Plain radiography still is required in the planning of treatment for urolithiasis.

INTRODUCTION: Nonenhanced computed tomography (NCT) is recognised as the most sensitive tool in diagnosis of renal tract calculi. However, its role as the sole imaging investigation, for decisions regarding management is less clear. OBJECTIVE: To determine the proportion of new stone patient referrals in which management is altered by interpretation of a plain abdominal kidneys, ureters and bladder (KUB) radiograph in addition to NCT. METHODS: One hundred consecutive new referrals to a national lithotripsy centre were considered prospectively for treatment of renal tract calculi. RESULTS: A significant change in management was undertaken in 17 patients on the basis of KUB findings. Eleven patients had radio-lucent ureteric stones, for which Extracorporeal Shockwave Lithotripsy (ESWL) was consequently not possible and who required endoscopic management. There were six inaccuracies in measurement of size or positioning on NCT. In a further 43 patients it was not possible to confirm management until the KUB was reviewed, although in these cases ESWL or expectant management was still pursued. Thus additional imaging with a KUB was required in order to confirm optimum management in 60 patients. CONCLUSION: Additional plain radiography confers a significant advantage in the planning of treatment for urolithiasis once the diagnosis has been established by NCT because of information it provides regarding radio-opacity as well as stone size and visibility. This information cannot be delivered by NCT alone. We therefore recommend that KUB imaging is performed on all new stone patients referred for treatment.

Pancreatic trauma in children.

BACKGROUND/PURPOSE: The aim of this study was to determine the etiology, associated injuries, and outcome of children with pancreatic injuries. METHODS: A retrospective review was conducted of children under 16 years with pancreatic trauma admitted to the Children's Hospital at Westmead (CHW) from January 1983 to September 2002. Deaths were reported to the New South Wales Paediatric Trauma Death Registry (State Registry) from January 1988 to September 2002. RESULTS: Sixty-five cases were identified: 46 patients were admitted to CHW, and 22 deaths were reported to the State Registry (including 3 deaths at CHW). The median age was 6 years (range, 1 to 14 years). Boys accounted for 60% (n = 40) of cases, decreasing to 50% (n = 11) of those that died. Motor vehicle injuries (MVI) were the most common mechanism, accounting for 40% of survivors and 77% of those who died. Children were restrained incorrectly in 48% of all cases and in 67% of those who died. Significantly more children who died had head, chest, and abdominal visceral injuries, compared with those who survived. Death occurred as a result of head injuries in 68%, with only 3 deaths directly attributed to pancreatico-duodenal injuries. CONCLUSIONS: Pancreatic injuries remain uncommon in children. The most frequent mechanism was MVI, with incorrect use of passenger restraints an important contributing factor. Whereas mortality was mainly caused by other injuries, 3 deaths were directly attributable to pancreato-duodenal trauma.

Application of the Meckel's scan in a case of gastric corrosive injury.

This report describes a useful application of (99m)Tc-pertechnetate abdominal scintigraphy (Meckel's scan) in the assessment of gastric viability after corrosive injury. The Meckel's scan provided information about residual gastric mucosal function and prognosis in a less invasive manner than more usual methods.

Hippocampus-dependent learning and memory is impaired in mice lacking the Ras-guanine-nucleotide releasing factor 1 (Ras-GRF1).

Previous results have suggested that the Ras signaling pathway is involved in learning and memory. Ras is activated by nucleotide exchange factors, such as the calmodulin-activated guanine-nucleotide releasing factor 1 (Ras-GRF1). To test whether Ras-GRF1 is required for learning and memory, we inactivated the Ras-GRF1 gene in mice. These mutants performed normally in a rota-rod motor coordination task, and in two amygdala-dependent tasks (inhibitory avoidance and contextual conditioning). In contrast the mutants were impaired in three hippocampus-dependent learning tasks: contextual discrimination, the social transmission of food preferences, and the hidden-platform version of the Morris water maze. These studies indicate that Ras-GRF1 plays a role in hippocampal-dependent learning and memory.

