Emir Q. Haxhija

Reduced severity of a mouse colitis model with angiotensin converting enzyme inhibition.

Ulcerative colitis is characterized by elevated rates of epithelial cell apoptosis, and an up-regulation of pro-apoptotic cytokines including tumor necrosis factor α (TNF-α). Recently, angiotensin converting enzyme (ACE) has been shown to promote apoptosis. In addition, pharmacologic ACE inhibition (ACE-I) both prevents apoptosis and reduces TNF-α expression in vitro. We hypothesized that ACE-I, using enalaprilat, would decrease colonic epithelial cell apoptosis and reduce colitis severity in the dextran sulfate sodium (DSS)-induced colitis model in mice. We assessed the severity of colitis, and colonic epithelial cell apoptosis, after administration of DSS. Mice were given either daily ACE-I treatment or daily placebo. ACE-I treatment markedly improved clinical outcomes. In addition, ACE-I treatment significantly reduced the maximum histopathologic colitis grade. ACE-I also dramatically reduced the epithelial apoptotic rate. To investigate the mechanism by which ACE-I reduced apoptosis; we measured TNF-α, Bcl-2, and Bax expression. TNF-α mRNA was significantly lower with ACE-I treatment compared to placebo at every time point, as was the ratio of Bax to Bcl-2. We conclude that ACE-I reduces the severity of DSS-induced colitis and reduces epithelial cell apoptosis.

IMPACT OF CALORIC INTAKE ON PARENTERAL NUTRITION-ASSOCIATED INTESTINAL MORPHOLOGY AND MUCOSAL BARRIER FUNCTION

BACKGROUND Parenteral nutrition (PN) is known to induce villus atrophy, epithelial cell (EC) apoptosis, and increase mucosal permeability. The study hypothesized that increasing amounts of energy delivery to mice would result in the best outcome, with the least effects on the mucosa. METHODS Mice were randomized to enteral controls (saline infusion with ad libitum enteral food) or to 1 of 3 PN groups (with no enteral nutrition): full (100% of daily average energy intake for the mouse), reduced (75% of energy intake) or very low (50% of energy intake). Mice received PN for 7 days. Mucosal morphology, EC apoptosis, and bacterial translocation were assessed. RESULTS Villus height decreased significantly with decreasing levels of caloric intake and was significantly lower in all PN groups compared with controls. Body weight loss was significantly greater in PN groups vs controls and was greatest in mice with the lowest caloric delivery. A consistent trend toward a higher EC apoptotic index with decreasing caloric intake was observed, and apoptosis in all PN groups exceeded controls (2-fold). All PN groups demonstrated greater bacterial translocation than controls. CONCLUSIONS PN induces intestinal EC apoptosis and villus and crypt atrophy, even at 100% of predicted energy needs, and such changes increased with greater reduction of energy intake. This study supports a concept that lack of enteral nutrition, rather than absolute caloric levels, is responsible for many of the adverse effects of PN. The study also allows the investigators to better optimize a mouse model of PN delivery.

Lung contusion-lacerations after blunt thoracic trauma in children

Chest trauma in children is an indicator of injury severity and is associated with a high mortality rate. The aim of this study was to investigate the impact of pulmonary contusion-laceration on short and long-term outcome of pediatric patients after blunt thoracic trauma. A retrospective analysis of records of 41 children aged 10 months to 17 years who were treated for pulmonary and associated injuries between 1986 and 2000 was done concerning mode of injury, types of injuries, management and outcome. In addition, a follow-up investigation was performed 4.5±1 years after injury. Of the patients 27 were involved in motor vehicle accidents (MVA group) and 14 patients suffered other types of accidents (others group). The mean injury severity score (ISS) was 30±2 (range 9–75) with no significant difference between the groups. Patients from the MVA group suffered more frequently bilateral pulmonary lesions and needed more often chest tube placement (p<0.05), 5 patients died (12%) all from the MVA group. The follow-up investigation of 34 patients showed unremarkable chest x-rays and normal lung function in all but 1 patient with bronchial asthma. In conclusion, children who recover after a pulmonary contusion-laceration trauma do not suffer from significant late respiratory problems.

