Abstract: Authors report modern diagnostic and therapeutic procedures used in the correct assessment and treatment of congenital lymphatic and chylous disorders. Lymphatic dysplasias can be clinically represented only by peripheral lymphedema or be associated with more complex dysfunctions of chyliferous vessels and the thoracic duct (chylous ascitis, chylothorax, etc.) It is, therefore, useful to perform a complete diagnostic evaluation of each patient before carrying out any therapeutical approach. Lymphoscintigraphy, lymphangio-MR, oil contrast lymphography, and lymphangio-CT are the common diagnostic tools used in these cases, variable associated depending above all on the complexity of the pathology. From the therapeutical point of view, microsurgical methods proved to bring successful and long lasting results, both with derivative lymphatic-venous anastomoses and reconstructive lymphatic-venous-lymphatic anastomoses. Better long-term results are obtained in earlier stages.
Abstract: We performed lymphoscintigraphy in 15 patients (newborns and children) affected by congenital lymphatic dysplasia. We suggest that lymphoscintigraphy is mandatory in all patients with signs of lymphatic dysplasia, including those with minimal and initial signs of lymphatic impairment, to obtain very early diagnosis and begin treatment.
Abstract: We report on two new patients with straight-chain acyl-coenzyme A oxidase deficiency. Early onset hypotonia, seizures and psychomotor delay were observed in both cases. Plasma very-long-chain fatty acids were abnormal in both patients, whereas the plasma levels of phytanic acid, pristanic acid, the bile acid intermediates DHCA and THCA, and erythrocyte plasmalogen levels were normal. Studies in fibroblasts from the two patients revealed a deficiency of one of the two peroxisomal acyl-CoA oxidases, that is, straight-chain acyl-CoA oxidase (ACOX1). Subsequent molecular analysis of ACOX1 showed a homozygous deletion, which removes a large part of intron 3 and exons 4-14 in the first patient. Mutation analysis in the second patient revealed compound heterozygosity for two mutations, including: (1) a c.692 G > T (p.G231V) mutation and (2) skipping of exon 13 (c.1729_1935del (p.G577_E645del).
Abstract: The authors report their experience in the diagnosis and treatment of lymphatic and chylous disorders in the thoracic and abdominal areas. Sixteen patients (10 adults, 6 children) affected by primary chylous ascites with associated syndromes and consequent immunological incompetence were studied. Diagnostic investigations included abdominal sonography scans, lymphoscintigraphy, and lymphography combined with computed tomography and laparoscopy. Surgical treatment included laparoscopy, drainage of ascites and/or the chylothorax, treatment of abdominal and retroperitoneal chylous leaks, exeresis of lymphodysplastic tissues, ligation of incompetent lymph vessels also by CO(2) LASER, and chylo-venous and lympho-venous microsurgical shunts. Eleven patients did not have a relapse of the ascites and four patients had a persistence of a small quantity of ascites with no protein imbalance. All patients had an improvement of their immunocompetence. Median follow-up was 5 years. We demonstrated that the use of microsurgery is remarkably advantageous for performing a causal treatment of the dysfunction.
Abstract: Authors report over 30 years of their own clinical experience in the treatment of chronic peripheral lymphedemas by microsurgical techniques performed at the Center of Lymphatic Surgery of the University of Genoa, Italy. Over 1,500 lymphedema patients were treated with microsurgical techniques. Derivative lymphatic-venous techniques were most often used. For those cases where a venous disease was associated to lymphedema, reconstructive lymphatic microsurgery techniques were performed (lymphatic-venous-lymphatic-plasty). Objective assessment was undertaken by water volumetry and lymphoscintigraphy. Volume changes showed a significant improvement in over 83%, with an average follow-up of more than 10 years. There was an 87% reduction in the incidence of cellulitic attacks after microsurgery. Microsurgical lymphatic-venous anastomoses have a place in the treatment of peripheral lymphedema and should be the therapy of choice in patients who are not sufficiently responsive to nonoperative treatment. Improved results can be expected with operations performed at earlier lymphedema stages.
