p11 in Cholinergic Interneurons of the Nucleus Accumbens Is Essential for Dopamine Responses to Rewarding Stimuli.

A recent study showed that p11 expressed in cholinergic interneurons (CINs) of the nucleus accumbens (NAc) is a key regulator of depression-like behaviors. Dopaminergic neurons projecting to the NAc are responsible for reward-related behaviors, and their function is impaired in depression. The present study investigated the role of p11 in NAc CINs in dopamine responses to rewarding stimuli. The extracellular dopamine and acetylcholine (ACh) levels in the NAc were determined in freely moving male mice using in vivo microdialysis. Rewarding stimuli (cocaine, palatable food, and female mouse encounter) induced an increase in dopamine efflux in the NAc of wild-type (WT) mice. The dopamine responses were attenuated (cocaine) or abolished (food and female mouse encounter) in constitutive p11 knock-out (KO) mice. The dopamine response to cocaine was accompanied by an increase in ACh NAc efflux, whereas the attenuated dopamine response to cocaine in p11 KO mice was restored by activation of nicotinic or muscarinic ACh receptors in the NAc. Dopamine responses to rewarding stimuli and ACh release in the NAc were attenuated in mice with deletion of p11 from cholinergic neurons (ChAT-p11 cKO mice), whereas gene delivery of p11 to CINs restored the dopamine responses. Furthermore, chemogenetic studies revealed that p11 is required for activation of CINs in response to rewarding stimuli. Thus, p11 in NAc CINs plays a critical role in activating these neurons to mediate dopamine responses to rewarding stimuli. The dysregulation of mesolimbic dopamine system by dysfunction of p11 in NAc CINs may be involved in pathogenesis of depressive states.

The Rho guanine nucleotide exchange factor ARHGEF5 promotes tumor malignancy via epithelial-mesenchymal transition.

Epithelial tumor cells often acquire malignant properties, such as invasion/metastasis and uncontrolled cell growth, by undergoing epithelial-mesenchymal transition (EMT). However, the mechanisms by which EMT contributes to malignant progression remain elusive. Here we show that the Rho guanine nucleotide exchange factor (GEF) ARHGEF5 promotes tumor malignancy in a manner dependent on EMT status. We previously identified ARHGEF5, a member of the Dbl family of GEFs, as a multifunctional mediator of Src-induced cell invasion and tumor growth. In the present study, ARHGEF5 was upregulated during tumor growth factor-ß-induced EMT in human epithelial MCF10A cells, and promoted cell migration by activating the Rho-ROCK pathway. ARHGEF5 was necessary for the invasive and in vivo metastatic activity of human colorectal cancer HCT116 cells. These findings underscore the crucial role of ARHGEF5 in cell migration and invasion/metastasis. An in vivo tumorigenesis assay revealed that ARHGEF5 had the potential to promote tumor growth via the phosphatidylinositol 3-kinase (PI3K) pathway. However, ARHGEF5 was not required for tumor growth in epithelial-like human colorectal cancer HCT116 and HT29 cells, whereas the growth of mesenchymal-like SW480 and SW620 cells depended on ARHGEF5. Induction of EMT by tumor necrosis factor-α or Slug in HCT116 cells resulted in the dependence of tumor growth on ARHGEF5. In these mesenchymal-like cells, Akt was activated via ARHGEF5 and its activity was required for tumor growth. Analysis of a transcriptome data set revealed that the combination of ARHGEF5 upregulation and E-cadherin downregulation or Snail upregulation was significantly correlated with poor prognosis in patients with colorectal cancers. Taken together, our findings suggest that EMT-induced ARHGEF5 activation contributes to the progression of tumor malignancy. ARHGEF5 may serve as a potential therapeutic target in a subset of malignant tumors that have undergone EMT.

Endoplasmic reticulum stress response in the rat contusive spinal cord injury model-susceptibility in specific cell types.

