Autopsy analysis in surgical patients: a basis for clinical audit.

An autopsy study was performed to quantify diagnostic fallibility in clinical surgery. Autopsy results in 312 surgical patients were compared with clinical findings. The primary clinical diagnosis was correct in 93 per cent of patients; complications had been correctly diagnosed in 60 per cent and error in treatment was found in 16 per cent.

Chemosensitivity testing of xenografted squamous cell carcinomas of the head and neck region.

Eight squamous cell carcinomas from the head and neck region were established as xenograft lines in nude mice and tested for their sensitivity to the antineoplastic drugs bleomycin and cisplatin. Tumor volume, histology, DNA flow cytometry and mitotic activity were used as parameters. One out of the 8 tumours appeared to be highly sensitive to bleomycin, while three other tumours were sensitive to both bleomycin and cisplatin.

Cerebral blood flow fluctuation in low-risk preterm newborns.

Cerebral blood flow (CBF) fluctuation was studied by analyzing Doppler internal carotid blood velocity recordings of 13 healthy preterm newborns obtained in the course of their first 5 days of life. As measures of fluctuation we used the interquartile range (IQR) and the coefficient of variation (CV) of the ensemble of heart beats of a 20-s recording. In this way we determined fluctuation of the following velocity curve parameters (VCPs): end diastolic velocity; mean velocity; peak systolic velocity and pulsatility index (PI).

Cell-kinetics and biochemical pharmacology of methotrexate and 6-mercaptopurine in human malignant T-lymphoblasts.

The cell-kinetics and biochemical pharmacology of simultaneous and sequential combination treatment with 0.02 microM methotrexate (MTX) and 2 microM 6-mercaptopurine (6MP) were studied in MOLT-4 malignant T-lymphoblasts. The results were compared with our data from earlier studies of separate treatment with these antimetabolites.

Identification and characterization of a new gene in the human Xq28 region.

A human Xqter chromosome cosmid library was screened with a mixed probe derived from porcine kidney mRNA. A new expressed gene was identified in a cosmid clone known to be part of a G6PD cosmid contig. This gene is most likely a housekeeping gene because the cDNA clone recognizes a 1 kb mRNA transcript in all cell lines and tissues tested.

Combined deficiencies of the pyruvate dehydrogenase complex and enzymes of the respiratory chain in mitochondrial myopathies.

In six patients with mitochondrial (encephalo-) myopathy investigations of skeletal muscle revealed a defect of pyruvate dehydrogenase complex (PDHC) in combination with one or more respiratory chain complex deficiencies. A combination of defects of this kind has not been reported previously. Five of the six patients presented within the 1st year of life and had a severe clinical course.

Hearing loss in Noonan syndrome.

A report is presented on a man of Turkish origin, with Noonan Syndrome and unilateral conductive hearing loss since early childhood. There was no history of otitis media. At the age of 23, exploratory tympanotomy revealed a total absence of the long process of the incus and a normal-looking tympanic membrane.

Mitochondrial creatine kinase containing crystals, creatine content and mitochondrial creatine kinase activity in chronic progressive external ophthalmoplegia.

Mitochondrial crystals containing mitochondrial creatine kinase (Mi-CK) protein were described recently. From in vitro studies it has been suggested that alterations in creatine concentration are connected to the occurrence of these crystals. In the present study free, phosphorylated and total creatine concentrations as well as Mi-CK activity were determined in muscle samples of six patients with chronic progressive external ophthalmoplegia (CPEO).

The value of laparoscopy in the management of the impalpable cryptorchid testis.

From January 1981 till October 1991, 47 diagnostic laparoscopies were performed in 50 impalpable testicles. In total, 28 intra-abdominal testes were found. In 14 cases no testes were found, but a deferential duct and vessels were seen.

Cytokeratin expression patterns in metastatic transitional cell carcinoma of the urinary tract. An immunohistochemical study comparing local tumor and autologous metastases.

The cytokeratin (CK) expression patterns of local, ie, primary or recurrent, high-grade-malignant transitional cell carcinomas (TCCs) of the human urinary tract and autologous lymphogenic and hematogenic metastases (n = 33) were compared. Special attention was paid to CK expression in the tumor invasion front and other areas where tumor-stroma interaction occurred to visualize cell populations with a metastatic phenotype. For this purpose, polypeptide-specific monoclonal antibodies to CKs 4, 7, 8, 10, 13, 14, 16, 17, 18, and 19 were used, employing the immunoperoxidase method.

Epidermal growth factor receptor-negative tumors are predominantly confined to the subgroup of estradiol receptor-positive human primary breast cancers.

A total of 725 human primary breast tumor biopsy samples were analyzed for epidermal growth factor receptor (EGFR) content, using a multiple-point EGFR assay standardized in accordance with the recommendations of the European Organization for Research and Treatment of Cancer Receptor Study Group. After the establishment of a lower cell membrane protein threshold of 0.2 mg of membrane protein per ml of assay buffer, the results of 27% (194 samples) of the EGFR determinations were excluded from the study because of insufficient assay membrane protein content.

Detection of numerical chromosome aberrations using in situ hybridization in paraffin sections of routinely processed bladder cancers.

An improved protocol for in situ hybridization (ISH) to routinely processed, paraffin-imbedded tissue sections from transitional bladder carcinoma (TCC) is presented. The protocol to detect numerical chromosome aberrations involved treatment of sections with thiocyanate prior to proteolytic digestion, resulting in reproducible ISH reactions. It was used to explore the influence of nuclear truncation in the detection of numerical chromosome aberrations and the detection of tumor cells among stromal and inflammatory cells, to compare the flow cytometric DNA index with chromosome copy number, and to study chromosome heterogeneity within tumors.

