AK2 deficiency compromises the mitochondrial energy metabolism required for differentiation of human neutrophil and lymphoid lineages.

Reticular dysgenesis is a human severe combined immunodeficiency that is primarily characterized by profound neutropenia and lymphopenia. The condition is caused by mutations in the adenylate kinase 2 (AK2) gene, resulting in the loss of mitochondrial AK2 protein expression. AK2 regulates the homeostasis of mitochondrial adenine nucleotides (ADP, ATP and AMP) by catalyzing the transfer of high-energy phosphate. Our present results demonstrate that AK2-knocked-down progenitor cells have poor proliferative and survival capacities and are blocked in their differentiation toward lymphoid and granulocyte lineages. We also observed that AK2 deficiency impaired mitochondrial function in general and oxidative phosphorylation in particular - showing that AK2 is critical in the control of energy metabolism. Loss of AK2 disrupts this regulation and leads to a profound block in lymphoid and myeloid cell differentiation.

[Catheter fracture and pulmonary embolization of the distal fragment: a rare complication of the totally implantable venous access port]. / Rupture du cathéter et migration du fragment distal vers les artères pulmonaires : une complication rare des chambres à cathéter implantables.

INTRODUCTION: Totally implantable venous access port plays a crucial role in the treatment of patients in oncology. However, its use can result sporadically in catheter fracture with catheter tip embolization into pulmonary arteries. CASE REPORTS: We report this unusual but potentially serious complication in four patients. In these patients, the port had been inserted percutaneously into the subclavian vein using the infra-clavicular approach. This side effect occurred late in three patients. In all patients, the catheter fracture was asymptomatic or pauci-symptomatic and was caused by the pinch-off syndrome. The retrieval of the embolized fragments was successfully performed by transcatheter procedure in the cardiac catheterisation laboratory. CONCLUSION: We reviewed the literature and the newest guidelines and recommendations to detail the clinico-radiological features, the possible causes of this complication and discussed means to recognize, manage and prevent it.

Age-standardized mortality rates by cause in Basra, Iraq: 1978 and 2007.

Mortality data are essential to identify the public health importance of different diseases and allocate resources appropriately. This descriptive study was carried out to assess the pattern of mortality in Basra governorate in southern Iraq using the death records from the civil registry system for 2 years (1978 and 2007). The overall age-standardized mortality rate was lower in 2007 than 1978 (7.95 versus 8.70 per 1000), so too were the age-specific mortality rates, with the exception of that for young adults, which was 22% higher. The leading cause of death in both years was cardiovascular diseases, while cancer was the third leading cause in 1978 and the second in 2007. Mortality rates were 45.5% lower for infectious diseases in 2007 compared with 1978, 39.5% lower for respiratory diseases, 50.0% lower for digestive system diseases, 66.7% higherfor congenital malformations and 4-fold higher for endocrine and nutritional diseases.

[Repair of nose, lips and chin mutilations. The customary repairs versus allografts]. / Réparation des mutilations du triangle nasolabio-mentonnier. Plasties conventionnelles versus allogreffes.

Central-facial mutilations, located within the nose lips and chin triangle, require great quality repairs regarding morphology and function. Plastic surgery history affords the ideas evolution in this field crossing over nose and lips reconstructions, which were the subject of successive reports within our society, in 1994 (nose reconstruction) and 2002 (lips reconstruction). Now a day, following this progress, the plastic surgeon has a large choice of reliable techniques. His choice is dictated by a precise evaluation of the limits of the substance loss to repair, according to a (mapping) classification of the nose-lip and chin triangle. This classification defines three units (nose-labial, bilabial and chin-labial) as reflexion bases to the therapeutic indications. This anatomical and surgical approach was built starting from a retrospective study of 195 central-facial mutilations caused by ballistic damage and dog bites. The results evaluation makes possible to carry out a reflexion on the potential indications regarding allograft as a therapeutic alternative to the traditional reconstructions of this territory.

Psychological aspects of orthognathic surgery and its effect on quality of life in Egyptian patients.

A study was made of 120 patients aged 11-33 years who underwent various types of orthognathic surgery in a Cairo hospital between 1998 and 2004. Patients answered a standardized questionnaire to identify motives for seeking surgery, the degree of satisfaction with the outcome and its effect on quality of life. Preoperatively, aesthetic reasons were the primary motive for seeking surgery in 95% of patients. Postoperatively, 85% of the patients were positive about the outcome of surgery as well as its effect on their quality of life. Postoperative improvement of facial aesthetics of the patients was associated with improvement of their quality of life in all aspects tested.

