Surgery of esophageal cancer]

From 1975 through 1988, 257 patients with carcinoma of the thoracic oesophagus have been treated in our department. Operability was 90% (232/257), overall resectability 77% (198/257) and for the operated group 85% (198/232). Hospital mortality was 9.6% but decreased to 3% over the period 1986-1988. There were 65% squamous cell epitheliomas and 35% adenocarcinomas. pTNM staging was as follows: Stage I: 11.6%, Stage II: 23.2%; Stage III: 37.9%; Stage IV: 27.3%. Overall survival was 62.5% after one year, 42.4% after 2 years and 30% after 5 years. According to the pTNM staging 5-year survival was 90% for stage I, 56% for stage II, 15.3% for stage III. There was no 5-year survival for patients with stage IV carcinoma. There were statistically significant differences according to tumour localisation, pathologic type, sex and age. Introducing extensive resection and extended lymphadenectomy seems to improve significantly survival in patients in whom an operation with curative intention was performed. The 1-year survival was 90.8 versus 72%, 2-year survival was 81 versus 46% and 5-year survival was 48.5 versus 41% for respectively radical and non-radical resections. Radical surgery in stage IV carcinoma substantially prolonged median survival from 6 months to 1 year. From this study it can be concluded that in experienced hands, surgery today offers the best chances for optimal staging, potential cure and prolonged high-quality palliation.     

The prevalence of A. actinomycetemcomitans, P. gingivalis and P. intermedia in selected subjects with periodontitis

Abstract. The present study was carried out in a private periodontal practice. 8 clinical criteria were chosen to select patients for microbiological examination. These criteria characterize prominent features of disease which at the start, during, or in the maintenance phase of treatment suggest difficulties in the progress of the periodontal therapy. Based on these clinical characteristics, an inventory was made of the prevalence of the 3 putative periodontal pathogens: Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia. Out of 320 referred patients 91 patients did meet 1 of the clinical criteria and consequently were selected for microbiological examination. Results showed that young patients (19–30 years) with periodontitis demonstrated the presence of A. actinomycetemcomitans more often (69%: p (0.005) compared to older age cohorts. A. actinomycetemcomitans was found more often when localized breakdown (in particular in the 1 st molar and incisor region) was observed and in patient who responded poorly to scaling and rootplaning. P. gingivalis and P. intermedia were most frequently recovered in patients showing primarily a bone loss pattern of angular defects of 5 mm. Retrospectively, these patients were further categorized, based on full mouth radiographs, in (1) patients with primarily horizontal bone loss and (2) patients with primarily angular bony defects. Results showed that A. actinomycetemcomitans occurred less frequently in patients showing horizontal bone loss ( p (0.05).     

Two tyrosinase nonapeptides recognized on HLA-A2 melanomas by autologous cytolytic T lymphocytes

A number of cytolytic T lymphocyte (CTL) clones derived from several melanoma patients have been found to recognize a majority of melanomas from HLA-A2 patients. We have reported previously that two such CTL clones recognize a product of the tyrosinase gene that is presented by HLA-A2. Here we show that one of these CTL clones recognizes a peptide encoded by the first nine amino acids of the putative signal sequence of tyrosinase. The other CTL clone recognizes a different tyrosinase peptide corresponding to amino acids 368–376. Both peptides contain consensus motifs of HLA-A2 binding peptides.     

