New frontiers in continuous ambulatory peritoneal dialysis.
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Dialysis Solutions↗
Biomedical subjects
J Walls
Publications and source records attributed to J Walls.
Effect of correction of acidosis on nutritional status in dialysis patients.
Malnutrition is a well-recognised feature of end-stage renal failure and contributes to the continuing high morbidity and mortality in this group of patients. One of the aetiological factors is metabolic acidosis which has been shown to increase protein degradation in both experimental models of chronic renal failure and in humans with uraemia. Many patients currently receiving haemodialysis have subnormal values of plasma bicarbonate. However, the values can be normalised by using a dialysate bicarbonate concentration of 35-40 mmol/l and in continuous ambulatory peritoneal dialysis (CAPD), a similar increment in plasma bicarbonate can be achieved using a dialysate lactate content of 35-40 mmol/l. In short-term studies in haemodialysis patients there is evidence of an increase in body weight and other anthroprometric parameters when the plasma bicarbonate has been normalised by increasing the dialysate bicarbonate content. A long-term study in CAPD patients has demonstrated increased body weight, tricep skinfold thickness and midarm muscle circumference in those patients with a plasma bicarbonate of 27.2 +/- 0.3 mmol/l, compared to those with a value of 23.0 +/- 0.3 mmol/l. These studies strongly suggest that correction of acidosis by increased dialysate buffering capacity will improve nutritional status for patients with end-stage renal failure.
Acidosis↗
Epidermal growth factor receptor and c-erbB-2 oncoprotein expression in female genital tract carcinosarcomas (malignant mixed müllerian tumors). Clinicopathologic study of 82 cases.
BACKGROUND: Epidermal growth factor receptor (EGFR) and c-erbB-2 (also known as HER-2/neu) oncoprotein (p185erbB-2) are members of the subfamily of tyrosine kinase, transmembrane receptors often implicated in human carcinogenesis. We hypothesize that expression of EGFR and p185erbB-2 adds useful prognostic and histogenetic information regarding female genital tract carcinosarcomas (FGTCSs). METHODS: Paraffin sections from 82 FGTCS (61 endometrium, 14 ovary, 5 cervix, and 2 fallopian tube), 56% of which exhibited heterologous elements, were stained using anti-EGFR (clone 31G7, Triton Diagnostics, Alameda, CA) and anti-p185erbB-2 (clone CB11, Novocastra Labs, UK). RESULTS: EGFR reactivity was present in 11 (13.4%) FGTCSs (55% carcinomatous component [CC] only, 18% sarcomatous component [SC] only, and 27% in both). EGFR was associated with adenosquamous histology of the CC (P < 0.05) and heterologous rhabdomyosarcomatous differentiation in the SC (P < 0.05); no other histopathologic features were correlated. p185erbB-2 reactivity was present in 79 (87.8% strong [S], 78% membrane [M], and 8.5% weak) FGTCSs (1% CC only, 0% SC only, and 99% in both). p185erbB-2 did not correlate with histopathologic features or EGFR. Seventy-seven patients had clinical follow-up for longer than 12 months. Approximately 49.3% and 72.3% of patients had recurrent disease by 12 and 80 months, respectively; all but 1 were dead from disease. 27% of patients were disease free after 15 to 307 months (median, 77 months; mean, 92 months). EGFR, but not p185erbB-2 expression predicted disease recurrence (P < 0.05). Recurrent disease was associated with Stage greater than I (P < 0.0001), vascular space invasion in resection specimens (P < 0.01), and deep myometrial invasion in hysterectomies (P < 0.05). EGFR was associated with Stage greater than I and did not help predict recurrence in good prognosis groups. CONCLUSIONS: p185erbB-2 overexpression in both CC and SC of FGTCS suggests a common carcinogenic mechanism for both components and supports the conversion-histogenesis hypothesis implicating a dominant role for the CC with the SC arising as a metaplastic change from the CC. EGFR may be expressed in either component and indicates aggressive biologic behavior; however, its prognostic utility is limited by its low predictive value for recurrence (40.3%), inability to foretell recurrence in good prognosis groups, and dependence on stage. High frequency of overexpression and dismal prognosis make FGTCS patients good candidates for trials of therapeutic strategies involving the p185erbB-2 receptor manipulations.
