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Biomedical subjects

R Ferguson

Publications and source records attributed to R Ferguson.

At least 37 records · Page 2Linked to original sources

Acute rejection episodes--best predictor of long-term primary cadaveric renal transplant survival.

Uniformly high 1-year primary cadaveric renal transplant survival has prompted an interest in establishing clinical factors associated with longer-term (i.e., more than 5-year) graft survival. We have studied 665 consecutive primary transplanted cadaveric kidneys using sequential quadruple immunosuppression with at least 1 year of follow-up (average 41.4 months). No attempt at HLA matching was made and all rejection episodes were confirmed by histology. Overall, 8-year patient and graft survival were 78% and 60%, respectively. Death as a cause of graft loss occurred in 103 patients. However, only 14 patients died from complications of immunosuppression. A multivariate analysis was performed using age, sex, blood type, race, presence of diabetes, HLA mismatch, current and maximum panel reactive antibody (PRA), time to first rejection episode, treatment of first rejection episode, and number of rejection episodes (none, one, or more than one). Number of rejection episodes was by far the most important co-variate (p = < 0.00001). In total, 53% of patients had no rejection episodes, 25% had one, and 22% had more than one. The occurrence of acute rejection did not correlate with the degree of HLA mismatch or PRA. Demographic and immunologic variables were similar for all three groups. Actuarial 8-year graft survival was negatively affected by rejection history (Fig. 1). Uncensored T1/2 in the group with no rejection episodes was 16.9 years, compared with 3.9 years in the group that experienced more than one such episode.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease

Discovery of D-amino-acid-containing ligands with selectide technology.

When all L-amino acid (aa) random peptide libraries synthesized on solid-phase particles were screened (Selectide Technology), we identified several peptide ligands (YG_F_) that interacted specifically with an anti-beta-endorphin monoclonal antibody (clone 3E7) (single-letter aa symbols; symbols '_' indicate variable aa). Here, we report on the screening of three different D-aa-containing pentapeptide libraries (XxXxX, xXxXx and xxxxx, wherein X = L-aa, and x = D-aa) with the same antibody, in which several D-aa-containing ligands were identified. The binding affinities of many of these D-aa-containing ligands were as least two orders of magnitude lower than that of YGGFL, for which the Ki is 17.5 nM.

Amino Acid Sequence

Enterobacter agglomerans--associated cotton fever.

Cotton fever is usually a benign febrile, leukocytic syndrome of unknown etiology seen in intravenous narcotic abusers. Cotton and cotton plants are heavily colonized with Enterobacter agglomerans. We report a case of cotton fever associated with E agglomerans in which the organism was first isolated from the patient's blood and secondarily from cotton that he had used to filter heroin. Enterobacter agglomerans is with most probability the causal agent of cotton fever. Patients presenting with the classic history should have blood cultures performed and should be started on a regimen of empiric antibiotic therapy.

Adult

Unexpected antinociceptive potency of cyclic [D-Tca1]CTAP: potential for a novel mechanism of action.

This study tested the hypothesis that compounds which may bind simultaneously to delta and mu receptors may be more potent antinociceptive agents than would be predicted from their binding affinities at individual mu and delta opioid receptors. D-Tca-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 ([D-Tca1]CTAP) (where D-Tca is a cyclic D-tryptophan analogue) was synthesized and evaluated in radioligand competition assays, opioid bioassays, and in an antinociceptive assay (the tail-flick test in mice). Additionally, the metabolic stability of [D-Tca1]CTAP was evaluated in striatal and cerebellar tissue slices. In rat brain in vitro, [D-Tca1]CTAP competed weakly for sites labelled by [3H]D-Phe-Cys-Tyr-D-Trp-Om-Thr-Pen-Thr-NH2 ([3H]CTOP) (mu-ligand), and [3H][D-Pen2,pCl-Phe4,D-Pen5]enkephalin (delta-ligand); [D-Pen2,D-Pen5]enkephalin (DPDPE) (delta-agonist) was 6.5-fold less and 230-fold more potent, respectively, against these ligands. Additionally, in mouse isolated vas deferens and guinea pig isolated ileum smooth muscle preparations, [D-Tca1]CTAP proved to be weak as either a delta (IC50 of approximately 2 microM) or mu (IC50 > 8 microM) receptor agonist. Surprisingly, however, i.c.v. [D-Tca1]CTAP produced antinociception with potency similar to DPDPE. The antinociceptive actions of [D-Tca1]CTAP were apparently not due to a metabolite or the release of endogenous opioids, as this compound proved stable in both striatal and cerebellar tissue slices and its antinociceptive actions were not enhanced by the 'enkephalinase' inhibitor thiorphan. The suggestion that [D-Tca1]CTAP might be acting by binding simultaneously to mu and delta receptors to produce its antinociceptive effect is supported by the demonstrated antagonism resulting from mu receptor blockade with either beta-funaltrexamine (beta-FNA) or naloxonazine, or by delta receptor blockade by ICI 174,864 ([N,N-diallyl-Tyr1,Aib2,3,Leu5] enkephalin). Furthermore, the antinociceptive properties of [D-Tca1]CTAP were antagonized by (naltrindole-5'-isothiocyanate) (5'-NTII), an antagonist at the delta 2 opioid receptor subtype, but not by the delta 1 antagonist [D-Ala2,D-Leu5,Cys6]enkephalin (DALCE). Additionally, no antagonism was produced by nor-binaltorphimine (nor-BNI), a kappa antagonist. From these data, [D-Tca1]CTAP appears to bind to mu, and 5'-NTII-sensitive delta 2, opioid receptors, and may represent the first of a class of compounds which may act at an opioid receptor complex via 'self-potentiation'.

Amino Acid Sequence

Risk factors for end-stage renal disease among minorities.

