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Biomedical subjects

P K Anderson

Publications and source records attributed to P K Anderson.

15 recordsLinked to original sources

Cytokine mRNA profiles for isocyanates with known and unknown potential to induce respiratory sensitization.

Isocyanates are low-molecular-weight chemicals implicated in allergic asthmatic-type reactions. Identification of chemicals likely to cause asthma is difficult due to the lack of a validated test method. One hypothesis is that differential cytokine induction (Th1 versus Th2 profiles) in the draining lymph node following dermal application can be used to identify asthmagens and distinguish them from contact allergens. In this study, we compared the cytokine mRNA profiles of six chemicals: toluene diisocyanate (TDI), diphenylmethane-4,4'-diisocyanate (MDI), dicyclohexylmethane-4,4'-diisocyanate (HMDI), isophorone diisocyanate (IPDI), p-tolyl(mono)isocyanate (TMI), and meta-tetramethylene xylene diisocyanate (TMXDI). Whereas TDI and MDI are well-known respiratory sensitizers, documentation for HMDI, IPDI, TMI, and TMXDI is limited, but suggests that HMDI and IPDI may have respiratory sensitization potential in humans and TMI and TMXDI do not. Following dermal exposure of BALB/c mice, all six isocyanates induced cytokines characteristic of a Th2 response. Although LLNAs suggested that the doses chosen for the RPA were immunologically equivalent, the isocyanates tested differentiated into two groups, high responders and low responders. However, two of the low responders (TMI and TMXDI) were further tested and induced higher levels of Th2 cytokine message than dinitrochlorobenzene (not an asthmagen). Further study of these chemicals is needed to determine whether the Th2 cytokine responses observed for these low responders is predictive of asthmagenic potential or represents an insufficient signal.

Allergens↗

Identifying airway sensitizers: cytokine mRNA profiles induced by various anhydrides.

Exposure to low molecular weight (LMW) chemicals in the workplace has been linked to a variety of respiratory effects. Within the LMW chemicals, one of the major classes involved in these effects are the acid anhydrides. The immunological basis of respiratory hypersensitivity involves CD4+ cells. By virtue of their induction of cytokines typical of CD4+ T-helper type 2 (Th2) cells-interleukin (IL)-4, 10, and 13-respiratory sensitizers may be identified and differentiated from contact sensitizers which induce Th1 cytokines (IL-2 and IFN-gamma). Our previous work suggested that the ribonuclease protection assay (RPA) was useful in identifying the respiratory sensitizer, trimellitic anhydride (TMA), based on quantitative differences in Th2 cytokine mRNA as compared to the contact sensitizer dinitrochlorobenzene (DNCB). Therefore, the purpose of the studies described in this report was to expand the chemicals tested in the RPA. To this end, four acid anhydrides with known respiratory sensitization potential, TMA, maleic anhydride (MA), phthalic anhydride (PA) and hexahydrophthalic anhydride (HHPA), were tested. Although previously determined to induce immunologically equivalent responses in a local lymph node assay (LLNA), the initial dose chosen (2.5%) failed to induce Th2 cytokine mRNA expression. To determine if the lack of cytokine expression was related to dose, LLNAs were conducted at higher doses for each of the anhydrides. The highest doses evaluated (four- to six-fold higher than those used in the initial RPA) gave equivalent proliferative responses for the various anhydrides and were used for subsequent RPA testing. At these higher doses, significant increases in Th2 versus Th1 cytokine mRNA were observed for all anhydrides tested. These results suggest that the RPA has the potential to serve as a screen for the detection of LMW airway sensitizing chemicals. However, the basis for selecting immunologically equivalent doses may require some modification.

Anhydrides↗

The emergence and dissemination of whitefly-transmitted geminiviruses in Latin America.

The proliferation and rapid dissemination of whitefly-transmitted viruses of important food and industrial crops in Latin America, have been the consequence of drastic changes in traditional cropping systems. Some of the expanding non-traditional cash and export crops, such as soybean and several vegetables, have served as suitable reproductive hosts for the whitefly Bemisia tabaci. This insect pest has been shown to transmit at least 20 different geminiviruses that affect different commercial and basic food crops in Latin America. This review summarizes the existing knowledge on this important group of viruses and their vector in this region.

Animals↗

Radiofrequency energy delivery to the gastroesophageal junction for the treatment of GERD.

