Consensus recommendations for management of head and neck cancer in Asian countries: a review of international guidelines.

Head and neck cancer (HNC) is a disease of the upper aerodigestive tract and is one of the most frequently diagnosed cancers worldwide. A high rate of cancers involving the head and neck are reported across the Asian region, with notable variations between countries. Disease prognosis is largely dependent on tumor stage and site. Patients with early stage disease have a 60-95% chance of cure with local therapy. Early diagnosis and appropriate treatment are important to increase the likelihood of cure and survival. However, the majority of patients present with locally advanced disease and require multimodality treatment. This necessitates, a multidisciplinary approach which is essential to make appropriate treatment decisions, particularly with regards to tolerability, costs, available infrastructure and quality of life issues. Unfortunately, majority of the studies that dictate current practice have been developed in the west where diseases biology, patient population and available infrastructure are very different from those in the Asian continent. With this in mind an expert panel of Head and Neck Oncologists was convened in May 2012 to review the National Comprehensive Cancer Network (NCCN) and the European Society for Medical Oncology (ESMO) clinical practice guidelines and develop practical recommendations on the applicability of these guidelines on the management of head and neck cancer for Asian patients. The objective of this review and consensus meeting was to suggest revisions, to account for potential differences in demographics and resources, to the NCCN and ESMO guidelines, to better reflect current clinical management of head and neck cancer within the Asian region for health care providers. These recommendations, which reflect best clinical practice within Asia, are expected to benefit practitioners when making decisions regarding optimal treatment strategies for their patients.

A whole genome methylation analysis of systemic lupus erythematosus: hypomethylation of the IL10 and IL1R2 promoters is associated with disease activity.

The etiology of systemic lupus erythematosus (SLE) involves a complex interaction of genetic and environmental factors. Investigations have shown that environmentally driven epigenetic changes contribute to the etiology of SLE. Here, we hypothesize that aberrant DNA methylation may contribute to the activation of the immune machinery and trigger lupus disease activity. A whole genome methylation array was applied to investigate the DNA methylation changes between 12 pairs of active SLE patients and healthy controls. The results were further confirmed in 66 SLE patients, 102 healthy controls. The methylation statuses of the IL10 and IL1R2 genes were significantly reduced in the SLE patient samples relative to the healthy controls (age-adjusted odds ratios, 64.2 and 16.9, respectively, P<0.0001). There was a trend toward SLE patients having hypomethylated IL10 and IL1R2 genes accompanied by greater disease activity. We observed that the methylation degree of IL10 and IL1R2 genes were reduced in the rheumatoid arthritis (RA) patients as well but the hypomethylation change was more significant in IL1R2 genes than in the IL10 genes in RA patients. This study demonstrated that DNA hypomethylation might be associated with SLE. Hypomethylated IL10 and IL1R2 genes may provide potential epigenetic markers as clinical predictors for autoimmune diseases.

A novel isoform of the 8p22 tumor suppressor gene DLC1 suppresses tumor growth and is frequently silenced in multiple common tumors.

The critical 8p22 tumor suppressor deleted in liver cancer 1 (DLC1) is frequently inactivated by aberrant CpG methylation and/or genetic deletion and implicated in tumorigeneses of multiple tumor types. Here, we report the identification and characterization of its new isoform, DLC1 isoform 4 (DLC1-i4). This novel isoform encodes an 1125-aa (amino acid) protein with distinct N-terminus as compared with other known DLC1 isoforms. Similar to other isoforms, DLC1-i4 is expressed ubiquitously in normal tissues and immortalized normal epithelial cells, suggesting a role as a major DLC1 transcript. However, differential expression of the four DLC1 isoforms is found in tumor cell lines: Isoform 1 (longest) and 3 (short thus probably nonfunctional) share a promoter and are silenced in almost all cancer and immortalized cell lines, whereas isoform 2 and 4 utilize different promoters and are frequently downregulated. DLC1-i4 is significantly downregulated in multiple carcinoma cell lines, including 2/4 nasopharyngeal, 8/16 (50%) esophageal, 4/16 (25%) gastric, 6/9 (67%) breast, 3/4 colorectal, 4/4 cervical and 2/8(25%) lung carcinoma cell lines. The functional DLC1-i4 promoter is within a CpG island and is activated by wild-type p53. CpG methylation of the DLC1-i4 promoter is associated with its silencing in tumor cells and was detected in 38-100% of multiple primary tumors. Treatment with 5-aza-2'-deoxycytidine or genetic double knockout of DNMT1 and DNMT3B led to demethylation of the promoter and reactivation of its expression, indicating a predominantly epigenetic mechanism of silencing. Ectopic expression of DLC1-i4 in silenced tumor cells strongly inhibited their growth and colony formation. Thus, we identified a new isoform of DLC1 with tumor suppressive function. The differential expression of various DLC1 isoforms suggests interplay in modulating the complex activities of DLC1 during carcinogenesis.

