Mutational analysis of the SOX9 gene in campomelic dysplasia and autosomal sex reversal: lack of genotype/phenotype correlations

It has previously been shown that, in the heterozygous state, mutations in the SOX9 gene cause campomelic dysplasia (CD) and the often associated autosomal XY sex reversal. In 12 CD patients, 10 novel mutations and one recurrent mutation were characterized in one SOX9 allele each, and in one case, no mutation was found. Four missense mutations are all located within the high mobility group (HMG) domain. They either reduce or abolish the DNA-binding ability of the mutant SOX9 proteins. Among the five nonsense and three frameshift mutations identified, two leave the C-terminal transactivation (TA) domain encompassing residues 402-509 of SOX9 partly or almost completely intact. When tested in cell transfection experiments, the recurrent nonsense mutation Y440X, found in two patients who survived for four and more than 9 years, respectively, exhibits some residual transactivation ability. In contrast, a frameshift mutation extending the protein by 70 residues at codon 507, found in a patient who died shortly after birth, showed no transactivation. This is apparently due to instability of the mutant SOX9 protein as demonstrated by Western blotting. Amino acid substitutions and nonsense mutations are found in patients with and without XY sex reversal, indicating that sex reversal in CD is subject to variable penetrance. Finally, none of 18 female patients with XY gonadal dysgenesis (Swyer syndrome) showed an altered SOX9 banding pattern in SSCP assays, providing evidence that SOX9 mutations do not usually result in XY sex reversal without skeletal malformations.      

A cohort study for the derivation and validation of a clinical prediction scale for hospital-onset Clostridium difficile infection

OBJECTIVE:

To develop and validate a clinical prediction scale for hospital-onset Clostridium difficile infection (CDI).

METHODS:

A community-based, 360-bed hospital located in the suburbs of a metropolitan area in the United States served as the setting for the present retrospective cohort study. The cohort consisted of patients admitted to the adult medical service over a six-year period from October 2005 to September 2011. The cohort was divided into derivation (October 2005 to September 2009) and validation (October 2009 to September 2011) groups. The primary outcome measure was hospital-onset CDIs identified as stool positive for C difficile after 48 h of hospital admission ordered for new-onset unformed stool by the treating physician.

RESULTS:

In the derivation phase, 35,588 patients were admitted to the medical service and 21,541 stayed in hospital beyond 48 h. A total of 266 cases of CDI were identified, 121 of which were hospital onset. The developed clinical prediction scale included the onset of unformed stool (5 points), length of hospital stay beyond seven days (4 points), age >65 years (3 points), long-term care facility residence (2 points), high-risk antibiotic use (1 point) and hypoalbuminemia (1 point). The scale had an area under the receiver operating curve (AUC) of 0.93 (95% CI 0.82 to 0.94) in predicting hospital-onset CDI, with a sensitivity of 0.94 (95% CI 0.88 to 0.97) and a specificity of 0.80 (95% CI 0.79 to 0.80) at a cut-off score of 9 on the scale. During the validation phase, 16,477 patients were admitted, of whom 10,793 stayed beyond 48 h and 58 acquired CDI during hospitalization. The predictive performance of the score was maintained in the validation cohort (AUC 0.95 [95% CI 0.93 to 0.96]) and the goodness-to-fit model demonstrated good calibration.

CONCLUSION:

The authors developed and validated a simple clinical prediction scale for hospital-onset CDI. This score can be used for periodical evaluation of hospitalized patients for early initiation of contact precautions and empirical treatment once it is validated externally in a prospective manner.     

Befunde in den Hauptentwicklungsstufen des Gebisses bei Dysgnathieträgern

Zusammenfassung In dieser Arbeit wurden die Gebisse von 31 männlichen und 45 weiblichen Dysgnathieträgern mit Hilfe des Berliner Meßsystems vermessen und die Ergebnisse mit Hilfe eines Computers ausgewertet. Es erfolgt der Vergleich der Parameter zwischen Probanden mit Progenie, Kreuzbiß, offenem Biß und Schmalkiefer. Die Veränderung der Werte wurden longitudinal in den Hauptentwicklungsstufen Milchgebiß, Wechselgebiß und im bleibenden Gebiß untersucht. Dabei werden auch nach der Behandlung noch zwischen den Anomaliegruppen bei einzelnen Werten signifikante Unterschiede gefunden.

