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Biomedical subjects

K A Porter

Publications and source records attributed to K A Porter.

At least 19 recordsLinked to original sources
PubMed2001

Variation in the progression of diabetic nephropathy according to racial origin.

BACKGROUND: In the United Kingdom, diabetic nephropathy is a leading cause of end-stage renal disease. There is a higher incidence amongst subjects of Indo-Asian and African-Caribbean origin compared with Caucasians that is not wholly explained by the differences in the prevalence of diabetes. Therefore, we postulated that this observation could be related to variations in the rate of progression of renal disease according to racial origin. METHODS: We conducted a retrospective case-note review of 1684 adult attendees of the diabetes clinic. Forty-five patients were found with renal impairment (serum creatinine > or = 170 micromol/l) due to diabetic nephropathy. The patients were of Indo-Asian (n=10), African-Caribbean (n=11), and Caucasian (n=24) origin. Progression of nephropathy was assessed by analysing (i) the doubling of serum creatinine through construction of Kaplan-Meier curves and (ii) the slope (beta) of the rate of change in serum creatinine using linear regression analysis in relation to demographic variables, putative risk factors for nephropathy and antihypertensive drug therapy. RESULTS: There were no statistically significant differences between systolic and diastolic blood pressure, glycaemic control, smoking habit, baseline proteinuria, and usage of angiotensin-converting enzyme inhibitors between the three groups. The proportion of patients doubling their creatinine was significantly higher in the Indo-Asian compared with the African-Caribbean and Caucasian groups (100, 45 and 50%; P=0.025 respectively). In addition, the mean (95% CI) of beta (micromol/l/month) was highest in the Indo-Asian (5.36 (2.21-8.52)) compared with the African-Caribbean (3.14 (0.82-5.46)) and Caucasian (2.22 (1.31-3.14)) groups (P=0.035). The mean ranks of beta were highest in the Indo-Asian group (P=0.038) after adjusting for marginal differences in blood pressure age, gender, baseline proteinuria, anti-hypertensive treatment, and smoking habit. CONCLUSIONS: In this small cohort of type 2 diabetic subjects with established renal disease, the rate of decline in renal function is accelerated in Indo-Asian subjects. This observation could be related to differences in renoprotection from antihypertensive therapy.

Black or African American↗
PubMed1998

Electrocautery as a factor in seroma formation following mastectomy.

BACKGROUND: Electrocautery has been postulated as a factor in the risk of seroma formation after mastectomy. METHODS: Eighty consecutive mastectomies in 74 patients were randomly assigned to dissection of the mastectomy flaps with either scalpel (n = 38) or electrocautery (n = 42). Total volume of fluid output through drains and aspirated from seromas was recorded. Other factors investigated included the type of drain utilized, estimated blood loss, and complications. RESULTS: Seromas developed in 16 wounds in the electrocautery group compared with 5 in the scalpel group (38% and 13%, respectively; P = 0.01). Other factors with an independent risk for seroma included use of Jackson-Pratt drains compared with Blake drains (P = 0.006), and lower estimated blood loss (P = 0.006). No differences in characteristics of patients or in other complications were noted. CONCLUSIONS: Use of electrocautery to create skin flaps in mastectomy reduced blood loss but increased the rate of seroma formation.

Aged↗
PubMed1997

Clinicopathological features of Zimbabwean patients with sustained proteinuria.