Neuro-mediators as predictors of paediatric atopic dermatitis.

BACKGROUND: Attempts to identify predictors of atopic dermatitis (AD) have focused on genetic and immunologic factors. However, the role of neuro-mediators remains to be elucidated. OBJECTIVE: To evaluate nerve growth factor (NGF) and vaso-active intestinal peptide (VIP) in predicting paediatric AD and assess their correlation with intrinsic and extrinsic types of AD. METHODS: We performed a nested case-control study in the prospective Taiwan birth panel cohort study. Cord and maternal plasma and questionnaires were gathered at birth. During follow-up, we identified 40 available AD cases, which were matched to 80 unaffected controls chosen from this cohort. The concentrations of IgE, NGF, and VIP in cord and maternal plasma of these subjects were performed by ELISA. Receiver-operating characteristic (ROC) curves were generated to see how well each biomarker could predict AD. RESULTS: The NGF levels were significantly higher in AD patients than controls (mean+/-SD: 65.47+/-44.45 vs. 49.21+/-12.18 pg/mL for cord plasma and 89.68+/-41.04 vs. 66.96+/-23.05 pg/mL for maternal plasma) (P<0.05). VIP levels were also higher but not statistically significant. Plasma NGF may be a better biomarker than IgE in detecting paediatric AD (area under the ROC curve=0.65 vs. 0.61 for cord plasma and 0.69 vs. 0.61 for maternal plasma). Maternal NGF levels were significantly higher in patients with both intrinsic (96.18+/-48.15 pg/mL) and extrinsic (86.18+/-37.23 pg/mL) types of AD compared with controls (66.96+/-23.05 pg/mL) (P<0.05). We assessed a significant correlation between self-reported stress during pregnancy and maternal NGF levels (r=0.22, P=0.02). CONCLUSION: Our results suggest that NGF is a good alternative biomarker in predicting children with a risk of AD.

Environmental risk factors for early infantile atopic dermatitis.

Previous studies of predictors of atopic dermatitis (AD) in Asia have had limited sample size and small numbers of variables focused primarily on family history or dietary exposures. The purpose of this study was to evaluate the influence of various environmental risk factors for early infantile AD. We used multistage, stratified systematic sampling to recruit 2048 mother-child pairs from the Taiwan national birth registration in 2003. Information on environmental risk factors for infant AD gathered by questionnaire were available from 1760 infants at 6 months of age. Multiple logistic regression was used to estimate adjusted odds ratios (aORs) and their 95% confidence intervals (CIs) for risk factors for AD after adjusting for potential confounders. AD was noted in 118 of 1760 (6.7%) of the infants. After adjusting for maternal age and education, family history of atopy, infant gender, and gestational age, fungi on walls of the house [aOR 2.14 (95% CI 1.41-3.22)] and frequent use of microwave oven at home [aOR 1.71 (95% CI 1.13-2.58)] increased the risk of early infantile AD. This study suggests that environmental factors do play a role in early infantile AD. Fungi, a kind of aeroallergen, are especially important in humid climate as in Taiwan and their impacts might be felt at the early infant stage. The hazards of microwave use should be paid more attention.

