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Biomedical subjects

M R First

Publications and source records attributed to M R First.

At least 109 records · Page 6Linked to original sources
PubMed1994

Safety and efficacy of recombinant human erythropoietin in correcting the anemia of patients with chronic renal allograft dysfunction.

Recombinant human erythropoietin (rHuEPO) is effective in correcting anemia in hemodialysis, peritoneal dialysis, and predialysis patients. Limited studies in patients with failing renal allografts suggest a similar efficacy but provide little information concerning benefits, dose requirements, or adverse events. This study examined these considerations in a group of 40 patients (18 men; 22 women) aged 40.3 +/- 13.8 yr with stable, chronic renal allograft failure. All patients had a hemoglobin < 95 g/L and a serum creatinine > 250 mumol/L at baseline. Patients received rHuEPO (50 U/kg sc) three times weekly for 24 wk along with iron po if serum ferritin was < 100 micrograms/L. Mean hemoglobin rose from 78.9 +/- 10.4 to 102.6 +/- 18.4 g/L after 24 wk. Mean rHuEPO dose at 24 wk was 129.8 +/- 81.9 U/kg per week. With oral iron supplementation only, serum ferritin fell throughout the 24 wk, whereas serum iron, transferrin saturation, and total iron-binding capacity remained stable. Quality of life was assessed by use of the general Sickness Impact Profile and the disease-specific Transplant Disease Questionnaire measures at baseline and every 8 wk during rHuEPO therapy. Significant improvement was noted in global Sickness Impact Profile scores and in four of five dimensions of the Transplant Disease Questionnaire. Serious adverse events were infrequent. No change in mean systolic or diastolic blood pressure was noted, although there was a significantly increased need for antihypertensive drugs in 18 patients (P = 0.0002). A significant inverse correlation was noted between baseline renal function and maintenance rHuEPO dose (r = -0.45; P < 0.05). Twelve patients returned to dialysis during the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

Clinical course of malignancies in renal transplant recipients.

BACKGROUND: The incidence of cancers after renal transplantation is significantly higher than in populations that have not undergone transplantation. The authors report a group of renal transplant patients from the University of Cincinnati who had cancer develop; the focus is on the patients' clinical course. METHODS: Since 1968, 876 renal transplantations have been performed for a variety of causes of end stage renal disease. Charts of transplant patients who had neoplasms were reviewed. RESULTS: Forty-four patients had epithelial skin cancers, and 36 had nonskin cancers or melanoma. No correlations could be established between disease course and type of immunosuppressive agent, type of disease for which transplantation was required, or type of renal allograft donor. The skin cancers demonstrated a propensity for multifocality: 22 of the 44 patients had multiple separate lesions develop. Of the patients with cancer not of the skin, six were treated surgically for carcinoma in situ, and none have experienced disease recurrence. Of 11 patients treated for early invasive disease, 6 are disease-free, 3 died of intercurrent disease, and 2 died of progressive disease 11 and 13 months, respectively, after disease diagnosis. Nineteen patients had advanced disease, and only 1 is alive and disease-free. Sixteen died of progressive disease at a median of 1 month from the time of diagnosis, and 2 died of intercurrent disease within 1 week of diagnosis. CONCLUSIONS: The natural history of cancers developing in renal transplant patients often is more aggressive than would be expected in patients who have not undergone transplants. The immunosuppression induced to allow viability of the renal allograft may allow tumor cells to thrive.

Adult↗
PubMed1993

Utility of bronchoalveolar lavage in assessing pneumonia in immunosuppressed renal transplant recipients.

