Pulmonary alveolar proteinosis induced by X-linked agammaglobulinemia:A case report

BACKGROUND Pulmonary alveolar proteinosis(PAP)and X-linked agammaglobulinemia(XLA)are rare diseases in children.Many theories infer that immunodeficiency can induce PAP,but these reports are almost all review articles,and there is little clinical evidence.We report the case of a child with both PAP and XLA.CASE SUMMARY A 4-month-old boy sought medical treatment due to coughing and difficulty in breathing for>2 wk.He had been hospitalized multiple times due to respiratory infections and diarrhea.Chest computed tomography and alveolar lavage fluid showed typical PAP-related manifestations.Genetic testing confirmed that the boy also had XLA.Following total lung alveolar lavage and intravenous immunoglobulin replacement therapy,the boy recovered and was discharged.During the follow-up period,the number of respiratory infections was significantly reduced,and PAP did not recur.CONCLUSION XLA can induce PAP and improving immune function contributes to the prognosis of children with this type of PAP.

Hydrocephalus Secondary to Intraventricular Myxopapillary Ependymoma: Case Report

Ependymomas are a somewhat diverse category of glial tumors that often develop from the lining of the brain’s ventricles, or the spinal cord’s central canal. They make up 5% of all neuroepithelial tumors, 10% of paediatric brain tumors, and up to 33% of brain tumors in children under the age of three. Hydrocephalus is one of the complications, and it can be identified as progressive macrocephaly or increasing head circumference crossing percentiles, nausea, vomiting, poor appetite, irritability, and regression of developmental milestones.

Current research of idiopathic normal pressure hydrocephalus:Pathogenesis,diagnosis and treatment

Idiopathic normal pressure hydrocephalus(iNPH)is caused by impaired cerebrospinal fluid absorption in the elderly;it is a surgically treatable form of dementia.Gait disturbance,dementia,and urinary incontinence are the triad of signs for iNPH.In addition to these clinical findings,imaging studies show characteristic ventricular enlargement.High Evans Index and‘disproportionately enlarged subarachnoid hydrocephalus’are other well-known imaging findings of iNPH.If the tap test shows improved symptoms,shunt surgery is performed.The disease was first described by Hakim and Adams in 1965,followed by the publication of the first,second,and third editions of the guidelines in 2004,2012,and 2020,respectively.Recent studies signal the glymphatic system and classical cerebrospinal fluid(CSF)absorption from the dural lymphatics as aetiological mechanisms of CSF retention.Research is also underway on imaging test and biomarker developments for more precise diagnosis,shunting technique options with fewer sequelae and complications,and the influence of genetics.Particularly,the newly introduced‘suspected iNPH’in the third edition of the guidelines may be useful for earlier diagnosis.However,less well-studied areas remain,such as pharmacotherapy in non-operative indications and neurological findings other than the triadic signs.This review briefly presents previous research on these and future issues.

CT Profile of Hydrocephalus in Children at the Charles de Gaulle Pediatric Teaching Hospital in Ouagadougou

Aim of the Study: The aim is to analyse the epidemiological, clinical and CT aspects of hydrocephalus in children. Method: This was a cross-sectional descriptive study with retrospective collection from 1 June 2021 to 31 December 2022 within the radiology department of Charles De Gaulle Pediatric Teaching Hospital in Ouagadougou, Burkina Faso. The study included the records of patients with hydrocephalus who underwent cerebral computed tomography within this radiology department. Results: Hydrocephalus is due to a disorder of the hydrodynamics of the cerebrospinal fluid causing an increase in the volume allocated to this fluid in the brain and being accompanied by an increase in the pressure of this fluid. Its diagnosis is established by Doppler ultrasound or MRI prenatally, transfontanellar ultrasound in newborns and young children whose fontanel is permeable and by CT or MRI in older children, who can also determine the etiology. MRI remains an imaging technique that is less available and less accessible than CT in developing countries like ours. In Burkina Faso, MRI is only available in two private health facilities. The objective of this study was to describe the epidemiological, clinical and computed tomography aspects of hydrocephalus in children at the Charles de Gaulle pediatric teaching hospital in order to contribute to the diagnostic assessment and better management of this pathology. Over 19 months, 105 cases of hydrocephalus were recorded out of a total population of 115 children, or an average of 6 cases per month. The mean age was 17.52 months, with extremes of 03 days and 13 years, and the sex ratio was 1.38. Macrocrania, convulsions and psychomotor retardation were the main clinical signs, with rates of 49%, 34% and 30% respectively. On cerebral CT scan, hydrocephalus was triventricular (41.90%), tetraventricular (40%), and predominantly non-communicating (60%), with a mean Evans score of 0.53. The aetiologies were malformations in 34.28% of cases, tumours in 10.47% and infections in 5.71%. Among the malformations, Arnold Chiari II syndrome associated with spina bifida and Dandy Walker syndrome were the most common, accounting for 25% each. Tumour causes were dominated by craniopharyngioma and astrocytoma, each accounting for 27.30% of cases. Conclusion: The incidence of hydrocephalus was high in our study. In the absence of MRI (due to its unavailability and inaccessibility), CT revealed hydrocephalus that was predominantly tri- and tetraventricular, and predominantly non-communicating.

