Congenital cystic adenomatoid malformation of the lung: indications and timing of surgery

We review a single surgeon and surgical centre's experience with congenital cystic adenomatoid malformation of the lung (CCAML) in relation to clinical spectrum, operative experience, and postoperative course. A retrospective hospital record review was done on surgically treated cases of CCAML over a 10-year period, focusing on number with antenatal diagnosis, spectrum of postnatal presentation, type of surgery performed, and outcome. Forty-seven patients from birth to 14 years of age underwent surgery for CCAML. Antenatal diagnosis (ante) was made in 30 cases. Of these, 10 became symptomatic before surgery. Six of the 17 postnatally-diagnosed (pnd) cases were an asymptomatic incidental finding. Overall, 16 were symptomatic in the 1st year of life, and five were symptomatic beyond 1 year of age. Symptoms varied from respiratory distress (seven ante, six pnd) to chronic cough (three, and recurrent chest infection (three ante, two pnd). All preoperative diagnoses were confirmed with chest CT. Most patients (25) were operated on before 3 months of age. Eleven were operated on in the first 2 weeks of life as emergency surgery for respiratory distress. The most common lobe involved was the right upper lobe (16), and lobectomy was performed in 42 cases, segmentectomy in four, and pneumonectomy in one. Seventeen cases were extubated immediately postoperatively; 29 required postoperative ventilation overnight, and nine needed more prolonged ventilation. Early postoperative complications included pneumothorax (two), pleural effusion (one), and chylous effusion (one). Late complications included recurrence in three cases (all segmentectomy), who then subsequently underwent lobectomy. There was one death from respiratory failure. Because there is an increasing trend in the detection of asymptomatic antenatally-diagnosed CCAML, consideration of early surgical excision to prevent complications is suggested by our series. CT scanning is mandatory for postnatal evaluation because chest x-ray could be normal. Safe elective excision after 3 months is supported by our low morbidity and less need for postoperative ventilation. Lobectomy is the procedure of choice to prevent recurrence.

Magnetic resonance imaging (MRI) and diseases of the liver and biliary tract. Part 1. Basic principles, MRI in the assessment of diffuse and focal hepatic disease

Magnetic resonance imaging (MRI) relies on the physical properties of unpaired protons in tissues to generate images. Unpaired protons behave like tiny bar magnets and will align themselves in a magnetic field. Radiofrequency pulses will excite these aligned protons to higher energy states. As they return to their original state, they will release this energy as radio waves. The frequency of the radio waves depends on the local magnetic field and by varying this over a subject, it is possible to build the images we are familiar with. In general, MRI has not been sufficiently sensitive or specific in the assessment of diffuse liver disease for clinical use. However, because of the specific characteristics of fat and iron, it may be useful in the assessment of hepatic steatosis and iron overload. Magnetic resonance imaging is useful in the assessment of focal liver disease, particularly in conjunction with contrast agents. Haemangiomas have a characteristic bright appearance on T-2 weighted images because of the slow flowing blood in dilated sinusoids. Focal nodular hyperplasia (FNH) has a homogenous appearance, and enhances early in the arterial phase after gadolinium injection, while the central scar typically enhances late. Hepatic adenomas have a more heterogenous appearance and also enhance in the arterial phase, but less briskly than FNH. Hepatocellular carcinoma is similar to an adenoma, but typically occurs in a cirrhotic liver and has earlier washout of contrast. The appearance of metastases depends on the underlying primary malignancy. Overall, MRI appears more sensitive and specific than computed tomography with contrast for the detection and evaluation of malignant lesions. (C) 2000 Blackwell Science Asia Pty Ltd.

Hand positioning sense in children with spina bifida myelomeningocele

This study was undertaken to establish whether children with myelomeningocele have abnormal kinaesthesia of the hands. Twenty-one children with myelomeningocele and 21 control children, aged between six and 12 years, were involved in the study. The level of kinaesthetic awareness in the hands was measured by examining the child's ability to copy hand positions, using visual cueing and kinaesthetic cueing. Both accuracy and speed of copying hand gestures were assessed. Children with spina bifida were significantly less accurate in achieving hand positions than the control group (chi((1))(2) 22.60, p < 0.001), with 73% of the children with spina bifida achieving accurate replications compared with 87% in the control group. Furthermore, children with myelomeningocele were shown to be slower than the controls (F-(1,F-2810) = 15.49, p < 0.001). The impaired kinaesthetic awareness found in this study is considered to be one of the factors behind the poor hand function observed in children with myelomeningocele.

