Severe combined immunodeficiency (SCID) associated neutropenia: a lesson from monozygotic twins.

A case of severe combined immunodeficiency (SCID) in monozygotic twin sisters was detected at 3 months of age with neutropenia in one twin and a normal differential count in the other. The neutropenic twin, suffering from severe skin ulcers, was successfully treated with granulocyte colony stimulating factor (G-CSF). Discordant occurrence of neutropenia in identical twins shows that there may be a non-genetic cause for the neutropenia in SCID. Suppression of myelopoiesis was probably induced by activated maternal T cells. The neutropenia in this case may thus be classified as SCID associated neutropenia, as opposed to reticular dysgenesis, in which the neutropenia is G-CSF refractory and is most probably caused by a genetic stem cell defect. A response to G-CSF in a neutropenic child with SCID can be clinically beneficial and might help to distinguish between G-CSF unresponsive reticular dysgenesis and G-CSF responsive SCID associated neutropenia.     

Impact of cochlear tonotopy on electrically evoked compound action potentials (ECAPs)

Background: A wide range of cochlear implant electrode designs exists. Lateral wall electrodes may be favored for their potential to preserve residual hearing by virtue of being thin and delicate; whereas perimodiolar electrodes may have advantages in case of profound hearing loss, due to electrode positioning in close proximity to the auditory nerve fibers.

Aim: The aim of this study was to investigate the impact of these two array designs on the interaction between electrodes and the auditory nerve in different tonotopic regions of the cochlea.

Patients and methods: A retrospective study of both adult and pediatric cochlear implant recipients (CI24RE/CI512 or CI422, Cochlear®) was undertaken. The differences of threshold Neural Response Telemetry (tNRT) acquired 12 months after surgery were analyzed with respect to the tonotopic location.

Results: The results of 168 implants showed that perimodiolar arrays had lowest thresholds in the basal region whereas straight arrays had lowest thresholds in the apex. Highest thresholds for both array types were encountered in the medial parts.

Conclusions and Significance: tNRTs differ depending on electrode type and location inside the cochlea. This should be considered pre implantation when choosing the electrode array type and post-implantation when mapping the CI program.     

Exogenous Surfactant Preserves Lung Function and Reduces Alveolar Evans Blue Dye Influx in a Rat Model of Ventilation-induced Lung Injury

Background: Changes in pulmonary edema infiltration and surfactant after intermittent positive pressure ventilation with high peak inspiratory lung volumes have been well described. To further elucidate the role of surfactant changes, the authors tested the effect of different doses of exogenous surfactant preceding high peak inspiratory lung volumes on lung function and lung permeability.

Methods: Five groups of Sprague-Dawley rats (n = 6 per group) were subjected to 20 min of high peak inspiratory lung volumes. Before high peak inspiratory lung volumes, four of these groups received intratracheal administration of saline or 50, 100, or 200 mg/kg body weight surfactant; one group received no intratracheal administration. Gas exchange was measured during mechanical ventilation. A sixth group served as nontreated, nonventilated controls. After death, all lungs were excised, and static pressure-volume curves and total lung volume at a transpulmonary pressure of 5 cm H2 O were recorded. The Gruenwald index and the steepest part of the compliance curve (Cmax) were calculated. A bronchoalveolar lavage was performed; surfactant small and large aggregate total phosphorus and minimal surface tension were measured. In a second experiment in five groups of rats (n = 6 per group), lung permeability for Evans blue dye was measured. Before 20 min of high peak inspiratory lung volumes, three groups received intratracheal administration of 100, 200, or 400 mg/kg body weight surfactant; one group received no intratracheal administration. A fifth group served as nontreated, nonventilated controls.

Results: Exogenous surfactant at a dose of 200 mg/kg preserved total lung volume at a pressure of 5 cm H2 O, maximum compliance, the Gruenwald Index, and oxygenation after 20 min of mechanical ventilation. The most active surfactant was recovered in the group that received 200 mg/kg surfactant, and this dose reduced minimal surface tension of bronchoalveolar lavage to control values. Alveolar influx of Evans blue dye was reduced in the groups that received 200 and 400 mg/kg exogenous surfactant.     

GlutathioneS-Transferase Activity in Aquatic Macrophytes with Emphasis on Habitat Dependence

GlutathioneS-transferase activity of both the microsomal and soluble fractions was determined in a variety of aquatic macrophytes. The examined enzyme extract was prepared from a combination of leaves and shoots. Four different model substrates were used. The highest conjugation rate was obtained for 1-iodo-2,4-dinitrobenzene, followed by 1-chloro-2,4-dinitrobenzene,p-nitrobenzoyl chloride, and 1,2-dichloro-4-nitrobenzene. Comparison of several samples ofNuphar luteaL. from two different lake areas revealed increased glutathioneS-transferase activity in plants from the site contaminated with polyaromatic hydrocarbons.     