A novel pathogenic splicing mutation of RPGR in a Chinese family with X-linked retinitis pigmentosa verified by minigene splicing assay

AIM:To report a novel splicing mutation in the RPGR gene(encoding retinitis pigmentosa GTPase regulator)in a three-generation Chinese family with X-linked retinitis pigmentosa(XLRP).METHODS:Comprehensive ophthalmic examinations including best corrected visual acuity,fundus photography,vision field,and pattern-visual evoked potential were performed to identify the disease phenotype of a six-yearold boy from the family(proband).Genomic DNA was extracted from peripheral blood of five available members of the pedigree.Whole-exome sequencing(WES),Sanger sequencing,and pSPL3-based exon trapping were used to investigate the aberrant splicing of RPGR.Human Splice Finder v3.1 and NNSPLICE v0.9 were used for in silico prediction of splice site variants.RESULTS:The proband was diagnosed as having retinitis pigmentosa(RP).He had severe symptoms with early onset.A novel splicing mutation,c.619+1G>C in RPGR was identified in the proband by WES and in four family members by Sanger sequencing.Minigene splicing assays verified that c.619+1G>C in RPGR would result in the formation of a damaging alternative transcript in which the last 91 bp of exon 6 were skipped,leading to the subsequent deletion of 623 correct amino acids(c.529_619del p.Val177Glnfs*16).CONCLUSION:We identify a novel splice donor site mutation causing aberrant splicing of RPGR.Our findings add to the catalog of pathological mutations of RPGR and further emphasize the functional importance of RPGR in RP pathogenesis and its complex clinical phenotypes.

X-linked Charcot-Marie-Tooth disease after SARS-CoV-2 vaccination mimicked stroke-like episodes: A case report

BACKGROUND Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) vaccinations have been administered worldwide, with occasional reports of associated neurological complications. Specifically, the impact of vaccinations on individuals with Xlinked Charcot-Marie-Tooth disease type 1(CMTX1) is unclear. Patients with CMTX1 can have stroke-like episodes with posterior reversible encephalopathy syndrome on magnetic resonance imaging(MRI), although this is rare.CASE SUMMARY A 39-year-old man was admitted with episodic aphasia and dysphagia for 2 d. He received SARS-CoV-2 vaccination 39 d before admission. Physical examination showed pes cavus and reduced tendon reflexes. Brain MRI showed bilateral, symmetrical, restricted diffusion with T2 hyperintensities in the cerebral hemispheres. Nerve conduction studies revealed peripheral nerve damage. He was diagnosed with Charcot-Marie-Tooth disease, and a hemizygous mutation in the GJB1 gene on the X chromosome, known to be pathogenic for CMTX1, was identified. Initially, we suspected transient ischemic attack or demyelinating leukoencephalopathy. We initiated treatment with antithrombotic therapy and immunotherapy. At 1.5 mo after discharge, brain MRI showed complete resolution of lesions, with no recurrence.CONCLUSION SARS-CoV-2 vaccination could be a predisposing factor for CMTX1 and trigger a sudden presentation.

