Urine of patients with acute kidney transplant rejection show high normetanephrine and decreased 2-hydroxyestrogens concentrations.

BACKGROUND: A shift from anti- to proinflammatory steroid hormones has been observed in chronic inflammation. We tested the hypothesis that this shift occurs also in kidney transplant rejection together with a rise of urinary catecholamine degradation product concentrations as a consequence of locally produced cytokines, thus further promoting rejection. METHODS: We examined 8 patients with an early rejection episode in the protocol biopsy ∼2 weeks, 9 with biopsy-proven rejection at 2-3 months, and 18 without rejection, both at 2 weeks and 3 months after transplantation. Metanephrine, normetanephrine, and 2- and 16-hydroxyestrogens concentrations were measured by EIA. RESULTS: The median urinary concentrations of normetanephrine, but not metanephrine, were significantly higher in acute kidney transplant rejection in the first 2 weeks after transplantation (P < .05). During acute kidney transplant rejection at 2-3 months, but not in the first 2 weeks, after transplantation, 2-, but not 16-hydroxyestrogens, concentrations were significantly decreased (P < .05). CONCLUSIONS: We demonstrated that the downstream product of noradrenaline conversion normetanephrine was elevated in kidney transplant rejection in the first weeks after transplantation. This change may promote rejection together with an important proinflammatory and mitogenic steroid hormone shift, which becomes increasingly relevant over time.

FOXP3+ regulatory T-cells in renal allografts: correlation with long-term graft function and acute rejection.

BACKGROUND: The interpretation of a cellular infiltrate as cytotoxic or tolerogen represents an unsolved challenge in current transplantation. The so-called regulatory CD4+ CD25+ T-cells which express the FOXP3 gene have received increasing interest with respect to this question. The existing studies concerning the role of FOXP3+ Tregs for transplant tolerance yielded contradictory results. METHODS: We examined the numbers of the FOXP3+ Tregs in two groups of renal allograft biopsies both showing cellular infiltration, but either without (n=29) or with signs of acute cellular rejection (n=26), by means of immunofluorescence and correlated the amount of FOXP3+ Tregs to renal function at the time of biopsy and after 1 and 2 years of follow up. RESULTS: The number of FOXP3+ Tregs within infiltrates in non-rejecting biopsies did not correlate with renal function after 1 and 2 years. There were no significant differences in the numbers of FOXP3+ Tregs between biopsies with or without borderline infiltrates. Increased numbers of FOXP3+ Tregs were not associated with an ameliorated severity of graft rejection and did not correlate with outcome after the rejection episode and renal function after 1 and 2 years. CONCLUSIONS: The identification of the FOXP3+ regulatory cells within the allograft cannot be considered as an appropriate marker for the interpretation of infiltrates as cytotoxic or tolerogenic or as a prognostic marker for later transplant function.

Percutaneous transluminal angioplasty as first-line treatment of transplant renal artery stenosis.

BACKGROUND: Transplant renal artery stenosis (TRAS) is a frequent complication after renal transplantation, however long-term follow-up data after interventional treatment are rare. PATIENTS: In our transplant center 11 of 264 consecutive renal transplant recipients (4.17%) were diagnosed with TRAS. In addition, TRAS occurred in 2 renal transplant recipients that had been transplanted at other centers but who had their follow-up examinations in our center. Either a rise of the serum creatinine level and/or worsened systemic hypertension or routine examination with color Doppler sonography were indications for further diagnostic workup. METHODS: Direct angiography of the transplant renal artery was performed followed by percutaneous transluminal angioplasty (PTA) after the diagnosis of TRAS was confirmed in all of these patients. RESULTS: The immediate success rate for PTA was 92.3% (12/13). Only 1 patient with a severe kinking of the transplant renal artery had to undergo surgery to restore renal function. No complications occurred after the interventions. Thereafter the patients were monitored for a mean observation period of 33.15 months. Serum creatinine levels were significantly lower after the intervention, and estimated glomerular filtration rate (eGFR) increased accordingly. With regard to blood pressure there was only a trend for lower blood pressure levels and less antihypertensive use, whereas the dose of the prescribed drugs decreased significantly with time after interventional treatment of TRAS. In addition, a long-lasting rise of the hemoglobin levels could also be demonstrated. CONCLUSION: In summary, the beneficial effect of PTA of TRAS on renal function is long-lasting. Therefore, PTA, usually combined with stent placement, should be first-line treatment in TRAS in all patients. Surgical revascularization is only warranted, if PTA fails.