OBJECTIVE: To describe clinico-pathological features of patients admitted with significant proteinuria. DESIGN: Hospital based prospective survey conducted from 1982 to 1987. SETTING: Paediatric and medical wards at both tertiary referral hospitals in Harare. SUBJECTS: 119 patients who presented with significant proteinuria were investigated. RESULTS: Of the primary nephritides, diffuse mesangial proliferative glomerulonephritis was the most common finding (25/119); IgM was the dominant or sole immunoglobulin identified in 17/25. Minor glomerular abnormalities were common (19/119); there were 11 patients with minimal change disease and this number accounted for 42% of the children aged three to 12 years who were nephrotic. This incidence is higher than previously reported from Africa. Diffuse membranous nephropathy was frequent (18/119); hepatitis B surface antigen was present in only five of these patients. Focal sclerosing glomerulo-sclerosis was as frequent as diffuse membranous nephropathy (18/119) and appeared to be idiopathic. Diffuse mesangiocapillary glomerulonephritis (membranoproliferative) was present in 15/119 patients; no causal association was made. CONCLUSION: The pattern of primary glomerulonephritis is described from 1982 to 1987. We describe a slightly higher number of patients with minimal change disease and minor glomerular abnormalities than previously reported and a surprisingly small number of patients with diffuse endocapillary glomerulonephritis. In common with other African series, no patient with IgA nephropathy was found.

Adolescent↗
PubMed1996

The current role of prophylactic mastectomy.

Prophylactic mastectomy has a role in preventing breast cancer in the woman at high risk. The rare indications for this operation are based on genetic and histologic factors that affect relative or cumulative risk. Evaluation of women at high risk must draw on multidisciplinary expertise, including genetic counseling. If prophylactic mastectomy is recommended, skin-sparing total mastectomy (not subcutaneous) with autogenous tissue reconstruction is the preferred approach.

BRCA1 Protein↗
PubMed1996

Breast cancer in elderly women: presentation, survival, and treatment options.

Recent data suggest that breast cancer in elderly women does not present as more advanced disease, nor is survival significantly inferior to that in younger women. Unfortunately, until recently, older women have been excluded from clinical trials that have determined survival benefit in both screening and treatment modalities. Unless co-morbid conditions adversely affect one's life expectancy or tolerance to therapy, older women should be treated with standard surgical procedures (including breast conservation, if so desired) for early-stage disease, as outcome is comparable to that in younger patients. Adjuvant tamoxifen therapy has proven survival benefit in women over 70 years of age with estrogen receptor-positive tumors and should be considered in all women with tumors greater than 1 cm in size. Older women may experience more chemotherapy-related toxicities. However, for those with a significant risk of recurrence due to tumor size or lymph node status, chemotherapy can be safely administered when factors such as age-related decline in creatinine clearance and co-morbid conditions are considered. Hormonal therapy (tamoxifen) is usually the first-line treatment option over chemotherapy for metastatic disease in the elderly unless the patient has an estrogen receptor-negative tumor, visceral-dominant disease, or significant disease-related symptoms. In the latter settings, chemotherapy can provide improved or more rapid response proportions but does not affect long-term survival.

Age Factors↗
PubMed1996

Inflammatory breast cancer.

Multimodal therapy with induction chemotherapy has improved significantly local disease control and overall survival in patients with IBC. This is now considered standard therapy for patients with this disease. Although survival has been improved, well over 50% of these patients will succumb to this disease. Ongoing and future investigations may better define the optimal approach for local control, the optimal duration of maintenance chemotherapy, and the possible role of biologic response modifiers and growth factors in further improving the outcome for patients with this disease.

Adenocarcinoma↗
PubMed1994

Cloning and sequence analysis of the rat augmenter of liver regeneration (ALR) gene: expression of biologically active recombinant ALR and demonstration of tissue distribution.

A full-length cDNA clone encoding a purified augmenter of liver regeneration (ALR) factor prepared from the cytosol of weanling rat livers was isolated. The 1.2-kb cDNA included a 299-bp 5' untranslated region, a 375-bp coding region, and a 550-bp 3' untranslated region. It encoded a protein consisting of 125 amino acids. The molecular weight of ALR calculated from the cDNA was 15,081, which is consistent with the size estimated by SDS/PAGE under reducing conditions. The molecular weight of the purified native ALR estimated by SDS/PAGE under nonreducing conditions was approximately 30,000; thus ALR apparently has a homodimeric structure. The recombinant ALR produced by expression of the cDNA in COS cells was tested in vivo in the canine Eck fistula model and found to have potency equivalent to the purified native ALR. The 125-aa sequence deduced from the rat ALR cDNA shows 50% homology to the amino acid sequence of the gene for oxidative phosphorylation and vegetative growth in the yeast Saccharomyces cerevisiae.

