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Biomedical subjects

G Kyriakides

Publications and source records attributed to G Kyriakides.

At least 19 recordsLinked to original sources
PubMed2004

Use of cyclosporine in renal transplantation.

Since 1983, cyclosporine has been the backbone of immunosuppression in clinical organ transplantation. Cyclosporine is usually used in combination with steroids and with another second-line immunosuppressant like azathioprine or mycofenolate mofetil. With these regimens, graft survival at 1 year exceeds 90% and long-term results are excellent. The main complication is renal toxicity, which is usually secondary to excessive exposure. The new microemulsion formulation of cyclosporine, introduced in recent years, has improved intestinal absorption and bioavailability and resulted in much less intrapatient variation than the older formulation. The introduction of 2-hour peak blood level monitoring, which corresponds closely to the area under the curve of the drug, allows more appropriate dosing, thus minimizing rejection owing to underexposure or toxicity owing to overexposure. As new effective immunosuppressants are currently becoming available for use in combination with cyclosporine, the transplant community can look forward to more effective and safer immunosuppression.

Azathioprine↗
PubMed2000

Septicemia due to multiresistant Klebsiella pneumoniae in a neonatal unit: a case-control study.

An unusually high incidence of septicemia due to multiresistant Klebsiella pneumoniae occurred in the Aristotle University Neonatology Department. Forty neonates suffered from 42 episodes of septicemia. Mortality was 43% ranging from 32% in neonates with birth weight (BW) - 1,500 g to 55% with < 1,500 g. No differences were found between 17 neonates who died and 23 survivors. All isolates were resistant to aminoglycosides, third-generation cephalosporins, and aztreonam, but susceptible to imipenem and ciprofloxacin. The neonates with septicemia due to K. pneumoniae were matched 1:1 with neonates without septicemia (31 pairs) or with neonates with septicemia due to other organisms (8 pairs) according to BW and time of admission. Factors associated with septicemia were mechanical ventilation (p = 0.004) and ongoing parenteral nutrition (p = 0.027). In a multivariate model, nutrition exhibited no independent association after adjusting for ventilation. No differences were detected between the patients with Klebsiella septicemia and those with septicemia due to other organisms. Enhanced Infection Control measures and a temporary change of antibiotic policy reduced this serious complication. Three small outbreaks of multiresistant K. pneumoniae previously reported in neonates are reviewed.

Case-Control Studies↗
PubMed1998

Loss of heterozygosity in polycystic kidney disease with a missense mutation in the repeated region of PKD1.

Loss of heterozygosity (LOH) is a molecular phenomenon that denotes the loss of one of the two alleles at a specific locus. It is frequently associated with tumour suppressor genes in various cancers and also with hyperproliferative disorders, although not exclusively. Interestingly, in conditions where there is an inherited germline mutation, the lost allele is always the functional one, thereby rendering a phenotypically dominant disease of recessive character at the cellular level. A disease more recently shown to be associated with LOH is polycystic kidney disease type 1, a systemic disorder characterized by significant pleiotropy. The main pathology is from renal cyst formation that eventually leads to end-stage renal failure during adult life. We describe the identification of a missense mutation in the repeated part of the PKD1 gene, exon 31, that substitutes valine for methionine. The mutation, M3375V, cosegregates with the disease phenotype in a large Cypriot family. During transplantation of one patient, one of the polycystic kidneys was removed and DNA was isolated from cystic epithelial cells. In 3 of 17 cysts examined with intragenic and flanking polymorphic markers on chromosome 16 we detected LOH, since the wild-type allele was lost, thereby rendering the affected kidneys of mosaic character. The degree of LOH was extensive and varied among the three cysts, supporting the multiplicity of expression of the phenomenon on different occasions. No LOH was detected for other selected loci examined. Our work further supports the hypothesis that the rate-limiting step in cyst formation may be the occurrence of a second somatic hit, although other factors may be also involved. The high frequency of mutations at this locus may, to a great extent, explain the variability in phenotype observed among patients in the same families, and the relatively high frequency of the disease worldwide.

Adult↗
PubMed1989

Long-term results of kidney transplantation at the University of Miami.