The major 8p22 tumor suppressor DLC1 is frequently silenced by methylation in both endemic and sporadic nasopharyngeal, esophageal, and cervical carcinomas, and inhibits tumor cell colony formation.

Identification of tumor suppressor genes (TSG) silenced by methylation uncovers mechanisms of tumorigenesis and identifies new epigenetic tumor markers for early cancer detection. Both nasopharyngeal carcinoma (NPC) and esophageal carcinoma are major tumors in Southern China and Southeast Asia. Through expression subtraction of NPC, we identified Deleted in Liver Cancer 1 (DLC1)/ARHGAP7 (NM_006094)--an 8p22 TSG as a major downregulated gene. Although expressed in all normal tissues, DLC1 was silenced or downregulated in 11/12 (91%) NPC, 6/15 (40%) esophageal, 5/8 (63%) cervical and 3/9 (33%) breast carcinoma cell lines. No genetic deletion of DLC1 was detected in NPC although a hemizygous deletion at 8p22-11 was found by 1-Mb array-CGH in some cell lines. We then located the functional DLC1 promoter by 5'-RACE and promoter activity assays. This promoter was frequently methylated in all downregulated cell lines and in a large collection of primary tumors including 89% (64/72) NPC (endemic and sporadic types), 51% (48/94) esophageal, 87% (7/8) cervical and 36% (5/14) breast carcinomas, but seldom in paired surgical marginal tissues and not in any normal epithelial tissue. The transcriptional silencing of DLC1 could be reversed by 5-aza-2'-deoxycytidine or genetic double knock-out of DNMT1 and DNMT3B. Furthermore, ectopic expression of DLC1 in NPC and esophageal carcinoma cells strongly inhibited their colony formation. We thus found frequent epigenetic silencing of DLC1 in NPC, esophageal and cervical carcinomas, and a high correlation of methylation with its downregulation, suggesting a predominant role of epigenetic inactivation. DLC1 appears to be a major TSG implicated in the pathogenesis of these tumors, and should be further tested as a molecular biomarker in patients with these cancers.

Paclitaxel, 5-fluorouracil and hydroxyurea concurrent with radiation in locally advanced nasopharyngeal carcinoma.

BACKGROUND: Concurrent chemoradiotherapy (CRT) is the standard treatment for locally advanced nasopharyngeal carcinoma (NPC). We conducted a phase II trial using paclitaxel, 5-fluorouracil and hydroxyurea concurrent with radiation (TFHX). PATIENTS AND METHODS: Fifty-nine patients with locally advanced NPC were treated with CRT consisting of 4-day continuous infusions of paclitaxel (20 mg/m(2)/d) and 5-fluorouracil (600 mg/m(2)/d), and oral hydroxyurea 500 mg bid for nine doses, every 3 weeks concurrent with radiotherapy (RT). RT consisted of once daily 200cGy fractions 5 times per week to a total of 7000cGy. RESULTS: Complete response was seen in 86% and 71% of patients at 4 and 12 months after CRT. The median follow-up was 34 months. Twenty-three patients experienced relapse. Sixteen deaths occurred: 13 from progressive disease. Three-year overall survival and progression-free survival were 72% and 54% respectively, with locoregional and distant control rates of 83% and 64% at 3 years respectively. Grade 3 to 4 acute toxicities included oropharyngeal mucositis in 81% of patients treated, dermatitis in 63%, weight loss in 32%, and neutropenia in 22%. Neutropenic fever was seen in 14%. There were no treatment-related deaths from acute toxicity. CONCLUSIONS: TFHX is shown to be feasible in NPC. Non-cross resistant induction chemotherapy should be further studied with this regimen.

Persistent pulmonary hypertension of the newborn: experience in a single institution.

