Underexpression of tumour suppressor LKB1 in clear cell renal cell carcinoma is common and confers growth advantage in vitro and in vivo.

BACKGROUND: Evidence suggests that dysregulation of energy-sensing pathways closely associates with renal cell carcinoma (RCC) development. The metabolic regulation is largely controlled by 5'-AMP activated protein kinase (AMPK) which is activated through phosphorylation by LKB1. METHODS: The expression of LKB1 was determined by reverse transcription-PCR using 10 clinical clear cell RCC (ccRCC) samples and their adjacent normal renal parenchyma, and by immunohistochemical staining of two tissue microarrays containing 201 ccRCC and 26 normal kidney samples. Expression of LKB1 was knocked down in human ccRCC 786-O cells (shLKB1) and compared with cells expressing scrambled control shRNA (shControl). AMPK signalling, proliferation, invasion, and VEGF secretion was measured. The cells were subcutaneously injected into mice to determine tumour growth in vivo. RESULTS: At the protein and transcript levels, a significant reduction in LKB1 expression in tumour compared with normal tissue was found. In vitro, knockdown of LKB1 resulted in reduced AMPK signalling and increased cellular proliferation, invasion, and VEGF secretion compared with shControl cells. In vivo, growth of shLKB1 ccRCC xenografts in nude mice was significantly increased compared with shControl xenografts. CONCLUSION: Collectively, our results suggest that LKB1 acts as a tumour suppressor in most sporadic cases of ccRCC and that underexpression of LKB1 is a common event in the disease.

Reliability of a multidimensional questionnaire for adults with treated complete cleft lip and palate.

The purpose of this study was to evaluate the reliability of a multidimensional questionnaire for Swedish adults with treated complete unilateral or bilateral cleft lip and palate (CLP). The questionnaire was designed to be used in the evaluation of adults with treated CLP after treatment. Before any conclusions were drawn from the results of the study we assessed the test-retest reliability of the questionnaire. The questionnaire included 168 questions and assessed the following domains: aesthetics, functions associated with CLP, satisfaction with treatment and perceived need for treatment, quality of life, depression and non-specific physical symptoms, body image, and jaw function. The subjects answered the questionnaire twice at a 2-3-week interval. Sixty-one adults (38 men, 23 women) mean age 24 years (range 20-29) participated in the study. The response rate for the questionnaire was acceptable at 75%. The test-retest reliability varied among the different domains. The reliability of questions regarding aesthetics, functions associated with CLP, and treatment satisfaction was good to excellent (intraclass correlation coefficient (ICC) = 0.51 to 0.89). Good to excellent (ICC = 0.61 to 1.0) reliability was also found for the quality of life in various life domains and the wellbeing scales. The reliability of the body image scale was moderate (kappa = 0.43-0.60) for most items and lower than that of other scales used in this study. The reliability of the mean depression symptom score (ICC = 0.93) and the mean non-specific physical symptoms score (ICC = 0.85) were excellent. The reliability of the mandibular function impairment was good (ICC = 0.67). The conclusion of the study is that an overall reliability was good for the multidimensional questionnaire.

Morphological characterization of the levator veli palatini muscle in children born with cleft palates.

OBJECTIVE: The aim of this study was to analyze, morphologically and biochemically, one of the soft palate muscles, the levator veli palatini (LVP), in children born with cleft palate. SUBJECTS AND METHODS: Biopsies were obtained from nine male and three female infants in connection with the early surgical repair of the hard and soft palate. Samples from five adult normal LVP muscles were used for comparison. The muscle morphology, fiber type and myosin heavy chain (MyHC) compositions, capillary supply, and content of muscle spindles were analyzed with different enzyme-histochemical, immunohistochemical, and biochemical techniques. RESULTS: Compared with the normal adult subjects, the LVP muscle from the infantile subjects with cleft had a smaller mean fiber diameter, a larger variability in fiber size and form, a higher proportion of type II fibers, a higher amount of fast MyHCs, and a lower density of capillaries. No muscle spindles were observed. Moreover, one-third of the biopsies from the infantile subjects with cleft LVP either lacked muscle tissue or contained only a small amount. CONCLUSIONS: The LVP muscle from children with cleft palate has a different morphology, compared with the normal adult muscle. The differences might be related to different stages in maturation of the muscles, changes in functional demands with growth and age, or a consequence of the cleft. The lack of contractile tissue in some of the cleft biopsies offers one possible explanation to a persistent postsurgical velopharyngeal insufficiency in some patients, despite a successful surgical repair.

Temporomandibular disorders in adults with repaired cleft lip and palate: a comparison with controls.

