[Prognostic factors in metastatic colorectal cancer in Tunisia: A retrospective study of 130 patients]. / Facteurs pronostiques des cancers colorectaux métastatiues (CCRM) en Tunisie. Etude retrospective à propos de 130 patients.

BACKGROUND: The survival of patients with a metastatic colon cancer has improved with palliative chemotherapy, targeted therapies and surgery. Several prognostic factors influencing the survival of these patients were identified in the literature represented mainly by clinical factors: general condition, number and site of metastases, rate of white blood cells, initial carcinoembryonic antigen (CEA) rate, hemoglobin level, and therapeutic factors mainly represented by resection of metastases. AIM: To evaluate within a Tunisian retrospective study the significant prognostic factors on survival of metastatic colorectal cancer (MCRC). METHODS: We collected retrospectively 130 patients with MCRC treated in Sfax from january 2000 to December 2007. Uni and multivariate analysis were performed according to cox model for the following factors : Age or > 40 years, gender, synchronous vs metachronous metastases, disease-free survival (DFI) 1 > 1year, tumor site(colon vs rectum), performance status or PS ( 0-1or 2-3), white blood cells count (< or > 103/ml3 , haemoglobin rate (Hb) or > 11g/dl, seric carcinoembryonic antigen rate (CEA) < vs > 10 ng/ml, number of metastatic sites (single vs multiple), site of metastatic site (liver vs extrahepatic) and resection or not of the metastatic localizations. RESULTS: Statistical analysis showed for univariate analysis the positive impact of : PS 1, (Hb) rate > 11 g/dl, CEA) < 10 ng/ml and resection of metastases, while in in multivariate analysis, they were : a good PS and Hb > 11 g/dl. CONCLUSION: Our retrospective study confirmed the known prognostic impact of simple clinical tools like a good performance Status and Hb > 11 g/dl, a (CEA) rate lower than 10 ng/ml and resection of metastases which were identified by several other series such as predictive factors of a better survival in patients with metastatic colorectal cancer.

Screening of SLC26A4 gene in autoimmune thyroid diseases.

The Pendred syndrome (PS) gene, SLC26A4, was involved in the genetic susceptibility of autoimmune thyroid disease (AITD) in Tunisian population. Recently, functional assays have shown a differential expression of SLC26A4 gene between Graves' disease (GD) and Hashimoto's thyroiditis (HT). Here, by the mean of DHPLC and HRM, we explored the 21 exons and their flanking intronic sequences of 128 patients affected with GD (n = 64) or HT (n = 64). The pathogenic effect of identified variations on splice was investigated using the web server HSF. Eighteen allelic variations were identified and ranged on missense, sens and splice variations. Nine identified variations (c.-66C>G, c.898A>C, c.1002-9A>C, c.1061T>C, c.1544 + 9G>T, c.1545-5T>G, c.1790T>C, c.1826T>G, c.2139T>G) were previously reported in hearing impairment studies. Forty-seven per cent (30/64) of GD patients and 37,5% (24/64) of HT patients present at least one variant in the explored sequences. Moreover, the analysis of the variant distribution between HT (9 (5'UTR), 12 exonic and 13 intronic) and GD (18 (5'UTR), 13 exonic and 5 intronic) patients showed a significant difference (χ² = 6.54, 2df, P = 0.03). Interestingly, missense changes (I300L, p.M283I, F354S and p.L597S) affected conserved residues of pendrin. On the other hand, the HSF analyses ascertain that some variants identified in HT disease are predicted to have a pathogenic effect on splice. In conclusion, our analysis of SLC26A4 sequence variations suggested a distinct genetics basis between HT and GD patients, which should be confirmed on a large cohort.

Mutations in a new gene encoding a protein of the hair bundle cause non-syndromic deafness at the DFNB16 locus.