Persistent pulmonary hypertension of the newborn (PPHN) remains one of the most challenging situations in the neonatal intensive care unit, and it is associated with high mortality and morbidity. The optimal treatment for PPHN is controversial. We report our 9-year experience in the management of PPHN through a retrospective review of 29 neonates with persistent pulmonary hypertension. The diagnosis of PPHN is made by echocardiography and/or preductal and postductal oxygen tension difference. The treatment modalities include supportive medical care, vasodilator therapy, mechanical ventilation and correction of underlying conditions. The wide diversity of etiologies of PPHN, the complications of vasodilator therapy, the management of assisted ventilation, the mortality and the morbidity are evaluated. There are 29 patients enrolled in this study, including 18 male and 11 female babies. Twenty-two patients (72%) are referred from other hospitals. The mean birth body weight is 2707 +/- 693 grams (range: 1450-4100 grams) and the mean gestational age is 37.1 +/- 3.1 weeks (range: 31-41 weeks). The underlying clinical conditions include meconium aspiration syndrome (n = 8), perinatal asphyxia (n = 7), respiratory distress syndrome (n = 5), sepsis and/or pneumonia (n = 4), congenital diaphragmatic hernia (n = 3) and idiopathic persistent fetal circulation (n = 2). In addition to supportive medical care and correction of underlying clinical conditions, most of the patients receive vasodilator therapy (Tolazoline) and nonhyperventilation respirator management. The overall mortality rate is 27.6% (8/29). The duration on ventilator therapy in the survival group (9.3 +/- 8.6 days) is not significantly different from in the mortality group (6.0 +/- 7.1 days) (p = 0.13). There is also no statistically significant difference between these two groups both in the maximal alveolar-arterial oxygen tension difference (594 +/- 53 mmHg and 613 +/- 37 mmHg, p = 0.145) and in the maximal oxygenation index (49.7 +/- 29.6 and 61.1 +/- 36.9, p = 0.172) before vasodilator therapy. However, twenty-four hours after treatment, these two parameters change significantly with the former changes to 426 +/- 198 mmHg and 643 +/- 7 mmHg, respectively (p < 0.001), and the latter changes to 21.6 +/- 15.8 and 82.3 +/- 54.8, respectively (p < 0.001). Skin rash, gastrointestinal hemorrhage, hypotension and hyponatremia are the most common complications of Tolazoline therapy. Eight patients have pulmonary complications including pneumothorax (n = 5) and pulmonary interstitial emphysema (n = 3). Two patients develop chronic lung disease. Three patients have neurodevelopmental handicap. In conclusion, we achieve a survival rate of nearly 75% in PPHN mainly with the administration of Tolazoline therapy and the nonhyperventilation respirator approach. Further well-controlled and multicenter studies with newer treatment modalities are crucial for the improvement of survival of PPHN in Taiwan.

Diagnostic pitfalls in congenital right diaphragmatic hernia.

Congenital diaphragmatic hernia (CDH) is a rare disease of newborns. Right-sided diaphragmatic hernia is even rarer. The clinical and radiological presentations, which are well documented in left-sided diaphragmatic hernia, are variable in right-sided diaphragmatic hernia. This makes the diagnosis of right-sided diaphragmatic hernia more difficult. During a 12-year period, seven cases of right-sided diaphragmatic hernia were collected from a single institution. Their presentations and clinical courses have been reviewed. Low prenatal diagnostic rate, various roentgenogram expressions after birth, and absence of specific clinical presentations were noted. These expressions may become pitfalls in diagnosis and lead to inappropriate treatment. From our experience in these 7 cases and a brief literature review, we try to emphasize the characteristics and the diagnostic pitfalls of this disease. In conclusion, right-sided congenital diaphragmatic hernia has a variable clinical spectrum with high mortality and morbidity. Careful evaluation of the clinical presentations, ultrasonography and chest films is mandatory for precise diagnosis.

Candidaemia in special care nurseries: comparison of albicans and parapsilosis infection.

