Syncytin-1 and its receptor is present in human gametes.

MAIN PURPOSE AND RESEARCH QUESTION: To determine whether the true fusogen Syncytin-1 and its receptor (ASCT-2) is present in human gametes using qRT-PCR, immunoblotting and immunofluorescence. METHODS: Donated oocytes and spermatozoa, originating from a fertility center in tertiary referral university hospital, underwent qRT-PCR, immunoblotting and immunofluorescence analyzes. RESULTS: Quantitative RT-PCR of sperm samples from sperm donors showed that syncytin-1 is present in all samples, however, protein levels varied between donors. Syncytin-1 immunoreactivity predominates in the sperm head and around the equatorial segment. The receptor ASCT-2 is expressed in the acrosomal region and in the sperm tail. Moreover, ASCT-2, but not syncytin-1, is expressed in oocytes and the mRNA level increases with increasing maturity of the oocytes. CONCLUSIONS: Syncytin and its receptor are present in human gametes and localization and temporal appearance is consistent with a possible role in fusion between oocyte and sperm.

A randomized study comparing short-time infusion of oxaliplatin in combination with capecitabine XELOX(30) and chronomodulated XELOX(30) as first-line therapy in patients with advanced colorectal cancer.

BACKGROUND: Chronotherapy is one of the several approaches to increase efficacy and reduce toxicity of chemotherapy. In a phase II study in the second-line in patients with metastatic colorectal cancer (mCRC), we found that chronomodulated XELOX (XELOX(30Chron)) was a well-tolerated regimen with potentially reduced toxicity. PATIENTS AND METHODS: One hundred and forty-one patients with unresectable mCRC were enrolled in a randomized study comparing standard XELOX (XELOX(30)), arm A, and XELOX(30Chron), arm B-both with short-time infusion of oxaliplatin-with the primary aim of reducing overall toxicity. RESULTS: Overall toxicity grade 2-4 was 90% versus 85%, P = 0.47 and grade 3-4 was 31% versus 37%, P = 0.6 in arm A and B, respectively. We found no significant differences in median overall survival (17.6 versus 15.5 months; P = 0.068) and median progression-free survival (8.9 versus 8.8 months; P = 0.7). The incidence of grade 3 neuropathy was 16% in arm A and 19% in arm B (P = 0.7) after a cumulative dose of oxaliplatin of 1000 mg/m(2). CONCLUSION: XELOX(30Chron) does not reduce toxicity or improve efficacy. A 30-min infusion of oxaliplatin is safe and does not increase the severity of chronic neuropathy.

Patient preference for oral or intravenous chemotherapy: a randomised cross-over trial comparing capecitabine and Nordic fluorouracil/leucovorin in patients with colorectal cancer.

Until recently, fluorouracil (F) and leucovorin (L) had been considered the standard therapy for patients with colorectal cancer. However, several studies have shown that oral therapy with UFT/L or capecitabine is as effective as intravenous (i.v.) therapy and in addition it is claimed that patients prefer oral to i.v. therapy as long as efficacy is not compromised. In a previous crossover study by Borner et al., it was shown that 26 out of 31 patients preferred oral therapy with UFT/L to i.v. FL (Mayo regimen) [Borner M, Schöffski P, de Wit R, et al. Patient preferences and pharmacokinetics of oral modulated UFT versus intravenous fluorouracil and leucovorin: a randomised crossover trial in advanced colorectal cancer. Eur J Cancer 2002;38:349-58]. The objective of the present study was to investigate patient preference between i.v. FL and oral capecitabine using the design described by Borner. The Nordic FL schedule is a bolus regimen with efficacy comparable to other i.v. regimens and at the same time a very tolerable and easy administered regimen. We randomised 60 patients with colorectal cancer (53 patients received adjuvant therapy and seven patients received palliative therapy) to start therapy with either oral capecitabine or Nordic bolus FL. After 6 weeks of therapy (two courses of capecitabine or three courses of Nordic FL) patients were crossed over to the other regimen. After having completed 12 weeks of therapy the patients (49 evaluable patients) were asked to choose one of the regimens for a further 12 weeks of therapy. Patients had more side-effect when treated with capecitabine and a total of 30 out of 49 (61%) preferred the Nordic FL regimen and 19 (39%) preferred capecitabine. We conclude that patients prefer the regimen with less toxicity and that it is of minor importance whether the medication is administrated orally at home or i.v. at the hospital.

