Birth of a healthy infant following trophectoderm biopsy from blastocysts for PGD of beta-thalassaemia major

PGD is a well accepted reproductive choice for couples at genetic risk and involves the diagnosis and transfer of unaffected IVF embryos. PGD for monogenetic diseases is most commonly accomplished by the biopsy of one or two blastomeres from cleavage stage embryos, followed by PCR-based protocols. However, PCR-based DNA analysis of one or two cells is subject to several problems, including total PCR failure, or failure of one allele to amplify. Trophectoderm biopsy at the blastocyst stage enables the removal of more than two cells for diagnosis while being non-invasive to the inner cell mass which is destined for fetal development. The aim of this study was to develop a safe, reliable technique for the biopsy of trophectoderm cells from human blastocysts. This case report demonstrates that removal of trophectoderm cells prior to blastocyst transfer is compatible with implantation and development to term. Here we report successful PGD for beta-thalassaemia following trophectoderm cell biopsy from blastocysts and the birth of a healthy infant.     

Diagnostische Bedeutung von Muskelbiopsien bei metabolischen Myopathien

Summary In the diagnosis of metabolic myopathies the use of biochemical methods, in addition to morphological examination of muscle biopsies, is often necessary in order to identify a specific metabolic defect. In order to narrow down the spectrum of biochemical methods, extensive clinical investigation and morphological examination, including histology, enzyme histochemistry and electromicroscopy if necessary have to be done beforehand. Patients are classified in the following groups: 1) progressive muscular weakness and/or muscle wasting with storage of a) glycogen, b) lipid or c) mitochondrial alterations; 2) recurrent rhabdomyolysis induced by fasting or exercise a) with glycogen storage or b) without any specific morphological alterations. The spectrum of metabolic defects comprises disorders of glycogen and glucose metabolism (deficiency of acid maltase, debranching and branching enzyme, phosphorylase, phosphofructokinase and other glycolytic enzymes), lipid metabolism (carnitine deficiency, carnitine palmitoyl transferase deficiency), mitochondria (respiratory chain disorders, pyruvate dehydrogenase deficiency) and others such as adenylate deaminase deficiency. In some of these e.g. infantile acid maltase deficiency and mitochondriopathies, it is clinically more important when organs other than muscle are affected; however, muscle biopsy is a useful substrate for diagnosis of these metabolic disorders.

Mit Unterstützung durch die DFG und die Friedrich Baur Stiftung, München     

Diagnostic impact of core-needle biopsy on fine-needle aspiration of non-Hodgkin lymphoma

We retrospectively reviewed 74 fine-needle aspiration (FNA) cases of presumptive non-Hodgkin lymphoma (NHL). All the cases had cytology and core-needle biopsy and 53 cases had concurrent flow cytometric analysis. FNA (cytology and flow cytometry) and core-needle biopsy were evaluated independently. FNA was diagnostic of diffuse large B-cell lymphoma (DLBL) in 25% (13/53) of cases and small B-cell NHL in 15% (8/53) of cases, whereas core-needle biopsy was diagnostic of DLBL in 37% (27/74) of cases and small B-cell NHL in 8% (6/74) of cases. Subclassification of small B-cell NHL was reached in 3/6 cases by core-needle biopsy. Insufficient cases were observed in both FNA (47%; 25/53) and core-needle biopsy (28%; 21/74) groups. With the combination of FNA and core-needle biopsy, diagnostic cases of DLBL increased to 43% (32/74) and insufficient samples were reduced to 16% (12/74). There was no clear advantage in the diagnosis and classification of small B-cell NHL by adding core-needle biopsy to FNA (14%; 10/74). We conclude that core-needle biopsy is a useful adjunct to FNA in the diagnosis of DLBL and shall be encouraged. In small B-cell NHL, core-needle biopsy does not add to the diagnostic ability of FNA. Cases insufficient for diagnosis may be seen in both core-needle biopsy and FNA. A combined approach reduces the number of insufficient cases and is recommended in routine FNA practice.     

Increased collagen around deformed finger nailfold capillaries in type I diabetes mellitus

Summary Quantitative finger nailfold capillary microscopy was performed in 25 patients with type I diabetes and in 27 healthy control subjects. In the last consecutive 6 patients and 7 controls of these populations, finger nailfold biopsies were taken. Measurements of loop width as an in vivo parameter for deformities of the capillary loops showed significantly higher values in diabetic patients than in controls. Histopathological examination showed markedly and significantly increased deposition of collagen in nailfold dermal papillae of the diabetic patients. The deposition of collagen was positively correlated with the number of capillary endothelial cells in the nailfold dermal papillae and with the size of the papillae in diabetic patients. It is concluded that, in addition to deformity of nailfold capillaries, collagen deposition may also be a sign of metabolic disturbance and perhaps of proliferation of capillary endothelial cells in diabetic microangiopathy.Supported by the Swiss National Fund for Scientific Research, grant number 3.904-0.86     

Psammoma bodies and optically clear nuclei in bronchiolo-alveolar cell carcinoma. Diagnosis by fine needle aspiration biopsy with histologic and ultrastructural confirmation

The fine needle aspiration cytology of two cases of bronchiolo-alveolar cell carcinoma of the lung having unusual features is reported. One case demonstrated numerous psammoma bodies in the cytologic smears, whereas the other case showed an abundance of cells with optically clear nuclei. Both peripherally located tumors were resected and confirmed as primary bronchiolo-alveolar cell carcinoma by histologic and ultrastructural examination. We believe this to be the first report describing these unusual features of bronchiolo-alveolar cell carcinoma diagnosed by fine needle aspiration cytology. Presented is a discussion of psammoma bodies and optically clear nuclei seen in primary and metastatic tumors of the lung. This will aid in the diagnosis of these cases.     