Rheumatic manifestations of psoriasis.

Psoriatic arthritis was described as a distinct rheumatic disease in the 1960s, and subsequently grouped among the spondyloarthropathies. Recently, other rheumatic manifestations of psoriasis, such as enthesopathy and osteoperiostitis, were recognized. This study attempts to examine the rheumatological and radiological manifestations of Psoriasis and their association with skin and nail disease. Eighty-one psoriatic outpatients were interviewed consecutively during 6 months. Questionnaires and indices were carried out to assess the extent and severity of skin and nail involvement, as well as the activity and severity of peripheral and axial rheumatic manifestations. Radiological examination of the hands, feet, spine and pelvis was also done for all patients. Fifty-nine psoriatic outpatients (73%) had rheumatic manifestations clinically and/or radiologically (Psoriatic arthropathy "PsA"). Clinical peripheral arthritis was found in 14 (23.7%) of the patients with PsA, being oligoarticular in 11, polyarticular in two, and exclusively of the distal interphalangeal (DIP) joints in one patient. Sacroiliitis and/or spondylitis were found in 38 (64.4%), enthesopathy in 36 (61%), dactylitis in two (3.3%), radiological DIP involvement in 24 (40.6%), and radiological osteoperiostitis in 49 (83%) of patients with PsA. Most PsA patients had more than one rheumatic manifestation, while four patients (6.7%) had isolated enthesopathy without any other rheumatic manifestations. Subungual hyperkeratosis of the nails was significantly correlated with PsA (p<0.05), as well as with clinical arthritis, enthesopathy, and DIP involvement (p<0.01), while other types of skin and nail lesions were correlated with selected rheumatic manifestations. The performance of existing criteria for PsA was poor, as individual sets favored either sensitivity or specificity. Psoriatic arthropathy (PsA), occurring in about three-quarters of hospital outpatients with psoriasis, is more common than previously thought. More sensitive and specific criteria for the diagnosis and classification of PsA need to be developed, taking into account the recently described clinical and radiological manifestations.

[Facial injuries treated in the Grenoble University Hospital. Epidemiological analysis of 961 patients managed in one year]. / Traumatismes faciaux au CHU de Grenoble. Etude épidémiologique de 961 dossiers sur une période de 365 jours.

INTRODUCTION: The purpose of this study was to determine the types of facial injuries treated in a one-year in a maxillo-facial unit operating in a mountainous region. METHODS: All patients admitted to the Grenoble University Hospital maxillo-facial unit for a one year period were studied. We noted cause of trauma, age, sex, type and location of fracture, type of soft tissue injury, time between trauma and surgery. RESULTS: A total of 994 patients presenting maxillo-facial trauma underwent surgery over one year; 30% of the unit's maxillo-facial surgical activity. On average, 80 patients were treated for maxillo-facial trauma per month, with a peak of 97 facial injuries in July; 65.6% were hospitalized in the maxillo-facial unit; 25,4% of the injured were aged between 21 and 30 years. Sex-ratio was 2.7M/1F. The most frequent cause was sports injuries (25.8%) followed, in decreasing order, by traffic injuries (23.1%), home injuries (17.6%), fight injuries (3.4%), work injuries (3.4%) and dog bites (3.2%). 10.5% of the injuries occurred in a mountainous setting and 40.7% were sports injuries, 95% of which during practice of winter's sports. Injuries included facial fractures (65.5%) with or without soft tissue damage, and soft tissue injuries only (34.5%); 33.6% of the patients had other lesions of the body. 67.2% underwent surgery within the first 24 hours and 86.9% before the fifth day. DISCUSSION: Sports accidents are the leading cause of facial trauma in the mountainous regions. Most facial injuries result from ski, surf and other winter sports accidents. Most of the victims were given surgical care within the first 24 hours following the accident.

[Beyond the lips. Reconstructive techniques and indications]. / Les lèvres dépassées. Techniques de reconstruction et indications.

Labial tissue defects that extend beyond the anatomic boundary of the labial region confront us with two distinct reconstructive problems. When the extension is centrifugal towards the periphery, the tissue loss is essentially tegumentary. The reconstructive aim in this case is not only to restore tissues of the perilabial areas with the best possible morphologic and functional harmony but also to place the reconstructed lip harmoniously and in good relation to these structures. In the case of posterior extension of tissue losses towards the jaws, it is mandatory to reconstruct the underlying bony and eventually alveolo-dental architecture prior to the lip reconstruction. The reconstruction strategy is emphasised by two cases of complex ballistic injury.