Abstract: This case report presents a hydroptic trisomy 21 fetus affected by lymphatic dysplasia with no other malformations. Our studies using CD31, CD34, smooth muscle actin, desmin, and D2-40 antibodies immunohistochemistry confirm the diagnosis of severe pulmonary lymphangiectasia associated with lymphangiectasia ih the mediastinum and small bowel.
Abstract: BACKGROUND: Rapid and reliable bed-side determination of blood glucose concentration is very important in the management of acutely ill infants and especially in premature newborns. HemoCue is an easy-to-use glucose analyser. The aim of the present study was to examine the usefulness of the HemoCue glucose analyser compared to a reference plasma glucose method (SYS, BM/Hitachi 747/737) in a neonatal intensive care unit (NICU). METHODS: Seventy-eight consecutive neonates admitted to our NICU were enrolled in the study. At the time of the study all patients were grouped according to nutritional management (parenteral or enteral nutrition), haematocrit values and birth weight. The effects of feeding management, haematocrit values, and birth weight on accuracy and precision of the device were evaluated. RESULTS: Overall data linear regression analysis yielded an r-value of 0.905 and the Bland-Altman method demonstrated that HemoCue overestimates plasma glucose by 0.932 mmol/L. Evaluation of our data by receiver operating characteristic curve demonstrated 100% sensitivity cutoff at 4.1 mmol/L. CONCLUSIONS: HemoCue cannot be used satisfactorily in the management of glycaemia in the NICU. In the preterm population, birth weight had a dramatic influence on HemoCue accuracy. Low haematocrit and parenteral feeding further contributed to a decrease in the accuracy of this device.
Abstract: A full-term male infant presented at birth with a hard swelling of the left knee. The lemon-sized lesion was fixed to the underlying knee muscles, while the overlying skin was stretched and shiny; there was no bruit. Radiography, sonography and MRI suggested a soft-tissue tumour. After surgical excision, histology showed the presence of fibrous and mesenchymal tissue, with mature adipose tissue. Fibrous hamartoma of infancy was diagnosed. Among soft-tissue tumours, fibrous hamartoma of infancy is a rare and benign lesion, occurring in the first 2 years of life. The tumour mainly affects the trunk, axilla, and upper extremities. This infant had unique involvement of the knee. The treatment of choice is local excision.
Abstract: Six newborns that presented at birth with nonimmune hydrops fetalis and for whom no cause could be found were investigated for the presence of lymphatic dysplasia. Careful analysis led to findings of some degree of lymphatic dysplasia in all patients. This suggests that lymphatic dysplasia may represent at least part of the causes that are responsible for the "idiopathic" form of nonimmune hydrops fetalis. Carefully searching for lymphatic dysplasia in these patients, and if indicated in their relatives, as well as establishing the exact nature of the lymphatic dysplasia must be carried out so as to provide proper genetic counseling to families with nonimmune hydrops.
Abstract: The secondary lymphedema of the upper limb (post-mastectomy lymphedema) has an incidence, in patients who underwent axillary lymphadenectomy for breast cancer, between 5 to 25%, up to 40% after radiotherapic treatment. We studied 50 patients treated for breast cancer. The patients were divided in two groups of 25 each, comparable for age, sex, pathology and treatment and followed up to 5 years after operation for breast. One group of 25 patients was controlled only clinically (physical examination, water volumetry) at 1-3-6 months and 1-3-5 years from breast cancer treatment. The other group of 25 patients was followed also by lymphatic scintigraphy performed pre-operatively and after 1-3-6 months and 1-3-5 years from operation. In the first group, followed only clinically, lymphedema appeared in 9 patients after a period variable from 1 week to 2 years, with highest incidence between 3 and 6 months. In the second group of 25 patients, the preventive therapeutic protocol allowed to have a clinically evident arm lymphedema only in 2 patients. The comparison of the two groups of 25 patients proved a statistically significant difference in the appearance of arm secondary lymphedema (p = 0.01, using Fisher's exact test). The diagnostic and therapeutic preventive procedures allow to reduce the incidence rate of lymphedema significantly, in comparison with patients who did not undergo this protocol of prevention.
