Biomedical subjects
Publications and source records attributed to G J Becker.
This paper reports an isolated case of the exceedingly rare cutaneo-skeletal condition craniomandibular dermatodysostosis, in which focal glomerular sclerosis and end-stage renal failure developed and renal transplantation was required.
Metastatic bacterial endophthalmitis is a rare but devastating complication of septicaemia. We present 3 recent cases occurring in dialysis patients. Septicaemic dialysis patients seem particularly prone to staphylococcal endophthalmitis which developed in the face of therapeutic serum concentrations of appropriate antibiotics in all 3 cases. Prompt treatment, including consideration of intravitreal antibiotics, is required if vision is to be preserved. Early signs of endophthalmitis should be actively sought in septicaemic dialysis patients, as they are easily overlooked.
We examined renal biopsy specimens from patients with mesangial IgA glomerulonephritis (n = 25; plasma creatinine 0.05-0.30 mmol/l) to ascertain whether the myofibroblast has a role in progressive renal interstitial fibrosis. Myofibroblasts were identified by morphology and alpha smooth muscle actin (alpha-SMA) immunostaining at the light and electron microscope level. Results were related to staining for interstitial leukocytes and collagen III. A control group consisted of 6 normal renal transplant donors from whom biopsy specimens were taken at the time of vascular anastomosis. The fractional volume of interstitial alpha-SMA staining was greater in patients with mesangial IgA glomerulonephritis than in the control group (17.2 vs. 1.3%; p < 0.001). alpha-SMA staining was increased in areas of interstitial fibrosis with prominent periglomerular and peritubular distribution. Ultrastructural studies established that alpha-SMA staining in the renal interstitium was intracellular, cytoplasmic, and confined to myofibroblast-like cells and processes. The alpha-SMA expression correlated with fractional volume of tubular atrophy/dilation (r = 0.79, p < 0.001), interstitial connective tissue (r = 0.66, p < 0.001), leucocytes (r = 0.72, p < 0.005), and collagen III (r = 0.71, p < 0.001). Staining correlated with renal function at the time of biopsy (r = 0.64, p < 0.005) and after 2 years of follow-up (r = 0.77, p < 0.01). In conclusion, cells with a myofibroblast-like phenotype have a significant role in the progression of tubulointerstitial injury.
We have examined the temporal and spatial distribution of myofibroblast-like cells, a phenotype with fibroblast and smooth muscle features, in an experimental model of renal infection. Escherichia coli organisms (10(5)) were inoculated directly into the renal cortex of Sprague-Dawley rats weighing 270 g. Saline was substituted in a control group. The animals were sacrificed at five time points up to day 24 (E. coli n = 8, controls n = 3 each interval). Myofibroblasts were identified by morphology and immunohistochemistry for alpha smooth muscle actin (alpha-SMA) and compared with staining for monocytes (ED-1), collagen III, and bromodeoxyuridine incorporation. Histological changes included a focal lesion in E. coli infected animals. Interstitial alpha-SMA staining was confined to spindle-shaped cells resembling myofibroblasts. The percent fractional area of alpha-SMA staining in the lesion increased from 0.12 +/- 0.09 at day 1 to 20.0 +/- 7.1 at day 3 (p < 0.005), decreasing progressively to 2.0 +/- 2.6 by day 24. This paralleled bromodeoxyuridine incorporation in myofibroblasts: 0.4 +/- 0.5 cells/0.25 mm2 at day 1, 105.0 +/- 36.3 at day 3, and 2.6 +/- 2.2 cells/0.25 mm2 at day 24. ED-1-positive cells increased from 374 +/- 200/0.25 mm2 at day 1 to 894 +/- 88 at day 3 (p < 0.01), declining to 230 +/- 108/0.25 mm2 by day 24. Intracellular collagen III and alpha-SMA stainings were colocalized at day 3. The fractional area of collagen III increased by day 24 (p < 0.05). In conclusion, myofibroblasts accumulate transiently during renal interstitial fibrosis and are derived at least in part from local proliferation.(ABSTRACT TRUNCATED AT 250 WORDS)
OBJECTIVE: To measure the reliability and preliminary validity of a grading instrument for editors to evaluate the quality of peer reviews. DESIGN: The consecutive sample design included 53 reviews of 23 manuscripts. Reviews were systematically assigned to interrater reliability (n = 41; power greater than 0.90 to detect a difference of greater than one point) and preliminary criterion-related validity (n = 12) subsamples. Content validity was closely examined. SETTING: Nonclinical. PARTICIPANTS: Three graders evaluated reliability. One individual examined content validity and two editors tested preliminary criterion-related validity. INTERVENTION (INSTRUMENT)--Attributes reflecting two basic dimensions, review content and format, were identified and scored (values are possible points/percent contribution): timeliness, 3/21%; grade sheet, 1/7%; etiquette, 1/7%; sectional narratives, 3/21%; citations, 2/14%; narrative summary, 2/14%; and insights, 2/14%. A scoring guide was provided. MAIN OUTCOME MEASURES: Statistical analyses used to test the interrater reliability of the total score included the intraclass correlation coefficient and analysis of variance with the expectation to uphold the null hypothesis. Kendall's coefficient of concordance was used to test preliminary criterion-related validity. RESULTS: The intraclass correlation coefficient was .84 (P < .001) and a lack of difference between mean scores was demonstrated by analysis of variance (P = .46). Content validity was confirmed and preliminary criterion-related validity was indicated (Kendall's coefficient of concordance = .94, P = .038). CONCLUSIONS: The instrument is reliable. Content validation has been completed, and further criterion-related validation is warranted.
