Plasmacytic cutaneous pathology: A review

We review the spectrum of cutaneous disorders associated with inflammatory and neoplastic plasmacytic pathology. Because plasma cells are derived from B‐lymphocytes our overview includes discussion of certain lymphoplasmacytic proliferations. It is structured along histopathological lines, addressing conditions characterized by (a) cutaneous plasma cell infiltrates, (b) deposits of plasma cell products or their derivatives in the skin and (c) miscellaneous, poorly understood cutaneous complications of plasmacytic disorders. Lesions arising primarily in the skin and those due to cutaneous involvement by multisystem disorders are addressed. The range includes a spectrum of tumefactive and circulatory manifestations. We highlight key clinical and pathological features of the different conditions and outline recent advances in our understanding of these entities. By emphasizing the dermatopathological characteristics of this spectrum of disorders we hope to hone the diagnostic accuracy of practitioners in the field.     

Follow up study of children born elsewhere but attending schools in Seascale, West Cumbria (schools cohort)

Records on 1546 children who were identified as having attended schools in Seascale up to November 1984 and were born since 1950 but not in the civil parish were studied. These children lived in or near Seascale for a period of time while they were attending one or more of three local schools and are an additional group to the 1068 children who were identified as born to mothers resident in Seascale in an accompanying study. Even though some of the schoolchildren apparently remained in the village for a short period only all but 7% were followed up through the National Health Service Central Register. Mortality among these children to 30 June 1986 is comparable to that expected at national rates. From all causes there were 10 observed deaths compared with 12.69 expected--a ratio of 0.79 (95% confidence interval 0.38 to 1.45)--and from cancer one observed death compared with 2.04 expected--a ratio of 0.49 (95% CI 0.01 to 2.73). No deaths from leukaemia or lymphoma were reported, but only 0.83 was expected. Since 1971 (the year when cases of cancer were first notified to the NHS Central Register) three non-fatal cases of cancer were reported, including two lymphomas, compared with 2.04 expected and two cases of carcinoma in situ of the cervix compared with 1.79 expected. In addition, there was a case of leukaemia among the schoolchildren which was known previously and had been diagnosed in 1968. There is an interesting difference between the results of this study and the results of the study of children born to mothers who were resident in Seascale. In the latter study there was an excess of leukaemia and of other cancers, but a similar finding is not apparent among children who spent some time at schools in Seascale but were born elsewhere. This raises the question of whether one or more aetiological factors in childhood cancer were acting on a locality specific basis before birth or early in life. This cannot be answered from these cohort studies, but it is hoped that the case-control study that is under way in West Cumbria will provide relevant information.     

Association Between Outpatient Follow-Up and Pediatric Emergency Department Asthma Visits

Background. The National Heart, Lung, and Blood Institute (NHLBI) guidelines recommend that patients receive a follow-up outpatient asthma visit after being discharged from an emergency department (ED) for asthma. Objective. To measure the frequency of follow-up outpatient asthma visits and its association with repeat ED asthma visit. Design. We conducted a retrospective cohort study of children with asthma using claims data from a university-based managed care organization from 01 1998 to 10 2000. We performed a multivariate survival analysis using Cox proportional hazards model to determine the effect of follow-up outpatient asthma visits on the likelihood of a repeat ED asthma visit, after controlling for severity of illness, patient age, gender, insurance, and the specialty of the primary care provider. Results: A total of 561 children had 780 ED asthma visits. Of these, 103 (17%) had a repeat ED asthma visit within 1 year. Almost two-thirds of children (66%) did not receive outpatient follow-up for asthma within 30 days of an ED asthma visit. Outpatient asthma visits within 30 days of an ED asthma visit are associated with an increased likelihood (relative risk = 1.80; 95% confidence interval 1.19, 2.72) for repeat ED asthma visits within 1 year. Conclusions. Most patients do not have outpatient follow-up after an ED asthma visit. However, those patients that present for outpatient follow-up have an increased likelihood for repeat ED asthma visits. For the primary care provider, these outpatient follow-up visits signal an increased risk that a patient will return to the ED for asthma and are a key opportunity to prevent future ED asthma visits.     

