Advances in the diagnosis of primary immunodeficiency disorders in childhood

Primary immunodeficiency disorders in childhood usually present as unusual, recurrent or severe infections, symptomatic infections with organisms of low pathogenicity, or as recognizable syndromes which are known to have associated immunological abnormalities. In many of the primary immunodeficiency disorders, there are known patterns of inheritance, and other family members may be affected. Some primary immunodeficiency disorders are relatively common, such as selective IgA deficiency, and often do not lead to major morbidity. Others, such as the severe combined immune deficiency syndromes, are relatively rare, and are fatal in early life if not recognized and treated early. Diagnosis of a primary immunodeficiency disorder depends on appropriate use of laboratory investigations. Often there will be abnormalities detected on a complete blood film and measurement of immunoglobulin isotypes. More complex investigations should be undertaken in conjunction with a paediatric immunology service. In recent years, many of the clinically defined primary immunodeficiency disorders have been shown to have associated specific gene defects. For some, this has led to the identification and characterization of defective or absent gene products. The consequences of this new knowledge are more accurate diagnosis, early diagnosis including antenatal diagnosis, detection of undiagnosed disease in other family members, and the potential for new therapies including gene or gene product therapy.

Primary Bartholin gland carcinoma: a report of seven cases

This study reviews our experience with 7 patients with primary Bartholin gland cancer (BGC) treated at the Queensland Gynaecological Cancer Centre (QCGC) and compares this with previously published data. A retrospective clinicopathologic review of all patients with primary BGC treated at QCGC from 1988 to 2000 was performed. Of the 7 patients treated, all underwent primary surgery and 5 of the 7 patients received radiotherapy postoperatively. All patients presented with a local swelling or a lump. Two had associated discharge and 2 had associated pain. Of the 7 patients, 2, 3 and 2 respectively were classified as having Stage IB, II or III disease. Five of the 7 patients had squamous cell carcinoma (SCC), one had adenoid-cystic carcinoma and 1 had a small-cell neuroendocrine cancer of the Bartholin gland. None of the patients with SCC developed recurrent disease. The patient with adenoid-cystic carcinoma experienced local recurrences at 4 years and again at 5 years and 3 months. Nine years after primary treatment she was diagnosed with pulmonary metastases. The patient with small-cell neuroendocrine cancer of the Bartholin gland was considered tumour-free after operation. Thorough imaging, including a CT scan of her chest, abdomen and pelvis showed no evidence of disease. She died 1 year and three months after diagnosis from disseminated pulmonary disease. We present the first report, of small cell neuroendocrine cancer of the Bartholin gland. Therapeutic principles in the management of vulval cancer at other sites appear to be appropriate for management of BGC.

Audit and comprehensive health assessment programme in the primary healthcare of adults with intellectual disability: a pilot study

International research has demonstrated significant shortcomings in the health of adults with intellectual disability (ID). Because general practitioners (GPs) are the main providers of primary healthcare for this population, strategies to improve general practice care are an important aspect of rectifying these shortcomings. The present pilot study aimed to determine the effect of various interventions on health maintenance activities and to assess their acceptability to GPs, with a view to informing larger scale studies. The GPs were recruited through an earlier questionnaire-based postal survey. The GPs identified all their adult patients with ID, then obtained consent for participation from three patients randomly selected by the investigators. The GPs completed two self-evaluation forms and case note audits 12 months apart, read a synopsis of the relevant literature provided by the researchers, and completed a comprehensive health assessment (CHA) of their three patients. Forty-five GPs agreed to participate in the CHA programme (CHAP), and 15 completed the project. Thirty-eight patients completed the project. The number of patient-GP dyads who completed the project was too small to demonstrate statistically significant changes in health issues over time. The GPs found that the synopsis of the literature was the best intervention for increasing knowledge and was also the most practical to use in general practice. The CHAP was the intervention that prompted the most action from the GP which would not have been undertaken otherwise. The CHAP appeared to provide a superior review process compared to the other interventions used in the present study. The numbers of health maintenance activities found to be overdue and the number of health issues detected as a result of the process were considerable. The CHAP served as a communication tool and an educative instrument, providing a basis for future studies and strategies to improve the general practice care of adults with ID.

Primary fallopian tube carcinoma: the Queensland experience

The purpose of this study was to review the experience with fallopian tube carcinoma in Queensland and to compare it with previously published data. Thirty-six patients with primary fallopian tube carcinoma treated at the Queensland Gynaecological Cancer Center from 1988 to 1999 were reviewed in a retrospective clinicopathologic study. All patients had primary surgery and 31/36 received chemotherapy postoperatively. Abnormal vaginal bleeding (15/36) and abdominal pain (14/36) were the most common presenting symptoms at the time of diagnosis. Median follow-up was 70.3 months and the median overall survival was 68.1 months. Surgical stage I disease (P = 0.02) and the absence of residual tumor after operation (P = 0.03) were the only factors associated with improved survival. Twenty of the 36 patients (55%) presented with stage I disease and survival was 62.7% at 5 years. No patient with postoperative residual tumor survived. The majority of the patients with fallopian tube carcinoma present with stage I disease at diagnosis, but their survival probability is low compared with that of other early stage gynecological malignancies. If primary surgical debulking cannot achieve macroscopic tumor clearence, the chance of survival is extremely low.