Rhombencephalitis caused by Listeria monocytogenes with hydrocephalus and intracranial hemorrhage:A case report and review of the literature

BACKGROUND Listeria monocytogenes(L. monocytogenes), a Gram-positive facultatively intracellular bacterium, is the causative agent of human listeriosis. Listeria infection is usually found in immunocompromised patients, including elderly people, pregnant women, and newborns, whereas it is rare in healthy people. L.monocytogenes may cause meningitis, meningoencephalitis, and some very rare and severe complications, such as hydrocephalus and intracranial hemorrhage,which cause high mortality and morbidity worldwide. Up to now, reports on hydrocephalus and intracranial hemorrhage due to L. monocytogenes are few.CASE SUMMARY We herein report a case of rhombencephalitis caused by L. monocytogenes in a 29-year-old man. He was admitted to the hospital with a 2-d history of headache and fever. He consumed unpasteurized cooked beef two days before appearance.His medical history included type 2 diabetes mellitus, and contaminated beef intake 2 d before onset. Cerebrospinal fluid analysis revealed Gram-positive rod infection, and blood culture was positive for L. monocytogenes. Magnetic resonance imaging findings suggested rhombencephalitis and hydrocephalus.Treatment was started empirically and then modified according to the blood culture results. Repeated CT images were suggestive of intracranial hemorrhage.Although the patient underwent aggressive external ventricular drainage, he died of a continuing deterioration of intracranial conditions.CONCLUSION Hydrocephalus, intracranial hemorrhage, and inappropriate antimicrobial treatment are the determinations of unfavorable outcomes.

Brucella meningoencephalitis with hydrocephalus masquerading as tuberculosis

Neurobrucellosis is a rare form of localized brucellosis usually with no systemic manifestations. We report a rare case of brucellosis presenting as meningoencephalitis associated with hydrocephalus.This patient had a lymphocytic predominant CSF and was initially treated with empirical anti tubercular therapy and steroids.A week later,when his CSF culture grew Brucella species,the treatment was changed to a combination of streptomycin,doxycycline and rifampicin and the patient improved with this therapy.This case illustrates the need to consider neurobrucellosis as a close differential diagnosis of neurotuberculosis in endemic areas when the patient presents with meningo encephalitis with lymphocytic CSF.

Lumboperitoneal shunts for the treatment of post-traumatic hydrocephalus

Objective: To assess the effectiveness and safety of lumboperitoneal shunt for treatment of post-traumatic hydrocephalus(PTH).Methods: A retrospective analysis of medical records of patients with lumboperitoneal shunts admitted in Shanghai Tenth People's Hospital from January 2014 to March 2017 was done.Experience with lumboperitoneal shunt placement for PTH was reviewed.The diagnosis of PTH was based on ventricular enlargement with the Evans' index(EI>0.3) before shunt implantation.Patients were evaluated for improvements in Glasgow Coma Scale(GCS), Glasgow Outcome Scale(GOS), and EI after shunt placement.Results: Totally, the study included 34 PTH patients with the average age of 49.32 years(range: 9–67 years).The average follow-up period was(3.9±3.5) months.Before lumboperitoneal shunt, the GOS score was(4±1), the GCS score was(8.53±3.38), and the EI score was(0.40±0.08).After shunt implantation, the GOS score was(3±1), the GCS score was(10.29±3.15), and the EI score was(0.34±0.13), respectively(P<0.05).Before lumboperitoneal shunt, 24(70.58%) patients had a GOS score of 4(vegetative state), and 10(29.42%) patients had a GOS score of 3(severe disabled).After lumboperitoneal shunt, 18(52.94%) patients had improvement in GOS(11 patients improve from GOS 4 to GOS 3, 5 patients from GOS 3 to GOS 2 and 2 patients from GOS 3 to GOS 1), 22(64.71%) patients achieved improvement in their GCS(14 patients GCS improvements ≥2 and 8 patients GCS improvement=1), 21(61.76%) patients had EI improvement(18 patients with EI<0.3).There was no complication in this study.Conclusion: Lumboperitoneal shunt placement is safe and effective for PTH, and serious complications are not observed.

