Islet Xenotransplantation: Are We Really Ready for Clinical Trials?

Four clinical trials of porcine islet transplantation have been reported, and there are verbal reports that clinical trials on much larger scales are continuing in centers in China and Russia. The four reported trials are briefly reviewed and, in the light of the present status of experimental islet xenotransplantation, consideration is given to whether such trials are currently justified. The Ethics Committee of the International Xenotransplantation Association has (1) emphasized the need for encouraging studies in non-human primates before clinical trials should be undertaken, (2) mandatory monitoring for the transfer of porcine microorganisms, and (3) careful regulation and oversight by recognized bodies. Other aspects of the topic, such as the need for informed consent, are briefly discussed. We conclude that, at the present time, more data documenting convincing efficacy, focused on clinically applicable immunosuppressive regimens, are needed to justify the initiation of closely monitored clinical trials. A clinical trial may then be justified even though the potential risk to the patients, and possibly for society, will not be zero.     

Notification of rheumatic fever in South Africa -- evidence for underreporting by health care professionals and administrators.

OBJECTIVE: To determine whether under-reporting of rheumatic fever occurs at hospital, municipal, provincial and national levels of the South African health system. BACKGROUND: Information on the incidence of rheumatic fever (RF) and the prevalence of rheumatic heart disease (RHD) is required for the prevention of valvular heart disease in developing countries. In South Africa, RF was made a notifiable condition in 1989. It has recently been suggested that the reporting of RF cases may be incomplete, possibly because of underreporting by health care professionals and deficient administration of the disease notification system in South Africa. METHOD AND RESULTS: We assessed whether underreporting of RF cases occurs by comparing the numbers of RF cases reported per year at hospital, municipal, provincial and national levels from 1990 to 2004. There was a fall in the number of RF cases reported per year at national and provincial level over the 15 years of observation. A detailed analysis of the number of RF cases reported at hospital, municipal and provincial level for a 5-year period showed that more cases were diagnosed in one hospital (serving a smaller population) than were captured at municipal and provincial level (serving a larger population), suggesting underreporting by health care professionals. There were discrepancies in the number of cases reported at municipal, provincial and national level, suggesting poor administration of the notification system. CONCLUSION: There appears to be underreporting of RF cases by health care professionals, and poor administration of the RF notification system. Health care professionals need to be educated about the statutory requirement to notify all RF cases in South Africa. An effective national disease notification system is required.     

The role of intraoperative monitoring of oculomotor and trochlear nuclei -safe entry zone to tegmental lesions.

OBJECTIVE: A safe entry zone to tegmental lesions was identified based on intraoperative electrophysiological findings, the compound muscle action potentials (CMAP) from the extraocular muscles, and anatomic considerations. This entry zone is bordered caudally by the intramesencephalic path of the trochlear, laterally by the spinothalamic tract, and rostrally by the caudal margin of the brachium of the superior colliculus. METHODS: Four intrinsic midbrain lesions were operated upon via the safe entry zone using the infratentorial paramedian supracerebellar approach. All lesions involved the tegmentum and included an anaplastic astrocytoma, a metastatic brain tumor, a radiation necrosis, and a cavernous angioma. CMAP were bilaterally monitored from the inferior recti (for oculomotor function) and superior oblique (for trochlear nerve function) muscles. RESULTS: In three of four cases, CMAP related to the oculomotor nerve were obtained upon stimulation at the cavity wall after removal of the tumor. Stimulation at the surface of the quadrigeminal plate, however, did not cause any CMAP response. Using this monitoring as an indicator, the lesions were totally removed. CONCLUSIONS: In the surgery of tegmental lesions, CMAP monitoring from extraocular muscles is particularly helpful to prevent damage to crucial neural structures during removal of intrinsic lesions, but less so to select the site of the medullary incision. The approach via the lateral part of the colliculi is considered to be a safe route to approach the tegmental lesions.     