Understanding pyoderma gangrenosum: a review.

CONTEXT: Diagnosis and management of pyoderma gangrenosum, a chronic, ulcerative cutaneous inflammatory disease often associated with systemic disease, requires a multidisciplinary approach. No large-scale, controlled trials have been conducted and, as a consequence, the knowledge of this condition is largely based on anecdotal reports. OBJECTIVE: To investigate current understanding of the diagnosis and management of pyoderma gangrenosum. DESIGN: Critical review article. Two hundred eighty-six articles, limited to articles in English and pertaining to humans, were retrieved and reviewed from a MEDLINE search spanning the years 1960-2000. CONCLUSIONS: Diagnosis of pyoderma gangrenosum often requires consultation by multiple specialists in different fields of medicine. Treatment is individually tailored and depends on disease severity and the presence of associated disease. Local treatment is sufficient for mild disease, and the use of immunosuppressive agents is reserved for severe or refractory cases, with cyclosporin being the agent of choice. The long-term outcome for these patients has not been established.

Retrospective review of reconstructive methods of conchal bowl defects following mohs micrographic surgery.

BACKGROUND: Mohs micrographic surgery has consistently been demonstrated to be the most effective method for excision of potentially aggressive lesions of the conchal bowl. A variety of techniques are employed to reconstruct the conchal bowl following surgery. OBJECTIVE: To explore the type and frequency of reconstruction techniques used and the factors influencing the surgeons choice of reconstruction METHOD: Retrospective analysis of 272 patients with conchal bowl tumors. RESULTS: Split thickness skin grafting was the preferred method of reconstruction. The histopathology of the lesions and the size of the post-Mohs defect did not influence the choice of technique, except for lesions less than 1 cm in which healing by secondary intention was favored. CONCLUSION: Tumor size, type, and aggressiveness did not influence repair technique choice. Surgeon preference was therefore the principle factor dictating method of reconstructive technique following Mohs micrographic surgery.

Identification of mesoderm development (mesd) candidate genes by comparative mapping and genome sequence analysis.

The proximal albino deletions identify several functional regions on mouse Chromosome 7 critical for differentiation of mesoderm (mesd), development of the hypothalamus neuroendocrine lineage (nelg), and function of the liver (hsdr1). Using comparative mapping and genomic sequence analysis, we have identified four novel genes and Il16 in the mesd deletion interval. Two of the novel genes, mesdc1 and mesdc2, are located within the mesd critical region defined by BAC transgenic rescue. We have investigated the fetal role of genes located outside the mesd critical region using BAC transgenic complementation of the mesd early embryonic lethality. Using human radiation hybrid mapping and BAC contig construction, we have identified a conserved region of human chromosome 15 homologous to the mesd, nelg, and hsdr1 functional regions. Three human diseases cosegregate with microsatellite markers used in construction of the human BAC/YAC physical map, including autosomal dominant nocturnal frontal lobe epilepsy (ENFL2; also known as ADNFLE), a syndrome of mental retardation, spasticity, and tapetoretinal degeneration (MRST); and a pyogenic arthritis, pyoderma gangrenosum, and acne syndrome (PAPA).

Physical localization of the mesoderm development (mesd) functional region.

The mesoderm development (mesd) functional interval is essential for primitive streak formation and mesoderm induction. Mesd is defined by overlapping albino (c) deletions on chromosome 7. We have constructed a bacterial artificial chromosome (BAC) contig that spans the mesd functional region. BAC end-sequence identifies three segments that recognize novel expressed sequences. Localization of the proximal breakpoints from Del(7)Tyr(c-3YPSd) and Del(7)Tyr(c-112K) within the contig defines a deletion interval of 310-350 kb that is essential for mesd function. Importantly, using BAC transgene rescue, we define a 75-kb mesd critical region containing at least one expressed sequence.

Physical localization of the mouse aryl hydrocarbon receptor nuclear translocator-2 (Arnt2) gene within the c112K deletion.