Of 631 renal allografts performed at our center between January 1, 1979 and June 30, 1989, 368 were from cadaver donors (CAD) and 263 were from living-related donors (LRD). The recipients were almost equally divided among 3 ethnic groups: Black, Hispanic, and non-Hispanic, non-Black (primarily of northern European background). Recipient ages ranged between 1 and 70 years. In the CAD group HLA matching was emphasized so that no patient received a kidney with less than a 1 DR match, and for the entire series there was a mean of 2.4 of 6 HLA antigens matched between donor and recipient. All patients (LRD and CAD) received at least 3 pretransplant blood transfusions. Overall actuarial 10-year patient and graft survival were 68% and 48% respectively, with 72% patient and 56% graft survival for LRD and 58% patient and 36% graft survival for CAD recipients. Factors adversely affecting long-term graft outcome were: a) Black race. Overall 10-year graft survival was 23% versus 55% for non-Blacks (p = 0.008); b) Type I Diabetes before transplant. Overall 10-year graft survival was 35% versus 51% for nondiabetics; and c) Compliance. This was the most significant factor influencing long-term survival, other than death due to cardiovascular disease. In a non-Black, nondiabetic category of less than 36 years of age at transplantation (n = 169), 10-year patient survival in LRD and CAD groups was 95% and 85%, respectively, and graft survival was 78% and 70%, respectively. This was markedly different from the entire series (p = 0.008). Even in this group, 4 of the 17 graft losses (including mortality) were due to documented prolonged noncompliance in teenagers. The 6 other deaths that occurred were due to hepatitis/cirrhosis (2), CMV (3), and AIDS (1). Among the factors not influencing graft survival in the CAD group was HLA matching after the minimum requirements were fulfilled, either by comparing 1 with 2 DR antigens, or total HLA (1-6) antigens matched.

Adolescent↗
PubMed1987

Single-dose captopril scintigraphy in the diagnosis of renovascular hypertension.

Renal scintigraphy with [99mTc]diethylenetriaminepentaacetic acid (DTPA) and/or sodium-iodine-131-o-iodohippurate (HIP) was performed before and after an oral dose of captopril (50 mg) in 18 patients with renovascular hypertension (RVH) due to renal artery stenosis (RAS) and 18 controls. In every patient with RVH, captopril induced, enhanced or sustained abnormal findings on HIP scintigraphy depending on the degree of RAS. With DTPA scintigraphy, renal function decreased after captopril in ten kidneys with RVH-related RAS and adequate baseline renal function, but this phenomenon was not evident in 11 kidneys with RVH and poor renal function. Captopril did not influence HIP or DTPA studies of kidneys with patent renal arteries (patients after successful renal angioplasty, patients with essential hypertension, contralateral kidneys of patients with unilateral RVH) or ipsilateral kidneys with mild and subcritical (less than 60%) RAS in patients without hypertension and/or normal renal vein renin activity. When HIP and DTPA scintigraphy were compared in the same patients, HIP demonstrated greater sensitivity and specificity than DTPA, particularly in patients with poor renal function. HIP scintigraphy before and after a single dose of captopril may provide a rapid sensitive and minimally invasive test for screening patients with hypertension.

Administration, Oral↗
PubMed1985

Long-term follow-up of canine segmental pancreatic autografts.

The functional and morphologic characteristics of free-draining, pancreatic segmental autografts (FDPS) were studied in 8 beagle dogs that had survived longer than 4 yr. After pancreatectomy, animals received FDPS autografts of the left pancreatic limb, representing approximately one-third of the total pancreas with iliac vessel anastamoses. The grafted recipients were given pancreatic enzyme supplements (Viokase). After transplantation (tx), all 8 animals sustained fasting euglycemia with no evidence of microvascular complications. After 4 yr, IVGTT revealed K-values (%/min) that were not significantly different from age-matched controls (2.9 +/- 0.5 versus 3.7 +/- 0.6, P greater than 0.05). Mean fasting serum insulin levels were significantly greater in the tx animals (49 +/- 5 microU/ml versus 12.2 microU/ml, P less than 0.001), although the incremental response to i.v. glucose (0.5 g/kg) was less than in controls (P less than 0.05). Mean fasting plasma C-peptide levels (0.09 +/- 0.01 pmol/ml versus 0.21 +/- 0.5 pmol/ml) and peak C-peptide responses to i.v. glucose were both significantly less than in controls. Sequential pancreatic biopsies up to 2.5 yr post-tx showed atrophy of the exocrine pancreas with coalescence of islets and mild fibrosis that did not progress with time. Immunoperoxidase stains confirmed the presence of insulin, glucagon, and somatostatin within nests of islet cells. Four years after transplantation of FDPS autografts in pancreatectomized dogs, excellent function is retained. The consequences of peripheral hyperinsulinemia remain to be determined.