[Medication-induced impairment of renal function: what is important?]. / Medikamenteninduzierte Störung der Nierenfunktion : Was ist zu beachten?

Non-steroidal antiphlogistics and COX-2 inhibitors routinely cause sodium retention and a blood pressure increase by about 5 mmHg, a decrease in renal function (by about 10 ml/min) and in 1-2% an acute renal failure. Prevention is possible by short-term, low-dose application, avoidance of dehydration, controlling serum creatinine levels 1 week after start of treatment in high-risk groups. Aminoglycosides cause acute renal failure in 10-20% which can be prevented by once daily dosing, meticulous drug monitoring. Radio contrast media cause, mostly dependent on baseline renal function, in 0-50% a radiocontrast-induced nephropathy. This can be prohibited with hydration, low volume of contrast medium, and low- (or iso)osmolar contrast medium. New preparations of vancomycin go along with a greatly reduced rate of nephrotoxicity. Drug monitoring and avoidance of a combination therapy with aminoglycosides will help to reduce toxicity. Medication-induced acute interstitial nephritis is a relevant differential diagnosis in acute renal failure: stop implicated medication, consider steroid application!

SDF-1 expression is elevated in chronic human renal allograft rejection.

The exact mechanism of acute and chronic allograft rejection still remains unclear. The chemokine SDF-1 as mediator of allograft rejection has been under intensive investigation in liver, cardiac and bone marrow transplantation, whereas in renal transplantation, there are no reports about SDF-1 to date. This study was performed to evaluate if SDF-1 might also play an important role in human renal graft biopsies. One hundred and ninety formalin-fixed, paraffin-embedded renal allograft biopsies were included in the analysis from patients with normal renal graft morphology (according to Banff 97 classification grade 1, n = 84), with acute interstitial rejection (Banff grade 4 type I, n = 10), with acute vascular rejection (Banff grade 4 type II, n = 21), with chronic allograft nephropathy (CAN, Banff grade 5, n = 23), and without rejection but with various other lesions (Banff grade 6, n = 42). SDF-1 was localized by immunohistochemistry. In biopsies with CAN, SDF-1 expression was significantly elevated in interstitial infiltrates and infiltrating neointimal cells of arteries compared with biopsies with normal renal graft morphology. This is the first study describing a role of SDF-1 in human renal allograft rejection. We were able to demonstrate in a large number of biopsies an upregulation of SDF-1 in patients with CAN. Whether SDF-1 has pro-inflammatory or protective properties in this setting has to be evaluated in further trials.

WWW accessible system for national/regional registries of clinical results of cord blood transplants: a tool to facilitate cooperative clinical research.

A system, accessible via internet, has been developed to support the Spanish Registry of Cord Blood Transplants (RETSCU). The system includes a database of clinical results directly accessible by transplant centers (TCs) and cord blood banks (CBBs) (restricted to own cases regarding primary data and unrestricted regarding statistics derived from validated data) and gives open access to Web pages containing results approved for publication. It also includes internal mail for two-way and broadcast messages. Patients' data are essentially those included in Eurocord forms. Additional features of the system are: confidentiality; inalterability of validated primary data; identifiability of data sources. The Unix central computer is accessible via the WWW. For security, data transmission is encrypted and passwords are required for access. Copies are regularly updated. Data can be loaded from CBBs and TCs. The procedure for creating and updating records is user-friendly, with the possibility of errors being minimized by extensive automated checks. Validation of patients' records by a manager is required before making data available for general statistical analysis. TCs and CBBs may retrieve data on their own cases, regardless of validation, as individual records or in tables directly transferable to common statistical programs. Statistical analysis may be done on validated data from all the patients in the Registry or from groups selected according to HLA compatibility and disease, type of transplant (related/unrelated), or protocol. Several similarly designed and managed national/regional Registries might be networked and their data integrated into a multinational Registry. Our system would require some additional developments to be used in this way.

