A new functional assay for the diagnosis of X-linked inhibitor of apoptosis (XIAP) deficiency.

X-linked inhibitor of apoptosis (XIAP) deficiency, caused by mutations in BIRC4, is an immunodeficiency associated with immune dysregulation and a highly variable clinical presentation. Current diagnostic screening tests such as flow cytometry for XIAP expression or lymphocyte apoptosis assays have significant limitations. Based on recent evidence that XIAP is essential for nucleotide-binding and oligomerization domains (NOD)1/2 signalling, we evaluated the use of a simple flow cytometric assay assessing tumour necrosis factor (TNF) production of monocytes in response to NOD2 stimulation by muramyl dipeptides (L18-MDP) for the functional diagnosis of XIAP deficiency. We investigated 12 patients with XIAP deficiency, six female carriers and relevant disease controls. Irrespective of the diverse clinical phenotype, the extent of residual protein expression or the nature of the mutation, the TNF response was severely reduced in all patients. On average, L18-MDP induced TNF production in 25% of monocytes from healthy donors or female carriers, while fewer than 6% of monocytes responded in affected patients. Notably, the assay clearly discriminated affected patients from disease controls with other immunodeficiencies accompanied by lymphoproliferation, hypogammaglobulinaemia or inflammatory bowel disease. Functional testing of the NOD2 signalling pathway is an easy, fast and reliable assay in the diagnostic evaluation of patients with suspected XIAP deficiency.

Glass-ionomer cements in dental practice: a national survey.

Certain characteristics of glass-ionomer cements would appear to make them desirable dental materials; however, many practitioners are reluctant to use them because of reports of postoperative sensitivity. The members of the Academy of Operative Dentistry were surveyed in order to assess quantitatively and qualitatively the use of glass-ionomer cements in their practices, as well as the incidence and nature of postoperative sensitivity. The following data were collected: 1) the past and present use of glass-ionomer cements, 2) reasons for disuse of glass-ionomer cements, 3) products which are or have been used, and 4) the incidence of and resolution of postoperative sensitivity. The results are presented and discussed. An interesting secondary finding identified that zinc phosphate when used as a luting agent may contribute to postoperative sensitivity more often than is appreciated.

In vitro color stability of provisional restorations.

A provisional restoration must protect the prepared tooth, provide comfort and function and be esthetically acceptable and color stable. This study measured the degree of color change of provisional restorations. Five commercially available resins were evaluated: Trim, Tab, Kind, Snap and Duralay. Five cylindrical samples of each resin were fabricated by mixing the powder and the liquid to a predetermined ratio and pouring the mix into a mold. The Minolta Chroma Meter II Reflectance was used to establish the baseline color L* a* b*. The resins were then subjected to accelerated in vitro aging in a Weather-O-Meter and color readings were recorded. The color differentials on delta E* were computed for each sample (delta E*ab = [(delta L*)2+(delta b*)2]1/2). The difference is a quantitative measurement of color change. The National Bureau of Standards describes delta E* as units (NBS Unit = delta E*ab x 0.92). With this parameter only the allowable delta E*ab need be specified rather than the range of allowable L*, a*, b* values. This is important for color comparison and quality control functions. The results showed that Kind had a slight color change delta E* = -1.72, Trim demonstrated the most color change delta E* = -13.84, while the remaining resins demonstrated a noticeable change in color due to in vitro aging.

[Measurement of LH in urine by HI-gonavis test for the predetermination of ovulation (author's transl)]. / LH-Bestimmungen im Urin mit dem HI-Gonavis-Test zur Ovulationsvoraussage.

The immunological LH/HCG test HI-Gonavis was used to measure the LH-excretion in urine of 30 patients during 1 to 3 cycles. The level of LH in plasma was determined simultaneously by radioimmunoassay. 12,5IU LH/L urine, the limit of sensitivity of HI-Gonavis, coincide with 7,2 mIU/ml plasma. 50 or 100 IU LH/L urine were found in patients showing a LH plasma level which was higher than 12,5 mIU/ml. In the ovulatory cycle this value is reached 1 day before the LH-peak. From the correlation of the preovulatory increase of LH in the plasma and the LH-excretion in the urine it can be concluded, that the detection of 50 IU LH/L urine indicates the ovulation within the next 12--30 hours. The practicability of this test for the predetermination of ovulation is demonstrated by examples.

[Letter: Therapy of hypogonadotropic ovarian insufficiency]. / Therapie bei hypogonadotroper Ovarialinsuffizienz

PIP: Hormone therapy for hypogonadotropic ovarian insufficiency may be substitutive or stimulative. For young girls, or where conception is not desired, substitution treatment with an estrogen-progesterone combination is recommended, to prevent further hypoplasia of the internal genitals; in cases where estrogen production is sufficient, cyclic treatment with progesterone is enough to induce menstruation. Stimulation of the ovaries is not sensible in the above cases because even when ovulation takes place, spontaneous cycles seldom result (except in hypogonadotropic oversuppression syndrome, i.e., postpill amenorrhea). Useful preparations for stimulation treatment of hypogonadotropic amenorrhea are clomiphene and gonadotropin, but not the weaker cyclofenil. Reports of success with clomiphene vary; failures may be treated with gonadotropin, a method which leads to ovulation in 80-90% of the cases and to conception in 50%. However, the potential complications (overstimulation of the ovaries, cysts, multiple births) make it advisable to reserve this treatment for clinical centers and cases of failure with clomiphene.^ieng

Serum tumor markers in metastatic breast cancer and course of disease.