STUDY DESIGN: Focus group study. OBJECTIVE: To investigate cell-specific endoplasmic reticulum (ER) stress reactions in contusive spinal cord by evaluating the expression of the glucose-regulated protein 78 (GRP78) and C/EBP homologous transcription factor protein (CHOP) using immunohistochemical staining. SETTING: Data were analysed at Tokai University School of Medicine in Japan. METHODS: The authors generated rat spinal cord injury (SCI) models using an IH-Impactor (100 kdyne(LI), 200 kdyne (HI)). Rats were killed at 1, 3, 5, 7 and 14 days post operation (dpo). Spinal cord sections were prepared and the expression ratio of GRP78 and CHOP was evaluated in oligodendrocyte precursor cells (OPCs) (NG2+), oligodendrocytes (OLs) (APC+), neurons (NeuN+) and astrocytes (GFAP+) using double immunohistochemical staining. We examined an area 8 mm distal from SCI-epicenter. RESULTS: Compared with the sham group, both injured groups had higher GRP78 expression ratio in contused spinal cord at 1 dpo. GRP78 expression ratio was highest in GFAP+ cells of both groups, and lowest in NG2+ cells. Although GRP78 was expressed strongly immediately after SCI in the both groups, increased CHOP expression was observed only in the HI group. The CHOP expression in NG2+ cells was significantly higher than that observed in GFAP+ cells at 5 dpo. CONCLUSION: Although the ER stress response contributes to cell survival in the low-stress SCI conditions, the ER stress response induces an apoptotic cascade in high-stress SCI conditions. The ER response varies according to cell type, with the highest observed in astrocytes, and the lowest observed in oligodendrocyte precursor cells.

Cuerpos extraños en vía aérea / Foreign body in airway

Los cuerpos extraños de la vía aérea constituyen un evento muy peligroso especialmente en niños, constituye la causa principal de muerte accidental en menores de un año y el riesgo se mantiene hasta los tres años. La prevención y el rápido diagnóstico puede salvar muchas vidas. La clínica en general puede ser muy variable desde el momento dramático de la inhalación con sofocación y ahogo hasta un examen normal una vez pasado el episodio agudo. Por esta razón el índice de sospecha y una buena historia a las personas que acompañan a los niños es fundamental.

Foreign body inhalation is a dangerous event, specially in children. It is the most common cause of accidental death in children under 1 year and the risk remains up to age 3 years. Prevention and rapid diagnosis can be life saving. The clinic presentation and radiologic findings may be variable, since the dramatic event of sudden sofocation and choking until normal exam upon the acute presentation has stopped. A good history and high index of suspicious is paramount.

Role of adenosine A1 receptors in the modulation of dopamine D1 and adenosine A2A receptor signaling in the neostriatum.

Adenosine is known to modulate the function of neostriatal neurons. Adenosine acting on A(2A) receptors increases the phosphorylation of dopamine- and cAMP-regulated phosphoprotein of M(r) 32 kDa (DARPP-32) at Thr34 (the cAMP-dependent protein kinase [PKA] site) in striatopallidal neurons, and opposes dopamine D2 receptor signaling. In contrast, the role of adenosine A(1) receptors in the regulation of dopamine/DARPP-32 signaling is not clearly understood. Here, we investigated the effect of adenosine A(1) receptors on D(1), D(2) and A(2A) receptor signaling using mouse neostriatal slices. An A(1) receptor agonist, 2-chloro-N(6)-cyclopentyladenosine (100 nM), caused a transient increase, followed by a transient decrease, in DARPP-32 Thr34 phosphorylation. Our data support the following model for the actions of the A(1) receptor agonist. The A(1) receptor-induced early increase in Thr34 phosphorylation was mediated by presynaptic inhibition of dopamine release, and the subsequent removal of tonic inhibition by D(2) receptors of A(2A) receptor/G(olf)/cAMP/PKA signaling. The A(1) receptor-induced late decrease in Thr34 phosphorylation was mediated by a postsynaptic G(i) mechanism, resulting in inhibition of D(1) and A(2A) receptor-coupled G(olf)/cAMP/PKA signaling in direct and indirect pathway neurons, respectively. In conclusion, A(1) receptors play a major modulatory role in dopamine and adenosine receptor signaling.

Demonstration of reversed flow in segmental branches of the portal vein with hand-held color Doppler ultrasonography after hematopoietic stem cell transplantation.

Hepatic veno-occlusive disease (VOD) is a severe complication of hematopoietic stem cell transplantation (SCT). When monitored with hand-held color Doppler ultrasonography during day -7 to +35 around SCT, reversed blood flow in the segmental branches of the portal vein was detected in nine of 56 patients who had undergone SCT. Three of nine patients had clinical evidence of VOD, but six patients did not fulfill the criteria for diagnosis of VOD initially. Two patients progressed to clinical VOD at a later date and the reversed portal flow disappeared with or without treatment for VOD in the other four patients. Monitoring for reversed portal flow with color Doppler ultrasonography may be a useful tool for the early diagnosis of VOD, and may improve prognosis by allowing early initiation of treatment.

