Distraktionsosteogenese der Mandibula bei kraniofazialen Fehlbildungen

In recent years, lengthening the human mandible by distraction osteogenesis has become an accepted treatment to correct severe mandibular hypoplasia. Using intraoral unidirectional and extraoral bidirectional distraction devices we report about our experiences and results in the application of the bone distraction technique in four selected cases of syndromal disease, including various forms of mandibular hypoplastic malformations. The patients involved were a boy with Pierre Robin syndrome, a girl with unilateral facial hypoplasia in Goldenhar's syndrome, a case with Nager's syndrome, and a rare case of midline deficiency caused by partial deletion of chromosome 18 (18p-syndrome). The distraction period lasted from 6 to 30 days and new bone formation, ranging from 6 to 28 mm, was achieved.     

Crystal structures of thrombin and thrombin complexes as a framework for antithrombotic drug design

Summary The wealth of structural information now available on thrombin, its precursors, its substrates and its inhibitors allows a rationalization of its many roles. -Thrombin exhibits an unusually deep and narrow active-site cleft, formed by loop insertions that are characteristic of thrombin. This canyon structure is one of the prime causes for the narrow specificity of thrombin. As a result of the conjunction of amino acid residues with similar properties such as charge or hydrophobicity, thrombin can be divided up into a number of functional regions. The apposition of the active site to a hydrophobic pocket (the apolar binding site) on one side and a basic patch (the fibrinogen recognition exosite) on the other allows for a fine-tuning of enzymatic activity, as seen for fibrinogen. These two sites are also optimally used by the leech-derived inhibitor hirudin, allowing the very tight binding observed; thrombin inhibition is effected by blocking access to the active site. Interactions with antithrombin III are tightened with the help of heparin, which binds to a second basic site (the heparin binding site). Non-proteolytic cellular properties are attributed to the rigid insertion loop at Tyr^60A. The observed rigidity of the thrombin molecule in its complexes makes thrombin ideal for structure-based drug design. Thrombin can be inhibited either at the active site or at the fibrinogen recognition exosite, or both. Structural information shows that binding at the former is enhanced by good fit of aromatic moieties to the aryl and S2 binding sites (the apolar binding site). Binding at the fibrinogen recognition exosite is facilitated by negatively charged groups. The unpredictable nature of inhibitor binding underlines the importance of experimental monitoring of structures of thrombin inhibitors in the drug design process.     

Computer-Controlled Treatment Delivery

Computer-controlled treatment machines and the delivery of conformal radiotherapy treatments using computer-controlled and/or automated delivery techniques have become an important new area of clinical and research activity in recent years. The historical experience with simple multileaf collimators and control systems used for dynamic conformal therapy has been expanded with the development of a number of different methods used to deliver modern conformal therapy treatments. Various approaches to these automated and semi-automated treatments are described. Safety considerations are a critical part of the automated delivery process, and are also briefly reviewed. Early experience with these techniques at a number of centers, is briefly described.     

Comparison of risk estimates for selected diseases and causes of death

BACKGROUND: Lifetime risk estimates of disease are limited by long-term data extrapolations and are less relevant to individuals who have already lived a period of time without the disease, but are approaching the age at which the disease risk becomes common. In contrast, short-term age-conditional risk estimates, such as the risk of developing a disease in the next 10 years among those alive and free of the disease at a given age, are less restricted by long-term extrapolation of current rates and can present patients with risk information tailored to their age. This study focuses on short-term age-conditional risk estimates for a broad set of important chronic diseases and nondisease causes of death among white and black men and women. METHODS: The Feuer et al. (1993, Journal of the National Cancer Institute) [15] method was applied to data from a variety of sources to obtain risk estimates for select cancers, myocardial infarction, diabetes mellitus, multiple sclerosis, Alzheimer's, and death from motor vehicle accidents, homicide or legal intervention, and suicide. RESULTS: Acute deaths from suicide, homicide or legal intervention, and fatal motor vehicle accidents dominate the risk picture for persons in their 20s, with only diabetes mellitus and end-stage renal disease therapy (for blacks only) having similar levels of risk in this age range. Late in life, cancer, acute myocardial infarction, Alzheimer's, and stroke become most common. The chronic diseases affecting the population later in life present the most likely diseases someone will face. Several interesting differences in disease and death risks were derived and reported among age-specific race and gender subgroups of the population. CONCLUSION: Presentation of risk estimates for a broad set of chronic diseases and nondisease causes of death within short-term age ranges among population subgroups provides tailored information that may lead to better educated prevention, screening, and control behaviors and more efficient allocation of health resources.     

Some dietary fibers reduce the absorption of carotenoids in women

Dietary fiber may be partly responsible for the lower bioavailability of carotenoids from food than from purified supplements. Due to the lack of detailed information available, we investigated the effects of different kinds of dietary fiber on the absorption of carotenoids and alpha-tocopherol. Six healthy young women received an antioxidant mixture consisting of beta-carotene, lycopene, lutein, canthaxanthin and alpha-tocopherol together with a standard meal. The meal did not contain additional dietary fiber or was enriched with pectin, guar, alginate, cellulose or wheat bran (0. 15 g. kg body weight(-1)). The increases in plasma carotenoid and alpha-tocopherol concentrations were followed over 24 h, and the areas-under-curves (AUC(24h)) were calculated. The mean AUC(24h) of beta-carotene was significantly (P < 0.05) reduced by the water-soluble fibers pectin, guar and alginate with a mean decrease of 33-43%. All tested fibers significantly reduced the AUC(24h) of lycopene and lutein by 40-74% (P < 0.05). The dietary fiber effect on the AUC(24h) of canthaxanthin was almost significant (P = 0.059) and there was no effect on the AUC(24h) of alpha-tocopherol. We conclude that the bioavailability of beta-carotene, lycopene and lutein given within a mixed supplement is markedly reduced by different kinds of dietary fiber.     