Hearing impairment affects about 1 in 1,000 children at birth. Approximately 70 loci implicated in non-syndromic forms of deafness have been reported in humans and 24 causative genes have been identified (see also http://www.uia.ac.be/dnalab/hhh). We report a mouse transcript, isolated by a candidate deafness gene approach, that is expressed almost exclusively in the inner ear. Genomic analysis shows that the human ortholog STRC (so called owing to the name we have given its protein-stereocilin), which is located on chromosome 15q15, contains 29 exons encompassing approximately 19 kb. STRC is tandemly duplicated, with the coding sequence of the second copy interrupted by a stop codon in exon 20. We have identified two frameshift mutations and a large deletion in the copy containing 29 coding exons in two families affected by autosomal recessive non-syndromal sensorineural deafness linked to the DFNB16 locus. Stereocilin is made up of 1,809 amino acids, and contains a putative signal petide and several hydrophobic segments. Using immunohistolabeling, we demonstrate that, in the mouse inner ear, stereocilin is expressed only in the sensory hair cells and is associated with the stereocilia, the stiff microvilli forming the structure for mechanoreception of sound stimulation.

[Myoplasty by reversal of the pectoris major muscle in the treatment of mediastinitis. A case report and review of the literature]. / Myoplastie par retournement du grand pectoral dans le traitement des médiastinites. À propos d'un cas et revue de la littérature.

Mediastinitis are among the most dreadful infectious complications following cardiac surgery. Their prognosis depends essentially on the precociousness of the diagnosis. In most of the cases, the medical treatment associated with an irrigation drainage is sufficient. But in case of severe sternal dehiscence, plastic surgery becomes necessary in order to fill up the loss with a well-vascularized tissue. We report the case of a 78-year-old patient, chronic bronchitic who presented, after a coronary artery bypass, an aseptic sternal dehiscence necessitating an osteosynthesis, then a Klebsiella pneumoniae mediastinitis with an enlarged sternal necrosis which was treated by bone resection and a myoplasty via reversal of the right pectoris major muscle. The postsurgery course was favourable. Now, after one-year remote, cicatrisation is complete and we have not noticed any infectious recurrence.

Two missense mutations in SLC26A4 gene: a molecular and functional study.

Mutations in the SLC26A4 gene encoding pendrin, an anion transporter, are responsible for non-syndromic hearing loss (HL) (DFNB4) and Pendred syndrome (PS). PS is a genetic disorder that causes early HL and affects the thyroid gland. Here, we report eight Tunisian families affected with profound HL. Clinical investigations revealed goiter in few patients. Genotyping using microsatellite makers showed linkage to SLC26A4, and missense mutations p.L445W and p.M147T were identified by sequencing and polymerase chain reaction-restriction fragment length polymorphism. The p.L445W mutation segregated in seven families and haplotype analysis suggested its founder effect. In order to understand the molecular pathogenic mechanisms of p.L445W and p.M147T mutations, SLC26A4 wild-type and mutant cDNA constructs were transiently expressed in COS7 cells and several human cell lines including Thyroid 8305C cells. Reverse transcription-PCR, western blot and immunofluorescence demonstrated that these two mutations abolished complex glycosylation of pendrin and prevented its targeting to the plasma membrane.

[Association of Parry-Romberg syndrome and paroxymal kinesigenic dyskinesia]. / Association syndrome de Parry-Romberg et dyskinésie paroxystique kinésigénique.

INTRODUCTION: Parry-Romberg syndrome is a rare entity of unknown etiology, characterized by hemifacial or hemibody atrophy affecting subcutaneous tissues. Its main clinical manifestations are neurological, ocular and dermatological. Paroxysmal kinesigenic dyskinesia (PKD) is characterized by brief episodes of choreic/dystonic movements triggered by sudden movements and improved by antiepileptic drugs particularly carbamazepine. It can be sporadic or familial with an autosomal dominant inheritance. Little is known about the pathophysiology of PKD, although a channelopathy is thought likely. The association of these two diseases is rare. CASE REPORT: Over three years, a 42-year-old patient progressively developed left hemiatrophy. Since age 14, he presented paroxysmal dystonic disorders of the limbs triggered by sudden movements and controlled by carbamazepine. The diagnosis of PKD associated with Parry-Romberg syndrome was established. Investigations revealed immunologic and diffuse electrophysiological abnormalities (EEG and EMG). CONCLUSION: PKD associated with Parry-Romberg syndrome is very rare but does not appear to be fortuitous. It suggests a common mechanism via an underlying channelopathy or dysimmune disorder.