MODIFIED GRAEB CRITERIA FOR PREDICTING THE POST-HEMORRHAGIC HYDROCEPHALUS IN INTRAVENTRICULAR HEMORRHAGE

Objective To set up a new grading system of intraventricular hemorrhage (IVH) and determine the value of predicting the probability of post-hemorrhagic hydrocephalus (PHH) in IVH. Methods We first modified the Graeb criteria, then compared the value of prediction for PHH assessed by the Graeb criteria with the modified Graeb criteria. One hundred and thirty one IVH patients were divided into two groups: the upper group (n=67) and the lower group (n=64). Gold standard of PHH was assessed by CT scan or by out-drainage. The diagno-stic parameters such as sensitivity (SE), specificity (SP) were analyzed. In the cutoff point of SE and SP curves, diagnostic efficiency (DE), and Kappa value (K) were analyzed. The probability of PHH was estimated by binary logistic regressions. Results In all ventricular group, to Graeb criteria in the cutoff point, SE, SP, and K was 0.78, 0.84, and 0.60; and to modified Graeb criteria SE, SP, and K was 0.90, 0.84, and 0.74 respectively. The probability of PHH from point of 3-12 was 0.011, 0.032, 0.085, 0.212, 0.435, 0.689, 0.865, 0.949, 0.981, and 0.994 respectively according to modified Graeb criteria. Conclusion The modified Graeb criteria combined with logistic regression were useful methods to assess the severity of IVH and to predict the probability of PHH in IVH.

Clinical observations of vitreoretinal surgery for four different phenotypes of X-linked congenital retinoschisis

AIM： To evaluate the outcomes of vitreoretinal surgery for four different phenotypes of X-linked retinoschisis （XLRS）. METHODS： This study included thirty-one eyes of 25 patients who developed XLRS with severe complications. Among the 31 eyes, there were 7 eyes with vitreous hemorrhage, 8 eyes with retinal detachment and vitreous hemorrhage, and 16 eyes with rhegmatogenous retinal detachment. All of the patients underwent standard three-port pars plana vitrectomy. All of the eyes were divided into 4 groups before surgery according to a modified classification scheme, with the first three groups as follows： group A, with foveal cystic schisis; group B with macular lamellar schisis; and group C with foveolamellar changes. Peripheral schisis was not present in these 3 groups; however, group D was a complex group with both macular and peripheral changes. One year after surgery, we analyzed the best corrected visual acuity and postoperative anatomical and functional outcomes of these 4 groups. RESULTS： There were 7 eyes in group A （22.6%）, 1 eye in group B （3.2%）, 15 eyes in group C （48.4%） and 8 eyes in group D （25.8%）. Postoperative anatomical and functional outcomes were satisfactory at the last visit, while the mean visual acuity was increased to 0.27±0.11, with a significant difference （t=-1.049, P=0.000） compared with the results before surgery （0.1±0.08）. Visual acuity was improved in 23 eyes （74.2%）. Complications were found in three eyes： two eyes with proliferative vitreoretinopathy and traction retinal detachment 10 and 12mo after surgery, respectively; and one eye with vitreous hemorrhage 15mo after surgery. These eyes were in groups C and D. The retinas remained attached in these 3 eyes after reoperation. CONCLUSION： We should pay greater attention to XLRS with foveolamellar changes because it is the most changeable phenotype. Once complications occur, vitreoretinal surgery can significantly improve visual acuity and restore the anatomic structure of the retina.

Endoscopic Third Ventriculostomy versus Ventriculo-Peritoneal Shunt for Infant Hydrocephalus

Introduction: Patients with hydrocephalus, which is the most pediatric neurological disorder, undergo Cerebrospinal fluid (CSF) diversion through third ventriculostomy or ventriculo-peritoneal shunt. Up to date, the optimal hydrocephalus treatment modality is not clear. Aim: We compared the outcome of endoscopic third ventriculostomy (ETV) versus ventriculo-peritoneal shunt (VP shunt) as a second surgical intervention in management of Infant hydrocephalus concerning success rate and complications. Patients and Methods: We conducted an observational study of 52 children with hydrocephalus (congenital or acquired) in whom CSF diversion was performed using either ETV or VP shunt in randomized control trial. Results: During the period examined, 52 children, 26 underwent ETV and 26 underwent VP shunt. The mean age was 11.0 ± 4.3 months in ETV and 11.3 ± 4.7 months in VP shunt. Postoperative infection in the ETV group was lower than in the VP shunt group (23.1% vs. 53.8% P = 0.045). Regarding operating time, In ETV group operation duration was 46.9 min and 64.3 min in the V-P shunt group (P = 0.13). There was no statistically significant difference between the two study groups regarding the rate of obstruction, change in occipital frontal circumference (OFC) or the need of revision surgery. One year survival for VP shunt group vs. ETV group was 46.2% vs. 65.4% respectively. Conclusion: ETV associated with lower rates of postoperative infection and shorter operation time with no significant difference in rates of obstruction, change in OFC and revision surgery in comparison to VP shunt.