Automated identification of cancerous smears using various competitive intelligent techniques.

In this study the performance of various intelligent methodologies is compared in the task of pap-smear diagnosis. The selected intelligent methodologies are briefly described and explained, and then, the acquired results are presented and discussed for their comprehensibility and usefulness to medical staff, either for fault diagnosis tasks, or for the construction of automated computer-assisted classification of smears. The intelligent methodologies used for the construction of pap-smear classifiers, are different clustering approaches, feature selection, neuro-fuzzy systems, inductive machine learning, genetic programming, and second order neural networks. Acquired results reveal the power of most intelligent techniques to obtain high quality solutions in this difficult problem of medical diagnosis. Some of the methods obtain almost perfect diagnostic accuracy in test data, but the outcome lacks comprehensibility. On the other hand, results scoring high in terms of comprehensibility are acquired from some methods, but with the drawback of achieving lower diagnostic accuracy. The experimental data used in this study were collected at a previous stage, for the purpose of combining intelligent diagnostic methodologies with other existing computer imaging technologies towards the construction of an automated smear cell classification device.

The most common chromosome aberration detected by high-resolution comparative genomic hybridization in vulvar intraepithelial neoplasia is not seen in vulvar squamous cell carcinoma.

We analyzed genetic changes in condylomas (four cases), vulvar intraepithelial neoplasia I-III (VIN I-III, eleven cases), and primary vulvar squamous cell carcinomas (VSCC, ten cases) by high-resolution comparative genomic hybridization (HR-CGH) and flowcytometry. All samples were also human papilloma virus (HPV)-genotyped. Gain of chromosome 1, the aberration most often seen in VIN III (67%), was not seen in HPV-positive or -negative VSCCs (0%). Both VIN III and VSCC frequently showed gain of 3q (56 and 70%, respectively). The VIN III samples often demonstrated gain of 20q (56%) and 20p (44%), and the VSCC samples gain of 8q (60%), loss of 3p (50%), and 8p (40%). None of the four most frequent changes in the VSCC samples occurred exclusively in the HPV-positive or -negative samples. As expected, we did not find any cytogenetic changes in condylomas and nearly any changes in VIN I-II.

Cytomegalovirus infection in classic, endemic and epidemic Kaposi's sarcoma analyzed by in situ hybridization.

In order to evaluate the association between cytomegalovirus (CMV) infection and Kaposi's sarcoma (KS) at the cellular level, four classic KS, five endemic (African) KS and 55 epidemic KS from 12 patients with AIDS were analyzed by in situ hybridization with a biotinylated specific CMV-DNA probe. CMV-DNA was sparsely demonstrated in the sarcomas in 10 of the patients with AIDS but in none of the classic or endemic sarcomas. The distribution and localization of the CMV-infected cells did not suggest CMV as a major pathogenic stimulus for the development of KS but rather as an opportunistic infection in severely immunosuppressed patients.

Accumulation of the proteolytic marker peptide ubiquitin in the trophoblast of mammalian blastocysts.

Ubiquitination is a universal protein degradation pathway in which the molecules of 8.5-kDa proteolytic peptide ubiquitin are covalently attached to the epsilon-amino group of the substrate's lysine residues. Little is known about the importance of this highly conserved mechanism for protein recycling in mammalian gametogenesis and fertilization. The data obtained by the students and faculty of the international training course Window to the Zygote 2000 demonstrate the accumulation of ubiquitin-cross-reactive structures in the trophoblast, but not in the inner cell mass of the expanding bovine and mouse blastocysts. This observation suggests that a major burst of ubiquitin-dependent proteolysis occurs in the trophoblast of mammalian peri-implantation embryos. This event may be important for the success of blastocyst hatching, differentiation of embryonic stem cells into soma and germ line, and/or implantation in both naturally conceived and reconstructed mammalian embryos.