The purpose of this study was to compare the diagnostic significance of serum tumor markers in metastatic breast cancer and to evaluate their usefulness in monitoring palliative treatment. One hundred sixty-two breast cancer patients with various disease involvement have been followed-up by serum beta-human chorionic gonadotrophin (beta-HCG), alkaline phosphatase (AP), phosphohexose isomerase (PHI), carcinoembryonic antigen (CEA), and tissue polypeptide antigen (TPA) analysis for 6 to 29 months. In metastatic disease, rates of elevated tumor marker levels ranging between 44% and 91% were found except for beta-HCG (13%). The low rate of positive beta-HCG values did not suggest that routine estimation may be useful. For the other markers, differences in positive rates were seen when site of metastasis, tumor burden, tumor activity, and stage of disease were taken into account. CEA and TPA were shown to be more sensitive indicators for metastatic disease than AP and PHI. TPA was more sensitive but less specific than CEA; both provided almost identical discrimination. In monitoring palliative treatment, a close correlation was found between the clinical course and changes of CEA. AP and PHI frequently became elevated only in very advanced disease, their elevation supported the clinical evidence of progression.

[The influence of endogenous hormones on the oestrogen and progesterone receptor determination in tissue of mammary carcinoma (author's transl)]. / Beeinflussung des Ostrogen- und Progesteronrezeptornachweises in Mammakarzinomgeweben durch endogene Hormone.

Oestrogen and progesterone receptors were determined in 48 primary tumors of invasive mammary carcinoma. 86% showed a positive oestrogen receptor binding, 53% were progesterone receptor positive. The binding capacity for oestradiol was 5-211 pmoles/g tissue protein, for progestin (R 5020) 7-146 pmoles. The question of the investigation was whether the content of determined receptors depends on endogenous oestradiol and progesterone concentrations. A clear dependence did not exist between the hormone level in the plasma, collected just before the excision of the tumor, and the amount of identifiable receptors in the tumor. On the contrary, in considering the quantities of endogenous hormones in the tissues, based on the plasma content of the tissue and the plasma hormone level, a correlation could be found. The content of identifiable receptors decreased with increasing amounts of endogenous hormones in the cytosol. It is postulated that rather the amount of endogenous hormones in the tissue than the plasma hormone level characterizes the degree of saturation of existing receptors by endogenous hormones. Apparently, the determined receptor concentrations at endogenous hormone values under 2 pmoles/g tissue protein reflect rather the true receptor content, whereas at higher values too low or false negative results should be reckoned with.

[Foreign body granulation in the breast after injection of a polyvinylpyrrolidone containing preparation. A case report (author's transl)]. / Fremdkörpergranulation in der Brustdrüse nach Injektion eines polyvinylpyrrolidonhaltigen Präparats. Eine Fallbeobachtung

A case is reported of a patient who developed large foreign body granulations in the breast and in the epigastric area after injection of a polyvinylpyrrolidone containing medication (Depot-Impletol).

Comparison of three epoxy die materials.

Sixty MOD inlay and 60 complete crown castings were fabricated on three epoxy die materials. The castings were evaluated with a specific criteria for fit, retention, and margin adaptation. Of the three materials tested, the castings fabricated on the Unitek die material had consistently higher ratings on the master die with the exception of unacceptable ratings in retention for the MOD inlay.

[Bilirubin level and estrogen elimination in newborns (author's transl)]. / Bilirubinspiegel und Ostrogenelimination beim Neugeborenen.

Free estradiol and estriol was determined radioimmunologically in cord blood and in peripheral venous blood during the third, fifth and seventh day of life. The steroid level of a group of children with icterus neonatorum simplex were compared with an anicteric control group. In spite of the higher level of estriol in cord blood during the first week of life, estriol was eliminated much more rapidly than estradiol and independent of the bilirubin level. Given the same initial values for estradiol in cord blood of both control groups, the estradiol elimination rate was significantly slower in icteric newborns. The level of estradiol in cord blood was significantly higher in newborn males than in newborn females. A higher level in cord blood, however, does not increase the risk of a later newborn hyperbilirubinemia. Our findings tend to indicate that no etiologic importance should be attached to the amount of estradiol and estradiol to be eliminated, for the development of icterus neonatorum simplex. At the same time, icteric newborns have a relative insufficiency in estradiol elimination but not, however, in estriol elimination.

[Light- and electronmicroscopic examinations on granulosa and theca of primordial-, primary-, secondary- and resting tertiary follicles of human ovaries (author's transl)]. / Die differenzierte Struktur und Funktion der Granulosa und Theka in verschiedenen Follikelstadien menschlicher Ovarien.