Relationship between the lateral acromion angle and rotator cuff disease.

One hundred consecutive magnetic resonance imaging (MRI) studies of the shoulder obtained for the purpose of evaluating rotator cuff symptoms were retrospectively reviewed to assess the relationship between acromion morphologic appearance and rotator cuff disease. The studies were reviewed simultaneously by two authors. Each cuff was assigned a tendon grade and an overall cuff score with MRI criteria previously described in the literature. A newly described "lateral acromion angle" was measured from a specified oblique coronal cut on each MRI study and was correlated with the corresponding MRI-determined rotator cuff score and supraspinatus tendon grade. Observed correlations were analyzed by using statistical methods. The average measured lateral acromion angle was 78 degrees, with a range from 64 degrees to 99 degrees. Eight shoulders had angles less than or equal to 70 degrees, and all eight of these patients were found to have full-thickness rotator cuff tears. As the lateral acromion angle decreased, a statistically significant increase in rotator cuff disease was noted (p < 0.0001). A significant correlation between increasing age and rotator cuff disease was also observed (p < 0.0001). Multiple regression analysis confirmed that both the lateral acromion angle and the age of the patient were independent predictors of rotator cuff score. Finally, although a trend was noted suggesting a correlation between acromion type (I--flat, II--curved, and III--hooked) and MRI-determined rotator cuff disease, this trend did not reach statistical significance (p = 0.12). Surgical correlation with MRI rotator cuff findings in 35 patients showed an MRI sensitivity of 100% and specificity of 83%. A statistically significant correlation between the lateral acromion angle and MRI-determined rotator cuff disease has been noted. The described angle may be a useful adjuvant in the evaluation and management of rotator cuff disease.

An analysis of 140 injuries to the superior glenoid labrum.

Between 1985 and 1993 140 injuries of the superior glenoid labrum were identified on arthroscopic evaluation and were recalled from a data bank of 2375 shoulder procedures performed during that time. The average patient age was 38 years, and 91% of the patients were men. The most common problem was pain, with 49% of all patients noting mechanical catching or grinding in their shoulders. No preoperative imaging modality consistently defined disease in the superior labral area. Fifty-five percent of all lesions were type II, 21% were type I, 10% were type IV, 9% were type III, and 5% were complex. Twenty-nine percent of lesions were associated with a partial-thickness tear of the rotator cuff, 11% with a full-thickness tear, and 22% with an anterior Bankart lesion. Twenty-eight percent of the superior labral lesions seen were isolated and did not have any associated rotator cuff or anterior labral disease. Type I lesions were debrided. Fifty-six percent of type II lesions were debrided in conjunction with an abrasion of the underlying glenoid rim. More recently suture anchors have been used to stabilize type II lesions. Treatment of type III and IV lesions depended on the extent of labral tissue disruption and involved either debridement or suture repair. Repeat arthroscopies were performed on 18 shoulders. Three of five type lesions treated with debridement and glenoid abrasion were healed. Four of five type II lesions treated with an absorbable anchor were healed. Three type III and one type IV lesion treated with debridement had normal superior labrums. Two type IV injuries treated with suture repair had completely healed. Two complex type II and III injuries treated with debridement and anchor fixation were healed.

Rate of degeneration of human acetabular cartilage after hemiarthroplasty.

Biopsy specimens of cartilage and subchondral bone were obtained from the weight-bearing dome of the acetabulum in twelve elderly patients who were having a revision of a hemiarthroplasty of the hip because of pain. Biopsy specimens of acetabular cartilage and subchondral bone were also obtained from eight patients of comparable age who were having a primary hemiarthroplasty for a displaced fracture of the femoral neck; these served as the control specimens. The specimens were stained with hematoxylin and eosin for the initial histological assessment of cartilage structure and cellularity as well as the integrity of the tidemark. Safranin-O and toluidine-blue stains were used to assess proteoglycan content. A histological grading scale was employed for comparative analysis of samples. The joint space of the hip was measured on the radiographs that were made before the revision and was correlated with the histological grade. Review of the histological specimens demonstrated considerable degeneration of acetabular cartilage in the patients who were having a revision of a hemiarthroplasty as compared with that in the age-matched control patients who were having a primary hemiarthroplasty. The progression in the severity of the degeneration correlated directly with the duration of articulation of the implant with the acetabulum. All six of the patients in whom the implant had been in situ for more than five years, and in whom the femoral stem was determined to be stable at the operation, had nearly complete loss of cartilage as seen on histological examination.(ABSTRACT TRUNCATED AT 250 WORDS)

The arthroscopic Mumford procedure: an analysis of results.