Neuroprotective mechanisms of lidocaine against in vitro ischemic insult of the rat hippocampal CA1 pyramidal neurons.

To compare neuroprotective effects of lidocaine and procaine against ischemic insult, intracellular recordings were made from rat hippocampal CA1 pyramidal neurons in slice preparations. Superfusion of the slices with oxygen- and glucose-deprived medium (in vitro ischemia) produced a rapid depolarization 6 min from the onset. When oxygen and glucose were reintroduced, the membrane depolarized further until it reached 0 mV, and thereafter the membrane showed no functional recovery. Pretreatment with lidocaine (10 microM), but not procaine (50 microM), restored the membrane potential after the reintroduction of oxygen and glucose. Lidocaine, compared to procaine, significantly inhibited the reduction in both tissue ATP content and flavoprotein fluorescence during and after in vitro ischemia. Under electron microscopy, only lidocaine well preserved the structure of mitochondria in the CA1 pyramidal cell body. Extracellular recordings revealed that procaine reduced the field postsynaptic potential whereas lidocaine augmented it. Both drugs reduced the presynaptic volley dose-dependently. Neither lidocaine nor procaine significantly affected a rapid rise of the intracellular Ca2+ level produced by in vitro ischemia in the CA1 region. All the results suggest that the neuroprotective lidocaine action is due to the protection of the mitochondria to maintain the tissue ATP content during and after in vitro ischemia.

Influence of transplanted dose of CD56+ cells on development of graft-versus-host disease in patients receiving G-CSF-mobilized peripheral blood progenitor cells from HLA-identical sibling donors.

We investigated effects of variations in the cellular composition of G-CSF-mobilized peripheral blood progenitor cell (G-PBPC) allografts on clinical outcomes of allogeneic PBPC transplantation. We retrospectively analyzed transplanted doses of various immunocompetent cells from 27 HLA-identical sibling donors in relation to engraftment, incidence of graft-versus-host disease (GVHD), and survival. Significant variability was documented in both absolute numbers and relative proportions of CD34+, CD2+, CD3+, CD4(high)+, CD4+25+, CD8(high)+, CD19+, CD56+, and CD56+16+ cells contained in these allografts. Stepwise Cox regression analysis revealed that the CD56+ cell dose was significantly inversely correlated with the incidence of GVHD. Thus, there was a significantly higher incidence of grade II acute GVHD in patients receiving a lower CD56+16+ cell dose (hazard ratio (HR) 0.0090; 95% confidence interval (CI), <0.00001-3.38; P=0.031), a higher incidence of chronic GVHD in those receiving allografts with a lower CD56+16+ to CD34+ ratio (HR <0.00001; 95% CI <0.00001-0.0007; P=0.0035), and a higher incidence of extensive chronic GVHD in those receiving allografts with a lower CD56+ to CD34+ ratio (HR <0.00001; 95% CI <0.00001-0.053; P=0.0083). These results suggest that CD56+ cells in G-PBPC allografts from HLA-identical sibling donors may play an important role in preventing the development of GVHD.

Covered expandable metallic stent placement for hemostasis of colonic bleeding caused by invasion of gallbladder carcinoma.

A 72-year-old Japanese man was admitted to our hospital complaining of right upper-quadrant abdominal pain, blood in his stool, and symptoms of anemia. On physical examination a hard mass, about 6 cm in diameter, was palpable in the right upper quadrant of the abdomen. Computed tomography revealed a gallbladder carcinoma which had invaded the transverse colon, with liver metastasis. We diagnosed gallbladder carcinoma, stage IVB. Colonoscopy was performed for persistent blood in the stools. This revealed an elevated lesion which appeared to be an invasion of gallbladder carcinoma, with diffuse bleeding from the right-side of the transverse colon. It proved difficult to stop this bleeding by ordinary therapeutic endoscopy. In order to achieve hemostasis we therefore inserted a covered Ultraflex metallic stent to compress the tumor. After stent placement, blood was no longer seen in the patient's stools, he became able to eat soft food and was discharged. This treatment was uninvasive and effective. Covered stent placement appears to be a new and useful method in the management of bleeding from malignant gastrointestinal tumors.