Abstract: BACKGROUND: Chylous ascites is the accumulation of triglyceride-rich, free, milk-like peritoneal fluid caused by the presence of intestinal lymph in the abdominal cavity. Primary chylous ascites is uncommon. We present our experience in the diagnosis and treatment of this condition. METHODS: Twelve patients (7 adults, 5 children) affected by primary chylous ascites were studied. Diagnostic investigations included abdominal sonography scans, lymphoscintigraphy, and lymphography combined with computed tomography (CT) with intravenous and intralymphatic lipid-soluble contrast, and laparoscopy. Magnetic resonance imaging was used when lymphography and lymphatic CT were not able to define the dysplasia well, or in the presence of lymphatic dilatation. Surgical treatment included laparoscopy (12/12), drainage of ascites (12/12), the search for and treatment of abdominal and retroperitoneal chylous leaks (12/12), exeresis of lymphodysplastic tissues (12/12), ligation of incompetent lymph vessels (9/12), carbon dioxide laser treatment (cut and welding effects) of the dilated lymph vessels using an operating microscope for magnification (9/12), and chylovenous and lymphovenous microsurgical shunts (7/12). RESULTS: Eight patients did not have a relapse of the ascites, and three patients had a persistence of a small quantity of ascites with no protein imbalance. Postoperative lymphoscintigraphy in seven patients confirmed better lymph flow and less lymph reflux. Median follow-up was 5 years (range, 3 to 7 years). We observed early relapse of chylous ascites in only one case that required a peritoneal-jugular shunt and led to good outcome. CONCLUSION: Primary chylous ascites is closely correlated to lymphatic-lymphonodal dysplasia that does not involve a single visceral district alone. Medical preoperative treatment played an essential role in the global management of this complex pathology. We demonstrated that the use of laparoscopy is remarkably advantageous for confirming diagnosis, for draining the ascites, and for evaluating the extension of the dysplasia. Our diagnostic work-up provided us with an exact diagnostic assessment and allowed us to plan a precise surgical approach.
Abstract: One of the main problems of microsurgery for lymphedema consists of the discrepancy between the excellent technical possibilities and the subsequently insufficient reduction of the lymphoedematous tissue fibrosis and sclerosis. Appropriate treatment based on pathologic study and surgical outcome have not been adequately documented. Over the past 25 years, more than 1000 patients with peripheral lymphedema have been treated with microsurgical techniques. Derivative lymphatic micro-vascular procedures has today its most exemplary application in multiple lymphatic-venous anastomoses (LVA). For those cases where a venous disease is associated to more or less latent or manifest lymphostatic pathology of such severity to contraindicate a lymphatic-venous shunt, reconstructive lymphatic microsurgery techniques have been developed (autologous venous grafts or lymphatic-venous-Iymphatic-plasty - LVLA). Objective assessment was undertaken by water volumetry and lymphoscintigraphy. Subjective improvement was noted in 87% of patients. Objectively, volume changes showed a significant improvement in 83%, with an average reduction of 67% of the excess volume. Of those patients followed-up, 85% have been able to discontinue the use of conservative measures, with an average follow-up of more than 7 years and average reduction in excess volume of 69%. There was a 87% reduction in the incidence of cellulitis after microsurgery. Microsurgical lymphatic-venous anastomoses have a place in the treatment of peripheral lymphedema and should be the therapy of choice in patients who are not sufficiently responsive to nonsurgical treatment. Improved results can be expected with operations performed earlier at the very first stages of lymphedema.