5-HT1A receptor agonists: recent developments and controversial issues

During the last decade, serotonin (5-HT)_1A receptors have been a major target for neurobiological research and drug development. 5-HT_1A receptors have been cloned and a variety of selective agonists, such as the aminotetraline 8-OH-DPAT and the pyrimidinylpiperazine ipsapirone, have become available. Demonstrations of apparent intrinsic activity of these ligands at 5-HT_1A receptors, however, depend highly on the particular assay system. This may be due to the possible existence of receptor subtypes and to assay (or brain region)-dependent differences in receptor reserve and the nature of receptor-effector coupling. Nevertheless, the apparent intrinsic activity of 8-OH-DPAT seems to be higher (although possibly not yet maximal) than that of the pyrimidinylpiperazines. In the brain, 5-HT_1A receptors are located presynaptically as somatodendritic receptors on 5-HT neurons and postsynaptically in particular limbic and cortical regions. Although it is generally accepted that presynaptic 5-HT_1A receptors control 5-HT neuronal activity, recent evidence suggests an additional role of postsynaptic 5-HT_1A receptors in cortex as part of a negative feedback loop. Anxiolytic and antidepressive properties of selective 5-HT_1A receptor agonists have now been confirmed by clinical studies. Although it is well established that the latter properties depend on theagonistic activity of these compounds, theoptimal level of intrinsic activity is still a matter of debate and may be dependent on the clinical indication. Such compounds may also have antiaggressive effects, and possibly anticraving effects (manifested by their alcohol intake-reducing effects in dependent animals), but the specificity of these so-called anti-impulsivity effects is still controversial and not yet tested clinically. Anticataleptic, antiemetic and neuroprotective properties have been demonstrated in different species. Behavioral studies on the mechanisms underlying the anxiolytic and antidepressive effects have examined the relative contribution of pre-and postsynaptic 5-HT_1A receptors by means of local cerebral application and lesion techniques. Most evidence points towards a critical involvement of presynaptic receptors in the anxiolytic effects of 5-HT_1A receptor agonists (although a possible contribution of postsynaptic receptors cannot be excluded). With regard to the antidepressive properties, a case can be made for the reverse; i.e., a strong involvement of postsynaptic receptors and a questionable contribution of presynaptic receptors. However, as the therapeutic effects of those 5-HT_1A receptor (partial) agonists which have been tested clinically require repeated administration, attention has been directed increasingly towards chronic studies. These studies have shown that a number of electrophysiological, biochemical, behavioral and endocrinological 5-HT_1A receptor-related events adapt differentially to repeated or sustained administration. Thus, several hypotheses accounting for the delayed onset of action have been advanced. Among these, time-dependent downregulation /desensitization of eitherpre- orpostsynaptic 5-HT_1A receptors, or cortical 5-HT₂ receptors have received much attention. However, these hypotheses have their weaknesses, and it is argued thatfunctional sensitization of particular postsynaptic 5-HT_1A receptor-mediated events remains a valuable alternate hypothesis. Basic research on the role of 5-HT_1A receptors in psychopathology and in the therapeutic effects of clinically effective therapeutics, as well as on the mechanism of action of 5-HT_1A receptor ligands, will enable rational design of ligands with particular profiles of intrinsic activity at different 5-HT_1A receptor populations, and may contribute to a more efficient treatment of a multiplicity of brain disorders.     

EndocrinologyHormonal profile during the follicular phase in cycles stimulated with a combination of human menopausal gonadotrophin and gonadotrophin-releasing hormone antagonist (Cetrorelix)

A third-generation gonadotrophin-releasing hormone antagonist(Cetrorelix) was used during ovarian stimulation in 32 patientsundergoing assisted reproduction, in order to prevent the prematureluteinizing hormone (LH) surge. In all patients, ovarian stimulationwas carried out with two or three ampoules of human menopausalgonadotrophin (HMG), starting on day 2 of the menstrual cycle.In addition, 0.5 mg of Cetrorelix was administered daily fromday 6 of HMG treatment until the day of ovulation inductionby human chorionic gonadotrophin (HCG). A significant drop inplasma LH concentration was observed within a few hours of thefirst administration of Cetrorelix (P<0.005). Moreover, noLH surge was detected at any point in the treatment period inany of the 32 patients. A mean oestradiol concentration of 2122±935ng/1 was observed on the day of the HCG administration, indicatingnormal folliculogenesis. Like LH, progesterone concentrationalso dropped within a few hours of the first administrationof Cetrorelix (P< 0.005). A 0.5 mg daily dose of Cetrorelixprevented a premature LH surge in all the 32 patients treated.     

Congenital pneumonia due to Mycoplasma pneumoniae.