X-linked juvenile retinoschisis： phenotypic and genetic characterization

Juvenile X-linked retinoschisis（XLRS, MIM#312700） belongs to a group of the vitreoretinal dystrophies. We aimed to describe the phenotype-genotype correlation of three XLRS cases in juveniles with different novel mutations from the Lithuanian population. The patients demonstrated macular retinoschisis and typical cyst-like cavities on spectral-domain optical coherence tomography（SD-OCT） images. The mean central foveal thickness was 569.7 μm. Two patients presented with peripheral retinoschisis. Flash electroretinogram demonstrated a reduced b/a ratio（〈1.0） in all patients. RS1（NM_000330.3） gene coding exons Sanger sequencing was performed. RS1 c.599 G〉T（p.R200 L） mutation was detected in one case, showing to be pathogenic in silico analysis. c.（92_97） ins C（p.W33 fs） mutation was identified for another patient, indicating the variant is possibly damaging in silico analysis. The third case was identified with a pathogenic mutation c.422 C〉G（p.R141 H）, HGMD CM981753. These are the first cases of XLRS in the Lithuanian population confirmed by molecular genotyping. Presented patients had a different genotype but similar phenotypic traits.

Hydrocephalus after subarachnoid hemorrhage:A metaanalytic comparison of aneurysm treatments

AIM： To compare two treatments for ruptured cerebral aneurysm with reference to the relative risk of develop-ing hydrocephalus.METHODS： We reviewed the English language litera-ture on the risk of developing hydrocephalus after an-eurysm treatment. Data were divided by type of study （randomized controlled trial, cohort trial, nonrandomized comparison, prospectively- and retrospectively-collected observational study）. They were also divided by type of aneurysm treatment （microvascular - clipping, or endo-vascular - coiling）. Additional predictive variables collected for each publication were average age, gender distribu-tion, measures of hemorrhage volume and subarachnoid hemorrhage severity, aneurysm locations, time to treat-ment, duration of follow-up and date of publication. Weemployed meta-analysis to calculate pooled risk ratios of developing hydrocephalus in cases receiving aneurysm clipping vs those receiving coiling. Meta-regression was used to correct pooled results for covariates.RESULTS： Because indications for the two treatments are different, there is little clinical equipoise for treat-ing most cases. The single randomized, controlled trial dealt with a small subset of ruptured aneurysms. Nei-ther this nor pooled values from other studies which compared the two treatments had the power to dem-onstrate signifcant differences between the two treat-ments. Nor was there an apparent difference when observational data were meta-analytically pooled. How-ever, when meta-regression was used to correct for predictive variables known to differ between the two treatment groups, a highly-significant difference ap-peared. Coiling is used more commonly in older, sicker patients with aneurysms in certain locations. These cases are more likely to develop hydrocephalus. When corrected for these covariates, the risk of hydrocepha-lus was found to be significantly lower in coiled vsclipped cases （P = 0.014）.CONCLUSION： Pooled observational data were nec-essary to demonstrate that coiling ruptured cerebral aneurysms is associated with a lower risk of developing hydrocephalus than is clipping.

CNKSR2 mutation causes the X-linked epilepsy-aphasia syndrome:A case report and review of literature

The mutation in CNKSR2 leads to a broad spectrum of phenotypic variability and manifests as an X-linked intellectual disability. However, we reported that the male patient in this study not only had intellectual disability but also epileptic seizures. In addition, there were progressive language impairment, attention deficit hype-ractivity disorder and autism. Electroencephalograms showed continuous spike-and-wave during sleep. Genetic testing revealed a de novo mutation of the CNKSR2 gene(c.2185C >T, p.Arg729Ter) in the child that was not detected in the parents. Therefore, the child was diagnosed with X-linked epilepsy aphasia syndrome. Deletion of the CNKSR2 gene has been rarely reported in epilepsy aphasia syndrome, but no de novo mutation has been found in this gene. This report not only adds to the spectrum of epilepsy aphasia syndrome but also helps clinicians in diagnosis and genetic counseling.

