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Biomedical subjects

P Kuo

Publications and source records attributed to P Kuo.

At least 19 recordsLinked to original sources
PubMed2001

Are concerns over right laparoscopic donor nephrectomy unwarranted?

OBJECTIVE: To examine the ability of several large, experienced transplantation centers to perform right-sided laparoscopic donor nephrectomy safely with equivalent long-term renal allograft function. SUMMARY BACKGROUND DATA: Early reports noted a higher incidence of renal vein thrombosis and eventual graft loss. However, exclusion of right-sided donors would deprive a significant proportion of donors a laparoscopically harvested graft. METHODS: A retrospective review was performed among 97 patients from seven centers performing right-sided laparoscopic donor nephrectomy. Surgical and postoperative demographic factors were evaluated. Complications were identified and long-term renal allograft function was compared with historical left-sided laparoscopic donor nephrectomy cohorts. RESULTS: Right laparoscopic donor nephrectomy was performed for varying reasons, including multiple left renal arteries or veins, smaller right kidney, or cystic right renal mass. Mean surgical time was 235.0 +/- 66.7 minutes, with a mean blood loss of 139 +/- 165.8 mL. Conversion was required in three patients secondary to bleeding or anatomical anomalies. Mean warm ischemic time was limited at 238 +/- 112 seconds. Return to diet was achieved on average after 7.5 +/- 2.3 hours, with mean discharge at 54.6 +/- 22.8 hours. Two grafts were lost during the early experience of these centers to renal vein thrombosis. Both surgical and postoperative complications were limited, with few long-term adverse effects. Mean serum creatinine levels were higher than open and left laparoscopic donor nephrectomy on postoperative day 1, but at all remaining intervals the right laparoscopic donors had equivalent creatinine values. CONCLUSIONS: These results confirm that right laparoscopic donor nephrectomy provides similar patient benefits, including early return to diet and discharge. Long-term creatinine values were no higher than in traditional open donor or left laparoscopic donor cohorts. These results establish that early concerns about high thrombosis rates are not supported by a multiinstitutional review of laparoscopic right donor nephrectomies.

Adolescent↗
PubMed2000

Liver transplantation improves cirrhosis-associated impaired oral glucose tolerance.

BACKGROUND: Thirty-five percent to 80% of cirrhotic patients have impaired glucose tolerance (IGT) or diabetes mellitus (DM). Diabetic cirrhotics have higher morbidity and mortality than nondiabetics. Therefore, it would be worthwhile to determine whether liver transplantation improves glucose homeostasis in these patients. METHOD: A total of 26 patients awaiting liver transplantation were evaluated for impaired glucose homeostasis by fasting blood glucose and/or oral glucose tolerance tests (OGTT). Five patients underwent transplant surgery within 1 year of OGTT and had a repeat OGTT 3-6 months after transplantation. RESULTS: Sixty-five percent (17/26) of the patients had abnormal glucose homeostasis. Twenty-three percent (6/26) met American Diabetes Association criteria for DM, and another 42.3% (11/26) had IGT. All patients had normal HbA1C levels. After transplantation, the 2-hr blood glucose improved in four patients and the mean 2-hr glucose level was reduced (204 +/- 94 vs. 132 +/- 53 mg/dl [mean +/- SD, P=0.051]). CONCLUSION: Liver transplantation can reverse cirrhosis-associated impaired glucose tolerance.

Adult↗
PubMed2000

Can seizures be the only manifestation of transient ischemic attacks? A report of four cases.

Several studies have investigated the frequency of epileptic seizures following ischemic strokes and transient ischemic attacks (TIAs). Little attention has been paid to the possibility that seizures may be precipitated by TIAs. We examined if seizures can be the only symptom of a TIA and how often this might occur. We performed a retrospective analysis of clinical charts and electroencephalograms of 160 consecutive patients evaluated for a first-ever seizure from January 1997 to December 1999 at Belluno General Hospital. From January to May 2000, 19 more first-ever seizure patients were evaluated directly. Four patients (2%) had seizures in the presence of important risk factors for ischemic stroke (atrial fibrillation in two patients, atrial fibrillation and ventricular mural thrombus in one patient, hemodynamically significant left carotid stenosis in one patient). Seizures were not accompanied by other neurological deficits or brain lesions on CT or MRI. As risk factors for brain ischemia are frequent in the general population not developing seizures, our results do not prove that the occurrence of seizures was more than casual in these patients. Yet they indicate that in a small percentage of patients, seizures can occur in a context highly suggestive of TIA, with no other focal deficits.