Alterations in glutathione and glutathione-related enzymes in a multidrug-resistant small cell lung cancer cell line

H69AR is a multidrug-resistant small cell lung cancer cell line derived from a drug-sensitive cell line, H69, by selection in doxorubicin. It is cross-resistant to a wide variety of natural product-type antineoplastic agents but does not overexpress P-glycoprotein. In the present study, the levels of GSH and GSH-related enzymes in the H69AR cell line were determined and compared with those found in H69 cells. Unlike other drug-resistant cell lines, GSH levels were diminished 6-fold in H69AR cells (0.67 +/- 0.28 microgram/mg of protein), compared with H69 cells (4.23 +/- 1.17 micrograms/mg of protein) (p less than 0.01). This unusually low level of GSH may explain the pronounced collateral sensitivity of H69AR cells to buthionine sulfoximine (BSO), an inhibitor of the rate-limiting enzyme in GSH biosynthesis (ID50 of 4.4 microM BSO for H69AR cells versus ID50 of 300 microM BSO for H69 cells). BSO did not enhance doxorubicin cytotoxicity in the H69AR cell line, despite further depletion of GSH. GSH-reductase (EC 1.6.4.2) activity was elevated 2-fold in H69AR cells, compared with sensitive H69 cells (75.34 +/- 14.94 versus 38.62 +/- 5.06 nmol of NADPH/min/mg of protein) (p less than 0.05). Both selenium-dependent and -independent GSH-peroxidase (EC 1.11.1.9) activities were unchanged in the resistant H69AR cell line, compared with its parent cell line. gamma-Glutamyl transpeptidase (EC 2.3.2.2) activity was 5-fold elevated in H69AR cells, compared with H69 cells (2.50 +/- 0.44 versus 0.46 +/- 0.21 nmol of p-nitroaniline/min/mg of protein) (p less than 0.01), whereas GSH-S-transferase (EC 2.5.1.18) activity was 10-fold higher (201.98 +/- 43.62 versus 19.77 +/- 1.72 nmol of 1-chloro-2,4-dinitrobenzene/min/mg of protein in H69AR and H69 cells, respectively) (p less than 0.01). The GSH-S-transferases from both cell lines were purified by affinity chromatography and immunoblot analysis identified the GSH-S-transferases as belonging to the anionic pi class. GSH-S-transferases from the mu or alpha classes were not detectable in either cell line. In conclusion, marked differences in GSH levels and the activities of three of four GSH-related enzymes were observed between the multidrug-resistant H69AR cell line and its parent cell line. Further study is required to determine whether these changes are causally related to the development of drug resistance in this model system.     

Modifications of the hydrophilicity of heterocyclic methacrylate copolymers for protein release

A series of copolymers comprising ethyl methacrylate (EM) and tetrahydrofurfuryl methacrylate (THFMA) gelled with either THFMA monomer or hydroxyethyl methacrylate (HEMA) monomer have been developed. In this paper, we examine the water uptake characteristics of the polymer systems and address the possibility of increasing the hydrophilicity of the systems by changing the ratios of the copolymers. We have investigated whether protein release from the polymers is related to the composition of the polymer systems. More protein was released from the polymers gelled with the more hydrophilic monomer (HEMA) than with THFMA. This was consistent with the calculated diffusion coefficients, which were 10 times greater for the polymers gelled with HEMA than those gelled with THFMA. Interestingly, the water uptake and protein release profiles were not dependent on the ratio of EM and THFMA in the copolymers. This is probably due to the conflicting roles of THFMA in the copolymer; it is both the more hydrophilic component as well as a cross-linking agent. In addition, it would appear that the structural and surface topography of these polymers had more significant effects on protein release than copolymer composition.     

Planning and spatial working memory in Parkinson''s disease.

The higher level cognitive function of planning was studied in a group of medicated Parkinson's disease patients and a group of matched control subjects, using a computerised version of Shallice's Tower of London task. Baseline measurement of the ability to execute a given plan of action, to generate low level strategies required for efficient searching, and spatial working memory capacity, all of which contribute to performance on the planning task, established that the Parkinson's disease group was unimpaired on any of these measures. On the Tower of London task, the Parkinson's disease group was also unimpaired in terms of the average number of moves required to solve a problem. However, a specific planning deficit was evident when "thinking" times were analysed, and this was after the confounding influence of motor initiation and execution times had been carefully extracted from total performance times. This finding is discussed in relation to putative functions of the frontal lobes and basal ganglia, and an attention-switching hypothesis is developed to account for it.