Medium term outcome for infant repair in tetralogy of Fallot: indicators for timing of surgery

Objective: To assess the impact of early corrective surgery on the short and medium term outcome in tetralogy of Fallot (TOF). Materials and methods: All patients under 12 months of age undergoing correction of isolated TOF between February 1997 and July 2003 were reviewed retrospectively. Outcome data for mortality, post-operative care management, major morbidity and clinical follow-up were analysed. Results: Fifty-two operations were performed. The mean age at surgery was 5 months (range 1–12) of whom 16 (30.8%) were less than 3 months old, including 2 neonates, 22 (42.3%) were 3–6 months old and 14 (26.9%) were 7–12 months old. There was 1 (1.9%) early death caused by a cerebro-vascular accident and 1 (1.9%) late death secondary to acute infective endocarditis. There were no differences in post-operative morbidities attributable to age. Patients under 3 months old required greater duration of post-operative ventilation, ITU stay and in-hospital stay. At a mean follow-up of 4.0 years (range 1.5–8.0), 33 (63.5%) patients had well-tolerated pulmonary regurgitation (PR) and 3 (5.8%) patients required re-operation for right ventricular outflow tract obstruction (RVOTO). All patients had right bundle-branch-block but with QRS < 150 ms. Conclusion: Early definitive repair of TOF can be performed safely on patients under 6 months old. Age at surgery does not appear to affect the medium term haemodynamic outcome. However, early surgery does escalate the need for ICU care. This data suggests repair in asymptomatic patients be delayed until 3–6 months of age.     

Physical and Sexual Abuse and their Relation to Psychiatric Disorder and Suicidal Behavior among Adolescents who are Psychiatrically Hospitalized

Adolescents who were psychiatrically hospitalized ( N = 105) were classified as sexually abused, physically abused, both sexually and physically abused, or not abused, and studied to determine the prevalence of suicidal behavior and psychiatric disorders. Self-reports of hopelessness, depression, coping, and self-concept were also examined. No difference in suicidal behavior or psychiatric disorder, based on abuse history, was found, with one exception. Adolescents who were sexually abused, particularly those who experienced the most severe sexual abuse, used negative coping strategies more often than those not sexually abused. Findings suggest that symptomatology of adolescents who are psychiatrically hospitalized does not differ markedly based on history of abuse.     

Proteolytic Processing Mechanisms in the Biosynthesis of Neuroendocrine Peptides: The Subtilisin-like Proprotein Convertases

The recent discovery of a novel family of precursor processing endoproteases has greatly accelerated progress in understanding the complex mechanisms underlying the maturation of prohormones, neuropeptides, and many other precursor-derived proteins. At least six members of this family have been found thus far in mammalian species, several having alternatively spliced isoforms, and related enzymes have been identified in many invertebrates, including molluscs, insects, nematodes, and coelenterates. The proprotein convertases are all dependent on calcium for activity and all possess highly conserved subtilisin-like domains with the characteristic catalytic triad of this serine protease (ordered Asp, His, and Ser along the polypeptide chain). Two members of this family, PC2(SPC2) and PC1/PC3(SPC3), appear to play a preeminent role in neuroendocrine precursor processing. Both convertases are expressed only in the brain and in the extended neuroendocrine system, while another important family member—furin/PACE (SPC1)—is expressed more ubiquitously, in almost all tissues, and at high levels in liver. SPC2 and SPC3 exhibit acidic pH optima and other properties which enhance their activity in the acidic, calcium-enriched environment of the dense-core secretory granules of the regulated pathway in neuroendocrine cells, while furin has a neutral pH optimum and is localized predominantly to the trans Golgi network where it is retained by a C-terminal transmembrane domain. Furin processes a wide variety of precursors in the constitutive pathway, such as those of growth factors, receptors, coagulation factors, and viral glycoproteins. Recent findings on the processing of proopiomelanocortin, proinsulin, proglucagon, and several other neuroendocrine precursors by SPC2 and SPC3 are discussed, along with information on the structure, properties, evolution, developmental expression, and regulation or the convertases. An inherited defect in the fat/fat mouse which affects the processing of proinsulin, and probably also many other prohormones, due to a point mutation in carboxypeptidase E has recently been identified and has begun to provide new insights into the functional integration of the individual processing steps.     

Crystalloids, colloids and kids: a review of paediatric burns in intensive care

This is a retrospective review of all burns patients admitted to a paediatric intensive care unit (PICU) over a 7 year period. Resuscitation fluid therapy and clinical course are presented. Ninety-eight new burns victims were admitted with a mortality rate of 10.2%, all in burns of greater than 25% body surface area (BSA). The incidence of ARDS was 20%, with an 18% mortality rate. Of 85 patients with burns greater than 5% BSA, 33 received the hospital-recommended colloid-based resuscitation formula, 46 received a combination of crystalloids and colloids and in 6 patients the resuscitation regimen was not able to be determined. The aetiology, age distribution, sex ratio, severity of burns and length of stay in hospital did not alter significantly over the study period. The number of burns admissions to PICU increased, as did their duration of intubation and ICU stay. The hospital-recommended resuscitation formula consistently underestimated the fluid volume required for adequate resuscitation. No statistically significant difference in adverse effects was found between the resuscitation groups. This study is unable to recommend a definitive approach to the fluid resuscitation of burns shock in paediatrics and the best approach is one of meticulous fluid resuscitation titrated on clinical effect.     