Prognosis of acute nonspecific abdominal pain. A prospective study.

In a prospective study of 230 patients followed up for 5 years after hospital admission for acute non-specific abdominal pain, 21 patients (9 patients) could not be traced, and 11 (5 percent) had died. Only one death was related to symptoms from the first admission. Of the remaining 198 patients, 77 percent were healthy and free of any symptoms during the observation period. Fourteen patients (7 percent) had been hospitalized once more due to acute abdominal pain; 5 had acute appendicitis. The others had diagnosed recurrences of nonspecific abdominal pain. Sixteen percent complained of continuing of intermittent abdominal symptoms, mainly of benign colonic or gynecologic origin, while malignant disease developed in 1 percent (or 4 percent of patients over 50 years of age). It is concluded that control of these patients is generally unnecessary, but when symptoms recur further examinations, especially for colonic or gynecologic disease, should be carried out. In patients over 50 years old, the possibility of malignant disease should be kept in mind.

Acute appendicitis. Prospective trial concerning diagnostic accuracy and complications.

In a prospective trial comprising 202 patients operated on because of suspicion of acute appendicitis, the diagnostic accuracy was 70 percent based on histologic examination of all removed appendices. The diagnostic accuracy was lowest in women less than 50 years old and in young patients (aged 20 years or less), being about 60 percent in both of these groups. The reasons were gynecologic disorders and uncharacteristic abdominal pains, respectively. Twenty-three of the 142 patients with acute appendicitis had perforation (16 percent). The frequency of perforation was significantly higher in patients more than 50 years old. Postoperative complications were seen in 11 percent of the patients. There was no significant difference in the frequency of complications in patients with a normal appendix and no other surgical abdominal disorder and patients with nonperforated appendicitis. However, there was a statistically significant difference between these two groups and the group with perforated appendicitis. In the latter group, postoperative complications occurred in 39 percent of the patients as opposed to 4 percent and 8 percent, respectively, in the former groups.

Regulation of ribosomal RNA gene expression in porcine oocytes.

In vitro production (IVP) of porcine embryos including in vitro maturation (IVM) of oocytes followed by in vitro fertilization (IVF) and in vitro culture (IVC) of the resultant embryos may result in live offspring, but it is still associated with great inefficiencies probably due to incomplete cytoplasmic maturation of the oocytes in vitro. Therefore, fundamental knowledge on the regulation of transcription during the oocyte growth phase when the messengers and protein synthetic machinery necessary for oocyte developmental competence are formed, is of great importance. In mammals, synthesis of RNA, up to 60-70% of which is ribosomal (rRNA), increases during oocyte growth and reaches a peak at the beginning of follicular antrum formation. In oocytes at the end of the growth phase, acquisition of full meiotic competence coincides with a markedly decreased rRNA transcriptional activity in the gametes. Our recent studies on the porcine oocyte growth phase have revealed a deeper molecular and biological insight into the complex regulation of rRNA transcription at different stages of follicular development. The data indicate that the so-called pocket protein, p130, is involved in the down-regulation of rRNA transcription at the end of the oocyte growth phase through an inhibition of the action of upstream binding factor (UBF). The latter protein is necessary for the function of RNA polymerase I (RNA Pol I), which is the actual enzyme driving rRNA gene transcription. Moreover, rRNA transcription also appears to be down-regulated by a decrease in the expression of mRNA encoding PAF53, an RNA Pol I-associated factor also required for the polymerase to exert its action. At the ultrastructural level, these molecular changes are paralleled by marginalization of the fibrillar centres of the oocyte nucleolus followed by compaction of the nucleolus into an inactive sphere of fibrils.

Value of the filter imprint technique in aspiration biopsy cytology.