Monitoring of cytomegalovirus reactivation after allogeneic stem cell transplantation: comparison of an antigenemia assay and quantitative real-time polymerase chain reaction.

Cytomegalovirus (CMV) antigenemia and quantitative real-time polymerase chain reaction (PCR) were compared for monitoring of CMV reactivation after allogeneic stem cell transplantation. The number of CMV antigen-positive cells by the antigenemia assay and the level of CMV DNA by real-time PCR correlated well. The sensitivity and specificity of the antigenemia assay was 55.4% and 95.5%, respectively, using real-time PCR as the reference standard. The probability of positive antigenemia at day 100 was 76.5%, with a median of first detection at day 37 in 51 patients, compared with a positive PCR of 84.3% and day 33, respectively. When HLA-identical sibling donor transplant recipients and other donor transplant recipients were analyzed separately, there was no difference between the two tests. However, temporal patterns of first detection of CMV antigen-positive cells and CMV DNA differed between HLA-identical and alternative recipients; patients without CMV (29%) or with sporadic positive PCR results (14%) were more common in HLA-identical sibling transplants, whereas patients with simultaneous antigenemia and positive PCR occurred more in alternative transplants (48%). Two of 51 patients (4%) developed CMV colitis despite antigenemia-guided prophylaxis, but both were successfully treated with ganciclovir. Although PCR is more sensitive than antigenemia, both tests are useful in the early detection of CMV after allogeneic stem cell transplantation.

Results of bowel plication in addition to primary anastomosis in patients with jejunal atresia.

BACKGROUND/PURPOSE: Disturbed intestinal transit (DIT) associated with bowel dilation occurs in some postoperative patients with jejunal atresia. Bowel plication (BP) has been introduced to prevent the DIT, but the long-term results of BP are unclear. METHODS: The authors reviewed the preoperative and operative records and postoperative clinical courses (for 2.3 to 7.0 years; mean period, 3.7 years) of 19 jejunal atresia patients, 4 of whom had undergone additional BP with primary anastomosis after dilated bowel resection or tapering jejunoplasty at neonatal surgery. The degree of DIT was evaluated by the clinical symptoms, weight gain, whether reoperation was performed, and duration from the operation to receiving an oral feeding volume of at least 130 mL/kg/d. The patients then were assigned 4 grades (0 to 3). To determine the presence or absence of bowel dilation at the BP site, the plain abdominal x-rays were reviewed. RESULTS: (1) Within 2 months after surgery, 4 patients without BP underwent operation because of severe DIT. The degree of postoperative DIT in patients who had received additional BP at neonatal surgery was less than that in patients without BP (mean grade, 0.50 v. 2.08). (2) The preoperative clinical features, operative method, and postoperative weight gain were almost similar in patients with and without BP. (3) On abdominal x-ray the bowel dilation remained 6 to 12 months after the operation, but was not observed over 1 year after the operation. CONCLUSIONS: In this preliminary study, the addition of BP after tapering jejunoplasty or resection of dilated bowel may be effective in preventing early postoperative DIT. Further study is necessary to evaluate the long-term results of additional BP at neonatal surgery. J Pediatr Surg 36:1752-1756.

Detection of hepatic oxidative DNA damage in patients with hepatoblastoma and children with non-neoplastic disease.

BACKGROUND: The authors have revealed a significant association between hepatoblastoma and low birth weight. This study was done to explore the evidence that liver cells were oxidatively damaged, based on the hypothesis that oxidative damage to DNA is involved in the development of hepatoblastoma in children of low birth weight. PROCEDURE: Oxidative DNA damage in the liver was examined by immunohistochemically detecting the presence of a DNA repair product, 8-hydroxy-2'-deoxyguanosine (8-OHdG), in five patients with hepatoblastoma and 14 children with non-neoplastic disease. RESULTS: Positive staining for 8-OHdG was observed in all five patients with hepatoblastoma. Distribution of 8-OHdG positivity was diffuse in the intralobular area in one patient and was restricted to the periportal area of the lobules in four patients. There was no apparent correlation between birth weight of the patients, histological findings in the liver, and the distribution of 8-OHdG positivity. In children with non-neoplastic disease, 8-OHdG was detected in nine of 14 patients, and 8-OHdG was positive in the intralobular area of the liver parenchyma except in one patient. CONCLUSIONS: These results suggest that the cause of oxidative DNA damage in patients with hepatoblastoma may be different from the cause, extensive parenchymal damage to the liver, in children with non-neoplastic disease, but the 8-OHdG formation is not specific to hepatoblastoma patients of low birth weight. Further studies to elucidate the true reason for the high incidence of hepatoblastoma in children of low birth weight are necessary.

