Gastro-intestinal stromal tumours (GISTs) - the Pretoria experience and a literature review.

AIM: To analyse the presentation and management of patients with gastrointestinal stromal tumours (GISTs) at Pretoria hospitals. DESIGN: A retrospective study was done in which all available clinical records of primary c-KIT positive GISTs were analysed. SETTING: Secondary and tertiary care institutions in Pretoria, including both private and public hospitals. Subjects. The population studied included all individuals treated at Pretoria hospitals from 17 July 2000 to 1 April 2009 who had a GIST confirmed with immunohistochemical c KIT staining. Patients with incomplete or inaccessible clinical records were excluded. Outcome measures. Patient demographics including gender, age and race; presenting symptoms and signs; results of special investigations; and treatment. RESULTS: Fifty-four cases were identified for inclusion in the study. The age of the subjects ranged from 15 to 83 years. The male-to-female ratio was 1.5:1. The organ most commonly affected was the stomach, and abdominal pain and weight loss were the most common presenting symptoms. Seventy-six per cent of the patients were treated surgically, and 24% received Imatinib. CONCLUSION: GISTs often present late with non-specific symptoms, and are frequently discovered incidentally. Large tumours tend to be malignant.

Personality and academic performance of three cohorts of veterinary students in South Africa.

To aid in selecting students for admission to undergraduate veterinary training, admissions procedures often take into account students' previous academic performance as well as the results of an interview. The study reported here investigated the relationship between personality and academic success. Students from three entry cohorts to the second year of study of a six-year BVSc program at the University of Pretoria completed the 16 Personality Factor Questionnaire. A meta-analytic approach was used to estimate the relationship between academic performance in two major final-year subjects and academic performance on entry, an interview score, and the personality factors. The study confirmed the value of previous academic performance and the interview in selecting students for the veterinary degree program. The findings also indicate that the inclusion of a measure of intellectual ability could be of value. The value of various personality characteristics in predicting good study habits and examination performance is highlighted by the study results: students were more successful if they were conscientious, emotionally stable, socially adept, self-disciplined, practical rather than imaginative, and relaxed rather than anxious. It appears worthwhile to consider including an appropriate personality questionnaire in the selection process to improve the accuracy of predictions of students' success. A sound personality make-up will not only increase the likelihood of academic success but should also be beneficial in the successful management of a veterinary practice and in enjoying veterinary science as a career.

Alkaline phosphatase isozymes in human testicular germ cell tumors, their precancerous stage, and three related cell lines.

The four known isozymes of the human alkaline phosphatase (ALP) were detected by isoelectric focusing in extracts of various types of germ cell tumors, three related cell lines, and their precancerous elements (atypical germ cells). In seminoma, placental alkaline phosphatase (PLAP) and germ cell alkaline phosphatase (PLAP-like) could be separated by isoelectric focusing following isolation by immunoaffinity. The occurrence of both isozymes in seminoma could explain partial heat sensitivity and variation in electrophoretic patterns of the seminoma isozyme frequently observed upon starch gels, in comparison to the normal placental phenotype. The four ALP isozymes are produced not only in germ cell tumors, but already in precancerous tissues. Quantitative analysis showed that the amount of the four isozymes varies in parallel in the tumors tested. Maximal expression was found in seminoma. The relation between ALP gene overexpression and gene amplification by polyploidy of chromosomes 1 and 2 in these lesions is discussed. On the other hand, the ectopic expression of intestinal alkaline phosphatase and PLAP associated with overexpression of PLAP-like in tumor cells as well as in their precancerous stage indicates gene activation by some unknown mechanisms, probably a regulatory process affecting the three tissue-specific ALP genes simultaneously.

Primary ciliary dyskinesia: a genome-wide linkage analysis reveals extensive locus heterogeneity.