Primary to secondary LOTE articulation: A local case in Australia

In this study of articulation issues related to languages other than English (LOTE), "articulation" is defined and the challenges surrounding it are overviewed. Data taken from an independent school's admission documents over a 4-year period provide insights and reveal trends concerning students' preferences for language study, LOTE study continuity, and reasons for LOTE selection. The data also provides an accounting of some multiple LOTE learning experiences. The analysis indicates that many students who begin a LOTE in the early grades are thwarted in becoming proficient, because (1) continuation in the language is impossible due to unavailability of instruction; (2) expanded learning is hampered by teachers' inability to deal with a range of learners, (3) extended learning is hampered by administrative decisions or policies, or (4) students lose interest in the first LOTE and switch to another. Finally, a call is made for data gathering and research in local contexts to gain a better understanding of LOTE articulation challenges at the local, state, national, and international levels.

Nuclear PTEN expression and clinicopathologic features in a population-based series of primary cutaneous melanoma

Germline mutations of the PTEN tumor-suppressor gene, on 10q23, cause Cowden syndrome, an inherited hamartoma syndrome with a high risk of breast, thyroid and endometrial carcinomas and, some suggest, melanoma. To date, most studies which strongly implicate PTEN in the etiology of sporadic melanomas have depended on cell lines, short-term tumor cultures and noncultured metastatic melanomas. The only study which reports PTEN protein expression in melanoma focuses on cytoplasmic expression, mainly in metastatic samples. To determine how PTEN contributes to the etiology or the progression of primary cutaneous melanoma, we examined cytoplasmic and nuclear PTEN expression against clinical and pathologic features in a population-based sample of 150 individuals with incident primary cutaneous melanoma. Among 92 evaluable samples, 30 had no or decreased cytoplasmic PTEN protein expression and the remaining 62 had normal PTEN expression. In contrast, 84 tumors had no or decreased nuclear expression and 8 had normal nuclear PTEN expression. None of the clinical features studied, such as Clark's level and Breslow thickness or sun exposure, were associated with cytoplasmic PTEN expressional levels. An association with loss of nuclear PTEN expression was indicated for anatomical site (p = 0.06) and mitotic index (p = 0.02). There was also an association for melanomas to either not express nuclear PTEN or to express p53 alone, rather than both simultaneously (p = 0.02). In contrast with metastatic melanoma, where we have shown previously that almost two-thirds of tumors have some PTEN inactivation, only one-third of primary melanomas had PTEN silencing. This suggests that PTEN inactivation is a late event likely related to melanoma progression rather than initiation. Taken together with our previous observations in thyroid and islet cell tumors, our data suggest that nuclear-cytoplasmic partitioning of PTEN might also play a role in melanoma progression. (C) 2002 Wiley-Liss, Inc.

Cost of malaria control in China: Henan's consolidation programme from community and government perspectives

Objective To assist with strategic planning for the eradication,of malaria in Henan Province, China, which reached the consolidation phase of malaria control in 1992, when only 318 malaria cases were reported, Methods We conducted a prospective two-year study of the costs for Henan's malaria control programme. We used a cost model that could also be applied to other malaria programmes in-mainland China, and analysed the cost of the three components of Henan's malaria programme. suspected malaria case management,, vector surveillance,,and population blood surveys. Primary cost data were collected from the government, and data on suspected malaria patient's were collected in two malaria counties (population 2 093 100). We enlisted the help of 260 village doctors. in six-townships or former communities (population 247 762), and studied all 12 315 reported cases of suspected malaria in catchment areas in 1994 and 1995. Findings The average-annual government investment in malaria control was estimated to be US$ 111 516 (case-management 59%; active blood surveys 25%;vector surveillance 12%; and contingencies and special projects 4%). The average cost (direct and indirect) for-patients seeking-treatment for suspected malaria was US$ 3.48, equivalent,to 10 days' income for rural residents. Each suspected malaria case cost the government an, average of US$ 0.78. Conclusion Further cuts in government funding will increase future costs, when epidemic malaria returns; investment in malaria control should therefore continue at least at current levels,of US$ 0.03 per person a risk.

Nutritional strategies for the prevention of hypocalcaemia at calving for dairy cows in pasture-based systems

This review considers the current literature on the macro-mineral nutrition of the soon-to-calve, or transition, dairy cow. Calcium is the main focus, since milk fever (clinical hypocalcaemia) appears to be the most common mineral-related problem faced by the transition cow Australia-wide. The importance of minimising calcium intake and optimising the balance of the key dietary electrolytes, sodium, potassium, sulfate, and chloride, in the weeks before calving is highlighted. Excess dietary potassium can, in some situations, induce milk fever, perhaps even more effectively than excess calcium. Excess sodium remains under suspicion. In contrast, excess dietary chlorine and, to a lesser extent, sulfur can improve the ability of the cow to maintain calcium homeostasis. Diets that promote either a hypomagnesaemia or hyperphosphataemia have also the potential to precipitate milk fever at calving. Current prevention strategies focus on the use of forages with moderate to low levels of calcium, potassium, and sodium, and also rely on or utilise addition of chloride and sulfate in the form of 'anionic' feeds. Anionic salts are one example of an anionic feed. However, legitimate questions remain as to the effectiveness of anionic salts in pasture-feeding systems. The causes and prevention of milk fever are considered from the perspective of the variety of Australian feedbases. Impediments to the use of anionic feeds in Australia feeding systems are outlined. The potential for improving maternal reserves of calcium around calving to reduce the risk of milk fever is also discussed.

