T cell subsets mediating rejection of established fetal pancreas grafts and failure to observe graft adaptation

The present study has attempted to elucidate the cellular mechanisms by which long-term established fetal pancreas allografts are rejected. We used an experimental model in which H-2b nude mice were made hyperglycemic by streptozotocin treatment and then engrafted with allogeneic fetal pancreas grafts. These grafts were functional in that engrafted animals returned to near normoglycemia while all animals left unengrafted subsequently died. The fetal pancreas grafts were allowed to reside in the immunoincompetent nude host for 6-9 months prior to T cell reconstitution, at which time animals were reconstituted with either negatively selected CD4+ or CD8+ H-2b T cell subpopulations. We found that a 6-9 month residence in an immunoincompetent host did not lead to a change in the immunogenicity of fetal pancreatic grafts in that both CD4+ and CD8+ T cell subsets were capable of rejecting these long-term established fetal pancreas grafts. The finding that isolated CD8+ spleen T cell subpopulations, which are only activated by antigen-presenting cells of donor origin bearing MHC class I alloantigen, were capable of effecting graft rejection suggested that APC of donor origin persisted in these long-term fetal pancreas allografts.     

Cemented and ingrowth fixation of the Miller-Galante prosthesis. Clinical and roentgenographic comparison after three- to six-year follow-up studies

One hundred thirty-nine cemented and 132 cementless Miller-Galante total knee prostheses were followed between three and six years (average, 43-44 months). The fixation technique was based on patient age, bone quality, and ability to delay full-weight bearing. Clinical follow-up studies were possible on 116 cemented knees. Fifteen knees were lost because of death before the three-year follow-up study, and eight knees required component removal. One hundred twenty-three cementless knees were available for clinical follow-up studies; there were three deaths, and six failures required component removal. No cemented failure was due to fixation, and three cementless failures were due to lack of tibial ingrowth in two and pain of undetermined etiology in one. Preoperative knee scores were slightly significant with cemented knees averaging 48 points and cementless knees averaging 52 points. A similar significant difference was maintained at the final follow-up study. No significant differences were noted for pain, limp, or support scores. Average range of motion was similar in the two groups. Radiolucent lines about the femoral component were rare. Cementless tibial radiolucencies were partial in up to 20% of examined zones, and complete tibial tray radiolucency was seen in only three patients. No correlation between radiolucency and knee scores was seen.     

Comparison of the blood-brain barrier and liver penetration of acridine antitumor drugs

Summary The blood-brain barrier penetration of amsacrine and its analogs 9-({2-methoxy-4-[(methylsulfonyl)-amino]phenyl}amino)-,5-dimethyl-4-acridine carboxamide (CI-921) and M-[2-(dimethylamino)ethyl]-acridine-4-carboxamide (AC) was measured in the barbiturate-anesthetized mouse. After intracarotid administration, AC was almost completery extracted (90%) in a single transit through the brain capillaries, whereas CI-921 (20%) and amsacrine (15%) were moderately extracted. AC is retained in the brain; no loss of AC from the brain was apparent at 1, 2, 4, or 8 min after injection. In contrast, after intraportal administration, 75% of the AC, 94% of the CI-921, and 57% of the amsacrine was extracted in a single transit through the hepatic vasculature. Rather than being retained in the mouse liver, these acridine antitumor agents show time-dependent loss (t _1/2=10 min for amsacrine and AC, 24 min for CI-921). We conclude that unlike most antitumor agents, these acridine drugs appear to penetrate the blood-brain barrier readily.This study was supported by the Auckland Medical Research Foundation (New Zealand), by the Medical Research Foundation (New Zealand), by the National Science Foundation (United States/New Zealand Cooperative Science Program), by the United States Veterans Administration, and by NIH grant NS 25554     

Lipoid Proteinosis: Case Report

A 20-month-old Kuwaiti girl had manifestations of lipoid proteinosis, a rare autosomal recessive disorder seen more commonly in Caucasians. This condition is diagnosed based on clinical, histopathologic, and ultrastructural criteria. Its biochemical and genetic aspects are still poorly understood.     

