Chronic cyclosporine nephrotoxicity in renal transplantation

Although extensively studied, the pathophysiologic characteristics of chronic cyclosporine (CsA) nephrotoxicity are still far from being completely understood. The recognition of chronic CsA nephrotoxicity in allografted kidneys is hampered by a lack of easily assessable sensitive and specific markers. Long-term results of CsA withdrawal trials and trials that evaluated CsA sparing or withdrawal after the diagnosis of chronic allograft nephropathy (CAN) have shown that chronic CsA nephrotoxicity has a more important role in the etiology of late transplant dysfunction than appreciated before. Various hypotheses have explained the renal structural changes of chronic CsA nephrotoxicity including ischemia, cellular toxicity, and the stimulation of renal fibrosis by growth factors or cytokines. Possible ways to prevent chronic CsA nephrotoxicity include improved therapeutic drug monitoring and CsA withdrawal or avoidance. Patients with aspecific CAN in late biopsy may benefit from withdrawal of CsA or a reduction of its dose. Current knowledge is being discussed. It is concluded that in the near future more strategies are likely to be used to prevent loss of allograft function as a result of drug toxicity.     

Constancy and variability of gallbladder ejection fraction: impact on diagnosis and therapy.

The main objective of this study was to test the constancy and variability of gallbladder (GB) ejection fraction (EF) in long-term studies to (a) determine whether EF ever becomes normal once it is low, (b) determine how long it takes for the EF to become abnormal once it is found to be normal, (c) explore the cause of low EF, and (d) define objective parameters for biliary and nonbiliary abdominal pain. METHODS: Fifty-two patients (42 women, 10 men) who underwent quantitative cholescintigraphy twice (total studies, 104), over a mean period of 38.54 mo between studies, were chosen for retrospective analysis. They were divided into the following groups: control (n = 13; nonbiliary abdominal pain), chronic acalculous cholecystitis (CAC) (n = 27; biliary abdominal pain), chronic calculous cholecystitis (CCC) (n = 6; biliary abdominal pain), and opioid (n = 6; nonbiliary abdominal pain). The last group had received an opioid before cholecystokinin-8 (CCK-8) infusion in one study but not in the other study. A GBEF value of > or =35% was considered normal with a 3-min infusion and > or =50% as normal with a 10-min infusion of CCK-8. RESULTS: The mean GBEF value was reproducible between the 2 sequential studies in the control group (66.0% +/- 20.5% vs. 73.9% +/- 17.7%), CAC group (24.4% +/- 22.3% vs. 16.9% +/- 10.9%), and CCC group (20.8% +/- 20.9% vs. 27.5% +/- 34.5%) but not in the opioid group (14.8% +/- 14.6% vs. 56.5% +/- 31.7%). The severity of GBEF reduction in CAC increased with time: 7.2% +/- 8.1% within 12 mo, 16.1% +/- 14.9% in 13-47 mo, and 23.5% +/- 21.3% in 48-168 mo. None of the 27 patients with CAC developed a gallstone as detected by ultrasound during the study period. In 5 patients with CAC, a mean period of 52.6 +/- 28.9 mo was required for conversion from normal to a low EF. CCK-induced cystic duct spasm is the etiology for low EF in both CAC and CCC. CONCLUSION: Normal and low GBEF values are reproducible in long-term studies. Once the EF reaches a low value, it does not return to normal, and a normal value requires many years to become abnormal. CCK-induced cystic duct spasm is the cause of low GBEF in CAC and CCC, and the severity of EF reduction is similar for both. Exclusion of opioid intake immediately before the study is critical before attributing a low GBEF value to an irreversible GB motor dysfunction.     

Normal cerebral perfusion measurements using arterial spin labeling: reproducibility, stability, and age and gender effects.

