National Health Service Trusts and the Royal College of Radiologists to conduct this work, and the risk/benefit of involvement. This work is important for the patient, parents, and society in general, and highly rewarding for clinical practitioners who are involved, but there are several issues with current practices that discourage active participation. With several members of the group either retired or close to retirement, the shortage of experts is becoming a pressing issue within the UK, which requires an engaged multidisciplinary group to come up with creative solutions. Here, the group provide a consensus opinion highlighting the current barriers and potential facilitators to increasing the number of radiologists willing to provide opinions to the court.

The MonteggiaFracture: literature review and report of a new variant.

INTRODUCTION: Giovanni Battista Monteggia first described the Monteggia fracture in 1814. The complexity of this injury was not fully appreciated until it was coined in English as a "Monteggia lesion" by Jose Luis Bado. The Bado classification divides Monteggia fractures into four types of true lesions, plus equivalent variants. CASE REPORT: This report describes a rare variant where the proximal radial disruption occurs through a Salter-HarrisType II fracture rather than a radial epiphysis dislocation. This is an unstable fracture configuration that has been successfully surgically treated by keeping to the principles of Monteggia fracture reduction. CONCLUSION: Even though this is not a classical dislocation of the radial head, this variant with a Salter-Harris fracture should be considered as one.

c-fos mRNA levels are increased by the cellular stressors, heat shock and sodium arsenite.

Rapid, transient expression of the c-fos proto-oncogene is induced by the beta-adrenergic agonist, isoproterenol, in vivo and by numerous factors promoting growth and differentiation in cultured cells. We wanted to determine whether cellular stressors, which are known to induce expression of the gene encoding the major heat shock protein, hsp 70, also induced expression of the c-fos gene. Our findings demonstrate that c-fos mRNA levels increase transiently under conditions of heat stress or sodium arsenite treatment which induce expression of hsp70 mRNA in cultured cell lines. When 3T3 cells are heat shocked in the presence of amiloride, an inhibitor of Na+/H+ exchange, the induction of c-fos mRNA is partially inhibited, whereas that of hsp70 is somewhat enhanced. However, neither response requires ongoing protein synthesis. In fact, dramatic superinduction of c-fos mRNA is observed in cells which are heat shocked in the presence of the protein synthesis inhibitor, anisomycin. A comparison of relative rates of protein synthesis and c-fos mRNA levels during either heat shock or sodium arsenite treatment suggests that the transient suppression of protein synthesis accompanying these treatments may be one factor responsible for the observed c-fos mRNA induction.

Chromosomal localization and nucleoside diphosphate kinase activity of human metastasis-suppressor genes NM23-1 and NM23-2.

Human metastasis-suppressor genes nm23-1 (NME1) and nm23-2 (NME2) are implicated in control of the metastatic potential of malignant cells. Using somatic cell hybrid analysis and fluorescence in situ hybridization we co-localized both genes to 17q21.3. The 17q21 region carries the locus responsible for early-onset familial breast-ovarian cancer and several other genes that are involved in tumorigenesis and differentiation and undergo frequent rearrangements during neoplastic development. Thus, our mapping places the NME genes in a region that may be subjected to multiple selection pressures. NME1 and NME2 genes were expressed as soluble proteins in a T7 bacterial expression system. Both proteins are independently active nucleotide diphosphate kinases and readily form intra- and intermolecular disulfide bonds. The biochemical properties of these proteins may explain the diversity of mature eucaryotic nucleoside diphosphate kinases.

10-Piperazinyl-4H-theino[3,2-b][1,5]- and -[3,4-b][1,5]benzodiazepines as potential neuroleptics.

The synthesis of 10-piperazinyl-4H-thieno[3,2-b][1,5]benzodiazepines is described. The activity of these compounds has been assessed on the basis of their ability to produce hypothermia in mice and block a conditioned avoidance response (CAR) and produce catalepsy in rats, and the results are compared with various classical and nonclassical neuroleptic drugs. A number of compounds (6, 17, 21, and 22) demonstrate potency greater than clozapine and also show low degree of catalepsy. It is believed that this profile of activity, unlike standard neuroleptics, is associated with the relative lack of extrapyramidal side effects in the clinic. The corresponding 9-piperazinyl-4H-thieno[1,4]benzodiazepines (12 and 35, limited analogues prepared in the respective series, were inactive.

Synthesis and dopamine antagonist activity of 2-thioether derivatives of the ergoline ring system.

