Outcomes at 3 years of a prospective pilot study of Campath-1H and sirolimus immunosuppression for renal transplantation

Campath-1H (alemtuzumab) induction was used for renal transplantation in combination with sirolimus as immunosuppression. We previously reported a high (28%) rate of early rejection with this regimen, and now report 3-year outcomes. Twenty-nine patients were recipients of either deceased donor or non-HLA (Human Leukocyte Antigen) identical living donor primary renal allografts. Clinical parameters including infection, malignancy, kidney function, and kidney histology were followed prospectively for 3 years. Three-year cumulative graft and patient survival were 96% and 100%, respectively. Twenty patients were maintained on steroid-free immunosuppressive regimens, and 15 patients were maintained on monotherapy for immunosuppression (12 on sirolimus). No serious infectious complications were observed and two patients developed basal cell skin cancer. The 3-year results of our initial pilot study demonstrate good graft (96%) and patient (100%) outcomes. Campath-1H induction has yielded a high proportion of patients maintained on immunosuppressive monotherapy (57%) without serious infectious- and no malignancy-related complications. The reported regimen yielded novel insights into both Campath-1H and sirolimus therapy in renal transplantation. Because of the higher incidence of early rejection, we recommend a modified strategy of immunosuppression including a brief course of a calcineurin inhibitor.     

Erythropoietin production in healthy volunteers subjected to controlled hypobaric hypoxia: further evidence against a role for adenosine

Aims Objective of this study was to investigate whether adenosine modulates renal erythropoietin production.
Methods In the present study erythropoietin production was stimulated by hypobaric hypoxia by subjecting healthy volunteers to a simulated altitude of 4000  m in a low pressure chamber for 5.5  h. During exposure to hypoxia the subjects received i.v. in a randomized, single-blind, cross-over fashion the non-specific adenosine antagonist theophylline, the adenosine reuptake inhibitor dipyridamole and placebo.
Results Contrary to the working hypothesis, theophylline did not decrease and dipyridamole did not further boost erythropoietin concentrations.
Conclusions The results are in agreement with our earlier study using haemorrhage as a controlled physiological stimulus of erythropoietin production, and would question a major role for adenosine as a mediator of renal erythropoietin production.     

The Resource-Based Relative Value Scale. Toward the development of an alternative physician payment system

This article describes the design and methods of a study currently under way to develop a Resource-Based Relative Value Scale (RBRVS); an alternative basis for establishing the payment rate for the services and procedures (S/Ps) of physicians in medical and surgical specialties. Physician resource inputs to be measured include (1) S/P time, (2) pre-S/P and post-S/P times, (3) intensity, (4) practice costs, including malpractice premiums, and (5) the cost of specialty training. These five factors will be combined to produce an RBRVS denominated in nonmonetary units. In the initial phase of the study, data on time and intensity will be obtained through a national survey of physicians who perform these S/Ps. In the second, consensus phase of the project, the investigators will convene a panel of representatives of the medical profession, third-party payers, consumers, and other interested parties to examine areas of agreement and disagreement as to how an RBRVS should be used for policy purposes. The final results of this study are expected by the summer of 1988.     

Inclusion cyst of the tunica albuginea: Demonstration by ultrasound

A 35-year-old man discovered a 1-cm nodule at the upper pole of the left testicle after blunt focal trauma. While the pain, tenderness, and location suggested hematoma or appendiceal torsion, the demonstration by ultrasound of the size, cystic nature, and extraparenchymal location was consistent with the rarely documented cyst of the tunica albuginea.     

Localization of Apaf1 gene expression in the early development of the mouse by means of in situ reverse transcriptase-polymerase chain reaction.

