PHARMACOKINETICS OF ALFENTANIL DURING AND AFTER A FIXED RATE INFUSION

Twenty-nine patients (age range 14–81 yr) undergoing orthopaedicsurgery received alfentanil 100 µg kg^–1 given astwo i.v. boluses followed by a fixed rate infusion of 1 µgkg^–1 min^–1 for 44–445 min. Additional 1-mgbolus doses of alfentanil were administered as required. Plasmasamples were assayed for alfentanil using radio-immunoassay.Pharmacokinetic parameters were estimated by a model-independentapproach and by curve-fitting. Regression analysis showed nostatistical relationship between T, CI or Vd and the durationof the infusion, total dose or body weight. We found no significantcorrelation between age and T of alfentanil for patients youngerthan 40 yr. For patients older than 40 yr, T increased linearlywith age. There was no significant decrease in Cl with age,although the lower values for CI (100–200 ml min^–1)were generally found in subjects older than 60 yr. The presentstudy demonstrated that a 100-µg kg^–1 loading doseand a 1-µg kg^–1 min^–1 infusion may be appropriatefor analgesia in general surgical procedures.     

Epstein-Barr virus DNA in Reed-Sternberg cells of Hodgkin''s disease is frequently associated with CR2 (EBV receptor) expression

We studied 44 cases of Hodgkin's disease for the presence of Epstein-Barr virus (EBV) DNA, its localization and the expression of the EBV receptor on the tumour cells. EBV DNA was found in 52% (16/31) of the Hodgkin's lymphomas using the polymerase chain reaction. With a very sensitive non-radioactive DNA in situ hybridization technique in combination with immunohistochemistry for CD 30 or CD 15 antigens, EBV DNA was localized to Reed-Sternberg cells and its mononuclear variants. The relationship between the presence of EBV DNA and the expression of the EBV-receptor CR2 (CD 21) on Reed-Sternberg cells was studied using the same techniques and two different monoclonal anti-CD 21 antibodies. CR2 could be detected on a substantial number of the Reed-Sternberg cells in EBV DNA positive Hodgkin's lymphomas (9/12; 75%), whereas in EBV negative cases positivity with anti-CD 21 was rare (1/13; 8%). The results indicate that CR2 expression on Reed-Sternberg cells and the presence of EBV DNA sequences are frequently associated in Hodgkin's lymphomas.     

Seasonal covariation of the circadian phases of rectal temperature and slow wave sleep onset

There is a scarcity of well-controlled studies of the seasonal variation in circadian rhythmicity. In the present study, the circadian phase of rectal temperature and the onset of slow wave sleep were studied in a series of twelve 24-h experiments, one each month of the year, for six healthy subjects under controlled conditions in a climatic chamber. In winter, as compared with summer, the average circadian rhythm of rectal temperature was phase delayed by 45 min, and the average onset of slow wave sleep was phase delayed by 40 min. The temporal relationship between the circadian phase of rectal temperature and the timing of slow wave sleep was maintained throughout the year. Habitual rising and retiring times covaried as well. Furthermore, the circadian rhythm of rectal temperature followed the timing of the photoperiod across the year, but had a much smaller range of seasonal variation. Apparently, the seasonal variation in the photoperiodic zeitgeber is largely compensated for by the stabilizing influence of secondary zeitgebers. However, in healthy subjects some effect of photoperiodic variation can still be observed.     

Distribution of extracellular matrix components and their receptors in human lymphoid tissue and B-cell non-Hodgkin lymphomas

In this study the distribution patterns of various extracellular matrix components and their receptors (i.e. β1 integrins) in B-cell non-Hodgkin lymphomas were examined and compared to those in reactive lymphoid tissue. Neoplastic follicles within follicular lymphomas showed similar patterns to that observed in reactive follicles, which appeared to be strongly associated with the presence of follicular dendritic cells. Diffuse lymphomas of low and intermediate malignancy grade revealed features comparable to those of interfollicular areas of reactive lymphoid tissue, irrespective to which compartment the tumour cells were related. Highly malignant lymphomas, however, displayed unique extracellular matrix configurations, resulting from active matrix degradation by macrophages; this may support rapid tumour growth. Extranodal lymphomas showed virtually the same matrix patterns as their nodal counterparts, suggesting that (malignant) lymphoid cells generate (at least partly) their own specific microenvironment. In reactive lymphoid tissue β1 integrins were mainly found on resident cells and except for α4, α5 (and β1) the lymphoid cells expressed very little, if any, β1 integrins. In comparison, expression of these integrins on lymphoma cells was reduced (follicular lymphomas) or could not be detected at all (diffusely growing lymphomas); this might contribute to the growth pattern and metastatic properties of the tumours.     

Trypsin-mediated semisynthesis of salmon calcitonin

Salmon calcitonin, CT(1-32)·NH₂, was synthesised by the trypsin-mediated coupling of the peptide fragments CT(1-24) and CT(25-32)·NH₂, prepared by conventional Fmoc solid-phase chemistry. Optimal conditions regarding reaction time course, pH, proportion of catalyst, substrate concentration and composition of the reaction medium were determined from initial studies on the coupling of CT(1-11) to CT(12-24) and of CT(12-24) to CT(25-32)·NH₂. For the final successful semisynthesis, we found that it was unnecessary to protect lysine residues not involved in the coupling, and that secondary hydrolysis at these sites could be prevented by increasing the pH of the reaction medium. The reaction achieved equilibrium after 30-45 min, with overall conversion of around 30% of the initial amount of CT(1-24) substrate into product. Yields were depressed due to cyclisation of the CT(1-24) substrate via air-oxidation of the Cys¹ and Cys⁷ residues.     

Are infantile myofibromatosis,congenital fibrosarcoma and congenital haemangiopericytoma histogenetically related?

Infantile myofibromatosis, congenital fibrosarcoma and congenital/infantile haemangiopericytoma are generally considered distinct entities. Overlapping microscopic features between infantile myofibromatosis and congenital fibrosarcoma, and between infantile myofibromatosis and congenital/infantile haemangiopericytoma, however, have been noted, but not formally reported. This report concerns six neonatal tumours, each exhibiting more than one of the above patterns, supporting a histogenetic relationship among these entities. Immunohistochemistry for smooth muscle actin was found to be useful in the diagnosis of congenital/infantile haemangiopericytoma, and also served to support a histogenetic relationship with the other two entities under consideration.