Relationships between muscle lactate accumulation and surface EMG activities during isokinetic contractions in man

Summary In order to investigate the relationship between metabolic state and myoelectrical activity in working muscle during short term intense exercise, eleven healthy males performed isokinetic knee extensions at an angular velocity of 180 deg · sec^–1 for 30 and 60 s. The median frequency (MF) of the surface electromyogram (EMG) recorded from vastus lateralis was decreased while the time lag of torque production after the onset of electrical activity (EMD) was increased during exercise. These changes (MF and EMD) corresponded well to muscle lactate accumulation in the same muscle. Over the exercise period, the integrated EMG/knee extension peak torque ratio (E/T ratio) was increased, which indicated a decrease in the efficiency of electrical activity. It was concluded that the changes in the frequency components of the EMG and in the contractile property of the muscle during short term intense exercise correlated with lactate accumulation in the identical muscle, and that the decrease in efficiency of the electrical activity in the muscle suggested peripheral fatigue.     

Expression of TNFalpha by muscle fibers in biopsies from children with untreated juvenile dermatomyositis: association with the TNFalpha-308A allele

Juvenile dermatomyositis (JDM) is the most common pediatric inflammatory myopathy. In patients with JDM, the A --> G polymorphism in the tumor necrosis factor alpha (TNFalpha)-308 promoter region (TNFalpha-308A) is associated with prolonged disease course and increased production of TNFalpha by peripheral blood mononuclear cells (Arthritis Rheum. 43, 2368-2377, 2000). Magnetic resonance imaging directed biopsies from 21 white children with untreated JDM were evaluated for TNFalpha expression. Using monoclonal antibody to TNFalpha, fresh frozen sections were processed by the standard immunohistochemical technique. We investigated the association among the expression of TNFalpha by muscle fibers, disease activity, duration of untreated disease, and the TNFalpha-308 polymorphism. Untreated children with JDM who had the TNFalpha-308A allele had an increased number of TNFalpha stained muscle fibers than children with the TNFalpha-308G allele (P = 0.001). There was no association with disease activity or duration of untreated disease. We speculate that muscle fiber production of TNFalpha provides a microenvironment in which TNFalpha acts synergistically with other mediators to prolong muscle fiber damage.     

Neuroendocrine carcinoma of the thymus: Aspiration biopsy,immunocytochemistry, and clinicopathologic correlates

We report three cases of well-differentiated neuroendocrine carcinoma originating primarily in the anterior mediastinum which had been initially investigated by fine-needle aspiration cytology in conjunction with immunocytochemistry and subsequently recognized as thymic in origin. Aspirates consisted of loosely cohesive or aggregated medium sized elements with round to oval nuclei and scanty cytoplasm. in all cases the Romanowsky stain provided an excellent delineation of definite paranuclear inclusion-like structures having a semicircular or discoid appearance which appeared to contain cytokeratin by immunocytochemical studies and were very similar to the intermediate filament paranuclear “buttons” found in neuroendocrine Merkel cell carcinoma of the skin. This appears to be a novel cytologic observation for thymic neuroendocrine carcinoma. We discuss the significance of the above cytologic and immunocytochemical findings and their possible role in the diagnosis of thymic neuroendocrine carcinoma by fine-needle aspiration biopsy. © 1995 Wiley- Liss, Inc.     

Applications of CT-adapted stereotaxis for the diagnosis and treatment of intracranial lesions

Summary Two hundred twenty five patients with intracranial lesions underwent diagnostic and therapeutic stereotactic surgery during the period 1978–1985. In the first 98 cases target coordinates were determined by transferring the information from the CT images to the standard stereotactic films. In the remainder, a simple, CT adapted stereotactic system has been used. Operations were as a rule performed under local anaesthesia. Positive histological diagnosis using paraffin embedding was achieved in 96% of the patients (biopsy success rate). Therapeutic procedures included abscess and cyst aspiration, cyst shunting, interstitial (Ir 192) or intracavitary (Y 90) irradiation and ventriculocisternostomy. Stereotactic surgery implied a refinement of the eventual therapeutic management in 90% of the cases. Transient neurological deficit occurred in 5.7% of the patients and there were three deaths (mortality rate 1.3%). Infection or other complications were not seen. The rationale and indications for non-functional stereotaxis are discussed.     

动态喉镜下咬检性切除早期声带癌

目的：利用动态喉镜观察声带振动及黏膜波动,以早期诊断声带癌,并在图象放大屏幕下活检性切除病变组织;术后动态观察手术侧声带振动及黏膜波的恢复情况,以冀早期发现声带癌复发。方法：对12例早期声带癌,利用动态喉镜活检性切除病变组织。经病理检查其中2例为原位癌,10例为表浅浸润癌。结果：术后11例恢复声带振动及黏膜波动;1例未恢复,予以预防性放疗。术后随访2年以上无肿瘤复发。结论：利用动态喉镜活检性切除早期声带癌并术后动态观察,于表麻下施术,患者痛苦小,治疗时间短,术后发声良好。