Zum Ossifikationsprinzip des Schildknorpels

Summary In the final analysis, the aetiology of the ossification of the human thyroid cartilage is still not clear. The two halves of the thyroid cartilage obtained from 94 corpses of both sexes having an age range of 15–79 years, were subjected to an X-ray examination. The ossified area was investigated morphometrically with the aid of the Leitz-Texture Analysis System, and evaluated statistically. In addition, the state of deformation in the plane during swallowing was investigated in both nonossified and ossified thyroid cartilages, using wire strain gauges. Ossification begins at the lateral and caudal edges at the age of about 16, reaches a maximum at about age 50, and then remains constant for the rest of life. There is no difference between the sexes except for the fact that ossification occurs some 3 years later in the female, and is less marked. The process of ossification occurs, to varying degrees, predominantly in four directions. It is most marked in the direction parallel to the caudal edge, and is less marked along the vertical line connecting the superior and the inferior cornua, vertically at the thyroid notch, and in the diagonal direction extending from latero-caudal to medio-cranial. The greatest extension occurs parallel to the caudal edge, to a lesser extent in the three other directions, and decreases from lateral to medial. Ossification occurs preferentially along the lines of maximum extension of the muscles attached to the thyroid cartilage. This stiffening of bone prevents the deformation of the cartilage during the act of swallowing, and is an example of the self-regulating adaptation of the connective and supportive tissue to mechanical stressing. On account of the different

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Mit Unterstützung durch die Deutsche Forschungsgemeinschaft (SFB 118)     

Morphine ingestion: Genetic control in mice

C57BL/6J mice will drink large amounts of, and display a highly positive preference for, morphine sulfate when it is dissolved in an aqueous solution of sodium saccharin. In identical test situations DBA/2J mice will drink very little of, and display a strong avoidance toward, the morphine-saccharin solution. This clear separation between morphine-accepting and morphine-rejecting animals within a single species combined with a quick and simple method of inducing high levels of morphine ingestion could facilitate the discovery of causal factors in opiate addiction.     

Deregulated TGF-beta signaling in leukemogenesis

Cellular homeostasis is tightly controlled by the various pathways that regulate cell proliferation and cell death. Breaking this balance is often associated with cancer development. The transforming growth factor-beta (TGF-beta) pathway plays an important role in cellular homeostasis by regulating cell growth inhibition, cellular senescence, differentiation and apoptosis. Deregulated TGF-beta signaling is known to be involved in a variety of human cancers, including those of the colon, pancreas, breast and prostate. While TGF-beta is a potent negative regulator of hematopoiesis, the role of aberrant TGF-beta signaling in leukemogenesis remains largely unknown. Recently, evidence demonstrating deregulated TGF-beta signaling in leukemogenesis, particularly in acute promyelocytic leukemia (APL), has started to emerge. In this review, we summarize the current progress towards the understanding of the molecular mechanisms by which aberrant TGF-beta signaling may participate in leukemogenesis.     

Flow cytometric DNA ploidy in salivary gland tumours

This study on 279 tumours of the salivary glands was conducted to analyse whether the assessment of DNA ploidy by flow cytometry may assist histopathology in discriminating benign from malignant types of tumours. The group of benign tumours included 164 pleomorphic adenomas, 51 Warthin's tumours, 7 basal cell adenomas, 2 lipomas as well as 5 other different tumours. All of the 229 benign tumours were diploid. The malignant tumours consisted of 18 adenoid cystic adenomas, 10 mucoepidermoid carcinomas, 5 acinic cell carcinomas, 5 carcinoma in pleomorphic adenoma as well as of 12 other malignancies belonging to 7 different tumour entities. Twelve of 50 malignant salivary gland tumours were aneuploid. There was no significant relationship between the DNA ploidy status and histopathological grading, lymph node metastasis and local recurrence development, respectively. In three cases which initially were taken for pleomorphic adenomas by routine histological examination, aneuploid cell populations exposed by DNA flow cytometric analysis gave rise to a closer inspection of the suspect lesions. Examination of consecutive slides actually revealed small assemblies of carcinoma cells that required a final diagnosis as non-invasive carcinoma in pleomorphic adenoma. The most obvious value of DNA flow cytometry in salivary gland tumours is thus its contribution to assist histopathology in identifying potentially malignant lesions.