Blacks, Hispanics, and American Indians are at increased risk of ESRD. Among blacks, hypertension, type II DM, and possibly type I DM are classic risk factors and pose an increased risk for disease. A unifying concept in both DM and hypertension appears to be increased glomerular pressures. The role of diuretics as an independent risk factor for ESRD is further advanced. At a minimum diuretics appear not to be renal protective. Glomerulonephritis also occurs more commonly in blacks. The underlying pathology is largely unknown. There is an increased rate of HAN- and HIV-associated nephropathy which does not explain the excess risk. Patterns of referral or other biases may be in effect. The increased incidence of ESRD in Hispanics is mainly related to DM although, hypertension also plays a role. There is also evidence that HIV-associated nephropathy may occur relatively more often than in whites. We have alluded to the increased incidence of ESRD among American Indians and noted that diabetes mellitus occurs more commonly in most tribal groups while glomerulonephritis occurs more frequently in the Zuni. That groups at increased risk of ESRD are at the lower spectrum of the SES raises this issue as a common risk factor for disease. It is unlikely that SES is an independent risk factor. Education, access to early interventions, and social behavioral factors must be incorporated into any model which proposes a reduction in the rate of ESRD in these groups. The treatment of hypertension with medications that may be renal protective or pose increased risk, especially insofar as diuretics are concerned, must be considered urgent grounds for future research.

Black or African American

Listeria-associated pericarditis in an AIDS patient.

Listeria monocytogenes is a pathogenic, facultative intracellular gram-positive rod, generally seen in cell-mediated immunocompromised states. In acquired immunodeficiency syndrome (AIDS), it most commonly presents as bacteremia or meningitis. An association with pericarditis has not been described previously in this group of patients. This article describes a case of pericarditis secondary to listeriosis involving a focal pancarditis and necrosis of the A-V node with subsequent refractory ventricular tachyarrhythmias in an immunodeficient patient presenting with altered mental status. Infectious etiologies should be considered for "benign" appearing pericardial effusions in AIDS patients and the diagnosis of listeriosis excluded in the presence of "diphtheroid-like" organisms.

Acquired Immunodeficiency Syndrome

Determinants of clean surgical wound infections for breast procedures at an oncology center.

OBJECTIVE: To determine the clean surgical wound infection rate for breast procedures and the risk factors predisposing patients to these infections. DESIGN: A survey study. SETTING: Oncology center. PATIENTS: A consecutive sample of adult female patients who underwent surgical breast procedures for suspected carcinoma of the breast. Patients undergoing excisional biopsy, lumpectomy, or mastectomy from January 1985 to January 1987 were included in the study. INTERVENTION: Clean surgical wound infection rates were derived overall and for each procedure type. The medical records of all patients were then reviewed to extract data on patient characteristics and operative information in order to assess the risk factors for infection. RESULTS: Among the breast procedures performed on 448 patients, the overall clean surgical wound infection rate was 8.7% (39/448). The clean surgical wound infection rate for each procedure type was as follows: biopsy 2.3%, lumpectomy 6.6%, and mastectomy 19%. In addition to the type of procedure, factors significantly (p less than .05) associated with the development of clean surgical wound infection in the univariate analysis included: presence of surgical drains (p less than .01); closed suction drainage (odds ratio [OR] = 16.5, 95% confidence interval [CI95] = 5.0-54.7); location of the drain (OR = 3.3, CI95 = 1.7-6.6); prolonged preoperative stay (OR = 1.2, CI95 = 1.0-1.5); length of surgery (OR = 2.2, CI95 = 1.7-3.0); and greater mean age (OR = 1.6, CI95 = 1.2-2.1). CONCLUSION: Clean surgical wound infections are not uncommon in patients undergoing breast procedures. Factors relating to both the patient and operative techniques contribute to the clean surgical wound infection rate. Further consideration should be given to perioperative antibiotic prophylaxis for selected breast procedures, and the role of surgical drains should be reassessed.

Biopsy

Venous occlusion: a rare complication of transvenous cardiac pacing.

Venous occlusion is an uncommon complication of transvenous cardiac pacing. Fibrotic occlusion of the right subclavian and innominate veins and stenosis of the left innominate vein, after the insertion of transvenous pacing wire, was corrected surgically with an external iliac vein graft.

Adult

Phase I/II trial of superselective arterial 5-FU infusion with concomitant external beam radiation for patients with either anaplastic astrocytoma or glioblastoma multiforme.

From August 1987 through September 1989, 25 patients with either anaplastic astrocytoma (8 patients) or glioblastoma multiforme (17 patients) were entered into a Phase I trial of combined intra-arterial 5-fluorouracil (5-FU) and external beam radiation therapy. The intra-arterial 5-FU was given in a superselective, supraopthalmic fashion, in escalating doses from 200 mg to 600 mg on a weekly basis during the radiotherapy. Each patient received from 1-4 courses of 5-FU. Radiotherapy consisted of 5,000 rads in 25 fractions given to partial brain fields including the mass and surrounding edema plus a 3-cm margin as defined by computed tomography scan. There were a total of 4 significant acute complications out of a total of 70 infusions. These included 3 ischemic events of which 2 were transient. In addition, 1 patient experienced a cerebral bleed. No patients developed ocular complications. Electroencephalograms (EEGs) were performed immediately before and during 21 intra-arterial infusions. Two patients developed significant EEG changes during intra-arterial infusion, and both of these patients experienced untoward reactions. The remaining patients showed no EEG changes during their infusions. The median survival for patients with glioblastoma multiforme was 15 months. We believe the toxicity of superselective intra-arterial 5-FU infusion combined with external beam radiotherapy is acceptable. This type of treatment deserves further study.

Adult