Abstract: Congenital pulmonary lymphangiectasia (PL) is a rare developmental disorder involving the lung, and characterized by pulmonary subpleural, interlobar, perivascular and peribronchial lymphatic dilatation. The prevalence is unknown. PL presents at birth with severe respiratory distress, tachypnea and cyanosis, with a very high mortality rate at or within a few hours of birth. Most reported cases are sporadic and the etiology is not completely understood. It has been suggested that PL lymphatic channels of the fetal lung do not undergo the normal regression process at 20 weeks of gestation. Secondary PL may be caused by a cardiac lesion. The diagnostic approach includes complete family and obstetric history, conventional radiologic studies, ultrasound and magnetic resonance studies, lymphoscintigraphy, lung functionality tests, lung biopsy, bronchoscopy, and pleural effusion examination. During the prenatal period, all causes leading to hydrops fetalis should be considered in the diagnosis of PL. Fetal ultrasound evaluation plays a key role in the antenatal diagnosis of PL. At birth, mechanical ventilation and pleural drainage are nearly always necessary to obtain a favorable outcome of respiratory distress. Home supplemental oxygen therapy and symptomatic treatment of recurrent cough and wheeze are often necessary during childhood, sometimes associated with prolonged pleural drainage. Recent advances in intensive neonatal care have changed the previously nearly fatal outcome of PL at birth. Patients affected by PL who survive infancy, present medical problems which are characteristic of chronic lung disease.
Abstract: Patent ductus arteriosus is one of the most common congenital abnormalities found in premature infants. Ibuprofen, a nonsteroidal drug that is commonly used as an antipyretic, analgesic and anti-inflammatory agent, is also used to induce closure of symptomatic patent ductus arteriosus in preterm infants. Recently, we gave L-lysine ibuprofen to a preterm infant with respiratory distress to induce closure of a patent ductus arteriosus, and the infant experienced pulmonary hypertension. Only 3 cases of pulmonary hypertension following early administration of an ibuprofen solution buffered with tromethamine have previously been reported. However, this severe side effect has never been observed in multicentre, randomized, double-blind controlled trials, nor in recent reviews or meta-analyses of L-lysine ibuprofen use.
Abstract: Body fluid is distributed among three major fluid spaces: plasma, interstitial fluid, and intracellular fluid. The distribution of fluid in each of these compartments is dramatically different in the fetus and newborn compared to the adult. In addition, the amniotic fluid that surrounds the fetus may also be considered an extension of the extracellular space of the fetus. The purpose of this review is to discuss the complex mechanism that regulates volume in the fetus and newborn as well as the regulation of fluid distribution between the plasma and interstitial fluid, while placing special emphasis on the role the lymphatic system plays in mediating and maintaining this distribution.
Abstract: We describe a female infant with a previously unreported combination of manifestations characterized by aplasia cutis, skull defect, brain heterotopia, mild congenital lymphedema, and intestinal lymphangiectasia. The association of intestinal lymphangiectasia and aplasia cutis, and the association of intestinal lymphangiectasia with brain heterotopia in the lymphedema-lymphangiectasia-mental retardation syndrome have been described in single reports. In one family, the association of cortical dysplasia and congenital lymphedema have been related to mutations in the RELN gene.
Abstract: The purpose of this methods paper is to offer pediatricians and nuclear medicine physicians a diagnostic protocol for performing lymphoscintigraphy in newborns that may be useful for enhancing diagnosis and management of newborns with congenital lymphatic abnormalities. Indications for lymphoscintigraphy, choice of tracer, optimal dose, routes of administration, methods of data acquisition, timing, and interpretation of results for newborns are presented and discussed.
Abstract: Congenital pulmonary lymphangiectasia (PL) is a rare developmental disorder involving the lung and is characterized by pulmonary subpleural, interlobar, perivascular, and peribronchial lymphatic dilatation. Both frequency and etiology are unknown. PL presents at birth with severe respiratory distress, tachypnea, and cyanosis, with a very high mortality rate at or within a few hours of birth. At birth, mechanical ventilation and pleural drainage are nearly always necessary to obtain a favorable outcome of respiratory distress. Home supplemental oxygen therapy and symptomatic treatment of recurrent cough and wheeze are often necessary during childhood, sometimes associated to prolonged pleural drainage. Recent advances in intensive neonatal care have changed the previously nearly fatal outcome of PL at birth. Patients affected by PL who survive infancy present medical problems which are characteristic of chronic lung disease.