PURPOSE: To determine if initial results obtained from diagnostic bronchoalveolar lavage (BAL) in immunosuppressed renal transplant patients with pulmonary infiltrates, fever, or hypoxemia can affect therapeutic decisions, morbidity, and mortality. DESIGN: A retrospective study of all BAL specimens obtained from renal transplant patients from January 1985 through June 1991. Initial results of Gram stain, cytology, cell differential count, and semi-quantitative bacterial cultures, all available within 24 hours of bronchoscopy, were compared with clinical outcomes and final diagnoses. SETTING: University hospital nephrology-transplant/pulmonary service. PATIENTS: Seventy renal transplant patients with a suspected pneumonia were stratified into 3 groups. A total of 48 patients underwent 58 bronchoscopies. Group 1 was comprised of 32 BALs that yielded 1 or more infectious organisms and was considered diagnostic. Group 2 (n = 26) were those BALs in which no organism was isolated and were thus nondiagnostic. Twenty-two additional immunosuppressed renal transplant recipients with pneumonia were considered by the admitting transplant nephrologist to have an uncomplicated community-acquired lung infection and thus were empirically treated and did not undergo BAL (Group 3). METHODS: BAL fluid analysis included cell differential count, cytopathologic examination, and culture for mycobacteria, legionella, fungi, viruses, and bacteria using a semi-quantitative technique. Etiologic diagnosis and the time of onset of the infectious processes were recorded. Therapeutic outcome and mortality were determined for each group. RESULTS: Thirty-nine etiologic organisms were found in 32 patients, with 6 patients having more than 1 infection. Twenty-two patients had 26 negative BALs, and 8 of these patients were clinically believed to have a volume overload state. Eight of 13 (61%) patients with bacterial pneumonia had BAL neutrophil counts greater than 20%, whereas 11 of 13 (84%) patients without bacterial pneumonia had neutrophil counts less than 20% (p < 0.05). Those patients with an infectious etiology remained in the hospital longer than patients without a specific etiologic organism identified (p < 0.02). Therapeutic decisions leading to the institution of specific antibiotics were more frequently made in patients with a diagnostic BAL (p < 0.0001). An overall 3-month mortality (16%) was low compared with the historical rate (30%). CONCLUSION: BAL is a useful procedure in the diagnosis of an infectious process in immunosuppressed renal transplant patients where initial results can alter therapy in more than 70% of cases.

Analysis of Variance↗
PubMed1993

Clinical correlations of cyclosporine-specific and -nonspecific assays in stable renal transplants, acute rejection, and cyclosporine nephrotoxicity.

Accurate and early diagnosis of the cause of renal transplant dysfunction is important in successful patient management. Controversy exists as to whether a cyclosporine-specific or -nonspecific method is more predictive of clinical events. In an attempt to answer this question, all episodes of acute renal dysfunction were reviewed in 322 stable renal transplant recipients over a 20-month period. To diagnose the cause of each episode of renal dysfunction, an analysis was made of patient demographics; weight; serum creatinine; cyclosporine dose; cyclosporine level, using a specific method--high-performance liquid chromatography (HPLC)--and a nonspecific method--fluorescent polarization immunoassay (FPIA); changes in cyclosporine dose; renal biopsy; and response to any therapeutic intervention. There were 138 patients, who developed 279 episodes of renal dysfunction. Causes of renal dysfunction were cyclosporine-related (n = 103), acute rejection (n = 63), extracellular fluid volume depletion (n = 27), other (n = 59), and unknown (n = 27). The mean HPLC cyclosporine level was significantly different in patients with acute cyclosporine toxicity (p < 0.001) and patients with acute rejection (p < 0.001) when compared to those with stable renal function; the mean FPIA cyclosporine levels were not significantly different between the three groups. However, a larger percentage of patients with rejection were subtherapeutic when measured by HPLC, while a higher proportion of patients with nephrotoxicity were above the therapeutic range measured by FPIA.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1993

Rapid detection of anti-OKT3 antibodies with the Transtat assay.