The albino deletions identify at least seven functional intervals essential for pre- and postnatal development in the 6- to 10-cM region surrounding the albino coat color (c = tyrosinase) locus on mouse chromosome 7. The c112K deletion identifies a putative thymus functional region not removed by the overlapping c3H deletion. Cloning the c3H proximal breakpoint provided a starting point for construction of an 840-kb BAC contig spanning the c112K and c3H (D7Ssb3Hp) proximal breakpoints. These breakpoints are separated by 320-350 kb. The aryl hydrocarbon receptor nuclear translocator-2 (Arnt2) is completely removed by the c112K deletion and spans 130-170 kb of the interval. Although Arnt2 is a candidate for the thymus defects in c112K homozygotes, the possibility that other as yet unidentified genes in the c112K deletion are responsible for the abnormalities has not been ruled out. Arnt2 is a member of the bHLH-PAS (Per, Ahr, Arnt, Sim) family of transcription factors and shares the highest similarity with Arnt. The survival of c112K homozygotes markedly contrasts the embryonic lethality observed in Arnt-deficient embryos and suggests distinct roles for these related transcription factors during embryogenesis.

Enteric beta-defensin: molecular cloning and characterization of a gene with inducible intestinal epithelial cell expression associated with Cryptosporidium parvum infection.

A growing body of evidence suggests that endogenous antibiotics contribute to the innate defense of mammalian mucosal surfaces. In the cow, beta-defensins constitute a large family of antibiotic peptides whose members have been previously isolated from the respiratory and oral mucosa, as well as circulating phagocytic cells. A novel bovine genomic clone with beta-defensin-related sequence [corrected] related to those of these alpha-defensins was isolated and characterized. The corresponding cDNA was isolated from a small intestinal library; its open reading frame predicts a deduced sequence of a novel beta-defensin, which we designate enteric beta-defensin (EBD). Northern blot analysis of a variety of bovine tissues revealed that EBD mRNA is highly expressed in the distal small intestine and colon, anatomic locations distinct from those for previously characterized beta-defensins. EBD mRNA was further localized by in situ hybridization to epithelial cells of the colon and small intestinal crypts. Infection of two calves with the intestinal parasite Cryptosporidium parvum induced 5- and 10-fold increases above control levels of EBD mRNA in intestinal tissues. An anchored-PCR strategy was used to identify other beta-defensin mRNAs expressed in the intestine. In addition to that of EBD, several low-abundance cDNAs which corresponded to other beta-defensin mRNAs were cloned. Most of these clones encoded previously characterized beta-defensins or closely related isoforms, but two encoded a previously uncharacterized prepro-beta-defensin. Northern blot evidence supported that all of these other beta-defensin genes are expressed at levels lower than that of the EBD gene in enteric tissue. Furthermore, some of these beta-defensin mRNAs were abundant in bone marrow, suggesting that in enteric tissue their expression may be in cells of hematopoietic origin. Extracts of small intestinal mucosa obtained from healthy cows have numerous active chromatographic fractions as determined by an antibacterial assay, and one peptide was partially purified. The peptide corresponded to one of the low-abundance cDNAs. This study provides evidence of beta-defensin expression in enteric tissue and that the mRNA encoding a major beta-defensin of enteric tissue, EBD, is inducibly expressed in enteric epithelial cells. These findings support the proposal that beta-defensins may contribute to host defense of enteric mucosa.

Inactivity-induced motor nerve terminal sprouting in amphibian skeletal muscles chronically blocked by alpha-bungarotoxin.