INTESTINAL INTRAEPITHELIAL LYMPHOCYTE DERIVED ANGIOTENSIN CONVERTING ENZYME MODULATES EPITHELIAL CELL APOPTOSIS

Background & Aims: Intestinal adaptation in short bowel syndrome (SBS) consists of increased epithelial cell (EC) proliferation as well as apoptosis. Previous microarray analyses of intraepithelial lymphocytes (IEL) gene expression after SBS showed an increased expression of angiotensin converting enzyme (ACE). Because ACE has been shown to promote alveolar EC apoptosis, we examined if IEL-derived ACE plays a role in intestinal EC apoptosis.Methods: Mice underwent either a 70% mid-intestinal resection (SBS group) or a transection (Sham group) and were studied at 7 days. ACE expression was measured, and ACE inhibition (ACE-I, enalaprilat) was used to assess ACE function.Results: IEL-derived ACE was significantly elevated in SBS mice. The addition of an ACE-I to SBS mice resulted in a significant decline in EC apoptosis. To address a possible mechanism, tumor necrosis factor alpha (TNF-α) mRNA expression was measured. TNF-α was significantly increased in SBS mice, and decreased with ACE-I. Interestingly, ACE-I was not able to decrease EC apoptosis in TNF-α knockout mice.Conclusions: This study shows a previously undescribed expression of ACE by IEL. SBS was associated with an increase in IEL-derived ACE. ACE appears to be associated with an up-regulation of intestinal EC apoptosis. ACE-I significantly decreased EC apoptosis.

Treatment of medial epicondylar apophyseal avulsion injury in children

ZusammenfassungOperationszielOperative Reposition und Retention der Apophyse des Epicondylus ulnaris zur Vermeidung von Gelenkinstabilitäten, bleibenden Fehlstellungen und Pseudarthrosen.IndikationenAbsolut: Intraartikulär dislozierte Apophyse des Epicondylus ulnaris, komplette Läsion des Nervus ulnaris.Relativ: Dislokation der Apophyse (> 4 mm) bei Kindern > 5 Jahre, wobei die Indikation mit zunehmender Dislokation, steigendem Alter oder besonderer sportlicher Aktivität des Kindes großzügiger zu stellen ist.KontraindikationenDislokation der Apophyse (≤ 4 mm) bei Kindern < 5 Jahre, sofern das Fragment nicht intraartikulär liegt.OperationstechnikOffene Reposition der Apophyse über einen ulnaren Zugang. Identifikation des Nervus ulnaris. Bei jüngeren Kindern bzw. bei sehr kleinen Fragmenten Fixation mit Kirschner-Draht. Schraubenfixation bei größeren knöchernen Fragmenten und älteren Kindern.WeiterbehandlungOberarmgipslonguette bis zum Abschluss der Wundheilung. Anschließend Oberarmgipsverband für 3 Wochen. Entfernung der Kirschner-Drähte nach 4–6 Wochen.Schraubenentfernung nach 8–12 Wochen. Physiotherapie nur, wenn 6 Wochen nach Entfernung des Gipsverbands noch eine deutlich eingeschränkte Beweglichkeit des Ellenbogengelenks vorliegt.ErgebnisseIm Zeitraum vom 01.01.1994 bis 31.12.2003 wurden 25 Kinder mit einem Durchschnittsalter von 12 Jahren wegen eines Apophysenabrisses am Epicondylus ulnaris mit offener Reposition und Kirschner-Draht-Fixation operiert.Durchschnittlich 3 Jahre nach dem Unfall konnten 14 dieser Kinder entsprechend einem Schema, das subjektive, klinische und radiologische Parameter bewertet, nachuntersucht werden. Zwei Kinder zeigten eine geringe Minderung der groben Kraft des verletzten Arms im Seitenvergleich. Ein Kind wies ein Ellenbogenflexionsdefizit von 10° auf, bei den übrigen Kinder fanden sich Bewegungseinschränkungen von maximal 5° im Seitenvergleich. In allen nachuntersuchten Fällen zeigte sich eine minimale Zunahme der Valgisierung des Ellenbogengelenks der Frakturseite im Vergleich zur unverletzten Seite (durchschnittlich 3°). Alle Frakturen waren innerhalb von 6 Wochen knöchern konsolidiert.AbstractObjectiveSurgical reduction and retention of apophyseal avulsion injuries at the medial epicondyle to prevent joint instability, lasting malalignment, or pseudarthrosis.IndicationsAbsolute: intraarticular apophyseal dislocation of the medial epicondyle, complete lesion of the ulnar nerve.Relative: dislocation of the apophysis (> 4 mm) in children > 5 years of age; the need for intervention increases in children as the degree of dislocation, age, and athletic activity increase.ContraindicationsDislocation of the medial epicondyle (≤ 4 mm) in children < 5 years of age, provided the fragment location is not intraarticular.Surgical TechniqueOpen reduction of the apophysis through a medial approach. Identification of the ulnar nerve. In young children or with small fragments fixation with Kirschner wire. Screw fixation in older children or for larger fragments.Postoperative ManagementLong upper-arm plaster cast until wound healing is achieved. Subsequently, upper-arm plaster cast for 3 weeks. Removal of Kirschner wires after 4–6 weeks, screw removal after 8–12 weeks. Physiotherapy only if marked reduction of elbow mobility is found 6 weeks after cast removal.ResultsFrom January 1, 1994 to December 31, 2003, 25 children with an average age of 12 years suffering from medial epicondylar avulsion fractures were operated on using open reduction and Kirschner wire fixation. An average of 3 years after the injury 14 of these children underwent follow-up examination using a procedure that took subjective, clinical and radiologic parameters into account. Two children showed a slight reduction in overall strength of the injured extremity when compared with the contralateral extremity. One child had a flexion deficit of 10°, all other children showed movement limitations of ≤ 5° compared to the contralateral extremity. In all the cases available to follow-up, there was a slight increase in valgus alignment of the elbow joint compared with the uninjured side (3° on average). All fractures consolidated within 6 weeks.