Effects of recombinant human endostatin on a human neuroblastoma xenograft.

New antitumor agents must be added to the current neuroblastoma treatment regimens to improve the clinical results. We investigated whether recombinant human endostatin (rhEndostatin), an antiangiogenic agent, is effective against human neuroblastoma in the human neuroblastoma xenograft model designated TNB9. When tumors on the back of nude mice grew to a weight of 90-95 mg, rhEndostatin 10 mg/kg/day was administered subcutaneously every day for 10 consecutive days. Mean relative tumor weight in mice administered rhEndostatin (n=5) was significantly less than that in controls (n=12) on days 2, 4, and 6 after the start of administration (p<0.01 on day 2, p<0.05 on days 4 and 6), and regression of tumor growth (TRW<1.0) was marked on day 2. The maximum inhibition rate (MIR) by rhEndostatin was 46.4%, indicating inefficacy, but it may not be appropriate to apply Battelle Columbus Laboratories criteria to this experimental model because rhEndostatin is a protein. After day 8, tumors in the experimental group increased in weight and were not statistically significantly different from those in controls. Recombinant human endostatin was used in tumors in the arterial system of the mouse in this experiment because eventually rhEndostatin, not recombinant mouse endostatin, may be used to treat advanced neuroblastoma in the clinical setting. The results show that there is little cross-reactivity of rhEndostatin with the human and mouse models and indicate that rhEndostatin could become an effective agent for the treatment of human neuroblastoma.

Magnetic resonance angiography of portal collateral pathways after hepatic portoenterostomy in biliary atresia: comparisons with endoscopic findings.

BACKGROUND/PURPOSE: This study was undertaken to assess the usefulness of magnetic resonance angiography (MRA) in detecting varices and to investigate the possibility of avoiding routine endoscopy after surgery for biliary atresia (BA). METHODS: The subjects are 21 patients who have undergone periodical MRA since 1996. The esophageal and gastric vessels were investigated as the sites of potential development of collateral vessels. The collateral vessels on MRA were compared with endoscopic findings. RESULTS: (1) Detection of collateral vessels: of 21 patients examined, 9 patients had 12 varices. MRA depicted collateral vessels in all of the 12 varices (sensitivity, 100%). However, all MRA findings, but one was compatible with endoscopic findings (specificity, 92.9%). Outside of a series of these 21 patients, there were 3 additional patients who had undergone endoscopic treatments previously with success, and in whom esophageal vessels were not depicted on MRA, but endoscopy showed remnant varices. (2) Time-dependent relationship between the appearance of collateral vessels and varices: of 4 varices that appeared after the start of MRA, 3 esophageal varices were found endoscopically simultaneously with or after delineation of collateral vessels on MRA. In the remaining patient, varices were found enodscopically 6 months before the MRA delineation, because a simultaneous MRA was not performed in this case. All these varices were in the early stage. CONCLUSIONS: MRA was highly sensitive and specific in detecting esophagogastric collateral vessels of the portal venous system. An endoscopic examination is unnecessary until collateral vessels are seen on MRA after surgery for BA.

Life-threatening mediastinal teratoma in a neonate.

This report describes a newborn with a large mediastinal teratoma (MT) presenting with severe respiratory distress (RD) at birth. At operation, there was no space for dissection because the huge cystic and solid tumor completely occupied the left hemithorax. After evacuation of the cystic component, the tumor was removed successfully. To our knowledge, only 16 newborn infants with MT presenting with RD have been reported. Operative morbidities occurred in one-half of the cases. We have reviewed the literature to discuss the potential risks of this entity.

Effects of brushing with a dentifrice for sensitive teeth on tubule occlusion and abrasion of dentin.