P53 and cyclin D1 staining patterns of malignant and premalignant oral lesions in age-dependent populations.

OBJECTIVE: Recent epidemiologic studies have identified a trend of increasing cancer incidence in younger patients. The purpose of this study was to determine whether this might be reflected by different molecular mechanisms for tumor development. STUDY DESIGN: Dysplastic and malignant oral lesions from age-distinct patient populations were immunohistochemically analyzed for expression of p53 and cyclin D1. Chi-square analysis was used to determine statistical significance. RESULTS: Eighty-two percent of "older" and 75% of "younger" carcinomas stained positively with p53; 63% of carcinomas in the older population and 55% of carcinomas in the younger population showed cyclin D1 positivity. Dysplasias showed similar cyclin D1 staining in both groups. Interestingly, 100% of "younger" dysplasias stained positively for p53, whereas 35.3% of "older" dysplastic lesions showed immunoreactivity. Staining of carcinomas was not statistically significant, whereas p53 staining of dysplasias proved highly significant (P < .025). CONCLUSIONS: p53 immunoreactivity is detectable at an earlier stage of carcinogenesis in younger patients than in the traditional risk population for oral cancer.     

Impairment of neocortical metabolism predicts progression in Alzheimer's disease

Progression rates of Alzheimer's disease (AD) vary considerably, and they are particularly difficult to predict in patients with mild cognitive impairment. We performed a prospective multicenter cohort study in 186 patients with possible or probable AD, mostly with presenile onset. In a cross-sectional analysis at entry, impairment of glucose metabolism in temporoparietal or frontal association areas measured with positron emission tomography was significantly associated with dementia severity, clinical classification as possible versus probable AD, presence of multiple cognitive deficits and history of progression. A prospective longitudinal analysis showed a significant association between initial metabolic impairment and subsequent clinical deterioration. In patients with mild cognitive deficits at entry, the risk of deterioration was up to 4.7 times higher if the metabolism was severely impaired than with mild or absent metabolic impairment. Copyrightz1999S.KargerAG, Basel     

Sphenoidal sinus mucocele after transsphenoidal surgery for acromegaly

This report concerns one case of a sphenoid sinus mucocele occurring 17 years after transsphenoidal surgery for acromegaly. In 1979, a 51-year-old man was successfully operated by the transnasal transsphenoidal approach for a growth hormone (GH) adenoma 1 cm in diameter. In 1996, the patient was hospitalized for headaches and diplopia. He presented a loss of right visual acuity with paralysis of the right oculomotor nerve. The basal GH level was normal with a satisfactory decrease after oral glucose ingestion. Pituitary sellar radiography showed a disappearance of the posterior clinoid while magnetic resonance imaging revealed the existence of a bilocular, circular, homogeneous lesion of the sphenoid sinus 3 cm in diameter with a posterior and lateral extension. The diagnosis of mucocele was confirmed by surgical treatment, allowing drainage of the mucocele through a transsphenoidal approach. The drained material was composed of sinus epithelium containing many polynuclear and resorptive cells. Postoperatively, the symptoms decreased dramatically, leading to full recovery of visual function and disappearance of the headaches. Apart from the tumor recurrence, the mucocele of the sphenoid sinus can be evoked as a possible long term complication of transsphenoidal sugery for pituitary adenoma. Received: 2 June 1998 / Accepted: 23 February 1999     

Proliferation kinetics of the dermal infiltrate in cutaneous malignant lymphomas

Summary To obtain information about the role of local proliferation in the pathogenesis of dermal infiltrate in malignant cutaneous lymphomas, we determined the percentage of ³H-thymidine-labeled infiltrating cells (³H-index).A linear correlation was found between proliferative activity and clinical stage in mycosis fungoides, i.e., the ³H-index is moderately elevated in stage I and high in stage III.The ³H-index is within normal range in dermal infiltrate of Sézary syndrome, diffuse lymphocytic lymphoma, as well as in lymphocytoma benigna cutis.In parapsoriasis en plaques two groups can be distinguished: in the smallplaque variant (chronic superficial dermatitis) the ³H-index is low, whereas the large-plaque variant (prereticulotic poikiloderma) shows strong proliferative activity.Thus, determination of proliferative activity seems to give new insights into the pathogenesis of dermal infiltrate in cutaneous lymphomas.Zusammenfassung Um die Bedeutung der lokalen Zellproliferation im dermalen Infiltrat bei cutanen malignen Lymphomen zu untersuchen, bestimmten wir den Prozentsatz der ³H-Thymidin-markierten Infiltratzellen (³H-Index.Zwischen dem klinischen Stadium der Mycosis fungoides und der Proliferationsaktivität des dermalen Infiltrats besteht eine lineare Beziehung; im Stadium I ist die Proliferation niedrig, im Stadium III sehr hoch.Nicht erhöht ist der ³H-Index im dermalen Infiltrat beim Sézary-Syndrom, diffusen lymphocytischen Lymphom sowie bei Lymphocytoma benigna cutis.Bei der Parapsoriasis en plaques müssen zwei Formen unterschieden werden: bei der kleinfleckigen Form (chronic superficial dermatitis) ist der ³H-Index niedrig, während die großfleckige Form (Präretikulotisches Poikiloderm) eine starke Proliferationsaktivität aufweist.Die Untersuchung des Proliferationsverhaltens gibt neue Einblicke in die Pathogenese des dermalen Infiltrats cutaner Lymphome.