Aged↗
PubMed1999

Bcl-2 leads to expression of anti-DNA B cells but no nephritis: a model for a clinical subset.

Transgenic mice expressing anti-DNA antibodies have been extensively studied as a model for understanding B cell regulation in systemic lupus erythematosus (SLE). BALB/c mice transgenic for the R4A-gamma2b heavy chain of an anti-double-stranded DNA (dsDNA) antibody produce two populations of high-affinity anti-dsDNA B cells, one deleted, and the other anergized. We generated double-transgenic BALB / c mice expressing both the R4A-gamma2b heavy chain and the anti-apoptotic bcl-2 gene in the B cell compartment to study whether bcl-2 overexpression differentially affected anergic and deleted B cells. The double-transgenic mice (R4A/bcl-2) express elevated serum titers of both high- and low-affinity anti-dsDNA antibodies and display rescue of autoreactive B cells that are normally either deleted or anergized. Despite the presence of anti-dsDNA antibodies in their serum, R4A/bcl-2-transgenic mice do not develop nephritis, demonstrating that overexpression of bcl-2 is not by itself sufficient to allow disease progression. This phenotype resembles that of some SLE patients who have high titers of anti-DNA antibodies without nephritis.

Amino Acid Sequence↗
PubMed1999

Crossreactive B cells are present during a primary but not secondary response in BALB/c mice expressing a bcl-2 transgene.

While it is clear that multiple genetic factors lead to autoimmune diseases such as systemic lupus erythematosus (SLE), it appears that an environmental stimulus is also required to trigger the disease in susceptible individuals. We have previously demonstrated that B cells making crossreactive antibodies that bind to both phosphorylcholine (PC), a component of pneumococcal cell wall polysaccharide, and double stranded DNA (dsDNA) can be found in BALB/c mice immunized with PC coupled to a protein carrier. While these B cells are normally eliminated in vivo by apoptosis, they can be recovered ex vivo by fusion with a cell line overexpressing the anti-apoptotic gene bcl-2. This observation led us to ask whether in vivo expression of bcl-2 might abrogate immunologic tolerance during an ongoing immune response. In the present study, we have examined BALB/c mice that constitutively express a bcl-2 transgene in the B cell compartment. Bcl-2 transgenic BALB/c mice have an expanded B cell number, but display no evidence of anti-dsDNA antibodies in the serum even following immunization with PC coupled to a protein carrier. Crossreactive anti-DNA, anti-PC B cells can be recovered by hybridoma technology late in the primary response, but do not appear in the memory B cell compartment. Thus, in vivo expression of bcl-2 can rescue B cell autoreactivity in the primary immune response, but is not sufficient for activation of these B cells or for their maintenance in the memory compartment.

Animals↗
PubMed1998

[Kidney-pancreas transplantation. Clinical results in 23 consecutive patients].

Immunosuppressive approaches to combined kidney-pancreas tx include quadruple therapy with either antilymphocyte globulin (ATG) or OKT3 for a short period (7-14 days) immediately after transplantation. Maintenance therapy with prednisone, azathioprine and cyclosporin is then used to ensure the long-term survival of the graft. This study reports 23 cases of combined kidney-pancreas tx under ATG induction (n = 7) and OKT3 induction (n = 16). Both groups had maintenance therapy with azathioprine, prednisone and cyclosporin. The follow-up was 12 months. Graft loss was 3 out of 7 vs 1 out of 16 (p < 0.05) for the kidney and 3 out of 7 vs 3 out of 16 for the pancreas in ATG treated vs OKT3 treated patients respectively. There were two deaths in the ATG group and one in the OKT3 group; two patients died with functioning graft, one in each group. The one year actuarial survival was 87% for graft and patient, 83% for kidney and 77% for pancreas. Combined kidney-pancreas tx with ATG or OKT3 have a similar outcome. OKT3 allows a longer period before the onset of rejection. There is a trend in survivals which suggests a better survival in OKT3 treated recipients. Infections and other complications were similar in ATG and OKT3 patients.

Adult↗
PubMed1997

Evaluation of potential genotoxicity of pulsed electric and electromagnetic fields used for bone growth stimulation.