[Schizophrenia and violence, incidence and risk factors: a Tunisian sample]. / Schizophrénie et violence: incidence et facteurs de risque à propos d'une population tunisienne.

INTRODUCTION: Schizophrenia appears to be the mental pathology the most associated with violence. The aim of this study is to show the incidence and the different risk factors of violence among schizophrenics. MATERIAL AND METHOD: We have compared a group of 30 violent schizophrenic inpatients with another group of 30 nonviolent schizophrenic inpatients hospitalised during the same period. These two groups have been matched according to age and gender. The comparison concerned: sociodemographic parameters, family and personal psychiatric history, legal antecedents, social insertion, clinic, Clinical Global Impressions (CGI), Global Impairment Scale (GIS) and Positive And Negative Syndrome Scale (PANSS) scores for admissions, familial support and insight, compliance to treatment, administered treatments, and awareness degree. RESULTS: Violent schizophrenics represent 18.07% of all hospitalisations and 26.08% of schizophrenic patients. When compared to violent schizophrenic patients, nonviolent schizophrenic patients have a better socioeconomic level (77% versus 43%), better professional adaptation (67% versus 10%) and familial support (60% versus 10%), better insight (87% versus 23%) and therapeutic control (70% versus 17%). Differences are significant. We found significantly more personal antecedents of inflicted violence within violent schizophrenics (50% versus 13%), more addictive behavior (53% versus 13%), and more paranoid and indifferentiated forms (87% versus 47%) than in nonviolent schizophrenics. The average of CGI scores was significantly higher within violent schizophrenics (5.27+/-0.8 versus 3.77+/-0.5). Conversely, the average of EGF scores was lowest (37.6+/-6.5 versus 47.8+/-5.6). The comparison of PANSS scores revealed that violent schizophrenic subjects are characterised by the existence of more positive signs and more general symptoms (34.4+/-4.7 versus 20.2+/-4.5; 55.1+/-11.4 versus 46.1+/-6.9). Violent schizophrenics are characterised by higher neuroleptic doses (2375+/-738 mg/d versus 1610+/-434 mg/d). Differences here are also significant. DISCUSSION: Addictive behaviour seems to considerably increase the risk of turning to violence. Thus in our study, 53% of violent patients showed an addictive behaviour. These results have also been reported by other authors. It is obvious that alcohol and drug abuse double the risk of violence among schizophrenic subjects. Psychotic decompensation and rich symptomatology increase the violent potential among the schizophrenics. In our study, the PANSS scores were higher among violent subjects. Nonviolent schizophrenic subjects have a lesser symptomatology of psychiatric disorders and a better outcome as shown by the CGI and EGF scores. In our study, the group of violent subjects needed higher neuroleptic doses and were noncompliant. Compliance permits the acquisition, and then maintains, the stability of the mental status and plays an essential role in decreasing dangerousness. In fact, violent schizophrenics exhibit low insight, implying diminished awareness of the legal implications of their acts, and are little aware of their illness and its dangerousness. In our study, we noted better familial support among nonviolent subjects. According to the literature, violent schizophrenics are characterised by a particularly hostile and rejecting familial environment. CONCLUSION: Awareness of these factors will allow us to provide improved prevention of violence within schizophrenic subjects.

[Myotonia and hypothyroidism]. / Myotonie et hypothyroïdie.

INTRODUCTION: Hypothyroidism is frequently associated with different neuromuscular disorders. However myotonia is rarely a revealing feature. CLINICAL CASES: Two patients aged 28 and 31 years consulted for a progressive myotonia. Blood and thyroid analysis revealed peripheral hypothyroidism with low FT4 and high TSH levels. Outcome was favorable with thyroid hormone substitution. Myotonia regressed and thyroid hormone levels returned to normal. CONCLUSION: Myotonia may reveal hypothyroidism. The pathogenic mechanism of this myotonia is an unknown. Good outcome with thyroid hormone substitution requires a systematic thyroid hormone screening in patients presenting neuromuscular manifestations.