OBJECTIVES: Candidaemia caused by Candida parapsilosis (CP) is being increasingly reported among infants in neonatal intensive care units (NICU). To assess relative severity, clinical manifestations of candidaemia caused by C. albicans (CA) and CP in a NICU were compared. METHODS: Between January 1994 and July 1997, episodes of candidaemia occurring among infants hospitalized in the NICU were identified in a children's hospital. The demographic characteristics, associated risk factors, clinical manifestations and outcome of the infants with CP fungaemia were collected and compared with those of the infants with CA fungaemia. RESULTS: Twenty-four episodes caused by CA and 22 episodes caused by CP were included in this study. No significant differences were found between the two groups for gestational age, birth weight, male gender, post-natal age at onset of candidaemia, frequency of antecedent neonatal events, prior duration of antibiotic therapy and hyperalimentation, as well as presence of central venous catheter (CVC). Infants with CA fungaemia were significantly more likely than those with CP fungaemia to present with hypoxaemia, bradycardia and respiratory distress requiring intubation, and have a longer prior duration of indwelling CVC and a higher dissemination rate. The eradication rate of candidaemia and overall case fatality rate were comparable in both groups. but CP fungaemia did not appear to cause acute lethal events. CONCLUSION: The presenting signs of CP fungaemia are relatively not so severe, but CP fungaemia, which is relatively difficult to eradicate, increases the morbidity and mortality of the infants.

Comparison of hemocytometer leukocyte counts and standard urinalyses for predicting urinary tract infections in febrile infants.

OBJECTIVES: To compare the accuracy of standard and hemocytometer white blood cell (WBC) counts and urinalyses for predicting urinary tract infection (UTI) in febrile infants. METHODS: Enrolled were 230 febrile infants < 12 months of age. All urine specimens were obtained by suprapubic bladder aspiration and microscopically analyzed by the standard urinalysis (UA) and by hemocytometer WBC counts simultaneously, and quantitative urine cultures were performed. Receiver-operating characteristic (ROC) curves were constructed for each method of UA. The optimal cutoff point of the UA test in predicting UTI was determined by ROC analysis. RESULTS: There were 37 positive urine cultures of at least 1,000 CFU/ml. Of these 37 patients, 9 females and 28 males, 1 had a positive blood culture (Escherichia coli). Thirty (81%) of the positive urine cultures had a bacterial colony count > or = 100,000 colony-forming units/ml, whereas the remaining had between 1,000 and 50,000 colony-forming units/ml. The area under the ROC curve for standard UA was 0.790 +/- 0.053, compared with 0.900 +/- 0.039 for hemocytometer WBC counts (P < 0.05). For hemocytometer WBC counts, the presence of < or =10 WBC/microl appeared to be the most useful cutoff point, yielding a high sensitivity (83.8%) and specificity (89.6%). Standard UA, with a cutoff point of 5 WBC/high power field, had a lower sensitivity (64.9%) and similar specificity (88.1%). The hemocytometer WBC counts showed significantly greater sensitivity and positive predictive value (83.8 and 60.8%, respectively) than the standard urinalysis (64.9 and 51.1%, respectively) (P < 0.05). The accuracy, specificity and likelihood ratio of hemocytometer WBC counts were also greater than that of standard UA (88.7, 89.6 and 8.08% vs. 84.3, 88.1 and 5.44%). CONCLUSION: Hemocytometer WBC counts provide more valid and precise prediction of UTI in febrile infants than standard UA. The presence of > or =10 WBC/microl in suprapubic aspiration specimens is the optimum cutoff value for identifying febrile infants for whom urine culture is warranted.

Urinary tract infection in febrile infants younger than eight weeks of Age.