The ability to successfully reuse OKT3, a mouse monoclonal antibody, is dependent upon the host's response to the antibody during and following the first treatment course. Antiidiotypic and/or antiisotypic antibodies may develop after exposure to OKT3. Antiidiotypic antibodies will bind OKT3, rendering it ineffective, while antiisotypic antibodies do not influence the efficacy of OKT3. A new membrane-based immunoassay, Transtat OKT3 (Sangstat Medical Corp, Menlo Park, CA) detects anti-OKT3 antibodies in less than 15 min. It allows simultaneous detection of antiidiotype and antiisotype antibodies. A total of 180 serum samples were initially analyzed by ELISA; results were negative, low-titer (1:100), or high-titer (> or = 1:1000). Retrospectively, these same samples were analyzed by Transtat for both anti-OKT3 (idiotype) and IgG2a (isotype). A total of 109 samples of 180 (60.6%) tested negative by ELISA and Transtat, while 71 (39.4%) tested positive. Of the negative samples by ELISA, 98 of 109 (89.9%) also tested anti-OKT3-negative by Transtat. Of the 109 specimens that were anti-OKT3 negative by Transtat, 98 (89.9%) tested negative by ELISA. There were 22 discrepant samples between the two methods; all were low-titer-positive (ELISA and Transtat). The 71 positive ELISA samples consisted of 53 low-titer (1:100) and 18 high-titer (> or = 1:1000), while the 71 anti-OKT3 positive Transtat samples consisted of 44 low-titer (1:10) and 27 high-titer (1:50). Sixty of 71 (84.5%) ELISA-positive samples were also positive by Transtat. Similarly, 60 of 71 (84.5%) Transtat-positive samples were also positive by ELISA. Of 71 patient samples positive for anti-OKT3 antibodies, 63 had an antiisotypic component present by Transtat. In conclusion, the Transtat OKT3 assay for measuring OKT3 and IgG2a antibodies offers a rapid and accurate assay for OKT3 monitoring.

Animals↗
PubMed1993

Prevention and management of the adverse effects associated with immunosuppressive therapy.

Advances in immunosuppressive therapy have resulted in significantly improved patient and graft survival after solid organ transplantation. However, increased use has brought attention to specific toxicities associated with the use of these agents. Corticosteroid therapy can result in a wide array of short and long term toxicities. Management of these effects has focused on alternate day and dosage reduction protocols. Myelosuppression, hepatotoxicity, alopecia and gastrointestinal adverse effects are associated with azathioprine and generally respond to a reduction in dosage or withdrawal. Cyclophosphamide myelosuppression is managed in a similar manner. Use of cyclosporin, while the mainstay of immunosuppressive therapy, is often complicated by several well documented adverse effects. Short and long term nephrotoxicity is often managed through pharmacokinetic dosing strategies as well as pharmacological intervention with calcium channel blockers, prostaglandin analogues, pentoxifylline and thromboxane antagonists. Cyclosporin-induced hypertension, hyperlipidaemia, hyperkalaemia and hyperuricaemia are generally responsive to appropriate dietary restrictions and pharmacological therapies. The adverse effects associated with polyclonal antilymphocyte agents (fever, chills, rash, arthralgias) occur in response to the administration of foreign protein substances but can be prevented by pretreatment with corticosteroids, diphenhydramine and paracetamol (acetaminophen). The administration of muromonab CD3 (OKT3) stimulates the release of cytokines resulting in potentially severe complications seen during the first 1 or 2 doses. Pretreatment with diphenhydramine, low dose corticosteroids and paracetamol as well as proper fluid management has reduced the incidence of this syndrome. However, agents such as high dose corticosteroids, indomethacin, pentoxifylline and anti-tumour necrosis factor monoclonal antibodies may further decrease the severity of cytokine-induced toxicity. Antimurine antibodies may also develop during muromonab CD3 therapy, potentially limiting the efficacy of this agent. However, continued concomitant immunosuppressive therapy has significantly reduced antibody formation. In summary, as newer agents are developed with narrow therapeutic windows, it will be critical to identify specific drug toxicity and to develop preventative and management therapeutic strategies.

Adrenal Cortex Hormones↗
PubMed1993

Safety and efficacy of kidney transplant biopsy: Tru-Cut needle vs sonographically guided Biopty gun.