Abstract: Creatine transporter deficiency is an X-linked disorder characterized by mental retardation and language delay. The authors report a patient affected by creatine transport deficiency caused by a novel mutation in the SLC6A8 gene. Impairment in social interaction represents a consistent clinical finding in the few cases described to date and may be a diagnostic clue for creatine transporter deficiency in males affected by mental retardation, seizures, and language impairment.
Abstract: We report on three infants with congenital chylothorax (CC) and congenital pulmonary lymphangiectasia (CPL). CPL appears to be a characteristic pathological finding in CC. Through the use of lymphoscintigraphy and computed tomography, this study suggests that CC and CPL are strongly correlated entities and that the dysplasia of the lymphatic system results in a pulmonary lymphatic obstruction sequence. The initial microscopic dilatation of the lymph channels may lead to progressive weeping of lymphatics and, consequently, to pleural effusion. Non-Immune Hydrops Fetalis (NIHF) may be the final consequence of impaired systemic venous return and may help to explain pleural-pulmonary involvement in this generalized lymph-vessel malformation syndrome.
Abstract: The aim of this preliminary study was to assess the possible presence of cholesterol oxidation products in 2 i.v. lipidic emulsions with different fatty acid compositions (long-chain triglyceride, medium-chain triglyceride-long-chain triglyceride). Because these emulsions are currently used in neonatal parenteral nutrition, their direct venous introduction might be potentially dangerous because of the possible atherogenic role of cholesterol oxidation products. The emulsions were analyzed when bottles were opened (ie, under normal condition of administration) and after a 12-hour direct experimental exposure to air and high (90%) oxygen concentrations. 7-Ketocholesterol and 5alpha-epoxycholesterol were chosen as markers of cholesterol oxidation and detected by gas chromatography-mass spectrometry of their trimethylsilyl ethers. The detected amounts were always very low and in some cases below the detection limit of the analytical method for the 2 cholesterol oxidation products (COPs; 0.1 and 0.3 microg/g of extracted lipids). Immediately after opening the bottles, their concentrations were lower in the emulsions containing the higher amounts of polyunsaturated fatty acids. Experimental hyperoxic exposure generally determined only a mild increase in the content of cholesterol oxidation biomarker, and after exposure to oxygen, the amounts of COPs were slightly higher than after exposure to air. The results of the present study are undoubtedly reassuring for the safety of neonates, although caution is always required when drawing conclusions from in vitro data.
Abstract: Congenital varicella syndrome refers to the spectrum of fetal anomalies associated with maternal varicella zoster virus (VZV) infection during the first trimester of pregnancy. The syndrome is rare and the risk to the fetus uncertain. We describe an unusual case of congenital varicella syndrome in which hydrocephalus was the main consequence and likely represented VZV reactivation in utero.
Abstract: We report a female infant with congenital lymphedema, facial anomalies, intestinal lymphangiectasia consistent with a diagnosis of Hennekam syndrome. At birth the patient presented with severe respiratory distress due to nonimmune hydrops fetalis, a congenital chylothorax (CC), and pulmonary lymphangiectasia. Hydrops fetalis may be present in newborns with the Hennekam syndrome. Lymphoscintigraphy can be useful in explaining pleural-pulmonary involvement of this generalized lymph vessel malformation syndrome.
Abstract: In the present study the entire NF1 coding region was analyzed for mutations in 132 unrelated Italian NF1 patients. Using PTT, SSCP, and DNA sequencing, we found 8 novel mutations. Clinical diagnosis of NF1 was established according to the NIH consensus criteria. We detected 59 truncated fragments, and 46 of them were characterized by SSCP and direct sequencing. Eight mutations represent novel changes that contribute to the germline mutational spectrum of the NF1 gene. In two patients, premature termination was due to substitutions at nucleotide c.3982C>T (Q1298X) and c.7411C>T (Q2471X), respectively. Two other mutations were caused by the deletions (1756delA, 4699delA), and two by the insertions (c.5266_5267insT, c.7464_7465insTCCA) of a small number of nucleotides. Lastly, we found 2 splice-site mutations (c.2252-2A>C, c.2251+1G>A).