Amino Acid Sequence↗
PubMed1994

Small-for-size liver transplanted into larger recipient: a model of hepatic regeneration.

Orthotopic liver transplantation was performed in 60 recipient rats weighing 200 to 250 gm. Sixty rats of the same strain were used as liver donors, 30 weighing 100 to 140 gm (small for size) and the other 30 weighing 200 to 250 gm (same size). After 1, 2, 3, 4, 7 and 14 days (n = 5 each) DNA synthesis, nuclear thymidine labeling and mitoses were increased in both the small-for-size and same-size groups, but significantly more in the former. These changes were maximal after 48 to 72 hr, similar to but later than the well-known regeneration response after partial hepatectomy, which peaks at 24 hr in rats. Indirect indexes of regeneration of the transplanted livers also were measured: plasma or serum ornithine decarboxylase; insulin and glucagon serum levels; estradiol and testosterone serum levels (and their nuclear and cytosolic receptors); and transforming growth factor-beta, c-Ha-ras and c-jun mRNA expressions. With the small-for-size transplantation, these followed the same delayed pattern as the direct regeneration parameters. The small livers gradually increased in size over the course of 1 to 2 wk and achieved a volume equal to that of the liver originally present in the recipient. In contrast, no significant liver weight gain occurred in the transplanted livers from same-size donors despite the evidence of regeneration by direct indexes, but not by most of the surrogate parameters, including ornithine decarboxylase.

Animals↗
PubMed1993

Functional imprinting and epigenetic modification of the human SNRPN gene.

The SNRPN gene encodes a small nuclear ribonucleoprotein subunit, SmN, thought to be involved in splicing of pre-mRNA. A closely related protein, SmB/B', is constitutively expressed in all tissues except the brain, where SmN is predominantly expressed. The mouse homolog of the SNRPN gene has been shown to be functionally imprinted in mouse brain, being expressed only from the paternally derived chromosome. SNRPN has been mapped to human chromosome 15q11-q13 within the shortest region of deletion overlap for the Prader-Willi syndrome. We have now demonstrated functional imprinting of the human SNRPN gene using reverse transcription followed by the polymerase chain reaction (RT-PCR). No expression was observed in cultured skin fibroblasts of Prader-Willi patients, but was found in all Angelman patients and normal controls examined. We have also demonstrated a parent-specific DNA methylation imprint within intron 5 of the SNRPN gene, which suggests an epigenetic mechanism by which parent-specific expression of this gene might be inherited. Our findings indicate that SNRPN is expressed only from the paternally derived chromosome 15 in humans and therefore may fulfill one major criterion for being involved in the pathogenesis of the Prader-Willi syndrome.

Angelman Syndrome↗
PubMed1993

Clinical features and natural history of central cavitary necrosis.

Central cavitary necrosis (CCN) is an unusual complication of acute pancreatitis in which the necrosis is confined almost entirely to the pancreatic parenchyma and there is little if any extrapancreatic necrosis. In our experience with 10 patients with CCN, clinical features suggested that the episodes of acute pancreatitis were initially severe, with high Ranson scores (mean, 4.2; range, 1-6), development of systemic complications, computed tomography (CT) grade of D or E by the Balthazar-Ranson scoring system, need for intensive care unit admission in 8 of 10 patients, and mean length of hospitalization of 56 days (range, 28-153 days). However, the incidence of infection was low (20%) and mortality was also low (10%). Factors that help explain a favorable prognosis were low APACHE-II scores at admission and at 48 h, absence of shock, paucity of extrapancreatic necrosis, and rapid resolution of clinical toxicity prior to the diagnosis of CCN by CT scan at a mean of 19.8 days (range, 9-63 days) after the onset of symptoms. Surgical debridement is indicated for complications such as secondary infection and ongoing pain. In the absence of complications, an attempt should be made to treat CCN medically.

Acute Disease↗
PubMed1992

Prognostic factors in sterile pancreatic necrosis.