A series of 2-thioether derivatives of a number of clavine alkaloid (ergoline) ring systems have been synthesized and tested for dopamine antagonist activity. Of the compounds tested 2-(methylthio)-agroclavine (8,9-didehydro-6,8-dimethyl-2-(methylthio)ergoline) (6) was the most potent and had a profile of activity in animal models indicative of potential antipsychotic activity. The synthesis and biological activity of a number of metabolites of 6, including the 13-hydroxy derivative, are also reported.

The HIV-1 nef protein does not have guanine nucleotide binding, GTPase, or autophosphorylating activities.

Recombinant HIV-1 Nef proteins with either thr-15 or ala-15 have been constructed and expressed in the T7 bacterial system. From the soluble portion of bacterial lysates both Nef(thr-15) and Nef(ala-15) have been purified to near homogeneity through 6 nondenaturing chromatographic steps in the presence of MgCl2. Neither purified proteins display the previously reported GTP binding activity. Additionally Nef(thr-15) does not have autophosphorylating activity with either [gamma-32P]GTP or [gamma-32P]ATP. Although GTPase activity is present in the preparations of Nef proteins, it does not increase during purification and is attributed to bacterial contaminations.

Lethal syndrome of slender bones, intrauterine fractures, characteristics facial appearance, and cataracts, resembling Hallermann-Streiff syndrome in two sibs.

We report on a family in which 1 males infant who died neonatally and 1 female fetus at 29 weeks of gestation had an identical condition resembling Hallermann-Streiff syndrome. The long bones were slender with a few fractures, the skull was underossified, and the face was characteristic of Hallermann-Streiff syndrome. Bilateral cataracts were identified in the male. We regard the condition in this family as a severe form of Hallermann-Streiff syndrome, which appears to have been lethal, at least in the liveborn male. This syndrome is usually sporadic. Recurrence in sibs suggests the possibility of autosomal-recessive inheritance, or of a dominant mutation with parental mosaicism.

Adrenergic receptors mediate changes in c-fos mRNA levels in brain.

Recent evidence supports a role for transient c-fos expression as one step in signalling pathways by which membrane receptor-ligand interactions are transduced into appropriate intracellular responses. The activity of adrenergic receptors is mediated by second messenger systems which include ion fluxes, changes in cAMP concentration and enhanced phosphoinositide turnover. In order to determine if C-fos induction was also a step in adrenergic signal transduction in the brain, we performed in vivo studies with drugs specific for different adrenergic receptor types. Unexpectedly, we found that the stress associated with a single intraperitoneal (i.p.) injection of drug vehicle produced a transient increase (averaging 4.0-fold) in c-fos mRNA levels in rat brain. Injection of the alpha 2-adrenoreceptor antagonist, yohimbine, produced a transient increase which was larger in magnitude (averaging 9.6-fold) and longer in duration than that produced by injection of the drug vehicle alone. In experiments designed to ask whether either of these inductions was mediated by specific types of adrenergic receptors, we found that the alpha 2- and beta-adrenoreceptors were involved in both responses, while the alpha 1-receptor played a role in mediating the yohimbine induction, but no detectable role in the solvent induction. One hypothesis consistent with our results is that the norepinephrine (NE) released due to the stress associated with an i.p. injection interacts with postsynaptic beta-adrenergic receptors, resulting in the observed c-fos mRNA induction. When the negative feedback effect of NE, mediated by presynaptic alpha 2-receptors, is blocked by yohimbine, the postsynaptic response is enhanced and prolonged.

Structure of the gene coding for the human retinoic acid-inducible factor, MK.

The retinoic acid-inducible MK gene shows a distinct developmental pattern of expression, which implies that it has potential growth regulation and differentiation functions, particularly in the brain. We report here the cloning of the human MK gene from a phage library constructed from placental tissue. The structure of this gene has been determined using Southern hybridization and DNA sequence analysis. An isolated fragment was cloned and found to contain sequences identical to those of a previously isolated human MK cDNA clone, MKHC4. The gene contains three introns within the MK coding region as well as additional sequence, which indicates the presence of an intron prior to the putative protein start site. As judged by sequence analysis of cDNA clones, primer extension studies, and Northern analysis, the most abundant human MK message corresponds to the major mRNA of the previously described mouse gene. Primer extension studies and cDNA sequence data suggest that minor messages may be transcribed from the human gene, but no evidence of additional messages has been found by Northern analysis. This is in contrast to the mouse MK gene, from which three mRNAs are transcribed. Nevertheless, the similarity in the overall genomic structure of the human and mouse genes is striking.