Abstract: The entire NF1 coding region was analyzed for mutations in a panel of 108 unrelated Italian NF1 patients. Using PTT, SSCP, and DNA sequencing, we found 10 mutations which have never been reported before. Clinical diagnosis of NF1 was established according to the NIH consensus criteria in 100 individuals, while 8 were young children with only multiple cafè-au-lait spots. We detected 46 truncated fragments, and 24 of them were fully characterized by SSCP and direct sequencing. Of the 24, 14 were known mutations (R304X, R681X, Q682X, R1306X, R1362X, R1513X, R1748X, Q1794X, R1947X, Y2264X, R2237X, 2674delA, 6789delTTAC, 2027insC). The other 10 mutations represent novel changes that contribute to the germline mutational spectrum of the NF1 gene (K810X, Q2595X, 6772delT, 7190delCT, 7331delA, 1021insTT, 3921insT, 4106insTA, 7149insC, 2033insCG / 2034delA). PTT in a large number of Italian NF1 patients supports the usefulness of this method for characterization of mutations in disorders where the responsible gene is very large and the disease-causing mutations often create a stop codon. In agreement with previous reports, no mutational hotspots within the NF1 gene were detected.
Abstract: We report on a male child with "apple-peel" atresia associated with microcephaly and ocular anomalies. To date, no magnetic resonance imagings have been published. We report on the fourth reported case with this phenotype, but the first to be studied by brain magnetic resonance imaging.
Abstract: The Hennekam syndrome is an infrequently reported heritable entity characterized by lymphedema, lymphangiectasia, and developmental delay. Here we add an additional 8 patients, and compare their findings to the 16 cases from the literature. The lymphedema is usually congenital, can be markedly asymmetrical, and, often, gradually progressive. Complications such as erysipelas are common. The lymphangiectasias are present in the intestines, but have also been found in the pleura, pericardium, thyroid gland, and kidney. Several patients have demonstrated congenital cardiac and blood vessel anomalies, pointing to a disturbance of angiogenesis in at least some of the patients. Facial features are variable, and are chiefly characterized, in a typical patient, by a flat face, flat and broad nasal bridge, and hypertelorism. Facial features are thought to mirror the extent of intrauterine facial lymphedema, or may be caused by lymphatic obstruction that affects the early migration of neural crest tissue. Other anomalies have included glaucoma, dental anomalies, hearing loss, and renal anomalies. The psychomotor development varies widely, even within a single family, from almost normal development to severe mental retardation. Convulsions are common. The existence of 10 familial cases, equal sex ratio, increased parental consanguinity rate (4/20 families), and absence of vertical transmission are consistent with an autosomal recessive pattern of inheritance. It seems likely that most (but not all) manifestations of the entity can be explained as sequences of impaired prenatal and postnatal lymphatic flow, suggesting that the causative gene(s) should have a major function in lymphangiogenesis.
Abstract: This study reviews nine new families with branchio-oto-renal (BOR) syndrome (Online Mendelian Inheritance in Man [OMIM] 113650). Diagnosis was made by studying 10 index cases, and then 22 other previously undetected patients were diagnosed within the nine families. The syndrome consists of conductive, sensorineural, or mixed hearing loss; preauricular pits; structural defects of the outer, middle, or inner ear; renal anomalies; lateral cervical fistulas, cysts, or sinuses; and/or nasolacrimal duct stenosis or fistulas. In our study, all patients first diagnosed in each familial group were recognized on the basis of severe renal anomalies associated with at least one of these symptoms. Our study showed that BOR syndrome is a misdiagnosed disorder, usually recognized in the presence of severe renal failure but often not diagnosed, especially in the adult in the presence of other isolated clinical signs, such as mild branchial or urological anomalies. We stress the meticulous search we performed for renal anomalies and/or hearing loss in all subjects showing minimal signs of branchial defects. BOR syndrome should be suspected in all cases of isolated urological anomalies, even if no other signs of the syndrome are present. After BOR syndrome has been diagnosed in a patient, all family members should be examined for the presence of the syndrome, even if there are only minimal stigmata of the disease.