The impact of a syndromal diagnosis on surgery for congenital minor ear anomalies.

Between 1964 and 1986, 104 ears of 86 patients with a minor congenital ear anomaly underwent an exploratory tympanotomy at the Institute of Otorhinolaryngology of the University Hospital Nijmegen. A classification of these anomalies is proposed based on the surgical findings and results. The 4 groups in this classification are: isolated stapes ankylosis, stapes ankylosis associated with an anomaly of the malleus and incus, an isolated anomaly of the malleus and incus with a mobile stapes footplate and finally, aplasia of the oval and/or round window.

Fetal periventricular hemorrhage in von Willebrand's disease: short review and first case presentation.

We present the first case of fetal periventricular hemorrhage due to type IIa Von Willebrand's disease. Discussed are the causal relationships between fetal hemostatic disorders and periventricular hemorrhage, the risks of labor and delivery, and the management with respect to antenatal diagnosis, fetal therapy, and delivery.

Surgery for congenital stapes ankylosis with an associated congenital ossicular chain anomaly.

The surgical findings and results are presented on 32 ears with congenital stapes ankylosis with an associated congenital anomaly of the ossicular chain. One third of the patients had a syndromal diagnosis. In 26 ears, stapedectomy could be performed.

Griscelli disease with cerebral involvement.

A 9-month-old Turkish boy was diagnosed as having Griscelli disease (Chediak-Higashi-like syndrome). Clinical signs consisted of silver-grey hair and a relatively light skin colour, recurrent episodes of fever, with or without detectable infections, increasing hepatosplenomegaly, hypotonia and motor retardation. Laboratory studies showed pancytopenia of varying degree but neither inclusion bodies nor vacuoles were seen in his leucocytes.

Identification of plasma membrane proteins involved in the hepatocyte invasion of Plasmodium falciparum sporozoites.

To determine whether surface proteins of hepatocytes might be involved in the sporozoite invasion, plasma membrane proteins were prepared from human livers with CHAPS (3-[(3-cholamidopropyl)-dimethylammonio]-1-propanesulphonate) and radiolabelled with 125I (Iodogen; 1,3,4,6-tetrachloro-3 alpha,6 alpha-diphenylglycoluril). The labelled proteins were incubated with Plasmodium falciparum sporozoites and cross-linked with DSP (dithio-bis-succinimidylpropionate). Radiolabelled proteins released by reduction after repeated washing of the sporozoite-complex were separated by SDS-PAGE and autoradiographed.

Nodular regenerative hyperplasia of the liver: an important cause of portal hypertension in non-cirrhotic patients.

In our hospital over the last 10 years a diagnosis of nodular regenerative hyperplasia was made for 13 patients. Sixty-nine percent of these patients had portal hypertension, representing 27% of all our patients with portal hypertension and a non-cirrhotic liver. Nodular regenerative hyperplasia was the second most frequent cause of portal hypertension in patients without cirrhosis.

Results of follow-up after removal of non-functioning pituitary adenomas by transcranial surgery.

The records of 53 patients who had undergone transcranial surgery for a non-functioning pituitary adenoma were reviewed. The most common symptom in these patients was visual loss (51 patients). Headache was the presenting symptom in 25 and hypopituitarism in 18.

Skin manifestations in congenital deficiency of leucocyte-adherence glycoproteins (CDLG).

In congenital deficiency of leucocyte-adherence glycoproteins (CDLG) there is an immunodeficiency with impaired leucocyte function and cutaneous and extracutaneous infections occur. In more than 30% of cases the condition has a fatal course. We report the skin manifestations of three siblings with CDLG in which areas of skin necrosis occurred that resembled pyoderma gangrenosum.

DNA content and Ks8.12 binding of the psoriatic lesion during treatment with the vitamin D3 analogue MC903 and betamethasone.

Twenty patients with psoriasis were treated with the vitamin D3 analogue MC903 and betamethasone ointment in a double-blind trial with a left-right comparison. In addition to the clinical severity scores, Ks8.12 binding which detects keratin 16 expression and the DNA synthesis were quantified using flow cytometry.

Binding of the major and large HBsAg to human hepatocytes and liver plasma membranes: putative external and internal receptors for infection and secretion of hepatitis B virus.

A likely mechanism of the strong hepatotrophism of the hepatitis B virus is the presence of specific receptors for the surface antigen of hepatitis B virus on hepatocyte membranes. To examine this hypothesis, we have performed binding studies using recombinant large (preS1 + preS2 + S) and major (S) proteins with adult human hepatocytes, rat hepatocytes, human fibroblasts, human peripheral blood mononuclear cells and plasma membranes derived from these cell types. We found that major HBsAg was able to bind specifically to human hepatocytes, human fibroblasts and human blood mononuclear cells.

An NcoI restriction fragment length polymorphism at the human steroid sulphatase gene locus.

The DNA diagnosis of X-linked recessive ichthyosis vulgaris (incidence: approx. 1 in 5000 males) can be complicated by the absence of restriction fragment length polymorphisms (RFLPs) in the STS (steroid sulphatase) gene. An RFLP sequence in NcoI-digested genomic DNA is reported, which it is hoped may prove helpful in diagnosis.