In 468 fine needle aspiration (FNA) biopsies, after smearing of the aspirate on glass slides, additional material was obtained by flushing the needle with a fixative. The cells were collected on Millipore filters, from which imprints were prepared. The filter imprints were found to be sufficiently cellular in 60% of the cases, which reduced by 33 (7.3%) the number of cases with unsatisfactory aspirates. Diagnostic specificity and sensitivity were not influenced by the technique. The filter imprint technique was of particular value in breast aspirates.

Tumours of the nose and maxillary sinus. Ten year survey from Kenya.

Between 1976-1985, 127 cases of malignant tumours of the nose and maxillary sinus were seen at the Department of Human Pathology, Kenyatta National Hospital, Nairobi, Kenya. Cancer of the nose and maxillary sinus was a common diagnosis accounting for 0.8 per cent of all malignancies. Despite this, the incidence was low probably because the rural Kenyans have difficulty in gaining access to the oncology facilities in Nairobi. Incidence rates standardized to world population per 100,000 persons-years were 0.16 for males and 0.12 for females. Clinical information showed that malignancy should be expected in patients with swelling of the cheek and involvement of the orbit. Compared with Denmark the proportion of undifferentiated carcinomas was significantly higher in Kenya. The well known fact that anaplastic carcinoma of the postnasal space is causally associated with the Epstein Barr virus makes it tempting to suggest that anaplastic carcinoma of the nose and maxillary sinus may also be of viral aetiology.

Breast cancer in Kenya: a histopathologic and epidemiologic study.

During 1981-1985, 417 cases of breast cancer were seen at the Department of Human Pathology, Kenyatta National Hospital, Nairobi, Kenya. During this period, 8041 cases of cancer were reported. Cancer of the breast accounted for 5% of all malignancies in Kenya and only second in number to cancer of the cervix. The incidence rate in females was 1.08 per 100,000 person-years. The incidence was low because the rural Kenyans have difficult access to the oncology facilities in Nairobi. The age specific incidence rates decreased after menopause. This is also found in other African countries but is in contrast with North America and Europe, where there is a rise after menopause. Young age of the first pregnancy, many pregnancies and a low fat content of the diet may contribute to the low incidence in post menopausal women. The distribution of the histological types was the same in Kenya with predominance of premenopausal cases and in the western world with predominance of postmenopausal cases. Invasive ductal carcinoma was the most common cancer type. Poorly differentiated tumours were common. This is probably explained by the fact that most patients seek medical help at a late state with advanced cancer. Only two cases of non-invasive intraductal carcinoma were found and in cases where lymphnodes were removed 88% had metastases.

Benign breast lesions in Kenya: a histological study.

During 1981-85, 1084 cases of benign breast lesions were seen at Kenyatta National Hospital, Nairobi, Kenya. In the same period, 417 cases of breast carcinoma were diagnosed. Amongst the benign lesions fibroadenoma was the most common diagnosis (531 cases) followed by mastopathy (177 cases). The incidence rate of fibroadenoma was 1.6 per 100,000 person-years. Classic tubular adenoma was seen in 26 cases and in 26 cases a mixture of fibroadenoma and tubular adenoma was seen. These findings suggest that breast adenoma is probably one tumour with different expressions of the glandular and fibrous areas. We found no specific gross or microscopical features by which it was possible with certainty to distinguish between fibroadenoma and giant fibroadenoma and therefore suggest that the term giant fibroadenoma be avoided. The histopathologic pattern of mastopathy showed great variation, but the lesions were without difficulty divided into three main categories, i.e. cystic, fibrous and hyperplastic mastopathy. This distinction is important as cases with marked epithelial hyperplasia have been shown to have an increased cancer risk. Except for low parity no similarities in risk factors for mastopathy and breast cancer have been shown so far.

Scleroma in Africa: a review of cases from Kenya.

Scleroma is a chronic granulomatous disease reported from many parts of the world. 5% of the cases are located in Africa. Ten cases of scleroma histologically diagnosed at the Department of Human Pathology, Kenyatta National Hospital, Nairobi are reported. Four of the 10 cases were males and six were females. They were aged between 18 and 53 years. The patients came from highland areas in Central and Western Kenya where an endemic focus may well exist.

An empirical study of stalking victimization.