Primary ciliary dyskinesia (PCD), or immotile cilia syndrome (ICS), is an autosomal recessive disorder affecting ciliary movement with an incidence of 1 in 20000-30000. Dysmotility to complete immotility of cilia results in a multisystem disease of variable severity with recurrent respiratory tract infections leading to bronchiectasis and male subfertility. Ultrastructural defects are present in ciliated mucosa and spermatozoa. Situs inversus (SI) is found in about half of the patients (Kartagener syndrome). We have collected samples from 61 European and North American families with PCD. A genome-wide linkage search was performed in 31 multiplex families (169 individuals including 70 affecteds) using 188 evenly spaced (19cM average interval) polymorphic markers. Both parametric (recessive model) and non-parametric (identity by descent allele sharing) linkage analyses were used. No major locus for the majority of the families was identified, although the sample was powerful enough to detect linkage if 40% of the families were linked to one locus. These results strongly suggest extensive locus heterogeneity. Potential genomic regions harbouring PCD loci were localised on chromosomes 3p, 4q, 5p, 7p, 8q, 10p, 11q, 13q, 15q, 16p, 17q and 19q. Linkage analysis using PCD families with a dynein arm deficiency provided 'suggestive' evidence for linkage to chromosomal regions 8q, 16pter, while analyses using only PCD families with situs inversus resulted in 'suggestive' scores for chromosomes 8q, and 19q.

Loss of heterozygosity on chromosome 16q, expression of her2/neu and p53 mutations in endometrial cancer.

We analyzed endometrial adenocarcinomas for mutations of the p53 anti-oncogene, expression of the HER2/neu oncogene and for loss of heterozygosity on chromosome 16q. p53 mutations were found in 3 of 25 tumors. Elevated expression of HER2/neu found in 7 of 24 tumors involves a mechanism other than gene amplification. LOH on chromosome 16q22-24 was observed in 4 of 13 informative tumors. Four of 25 endometrial tumors exhibited two or more alterations. Tumors with the highest HER2/neu protein level exhibited a negative progesterone receptor status. Accumulation of these changes may determine the biological behaviour of a subset of endometrial tumors.

Differentiation potential of ovarian dysgerminoma: an immunohistochemical study of 15 cases.

An immunohistochemical study of 15 ovarian formalin-fixed, paraffin-embedded dysgerminomas showed positive staining of tumor cells for vimentin in all cases. Ten dysgerminomas stained for cytokeratin 18. Desmin positivity of single tumor cells was detected in four dysgerminomas. Glial fibrillary acidic protein was present in two tumors. Prominent human beta chorionic gonadotropin staining was seen in one tumor. S-100 protein was found in two and carcinoembryonic antigen in one of the dysgerminomas. Placental alkaline phosphatase was present in 12 of the 15 tumors studied. The heterogeneity of the cytoskeletal profile and of other markers showed some similarities to our previously published results on testicular seminomas. Thus, in contrast to previous concepts, dysgerminoma, as is the case with its testicular counterpart the seminoma, appears to be capable of further differentiation, albeit at a primitive level. Our observations also may help to elucidate the relationship between dysgerminoma and other nondysgerminomatous ovarian germ cell tumors, and may be of help in the differential diagnosis with poorly differentiated carcinoma, ovarian lymphoma, or other germ cell tumors.

PEG-m-THPC-mediated photodynamic effects on normal rat tissues.