By using a dentifrice or toothpaste for sensitive teeth, the brushing-induced effects on dentinal tubule occlusion and abrasion of human sound dentin were investigated with a scanning electron microscope and a scanning laser microscope. The dentifrice contained diatomaceous earth and silica as abrasives and strontium chloride hexahydrate as an active ingredient. Thirty dentin pieces of human premolar teeth with an average of 20% occluded dentinal tubules were attached to resin plates and exposed to the oral cavities of five adult subjects for 2, 4, and 8 weeks. Brushing with and without dentifrice was performed 1 min per day, respectively. Brushing with the dentifrice gradually decreased the mean average of occluded tubules from about 91 to 77% during 2 to 8 weeks, although there were no significant differences among the individual values. However, the mean abrasive loss of the dentin surfaces brushed with dentifrice significantly increased from about 52 to 143 microm in depth. The brushed surfaces of the dentin showed a rough topography with numerous toothbrush scratches but no organic pellicle was found. On the other hand, brushing without dentifrice caused about 99% of the dentinal tubules to occlude in 2 and 4 weeks and 100% in 8 weeks. The brushed dentin surfaces at 8 weeks were entirely covered with organic pellicle containing fine mineral granules derived from saliva, and the abrasive loss was about 1.4 microm in mean depth. Such results indicate that brushing with abrasive dentifrices for sensitive teeth remarkably erodes dentin, and suggest that the brushing should cause the dentinal tubules to open again for a certain period of time.

Inflammatory pseudotumor of the liver: case report and review of the literature.

Inflammatory pseudotumor is a rare lesion that generally is considered to be benign in biological behavior, although some may recur or metastasize. The authors report on a patient with inflammatory pseudotumor of the liver whose preoperative radiologic findings resembled those of focal nodular hyperplasia. The biological investigation showed a polyclonality of the cells and diploidy of the DNA content and suggested benign characteristics of the lesion. J Pediatr Surg 36:663-666.

Identification and characterization of two novel mutations (Q421 K and R123P) in congenital factor XII deficiency.

The factor XII genes of two unrelated factor XII-deficient Japanese families were screened, and two novel mutations were identified. A heterozygous mutation (Q421K) was identified in the gene of a cross-reacting material (CRM)-negative patient with reduced FXII activity (entitled Case 1). No mutations were discovered in the other allele. Case 2 was a CRM-negative patient with severe FXII deficiency. In this case, a homozygous mutation (R123P) was discerned. Expression studies in Chinese Hamster Ovary (CHO) cells demonstrated accumulation of mutant Q421 K factor XII in the cell, and insufficient secretion, while the R123P mutant showed lower levels of accumulation than wild-type, and no evidence of secretion in culture supernatant. In the presence of proteasome inhibitor, all types of FXII (wild-type. Q421K, R123P) accumulated in the cells. Protease protection experiments using the microsomal fraction of these cell lines demonstrated that while 20% wild-type FXII (total wild-type:100%) and 10% R123P mutant (total R123P-type: 40%) were resistant to treatment with trypsin, 50% Q421K-type FXII (total Q421K-type:130%) remained resistant to digestion. From these results, we conclude that Q421K is less susceptible to proteasome degradation than wild-type, but is unable to exit the ER efficiently, resulting in insufficient secretion phenotype. In contrast, R123P is susceptible to proteasome degradation and is not secreted.

Risk of contralateral manifestation in children with unilateral inguinal hernia: should hernia in children be treated contralaterally?

PURPOSE: This study was done to identify risk factors for metachronous manifestation of contralateral inguinal hernia in patients with unilateral inguinal hernia. METHODS: Characteristics of 156 patients with metachronous contralateral hernia were compared with those of 156 patients with unilateral hernia who were ascertained not to have presented with contralateral hernia. RESULTS: There was a tendency for the hernia to be more often on the left side in 88 of 156 patients (56.4%) with contralateral manifestation compared with 70 of 156 patients (44.9%) in the control group (P =.054). The age at hernia repair of the patients with contralateral manifestation, 1 to 120 months (median, 14 months), was significantly younger than the 1 to 149 months (median, 20 months) of the control patients (P =.016). More patients with contralateral manifestation had a family history of inguinal hernia, and the percentage, 24.4%, was significantly higher than the 14.7% in the control group (P =.046). A univariate analysis with the Cox regression models found that hernia on the left side and a positive family history were significantly associated with the metachronous manifestation of contralateral hernia (hazard ratio [HR], 1.40; P =. 037 and HR, 1.59; P =.013, respectively). CONCLUSION: The risk of metachronous manifestation of contralateral hernia is high in patients with left-side hernia and in those with a family history, and the incidence of contralateral hernia is at most 10% in these patients. The authors think that the incidence is still too low to justify routine exploration and surgery for a patent processus vaginalis. Contralateral exploration should therefore be reserved for high-risk patients in whom second anesthesia and surgery have to be avoided.