A total of 50 arthroscopic distal clavicle resections were performed for acromioclavicular joint pathology at our institution between 1990 and 1993. Follow-up on 50 shoulders (100%) was obtained at an average postoperative time of 2 years. Data were collected via physical examination, radiograph review, University of California at Los Angeles (UCLA) shoulder score, and questionnaire. Average patient age was 42 years. Preoperatively all patients showed acromioclavicular joint tenderness, whereas 80% had a positive adduction test. The diagnosis of acromioclavicular degeneration was made by a combination of physical examination and radiographs (100%), acromioclavicular joint injection (4%), bone scan (44%), and magnetic resonance imaging (30%). Intraoperatively, a Claviculizer (Smith-Nephew Dyonics, Andover, MA) burr was used through standard portals in a subacromial approach to the acromioclavicular joint. There were no intraoperative complications. Forty-one patients (82%) had their general anesthetic augmented with an intrascalene block, and all procedures were done on an outpatient basis. The average distal clavicle resection was 14.8 mm. Calcifications within the resected clavicle zone were noted in the shoulders of four of the patients (16%) who returned for radiographic follow-up. The UCLA shoulder score ranked 47 shoulders (94%) good to excellent and 3 fair (6%). Subjective patient satisfaction recorded 47 (94%) good to excellent results, with an average pain relief grade of 87%. Forty-five patients (98%) would recommend the procedure. The arthroscopic Mumford procedure effectively treats acromioclavicular joint pathology. The amount of bone removed can be precisely determined with the Claviculizer burr and reliably reproduced. The procedure has low associated morbidity and high patient satisfaction regarding functional outcome.

Tuberculosis of the foot: a case report.

A case of tuberculosis of the foot that was delayed in diagnosis is presented. Common pitfalls of diagnostic evaluation as well as pathogenesis and recent epidemiologic trends are discussed. It is hoped that such reports will serve to heighten awareness of the return of this mighty pathogen.

Long-term followup of the modified Bristow procedure.

A total of 86 modified Bristow procedures were performed for anterior shoulder instability between 1975 and 1987. Followup on 79 shoulders (92%) was obtained at an average postoperative time of 8.6 years. The redislocation rate was 4%. Average motion loss was 5 degrees of internal rotation and 9 degrees of external rotation. Fifteen percent of the patients examined expressed mild apprehension with the shoulder abducted and externally rotated. Radiographic bone union of the coracoid transplant was noted in 82% of patients. Additional surgical procedures were required in 14% of patients. Seventy-three percent of the reoperations were for screw removal because of persistent shoulder pain. The average subjective shoulder function was rated at 86% of preinjury level. All throwing athletes were able to return to throwing, although 54% of the patients with dominant shoulder involvement noted a decrease in throwing velocity. Ninety-seven percent of the patients rated their results as good or excellent.

The allman modification of the bristow procedure for recurrent anterior glenohumeral instability.

The Bristow procedure has undergone several modifications since Latarjet's original description in 1954. Throughout all the variations, the main principle remains in that the transferred bone block and muscle unit act as a mechanical buttress and sling to reinforce the weak anterior glenohumeral capsule. Several authors have reported satisfactory follow-up results with low rates of dislocation. However, multiple reports exist of complications involving hardware migration and damage to neurovascular structures. We review our previously reported follow-up on 79 shoulders after an Allman modification of the Bristow procedure at an average postoperative time of 8.6 years. The redislocation rate was 4% with average loss of external rotation of 9 degrees and internal rotation 5 degrees . Fourteen percent of shoulders required reoperation, the majority for screw removal. The likelihood of a quick return to full participation in athletics is good, except for the throwing athlete. The modified Bristow procedure provides excellent long-term stability with minimal loss of external rotation. Intraoperative radiographs are recommended to assure proper bone block placement. Patient satisfaction remains high regarding functional outcome.

