Use of ultrasound to assess healing of a mandibular distraction wound.

PURPOSE: A standardized, noninvasive technique to assess healing of the mandibular distraction wound is not available. Current methods include clinical examination, plain radiography, and computed tomography. These imaging techniques are expensive and obligate the patient to serial radiation exposure. In addition, anatomic overlap and metal artifacts may obscure the distraction gap. In contrast, ultrasound has been shown to be a noninvasive, efficient, and inexpensive way to evaluate bone healing. The purpose of this study was to test the feasibility of ultrasound to evaluate an experimental mandibular distraction osteogenesis wound. MATERIALS AND METHODS: Distraction devices were placed via a submandibular incision into 24 minipigs. The protocol consisted of 0-day latency and distraction rates of 1, 2, or 4 mm/d for a 12-mm gap. The wounds were assessed in vivo after 0, 8, 16, and 24 days of neutral fixation. Ex vivo radiographs were used to estimate bone fill using a semiquantitative score. A semiquantitative ultrasound score was assigned, and the beam penetration depth was measured in millimeters. RESULTS: In all groups, clinical stability of the distraction wound increased with the duration of fixation. Plain radiographs, taken during neutral fixation, showed that the desired distraction gap was achieved and maintained. The ultrasound score increased with fixation time, whereas beam penetration depth decreased as expected. Ex vivo radiographs showed increasing bone fill score with time and paralleled the ultrasound score. CONCLUSIONS: The results of this feasibility study indicate that ultrasound is potentially useful for the assessment of bone formation in distraction osteogenesis wounds.     

Two novel mutations at exon 8 of the Sequestosome 1 (SQSTM1) gene in an Italian series of patients affected by Paget's disease of bone (PDB).

PDB is genetically heterogeneous. Mutations of the sequestosome1 gene have been reported in sporadic and familial forms of Paget's in patients of French Canadian and British descent. Mutational analyses in different ethnic groups are needed to accurately investigate hereditary diseases. We describe two novel mutations of sequestosome1 in 62 Italian sporadic patients, confirming the role of the encoded protein in this disorder. INTRODUCTION: Paget's disease of bone (PDB) is a relatively common disease of bone metabolism reported to affect up to 3% of whites over 55 years of age. The disorder is genetically heterogeneous, and at present, there is scientific evidence that at least eight different human chromosomal loci are correlated with its pathogenesis. Mutations of the sequestosome1 (SQSTM1) gene were identified as responsible for most of the sporadic and familial forms of Paget in patients of French Canadian and British descent. Such mutations were located at exon 7 and 8 levels, encoding for the ubiquitin protein-binding domain (UBA) and representing a mutational hot spot area. MATERIALS AND METHODS: To verify the involvement of this gene in Italian subjects affected by PDB, we performed mutational analysis in 62 sporadic PDB cases. RESULTS: We described three different mutations at exon 8 level: P392L, already described in the French Canadian population and families predominantly of British descendent, and two novel mutations consisting of the amino acid substitutions M404V and G425R. No significant differences in the clinical history of PDB have been observed in patients with SQSTM1 mutations in respect to those without. CONCLUSIONS: Even though our findings suggest a minor involvement of the SQSTM1 gene in the pathogenesis of sporadic Italian Paget's cases, the identification of different significant mutations within the SQSTM1 gene in unrelated, but clinically similar individuals, offers extremely convincing evidence for a causal relationship between this gene and PDB. Longitudinal studies are needed to assess the penetrance of genotype/phenotype correlations. Our findings confirm the evidence of a clustered mutation area at this level in this disorder.     

Carvedilol protects ischemic cardiac mitochondria by preventing oxidative stress.

Ischemia negatively affects mitochondrial function by inducing the mitochondrial permeability transition (MPT). The MPT is triggered by oxidative stress, which occurs in mitochondria during ischemia as a result of diminished antioxidant defenses and increased reactive oxygen species production. It causes mitochondrial dysfunction and can ultimately lead to cell death. Therefore, drugs able to minimize mitochondrial damage induced by ischemia may prove to be clinically effective. We analyzed the effect of carvedilol, a beta-blocker with antioxidant properties, on mitochondrial dysfunction. Carvedilol decreased levels of TBARS (thiobarbituric acid reactive substances), an indicator of oxidative stress, which is consistent with its antioxidant properties. Regarding cell death by apoptosis, although ischemia did increase caspase-8-like activity, there were no changes in caspase-3-like activity, which is activated downstream of caspase-8; this may indicate that the apoptotic cascade is not activated by 60 minutes of ischemia. We conclude that carvedilol protects ischemic mitochondria by preventing oxidative mitochondrial damage, and, by so doing, it may also inhibit the formation of the MPT pore.     

An unusual association with Raynaud's phenomenon

A 36-yr-old lady with a year of typical Raynaud's and polyarthralgiahad a normal examination other than cold peripheries and bloodpressure of     

Gaucher disease: abdominal MR imaging findings in 46 patients.