Adult↗
Cyclosporin A and multiple fibroadenomas of the breast.
Multiple bilateral fibroadenomas are uncommon. This finding in four women who had received renal transplants prompted further inquiry. A prospective study was performed on 39 women under the age of 55 years who had received a renal transplant at least 1 year earlier. Clinical examination and breast ultrasonography were performed. Factors considered included immunosuppressive therapy, concurrent medication and renal function. Blood was taken for estimation of oestradiol, prolactin, follicle-stimulating hormone (FSH) and sex hormone binding globulin levels. Fibroadenomas were found in 13 of 29 women who had received cyclosporin A: multiple in ten and bilateral in five. No abnormal breast findings were seen in 10 patients immunosuppressed with steroids and azathioprine alone (chi 2 = 7.30, 1 d.f., P < 0.01). Serum oestradiol concentration was raised in women with fibroadenomas compared with that in those with normal breasts (P < 0.05) and the level of FSH was lower (P < 0.01). Cyclosporin A may act on breast fibroblasts by humoral mechanisms and direct action.
Adult↗
The beneficial effects of oral nifedipine on cyclosporin-treated renal transplant recipients--a randomised prospective study.
The aim of this study was to test the hypothesis that nifedipine will improve graft survival in cyclosporin A (CyA)-treated renal transplant recipients. One hundred and forty-seven patients were randomised to one of three regimens. Group A received CyA, 7 mg/kg per day, and prednisolone; group B followed the same regimen as group A plus oral nifedipine and group C received CyA, 4 mg/kg per day, prednisolone and azathioprine. Calcium channel blockers were avoided in groups A and C. The crude 2-year (P = 0.0223) and 4-year (P = 0.0181) graft survival was significantly better in group B (86% and 81%, respectively) than in group A (75% and 63%, respectively). Delayed initial function was seen least frequently in group B (10.2%) compared to groups A (31%) and C (28%; P < 0.01). Group B also experienced fewer rejection episodes than groups A and C (P < 0.05). We conclude that the combination of oral nifedipine and CyA significantly improves initial graft function, rejection frequency and long term graft survival.
Administration, Oral↗
Transformation in recurrent ovarian granulosa cell tumors: Ki67 (MIB-1) and p53 immunohistochemistry demonstrates a possible molecular basis for the poor histopathologic prediction of clinical behavior.
Ovarian granulosa cell tumors (GCTs) behave unpredictably. Stage I patients suffer recurrences many years after treatment, and histopathologic evaluation of the primary GCT offers only a few clues. Grading, in particular, is largely ineffective. Ki67 (MIB-1) and p53 monoclonal antibodies (active on paraffin embedded tissues) provide insight into nuclear proliferation and control, respectively. In this study, the authors hypothesized that these molecular markers will help predict the clinical behavior of GCTs. Paraffin sections from 68 GCTs (arising in 56 patients: 53 primary and 15 recurrent) including 34 typical and 27 diffuse adult, and seven juvenile types were immunostained for Ki67 (MIB-1 clone; Immunotech, Westbrook, ME) and p53 (DO7 clone; Novacastra Laboratories, UK). The Ki67 proliferation index (Ki67PI = percentage immunoreactive on a count of at least 400 nuclei) ranges from 1 to 50% (mean, = 12.2%; median, 9.3%). Nineteen percent of GCTs exhibited focal p53 immunoreactivity; the number of GCTs and proportion of nuclei decorated were as follows: four, <1%; seven, 1% to 10%; and one, 20%. Ki67PI was higher in recurrent tumors (P<.001) and correlated with mitotic rate (r = .75; P<.0001). p53 staining was associated with juvenile type GCTs (P<.001) and higher Ki67PI (P<.005). Other histopathologic features exhibited no association with p53 staining or Ki67PI. Follow-up was available for 54 of 56 patients: 18 suffered recurrences after 16 to 229 months (mean, 72.1 months; median 59 months), and 36 were disease free 16 to 369 months (mean, 78.2 months; median, 70 months) after diagnosis. Curiously, high Ki67PI and mitotic rates of primary GCT correlated weakly with a disease-free course (P=.03 and .07 respectively). Disease recurrence was associated with stage >I (P<.0005), vessel invasion in the capsule (P<.001), ruptured tumors (P<.005), and older patients (P<.02). p53 staining and size or subtype of GCT exhibited no prognostic value. For 12 patients, paired primary and first recurrence of GCT showed a striking increase in Ki67PI (P<.00005) and mitotic activity (P<.02) in the recurrence. p53 expression also appeared (de novo) in two recurrent GCTs. The interpretation of focal p53 staining (>10% nuclei decorated in only one GCT) is controversial. Some investigators suggest that this represents overexpression of wild type p53 rather than p53 gene mutation. Primary GCTs exhibit a wide spectrum of proliferative activity, and the seven juvenile GCTs (the most proliferative type) demonstrated no recurrences in this study. Recurrent GCTs displayed a transformation of molecular markers to increased proliferative activity and overexpression of p53, fundamentally, by these markers, a different GCT than the primary one. These findings suggest a molecular basis for the lack of histopathologic predictors for recurrence. Factors other than proliferation of the primary GCT (which relates most closely to grading) either extrinsic to the neoplasm (host dependent) or as yet undetectable must determine malignant behavior.