Expression of specific glycoconjugates in both primary and secondary olfactory pathways in BALB/C mice

Binding of cell surface carbohydrates to their receptors specifically promotes axon growth and synaptogenesis in select regions of the developing nervous system. In some cases these interactions depend upon cell-cell adhesion mediated by the same glycoconjugates present on the surface of apposing cells or their processes. We have previously shown that the plant lectin Dolichos biflorus agglutinin (DBA) binds to: a subpopulation of mouse primary olfactory neurons whose axons selectively fasciculate prior to terminating in the olfactory bulb. In the present study, we investigated whether these glycoconjugates were also expressed by postsynaptic olfactory neurons specifically within the olfactory pathway. We show here for the first time that DBA ligands were expressed both by a subset of primary olfactory neurons as well as by the postsynaptic mitral/tufted cells in BALB/C mice. These glycoconjugates were first detected on mitral/tufted cell axons during the early postnatal period, at a time when there is considerable synaptogenesis and synaptic remodelling in the primary olfactory cortex. This is one of the few examples of the selective expression of molecules in contiguous axon tracts in the mammalian nervous system. These results suggest that glycoconjugates recognized by DBA may have a specific role in the formation and maintenance of neural connections within a select functional pathway in the brain. J. Comp. Neurol. 443:213-225, 2002. (C) 2002 Wiley-Liss, Inc.

Axon navigation in the mammalian primary olfactory pathway: Where to next?

The process of establishing long-range neuronal connections can be divided into at least three discrete steps. First, axons need to be stimulated to grow and this growth must be towards appropriate targets. Second, after arriving at their target, axons need to be directed to their topographically appropriate position and in some cases, such as in cortical structures, they must grow radially to reach the correct laminar layer Third, axons then arborize and form synaptic connections with only a defined subpopulation of potential post-synaptic partners. Attempts to understand these mechanisms in the visual system have been ongoing since pioneer studies in the 1940s highlighted the specificity of neuronal connections in the retino-tectal pathway. These classical systems-based approaches culminated in the 1990s with the discovery that Eph-ephrin repulsive interactions were involved in topographical mapping. In marked contrast, it was the cloning of the odorant receptor family that quickly led to a better understanding of axon targeting in the olfactory system. The last 10 years have seen the olfactory pathway rise in prominence as a model system for axon guidance. Once considered to be experimentally intractable, it is now providing a wealth of information on all aspects of axon guidance and targeting with implications not only for our understanding of these mechanisms in the olfactory system but also in other regions of the nervous system.

Laminar disorganisation of mitral cells in the olfactory bulb does not affect topographic targeting of primary olfactory axons

Primary olfactory neurons expressing the same odorant receptor protein typically project to topographically fixed olfactory bulb sites. While cell adhesion molecules and odorant receptors have been implicated in guidance of primary olfactory axons. the postsynaptic mitral cells may also have a role in final target selection. We have examined the effect of disorganisation of the mitral cell soma layer in mutant mice heterozygous for the beta-subunit of platelet activating factor acetylhydrolase (Lis1(-/+)) on the targeting of primary olfactory axons. Lis1(-/+) mice display abnormal lamination of neurons in the olfactory bulb. Lis1(-/+) mice were crossed with the P2-IRES-tau:LacZ line of transgenic mice that selectively expresses beta-galactosidase in primary olfactory neurons expressing the P2 odorant receptor. LacZ histochemistry revealed blue-stained P2 axons that targeted topographically fixed glomeruli in these mice in a manner similar to that observed in the parent P2-IRES-tau:LacZ line. Thus, despite the aberrant organisation of postsynaptic mitral cells in Lis1(-/+) mice, primary olfactory axons continued to converge and form glomeruli at correct sites in the olfactory bulb. Next we examined whether challenging primary olfactory axons in adult Lis(-/+) mice with regeneration would affect their ability to converge and form glomeruli. Following partial chemical ablation of the olfactory neuroepithelium with dichlobenil, primary olfactory neurons die and are replaced by newly differentiating neurons that project axons to the olfactory bulb where they converge and form glomeruli. Despite the aberrant mitral cell layer in Lis(-/+) mice. primary olfactory axons continued to converge and form glomeruli during regeneration. Together these results demonstrate that the convergence of primary olfactory axons during development and regeneration is not affected by gross perturbations to the lamination of the mitral cell layer. Thus, these results support evidence from other studies indicating that mitral cells do not play a major role in the convergence and targeting of primary olfactory axons in the olfactory bulb. (C) 2002 Elsevier Science B.V. All rights reserved.