Prediction of outcome by lymph node ratio in patients with parotid gland cancer.

OBJECTIVE: Lymph node ratio (LNR) has been shown to be an independent predictor of recurrence risk and survival in different entities of carcinoma. METHODS: In this retrospective chart review, 128 patients with parotid gland cancer (PGC) subsequently treated by primary surgery were included. About 64% (n = 82) of these patients were additionally treated with adjuvant radiotherapy. Five-year overall survival rates were determined by subgroups based on LNR value. RESULTS: Lymph node ratio was found to be significantly associated with overall survival rate (P < 0.001). Using univariate analyses, pathological tumour-node-metastasis (TNM)-stage, UICC-stage grouping and extracapsular spread were found to be significant predictors of overall survival (P < 0.001). However, with a multivariate analyses, LNR remained the only independent predictor of overall survival (P = 0.043). CONCLUSIONS: After surgery for PGC, evaluation of the neck using LNR was found to reliably stratify the overall survival rate.

[Meningioangiomatosis with associated meningioma in a 4-year-old girl presenting with a focal seizure]. / Meningeoangiomatose mit assoziiertem Meningeom bei 4-jährigem Mädchen mit fokalem Krampfanfall.

Meningioangiomatosis is regarded as a rare, benign, hamartomatous malformation. Histopathologically, the lesion is characterized by circumscribed transcortical and leptomeningeal meningovascular proliferation with focal calcifications. It may be classified into cases with predominant cellular or vascular features and may occur in association with neurofibromatosis, mostly of type 2, but sporadic cases are more frequently reported. Sporadic cases often present initially with seizures and can be treated surgically. However, a certain percentage of patients will need ongoing anticonvulsive therapy. The lesions are seldom associated with an overlying meningioma. These are usually benign lesions that must be strictly separated from an invasive anaplastic meningioma, which would warrant an adjuvant therapy. We report on a 4-year-old girl who presented with spontaneous, predominantly cellular meningioangiomatosis with associated fibrous meningioma. Focal immunopositivity of the meningioangiomatosis for CD34 was helpful in ruling out an invasive meningioma.

Specific bronchoalveolar lavage fluid T cells associate with disease in a pair of monozygotic twins discordant for sarcoidosis.

A 49-year-old Caucasian woman had an acute onset of sarcoidosis. Bronchoscopy with bronchoalveolar lavage (BAL) showed a pronounced accumulation of BAL fluid CD4+ T cells expressing the T-cell receptor (TCR) AV2S 3 gene. In line with this observation, the patient was HLA-DR 17 positive, previously shown to strongly correlate with lung compartmentalized AV2S3+ T cells. At follow-up after recovery, reduced numbers of BAL fluid AV2S3+ T cells were found. Interestingly, BAL fluid of a healthy monozygotic twin sister contained normal numbers of AV2S3+ lung T cells. This report shows the T-cell repertoire of BAL fluid T cells to correlate with the disease (sarcoidosis). indicating a local and specific immune response triggered by an unknown antigen in sarcoidosis.

Expression of an alternative Dnmt1 isoform during muscle differentiation.

The methylation pattern of genomic DNA undergoes dramatic changes during mammalian development, with extensive de novo methylation occurring during gametogenesis and after implantation. We identified an alternative Dnmt1 transcript in skeletal muscle by Northern blot analysis and cloned the corresponding cDNA by rapid amplification of cDNA ends and reverse transcription-PCR. Using an in vitro skeletal muscle differentiation system, we show that this alternative Dnmt1 isoform is specifically expressed in differentiated myotubes, whereas the ubiquitously expressed isoform is down-regulated during myogenesis. Sequence analysis showed that this skeletal Dnmt1 isoform is identical to the one present in testis, which had been described as untranslatable. Here we present evidence that this alternative Dnmt1 transcript present in testis and skeletal muscle is translated despite the presence of several out-of-frame upstream ATGs and gives rise to a shorter Dnmt1 isoform, which could play an active role in the change of DNA methylation patterns during gametogenesis and myogenesis.

Serotonin transporter (5-HTT) gene polymorphisms are not associated with susceptibility to mood disorders.

In a population-based association study, we tested the hypothesis that allelic variants of the human serotonin transporter (5-HTT) gene confer susceptibility to mood disorders. Both a biallelic repeat polymorphism in the 5' promotor region that differentially modulates gene expression and a second intron variable-number-tandem-repeat (VNTR) marker were genotyped in 294 controls and 115 patients with mood disorders. Subjects were of West European descent and included 36 patients with major depressive disorder (MDD) and 79 patients with bipolar I disorder (BD). No significant differences in genotype or allele frequencies were found at either locus between controls and combined patients, nor between controls and MDD or BD patients separately. Thus, our data do not support the association between depressive disorder and a nine-repeat allelic variant of the 5-HTT VNTR marker recently reported by Ogilvie et al. (Lancet 347:731-733, 1996). More importantly, no association between alleles conveying functional differences in 5-HTT gene expression and MDD or BD could be found. Taken together, our data suggest that the 5-HTT gene is not commonly involved in the susceptibility to mood disorders.