BACKGROUND: In this multi-center study, the feasibility, safety, and efficacy of radiofrequency (RF) energy delivery to the gastroesophageal junction (GEJ) for the treatment of gastroesophageal reflux disease (GERD) were investigated. METHODS: Forty-seven patients with classic symptoms of GERD (heartburn and/or regurgitation), a daily anti-secretory medication requirement, and at least partial symptom response to drugs were enrolled. All patients had pathologic esophageal acid exposure by 24-hour pH study, a 2 cm or smaller hiatal hernia, grade 2 or less esophagitis, and no significant dysmotility or dysphagia. RF energy was delivered with a catheter and thermocouple-controlled generator to create submucosal thermal lesions in the muscle of the GEJ. GERD symptoms and quality of life were assessed at 0, 1, 4, and 6 months with the short-form health survey (SF-36). Anti-secretory medications were withdrawn 7 days before each assessment of symptoms and pH/motility study. Medication use, endoscopic findings, esophageal acid exposure, and motility were assessed at 0 and 6 months. RESULTS: Thirty-two men and 15 women underwent treatment. At 6 months there were improvements in the median heartburn score (4 to 1, p < or = 0.0001), GERD score (26 to 7, p < or = 0.0001), satisfaction (1 to 4, p < or = 0.0001), mental SF-36 (46.2 to 55.5, p = 0.01), physical SF-36 (41.1 to 51.9, p < or = 0.0001), and esophageal acid exposure (11.7% to 4.8%, p < or = 0.0001). Esophagitis was present in 25 patients before treatment (15 grade 1 and 10 grade 2) and 8 had esophagitis at 6 months (4 grade 1 and 4 grade 2, p = 0.005). At 6 months, 87% no longer required proton pump inhibitor medication. There was no significant change in median lower esophageal sphincter pressure (14.0 to 12.0 mm Hg, p = 0.19), peristaltic amplitude (64 to 66 mm Hg, p = 0.71), or lower esophageal sphincter length (3.0 to 3.0, p = 0.28). There were 3 self-limited complications (fever for 24 hours, odynophagia lasting for 5 days, and a linear mucosal injury that was healed after 3 weeks). CONCLUSION: RF energy delivery significantly improved GERD symptoms, quality of life, and esophageal acid exposure while eliminating the need for anti-secretory medication in the majority of patients with a heterogeneous spectrum of clinical disease severity but with minimal active esophagitis or hiatal hernia.

Adult↗

The evolving role of community-based general paediatricians: the Barwon experience.

OBJECTIVE: To detail the acute and chronic paediatric service and community-orientated activities and responsibilities of community-based general paediatricians. METHODOLOGY: Data were collected over the 12 months July 1996 to June 1997 relevant to (i) acute neonatology and paediatrics, (ii) the different community paediatric service organizations with which the paediatricians were involved, and (iii) the quantification of the amount of time spent in non-consulting paediatric work. RESULTS: Findings revealed decreasing hospital admissions, infrequent severe neonatal resuscitation requirements, extensive involvement in community organizations and a great deal of time spent in non-consulting paediatric work. CONCLUSIONS: Ongoing training and upgrading in acute paediatric diagnostic and procedural skills, rationalization of resuscitation expertise, training in management and administrative skills and models of care for the chronically ill should become part of the training of community-based general paediatricians.

Acute Disease↗

A 12-month profile of community paediatric consultations in the Barwon region.

OBJECTIVE: To determine the profile of all consultations carried out in paediatricians offices in the Barwon region over a 12-month period. METHODOLOGY: The age, sex, category, diagnosis, and outcome of all non-hospital-based paediatric consultations carried out in the Barwon region were documented prospectively on a day by day basis. Relevant demographic data and information on Barwon children treated elsewhere were also collected. The frequency of different categories of illness, systems involved and groups of diagnoses was determined. RESULTS: A total of 14,711 consultations was carried out in the region with 10% of the childhood population having contact with the paediatricians during the year; 3135 new patients or problems were seen with 34.8% of all consultations involving behavioural problems and 76% of these relating to ADHD. The most frequent medical diagnostic group was CNS/disability being 16% of all consultations. At least 50% of the medical consultations involved chronic illness. CONCLUSIONS: Behavioural difficulty, chronic disability, and learning problems represent a significant part of the workload of community-based general paediatricians. Appropriate exposure during paediatric training should be given to these issues along with more sophisticated training in the medical, social and psychological complications of chronic illness and its effect on clients and families.

Adolescent↗

The bone-marrow infiltration pattern in B-cell chronic lymphocytic leukemia is not an important prognostic factor. Danish CLL Study Group.