[Clinical case of the month. Histological discovery of a lung cancer in an enormous emphysematous bulla]. / Le cas clinique du mois. Découverte histologique d'un cancer du poumon dans une énorme bulle d'emphysème.

The development of a lung cancer in young patients with emphysematous bullae is a classical, albeit rare, event. These patients can however be operated upon for the resection of a giant bulla causing respiratory distress. We report the case of a 41 year old male patient who was submitted to the resection of a giant right apical emphysematous bulla. The histopathological examination of the fragment revealed an undifferentiated lung carcinoma the diameter of which was less than one centimeter. This observation underlines the need for a systematic examination of the resected material and for a careful radiological follow-up of such patients.

[Management of isolated iliac aneurysms: A Tunisian center experience]. / Traitement des anévrismes iliaques isolés : expérience d'un centre tunisien.

Isolated aneurysms of the iliac arteries are rare. The diagnoses of these aneurysms become easier with non-invasive radiologic investigations. The development of endovascular treatment is a recent alternative to surgical treatment. We report our experience in the management of 8 cases of isolated iliac aneurysms in the department of cardiovascular and thoracic surgery of the Habib Bourguiba Hospital of Sfax.

[Surgical and endoluminal management of the inflammatory aortitis: A Tunisian center experience]. / Traitement chirurgical et endovasculaire des atteintes aortiques inflammatoires : expérience d'un centre tunisien.

Non-infectious aortitis is usually due to giant-cell arteritis, Takayasu disease or Behçet disease. The main aortic lesions are stenoses, occlusions and aneurysms in the Takayasu disease and aneurysms in the Behçet disease and giant-cell arteritis. Treatment is based on corticosteroid therapy and surgery. Endoluminal management is now the rule. We report a retrospective descriptive study of 10 patients who underwent surgical or endoluminal management of inflammatory lesions of the aorta between January 2000 and December 2015. There were 4 cases of Takayasu disease and 6 cases of Behçet disease. The aortic lesions were aneurysmal in all of the patients with Behçet disease. In the patients with Takayasu disease, aortic occlusions predominated, associated with other arterial lesions. Four patients with Behçet disease were managed surgically, and 2 patients underwent endovascular repair. All of the patients with Takayasu disease underwent surgery. Two patients died in the postoperative period, and two patients died during long-term follow-up. Systematic screening, as well as regular monitoring of the entire aorta during the follow-up, is necessary due to the frequency of aortic aneurysms.

[Post-traumatic carotido-jugular fistula: Case report and review of the literature]. / Fistule carotido-jugulaire post-traumatique : à propos d'un cas opéré.

The neck, being not protected by skeleton, is vulnerable to external trauma and injury which can involve blood vessels, muscles, nerves, and trachea. Carotid injuries can be potentially life-threatening by hemorrhage and stroke. We present a case of a 26-year-old manual worker who presented a neck injury caused by a metallic projectile. The injury involved the right common carotid artery with an internal jugular vein fistula, and tracheal damage. The patient was managed with surgical repair of the tracheal lesion, reconstruction of the carotid section using a PTFE graft bypass, and ligation of the internal jugular vein. In the immediate postoperative period, the patient presented with no neurological deficits, but he did develop a pulmonary infection that resolved with antibiotic therapy. The follow-up is now 3months. The patient is doing well without any neurological disorder.

[Prevalence of celiac disease serological markers in Tunisian type 1 diabetic adults]. / Prévalence des marqueurs sérologiques de la maladie coeliaque chez des adultes tunisiens diabétiques de type 1.