There is a positive correlation between contractile inactivity and the initiation of motor neuron sprouting. However, the exact mechanism responsible for this neuronal growth remains obscure. In a previous study (M. M. Wines and M.S. Letinsky, 1988, J. Neurosci. 8: 3909-3919) we investigated this phenomenon by inducing chronic contractile inactivity of an amphibian muscle by exposure to formamide and found that motor neuron sprouting occurs in the presence of normal pressynaptic transmitter release and propagated muscle fiber action potentials. The present study investigates motor neuron sprouting in response to inactivity produced when neuromuscular transmission is blocked by chronic exposure to alpha-bungarotoxin (alpha-BTX). The alpha-BTX-induced muscle paralysis was maintained for 1-63 days by repetitive application of the toxin to the cutaneous pectoris muscle of adult Rana pipiens. During the chronic alpha-BTX treatment end-plate potentials were reduced below threshold, which therefore removed both muscle fiber action potentials and contractile activity. Our findings showed only terminal sprouting. Also, higher sprouting frequencies (up to 100% of the observed terminals) were observed after chronic alpha-BTX treatment, compared to the sprouting response induced by formamide treatment. In view of our earlier formamide results, these observations suggest that the inhibition of the postsynaptic acetylcholine response, and consequently inhibition of muscle fiber electrical and contractile activity, produces a stronger stimulus to motor neuron sprouting than the presence of contractile inactivity alone coupled with normal synaptic transmission and muscle electrical activity.

Partial denervation of amphibian skeletal muscle does not induce neuronal growth at the node of Ranvier.

Following partial denervation of a striated muscle sprouting occurs at the nodes of Ranvier and terminal arborizations of the intact motor neurons. We studied the sprouting response of intact frog (Rana pipiens) motor neurons to partial denervation of the cutaneous pectoris muscle (CP). In the 5-19 days following partial denervation of the CP muscle, tetranitroblue tetrazolium-stained motor neurons exhibited sprouting. However, the mixed response of both nodal and terminal sprouting characteristic to mammalian muscle was replaced by a preferential response of only terminal sprouting. Histological examination showed that in many cases these terminal sprouts appeared to reinnervate abandoned junctional sites on adjacent denervated fibers. Given that nodal sprouting failed to occur for the duration of the experiment, these preliminary results suggest that the cues responsible for nodal sprout formation in the amphibian may differ from those in the mammal.

Gaining access to school for the child with a tracheostomy.

Admission to school for a child with a tracheostomy can present numerous problems. Reasons cited by school authorities for denying access to school for these children include liability issues, financial constraints, inadequately trained health personnel in the schools, logistic problems, and the fears of school staff. Attempting to exclude children with tracheostomies from school is discriminatory and illegal. At the Children's Hospital National Medical Center a model program was developed to resolve conflicts and facilitate the assimilation of the child with a tracheostomy into the school system.

Motor nerve terminal sprouting in formamide-treated inactive amphibian skeletal muscle.

Motor axons can form sprouts from their terminal arborizations in response to partial denervation, and when exposed to pharmacological blocking agents like TTX, botulinum toxins alpha-bungarotoxin, or curare. Each of these experimental procedures has cessation of muscle contractile activity as a common feature. We tested the specific role of muscle fiber inactivity in regulating nerve terminal sprouting by chronically treating adult frog (Rana pipiens) cutaneous pectoris muscles with formamide. Exposure to formamide, unlike the other compounds used to study sprouting, selectively inhibits muscle contractions without blocking pre- or postsynaptic transmission or muscle fiber action potentials. Repeated formamide applications were used to achieve chronic block of muscle contractile activity in vivo for up to 6 weeks. Motor axons in formamide-treated inactive muscle sprouted only from their terminal arborizations, but not from nodes of Ranvier. The onset of this sprouting was protracted compared with that seen in pharmacologically blocked mammalian muscles, and sprouts in formamide-treated muscles were more complex and ornate. The frequency of sprouting terminals was less in these formamide-treated muscles than that seen after alternate methods of contractile block, and this suggests that contractile inactivity alone serves as only a moderate cue for sprouting. The possibility is discussed that the prolific sprouting seen following neurotoxin administration may, in fact, be due to perturbations in synaptic transmission or muscle electrical activity rather than muscle fiber inactivity.

Neuromuscular relationships in a muscle having segregated motor endplate zones. I. Anatomical and physiological considerations.