Abnormal extracellular matrix protein transport associated with increased apoptosis of vascular smooth muscle cells in Marfan syndrome and bicuspid aortic valve thoracic aortic aneurysm

Background - Marfan syndrome (MS) is a genetic disorder caused by a mutation in the fibrillin gene FBN1. Bicuspid aortic valve (BAV) is a congenital heart malformation of unknown cause. Both conditions are associated with ascending aortic aneurysm and premature death. This study examined the relationship among the secretion of extracellular matrix proteins fibrillin, fibronectin, tenascin, and vascular smooth muscle cell (VSMC) apoptosis. The role of matrix metalloproteinase (MMP)- 2 in VSMC apoptosis was studied in MS aneurysm. Methods and Results - Aneurysm tissue was obtained from patients undergoing surgery ( MS: 4 M, 1 F, age 27 - 45 years; BAV: 3 M, 2 F, age 28 - 65 years). Normal aorta from subjects with nonaneurysm disease was also collected ( 4 M, 1 F, age 23 - 93 years). MS and BAV aneurysm histology showed areas of cystic medial necrosis (CMN) without inflammatory infiltrate. Immunohistochemical study of cultured MS and BAV VSMC showed intracellular accumulation and reduction of extracellular distribution of fibrillin, fibronectin, and tenascin. Western blot showed no increase in expression of fibrillin, fibronectin, or tenascin in MS or BAV VSMC and increased expression of MMP-2 in MS VSMCs. There was 4-fold increase in loss of cultured VSMC incubated in serum-free medium for 24 hours in both MS ( 27 +/- 8%) and BAV ( 32 +/- 14%) compared with control ( 7 +/- 5%). Conclusions - In MS and BAV there is alteration in both the amount and quality of secreted proteins and an increased degree of VSMC apoptosis. Up-regulation of MMP-2 might play a role in VSMC apoptosis in MS VSMC. The findings suggest the presence of a fundamental cellular abnormality in BAV thoracic aorta, possibly of genetic origin.

The Cotard syndrome. Report of two patients: with a review of the extended spectrum of 'délire des négations'

The Cotard syndrome is characterized by the delusion where an individual insists that he has died or part of his body has decayed. Although described classically in schizophrenia and bipolar disorder, physical disorders including migraine, tumour and trauma have also been associated with the syndrome. Two new cases are described here, the one associated with arteriovenous malformations and the other with probable multiple sclerosis. The delusion has been embarrassing to each patient. Study of such cases may have wider implications for the understanding of the psychotic interpretation of body image, for example that occurring in anorexia nervosa.

Maternal valproate dosage and foetal malformations

Objective - To study the possible dose dependence of the foetal malformation rate after exposure to sodium valproate in pregnancy Methods - Analysis of records of all foetuses in the Australian Registry of Antiepileptic Drugs in Pregnancy exposed to valproate, to carbamazepine, lamotrigine or phenytoin in the absence of valproate, and to no antiepileptic drugs. Results - The foetal malformation rate was higher (P < 0.05) in the 110 foetuses exposed to valproate alone (17.1%), and in the 165 exposed to valproate, whether alone or together with the other antiepileptic drugs (15.2%), than in the 297 exposed to the other drugs without valproate (2.4%). It was also higher (P < 0.10) than in the 40 not exposed to antiepileptic drugs (2.5%). Unlike the situation for the other drugs, the malformation rate in those exposed to valproate increased with increasing maternal drug dosage (P < 0.05). The rate was not altered by simultaneous exposure to the other drugs. Valproate doses exceeding 1400 mg per day seemed to be associated with a more steeply increasing malformation rate than at lower doses and with a different pattern of foetal malformations. Conclusion - Foetal exposure to valproate during pregnancy is associated with particularly high, and dose-dependent risks of malformation compared with other antiepileptic drugs, and may possibly involve different teratogenetic mechanisms.

Neonatal calyceal dilation and renal fibrosis resulting from loss of Adamts-1 in mouse kidney is due to a developmental dysgenesis

Background. A disintegrin and metalloproteinase with thrombospondin motifs 1, Adamts-1, is important for the development and function of the kidney. Mice lacking this protein present with renal lesions comprising enlarged calyces, and reduced cortex and medulla layers. Our current findings are consistent with the defect occurring due to a developmental dysgenesis. Methods. We generated Adamts-1 null mice, and further investigated their kidney phenotype in a time course study ranging from E18.5 to 12 months of age. Immunohistochemistry was used to assess the localization of type IV collagen, TGF-beta and F4/80-positive macrophages in the kidneys of Adcants-1 null mice compared to wild-type control animals. The expression of Adamts-1 mRNA was determined in metanephric kidney explants by in situ hybridization. Results. Adamts-1 null mice have a gross kidney defect. At day 18.5 of gestation, the Adcants-1 null kidney has a normal appearance but at birth when the kidney begins to function, the defect becomes evident. During development of the kidney Adamts-1 expression was specifically detected in the developing loops of Henle, as well as in the proximal and distal convoluted tubules. Expression was not detected in the ureter, ureteric bud or its derivatives as had been previously suggested. At 6 months and I year of age, the Adamts-1 null mice displayed interstitial fibrosis in the cortical and medullary regions of the kidney. At I year of age, the Adamts-1 null mice displayed mild interstitial matrix expansion associated with increased collagen type IV expression, without apparent tubular dilatation, compared to wild-type animals. Immunohistochemical analysis demonstrated TGF-beta protein localized to infiltrating macrophages and glomeruli of Adamts-1 null mice. Conclusions. Adamts-1 is required for the normal development of the kidney. The defect observed in its absence results from a dysgenic malformation affecting the medulla that becomes apparent at birth, once the kidneys start to function.