A novel allelic variant of the human serotonin transporter gene regulatory polymorphism.

Allelic variation of the human serotonin transporter gene (SLC6A4) has recently been shown to modulate anxiety-related traits. A tandemly repeated sequence in close proximity to the promoter was found to be represented by a long (L) and short (S) variant, differentially modulating gene expression in vitro. Specifically, allele S, generated by a deletion of 44 bp involving repeats VI to VIII, reduced transcriptional efficiency, gene expression, and 5-hydroxytryptamine uptake and was associated with increased neuroticism scores. We have now identified a novel allelic variant of this promoter-linked polymorphism that is significantly larger than the L allele and which we have designated allele XL (for "extra large"). Sequence analysis revealed that XL arose through duplication of an internal segment composed of repeat elements VI to IX, comprising 85 bp in total, and, most notably, including the segments deleted in the S allele. Additional allelic variants larger than human allele L were observed predominantly in various nonhuman primates. Preliminary data indicated that these variable allelic extensions similarly originate from this specific repeat region. These allelic variants may serve as a valuable model system to further elucidate the relationship between repeat structure, regulatory properties, and behavioral correlates. Finally, allelic variants were found to vary significantly among different human populations, with allele XL being uniquely present in individuals of African origin, allele L most frequent in Africans and Caucasians of Western European descent, and allele S most abundant in East Asians.

Paroxetine as antidepressant in combined antidepressant-neuroleptic therapy in delusional depression: observation of clinical use.

The combination of antidepressive and antipsychotic (neuroleptic) medication is often used in the psychopharmacological treatment of delusional depression. In most studies of the treatment of delusional depression, tricyclic antidepressants have been used, and very little has been written about experience with SSRIs such as fluvoxamine, fluoxetine, or paroxetine. This paper therefore presents the preliminary findings of an open clinical study in which 14 delusional depressed inpatients, consecutively admitted to our Depression Unit, were given paroxetine combined with either zotepine or haloperidol. It was possible to observe a significantly impressive decline in the HAMD (24-item version) total score, of so-called delusional items (HAMD subscore of items 2, 17, 18, 20, 23, 24) and of the subscore of remaining HAMD items over 21 treatment days. There were no unusual side-effects.

Identification of three novel mutations in the CFTR gene using temperature-optimized non-radioactive conditions for SSCP analysis.

Optimal temperature conditions for the detection of 28 known mutations on 15 exons of the human cystic fibrosis transmembrane conductance regulator gene by single strand conformation polymorphism analysis using the Diagen TGGE Apparatus were established. This procedure was applied to the detection of unknown mutations in 58 non-deltaF508 chromosomes. Three novel mutations, -471del3 (5' flanking region), 3171insC (exon 17a) and 4700(T)8/9 (3' non-translated region) of the CFTR gene were found. Mutation 3171insC occurred in conjunction with the delta F508 mutation on the other allele of a child presenting with severe pathology. Mutation -471del3 has so far only been found in one healthy individual and her father, and 4700(T)8/9 is a DNA sequence polymorphism.

Paroxetine in the treatment of inpatients with non-delusional endogenous or neurotic depression.

The clinical course of 35 depressed inpatients (19 women, 16 men; 19 endogenous, 16 neurotic depression (ICD-9 diagnoses); mean age 46.7 years) who were treated with paroxetine 20 mg/d was observed over 21 days using the Hamilton Depression Scale (HAMD). For both types of depression there was a significant decrease from day 1 to day 21 in the mean HAMD total score and in a subscore of cognitive and somatic items. The mean value of the HAMD suicide item increased in 3 cases and decreased in 25.

Non-isotopic analysis of single strand conformation polymorphism (SSCP) in the exon 13 region of the human dystrophin gene.

More than 30% of Duchenne and Becker muscular dystrophy (DMD/BMD) patients have no gross DNA rearrangements like deletions or duplications. The large size of the coding sequence of the dystrophin gene (11 kilobases) complicates systematic identification of point mutations. Recently reported approaches based on genomic DNA or mRNA show that chemical cleavage of mismatches is an effective but time consuming and technically demanding method for the identification of point mutations in the human dystrophin gene. We have used a fast and convenient system consisting of PCR amplification of genomic DNA, non-isotopic SSCP analysis, and direct sequencing of PCR products for the detection of mutations in exon 13 and adjacent intron sequences. Sixty-eight DMD patients without detectable deletions or duplications were analysed, resulting in the identification of a point mutation in the coding sequence and two polymorphisms in the 5' flanking intron. The C to T change of the first nucleotide in the third triplet leads to a stop codon and seems to be the cause of the functional deficiency of the gene product in this patient.