Adolescent↗
A comparison of axillary node status between cancers detected at the prevalence and first incidence breast screening rounds.
Screen-detected breast cancers are smaller than those detected in symptomatic populations and, for any given size, they are associated with fewer lymph node metastases. The management of axillary lymph nodes in patients with screen-detected breast cancer remains controversial. We have previously reported that prevalence (initial screen)-detected cancers are associated with nodal metastases in 17.4% of cases overall. Cancers < or = 10 mm, of any grade, are associated with metastases in only 5% of cases, and grade I cancers <30 mm are not associated with metastases. This led to our recommendation that axillary surgery is unnecessary for these groups of women. The present study compared the nodal status of cancers detected at the prevalence and first incidence (second) screens in order to determine whether our recommendation is appropriate for cancers detected at the first incidence screen. Overall, 30.1% of cancers detected in the first incidence screen presented axillary nodal metastases. At all size ranges, cancers detected at the first incidence screen were associated with significantly more lymph node metastases than prevalence-detected cancers. In particular, cancers < or = 10 mm were associated with metastases in 14.3% of cases. With the possible exception of grade I cancers, we believe that surgical staging of the axilla is essential for cancers detected at the first incidence screen, irrespective of size.
Aged↗
Fibronectin production by human tubular cells: the effect of apical protein.
In progressive renal disease the degree of renal failure correlates with interstitial scarring and the rate of progression correlates with the degree of proteinuria. This has led to the hypothesis that proteinuria may cause interstitial scarring. Human tubular cells (HTC) grown on permeable membrane supports were characterized to be predominantly of proximal tubular origin. HTC produce the matrix protein fibronectin in a polarised fashion the ratio of basolateral to apical secretion being 2.9 +/- 0.2 at 48 hours. The addition of serum proteins (1.0 mg/ml) to the apical medium resulted in increased basolateral secretion of fibronectin, 2.62 +/- 0.23-fold after 24 hours and 2.40 +/- 0.16-fold after 48 hours. Serum fractionation revealed that the stimulant to fibronectin production had a molecular weight 40 to 100 kDa. Platelet derived growth factor secretion was also stimulated to apical exposure to serum but transforming growth factor beta secretion was not detected. Addition of neutralizing anti-PDGF antibodies did not decrease fibronectin secretion. The activity of serum was not reproduced by albumin or by transferrin. Exposure of HTC to serum resulted in increased release of lactate dehydrogenase, suggesting a degree of cytotoxicity. This evidence could provide a mechanism for the link between proteinuria and interstitial scarring.
Albumins↗
Urticaria, arthralgia, and nephropathy without amyloidosis: another variant of the Muckle-Wells syndrome?
The term Muckle-Wells syndrome (MWS) describes an autosomal dominant disorder characterised by various combinations of urticaria, sensorineural deafness, amyloidosis, arthralgia and skeletal abnormalities. We describe a family with nephropathy and several symptoms of MWS, but no evidence of deafness or amyloidosis. Since nephropathy without amyloidosis has never been reported in MWS, but deafness is a feature of all reported pedigrees, we conclude that members of this family have a previously unreported inherited predisposition to urticaria, arthralgia and nephropathy which is distinct from the MWS phenotype.