Abstract: We describe two newborn brothers with a pattern of malformation characterized by the persistence of Müllerian duct derivatives, intestinal lymphangiectasia, hypertrophied alveolar ridges, and early death. Postmortem examination showed the presence of a rudimentary uterus, fallopian tubes, the upper third of a vagina, a prostate of normal shape, a dilated colon, and generalized intestinal and pulmonary lymphangiectasia. The syndrome was first delineated by Urioste and co-workers [1993: Am J Med Genet 47:494-503]. These cases confirm the existence of a definite and distinct entity.
Abstract: OBJECTIVE: To compare the effectiveness of the Infant Flow Driver (IFD) with single prong nasal continuous positive airway pressure (nCPAP) in preterm neonates affected by respiratory distress syndrome. DESIGN: Randomised controlled study. PATIENTS: Between September 1997 and March 1999, 36 preterm infants who were eligible for CPAP treatment were randomly selected for either nCPAP or IFD and studied prospectively for changes in oxygen requirement and/or respiratory rate. The requirement for mechanical ventilation, complications of treatment, and effects on mid-term outcome were also evaluated. RESULTS: Use of the IFD had a significantly beneficial effect on both oxygen requirement and respiratory rate (p < 0.0001) when compared with nCPAP. Moreover, O(2) requirement and respiratory rate were significantly decreased by four hours (p < 0.001 and p < 0.03 respectively). The probability of remaining supplementary oxygen free over the first 48 hours of treatment was significantly higher in patients treated with the IFD than with nCPAP (p < 0.02). IFD treated patients had a higher success (weaning) rate (94% v 72 %) and shorter duration of treatment (49.3 (31) v 56 (29.7) hours respectively; mean (SD)), although the difference was not significant. CONCLUSIONS: IFD appears to be a feasible device for managing respiratory distress syndrome in preterm infants, and benefits may be had with regard to oxygen requirement and respiratory rate when compared with nCPAP. The trend towards reduced requirement for mechanical ventilation, shorter clinical recovery time, and shorter duration of treatment requires further evaluation in a multicentre randomised clinical trial.
Abstract: Neonatal hemochromatosis (NH) is a rare clinical-pathologic entity defined by severe neonatal liver failure (NLF) of intrauterine onset associated with extrahepatic siderosis that spares reticuloendothelial elements. Whether this entity is the result of a distinct disease process or is the pathologic end-result of many other forms of NLF remains to be assessed. Death from multisystem organ failure usually occurs in the first few days or weeks of life. We report two sisters with neonatal hemochromatosis with different outcome. The first died at 21 days of life for multiorgan failure and sepsis. The second was diagnosed and treated very early by aggressive support with fresh-frozen plasma, packed red cells, platelets, coagulation factors, diuretics, and pressors, and she is well at 2-year-follow-up. The few therapeutic options are discussed. In general, few patients survived NH. Among patients treated only by medical approachs and that did not undergo orthotopic liver transplantation (OLTX), favorable outcome is only very rarely reported. For management of NH infants early recognition of the disease is critical. Our experience seems to suggest that as early is the start of treatment as high is the possibility of survival. At this moment very early aggressive supportive treatment should appear to be the most useful approach to stabilize the patient hoping in spontaneous liver recovery, or, in turn, to permit OLTX before septic complications bring to clinical decline.
Abstract: Neonatal hemochromatosis is a rare congenital disorder which affects both fetuses and newborns. It is characterized by hepatocellular failure, often appearing on the first day of life in the form of coagulopathy, hypoalbuminemia, hypoglycemia, and jaundice. Most of the affected infants die early in life, and definitive diagnosis has often been made only by post-mortem evaluation. With the help of MRI, plus increasing awareness of the disorder, diagnosis is now often made early, even in utero. Duplex Doppler sonography does not provide information on siderosis but shows abnormalities in the liver or blood-flow patterns associated with liver disease.