Mechanismen der arteriellen Restenose und Therapieansätze zur Prävention

Both vascular surgery and endovascular interventions traumatise the arterial wall, especially the endothelium. The vessel responds with neointimal hyperplasia and/or constrictive remodelling, and this is still the limiting factor in curative interventions. Stent placement prevents constrictive remodelling but is the main trigger for in-stent restenosis. Hyperproliferation of neointimal tissue is the main response to arterial thrombosis, local inflammation or medio-intimal injury such as occurs, for example, after balloon dilatation in the region of arterial anastomoses or of a thrombectomy (Fogarty-manoeuvre). At present, research on prevention of restenosis is focused on inhibiting neointimal hyperproliferation by using drug-eluting stents, and especially sirolimus- or paclitaxel-eluting stents. In addition, further experimental research work is in progress, with the aim of esablishing new treatment regimens and solving the problem of neointimal formation, thrombosis and constrictive remodelling. These include both local and systemic pharmacological therapy, brachy- and laser therapy, and many genetic treatment options, some of which are currently the subjects of experimental studies and early-stage clinical trials. Gene therapy seems like a promising way of preventing restenosis, but has not yet been tested in clinical trials. In the near future, selective, simultaneous, and perhaps even polyphasic regulation for gene silencing of two or more genes involved in the development of restenosis could improve the long-term patency rate.     

Die Behandlung der Apophysenabrissverletzung des Epicondylus ulnaris im Kindesalter

OBJECTIVE: Surgical reduction and retention of apophyseal avulsion injuries at the medial epicondyle to prevent joint instability, lasting malalignment, or pseudarthrosis. INDICATIONS: Absolute: intraarticular apophyseal dislocation of the medial epicondyle, complete lesion of the ulnar nerve. Relative: dislocation of the apophysis (> 4 mm) in children > 5 years of age; the need for intervention increases in children as the degree of dislocation, age, and athletic activity increase. CONTRAINDICATIONS: Dislocation of the medial epicondyle (< or = 4 mm) in children < 5 years of age, provided the fragment location is not intraarticular. SURGICAL TECHNIQUE: Open reduction of the apophysis through a medial approach. Identification of the ulnar nerve. In young children or with small fragments fixation with Kirschner wire. Screw fixation in older children or for larger fragments. POSTOPERATIVE MANAGEMENT: Long upper-arm plaster cast until wound healing is achieved. Subsequently, upper-arm plaster cast for 3 weeks. Removal of Kirschner wires after 4-6 weeks, screw removal after 8-12 weeks. Physiotherapy only if marked reduction of elbow mobility is found 6 weeks after cast removal. RESULTS: From January 1, 1994 to December 31, 2003, 25 children with an average age of 12 years suffering from medial epicondylar avulsion fractures were operated on using open reduction and Kirschner wire fixation. An average of 3 years after the injury 14 of these children underwent follow-up examination using a procedure that took subjective, clinical and radiologic parameters into account. Two children showed a slight reduction in overall strength of the injured extremity when compared with the contralateral extremity. One child had a flexion deficit of 10 degrees, all other children showed movement limitations of < or = 5 degrees compared to the contralateral extremity. In all the cases available to follow-up, there was a slight increase in valgus alignment of the elbow joint compared with the uninjured side (3 degrees on average). All fractures consolidated within 6 weeks.     

Academic Degrees and Clinical Practice Characteristics: The University of Washington Physician Assistant Program: 1969-2000

CONTEXT: The physician assistant profession has been moving toward requiring master's degrees for new practitioners, but some argue this could change the face of the discipline. PURPOSE: To see if there is an association between physician assistants' academic degrees and practice in primary care, in rural areas, and with the medically underserved. METHODS: Surveys were sent to 880 graduates of the first 32 University of Washington physician assistant classes through 2000. Respondents noted their academic degree at program entry and the highest degree attained at any time up to the time of survey. Relationships between practice characteristics and academic degree levels were tested by unadjusted odds ratios and logistic regression after controlling for year of graduation and sex. RESULTS: Of the 478 respondents, 54% worked in primary care, about 30% practiced in nonmetropolitan communities, and 42% reported providing care for the medically underserved. Respondents with no degree (33% of total at entry, 24% at survey) were significantly more likely than degree holders to work in primary care and nonmetropolitan areas. Respondents with no degree at program entry were significantly more likely, and those with no degree at the time of the survey were marginally more likely, to self-report work with the medically underserved. CONCLUSION: Respondents with no academic degree are significantly more likely to demonstrate a commitment to primary, rural, and underserved health care. These findings may inform the national debate about the impact of required advanced degrees on the practice patterns of nonphysician providers.