Adolescent↗
Albumin endocytosis is regulated by heterotrimeric GTP-binding protein G alpha i-3 in opossum kidney cells.
Proteinuria is an adverse feature in patients with renal disease, possibly due to toxicity of albumin to proximal tubular cells. Albumin is reabsorbed from tubular fluid by receptor-mediated endocytosis. The mechanism of regulation of the endocytosis is unknown. The large quantities of G proteins in proximal tubular cell apical membranes suggests that they may have a regulatory role in endocytosis. 125I-labeled albumin uptake was measured in opossum kidney (OK) cells. This is a saturable process with high-affinity [apparent dissociation constant (Kd) = 24.3 mg/l] and low-affinity (Kd = 15.9 g/l) components. The endocytic uptake of gold-albumin into OK cells was confirmed by electron microscopy. 125I-albumin endocytosis in OK cells was inhibited by pertussis toxin, but cholera toxin had no effect. Pertussis toxin also inhibited uptake of [3H]inulin. OK cells were stably transfected with a cDNA for the G protein subunit G alpha i-3 and transfectants were screened by immunoblotting. Several G alpha i-3-overexpressing clones were detected. OK cells overexpressing G alpha i-3 demonstrate increased 125I-albumin uptake, which is abolished by pertussis toxin, in both a concentration- and time-dependent manner. These results suggest that albumin endocytosis in OK cells is regulated by the G protein G alpha i-3.
Animals↗
Renal effects of metabolic acidosis in the normal rat.
Metabolic acidosis causes renal growth and proteinuria, and may contribute to the progression of CRF. This study assessed the effects of HCI-induced acidosis on the structure and function of normal kidneys. Acidosis was induced in 12 rats by dietary HCl. After 2 weeks, acidotic animals had higher kidney/body weight ratios (0.47 +/- 0.10 vs. 0.35 +/- 0.10 g%, p < 0.001) and higher kidney protein content (123 +/- 3 vs. 111 +/- 4 mg/kidney, p < 0.05) than controls, but tubular nuclear densities were lower, suggesting tubular hypertrophy. Acidotic animals developed tubular proteinuria (16.4 +/- 2.6 mg/day after 2 weeks of acidosis vs. 2.9 +/- 0.3 mg/day at baseline; p < 0.001), and the pattern of immunohistochemical staining for Tamm-Horsfall protein suggested tubular injury. These data suggest that a tubulotoxic effect of metabolic acidosis may contribute to the progression of CRF.
Acidosis↗
Amino acid profiles and muscle protein composition in rats with a reduced renal mass in the fed state.
In severe chronic renal failure (CRF) with associated metabolic acidosis, abnormalities in protein metabolism and amino acid (AA) profiles in the fed state are well described. To evaluate the effect of early uraemia and the influence of acid-base status on protein metabolism and AA profiles, three groups of pair-fed rats were studied: group I - rats with 1+ 1/2 nephrectomy; group II - rats with 1+ 1/2 nephrectomy receiving NaHCO3 supplementation, and group III - sham-operated rats with NaHCO3 supplementation. After 4 weeks, serum creatinine values were similar in groups I and II (111 +/- 5 and 119 +/- 4 mumol/l) and higher than in group III (51 +/- 5 mumol/l, p < 0.0001); HCO-3 was reduced only in group I (22.4 +/- 0.8 mmol/l) compared to group II (28.3 +/- 0.6 mmol/l, p < 0.001) and group III (28.2 +/- 1.3 mmol/l, p < 0.001). In the uraemic animals (groups I and II) arterial AA profiles showed increased levels of phenylalanine, glycine, glutamate, proline and alanine. The marked increase of threonine in group I was corrected by NaHCO3 supplementation in group II. The total nonessential AA were higher both in group I (1,832 +/- 53 mumol/l, p < 0.05) and group II (1,788 +/- 103 mumol/l, p < 0.05) than in group III (1,542 +/- 54 mumol/l). These results are similar to those described in the fed state of uraemic patients. Intracellular AA changes were detected, especially in group II namely increased glycine and a decrease in threonine and serine levels. No signs of malnutrition or changes in alkali-soluble protein (ASP) or ASP/DNA ratio in liver and muscle were observed. These results show that AA abnormalities in the fed state occur early in the course of CRF, and that the marked increase of threonine is corrected by NaHCO3 supplementation. These data suggest that either an impaired utilization of the ingested proteins might occur before the appearance of major alterations in endogenous protein metabolism or acid-base status might alter AA metabolic rate per se.