The cranial portion of the rat anterior gracilis muscle is innervated by the obturator nerve at two discrete motor endplate zones of which the distal is supplied by well-defined branches of the nerve. Prior to the use of this muscle in a study of motoneuron sprouting, further morphological and physiological studies have shown that its fibers vary in length but a number traverse the whole muscle or are long enough to extend through both endplate zones. The distribution of muscle fiber types is typical of a rat fast-twitch muscle, and each fiber is innervated at a single endplate. Myography showed that the spinal cord segments, which may contribute to the muscle's innervation, are L2, 3, and 4, of which L3 is constant and predominant, and that denervation of the distal endplate zone leads to a 50% reduction of the maximum isometric tension developed by the muscle. Antidromic stimulation of nerves supplying the distal endplate zone produced contraction of the proximal part of the muscle and, following similar antidromic stimulation, intracellular recordings made at proximal zone endplates showed the presence of endplate potentials. It was concluded from these data that endplates at both the proximal and distal zones can form part of the same motor unit.

Neuromuscular relationships in a muscle having segregated motor endplate zones. II. The response to partial denervation.

The cranial belly of the anterior gracilis muscle of the rat has two discrete motor endplate zones. A proximal zone is innervated by short branches of the obturator nerve, and a distal zone is innervated by (usually) two longer branches. Each muscle fiber is innervated at a single motor endplate although a substantial number lie within both endplate zones. In addition, motor units are divided between the two zones. In order to dissociate the role of the denervated endplate from that of the denervated muscle fiber in the promotion of motoneuron sprouting, the distal endplate zone in this model was denervated and the response at the proximal zone was studied. Comparisons were made with partial denervation of the muscle by division of the L4 ventral ramus and with partial denervation of the distal endplate zone. Denervation of the distal endplate zone produced profuse terminal sprouting at the proximal zone whereas division of L4 predominantly produced nodal sprouting at both zones. Partial denervation of the distal zone resulted in nodal sprouts in that zone and again mainly terminal sprouts at the proximal zone. The repeated association of terminal sprouting with division of the motor axons supplying the distal zone together with the knowledge that motor units are distributed between the two zones led to the conclusion that the terminal sprouting was stimulated by the reduction in size of motor units rather than by the presence of denervated muscle fibers in the vicinity of the endplates.

Central core degeneration after tenotomy in soleus muscles of hyperthyroid rats.

Tenotomy of the rat soleus muscle is followed by a central degeneration of slow, fatigue-resistant muscle fibers. Previous experiments showed that fast, fatigable fibers of the gastrocnemius when transformed to slow, fatigue-resistant fibers by cross-reinnervation also develop lesions after tenotomy. The experiments described in this communication were carried out to discover whether the susceptibility of fibers to lesions was determined by their fiber type or the nature of their innervation. Rats were rendered hyperthyroid by the administration of sodium 3,3',5-triiodo-L-thyronine (T3) for 7 to 10 weeks. Tenotomy of the soleus muscles was then carried out and the experimental and contralateral muscles were removed and stained for myosin ATPase activity after a further 2 weeks. The hyperthyroid state of each animal was confirmed by the assay of succinate dehydrogenase activity of liver and the contralateral muscle. After acid preincubation, whole muscle fiber type counts of contralateral muscles showed a statistically significant change from a predominantly acid-stable population of fibers to acid-labile fibers. In addition, many fibers of intermediate staining properties were seen. When the experimental muscles were examined, all three varieties of fiber showed central degeneration. The nature of the fiber type change induced by T3 and the role that innervation might play in this is discussed. It was concluded that the susceptibility of fibers to the lesions that follow tenotomy is dependent on the nature of their innervation rather than their fiber type.

Fiber type changes in denervated soleus muscles of the hyperthyroid rat.

The thyroid status of rats is known to influence the histochemical and biochemical myosin adenosine triphosphatase (M-ATPase) activity of the soleus muscle. In the hypothyroid state, denervated soleus muscles are not subject to that influence. Our experiments indicated that in the hyperthyroid state fibers of the denervated soleus muscle show a profound change from acid-stable M-ATPase positive to acid-stable M-ATPase negative. We concluded that this change was induced by the hyperthyroid state and was not neurally mediated.