The use of a hand-held metal detector for localisation of ingested metallic foreign bodies: a critical investigation

Ingested metallic foreign bodies (MFBs) are usually diagnosed by taking X-ray films of the neck, chest and/or abdomen. This study evaluates the use of a hand-held metal detector (HHMD) for the diagnosis and localisation of MFBs. In a prospective study, 53 consecutive paediatric patients with history of a swallowed MFB were examined with X-rays and HHMD. In 47 children, the MFB could be verified radiologically. Coins were most frequently swallowed. The HHMD could detect and locate all coins but only 47% of other MFBs. There were no false-positive results. A HHMD is an effective tool for screening the location of suspected ingested coins. This method is easy, inexpensive and free of radiation. Very small MFBs cannot be reliably detected. Conclusion:if an innocuous metallic foreign body is clearly identified with a hand-held metal detector in the stomach or lower gastrointestinal tract of an asymptomatic child, additional radiological confirmation is not required.

Modulation of mouse intestinal epithelial cell turnover in the absence of angiotensin converting enzyme

Angiotensin converting enzyme (ACE) has been shown to be involved in regulation of apoptosis in nonintestinal tissues. This study examined the role of ACE in the modulation of intestinal adaptation utilizing ACE knockout mice (ACE-/-). A 60% small bowel resection (SBR) was used, since this model results in a significant increase in intestinal epithelial cell (EC) apoptosis as well as proliferation. Baseline villus height, crypt depth, and intestinal EC proliferation were higher, and EC apoptosis rates were lower in ACE-/- compared with ACE+/+ mice. After SBR, EC apoptosis rates remained significantly lower in ACE-/- compared with ACE+/+ mice. Furthermore, villus height and crypt depth after SBR continued to be higher in ACE-/- mice. The finding of a lower bax-to-bcl-2 protein ratio in ACE-/- mice may account for reduced EC apoptotic rates after SBR in ACE-/- compared with ACE+/+ mice. The baseline higher rate of EC proliferation in ACE-/- compared with ACE+/+ mice may be due to an increase in the expression of several EC growth factor receptors. In conclusion, ACE appears to have an important role in the modulation of intestinal EC apoptosis and proliferation and suggests that the presence of ACE in the intestinal epithelium has a critical role in guiding epithelial cell adaptive response.