Acid-Base Equilibrium↗
Proteinuria: a mediator of interstitial fibrosis?
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Animals↗
Association of p53 and WAF1 expression with apoptosis in diffuse alveolar damage.
Little is known about alterations in cell cycle regulatory proteins such as p53 and WAF1 in diffuse alveolar damage (DAD). We hypothesized that up-regulation of p53 and WAF1 in type II pneumocytes in DAD is associated with underlying DNA damage and apoptosis. Twenty cases of DAD and twenty control specimens of lung adjacent to resected tumors were studied. Immunohistochemical stains with antibodies recognizing p53 and WAF1 were performed, and apoptosis was assessed in sixteen cases by the nick end-labeling method. We identified p53 expression and apoptosis in all cases of DAD but not in any of the control lungs. We detected WAF1 expression in nineteen of twenty cases of DAD and in sixteen of twenty control lungs. In general, the distribution and intensity of WAF1 staining were greater in DAD than in control lungs. Staining for both p53 and WAF1 and labeling of apoptotic cells in DAD were usually focal ( < 10% of cells) and predominantly localized in type II pneumocytes. We conclude that increased p53 and WAF1 expression in DAD reflects normal physiological up-regulation in response to cellular and DNA damage and is associated with apoptosis of type II pneumocytes. p53-dependent apoptosis may contribute to the pathogenesis of this disease.
Adolescent↗
Parathyroid hormone-related protein, bone metastases and hypercalcaemia of malignancy.
Breast cancer patients frequently develop bone metastases. A newly discovered peptide, Parathyroid Hormone Related Protein (PTHrP), causes humoral hypercalcaemia of malignancy. We have studied whether production of this protein by breast cancers leads to the development of bone metastases or hypercalcaemia. PTHrP was produced by nearly 60% of early breast cancers and its production by the tumours was associated with malignant mammographic microcalcification, and the development of both bone metastases and hypercalcaemia. The hypercalcaemia associated with bone metastases has been shown to have a significant humoral component and measurement of plasma PTHrP in patients with hypercalcaemia is diagnostically useful. Potential mechanisms of preventing bone metastasis are discussed.
Biomarkers, Tumor↗
Subchronic use of the St. Jude centrifugal pump as a mechanical assist device in calves.
The purpose of this experiment was to study the effects of the St. Jude Lifestream centrifugal pump on hemodynamic and hematologic parameters and the incidence of postmortem findings in a subchronic ex vivo left ventricular assist animal model. Five calves were implanted with the pump as a left ventricular assist device (left atrial to thoracic aorta bypass) and studied for 96 h of continuous pumping under identical conditions. Heparin (100 IU/kg) was administered only in the initial saline pump prime. Throughout the protocol, mean arterial and central venous pressures averaged 102.1 +/- 4.6 and 3.4 +/- 2.2 mm Hg, respectively. Pump flow was 47.8 +/- 8.4 ml/kg/min at a mean pump speed of 1,676.3 +/- 106.1 rpm. No clinical abnormalities or mechanical malfunctions attributable to the pump were detected during the 96 h of continuous pumping for each calf. Mean plasma-free hemoglobin after 96 h was 3.9 +/- 3.7 mumol/L (p = 0.337 compared to baseline). At post mortem, renal infarctions were detected in 1 calf. No other pump-associated lesions were detected in any of the other calves. We have concluded that the St. Jude Lifestream centrifugal pump functions reliably during 96 h of continuous left heart bypass in a calf model.
Animals↗
Interstitial inflammation and scarring: messages from the proximal tubular cell.
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Atrophy↗
Report on renal disease in diabetes.
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Albuminuria↗