Apoptosis is an essential ubiquitous process that controls the duration of the life span of cells, thus playing a crucial role in morphogenetic, histogenetic, and phylogenetic developmental processes. Apaf1 (apoptosis protease activating factor 1) is one of the central mediators of the intrinsic apoptotic pathway and a part of the apoptosome, which activates procaspase-3 and promotes cell death. Gene knockout of Apaf1 in mice leads to late embryonic lethality with malformations such as the persistence of interdigital webs and hyperplasia of brain and retina. Therefore, Apaf1 is generally believed to play a crucial role in developmental apoptosis and have a widespread expression. However, its pattern of expression in early development remains unknown. To specify whether Apaf1 indeed plays this key role, we investigated the pattern of gene expression for Apaf1 in mouse embryos on day 7, 9, and 12 of development. Our results show, that gene expression for Apaf1 first occurs within the embryo between day 7 and 9 of development, becoming more widespread toward day 12 and then includes structures, such as yolk sac, mesenchyme, cartilage, heart anlage, otic vesicle, peridermis, and anlagen of the spinal ganglia and vertebral bodies. Our results also show that gene expression for Apaf1 is not ubiquitous in early mouse development. This finding indicates that cell death processes are independent of or less dependent on Apaf1 during this time. Of interest, an active gene expression for Apaf1 is also present in organ anlagen such as heart or intestine, in which no obvious phenotype is seen after Apaf1 deletion. This finding suggests a possible role for Apaf1 in such anlagen as a putative alternative compensatory pathway, which could be switched on in the case of defects in the mediators that are normally involved in such organs.     

Sildenafil Prevents Cardiovascular Changes after Bone Marrow Fat Embolization in Sheep

Background: Sudden, intraoperative cardiovascular deterioration as a result of pulmonary embolization of bone marrow fat is a potentially fatal complication during total hip and knee arthroplasty, intramedullary nailing, and spine surgery. Anesthetic management is challenging in the presence of increased right ventricular afterload due to pulmonary hypertension. Selective pulmonary vasodilation may be an appropriate prophylactic or therapeutic measure. The effect of sildenafil (phosphodiesterase inhibitor) on cardiovascular deterioration after bone marrow fat embolization was therefore investigated.

Methods: Bone cement (polymethylmethacrylate) was injected into three lumbar vertebrae in 12 sheep. Invasive blood pressures and heart rate were recorded continuously until 60 min after the last injection. Cardiac output and arterial and mixed venous blood gas variables were measured at selected time points. Before the first cement injection, 6 animals received a bolus injection (0.7 mg/kg) of sildenafil, with continuous infusion (0.2 mg [middle dot] kg-1 [middle dot] h-1) thereafter. Postmortem lung and kidney biopsies were taken for semiquantitative analysis of intravascular fat.

Results: Fat embolism was associated with a transient increase (21 +/- 7mmHg) in pulmonary arterial pressure. A transient decrease in arterial blood pressure and temporary increases in central venous pressure and dead space were also observed. No significant changes in any cardiovascular variable were observed after fat embolism in the sildenafil group. There was significantly (P < 0.05) less intravascular fat in the lungs of the sildenafil (median count of 5 emboli per microscopic view) compared with the control group (median count of 1).     

Relative effects of diarrhea, fever, and dietary energy intake on weight gain in rural Bangladeshi children

Quantitative studies of morbidity, food intake, and somatic growth were done prospectively during 14 mo for 70 children aged 5-18 mo in two Bangladeshi villages. When random-effect regression models were used, monthly changes in weight were inversely related to proportions of days in the month with fever and diarrhea and positively related to energy intake per kilogram body weight. Interestingly, weight changes did not vary with age in this interval. Estimates indicate that increasing energy intakes to the recommended World Health Organization level would have a significantly greater effect on weight gain than would the elimination of diarrhea and fever. With energy at recommended intake and diarrhea and fever prevalence as found in US children, weight gain is predicted to be near that of the international reference population. Therefore, interventions aimed at improving dietary intake may be as important as infection-control programs for improving growth of children in poor developing nations.     

Normal rates of forgetting of verbal and non-verbal material in Alzheimer's disease

Recent work has suggested that patients with damage to temporal lobe structures, such as patients with Alzheimer's Disease (AD), lose information from memory at an abnormally rapid rate. In contrast, data from other studies suggest that the rate of forgetting in AD is normal. In the present study, 62 patients with mild to moderate AD and 64 elderly controls were tested for their immediate and delayed recall of a short verbal passage and a modified Rey complex figure. The results suggest that although AD patients recalled less than controls, they did not forget at a faster rate during the 30 minute retention interval, supporting the finding that these memory impaired patients do not have an abnormal rate of forgetting. The data also suggest that poor initial encoding of the stimuli may be the cause of the AD patients' impaired recall.