Oxidative modification and inactivation of the proteasome during coronary occlusion/reperfusion.

Restoration of blood flow to ischemic myocardial tissue results in an increase in the production of oxygen radicals. Highly reactive, free radical species have the potential to damage cellular components. Clearly, maintenance of cellular viability is dependent, in part, on the removal of altered protein. The proteasome is a major intracellular proteolytic system which degrades oxidized and ubiquitinated forms of protein. Utilizing an in vivo rat model, we demonstrate that coronary occlusion/reperfusion resulted in declines in chymotrypsin-like, peptidylglutamyl-peptide hydrolase, and trypsin-like activities of the proteasome as assayed in cytosolic extracts. Analysis of purified 20 S proteasome revealed that declines in peptidase activities were accompanied by oxidative modification of the protein. We provide conclusive evidence that, upon coronary occlusion/reperfusion, the lipid peroxidation product 4-hydroxy-2-nonenal selectively modifies 20 S proteasome alpha-like subunits iota, C3, and an isoform of XAPC7. Occlusion/reperfusion-induced declines in trypsin-like activity were largely preserved upon proteasome purification. In contrast, loss in chymotrypsin-like and peptidylglutamyl-peptide hydrolase activities observed in cytosolic extracts were not evident upon purification. Thus, decreases in proteasome activity are likely due to both direct oxidative modification of the enzyme and inhibition of fluorogenic peptide hydrolysis by endogenous cytosolic inhibitory protein(s) and/or substrate(s). Along with inhibition of the proteasome, increases in cytosolic levels of oxidized and ubiquitinated protein(s) were observed. Taken together, our findings provide insight into potential mechanisms of coronary occlusion/reperfusion-induced proteasome inactivation and cellular consequences of these events.

Haplotypes of four novel single nucleotide polymorphisms in the nicotinic acetylcholine receptor beta2-subunit (CHRNB2) gene show no association with smoking initiation or nicotine dependence.

Several types of evidence, including experiments with mice that lack the nicotinic acetylcholine receptor beta2-subunit gene (CHRNB2), have suggested that a beta2-containing nicotinic receptor is necessary for at least some of the reinforcing properties of nicotine. However, sequence variations in CHRNB2 have not been reported, and its role in influencing human smoking behavior and nicotine dependence is not known. We screened most of the introns and exons and found five novel single nucleotide polymorphisms (SNPs). We tested four of these SNPs in three large, carefully selected samples: nonsmokers (n = 317) and regular smokers low levels of nicotine dependence (ND, n = 238), or smokers with high-ND (n = 317). None of the four polymorphisms we tested, nor their estimated haplotypes, were associated with smoking initiation or progression to nicotine dependence.

[Prominent ears: a simple ambulatory technique under local anesthetic]. / Oreilles proéminentes: une technique simple, sous anesthésie locale, en ambulatoire.

We present a simple otoplasty technique for the correction of prominent ears. Children can be operated starting from 8 years old, after meticulous analysis of the deformity which usually associates chonchal malposition and failure of scapha folding. Chonchal malposition can be corrected by a posterior access and chonchal-mastoid sutures. Failure of scapha folding can be corrected by an anterior access, cartilage scoring and mattress sutures. Our retrospective study of 368 patients shows 83% very good and good results. The morbidity rate is low and comparable to that of other studies. This technique is simple, didactic, easily performed under local anesthesia on an outpatient basis. Moreover, it is not aggressive and is easily adaptable to various deformities.

Susceptibility genes for nicotine dependence: a genome scan and followup in an independent sample suggest that regions on chromosomes 2, 4, 10, 16, 17 and 18 merit further study.