Should valproate be taken during pregnancy?

The Australian Registry of Antiepileptic Drug Use in Pregnancy includes 172 instances in which women took sodium valproate, with or without other antiepileptic drugs, during pregnancy. These pregnancies resulted in a substantially higher (p < 0.05) rate of malformed offspring (15.1%) compared with 348 pregnant women who took antiepileptic drugs other than valproate (2.3%) and 40 pregnancies in epileptic women who took no antiepileptic drugs (2.5%). At valproate doses of 1400 mg and below per day, the mean rate of pregnancies with fetal malformations was 6.42% and did not seem to be dose-dependent. At higher valproate doses, the mean rate of pregnancy with fetal malformation was 33.9% and appeared to increase with increasing drug dosage. This finding suggests the need for reappraisal of the use of valproate in women who may become pregnant or are pregnant whilst the drug is taken. The therapeutic policy adopted may depend on whether valproate doses below 1400 mg per day are regarded as safe for the fetus. This study indicates that the risk of malformation associated with such doses was just statistically significantly (p < 0.05) higher than that associated with other antiepileptic drugs. Various possible clinical scenarios are discussed.

Macrophage-specific expression of human lysosomal acid lipase corrects inflammation and pathogenic phenotypes in lal(-/-) mice

Lysosomal acid lipase (LAL) hydrolyzes cholesteryl esters and triglycerides to generate free fatty acids and cholesterol in the cell. The downstream metabolites of these compounds serve as hormonal ligands for nuclear receptors and transcription factors. Genetic ablation of the lal gene in the mouse caused malformation of macrophages and inflammation-triggered multiple pathogenic phenotypes in multiple organs. To assess the relationship between macro phages and lal(-/-) pathogenic phenotypes, a macrophage-specific doxycycline-inducible transgenic system was generated to induce human LAL (hLAL) expression in the lal(-/-) genetic background under control of the 7.2-kb c-fins promoter/intron2 regulatory sequence. Doxycycline-induced hLAL expression in macrophages significantly ameliorated aberrant gene expression, inflammatory cell (neutrophil) influx, and pathogenesis in multiple organs. These studies strongly support that neutral lipid metabolism in macrophages contributes to organ inflammation and pathogenesis.

The human genome and gene expression profiling

The mapping and sequencing of the human genome has generated a large resource for answering questions about human disease. This achievement is akin in scientific importance to developing the periodic table of elements. Plastic surgery has always been at the frontier medical research. This resource will help us to improve our understanding on the many unknown physiological and pathogical conditions we deal with daily, such as wound heating keloid scar formation, Dupuytren's disease, rheumatoid arthritis, vascular malformation and carcinogenesis. We are primed in obtaining both disease and normal tissues to use this resource and applying it to clinical use. This review is about the human genome, the basis of gene expression profiling and how it will affect our clinical and research practices in the future and for those embarking on the use of this new technology as a research tool, we provide a brief insight on its limitations and pitfalls. (C) 2006 The British Association of Plastic Surgeons. Published by Elsevier Ltd. All rights reserved.

Increased DNA Methylation at the AXIN1 Gene in a Monozygotic Twin from a Pair Discordant for a Caudal Duplication Anomaly

The AXIN1 gene has been implicated in caudal duplication anomalies. Its coding region was sequenced in both members of a monozygotic ( MZ) twin pair discordant for a caudal duplication anomaly, but no mutation was found. Using bisulfite sequencing, we examined methylation at the promoter region of the AXIN1 gene in these twins and in twin and age-matched singleton controls. Methylation of the promoter region in peripheral blood mononucleated cells was variable among individuals, including MZ pairs. In the MZ pair discordant for the caudal duplication, this region of the affected twin was significantly more methylated than that of the unaffected twin (), which was significantly more P < .0001 methylated than those of the controls (). We have confirmed that this CpG island does function as a promoter P = .02 in vitro and that its activity is inversely proportional to the extent of methylation. This finding raises the possibility that hypermethylation of the AXIN1 promoter, by mechanisms as yet undetermined, is associated with the malformation. This case may be paradigmatic for some cases of MZ discordance.

The Bioeroding Sponge Aka paratypica, a Modern Tracemaking Analogue for the Paleozoic Ichnogenus Entobia devonica

Many attempts have been made by ichnologists to match bioerosion traces to their respective tracemakers. This task has been considered difficult, especially for fossil samples. The present study demonstrates that the Australian bioeroding sponge Aka paratypica can generate a cavity similar to the ichnospecies Entobia devonica. The modern sponge and its cavity are redescribed and compared to the fossil boring. A. paratypica has white fistules and soft, mucoid endosomal tissue. Spicules are stout oxeas with often telescoped or mucronate tips. Observed borings of A. paratypica are rounded and cavernous, with canals and apertures radiating from the chambers in all directions. It was noted that the internal openings of such canals are covered with porous nodules, which may act as sieves against larger particles or intruding endofauna. No obvious microsculpturing was observed in the erosion scars. A. paratypica borings are analogous to ancient E. devonica borings, which to date were only known from the fossil record.