Die Behandlung der Apophysenabrissverletzung des Epicondylus ulnaris im Kindesalter

ZusammenfassungOperationszielOperative Reposition und Retention der Apophyse des Epicondylus ulnaris zur Vermeidung von Gelenkinstabilitäten, bleibenden Fehlstellungen und Pseudarthrosen.IndikationenAbsolut: Intraartikulär dislozierte Apophyse des Epicondylus ulnaris, komplette Läsion des Nervus ulnaris.Relativ: Dislokation der Apophyse (> 4 mm) bei Kindern > 5 Jahre, wobei die Indikation mit zunehmender Dislokation, steigendem Alter oder besonderer sportlicher Aktivität des Kindes großzügiger zu stellen ist.KontraindikationenDislokation der Apophyse (≤ 4 mm) bei Kindern < 5 Jahre, sofern das Fragment nicht intraartikulär liegt.OperationstechnikOffene Reposition der Apophyse über einen ulnaren Zugang. Identifikation des Nervus ulnaris. Bei jüngeren Kindern bzw. bei sehr kleinen Fragmenten Fixation mit Kirschner-Draht. Schraubenfixation bei größeren knöchernen Fragmenten und älteren Kindern.WeiterbehandlungOberarmgipslonguette bis zum Abschluss der Wundheilung. Anschließend Oberarmgipsverband für 3 Wochen. Entfernung der Kirschner-Drähte nach 4–6 Wochen.Schraubenentfernung nach 8–12 Wochen. Physiotherapie nur, wenn 6 Wochen nach Entfernung des Gipsverbands noch eine deutlich eingeschränkte Beweglichkeit des Ellenbogengelenks vorliegt.ErgebnisseIm Zeitraum vom 01.01.1994 bis 31.12.2003 wurden 25 Kinder mit einem Durchschnittsalter von 12 Jahren wegen eines Apophysenabrisses am Epicondylus ulnaris mit offener Reposition und Kirschner-Draht-Fixation operiert.Durchschnittlich 3 Jahre nach dem Unfall konnten 14 dieser Kinder entsprechend einem Schema, das subjektive, klinische und radiologische Parameter bewertet, nachuntersucht werden. Zwei Kinder zeigten eine geringe Minderung der groben Kraft des verletzten Arms im Seitenvergleich. Ein Kind wies ein Ellenbogenflexionsdefizit von 10° auf, bei den übrigen Kinder fanden sich Bewegungseinschränkungen von maximal 5° im Seitenvergleich. In allen nachuntersuchten Fällen zeigte sich eine minimale Zunahme der Valgisierung des Ellenbogengelenks der Frakturseite im Vergleich zur unverletzten Seite (durchschnittlich 3°). Alle Frakturen waren innerhalb von 6 Wochen knöchern konsolidiert.AbstractObjectiveSurgical reduction and retention of apophyseal avulsion injuries at the medial epicondyle to prevent joint instability, lasting malalignment, or pseudarthrosis.IndicationsAbsolute: intraarticular apophyseal dislocation of the medial epicondyle, complete lesion of the ulnar nerve.Relative: dislocation of the apophysis (> 4 mm) in children > 5 years of age; the need for intervention increases in children as the degree of dislocation, age, and athletic activity increase.ContraindicationsDislocation of the medial epicondyle (≤ 4 mm) in children < 5 years of age, provided the fragment location is not intraarticular.Surgical TechniqueOpen reduction of the apophysis through a medial approach. Identification of the ulnar nerve. In young children or with small fragments fixation with Kirschner wire. Screw fixation in older children or for larger fragments.Postoperative ManagementLong upper-arm plaster cast until wound healing is achieved. Subsequently, upper-arm plaster cast for 3 weeks. Removal of Kirschner wires after 4–6 weeks, screw removal after 8–12 weeks. Physiotherapy only if marked reduction of elbow mobility is found 6 weeks after cast removal.ResultsFrom January 1, 1994 to December 31, 2003, 25 children with an average age of 12 years suffering from medial epicondylar avulsion fractures were operated on using open reduction and Kirschner wire fixation. An average of 3 years after the injury 14 of these children underwent follow-up examination using a procedure that took subjective, clinical and radiologic parameters into account. Two children showed a slight reduction in overall strength of the injured extremity when compared with the contralateral extremity. One child had a flexion deficit of 10°, all other children showed movement limitations of ≤ 5° compared to the contralateral extremity. In all the cases available to follow-up, there was a slight increase in valgus alignment of the elbow joint compared with the uninjured side (3° on average). All fractures consolidated within 6 weeks.