Abdominal magnetic resonance imaging findings were reviewed in 46 patients with Gaucher disease. All patients had hepatosplenomegaly at the time of initial imaging. Splenic nodules were present in 14 patients (30%) and varied in signal intensity. These nodules were isointense on T1-weighted and hypointense on T2-weighted images. Splenic infarcts were seen in 15 patients (33%), and four of these patients (9%) also had subcapsular fluid collections. Both nodules and infarcts were present in the spleen in four patients (9%). Pathologic correlation was performed with specimens from two patients who underwent partial splenectomy. Focal areas of abnormal signal intensity were noted in the liver in nine patients (20%). They were either stellate or segmental, and may represent fibrotic septa with ischemic changes associated with aggregates of Gaucher cells. No changes were noted in the kidneys or abdominal lymph nodes.     

Age-related changes in the turnover rates of D1-dopamine receptors in the retina and in distinct areas of the rat brain

The steady-state density and the turnover rates of D₁-dopamine receptors were investigated in the striatum, nucleus accumbens, substantia nigra, and retina of adult (3-month-old) and aged (23-month-old) rats. The turnover rates were measured by monitoring the repopulation kinetics of D₁-dopamine receptors labeled with [³H]-SCH 23390 after the irreversible inactivation induced by a single dose of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ, 10 mg/kg, s.c.). In all the neural tissues examined, the repopulation of D₁ dopamine receptors could be adequately described by a theoretical model that assumes a constant rate of receptor production (i.e. zero order) and a rate of degradation that is dependent on the receptor density at any time (i.e. first order). The results obtained indicate that the reduction in the density of D₁-dopamine receptors in the striatum, nucleus accumbens and substantia nigra of aged rats is the result of a larger decrease in the receptor production rate (−44 to −60%) than in the receptor degradation rate (−21 to −46%). By contrast, the production rate of D₁-dopamine receptors in the retina of aged rats remains unchanged, whilst the degradation rate is reduced by 25%. This results in an age-related increase in the density of D₁-dopamine receptors in the rat retina.     

Spectrophotometric method of quantifying adult cat flea (Siphonaptera: Pulicidae) feces.

Cat flea, Ctenocephalides felis felis (Bouché), feces are an essential part of larval nutrition under natural conditions. The mass values of adult flea feces can be measured by dissolving samples of flea feces in Drabkin's reagent, filtering, centrifuging, and measuring absorbance spectrophotometrically at 540 nm. Either flea feces or air-dried host blood can be used to generate the standard curve used to convert absorbance (optical density) values into mass values. Debris collected from flea-infested house cats averaged 23.02 mg debris per cat per h with an average of 10.41 mg flea feces per cat per h. Flea feces deposited in the environment serve as potential larval food. Adult flea feces comprised an average of 44.28% of the debris deposited from infested domestic house cats in this study.     

Power calculation for cohort studies with improved estimation of expected numbers of deaths

Summary This paper focuses on improving the accuracy of sample size calculations for cohort studies by careful calculation of the expected number of deaths in the population, taking into account either prior information or realistic assumptions about variables which may affect the mortality or incidence. Sometimes small changes in the assumptions can dramatically alter the expected numbers and may necessitate modifications in the design of the study. Possible modification include extension of the follow-up time, and recognition that the real strength of the study may lie in the potential for pooling several similar studies. The problem will be discussed with reference to two examples of occupational cohort studies where differing prior information was available.

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Zusammenfassung Diese Arbeit beschäftigt sich mit der Genauigkeit der Berechnung des Stichprobenumfangs in Kohortenstudien, wenn detaillierte Berechnungen für die erwartete Zahl der Verstorbenen berücksichtigt werden. Dies kann entweder durch die Ausnutzung vorhandener Informationen oder durch realistische Annahmen über die Faktoren, die Mortalität oder Inzidenz beeinflussen, geschehen. Schon kleine Unterschiede in diesen Annahmen kann die erwartete Zahl der Verstorbenen erheblich verändern und es notwendig machen, das Design einer Studie zu verändern. Solche Modifikationen bestehen z.B. in der Verlängerung der Follow-up Zeit der Studie oder in der Einsicht, dass es nötig ist, Daten aus mehreren Studien zusammenzufassen. Die Probleme werden anhand von zwei Beispielen aus dem Bereich der Berufsepidemiologie diskutiert.

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Résumé Cet article concerne la précision des estimations de taille d'échantillons pour les études de cohortes. Le calcul précis du nombre de décès attendus dans la population prend en compte les variables susceptibles d'affecter la mortalité ou l'incidence, provenant soit d'une connaissance préalable, soit d'hypothèses réalistes. De modestes changements d'hypothèses peuvent parfois altérer de façon substantielle les nombres attendus et nécessiter des modifications dans le protocole de l'étude. Parmi les modifications possibles, il faut citer la prolongation du temps de suivi de l'étude ainsi que le constat que la valeur réelle de l'étude pourrait reposer sur la possibilité de mise en commun de plusieurs études similaires. Le problème est discuté à l'aide de deux exemples d'études de cohortes professionnelles pour lesquelles différentes informations préalables sont disponibles.