OBJECTIVE: To assess the usefulness of laboratory parameters, including peripheral white blood cell (WBC) count, C-reactive protein (CRP) concentration, erythrocyte sedimentation rate (ESR), and microscopic urinalysis (UA), for identifying febrile infants younger than 8 weeks of age at risk for urinary tract infection (UTI), and comparison of standard UA and hemocytometer WBC counts for predicting the presence of UTI. METHODS: A total of 162 febrile children <8 weeks of age were enrolled in this prospective study. All underwent clinical evaluation and laboratory investigation, including WBC count and differential; ESR; CRP; blood culture; a lumbar puncture for cell count and differential, glucose level, protein level, Gram stain, and culture; and a UA and urine culture. All urine specimens were obtained by suprapubic aspiration and microscopically analyzed with standard UA as well as with hemocytometer WBC counts. Quantitative urine cultures were performed. Sensitivity, specificity, accuracy, likelihood ratios, and receiver operating characteristic (ROC) curves were determined for each of the screening tests. RESULTS: There were 22 positive urine culture results of at least 100 colony-forming unit/mL. Eighteen of these 22 patients were males, and all were uncircumcised. There were significant differences for pyuria >/=5 WBCs/hpf, pyuria >/=10 WBC/microL, CRP >20 mg/L, and ESR >30 mm/hour between culture-positive and culture-negative groups (P <.05). The ROC area for hemocytometer WBC count, standard UA, peripheral WBC count, ESR, and CRP concentration were.909 +/-.045,.791 +/-.065,.544 +/-.074,. 787 +/-.060, and.822 +/-.036, respectively. The ROC curve analysis indicates that the CRP, ESR, and standard UA were powerful but imperfect tools with which to discriminate for UTI in potentially infected neonates. Hemocytometer WBC counts had the highest sensitivity, specificity, accuracy, and likelihood ratios for identifying very young infants with positive urine culture results. For all assessments, hemocytometer WBC counts were significantly different, compared with the standard urinalysis. ESR, CRP, and peripheral WBC counts were not helpful in identifying UTI in febrile infants. CONCLUSION: UTI had a prevalence of 13.6% in febrile infants <8 weeks of age. The CRP, ESR, and standard UA were imperfect tools in discriminating for UTI, and the sensitivity of these laboratory parameters was relatively low. Hemocytometer WBC count was a significantly better predictor of UTI in febrile infants.

Vallecular cyst: an uncommon cause of stridor in newborn infants.

UNLABELLED: Vallecular cyst, a rare but generally benign lesion in the larynx, may cause stridor and even life-threatening airway obstruction in early infancy. We retrospectively studied 14 cases of newborn infants with vallecular cyst. There was no gender predilection and most cases were full-term and appropriate for gestational age. The clinical presentations included stridor, chest wall retraction, feeding difficulties and failure to thrive. Laryngomalacia was the most common associated anomaly. Flexible laryngoscopy was sufficient for diagnosing the vallecular cyst and larygmalacia. Maintenance of airway patency, nutritional support, and de-roofing of the cyst were the mainstays of management. CONCLUSION: Vallecular cyst should be included in the differential diagnosis of stridor in newborn infants. Respiratory and feeding difficulties in these patients can be dramatically improved after appropriate surgical removal of the cyst.

Image data compression using cubic convolution spline interpolation.

A new cubic convolution spline interpolation (CCSI )for both one-dimensional (1-D) and two-dimensional (2-D) signals is developed in order to subsample signal and image compression data. The CCSI yields a very accurate algorithm for smoothing. It is also shown that this new and fast smoothing filter for CCSI can be used with the JPEG standard to design an improved JPEG encoder-decoder for a high compression ratio.

Treatment and outcome of congenital diaphragmatic hernia.

BACKGROUND AND PURPOSE: Congenital diaphragmatic hernia (CDH) is a challenging condition and is associated with a high mortality rate; optimal therapy remains unclear. This retrospective study describes the clinical characteristics of treatment and outcome in 48 infants with CDH. METHODS: Twenty-eight male (58%) and 20 female (42%) infants with CDH were treated from 1987 through 1998. The goals of the ventilator strategy were permissive hypercapnea (PaCO2 < or = 55 mm Hg) and avoidance of hyperventilation. Infants were initially ventilated with an intermittent mandatory rate of 40 to 60 per minute, peak inspiratory pressure of 20 to 25 cm H2O, and positive end-expiratory pressure of 5 cm H2O. High-frequency positive pressure ventilation was used if hypoxemia or severe hypercapnea (PaCO2 > 60 mm Hg) occurred. Most infants underwent repair after 3 days of age and only four infants underwent early repair within 24 hours of birth. A prophylactic chest tube was placed in the ipsilateral hemithorax postoperatively in all patients treated before 1996. The severity of respiratory distress was estimated by alveolar-arterial oxygen difference, oxygenation index, and alveolar-arterial ratio. RESULTS: Forty-six patients presented with Bochdalek CDH, and two with Morgangni CDH. Antenatal diagnosis was made in 10 cases. Respiratory distress was the major manifestation and usually occurred immediately after birth. Six cases were diagnosed several months after birth and presented mainly with gastrointestinal symptoms. Eleven patients died before surgery and 37 patients underwent surgical repair. Two infants died postoperatively because of congestive heart failure and tension pneumothorax, respectively. The overall mortality rate was 27%. The major causes of mortality were severe respiratory failure, persistent pulmonary hypertension, pneumothorax, and associated anomalies. CONCLUSION: Nearly 75% of patients in this series survived. This suggests that noninvasive respiratory care combined with delayed surgery may be an acceptable strategy for the treatment of CDH, and can be used in most medical institutions without equipment for extracorporeal membrane oxygenation therapy.