OBJECTIVE: We evaluated the safety and efficacy of using a 14-gauge Tru-Cut needle without imaging guidance vs using an 18-gauge Biopty gun with sonographic guidance for percutaneous biopsy of kidney transplants. MATERIALS AND METHODS: We retrospectively analyzed data from 105 biopsies (in 68 patients) in which the Biopty gun with an 18-gauge needle was used and data from 100 biopsies (in 64 patients) in which a 14-gauge Tru-Cut needle was used. RESULTS: Significantly fewer major complications (p = .03) occurred when the Biopty gun was used (2%) vs when the Tru-Cut needle was used (10%). Two major complications (2%), both hematuria requiring transfusion, occurred in the 105 biopsies performed with the Biopty gun. Major complications occurred in 10 (10%) of the 100 biopsies done with the Tru-Cut needle: three obstructed allografts caused by blood clots, two episodes of hypovolemic shock, one case of shock and obstruction, and four intraperitoneal hemorrhages (one of which required nephrectomy). Biopsy specimens were adequate for histopathologic diagnosis in more than 98% of cases for both the Biopty gun and the Tru-Cut needle. CONCLUSION: We conclude that imaging-guided percutaneous biopsy of renal allografts with a Biopty gun is as accurate as and safer than biopsy with the Tru-Cut needle.

Adult↗
PubMed1993

Effect of race on renal transplant outcome.

Renal transplant outcome was compared in whites and blacks at a single center. All recipients transplanted between 1984 to 1991 were included in this study. White and black recipients were followed for a mean period of 37.6 (1-96) months. The age, sex, follow-up period, immunosuppressive protocol, number of retransplants, HLA mismatches and etiology of renal disease were comparable in the two races. Overall graft survival was lower in black recipients (p=0.0300). Graft survival in all cadaver (p=0.0520) and primary cadaver (p=0.1430) transplants was lower in blacks, though this was not statistically significant. Percentage of graft losses during the follow-up was higher in black 53/108 (49%), than white recipients 82/257 (32%)(p=0.002), as were cadaver graft losses due to rejection, 39/92 (42%) in blacks, 54/190 (28%) in whites (p=0.02). There was no significant difference in graft losses due to rejection between races in the 1 yr post transplant, but there were significantly more graft losses after 1 yr in blacks 16/83 (19%) compared to whites (16/156(10%)(p=0.05). In cadaver grafts functioning for 6 months, subsequent survival was lower in black recipients (p=0.0418). There was lower patient survival in blacks during the mean follow-up period of 37.6 months (1-96). In conclusion, lower graft survival in blacks can be partially explained by fewer LRD transplants in black recipients. Persistent lower graft survival in all black recipients and significantly more losses due to rejection beyond 1 yr may be related to immunological differences, poor compliance, or a combination of both.

Adult↗
PubMed1993

Prednisone withdrawal in HLA identical and one haplotype-matched live-related donor and cadaver renal transplant recipients.

Prednisone withdrawal was attempted in 121 of 915 renal transplants recipients between 1967 to 1992. There were 57 males, 64 females. Age range was 21 to 62 (mean 39.2 years). Etiology of renal failure was chronic glomerulonephritis (54), diabetic nephropathy (36), interstitial disease (17), hypertensive nephrosclerosis (6), and other (8). Kidney source was from HLA-identical living-related donors (LRD) in 54 (Group I), one haplotype-matched LRD in 23 (Group II), and cadaver in 44 (Group III). Prior to the introduction of cyclosporin A (CsA) in 1984, prednisone withdrawal was attempted only in Group I. After 1984, prednisone withdrawal was also attempted in patients in Groups II and III, selected on the basis of having had no rejection episodes during the six months after transplantation. Forty-five patients in Group I were treated with azathioprine (Aza) and prednisone, and the remaining patients in Groups I to III were treated with Aza, prednisone and CsA. Mean follow-up was 93 months (6 to 207). Prednisone was gradually tapered and withdrawn in 94 of 121 patients after a mean period of 22.5 months (9 to 60). In 27 other patients, the prednisone dosage has been tapered to 5 mg/day or less with the aim of discontinuing the drug. There were seven episodes of acute rejection (3 during taper, and 1 each at 6, 7, 24 and 114 months after prednisone withdrawal); all seven were successfully reversed. Four other patients developed chronic vascular rejection (2 during taper and 2 after withdrawal).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