Cigarette smoking is associated with considerable morbidity, mortality, and public health costs. Genetic factors influence both smoking initiation and nicotine dependence, but none of the genes involved have been identified. A genome scan using 451 markers was conducted to identify chromosomal regions linked to nicotine dependence in a collection of 130 families containing 343 genotyped individuals (308 nicotine-dependent) from Christchurch, New Zealand. By pairwise analysis, the best result was with marker D2S1326 which gave a lod score under heterogeneity (H-LOD) of 2.63 (P=0.0012) and a nonparametric linkage (NPL, Zall) score of 2.65 (P=0.0011). To identify regions that warranted further study, rather than comparing the pairwise scores from the scan to theoretical thresholds, we compared them to an empirical baseline, found here to be H-LOD scores of 0.5 and Zall scores of 1.0. We also found a number of large (31-88 cM) regions where many (8-16) consecutive markers yielded small but positive Zall scores. Selected regions of chromosomes 2, 4, 10, 16, 17 and 18 were investigated further by additional genotyping of the Christchurch sample and an independent sample from Richmond, Virginia (91 families with 264 genotyped individuals, 211 nicotine-dependent). Multipoint nonparametric analysis showed the following maximums for the Christchurch sample: Chr. 2 (Zlr=2.61, P=0.005), Chr. 4 (Zlr=1.36, P=0.09), Chr. 10 (Zlr=2.43, P=0.008), Chr. 16 (Zlr=0.85, P=0.19), Chr. 17 (Zlr=1.64, P=0.05), Chr. 18 (Zlr=1.54, P=0.06). Analysis of the Richmond sample showed the following maximums: Chr. 2 (Zlr=1.00, P=0.15), Chr. 4 (Zlr=0.39, P=0.34), Chr. 10 (Zlr=1.21, P=0.11), Chr. 16 (Zlr=1.11, P=0.13), Chr. 17 (Zlr=1.60, P=0.05), Chr. 18 (Zlr=1.33, P=0.09). It is probable that the small samples used here provided only limited power to detect linkage. It may have been difficult therefore to detect genes of small effect, or those that are influencing risk in only a small proportion of the families. When simply judged against the usual standards of linkage significance, none of the individual regions yielded strong evidence in either sample. Some or all of the most positive results in the genome scan of the Christchurch sample, therefore, could be due to chance. However, the presence in the Christchurch scan of multiple large regions containing many consecutive positive markers, coupled with the relatively positive results in these same regions in the Richmond sample, suggests that some of these regions may contain genes influencing nicotine dependence and therefore deserve further study.

Supportive care of cancer patients in Dubai.

Supportive care of cancer patients starts from the first day of diagnosis. It is a comprehensive approach involving psychosocial, physical and spiritual supports. Maximum efforts are put in to keep the patients as comfortable as possible during diagnosis, during treatment and during the terminal stages of their disease.

Treatment of advanced squamous cell carcinoma of the skin with cisplatin, 5-fluorouracil, and bleomycin.

The authors treated 14 patients with advanced squamous cell carcinoma (SCC) of the skin or lip with one to four cycles of combination chemotherapy consisting of cisplatin by bolus injection, and 5-fluorouracil (5-FU) and bleomycin by continuous 5-day infusion. Objective responses were seen in 11 of the 13 evaluable patients (84%). Four patients had a complete remission (30%) and seven patients, a partial remission (54%). Local control after definitive complementary radiation and/or surgical treatment was achieved in seven patients. Toxic side effects was acceptable; they consisted of nausea and vomiting in all patients, transient skin changes, hematologic (Grade 3/4) abnormalities in four patients, and pulmonary fibrosis in one elderly patient. These results show that this chemotherapy combination could play a role in reducing the tumor mass and in facilitating definitive treatment to obtain better functional and cosmetic results in advanced SCC of the skin.

[Role of micro-anastomosed muscular transplantation in corrective surgery of permanent facial paralysis]. / Place des transplantations musculaires micro-anastomosées dans la chirurgie correctrice de la paralysie faciale définitive.

Vascularized and reinnervated transfer of a muscle from the body to the face is never a simple procedure. It is important to evaluate the pre-operative state of facial muscles. It is difficult to define the correct indications for the various surgical techniques proposed: muscle selection, selection of recipient vessels, selection of a reinnervation method, the positioning of the transferred muscle. The authors present a series of 12 cases of long standing facial paralysis for more than 3 years. Results are presented. The authors think that the ideal muscular transfer is still unknown. In principle, nothing can replace facial muscles except facial muscles. Currently, the authors prefer the latissimus dorsi flap with partial transfer. For reinnervation, the facial nerve must take the priority, while all other reinnervation technics should take second place. In all cases, great attention must be paid to the positioning of the muscle, the usefulness of conventional palliative procedures and the continuous moral support to all of these patients.

Small sucrose density gradients: reproducible and automatic fractionation using a commercial fraction collector (Pharmacia).

A simple, inexpensive modification of a programmable commercial fraction collector (Frac 100; Pharmacia, Sweden) was described. This modification allowed reproducible automatic fractionation of small sucrose gradients by rinsing the hanging drop at the delivery head of the fraction collector into the sampling tube, using signals from the fraction collector to control this specialized function. The described principle may also be useful whenever fraction size is near to drop volume and high resolution and reproducibility are desired.