Adrenal Hemorrhage as a Rare Cause of Neonatal Anemia Associated with Hydrocephalus Secondary to Intraventricular Hemorrhage—A Case Report

Neonatal adrenal hemorrhage is frequently associated with birth trauma, perinatal asphyxia, intrauterine infection, coagulation defects and thromboembolism. It has varied clinical presentation depending on degree of hemorrhage and amount of adrenal cortex compromised by hemorrhage. The most common clinical presentations are persistent jaundice and flank mass. We report a case of left sided adrenal hemorrhage in a breech delivered male neonate with perinatal asphyxia presented with anemia and fever. On further evaluation, he was also having moderate communicating hydrocephalus secondary to intraventricular hemorrhage. The adrenal hemorrhage was managed conservatively. Subsequent abdominal ultrasound showed resolving adrenal hemorrhage. Right ventriculoperitoneal shunt was done for hydrocephalus. Postoperative course was uneventful. The patient is asymptomatic at follow-up.

Targeting X-linked inhibitor of apoptosis protein inhibits pancreatic cancer cell growth through p-Akt depletion

AIM: To determine whether lentivirus-mediated shRNA targeting the X-linked inhibitor of apoptosis protein (XIAP) gene could be exploited in the treatment of pancreatic cancer. METHODS: Human pancreatic cancer cells Panc-1, Mia-paca2, Bxpc-3 and SW1990, infected with lentivirus, were analyzed by real-time polymerase chain reaction (PCR). Western blotting was used to examine XIAP protein levels, survivin and p-Akt to confirm the result of real-time PCR and determine the possible mechanism. The 3-(4,5-cimethylthiazol-2-yl)-2,5- diphenyl tetrazolium bromide (MTT) assay was used to measure IC50 to determine chemosensitivity to the chemotherapeutic drugs 5-fluorouracil (5-FU) and gemcitabine. A colony assay, MTT assay and a tumorigenicity experiment were used to study cell proliferation in vitro and in vivo . Caspase-3/7 activity, 4',6-diamidino-2-phenylindole-staining and flow cytometric measurements were used to study apoptosis in SW1990 cells. RESULTS: XIAP proteins were found to be differen- tially expressed among pancreatic cancer cell lines Panc-1, Mia-paca2, Bxpc-3 and SW1990. Data of real-time PCR and Western blotting showed that XIAP was reduced persistently and markedly by lentivirus-mediated shRNA. Downregulation of XIAP by transfection with XIAP shRNA resulted in decreased p-Akt expression. XIAP shRNA also inhibited the growth of pancreatic cancer cells in vitro and in vivo , enhanced drug-induced apoptosis and increased chemosensitivity to 5-FU and gemcitabine. Results also suggest that inhibition of XIAP and subsequent p-Akt depletion may have an anti-tumor effect through attenuating the ability of cancer cells to survive. CONCLUSION: Lentivirus-mediated gene therapy is an attractive strategy in the treatment of pancreatic cancer and justifies the use of lentivirus in pancreatic cancer gene therapy studies.

Non-Tumor Obstructive Hydrocephalus Treated with Endoscopic Third Ventriculostomy in Cameroon

Objective: In Sub-Saharan Africa, shunt dependence is a real threat for patients. For this reason, any method allowing shunt independence such as endoscopic third ventriculostomy should be promoted. The goal of this study was to show the advantages of neuroendoscopy in treating non-tumor obstructive hydrocephalus in Cameroon. Methods: We retrospectively reviewed the cases of non-tumor obstructive hydrocephalus treated with endoscopic third ventriculostomy in our hospital. Results: Twenty patients (15 males, 5 females) underwent endoscopic third ventriculostomy as first choice treatment for non-tumor obstructive hydrocephalus. Their ages ranged from six months to 41 years (mean 11.96 years, median 20.75 years). Fourteen patients (70%) were children (≤18 years old), 6 were adults, 7 were under age of two years and 3 were below one. Computed tomography scan was the radiological tool used in all cases. None did a magnetic resonance imaging scan. Etiology of hydrocephalus was aqueductal stenosis in 18 cases and stenosis of the foramina of Luschka & Magendie in two. Aqueductal stenosis was associated with myelomeningocele in one case and shunt failure in another one. Endoscopic third ventriculostomy was successful in alleviating clinical symptoms with shunt independence in 19 cases (95%), but failed in one case. ETV success was not related to patient age. Cerebrospinal fluid leak occurred in two patients as post-operative complication (10%). Overall, ETV diminished treatment cost by 600 USD. Conclusion: Even in areas with limited medical equipment like in Sub-Saharan Africa where shunt dependence is a real danger, ETV can be routinely used to successfully treat non-tumor obstructive hydrocephalus.