Botrocetin agglutination of rat megakaryocytes: a rapid method for megakaryocyte isolation.

Botrocetin isolated from the venom of Bothrops jaracara has been shown by others to induce binding of von Willebrand Factor to glycoprotein Ib and thereby produce platelet agglutination in a wide range of animal species. We have found that botrocetin also facilitates the agglutination of megakaryocytes and have used this property to develop a method to isolate megakaryocytes from rat bone marrow. When botrocetin is added to a mixture of rat bone marrow, rat platelets, and rat plasma, coagglutination of megakaryocytes and platelets occurs. The agglutinated complexes, containing > 95% of the megakaryocytes, may then be separated from the remaining marrow cells by filtration. Megakaryocytes account for 39% (range 30%-48%) of the isolated cells and 83% (range 77%-88%) of the isolated cell mass. This method allows the virtually complete removal of megakaryocytes from bone marrow as well as their isolation to a high degree of purity. It should provide a useful, inexpensive, general method for the rapid isolation of megakaryocytes from multiple, small marrow samples from a wide range of species.     

Knee-chest vs horizontal side position during induction of spinal anaesthesia in patients undergoing lumbar disc surgery

In the prone knee-chest position the spread of plain 0.5% bupivacaine in the cerebrospinal fluid and associated haemodynamic changes may be different compared with the horizontal position. A randomized comparison was performed in 40 ASA I-II patients, aged 24-61 yr, undergoing lumbar disc surgery. Subarachnoid injection (27-gauge needle) at the L2-3 interspace with 3 ml of 0.5% bupivacaine was performed with the patient in the operative knee-chest position (prone knee-chest group, n = 20) or in the horizontal side position (supine side horizontal group, n = 20). Patients in the supine side horizontal group were turned into the horizontal supine position for 20 min, and subsequently they were placed in the operative knee-chest position. In three patients in the prone knee-chest group, the spinal needle was replaced by a larger needle (25-gauge). The final cephalad extension of sensory analgesia on skin tested by pinprick was T5 (median) in the prone knee-chest group and T6 in the supine side horizontal group. Recovery was also similar, on average 210 min from injection in both groups. The mean decrease in systolic arterial pressure was somewhat greater in the prone knee-chest group (30 mm Hg) than in the supine side horizontal group (13 mm Hg). The need for ephedrine occurred earlier in the supine side horizontal group (three patients, all within 10 min from local anaesthetic injection) than in the prone knee-chest group (six patients, all after 15 min). Four of the latter patients also required administration of an anticholinergic for bradycardia compared with two patients in the supine side horizontal group. Light sedation was given to five patients in the prone knee-chest group and to four in the supine side horizontal group because of numbness and aching in the shoulders. We conclude that spinal block was similar in the two groups but there was a tendency to more frequent episodes of haemodynamic deterioration in the knee-chest position.      

Doctors on the medical profession

Over the past two to three decades there has been vigorous debate in the sociological literature as well as in popular forums concerning the changing social position and status of the medical profession and the extent to which consumerism has entered the doctor-patient relationship. Few qualitative sociological inquiries, however, have directly sought the views of medical practitioners themselves on these issues. To address this hiatus, this article discusses the findings from an empirical study using semi-structured indepth interviews with 20 doctors living and working in Sydney about their views on the contemporary status of the medical profession and their experiences of medical practice. Three major aspects are discussed: the extent to which the social position of doctors has changed, the impact of consumerism on medical practice and the qualities of a ‘good’ doctor. The implications of these data for theorising the nature of contemporary medical practice, power and professional status is explored, with particular reference to the insights offered by Foucauldian theory.     

Hypothesis: Pathogenesis of postmenopausal hot flush

The pathogenesis of postmenopausal hot flush is still poorly understood. A hypothesis is presented where the perimenopausal decline in circulating estrogen levels may increase central norepinephrine and LH-RH secretion and produce a downward setting of the central thermostat resulting in a hot flush.