The purpose of this study was to investigate the prevalence of temporomandibular disorders (TMD), and assess psycho-social distress in adult subjects with repaired complete cleft lip and palate (CLP). Sixty-three adults (42 males and 21 females, mean age 24.2 years, range 19.5-29.2) with repaired CLP (CLP group) were compared with a group of 66 adults without cleft (non-cleft group, 49 males and 17 females, mean age 25.5 years, range 20.2-29.9). All subjects underwent a clinical TMD examination, which followed the guidelines in the Research Diagnostic Criteria for TMD (RDC/TMD). Jaw function was assessed by evaluating answers to the mandibular function impairment questionnaire (MFIQ). Tension-type headache was diagnosed according to the International Headache Society (IHS) classification. Psychological status was assessed using the depression score and the non-specific physical symptom score with subscales of the Revised Symptom Checklist-90 (SCL-90-R). The prevalence of reported pain in the face, jaws and/or TMJs was 14 and 9 per cent for the CLP and non-cleft group, respectively, and did not differ significantly between the groups. The CLP group exhibited a significantly reduced jaw-opening pattern (P < 0.001) and a higher frequency of crossbites (P < 0.05) compared with the non-cleft group. Whilst jaw function was similar in both groups, a few items, e.g. speech and drinking, were significantly more impaired (P < 0.01) in the CLP group than in the non-cleft group. There were no significant differences between the two groups concerning tension-type headache or psycho-social distress. The study found that overall TMD pain or psycho-social distress was not more common in this CLP group than in a non-cleft group.

Quality of life in adults with repaired complete cleft lip and palate.

OBJECTIVE: This study evaluated the quality of life in adult Swedish subjects with repaired complete cleft lip and palate (CLP). DESIGN/PATIENTS: Sixty-eight adults with repaired CLP were compared with a group of 66 adults without cleft matched by gender and age. OUTCOME MEASURES: The outcome measures included a self-report questionnaire concerning quality of life in general, well-being, and health-related quality of life. RESULTS: The CLP group rated their quality of life significantly lower than did the control group in the areas of life meaning (p <.05), family life (p <.0001), and private economy (p <.01). There were no significant differences between the groups concerning well-being. In the CLP group, the health-related quality of life was significantly lower concerning global life (p <.0001), disturbance to life (p <.01), well-being (p <.0001), social contacts (p <.0001), and family life (p <.05) but significantly higher concerning ability to make the most of leisure time (p <.001) and to be active (p <.001). CONCLUSIONS: The CLP group perceived a marked impact of the handicap on their lives concerning global aspects, well-being, and social life. More practical and tangible aspects of their daily living, however, were not affected, and only some minor aspects of their quality of life in general were poor in comparison with the control group, which indicates a fairly good life adjustment in spite of the handicap.

Periodontal evaluation of teeth in bone grafted regions in patients with unilateral cleft lip and cleft palate.

In 28 patients with unilateral cleft lip and cleft palate who were provided treatment that included bone grafting at an age of 8 to 13 years, periodontal conditions of teeth in the cleft region were monitored from a time point before bone grafting until the canine was fully erupted through the grafted region. Widths of keratinized and attached gingiva tended to increase between preoperative and postoperative examinations. Gingival recession was observed preoperatively for the tooth mesial to the cleft in 14 of the 28 patients. Postoperatively, only three of these patients showed recession. Improvements of the marginal bone level were observed both for teeth mesial and distal to the cleft. Canines having erupted through the grafted defect showed periodontal conditions similar to those of the contralateral canine. The findings demonstrate that treatment, which included osseous grafting before the eruption of the canine, resulted in satisfactory periodontal conditions for teeth in the cleft region.

Ectopic eruption of the maxillary first permanent molars in children with cleft lip and/or palate.

The purpose of this study was to analyse the prevalence of ectopic eruption of maxillary first permanent molars in children with cleft lip and palate, and evaluate the influence of both local and genetic factors. Radiographs from 225 children, 125 girls and 100 boys, were studied. The prevalence in cleft children was found to be more than four times higher than in non-cleft children (4.3 per cent). In children with cleft lip or cleft lip and alveolar process the prevalence was 15.4 per cent and in children with cleft palate only it was 28.8 per cent. A notable finding is that the ectopically erupting molar was not related to the cleft side. In children with surgically corrected cleft lip in combination with cleft palate or with cleft palate only, the surgery may have influenced the prevalence to some extent, but the main explanation for the increased prevalence of ectopic eruption in cleft children is a genetic aetiology.

Quantitative evaluation of the soft tissue profile in the planning of orthognathic surgery.

The clinical application of a proportional soft tissue profile analysis based on natural head position is presented. The analysis provides data concerning the morphological basis of facial disharmony in individual cases. The use of this information during treatment planning and evaluation of treatment results after orthognathic surgery is demonstrated in four patients with severe deviation from midnormal profiles.

Lip and nose morphology in patients with unilateral cleft lip and palate from four Scandinavian centres.