Fluconazole therapy in neonatal candidemia.

We reviewed 62 episodes (from 59 infants) of neonatal candidemia that occurred between January 1994 and June 1999. Except 5 term babies, all infants were premature (median gestational age [GA], 30 weeks) and birth weight was less than 2,500 g (median, 1,300 g). Most infants had reported risk factors and other neonatal problems. The age at onset of candidemia ranged from 15 to 173 days with a median of 34 days. In addition to catheter removal, all but one infants received antifungal agents and candidemia was eradicated subsequently in 46 episodes (75%). Eighteen infants with 19 episodes ever received fluconazole therapy. Fluconazole was administered as the first line agent in 6 episodes and successfully cleared candidemia in 5 episodes. Fluconazole was used as an alternative agent in an additional 13 episodes after amphotericin B (am B) +/- flucytosine were given for a period without a satisfactory result and eradication of candidemia was achieved in 8 episodes subsequently. All 18 infants tolerated fluconazole well and no withdrawal was required on account of its adverse effect. In contrast, am B alone was administered as the first line agent in 55 episodes and successfully cleared candidemia in 32 episodes (58%). This retrospective analysis suggests that fluconazole appears to be safe in neonates and can be used as an alternative agent in treating neonatal candidemia. A large-scaled prospective study may be needed.

Hirschsprung's disease presenting with diffuse intestinal pneumatosis in a neonate.

In the neonate, pneumatosis intestinalis is almost always associated with necrotizing enterocolitis. The manifestation of diffuse intestinal pneumatosis in Hirschsprung's disease has been reported rarely. It may occur as a result of Hirschsprung's disease complicated with enterocolitis. We report a two-day-old female baby born at term with the problems of failure to pass meconium, progressive abdominal distension and bile stained vomiting. There was an early roentgenographic presentation of pneumatosis intestinalis which might have led to a diagnosis of necrotizing enterocolitis. However, the intestinal pneumatosis resolved within 48 hours. After anorectal manometry and contrast enema examination, an ileostomy was performed at the age of 23 days, and multiple biopsies of intestine showed aganglionosis up to the ileum at the level of 85 cm above the ileocecal valve. Unfortunately, the patient developed short bowel syndrome after operation and died suddenly after an accidental choking at the age of three months. This case suggests that Hirschsprung's disease may have an unusual early roentgenographic presentation with diffuse intestinal pneumatosis in the first few days of life. Anorectal manometries and suction biopsies are crucial for further diagnosis.

Neonatal necrotizing fasciitis: a report of three cases and review of the literature.