Regulatory Effects of X-linked Inhibitor of Apoptosis Protein and Pro-apoptotic Protein Smac on Apoptosis Resistance to Chemotherapy in Pancreatic Cancer Cells~*

Objective： To investigate the relation of X-linked inhibitor of apoptosis （XIAP） and second mitochondria-derived activator of caspase （Smac） signaling pathway to chemoresistance in human pancreatic cancer Panc-1 and BXPC-3 cells. Methods： Apoptosis and the changes of XIAP expression in permeabilized cells induced by cisplatin and 5-fluorouracil （FU） were measured by flow cytometry. The cytosolic expression of XIAP, Smac and caspase-3 was detected by Western blot. A recombinant plasmid vector pEGFP-N1/Smac was constructed and transfected into of Pancol cells. The effect of cytosolic overexpression of Smac on apoptosis of Panc-1 cells was evaluated by flow cytometry. Results： Panc-1 was more resistant to cisplatin or 5-FU induced apoptosis than BXPC-3. Western blot revealed that chemoresistant Panc-1 highly expressed XIAP, and increased cytosolic expression of Smac might be responsible for the marked down-regulation of XIAP in chemo-sensitive BXPC-3 cells after exposure to cisplatin or 5-FU. Furthermore, cytosolic overexpression of Smac could significantly down-regulate the levels of XIAP and promote the activity of caspase-3, as well as sensitize Panc-1 cells to anticancer drug-induced apoptosis. Conclusion： Anticancer drug-induced apoptosis requires mitochondrial release of Smac and downregulation of XIAP, which may be an important determinant of chemo-sensitivity in pancreatic cancer cells. Up-regulation of cytosolic expression of Smac may act as an effective modifying signal to overcome apoptosis resistance to chemotherapy in pancreatic cancer cells.

Expression of second mitochondria-derived activator of caspases, X-linked inhibitor of apoptosis protein, and caspase-3 in pituitary adenomas

Studies concerning correlations between pituitary adenomas and cell apoptosis have mainly focused on upstream apoptosis signaling, but seldom on downstream mediators. In the present study, second mitochondria-derived activator of caspases （Smac）, X-linked inhibitor of apoptosis protein （XIAP）, and caspase-3 protein were qualitatively analyzed using immunohistochemistry, and quantified by western blot. Smac, XIAP, and caspase-3 mRNA expressions were detected by reverse transcription-PCR. Results showed that XIAP protein and mRNA expressions were greater in the invasive pituitary adenoma group compared with the noninvasive pituitary adenoma group. However, Smac and caspase-3 protein and mRNA expressions were lower in the invasive pituitary adenoma group compared with the noninvasive pituitary adenoma group. In the invasive pituitary adenomas, Smac expression was positively correlated with caspase-3 protein and mRNA expression （Protein： r = 0.55, P 0.01; mRNA： r = 0.50, P 0.01）. Smac and caspase-3 expressions were negatively correlated with XIAP protein and mRNA expression （Protein： r = -0.56, -0.64, P 0.01; mRNA： r = -0.69, -0.67, P 0.01）. However, no significant differences in correlation among Smac, XIAP, and caspase-3 were detectable in noninvasive pituitary adenomas. These data indicated that high expression of XIAP and low expression of Smac and caspase-3 suppressed cell apoptosis and led to enhanced invasiveness of pituitary adenomas. Thus, Smac, XIAP, and caspase-3 may be useful markers in determining the invasive behavior of pituitary adenomas.