Light- and electromicroscopic examinations were performed on granulosa and theca of primordial-, primary-, secondary- and resting tertiary follicles of human ovaries. These examinations were intended to clarify how far correlation exist between the structural components of the different tissue formations of the follicles and their determined functions. Remarkably many intraplasmatic filaments were found in the cytoplasm of granulosa cells of primordial-, primary- and secondary follicles. In the resting tertiary follicles the electronmicroscopy defines the majority of the follicle granulosa cells as proteinsynthetic active cells with abundant rough endoplasmatic reticulum. Most of the nuclei contain several nucleoli. An interesting finding compared with the granulosa cells of earlier developing stages of the follicle is the presence of single or grouped fat droplets in the cytoplasm, whereas metaplastic structures like filaments and/or microtubules are rare. The theca cells aroung the primordial-, primary- and secondary follicle were characterized by electromicroscopy as typical stroma cells. These cells of the resting tertiary follicles in the theca interna and externa show characteristic submicroscopic criteria of active steroidbiosynthesis. Their cytoplasm is especially rich of smooth endoplasmatic reticulum about from that there are tubular mitochondria and diffus fat droplets. Regarding the functional meaning of the different tissue formation of the follicles the existence of filamentous material in the membrana granulosa of primordial-, primary- and secondary follicles demonstrates an important finding. Apparently the presence of these metaplastic structures in the follicle granulosa cells play a role in the formal development of the zona pellucida and the Call-Exner-bodies. The structural organisation of the granulosa cells of resting tertiary follicles shows a high proteinsynthetic activity which plays a role in the metabolism of oocyte and the follicular fluid production. So far there are no definite submicroscopic criteria for steroidbiosynthesis. The structural differentiation of the normal stroma cells around primordial-, primary- and secondary follicles leads to definite submicroscopic steroidcells in the resting tertiary follicle. According to our results the process of the transformation of follicular granulosa cells in steroidbiosynthetic active cells in the resting tertiary follicle is not complete.

[Light and electronmicroscopic examinations on granulosa and theca of preovulatory and freshly ruptured follicles of human ovaries (author's transl)]. / Die differenzierte Struktur und Funktion der Granulosa und Theka in verschiedenen Follikelstadien menschlicher Ovarien. 2. Der reifende, reife, sprungreife und frisch geplatzte Follikel

In a first paper, the structural and functional relationship of granulosa and theca of follicles during early development stages was reported. On the special question of whether and from which moment these two tissue formations are involved in the steroidbiosynthesis, our electronmicroscopic examinations have given a further insight to this. Neither the granulosa nor the theca folliculi of primordial, primary and secondary follicles show definite morphologic submicroscopic criteria of the steriodbiosynthesis. In the resting tertiary follicle, the electronmicroscopy defines the theca cells as steroidbiosynthetic active cells, whereas the granulosa cells of this stages of follicle demonstrate the morphologic characteristics of protein-synthetic active cells. Our, under physiological conditions, systematically conducted light and electronmicroscopic studies of preovulatory and freshly ruptured follicles showed remarkable structural changes in the granulosa, as well as in the theca folliculi. For the follicle granulosa cells of the preovulatory follicle, the studies could demonstrate a structural transformation process of proteinsynthetic active to steroidbiosynthetic active cells. This transformation process can be seen in the nucleus. Especially recognizable is the continuous change from rough to smooth endoplasmatic reticulum in the cytoplasm of most of the follicle granulosa cells, which apart from that, often displayed whorle-like formations. Furthermore, we noticed striking changes of the paraplasmatic structures, especially of the fat, present in various stages in the cytoplasm of the follicle granulosa cells. We also noticed large mitochondria, which showed a lot of vesicular cristae. Numerous existing Golgi-fields contained many little homogenous fat-like droplets, which were surrounded by a thin osmiophilic membrane. This recognizable transformation process of the proteinsynthetic active granulosa cells to the steroid cells is quite completed in freshly ruptured follicles, according to our examinations. Although the theca cells have already been defined submicroscopically in the resting tertiary follicle as steroidbiosynthetic active cells, we see in this cellgroup in the preovulatory, as well as in the freshly ruptured follicle a remarkable conspicuous size-increase of the mitochondria. Apart from that, there are wide areas which are solely occupied by smooth endoplasmatic reticulum, whereas other structures, for example fat, are scarely seen. As our examinations have shown, there is a close relationship between the transformation process in the granulosa and the theca of preovulatory follicles and the theca of preovulatory follicles that, the increasing concentration of progesteron in serum, which begins prior to the ovulation can be regarded as a product of the follicle granulosa cells being transformed to steroid cells.

Quantitative evaluation of proximal tooth movement effected by wedging: a pilot study.

The major purpose of this pilot study was to develop a method to accurately measure proximal tooth movement. A preliminary clinical evaluation of anterior and posterior tooth movement was performed with five patients. The patients were carefully chosen to eliminate as many variables as possible. The controlled patient criteria included periodontal health, proximal contacts, the age of the patients, and the teeth selected for anterior and posterior displacement. The small sample size dictates that additional experimentation must be performed before definitive conclusions can be drawn.