Animals↗
PubMed1984

Massive hematuria following percutaneous biopsy of renal allograft. Successful control by selective embolization.

We report on a patient who underwent a percutaneous needle biopsy of a renal allograft for evaluation of compromised function. Gross hematuria occurred immediately and persisted for three weeks, interrupted only by long intervals of anuria due to obstruction by a clot. The bleeding was controlled successfully by selective transcatheter embolization with a coli and an absorbable gelatin sponge (Gelfoam). The techniques and complications of allograft biopsy procedures are reviewed, and the management of hematuria occurring after a percutaneous needle biopsy is discussed. A percutaneous needle biopsy is the preferred method of sampling the transplanted kidney, with an adequate specimen obtained in 96% of cases. Hematuria, that has been reported to complicate 7% of percutaneous biopsy procedures, is usually transient, and only rarely is intervention required. Angiographically directed selective embolization is an effective technique for controlling massive or prolonged urinary hemorrhage after renal allograft biopsy.

Adolescent↗
PubMed1982

A method for large-scale, high-yield isolation of canine pancreatic islets of Langerhans.

A modified collagenase digestion method is described for the isolation of large numbers of islets from the canine pancreas (approximately 3,500 islets/g). The islets isolated by this technique remained viable and released insulin in response to secretagogues after one week of maintenance in tissue culture. Islets isolated from a single donor pancreas were re-implanted into the spleen of the same animal made diabetic by subtotal pancreatectomy and two injections fo streptozotocin. Hyperglycemia was corrected in two dogs and decreased in a third dog followed for 30 days. The islet isolation method is described, therefore, provides a sufficiently large yield of viable islets from one donor pancreas to correct or improve diabetes in a recipient animal.

1-Methyl-3-isobutylxanthine↗
PubMed1982

Studies on the survival of simultaneous canine renal and segmental pancreatic allografts.

Prolonged survival of the vascularized free-draining intraperitoneal pancreatic segmental allografts (FDPS) has been observed previously in immunosuppressed beagle littermates matched for low mixed lymphocyte culture (MLC) reactivity. When rejection (hyperglycemia) did occur, it was abrupt, unpredictable, and irreversible. This contrasts with renal allograft rejection in which elevations of serum creatinine are reversible with increased immunosuppression. In the present experiments, low MLC-reactive littermate pairs underwent simultaneous transplantation of kidney and FDPS allografts from the same donor. Increases in serum creatinine from 0.5 mg/dl to 1.5 mg/dl (renal rejection) occurred 4 to 5 days after transplantation (mean = 20.5 +/- 4.1) and preceded the onset of hyperglycemia by 6 to 22 days (mean = 1.06 +/- 4.6) in nonimmunosuppressed animals. At the onset of kidney rejection but before hyperglycemia developed, renal allograft biopsies revealed generalized mononuclear infiltration, while FDPS biopsies showed diffuse interstitial infiltration, but islets of Langerhans appeared to be spared. Treatment intervention with azathioprine and corticosteroids at the time of creatinine elevation prevented the onset of hyperglycemia from 46 to greater than 260 days in four of nine animals. Biopsies after 2 weeks of therapy showed resolution of the lymphoid infiltrates in the kidney and limitation of infiltrates to perivascular areas in the FDPS allografts. Immunological monitoring of peripheral blood lymphocyte function demonstrated the development of positive in vitro cell-mediated lymphocytoxicity shortly before the onset of hyperglycemia but only after creatinine elevation was well established and biopsies revealed evidence of rejection in both the renal and FDPS allografts.

Animals↗