OBJECTIVE: Necrotizing fasciitis (NF) is a predominantly adult disorder, with bacterial infection of the soft tissue. In children, it is relatively rare and has a fulminant course with a high mortality rate. In the neonate, most cases of NF are attributable to secondary infection of omphalitis, balanitis, mammitis, postoperative complications, and fetal monitoring. The objective of this communication is to report 3 cases of neonatal NF and provide a literature review of this disorder. RESULTS: This review yielded 66 cases of neonatal NF. Only 3 cases were premature. There was no sex predilection and the condition rarely recurred. Several underlying conditions were identified that might have contributed to the development of neonatal NF. These included omphalitis in 47, mammitis in 5, balanitis in 4, fetal scalp monitoring in 2, necrotizing enterocolitis, immunodeficiency, bullous impetigo, and maternal mastitis in 1 patient each. The most common site of the initial involvement was the abdominal wall (n = 53), followed by the thorax (n = 7), back (n = 2), scalp (n = 2), and extremity (n = 2). The initial skin presentation ranged from minimal rash to erythema, edema, induration or cellulitis. The lesions subsequently spread rapidly. The overlying skin might later develop a violaceous discoloration, peau d'orange appearance, bullae, or necrosis. Crepitus was uncommon. Fever and tachycardia were frequent but not uniformly present. The leukocyte count of the peripheral blood was usually elevated with a shift to the left. Thrombocytopenia was noted in half of the cases. Hypocalcemia was rarely reported. Of the 53 wound cultures available for bacteriologic evaluation, 39 were polymicrobial, 13 were monomicrobial, and 1 was sterile. Blood culture was positive in only 20 cases (50%). Treatment modalities included the use of antibiotics, supportive care, surgical debridement, and drainage of the affected fascial planes. Two of the 6 cases who received hyperbaric oxygen therapy died. The overall mortality rate was 59% (39/66). In 12 cases, skin grafting was required because of poor granulation formation or large postoperative skin defects among the survivors. CONCLUSION: Neonatal NF is an uncommon but often fatal bacterial infection of the skin, subcutaneous fat, superficial fascia, and deep fascia. It is characterized by marked tissue edema, rapid spread of inflammation, and signs of systemic toxicity. The wound cultures are predominantly polymicrobial and the location of initial involvement depends on the underlying etiologic factor. High index of suspicion, prompt aggressive surgery, appropriate antibiotics, and supportive care are the mainstays of management in the newborn infant with NF.

The role of pulmonary inflammation in the development of pulmonary hypertension in newborn with meconium aspiration syndrome (MAS).

1. There was no clear correlation between the tracheal aspirate cytokines and the elevation of pulmonary arterial pressure in newborn piglets with MAS. The use of dexamethasone significantly suppressed tracheal aspirate cytokines but did not significantly alter pulmonary arterial pressure. Dexamethasone significantly increased the cardiac stroke volume and blood pressure. 2. Early dexamethasone therapy (< 12 hrs) for one week in infants with MAS significantly improved pulmonary ventilation and facilitated weaning from mechanical ventilation. 3. The mechanisms for the improvement in cardiopulmonary status following early dexamethasone therapy in MAS remain unclear. An overall improvement in cardiac hemodynamics, along with a significant decrease in lung inflammation may be responsible for the improvement.

Prevention of chronic lung disease in preterm infants by early postnatal dexamethasone therapy.

Recent studies suggest that early dexamethasone therapy may lessen the pulmonary inflammation in preterm infants with respiratory distress syndrome (RDS). To investigate whether early (<12 hr) postnatal dexamethasone therapy would reduce the incidence of chronic lung disease (CLD), a randomized, double-blind, controlled trial was conducted in 40 infants (birth weights from 500 to 1,999 gm) who had severe RDS and required mechanical ventilation within 6 hr of birth. All infants received one dose of Survanta before they were randomly assigned to control (saline placebo) or dexamethasone-treated groups (0.5 mg/kg/d for 1 week, then tapered over 3 weeks). Sequential analysis was performed with the end point of assessment being the presence or absence of CLD on postnatal Day 28. Statistical significance favoring dexamethasone was reached when 12 consecutive pairs in which one infant had CLD and the other did not have CLD showed that ten pairs favored dexamethasone and two pairs favored control treatment. Among the survivors, 12/15 were extubated in the dexamethasone group and 9/16 in the control group at the end of study. Infants in the treated group had transient hyperglycemia and hypertension. There was no difference between the groups in mortality and in incidence of sepsis or intraventricular hemorrhage. We conclude that early postnatal dexamethasone therapy is potentially effective in the lessening of CLD in preterm infants. To substantiate our result, large randomized controlled trials are needed and warranted.