OBJECTIVE: to evaluate the prevalence of celiac serological markers; anti-transglutaminase (ATGt), anti-endomysium (AE), anti-gliadin (AGD) and anti-reticulin (AR) antibodies; in type 1 diabetic Tunisian adults. SUBJECTS AND METHODS: 261 type 1 diabetic patients aged from 16 to 60 years were enrolled in this prospective study. IgG and IgA transglutaminase and gliadin were measured with ELISA. IgA AE were tested by indirect immunofluorescence using 2 substrates; monkey oesophagus and human umbilical cord. AR were detected by indirect immunofluorescence on rat liver, kidney and stomach. Sera IgA level was measured by turbidimetry. RESULTS: 83/261 of diabetics were positive for at least one antibody, 5.7% had ATGt-A, 3.4% AE on monkey esophagus, 3.1% AE on umbilical cordon, 18% AGD-A, 19.5% AGD-G and 3.1% AR. There was an excellent concordance between AE and ATGt (r = 0.9). Out of the 261 diabetics, 5 had an IgA deficiency and one of them has IgG AE and ATGt. CONCLUSION: serological markers of celiac disease seem to be frequent in diabetics. Nevertheless, diagnosis must be confirmed by histological studies which allow us to know the real prevalence of celiac disease in diabetic adults.

[Massive hemoptysis: experience of a surgical unit]. / Hémoptysies massives: expérience d'une unité chirurgicale.

Massive hemoptysis is a clinical entity characterized by its unpredictable and potential lethal course. We studied retrospectively the observations of 25 patients hospitalized in our surgical unit. We collected all the demographic, clinical and surgical data. A male predominance with a sex-ratio of 2,1 was noted. The average age was 45 years, with extremes of 17 and 75. The dominant cause was bronchiectasis. Twenty patients were operated on. The surgery consisted of a pulmonary resection in 9 cases (45%), an atypical lung resection in 4 cases (20%), a resection of an aspergilloma in 2 cases (10%), a kystectomy of hydatic cyst in 4 cases (20%) and one arterial ligature (5%). Five patients (25%) had emergent surgery, and 15 (75%) delayed surgery. Hospital mortality was 20% in the first group and 6.66% in the second. No recurrence of bleeding was observed after an average follow-up of 7 months. Surgery remains a therapy of choice for massive hemopysis. It must as far as possible be avoided during active bleeding.

[Popliteal artery pseudoaneurysm caused by femur exostosis: A pediatric case]. / Faux anévrisme de l'artère poplitée secondaire à une exostose fémorale chez un enfant : à propos d'un cas opéré.

Exostoses, or osteochondromas are benign bone tumors that have developed on the bone surface. These benign tumors can be asymptomatic or lead to complications, for instance arterial pseudoaneurysm. We report a case of a pseudoaneurysm of the popliteal artery treated surgically in a 17-year-old girl with a solitary exostosis of the right femur. Surgery was closure of the pseudoaneurysm and a bypass using a venous graft.

Novel missense mutations of TMPRSS3 in two consanguineous Tunisian families with non-syndromic autosomal recessive deafness.

Recently the TMPRSS3 gene, which encodes a transmembrane serine protease, was found to be responsible for two non-syndromic recessive deafness loci located on human chromosome 21q22.3, DFNB8 and DFNB10. We found evidence for linkage to the DFNB8/10 locus in two unrelated consanguineous Tunisian families segregating congenital autosomal recessive sensorineural deafness. The audiometric tests showed a loss of hearing greater than 70 dB, in all affected individuals of both families. Mutation screening of TMPRSS3 revealed two novel missense mutations, W251C and P404L, altering highly conserved amino acids of the serine protease domain. Both mutations were not found in 200 control Tunisian chromosomes. The detection of naturally-occurring TMPRSS3 missense mutations in deafness families identifies functionally important amino acids. Comparative protein modeling of the TMPRSS3 protease domain predicted that W251C might lead to a structural rearrangement affecting the active site H257 and that P404L might alter the geometry of the active site loop and therefore affect the serine protease activity.

Pendred syndrome: phenotypic variability in two families carrying the same PDS missense mutation.