Although the overall mortality in sterile pancreatic necrosis is low, patients who experience systemic complications may have a higher mortality. To study the impact of systemic complications and other factors on survival, possible prognostic factors were evaluated among 26 patients who experienced at least one systemic complication. Mortality was 38%. Factors that correlated with a fatal outcome were high Ranson's scores during the first 48 hours (P = 0.01), high APACHE-II scores at admission (P = 0.04) and at 48 hours (P = 0.03), shock (P < 0.001), renal insufficiency (P < 0.05), multiple systemic complications (P < 0.001), and high body mass index (P = 0.01). Most systemic complications occurred during the first 2 weeks of illness. Logistic regression analysis showed that shock was the best predictor of a fatal outcome. Patients with favorable prognostic factors survived whether treated medically or surgically, whereas those with unfavorable factors had a fatal outcome whether treated medically or surgically. It is concluded that patients with severe sterile necrosis have a high mortality rate and that shock and other prognostic factors identify which patients are most likely to have a fatal outcome.

Adult↗
PubMed1991

Studies on mechanisms of augmentation of liver regeneration by cyclosporine and FK 506.

Evidence could not be found of immune modulation of liver regeneration. The powerful immunosuppressive drug FK 506, which augments the response after partial hepatectomy in normal rats, had the same effect in T cell-deficient nude rats. The cytotoxicity of natural killer cells in treated nude rats was not significantly changed by FK 506 therapy. However, the serum of FK 506-treated nude rats increased hepatocyte proliferation when added to third-party hepatocyte cultures, suggesting that FK 506 had induced a serum growth factor in the nude rats or had suppressed an inhibitory factor. A hypothesis was advanced that FK 506 (and cyclosporine) affects hepatic growth by nonimmunological pathways.

Animals↗
PubMed1991

Cyclosporine and liver regeneration studied by in vivo 31P nuclear magnetic resonance spectroscopy.

The changes in fructose-1-phosphate (F-1-P), intracellular pH, and ATP content of the liver after a fructose challenge were investigated noninvasively in vivo using phosphorus-31 nuclear magnetic resonance spectroscopy of dog liver four days after a portacaval shunt (PCS) with or without portal venous infusion of cyclosporin (CsA). The F-1-P metabolism was slower in PCS dogs (N = 2) as compared to either the normal (N = 2) or PCS + CsA-treated dogs (N = 3) (P less than 0.05). The intracellular pH temporarily decreased from 7.3 +/- 0.05 to 7.0 +/- 0.05 during the fructose challenge. The regenerative indexes were increased in the PCS + CsA group (P less than 0.01). These data obtained in vivo using 31P-NMR spectroscopy in the liver following a portacaval shunt, suggest that: (1) the energy status of the liver and the metabolic response to fructose are reduced in PCS compared to normal animals and (2) CsA treatment enhances the regenerative response of the liver and prevents the reduction in hepatic function associated with portacaval shunting.

Acid-Base Equilibrium↗
PubMed1991

Hepatotrophic effects of FK506 in dogs.

Portacaval shunt (Eck fistula) in dogs causes hepatocyte atrophy and organelle disruption, as well as tripling of hepatocyte mitoses. After submitting dogs to this procedure, FK506 was infused into the tied-off left portal vein. The size, anatomic quality, and replication of hepatocytes were enhanced in the portion of liver infused with FK506, with a significant spillover effect in the noninfused portion. These hepatotrophic qualities of FK506 may explain part of FK506's efficacy for the treatment of chronic liver rejection. Also, the observations support a trial with this drug for the treatment of autoimmune liver diseases because, in addition to turning off the immunologic genesis of such disorders, repair and regeneration of the damaged liver may be augmented. Finally, these hepatrophic qualities are part of an emerging spectrum of biologic effects caused by drugs that may modulate the enzyme cis-trans peptidyl-prolyl isomerase (PPIase), the principal constituent of the cytosolic binding sites of FK506, repatomycin, cyclosporine, and presumably other immunosuppressive drugs as yet undiscovered.

Amino Acid Isomerases↗