Before meaningful conclusions can be drawn from clinical measures of cerebral blood perfusion, the precision of the measurement must be determined and set in the context of inter- and intrasubject sources of variability. This work establishes the reproducibility of perfusion measurements using the noninvasive MRI technique of continuous arterial spin labeling (CASL). Perfusion was measured in 34 healthy normal subjects. Intersubject variability was assessed, and age and gender contributions were estimated. Intersubject variation was found to be large, with up to 100% perfusion difference for subjects of the same age and gender. Repeated measurements in one subject showed that perfusion remains remarkably stable in the short term when compared with intersubject variation and the large capacity for perfusion change in the brain. A significant decrease in the ratio of gray-matter to white-matter perfusion was found with increasing age (0.79% per year (P < 0.0005)). This appears to be due mainly to a reduction in gray-matter perfusion, which was found to decrease by 0.45% per year (P = 0.04). Regional analysis suggested that the gray-matter age-related changes were predominantly localized in the frontal cortex. Whole-brain perfusion was 13% higher (P = 0.02) in females compared to males.     

Survivorship of cemented knee replacements

The survivorship method of analysis has been used to compare the failure rate and overall success of 1,430 cemented primary total knee arthroplasties performed at The Hospital for Special Surgery over a 15-year period. There were 224 total condylar prostheses with a polyethylene tibia, 289 of the posterior stabilised type with an all polyethylene tibia, and 917 posterior stabilised with a metal-backed tibial component. There were 12 failures in the total condylar series, giving an average annual failure rate of 0.65% and a 15-year success rate of 90.56%. The posterior stabilised prosthesis with a polyethylene tibia showed an average annual failure rate of 0.27% and a 10-year success rate of 97.34%, and this prosthesis with a metal-backed tibial component gave an annual failure rate of 0.19% and a seven-year success rate of 98.75%. The overall survival rate was not influenced by sex or age, diagnosis or the percentage of ideal body weight. No metal-backed tibial components have yet needed revision for loosening. It seems that infection will be the major cause of failure.     

Essential drugs in primary health care

On September 7-8, 1988, health professionals attended a national seminar at the National Institute of Public Cooperation and Child Development in New Delhi to review policies of each government department in India that dispenses essential drugs to PHC workers. Another objective included the need to agree on what essential drugs should be distributed by the various types of PHC workers. The consensus of the group was that the different levels of health services and competence of the PHC workers should determine the basic list of PHC essential drugs. In addition, the morbidity pattern in the community, safety, effectiveness, and cost of the drugs must also determine which drugs are essential. Anganwadi workers/village health guides should all have a kit with 17 of the 75 essential drugs, such as vitamin A solution, oral rehydration solution packets, choloroquine, and chlorine tablets. In addition to the same 17 drugs, all subcenters should have in stock aspirin, metoclopramide, oral contraceptives, methergin in both tablet and injection form, and activated charcoal. Each PHC center should have all of the above and the remaining 53 drugs which include antibiotics, bronchodialators, eye drops, injections, vaccines (e.g., DPT and BCG), ointments, antileprosy drugs, and snake venom. The quantity of each drug should be based on the morbidity pattern, seasonal trend, and sickness load of the area. All PHC workers should attend inservice training where tested and effective training modules and charts in each local language are used to learn how to judiciously prescribe these drugs. Further, this essential drug program should be continuously monitored and evaluated.     

Melanoma of the upper aerodigestive tract: a review of 21 cases

In this report 21 cases of primary malignant melanoma arising from the mucosa of the upper aerodigestive tract are reviewed. The patients ranged in age from 30 to 86; mean age was 67 years. There were 10 men and 11 women. All but one patient were white. Sites of involvement were: nose and paranasal sinuses, oral cavity and labial mucosa, parotid duct, and larynx. Surgery was the primary method of treatment. The 2-year survival rate was 44% (7/16) and the 5-year survival rate was 13% (2/15). Regional metastases were seen in 19% (4/21) while distant metastases was seen in 55% (11/21). The local recurrence rate was 69% (11/16). Distant metastases were usually associated with uncontrolled disease at the primary site. This fact as well as the low incidence of regional metastases lead us to conclude that better local control rather than regional lymphatic control is necessary if decreased distant metastases and increased survival are to be achieved.