Focal reduction of villous blood flow in early indomethacin enteropathy: a dynamic vascular study in the rat

Background—Oral indomethacin causes villousshortening, microvascular damage, and distortion, which might inducemucosal ischaemia and necrosis.
Aims—In order to determine the early events inindomethacin induced jejunal injury we examined the temporal relationsbetween morphological damage and changes in villous blood flowfollowing indomethacin.
Methods—In anaesthetised rats, mid jejunal villiwere exteriorised in a chamber and observed by fluorescence microscopy.Blood flow in surface capillaries was calculated from velocities and diameters. Indomethacin was applied by both luminal and intravenous routes for 90 minutes, after which the animal was perfusion fixed andthe villi were processed for histological examination. Control animalsreceived intravenous or luminal bicarbonate (1.25%).
Results—Blood flow slowed in individual villi at20 minutes, and progressed to complete stasis (in another group) by 45 minutes. Histological examination at 20 minutes revealed microvascular distortion, but no villous shortening: crypt depth:villous height ratios were 0.356 (0.02) in test and 0.386 (0.01) in surrounding villi(p>0.5). At stasis, the villi under study showed epithelial clumpingand were shortened: crypt depth:villous height ratios were 0.92 (0.2)in test and 0.42 (0.06) in surrounding villi (p<0.02). Vehicle alonehad no effect on either blood flow or histology.
Conclusions—Focal slowing of villous blood flowand microvascular distortion precede villus shortening and epithelialdisruption, and indicate that damage to surface microvasculature is anearly event in indomethacin induced mucosal injury in this model.

Keywords:indomethacin; jejunum; villi; microcirculation; endothelium; microthrombi

     

Syndrome of Inappropriate Antidiuresis in Ovarian Serous Carcinoma with Neuroendocrine Differentiation

A 58-year-old postmenopausal woman with primary ovarian serous carcinoma presented with the syndrome of inappropriate antidiuresis (SIAD). Preoperative workup showed serum sodium level of 110 mEq/liter and antidiuretic hormone level of 3.3 pg/ml. The serum and urine osmolarity were 239 and 371, respectively. Antidiuretic hormone was demonstrated in tumor cells by immunohistochemistry. To the best of the authors’ knowledge, this represents the first case of SIAD due to primary ovarian tumor.     

Thiol Reduction of 3′-Azidothymidine to 3′-Aminothymidine: Kinetics and Biomedical Implications

The ability of thiols to reduce 3-azidothymidine (AZT) to 3-aminothymidine has been investigated. Incubation with glutathione, dithiothreitol (DTT), or mercaptoethanol at pH 7.2 and 37°C leads to quantitative reduction of the azido moiety to an amine. The reaction is first order in AZT and first order in reducing agent (mono- or dithiol). The second-order rate constants are 2.77 × 10^–3, 6.55 × 10^–5, and 6.35 × 10^–6 M ^–l sec^–1 for the dithiothreitol, glutathione, and mercaptoethanol reductions, respectively. The thiol reduction of alkyl azide to amine under mild conditions is a synthetic method particularly suitable for water-soluble azido compounds that are sensitive to catalytic hydrogenation. The potential for the mono- or dithiol-mediated reduction of alkyl azides under biological conditions must be considered when conducting studies of azido drugs.     

Factors influencing the likelihood of successful decisions to treat dentin caries from bitewing radiographs

The purpose of this study was to describe the role played by the ability to estimate caries depth in successfully deciding to treat dentin caries when making use of bitewing radiographs as a diagnostic test. A 10% random sample (n = 444) of Dutch dental practitioners was sent a two-wave questionnaire concerning radiographic caries diagnosis and restorative treatment decision making. The second wave consisted of simulated bitewing radiographs of 105 tooth surfaces with and without dentin caries according to two measuring standards: (a) a micro-radiographic "gold" standard and (b) a norm of expert observers. The dentists were asked to diagnose caries at 4 depths of penetration using a 5-point certainty scoring system to measure diagnostic ability; and to make a treatment decision for each surface. The overall response was 61% (273). A regression analysis was carried out using the chance per dentist of correctly deciding to treat dentin caries as the dependent variable. The degree of agreement with the experts' diagnosis of radiographic caries depth was used to create variables measuring diagnostic ability. Five significant (P less than 0.05) variables explained 60% (R2 = 0.60) of the variation in decision making. The best diagnostic ability variable explained 47% of the variation while the treatment criterion reportedly used explained 3%. We conclude that the ability of practitioners to interpret radiographs plays a major role in treatment decision making and that their reported treatment decision making criteria should not be taken at face value.