Ontogeny and cellular expression of MHC and leucocyte antigens in human retina

We have investigated the ontogeny of MHC class I, class II, CD45, and macrophage antigens in wholemounts of normal human fetal retina at 10–25 weeks gestation (WG) using monoclonal antibodies and immunogold histochemistry. MHC class I antigens were expressed on retinal vascular endothelial cells and provided a useful marker of vessel organization from 14–25 WG. Microglial cells expressed immunoreactivity to MHC class I, class II, and CD45 antigens from 10 WG (pre-vascularization) and macrophage S22 (Mac S22) antigen from 14 WG (post-vascularization), although none of the antigens tested were detected on neuronal or macroglial elements. Microglia expressing MHC, CD45, and macrophage antigens occurred in both ramified and rounded forms with no close correlation being observed between morphology and antigenicity. The numbers of immunoreactive cells labeled with each of the four markers increased steadily throughout gestation in all specimens studied. Equivalent numbers of microglia expressed MHC class I, class II, and CD45 antigens in retinae at similar gestational ages; however, our data indicate that microglia expressing Mac S22 antigen comprise approximately 40% or less of the population of MHC and CD45-immunoreactive cells during development. Topographical analyses suggest that MHC class I, class II, and CD45-positive microglia enter the retina from both the peripheral retinal margin and the optic disc from at least 10 WG; Mac S22-positive cells appear in association with the development of the retinal vasculature and enter the retina via the optic disc after 14 WG. © 1995 Wiley-Liss, Inc.     

Do skin prick and conjunctival provocation tests predict symptom severity in seasonal allergic rhinoconjunctivitis?

BACKGROUND: In the investigation of seasonal allergic rhinoconjunctivitis (SAR), quantitative skin and conjunctival allergen challenge tests are used to measure individual allergen sensitivity. These tests are reproducible and relate well to prevalence but their relationship to symptom severity is less well established. OBJECTIVE: We wished to determine if quantitative skin prick tests (QSPT) and conjunctival provocation tests (CPTs) using a single grass pollen allergen extract are reproducible and predict symptom severity in SAR. METHODS: We retrospectively analysed data from 91 participants in a previously published randomized placebo controlled study of low dosage allergen immunotherapy who were randomized to receive placebo treatment. We examined the relationship between pre-seasonal QSPT, CPT and SAR symptoms. RESULTS: We found a high level of reproducibility when repeated measures were compared for both the QSPT (P < 0.001) and the CPT (P < 0.001) and moderate correlation (0.49) between the standard skin prick test (SPT) and the QSPT (P < 0.001). We found weak negative correlation (-0.27) between the QSPT and the CPT (P < 0.001). We found no correlation between seasonal symptom, use of rescue medication or quality of life (QOL) scores and pre-seasonal QSPT or CPT. Conclusion In the assessment of seasonal rhinoconjunctivitis, quantitative skin and conjunctival allergen challenge tests are strongly reproducible, although there is no correlation between these tests and seasonal symptom, use of rescue medication or QOL scores.     

Cervical Cancer with Paraaortic Metastases: Significance of Residual Paraaortic Disease after Surgical Staging

Cervical carcinoma frequently metastasizes to the paraaortic region, necessitating extended field radiotherapy to effect a cure. As imaging modalities are unreliable in identifying all cases of paraaortic nodal metastases (PAN), surgical staging is often utilized prior to radiotherapy. This study was aimed at identifying factors predictive of survival in women with cervical carcinoma and paraaortic metastases. In particular, survival based on extent of paraaortic disease was examined. The study group consisted of 43 women (stages IB–IVB) identified between 1982 and 1993 who were treated with extended field radiation for cervical carcinoma with histologically confirmed paraaortic metastases. The estimated 5-year survival for the study population was 24% with a median survival of 18 months. Pelvic tumor size had a significant impact on survival with the median survival being 34 months if the primary lesion was <6 cm compared to 14 months if ≥6 cm (P= 0.01). Eight of the 26 (31%) women without residual PAN disease after surgical staging remain alive and disease free (mean follow-up, 74 months). In contrast, only 1 of the 17 (6%) women with gross residual PAN is alive 71 months after treatment (P= 0.05). However, a comparison of Kaplan–Meier survival curves did not show a statistically significant advantage to the surgical excision of grossly involved PAN (P= 0.98). Although long-term survival among women with grossly involved, unresected paraaortic metastases is uncommon, further study is necessary to elucidate the role of surgical excision of bulky aortic disease in women with cervical cancer.     

The current status of thrombolytic therapy

Fibrinolytic therapy substantially reduces mortality from acute myocardial infarction. Patient selection is, however, important. The patient must present within 12 hours of the onset ofischaemic symptoms, have definite ECG changes of ST elevation or left bundle branch block and no contraindications. The major contraindications are those for risk of an intracerebral bleed, recent stroke, intracranial tumour or risk of a major systemic bleed. Age and hypertension are not contraindications but may modify the regimen used.
Heparin is required with recombinant tissue plasminogen activator but is optional with streptokinase.
The recent COBALT trial suggests that the accelerated weight related t-PA regimen given over 90 minutes is more satisfactory than double bolus t-PA. However, inpatients under 75 years of age, the two regimens were equivalent.
For patients suffering acute myocardial infarction, practitioners should now individualise choice of therapy, rather than give the same cocktail to all patients. The choice of regimen will depend on the cardiac risk, the stroke risk, the bleeding risk and the cost.     

Copper radionuclides and radiopharmaceuticals in nuclear medicine

The chemistry, radiochemistry, radiobiology, and radiopharmacology of radiopharmaceuticals containing copper radionuclides are reviewed. Copper radionuclides offer application in positron emission tomography, targeted radiotherapy, and single photon imaging. The chemistry of copper is relatively simple and well-suited to radiopharmaceutical application. Current radiopharmaceuticals include biomolecules labelled via bifunctional chelators primarily based on cyclic polyaminocarboxylates and polyamines, and pyruvaldehyde-bis(N⁴-methylthiosemicarbazone) (PTSM) and its analogues. The chemistry of copper, of which only a fraction has yet been exploited, is likely to be applied more fully in the future.     

Asbestos fiber type in malignant Mesothelioma: An analytical scanning electron microscopic study of 94 cases

Although the association between asbestos exposure and malignant mesothelioma is indisputable, controversy continues regarding the relative contribution of the various types of asbestos fibers to the development of mesothelioma. We examined the types of asbestos fibers recovered from lung parenchyma in more than 90 cases of malignant mesothelioma from the United States, using an analytical scanning electron microscope. Almost half of the patients were former asbestos insulators or shipyard workers. The fibers were recovered from lung tissues obtained at autopsy or surgical resection by means of a sodium hypochlorite digestion procedure. Amosite absestos was identified in 81% of the cases and accounted for 58% of all fibers 5 μm or greater in length. Tremolite/actinolite/anthophyllite were identified in 55% of the cases and accounted for 10% of all fiber types. Chrysotile was identified in 21% of the cases and accounted for 3% of fibers exceeding 5 μm in length. Crocidolite was found in 16% of the cases and accounted for 3% of fibers exceeding 5 μm in length. Nonasbestos mineral fibers (commonly found in the lungs of the general population) were observed in 71% of the cases and accounted for 25% of all fibers 5 μm or greater in length. The findings in this study are at odds with the assertion that crocidolite asbestos is responsible for most mesotheliomas in the United States. © 1993 Wiley-Liss, Inc.