This article empirically studies the phenomenon of stalking and its victims by utilizing a random sample of college students at a large public University. The study found that 25% of the women and 11% of the men had been stalked at some point in their lives and that six percent were currently being stalked. Additionally, the study found that the majority of stalking victims are women who are stalked by male offenders. The sample reported being stalked for an average of 347 days and having engaged in a variety of actions in response. A substantial number of victims reported being threatened by their stalkers. This threat was associated with higher levels of fear among the victims and a greater chance of physical attack by the stalkers, particularly for the female victims.

[A model for estimation of productivity and costs at a deparment of histopathology]. / Model til beregning af produktion og omkostninger på patologisk anatomisk afdeling.

Two cost calculation models were used. The "top down" model calculated an average cost of all investigations; this proved suitable for the calculation of the costs of autopsies and electron microscopical specimens. The "bottom up" model calculated the cost of an individual investigation, depending on the resources used in handling each particular specimen; it was necessary to adopt this model for specimens sent for microscopy. Information about the type of specimen and technical details were registered in a computer system. Production was registered in points and the costs were distributed between the clinical departments. The study showed that the cost of the histological specimens varied considerably depending on the material received from the clinical departments. A model using points for technical details in a department of cyto- and histopathology is suitable for calculating production and cost.

[EDP registration of the types of tests, working procedures and diagnosis in a department of histopathology. Minimum dataset for assessment of the workload]. / Edb-registering af prøvetyper, arbejdsprocedurer og diagnoser på patologisk anatomisk afdeling.Minimumdatasoet for opgørelse af ressourceforbrug.

The aim of the study was to develop a computer-based system for measuring workload in a department of histo- and cytopathology using routine registration of a minimum dataset. A group with representatives from the laboratory technicians, the pathologists and the secretaries defined 18 types of specimens. By studying each step of specimen processing it was shown, that 14 items for technical details could cover all the work done in the department. This information was collected in a computer-based system connected to the hospital network. The measurement of workload is essential for the efficient management of laboratory services. The registration of specimen types and a minimum dataset for specimen processing describes the work done in a department of histo- and cytopathology.

[A time study in a department of histopathology]. / Tidsstudie på patologisk anatomisk afdeling.

In the Department of Histo- and Cytopathology, Herlev University Hospital, Copenhagen, a time study was performed according to the principles known from work sampling. From 22.11-12.12.1993 laboratory technicians, pathologists and secretaries were interviewed and an activity form was filled in. Six thousand nine hundred and fifty interviews were performed and the time study showed that for all groups of personnel 40% of the time was used on specimens sent for microscopy, 5% on autopsies (excl. microscopy), 15% on teaching and research, 20% on scientific meetings, reading and administration and 20% on other activities e.g. lunch, holiday, absence owing to illness. There was little variation for the different groups of personnel. On the other hand the time used on specific laboratory procedures, e.g. serial cutting, special-, and immunostaining, varied considerably for laboratory technicians, pathologists and secretaries respectively. Time studies, especially "work sampling" yield important information for the planning of laboratory services and provide documentation also for the time not directly related to routine work.

Computer-assisted diagnosis in gastroenterology.

During the last 20 years, Danish gastroenterologists and biostatisticians have been involved in practical and theoretical research aimed at providing computer-assisted decision support in clinical practice. On the practical side, we summarize two clinical applications, one in the acute abdomen, the other in jaundice. The former project is part of a worldwide effort which appears able to reduce considerably the perforated appendix rate and the negative laparotomy rate. In the latter project, also entwined in international activities, three methods of early statistical discrimination of jaundice causes have been tested, and it has been shown how ultrasonographic data can be incorporated into the diagnostic assessment. On the theoretical side, a Dutch-Danish group has been looking into how one best designs a trial and analyses its data in the context of measuring the quality and impact of machine-made diagnostic advice. Having pointed out the international ramifications of these activities, we outline what may lie ahead: Gastroenterologists must be prepared to join large-scale field trials of clinical advice-giving software. In the future, however, such software will often become embedded in general hospital recordkeeping systems.