---

Summary In this study dental plaster casts of 31 male and 45 female subjects were measured using the Berlin measurement system and evaluated with the aid of a computer. The parameters of subjects with class III malocclusion, crossbite, open bite and class II/1 malocclusion were compared. The changes were studied longitudinally in the main developmental stages, namely the deciduous, mixed and permanent dentitions. Significant differences were found also following treatment between the malocclusion groups.

---

Résumé On a mesuré les dentures de 31 hommes et 45 femmes présentant des dysgnathies à l'aide du système de mesure mis au point à Berlin; les valeurs ainsi établies on fait l'objet d'un traitement sur ordinateur. On a procédé à la comparaison des paramètres des sujets atteints de prognathie inférieure, occlusion croisée, béance et endognathie. On a étudié la modification des valeurs de manière longitudinale, en suivant les principales étapes d'évolution: denture lactéale, denture mixte et denture permanente. L'examen a permis, même après le traitement, d'établir, pour chacune des valeurs, des différences importantes d'un groupe d'anomalie à l'autre.

     

Ameloblastoma: current etiopathological concepts and management

Ameloblastoma is a benign odontogenic tumor of epithelial origin. It is locally aggressive with unlimited growth capacity and has a high potential for malignant transformation as well as metastasis. Ameloblastoma has no established preventive measures although majority of patients are between ages 30 and 60 years. Molecular and genetic factors that promote oncogenic transformation of odontogenic epithelium to ameloblastoma are strongly linked to dysregulation of multiple genes associated with mitogen‐activated protein kinase, sonic hedgehog, and WNT/β‐catenin signaling pathways. Treatment of ameloblastoma is focused on surgical resection with a wide margin of normal tissue because of its high propensity for locoregional invasion; but this is often associated with significant patient morbidity. The relatively high recurrence rate of ameloblastoma is influenced by the type of molecular etiological factors, the management approach, and how early the patient presents for treatment. It is expected that further elucidation of molecular factors that orchestrate pathogenesis and recurrence of ameloblastoma will lead to new diagnostic markers and targeted drug therapies for ameloblastoma.     

Langzeitergebnisse nach lumbalen Bandscheibenerkrankungen

The therapeutic results of operatively and conservatively treated patients with lumbar disc syndromes were reviewed in a retrospective study. The patients were treated during a 10-years period (1976-1985). A total of 330 patients with lumbar disc prolapses were treated in the hospital during this period 44% were treated surgically. The data on 100 operated and 100 conservatively treated cases, registered in this random test sample, have been compared with respect to: pain; neurological deficits; subjective problems and sociomedical questions. The average patient age of both groups was about 41 years, and the patients predominant were male (about 70%). The therapeutic results of both operatively and conservatively treated patients were good, which is also by the high percentage of employment (80%-90%) in the two treatment groups. The critical evaluation showed more neurological disturbances and limited vocational activity in the group of cases operated upon. More than 70% of the operated cases showed radicular syndromes of the follow-up examination although it was not of essential functional importance. The period inability to work and the percentage of disablement were also much higher in this group. The pain symptoms were particularly relevant in our examination. Only 12%-16% of the patients in the two groups that took part in the follow-up examinations reported freedom from pain. It was apparent that atypical pain syndromes were correlated with personality psychological disturbances. Nearly one-third of our patients mentioned psychological problems. The prognosis of the conservative treatment of lumbar disc prolapse was equivalent to operative therapy (disregarding the absolute indications for operations). There were no definite advantages found for either of the two methods of treatment. The necessity for a specialized follow-up treatment of patients with sciatica due to herniated lumbar discs is discussed, and differentiated selection for operative therapy is given. Here the treatment of pain should be considered most important.