Photodynamic therapy (PDT) of malignancies uses light to activate a photosensitizer preferentially accumulated in cancer cells. The first pegylated photosensitizer, tetrakis-(m-methoxypolyethylene glycol) derivative of 7,8-dihydro-5,10,15,20-tetrakis(3-hydroxyphenyl)-21-23-[H]-porphyrin (PEG-m-THPC), was evaluated in non-tumor-bearing rats. The aim of this study was to assess the photodynamic threshold for damage and its sequelae in normal rat tissue. Thirty-five Fischer rats were sensitized with 3, 9 or 30 mg/kg body weight PEG-m-THPC. Colon, vagina and perineum were irradiated with laser light of 652 nm wavelength and an optical dose of 50, 150 or 450 J/cm fiber length. Temperature in the pelvis was measured during PDT. Three days following PDT the effect on skin, vagina, colon, striated muscle, connective tissue, nerves and blood vessels was assessed by histology. The healing of the above-mentioned tissues was assessed on two rats 3 and 8 weeks after PDT using 9 mg/kg PEG-m-THPC activated with 450 J/cm laser light. No dark toxicity was observed. PDT using 30 mg/kg PEG-m-THPC induced severe necrosis irrespective of the optical dose. Body weight of 9 or 3 mg/kg activated with less than 450 J/cm induced moderate or no damage. No substantial increase in body temperature was seen during PDT. Tissues with severe PDT-induced damage seem to have a good tendency to regenerate. We conclude that within the dose required for tumor treatment PEG-m-THPC is a safe photosensitizer with promising properties. PDT of the colon mucosa below 9 mg/kg PEG-m-THPC and 150 J/cm seems to be safe. All other tissues can be exposed to 9 mg/kg PEG-m-THPC activated with less than 450 J/cm laser light with little side effects.

m-THPC-mediated photodynamic therapy (PDT) does not induce resistance to chemotherapy, radiotherapy or PDT on human breast cancer cells in vitro.

Photodynamic therapy (PDT) uses laser light to activate a photosensitizer that has been absorbed preferentially by cancer cells after systemic administration. A phototoxic reaction ensues resulting in cell death and tissue necrosis. Some cells, however, may survive PDT. This study was performed to determine if surviving human breast cancer cells (MCF-7) can become resistant to PDT, chemotherapy or radiotherapy. The MCF-7 cells were cultured under standard conditions prior to being exposed to the photosensitizer, 5,10,15,20-meta-tetra(hydroxyphenyl)chlorin (m-THPC), for 24 h and then irradiated with laser light (652 nm). Surviving cells were allowed to regrow by allowing a 2 week interval between each additional PDT. After the third and final treatment, colony formation assays were used to evaluate the sensitivity of cultured cells to ionizing radiation and PDT and the ATP cell viability assay tested in vitro chemosensitivity. Flow cytometry was used to analyze the cell cycle. No alterations in the cell cycle were observed after three cycles of PDT with m-THPC. Similar responses to chemotherapy and ionizing radiation were seen in control and treatment groups. The m-THPC-sensitized PDT did not induce resistance to subsequent cycles of PDT, chemo- or radiotherapy. Photodynamic therapy with m-THPC may represent a novel adjunctive treatment of breast cancer that may be combined with surgery, chemotherapy or ionizing radiation.

Hypercalcemic-type of small cell carcinoma of the ovary: characterization of a new tumor line.

BACKGROUND: The aim of this study was to develop and characterize a mouse xenograft model for the hypercalcemic-type of small cell carcinoma of the ovary (HTSCCO). PATIENTS AND METHODS: Tumor fragments were removed from a patient and cultured in six subsequent generations of nude mice. Histology, comparative genomic hybridization (CGH), electron microscopy and serum calcium levels were investigated. RESULTS: Morphology remained the same from the primary tumor of the patient through the 6th passage in the mouse. Serum calcium levels were significantly higher in the tumor-bearing mice compared to controls. CGH of the HTSCCO did not show evidence of a close relationship to either a germ cell tumor or an epithelial ovarian cancer. CONCLUSION: Some evidence was provided that the HTSCCO is an inhomogeneous tumor that is neither related to a germ cell tumor nor to an epithelial ovarian cancer, but is a distinct tumor entity.

How do health service managers respond to qualitative research?

During 1992 a qualitative evaluation of a government health service-run community health worker (CHW) project in South Africa found that project workers were doing good work despite serious structural shortcomings related to lack of community participation and inadequate integration of the project in the health district system. Recommendations were made to develop the project in order to enhance community involvement, to build closer integration between the project and the services offered at the health centre, and to collaborate with non-government CHW projects in neighbouring areas. The evaluation study was followed up one year later by interviews with health managers to determine their response to the evaluation. The managers reported that they had found the qualitative data valuable for understanding how clients perceived the health service, and for planning a more community-responsive service. Despite this, the recommendations from the evaluation were not implemented and political developments in the district resulted in the CHW project being closed down. It is concluded that qualitative evaluators need to carefully explore the political context of primary health care interventions in order that their research provides useful data for decision-making.