Sirolimus for the Treatment of a Massive Capillary-Lymphatico-Venous Malformation: A Case Report.

Management of patients with complex vascular anomalies (VAs) is often associated with significant morbidity and mortality because of the lack of effective treatment modalities that may lead to significant improvement of the disease and/or healing. Recently, reports of treatment of patients with complex VAs with sirolimus revealed encouraging results. Sirolimus inhibits the mammalian target of rapamycin, which acts as a master switch of numerous cellular processes. We report a successful use of sirolimus for the treatment of a patient with a complex CLVM of the trunk and the right lower extremity believed to be untreatable. Our patient had 44 hospitalizations during the 10-year period, with various unsuccessful treatments and continuous deterioration of his clinical condition, ending up in a wheelchair. His condition reversed to normal everyday activities 9 months after initiation of sirolimus therapy. We conclude that sirolimus is a very promising therapeutic option for children with complex VAs of capillary-lymphatico-venous type.

Reaction of term newborns with prolonged postnatal dyspnoea to early oxygen, mask continuous positive airway pressure, and volume expansion: A prospective, randomised, clinical trial

AbstractIn a prospective, randomised, open trial 103 term newborns with persisting dyspnoea, tachypnoea and/or cyanosis were treated with oxygen for 5–10 min and then with oxygen plus mask continuous positive airway pressure (CPAP) for another 5–15 min. Cases with overt prenatal or intrapartum obstetric pathology had been excluded from the study. Forty-one infants (40%) responded to this procedure within 10–25 min. The remaining 62 infants (60%) were randomly allocated to one of three forms of further treatment: continuation of mask CPAP for 20 min (group A,n=24), volume expansion with 9 ml of 3 ml albumin, 3 ml glucose, and 3 mEq of sodium bicarbonate (group B,n=24), or volume expansion with 4.5 ml albumin and 4.5 ml glucose (group C,n=14). There was no statistical difference in birth weight, gestational age or Apgar scores at 1 and 5 min between the infants of the groups. Time to normalisation of symptoms was significantly shorter in the volume expansion groups (B: 45±41 min, range 20–180, and C: 80±72 min, range 20–210) than in the mask CPAP group (A: 224±256 min, range 30–1200,P=0.02). There were statistical differences in umbilical cord and capillary pH values among the infants of the three groups, but the response to therapy was not related to the degree of acidaemia. Thirty-four infants (33%) who did not respond were admitted to a special care unit for further examination (group A: 21/24, group B: 7/24; group C: 6/14). Of these, 23 had no abnormal findings, 8 infants had radiological signs of transitory respiratory distress, and 1 had a nontension pneumothorax. Septicaemia was found in two infants. No infant was intubated. At discharge all 103 infants did well.ConclusionIncremental application of simple primary care procedures including volume expansion (with or without alkali) in term newborns with persisting postnatal tachypnoea and dyspnoea helps avoid overtreatment and unnecessary separation from the mothers in most cases and reliably selects infants who need close monitoring or special treatment.