In a multicentre study of 635 consecutive newly diagnosed patients with B-CLL, the histological bone marrow (BM) specimens were reviewed independently by each of 3 pathologists and found evaluable for BM infiltration pattern in 575 patients, 404 of whom had a CD5+, mainly FMC7-, faint surface-membrane immunoglobulin (SIg) fluorescence-intensity ppenotype. In these 404 patients the following BM infiltration patterns were found: mixed nodular-interstitial (30%), moderate interstitial (44%), heavy interstitial (20%) and diffuse packed (6%). In univariate survival analysis, significant differences were found according to BM pattern (p < 0.05), the presence of nodules being a favorable prognostic sign. In multivariate survival analysis in a model including age, clinical stage, BM pattern, BM lymphocytosis, WBC and sex, only age and stage but not BM pattern or BM lymphocytosis had independent prognostic significance. In stage A, progression-free survival was significantly longer in patients with nodular than in patients with non-nodular bone-marrow pattern. The overall survival of these patients, however, did not differ, possibly owing to the prompt and prolonged treatment given to most patients at the time of progression to stage B or C. We conclude that in CD5+, SIg(faint), mainly FMC7-B-CLL, bone-marrow histology may predict unstable disease in early clinical stage but is not important for treatment decisions, when these are based on clinical stage.

Age Factors↗

Smear misclassification in a cervical cancer screening programme.

A nested case-control study was undertaken in the Maribo County cohort of 27,811 women with negative Pap smears. Sixty women who later developed invasive cervical cancer constituted the cases, and five matched controls were selected from the cohort for each case. A total of 633 previous, negative smears for the cases and controls were reviewed independently by two pathologists. The review showed misclassification to be frequent in these smears collected in the period 1966-82. Thirty-five smears were considered positive at the review. The misclassification was differential in respect to the women's later disease status. The odds ratio for patients compared with controls for having at least one positive smear was 22.12 (95% CI 7.54-64.94). We were unable to identify specific characteristics of misclassified smears coming from later cases. Koilocytosis/dyskeratosis, herpes virus changed cells and hyperkeratosis were equally rare in smears from patients and controls. The Maribo County data indicate that the fraction of preventable cases of invasive cervical cancer in women aged 30-64 within the first 5 years after a negative smear could be increased from 62-72% to 83-86%, if misclassification of true positive smears could be eliminated. As a rough estimate, this would be at the cost of a 2% increase in the work load. It should be remembered that there is a large element of extrapolation in applying these results based on relatively poor quality specimens from 1966-82 as compared to a modern screening service.

Adenocarcinoma↗

Prolonged jaundice following ketoconazole-induced hepatic injury.

Two patients developed prolonged and progressive jaundice associated with ketoconazole-induced hepatic injury although the drug was discontinued before or shortly after the onset of symptoms of hepatic toxicity. One patient, who had been jaundiced for eight weeks and was not improving, showed prompt clinical improvement and progressive resolution of jaundice following therapy with prednisolone. Liver biopsy before therapy showed marked cholestasis in all acinar zones and moderately severe fibrosis in the space of Disse. The other patient, who was less severely jaundiced, showed spontaneous resolution although he remained jaundiced for 11 weeks. Liver biopsy performed three weeks after onset of symptoms showed a moderate degree of cholestasis in acinar zone 3 and collagen deposition about the terminal hepatic venules and within the space of Disse. These cases are reported because of the unique clinical course, documentation of the morphologic features, and experience with corticosteroid therapy.

Adult↗

Pesticide use, alternatives and workers' health in Cuba.

Cuba provides a unique example of a country that is actively implementing a program to reduce its dependence on pesticides. This paper addresses Cuba's current efforts to develop and implement alternatives to pesticides and legislation to limit exposure and protect workers in the interim. In 1980 Cuba embarked on a national program to utilize alternatives to chemical pest control. This three-part program includes expansion of knowledge of Cuban agro-ecology in order to implement cultural control practices; research and implementation on biological control of pests; and research on plant resistance and development of resistant crop varieties. To date, the program has enabled Cuba to reduce pesticide usage in sugar cane, citrus, tobacco, corn, and vegetable crops, among others. While alternatives to chemical pest control are being developed, the Cubans are paying special attention to regulating pesticide use and the safety of workers and members of the public exposed to toxic chemicals. In addition to the Resolution on Health and Safety (1967) and the Safety and Health Law (1978) which cover all workers, including Cuba's 250,000 agricultural workers, the Ministry of Public Health promulgated Resolution 335 in 1967. This resolution addresses requirements and administration of structural pest control, production, importation, transport and storage of pesticides, as well as requirements for worker contact with pesticides, pesticides for domestic use, aerial application of pesticides, and violations of the regulations. The paper concludes with a description of how the system works on the provincial level, as exemplified by Villa Clara, and the steps that have been taken to eliminate worker exposure to pesticides, to utilize pesticides which pose less of a hazard to workers, and to assure early detection of ill effects.

Agricultural Workers' Diseases↗