Gastric pressure response to low dose dopamine infusion in normal man.

The gastric pressure response to distension was measured during intravenous infusion of dopamine at a rate of 2 mug min(-1)kg(-1) over 2h 50min in 5 normal volunteers to determine whether dopamine at this dose potentiated gastric adaptive relaxation, leading to a fall in gastric pressure and thus a potential delay in gastric emptying. This would be of obvious importance in patients being given dopamine at this dose to support renal function and at the same time being fed by nasogastric tube. The pressure response decreased during the first hour in all five subjects (p < 0.01). In 2 it recovered during the third hour to pre-infusion values, but in 2 it remained diminished; in 1 subject the results were equivocal. Circulating dopamine, noradrenaline and adrenaline concentrations all increased during dopamine (p < 0.05), but compared with control there was no difference in plasma free fatty acids, glycerol, cortisol or glucose concentrations. Dopamine at 2 mug min(-1) kg(-1) produced a transient fall in gastric pressure in all subjects, and a persistent fall in some. The changes in gastric pressures were seen at infusion rates that produced no metabolic or inotropic effects.

Colonic wall thickening is related to age and not dose of high strength pancreatin microspheres in children with cystic fibrosis.

OBJECTIVE: Colonic fibrosis causing stricture is a recently described complication in cystic fibrosis (CF). Studies have suggested that ultrasound evidence of bowel thickening predicts this complication and that it is prevalent among children receiving large doses of high-strength pancreatin preparations. We performed ultrasound studies on our patients to look for evidence of bowel wall thickening or early stricture. METHOD: Detailed colonic ultrasounds were carried out in 33 children with CF including 25 who had been receiving high-strength pancreatin (Creon 25,000) continuously for 3 years at the time of study. RESULTS: Median lipase intake was 19 330 U/kg/day (range 0-59 880 U/kg/day) and median protease intake was 387 U/kg/day (range 0-1170 U/kg/day). The combined thickness of mucosa, sub-mucosa and muscle layers was measured in ascending, transverse and descending colon using a 7.5 MHz transducer. Measurements were also made in nine healthy controls. There was no relationship between enzyme dosage and colon thickness but simple regression identified a significant relationship (P < 0.001) between age and maximum colon thickness in all three areas. The colon of CF children was up to 50% thicker than in controls. CONCLUSIONS: Thickening of the order described elsewhere did not occur among any of the children studied. The results suggest that the most important factor determining the thickness of the CF colon is age.

Bladder capacity in infants.

Bladder capacity was measured at micturating cystourethrography and normal ranges were established for children up to 1 year of age. Bladder capacity was compared with patient weight and distance from first lumbar to third lumbar vertebrae (L1 to L3). The simplified formula--Capacity (mL) = 7 x weight (kg)--was shown to give a reliable estimate of the expected bladder capacity in infants independent of age; this is useful in those infants whose weight lies outside the normal range for their age. Similarly, a formula was deduced relating expected bladder capacity to the measured L1 to L3 distance on an anteroposterior radiograph, which is of potential use to radiologists.

Taurodontism and disproportionate short stature.

A 13-year-old boy with taurodontism and disproportionate short stature is described. Parental consanguinity suggests the possibility of an autosomal recessive mode of inheritance.

Management of a heavily exuding, painful wound with necrotising subcutaneous infection.

Wounds with necrotising fasciitis are often malodorous and produce copious exudate. Selecting appropriate dressings can alleviate these symptoms and improve the patient's quality of life within a short time period.

The role of magnetic resonance imaging in the investigation of spinal dysraphism in the child with lower limb abnormality.

A review of magnetic resonance imaging (MRI) performed to exclude the presence of spinal dysraphism in children presenting with lower limb pathology is unrewarding in the absence of abnormal neurology. Over a 5-year period, 29 children ages 2 weeks to 15 years with a mean age of 6 years presenting with lower limb abnormalities were referred for MRI of the spine to exclude an occult neurologic cause for the deformities. More than one limb abnormality, for example pes cavus and limb length discrepancy, was present in 93% of the children, and 11 children had severe or recurrent talipes equinovarus deformity. Only two children (7%), both of whom had abnormal limb neurology, had abnormal MRI scans. In the absence of a demonstrable neurologic deficit in the lower limb, there appears to be no advantage in requesting MRI of the spine in children presenting with lower limb abnormality.