A case of probable vertical transmission of Mycoplasma pneumoniae is presented. The presence of M pneumoniae was demonstrated by the polymerase chain reaction (PCR) in the nasopharyngeal aspirate of a newborn who developed pneumonia shortly after birth. This result was confirmed by performing a second PCR, amplifying another part of the genome of M pneumoniae. It is concluded that M pneumoniae can be added to the long list of pathogens known to cause congenital pneumonia.     

Measuring oscillatory potentials: Fourier analysis

Studying the oscillatory potentials in diabetic retinopathy, the authors experienced several problems interpreting results of digital filtering. The main problem was the separation of the first potential from the a-wave, since their frequencies are within the same range. To improve the procedure of measuring implicit times and of calculating amplitudes, the filtering was started with a finite impulse response filter and followed by a fast Fourier transform. The power of the oscillatory potential was calculated by determining the dominant frequency in the Fourier transformed response and expressed in microwatts. A group of normal subjects was compared with a group of early diabetic retinopathy patients. It appears that even in pathological circumstances a quantitative expression of the oscillatory potential is possible.     

Cocaine use among heroin users in Spain: the diffusion of crack and cocaine smoking. Spanish Group for the Study on the Route of Administration of Drugs

STUDY OBJECTIVE: To describe the prevalence and patterns of use of crack and cocaine hydrochloride among heroin users in Spain. To explore if the expansion of heroin smoking is accompanied by a similar phenomenon for cocaine. DESIGN: Cross sectional study in 1995. Face to face interviews using a structured questionnaire. SETTING: Three cities with different prevalences of heroin use by smoking: high (Seville), intermediate (Madrid), and low (Barcelona). PARTICIPANTS: 909 heroin users, 452 in treatment and 457 out of treatment. MAIN RESULTS: Last month prevalence of crack use was 62.3% in Seville, 19.4% in Madrid, and 7.7% in Barcelona. Most users in Madrid (86.5%) and Barcelona (100%) generally prepared their own crack, usually with ammonia as alkali; in Seville most users (69.7%) bought preprocessed crack. The proportion of users who began taking cocaine (crack or cocaine hydrochloride) by smoking has increased progressively since the seventies, rising to 74.1% in Seville, 61.5% in Madrid, and 28% in Barcelona in 1992-1995, with the earliest increase in Seville. The factors associated with crack use were: residence in Seville (odds ratio (OR) = 16.3), cocaine hydrochloride use mainly by smoking (OR = 5.0), by sniffing (OR = 2.7) or by injecting (OR = 2.5), heroin use mainly by smoking (OR = 2.8) and weekly use of cannabis (OR = 1.9). CONCLUSIONS: In Spain smoking cocaine may be progressively diffusing from the south west to the north east, similar to what has happened with smoking heroin, but beginning later in time. The factors associated with smoking cocaine are basically ecological or cultural in nature (characteristics of the available drugs and the main route of heroin administration in each city).

 

     

Sertoli细胞诱导大鼠肝内胰岛移植物免疫豁免的实验研究

目的 探究睾丸Sertoli细胞能否对肝内共移植的胰岛移植物提供免疫豁免作用以及共移植的睾丸Sertoli细胞最佳数量。方法将同种大鼠胰岛及不同数量的睾丸Sertoli细胞同时移植于糖尿病受体的肝内,观察移植物存活情况、胰岛功能、并检测移植物内胰岛素和Fas配体(FasL)表达以及浸润淋巴细胞凋亡情况。结果单纯胰岛移植组平均存活期为(5.6±0.8)d,同时与胰岛细胞在肝内共移植的睾丸细胞数增加至1×107个时,平均存活期为(41.4±4.61)d,明显延长(P<0.05),胰岛移植物中有大量表达FasL的睾丸细胞和表达胰岛素的胰岛细胞.在移植物周围有大量浸润的淋巴细胞凋亡。结论睾丸Sertoli细胞与胰岛细胞同时在肝内共移植,通过诱导局部豁免而延长胰岛移植物的存活时间,且同时共移植1×107个Sertoli细胞时效果最好。