Medical devices emitting pulsed electric and electromagnetic fields have been found to be effective for a number of clinical applications including stimulation of bone and tissue growth. To determine whether pulsed fields of the type used in these clinical applications present a mutagenic hazard, electric and electromagnetic fields at two exposure levels were tested in the Ames test, CHO cell chromosomal aberration assay, BALB/3T3 cell transformation assay and unscheduled DNA synthesis assay in primary rat hepatocytes. For both field types, initial and independent repeat studies were performed for each assay at both clinical and supra clinical doses. In all assays, the results show a lack of cytotoxic, transforming and mutagenic activity. The data suggest that pulsed electric and electromagnetic fields of the type and dose levels used in bone growth stimulation lack mutagenic and transforming activity.

3T3 Cells↗
PubMed1997

Studies on the structure, regulation, and pathogenic potential of anti-dsDNA antibodies.

Studies of anti-double-stranded (anti-ds)DNA antibodies have provided insights into how and why these antibodies arise in systemic lupus erythematosus. In this review we discuss the experimental approaches that have been used by our laboratory to study these autoantibodies. Structure/function analyses including site-directed mutagenesis have helped characterize the molecular genetics of anti-dsDNA antibodies, and more recently peptide libraries have been used to define molecular motifs that these antibodies bind. Most of the pathogenic anti-dsDNA antibodies observed in lupus are somatically mutated. We demonstrated in vitro and in vivo that anti-bacterial antibodies can mutate to acquire specificity for dsDNA. Furthermore, using a fusion partner constitutively expressing bcl-2, NSO(bcl-2), we have shown the existence of anergic or preapoptotic B cells making antibodies that cross-react with both bacterial antigen and dsDNA. Whether defects in the regulation of these antibodies might contribute to serum expression of anti-dsDNA antibodies in some individuals remains unknown. A major emphasis of this review is the regulation of anti-dsDNA antibodies in a transgenic mouse model harboring the gene for the heavy chain of a pathogenic anti-dsDNA antibody. Nonautoimmune transgenic mice effectively regulate autoreactive B cells by anergy and deletion, while their autoimmune counterparts do not. The vast majority of anergic B cells expressing high-affinity transgenic anti-dsDNA antibody fail to display allelic exclusion of the heavy chain. We postulate that this may be one mechanism that allows them to escape deletion. Comparative studies on light chain usage in both the autoimmune and the nonautoimmune transgenic mouse strains have demonstrated that within the autoreactive B-cell population, there are subsets that are differentially regulated. Ultimately transgenic animals making pathogenic autoantibodies may provide us with a system for testing novel therapies for autoimmune disease.

Animals↗
PubMed1997

Overexpression of bcl-2 alters usage of mutational hot spots in germinal center B cells.

Bcl-2 is an anti-apoptotic gene important in B cell development. In order to study how apoptosis regulates somatic hypermutation and selection of B cell clones in the germinal center, we examined the antibody response to phosphorylcholine (PC) in transgenic mice overexpressing bcl-2 in the B cell compartment. The anti-PC antibody response is dominated by the S107V1 variable region heavy chain gene. We, therefore, analyzed S107V1-encoded heavy chains from germinal center cells. The proportion of germinal center sequences that were mutated, and the frequency of mutations did not differ significantly between the two groups of mice. No significant differences were found in the clustering of replacement mutations in the complementarity determining regions (CDRs) and in replacement to silent (R:S) mutation ratios. A significant difference between bcl-2 transgenic mice and controls, however, was found in the targeting of mutations to oligonucleotide motifs presumed to be mutational "hot spots." While non-transgenic mice displayed the expected clustering of mutations in hot spots, mutations from bcl-2 transgenic mice lacked this pattern. This observation suggests that the mechanism for somatic hypermutation includes two distinct functions, a non-specific mutational apparatus and a mechanism to target mutation to hot spots, and that in certain circumstances these functions may be uncoupled.

Amino Acid Sequence↗
PubMed1996

Pulmonary hypertension: considerations in the liver transplant candidate.

Pulmonary hypertension is a potentially lethal complication of end-stage liver disease with a prevalence of 2%. In the setting of liver transplantation, the prevalence may be as high as 12%. Given the potential importance of this syndrome to the transplantation community, the purpose of this review is to summarize the current state of understanding of portopulmonary hypertension and to suggest potential management strategies for (1) liver transplant candidates with suspected pulmonary hypertension and (2) intraoperative pulmonary hypertension following liver allograft reperfusion.

Animals↗
PubMed1995

The incidence of renal failure in one hundred consecutive heart-lung transplant recipients.