Platelet activating factor (PAF) inhibitor (TCV-309) reduces caerulein- and PAF-induced pancreatitis. A morphologic and functional study in the rat.

Caerulein-induced acute pancreatitis was studied in rats. Consistent with this type of acute pancreatitis morphological (edema, leukocytic infiltration and acinar cell vaculization) and biochemical (increase in pancreatic protein content. PAF release and serum amylase) changes developed 5 hours after caerulein administration. In addition increase in pancreatic weight and decrease in pancreatic blood flow were noticed. PAF administration caused pancreatic damage similar in some parameters to caerulein-induced pancreatitis, along with reduction of pancreatic blood flow, increase in pancreatic protein content, and serum amylase. TCV-309, a selective PAF antagonist, administered prior to caerulein and/or PAF, reduced caerulein-induced pancreatitis and prevented PAF-induced pancreatitis. Results of our present studies indicate the crucial role of PAF in pathogenesis of experimental acute pancreatitis.

Skateboard and in-line skate fractures: a report of one summer's experience.

During a 5 month period, 26 skateboarding and 10 in-line skating fractures were seen at our institution. The radius was the most commonly injured bone in both groups. Forty-two percent of skateboard fractures required reduction and another 16% required operative intervention. Epiphyseal fractures occurred in 42% of the skateboard riders who were skeletally immature. A greater proportion of high-energy fracture patterns was recorded in contrast to earlier reports. Also, a trend towards injuries occurring on the street, as opposed to home, has been noted. Skateboard riders continue to shun protective gear and hitting a surface irregularity is the most common cause of fall. In-line skaters, on average, wear more protective gear and are more likely to continue riding after their injury. Routine protective gear and avoidance of street riding should be encouraged. Instructions stressing balance and control as opposed to showmanship are recommended. Caution is given to first time in-line skaters, as this appears to be an injury-prone period.

The effect of antagonist of receptors for gastrin, cholecystokinin and bombesin on growth of gastroduodenal mucosa and pancreas.

The effects of gastrin, cholecystokinin (CCK) and bombesin on the DNA synthesis, as a biochemical indicator of trophic action in the gastroduodenal mucosa and the pancreas, have been examined in rats fasted for 48 h and in rats refed for 16 h with or without administration of specific receptor antagonists for bombesin, gastrin and CCK. Bombesin and gastrin administered three times daily for 48 h in fasted rats significantly increased the rate of DNA synthesis as measured by the incorporation of [3H] thymidine into DNA in each tissue tested. CCK significantly increased DNA synthesis in the duodenal mucosa and pancreatic tissue, but not in the gastric mucosa. The stimulation of DNA synthesis induced by bombesin in the gastroduodenal mucosa and pancreas was abolished by bombesin/GRP receptor antagonist, RC-3095. RC-3095 did not affect DNA synthesis stimulated by gastrin and CCK in these tissues. L-365,260, a receptor antagonist for gastrin suppressed the DNA synthesis induced by gastrin but not by CCK or bombesin in the gastrointestinal mucosa and pancreas. L-364,718, a specific antagonist for CCK receptors was effective only against CCK stimulated duodenal mucosa and pancreatic growth. Refeeding of 48 h fasting rats strongly enhanced the DNA synthesis in all tissues tested, and this effect was significantly reduced in the gastroduodenal mucosa by blocking only gastrin receptors (with L-365, 260) and that in the duodenal mucosa and the pancreas by antagonizing of CCK receptors (with L-364,718). Antagonism of bombesin receptors (with RC-3095) did not significantly affect the stimulation of DNA synthesis induced by refeeding in all tissues tested. This study indicates that the stimulation of DNA synthesis can be achieved by exogenous gastrin, CCK and bombesin acting through separate receptors, but that only gastrin and CCK play the major role in the postprandial stimulation of the growth of gastroduodenal mucosa and pancreatic tissue.