Sixty patients with unilateral cleft lip and palate were compared for lip and nose appearance. All patients were photographed from an anteroposterior and a basal view at 7-10 years of age. The photographic registration method was tested for validity and accuracy. Although the four groups of 15 patients each were treated according to different protocols, many similarities were found with shorter lip heights at the cleft side and inclination of the rima oris. Asymmetry of nose and retropositioning at the cleft side naris were generally seen. Significantly straighter noses were demonstrated in the group treated with a two-stage lip nose operation combined with nose plugs, and the two groups where vomer flaps were used showed the greatest deviation of the nose.

Dentofacial relations in young adults with unilateral complete cleft lip and palate. A follow-up study.

A retrospective study was made on 30 patients born between 1958 and 1969 with unilateral complete cleft lip and palate (C-UCLP) and operated on at the Department of Plastic Surgery, University Hospital, Umeå, Sweden. All patients were operated on by the same surgeon. The results are based on data from records at 5, 10, 16 and 20 years of age. The facial morphology of the cleft children at 5 years of age was rather close to that of the normal children. During growth the faces became retrognathic, more visibly so in the maxilla resulting in straight or concave profiles. This was more evident among the boys. There were no differences regarding maxillary growth between children bone grafted at 10 to 16 years of age and those bone grafted after 16 years of age or not at all. Although surgical procedures and orthodontic treatment varied, 70% had less than 3 teeth in crossbite relationships at 20 years of age. An important factor to take into consideration is the fact that in addition to the influence that the cleft morphology and treatment have on the dentofacial growth, other dentofacial growth patterns also exist among the cleft patients. Generally the groups of patients reported are rather small and therefore conditions like these can have a strong influence on the results.

Craniofacial and occlusal characteristics in unilateral cleft lip and palate patients from four Scandinavian centres.

Craniofacial morphology and dental occlusion were studied at early school age in 15 consecutive patients with unilateral cleft lip and palate from each of four Scandinavian cleft centres. Treatment differed mainly in the techniques of palatal repair. Push-back closure of the palate particularly impaired maxillary development, which resulted in an increased incidence of crossbite and reduced intercanine distance when compared with patients who had been operated on by the von Langenbeck method or in whom the anterior palate had not yet been closed.

The influence of activator treatment on skeletal growth in Angle Class II: 1 cases. A roentgenocephalometric study.

The aim of this study was to evaluate possible skeletal effects of activator treatment on children with Angle Class II:1 malocclusions. The material consisted of lateral roentgenocephalograms of 31 girls and 22 boys, 8-14 years of age, who were treated with Andresen activators for an average period of 2.5 years. Growth and treatment effects were determined by comparing measurements on cephalograms of a group of untreated children with the same facial morphology and growth rate. The cephalograms were superimposed on the sella-nasion line and on the internal structures of the mandible. The activator treatment had a significant effect on the sagittal intermaxillary relationship and the anterior facial height. Among the girls the decreased ANB angle was mainly due to a retarded forward growth of the maxilla, while this decrease among the boys depended more on increased mandibular growth. Another feature was the anterior rotation of the mandible in the activator subjects although to a lesser extent than in the control groups. The total amount of condylar growth did not differ between the groups, but the direction of growth did. In the activator groups the growth was in a more superior-posterior direction than among the controls, thus contributing to the increased total length of the mandible in the activator groups.

[Neurilemmoma of the stomach. Presentation of a case]. / Il neurilemmoma dello stomaco. Presentazione di un caso.

The paper describes a recent case of neurilemmoma of the stomach. Following a review of the literature, the Authors focus their attention on the diagnostic difficulties and the choice of therapy. Tomography, arteriography and gastroscopy with multiple biopsies may at times be misleading depending on the development of the tumour. Most Authors agree that local resection or, when possible, enucleation are the most appropriate forms of therapy.

Intermediate bone grafting of alveolar clefts.

During the five year period 1980 to 1985 bone grafting was performed in 37 cleft patients before the eruption of the canine tooth (group IBG) and in 30 patients after the eruption of the canine tooth (group SGB). The initial healing was more favourable in the IBG group. In 72.5% of the clefts oro-nasal fistulae were present preoperatively. In all cases the fistulae were successfully closed. In the IBG group with orthodontic closure of the gap in the dental arch the interdental bone height in the grafted area was more than 75% of normal bone height in all clefts. In group SBG this situation was found in only 66% of the bone-grafted areas. There seems to be a clear relation between the age or the developmental stage of the canine tooth on the one hand and the possibility of orthodontic closure of the gap in the dental arch and good interdental bone height on the other hand. This also leads to the suggestion that if bone grafting to the alveolar cleft is required the operation should be performed before the eruption of the canine tooth on the cleft side.