Effects of tracheostomy on human tracheobronchial mucosa: a scanning electron microscopic study.

The protective functions missing in the upper airways of tracheostomy patients lead to functional and morphological changes in the lower respiratory tract. To obtain detailed data from the surface of the tracheobronchial mucosa, a scanning electron microscopic study was performed. Mucosal biopsies were taken from different sites of the tracheobronchial tree in 5 healthy control subjects, 5 patients with tracheostomy after laryngectomy, and 5 tracheostomy patients not affected by a history of smoking. Following scanning electron microscopic examination, the specimens were evaluated morphometrically. The percentage ciliary border and the individual mucosal surface changes depended on the biopsy site and the degree of previous damage. Individual structural alterations consisted of squamous metaplasia, giant cilia, compound cilia, and microplicae. Giant cilia represented an impressive form of differentiation in chronic bronchitis recognizable by scanning electron microscopy.

Correlative histological and ultrastructural study of unusual changes in human tracheobronchial epithelium.

In tracheostomy patients with chronic bronchitis, scanning electron microscopy reveals detailed surface changes in the tracheobronchial mucosa. The principle of intermicroscopic correlation, i.e., the sequential examination of a specimen by different microscopic procedures, is illustrated with giant cilia. After re-embedding the scanning electron microscopic specimens and precisely locating a ciliary convolution by light microscopy in semithin section, the giant cilia were studied in ultrathin sections by transmission electron microscopy. The cilia were shown to be at least 9 microns long (normal ciliary length = 4-6 microns). Central and peripheral microtubular axonemal structures with a 9 + 2 arrangement were clearly shown in both longitudinal and cross section. Giant cilia, thus, most closely resemble outgrowths of normal cilia. If they are motile at all, they seem unlikely to effect a transport function coordinated in direction and time.

Enhanced photodynamic effects using fractionated laser light.

Photodynamic eradication of tumour cells depends on the presence of a photosensitizer and light delivery to the cells. The present study investigated the influence of fractionated light (on-off mode) on cell killing as documented by a colony-forming assay. Photosensitizers were m-THPC (ethanol soluble, Foscan) and m-THPC-MD (water soluble, both from Scotia Pharmaceuticals, Guildford, UK). Fractionated laser light at a wavelength of 652 nm with a light duration of 0.05 s was more effective than continuous illumination at the same power density for both photosensitizers. We propose that fractionated laser light is more toxic due to short phases of recovery during the dark intervals, probably resulting in more singlet oxygen under these conditions. By use of Foscan, for example, and fractionated laser light, a similar effect is expected for the treatment of solid tumours. In this case we expect improvements in photodynamic therapy (PDT) for patients by lowering the concentrations of photosensitizer and/or by reducing the applied light dose.

Primary ciliary dyskinesia with situs inversus totalis, hydrocephalus internus and cardiac malformations in a dog.

A nine-month-old golden retriever bitch was presented with exercise intolerance and recurrent nasal discharge. Based on clinical, radiographic and ultrasonographic examination, a diagnosis of rhinitis, situs inversus totalis and tricuspid valve insufficiency was established. The results of video- and electron microscopy studies of the respiratory epithelium were compatible with primary ciliary dyskinesia (PCD). However, no evidence of a primary ultrastructural defect of the cilia was found. The dog was euthanased because of the poor prognosis. At necropsy, a hydrocephalus internus and a subaortic stenosis were additionally diagnosed. PCD, in combination with situs inversus, has been previously reported in golden retrievers, but without a concomitant hydrocephalus internus. Furthermore, concomitant occurrence of internal cardiac malformation and PCD has not previously been reported in the dog.