Abstract: Cell senescence produces changes in the expression of specific genes, suggesting that senescent cells express an altered pattern of transcription factors. Here we describe how the DNA binding activity of the activator protein 1(AP-1) complex is altered in the fibroblasts of a geroderma osteodysplastica patient in response to extracellular stimuli.
Abstract: Sebaceous nevus (SN) syndrome is a neurocutaneous disorder characterized by a distinctive skin lesion in association with epilepsy and mental retardation. In one group of patients, brain lesions may be consequent to vascular abnormalities ("vascular variant"); another group of SN patients presents ipsilateral hemimegalencephaly, gyral anomalies, and facial hemihypertrophy ("neurologic variant" or "SN with hemimegalencephaly"). In the latter group, facial hemihypertrophy does not appear to be a constant feature and was not present in our 2 SN patients with hemimegalencephaly. Considering that about half of the SN patients with hemimegalencephaly described so far do not have facial asymmetry, we suggest the existence of a separate subgroup of SN patients with hemimegalencephaly and without facial hemihypertrophy. In these patients, the only clinical diagnostic clue is a nevus that is barely visible until puberty.
Abstract: Autosomal recessive mode of inheritance of a Coffin-Siris like syndrome: Coffin-Siris syndrome is a rare mental retardation/multiple congenital anomalies syndrome; so far its pattern of inheritance is under debate. We report a child affected by this syndrome, the pedigree of which is consistent with autosomal recessive inheritance.
Abstract: The association of Rubinstein-Taybi syndrome (RTS) and slipped capital femoral epiphysis (SCFE) is described in a girl aged 9 years and 10 months. SCFE has never been reported associated with RTS, neither as an isolated anomaly, nor in a familial pedigree. However, a "stiff gait" is frequently described in RTS patients and, furthermore, obesity is a frequent feature of RTS patients. Some reports in the literature suggest the need for an early diagnosis of SCFE among adolescent relatives of patients with SCFE. Since many SCFEs are asymptomatic and an early diagnosis is essential for a favorable prognosis, we suggest an annual echotomographic or radiological examination of the hips in RTS patients.
Abstract: The authors describe a case of follicular cyst of the jaw diagnosed in a male infant who was 2 years and 4 months old. The authors discuss recent advances in the classification of this disorder and the difficulties that arise in performing differential diagnosis; some peculiar features of the described case are discussed.
Abstract: We describe a patient with methylmalonic aciduria and homocystinuria due to a defect in cobalamin metabolism of the Cbl-C type mutant (McKusick 277400). Our case was diagnosed within the first 2 months of life by amino acid analysis (ion-exchange chromatography) and by biochemical studies in cultured fibroblasts ([14C]propionate incorporation, methionine and serine formation). We discuss the clinical course and the biochemical evolution after 2 years of hydroxycobalamin treatment that led to an improvement in general clinical condition and neurological performance.
Abstract: We have studied a 15-year-old girl (P1) suffering from the Hutchinson-Gilford syndrome (progeria) associated with a severe insulin resistance. Insulin binding activity to P1 erythrocytes was 85% reduced when compared to that measured in ten normal controls matched for sex and age. This finding was confirmed in Epstein-Barr virus (EBV)-transformed lymphoblasts and depends on a reduction in insulin receptor number. Also the amount of total insulin receptors, [35S]methionine labeled and immunoprecipitated, was 90% reduced in P1 lymphoblasts when compared to controls. Next, we measured insulin receptor mRNA levels and we found undetectable levels of insulin receptor transcript in P1 EBV-transformed lymphoblasts, in the absence of any rearrangement of insulin receptor gene as evaluated by Southern blot analysis. The marked reduction in insulin receptor gene expression probably accounts for the severe insulin resistance presented by the patient. Despite extensive studies, the molecular basis of progeria is still unknown. The near complete absence of a molecule crucial in the transduction of cell growth and differentiation signals could be involved in the accelerated aging of the patient.
Abstract: The authors describe a case of Crouzon syndrome, characterized by unusually early and serious symptoms, and surgically corrected during the fifth month of life, with good clinical and aesthetic results.