Pendred syndrome comprises congenital sensorineural hearing loss, thyroid goiter, and positive perchlorate discharge test. Recently, this autosomal recessive disorder was shown to be caused by mutations in the PDS gene, which encodes an anion transporter called pendrin. Molecular analysis of the PDS gene was performed in two consanguineous large families from Southern Tunisia comprising a total of 23 individuals affected with profound congenital deafness; the same missense mutation, L445W, was identified in all affected individuals. A widened vestibular aqueduct was found in all patients who underwent computed tomography (CT) scan exploration of the inner ear. In contrast, goiter was present in only 11 affected individuals, who interestingly had a normal result of the perchlorate discharge test whenever performed. The present results question the sensitivity of the perchlorate test for the diagnosis of Pendred syndrome and support the use of a molecular analysis of the PDS gene in the assessment of individuals with severe to profound congenital hearing loss associated with inner ear morphological anomaly even in the absence of a thyroid goiter.

Diagnosis of human hydatidosis: comparison between imagery and six serologic techniques.

Echography and/or chest radiograph in association with six serologic (immunologic) methods were tested for their ability to diagnose human hydatidosis. The immunologic techniques used were latex agglutination, counter immunoelectrophoresis, enzyme-linked immunosorbent assay (ELISA) with whole hydatid fluid and with antigen 5, a thermobabile lipoprotein that elicits the arc 5 precipitin line in immunoelectrophoresis. In this report, the results of examinations of 273 patients are presented. Of these, 243 cases were surgically proven to have hydatidosis, whereas 30 of the 273 that were strongly suspected of having hydatid cysts by radiology were shown to have other pathologies. The ELISA was more sensitive than the other methods, with 204 of 243 sera shown to be positive. The remaining 39 sera that gave false-negative results were tested using two recently developed methods, enzyme-linked immunoelectrodiffusion assay (ELIEDA) and immunoblotting (electrophoretic migration of hydatid fluid antigens under denaturing but nonreducing conditions, blotting, and immunoenzymatic assay). Immunoblotting, using our experimental conditions, had a greater sensitivity than the ELIEDA with this technique. Four of 37 sera showed one to three bands of 65, 12, and 8 kD. The sensitivity of the ELISA did not increase with either the size or type of cyst. Comparison of radiology with serology confirmed a good correlation between the two methods. Nevertheless, serology is more specific but less sensitive than imagery.

The effects of drainage with a Redon versus a conventional drain on postoperative pain and blood loss after valve replacements.

AIM: The aim of this study was to assess the influence of drainage with a Redon drain versus a conventional drain on postoperative pain and blood loss after valve replacements. METHODS: After approval by the local Ethics Committee and written informed consent, 30 patients, 20-60 years of age, scheduled for first elective valve replacement were included. After standardized anaesthetic regimens, cardiopulmonary bypass and coagulation therapy procedures and at the end of the operation, the patients were randomly assigned to 1 of 2 groups: (GI, n=15): drainage with 4 Redon drains; (GII, n=15): drainage with 2 conventional drains. Postoperative pain intensity at rest (VAS-R), during coughing and mobilization (VAS-M) in bed was independently evaluated using a visual analogue scale (VAS 100 mm) at 6 hourly intervals until 48 h after admission to the ICU (Ho). All patients received 2 g of paracetamol after obtaining the VAS score (8 g/24 h). No other analgesic agents were used. All patients were submitted to 2D echocardiography to verify the presence of pericardial effusion 24 h after surgery. Values are expressed as means. Pearson's chi squared and ANOVA (for repeated measurements) were used for statistical analysis. P<0.05 was considered significant. RESULTS: There was no statistically significant difference in the mean postoperative VAS-R and VAS-M, and in the mean postoperative total blood drainage 822.3 ml in GI, versus 704.3 ml in GII. Non pericardial effusion was found, and we did not see side-effects in any of the patients. CONCLUSIONS: We have shown that drainage with a Redon drains versus a conventional drain does not influence postoperative pain intensity and blood loss after valve replacements.