Between March 1981 and November 1992, 100 heart-lung transplantations were performed at our institution. We report on the renal function in the 67 patients who survived a minimum of 6 months posttransplantation, and who were aged more than 10 years at the time of transplant. Renal function was determined by serial measurement of serum creatinine. Mean serum creatinine increased from 0.96 +/- 0.03 mg/dL at baseline to 1.55 +/- 0.07 mg/dL at 6 months posttransplantation, to 1.88 +/- 0.11 mg/dL at the end of follow-up (mean follow-up, 50.0 months; range, 6 to 140 months). The decline in renal function was biphasic, with a rapid decrease in the first 6 months, followed by a much slower decline. Three patients developed end-stage renal failure. This compares with 14 of 416 cardiac transplant recipients at Stanford who developed end-stage renal failure over the same period. We conclude that in our large series at a single center the incidence of renal impairment and end-stage renal failure is low and similar between heart-lung and heart transplant patients.

Adolescent↗
PubMed1995

Postischemic injury, delayed function and Na+/K(+)-ATPase distribution in the transplanted kidney.

We evaluated the postischemic renal injury in 22 patients undergoing renal transplantation. Renal tissue obtained 45 to 60 minutes after reperfusion of the allograft was stained with specific antibodies against the delta subunit of Na+/K(+)-ATPase, fodrin and ankyrin. The distribution of each cytoskeletal protein was analyzed by laser confocal microscopy. Subsequent allograft function was assessed on two occasions, 1 to 3 and 36 hours post-reperfusion, respectively. Recipients were divided into two groups: those who achieved a normal GFR on post-transplant day 3 (group 1, N = 12) and those with persistent hypofiltration (group 2, N = 10). Patients of both groups exhibited impaired sodium reabsorption and isosthenuria one to three hours postoperatively, but these abnormalities persisted on day 3 only in group 2 subjects with persistent hypofiltration. Abnormalities of Na+/K(+)-ATPase, ankyrin and fodrin were confined to proximal tubule cells and were marked only in the subjects of group 2. They consisted of redistribution of each cytoskeletal protein from the basolateral membrane to the cytoplasm. We conclude that postischemic injury to a renal allograft results in a loss of polarity of proximal tubule cells. We propose that ensuing impairment of proximal sodium reabsorption could activate tubuloglomerular feedback, thereby contributing to the protracted hypofiltration that characterizes this form of postischemic, acute renal failure.

Adolescent↗
PubMed1992

Novel method for isolating mammalian cells defective in fluid-phase endocytosis.

A new method for isolating mutants defective in fluid-phase endocytosis has been developed based on the observation that endocytosed horseradish peroxidase can be made lethal to cells. The method was used to isolate a mutant from Chinese hamster ovary cells, termed HRP-1, that was temperature-sensitive for viability and had a 70% reduction in the rate of horseradish peroxidase endocytosis at the restrictive temperature. At high temperature, HRP-1 cells were also defective in the secretory path and their Golgi complex disappeared at the resolution of fluorescence microscopy. These properties are similar to two previously described mutants of CHO cells, DS28-6 and V.24.1. In complementation tests, mutants HRP-1, DS28-6, and V.24.1 all appeared to be in the same complementation group.

3,3'-Diaminobenzidine↗
PubMed1992

Laser surgery procedures in the operational KC-135E aviation environment.

The operational aviation and space environments present a potential for surgical trauma to aircrew and passengers. Current wound care techniques for trauma in the aviation and space medicine environment focus on classical surgical management of wounds. Medical lasers used in these environments can provide rapid control of bleeding wounds, reduce aircraft environmental contamination from body fluids and secretions, and foster rapid triage of injured personnel. Self-contained and reusable medical lasers have the potential to reduce the material supply of medical kits in the aviation and space environment. A miniaturized carbon dioxide laser was used to establish protocols and procedures for use on operational military KC-135E aircraft. Laser surgery was performed to demonstrate laser efficacy and safety in flight.

Aerospace Medicine↗
PubMed1991

Managing aphthous ulcers: laser treatment applied.

The recurrent aphthous ulcer is a common oral ulcerative condition. Therapies are pharmaceutical in nature, remain palliative and do not alleviate pain. Carbon dioxide laser therapy was used to treat a minor form of the ulcer (canker sore); the laser therapy reduced or eliminated the pain and inflammation with normal wound healing.

Adult↗