Twenty-five (3%) of 865 patients with IgA nephropathy presented with acute renal failure (ARF). These patients were matched with 25 patients in the same series who presented with irreversible renal impairment. Patients with acute renal failure had a significantly higher incidence of macroscopic hematuria and red blood cells in tubules. Conversely, a greater percentage of patients with irreversible renal failure had > or = 40% sclerosed glomeruli. The long-term prognosis for patients presenting with ARF appears excellent with only 1 (4%) patient developing chronic renal failure after a mean follow-up of 65 months. Mechanisms of acute renal failure in IgA nephropathy are discussed.
Morphometric quantitative analysis of the renal arterioles (arteriole wall thickness and overall vessel size) in renal biopsies from 21 cadaveric renal allograft recipients taken immediately prior to (0 months) and 3 months after transplantation was carried out using a computer-aided image analyzer. Patients (n = 10) who received standard therapy (cyclosporine, azathioprine and prednisolone) showed an increase in arteriole wall thickness at 3 months compared to 0 months (p < 0.01). Patients (n = 11) who received standard therapy and oral diltiazem (60 mg t.d.s.) showed no such change in the arteriole wall thickness between 0 and 3 months. As cyclosporine toxicity and/or chronic vascular rejection are associated with an increase in arteriole wall thickness, the differences observed in this study may imply a protective role for diltiazem on renal arterioles.
A variety of intravascular stents are currently under investigation and in various stages of achieving governmental approval for clinical application. The Palmaz balloon-expandable stent has recently been approved for use in the iliac arteries based on specific indications for application. Stents are generally described according to their method of deployment and are either balloon-expandable or self-expanding. Clinical application has been proved in the iliac arteries, where the use of stents has greatly enhanced the treatment of patients with total occlusions, complex dissections, and restenoses. Additionally, there is promise that stents will enhance the percutaneous treatment of renal artery ostial lesions, infrainguinal arterial lesions, and strictures in large veins. Clearly, the increasing application of intravascular stents has ushered in a new era of percutaneous intervention.
In a retrospective review, a low-dose urokinase (UK) infusion regimen (mean, 87,000 U of UK per hour and 100 U of heparin per hour) was evaluated for lower extremity arterial and graft occlusions. Results of 132 infusions in 111 patients were analyzed to determine efficacy, limb salvage, and complications. Angiographic success was achieved with 126 infusions (95%), and amelioration of presenting signs and symptoms was achieved after 116 infusions (88%). Patients who underwent additional percutaneous procedures were more likely to have a successful outcome. There was no significant difference in success rates for patients receiving low-dose heparin through the arterial sheath (n = 101) versus those receiving concomitant systemic heparinization (n = 29), (P = .08) [corrected]. Of 88 threatened extremities (with rest pain, cold, ulcers, or gangrene), nine were amputated (limb salvage = 90%), accounting for 82% (nine of 11) of amputations in the overall study. Patients with zero- or one-vessel runoff before infusion were more likely to require limb amputation compared with the group with two- or three-vessel runoff before infusion (P less than .01). Major periprocedural complications occurred in nine of 132 (7%) infusions, five of which necessitated specific surgery and/or transfusion for bleeding. Pericatheter thrombosis was not encountered in either subgroup. This standard local low-dose infusion represents a safe and effective treatment for lower extremity arterial and graft occlusions.
The effect of pH neutralization on the pain experienced during intradermal lidocaine administration was investigated in a prospective blind study of 20 adult volunteers. A plain solution (pH congruent to 6.1) and three different buffered solutions of 1% lidocaine (pH values of 6.8, 7.0, and 7.2) were prepared, and a 0.5-mL intradermal injection of each was administered to the volar aspect of the forearm. Pain associated with lidocaine infiltration was rated with a linear visual analogue scale. Solutions with a pH of less than 6.8 (unbuffered lidocaine in this study) predictably produced a burning pain sensation on injection. However, buffering of 1% lidocaine above a pH of 6.8 significantly (P less than .05) reduced the mean quantitative pain estimates compared with the nonbuffered controls.
A transjugular intrahepatic portosystemic shunt (TIPS) can be created percutaneously with the Palmaz balloon-expandable stent. This article describes a transjugular-only approach with a 16-gauge needle. A functional and efficacious shunt can be achieved in most cases with stent diameters of 8-10 mm. Occasionally, a 12-mm-diameter shunt is necessary for effective variceal decompression. The procedure is considered successful when the portosystemic gradient is lowered to 12 mm Hg or less after stent placement. Hepatic vein stenosis in the shunt outflow can develop after the TIPs procedure. This complication has been treated successfully with additional stent placement. TIPS can undoubtedly be performed successfully and safely with a transjugular-only approach; however, the full impact of TIPS on the treatment of portal hypertension remains to be determined.
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Mechanisms of progression of chronic renal failure (CRF) have been well documented in the rat but may not be relevant in man. Factors which may modify clinical CRF include underlying disease, diet, hypertension, intercurrent events, and adverse or beneficial effects of drug therapy. It has been argued that progression in many forms of renal disease is inexorable below a certain level of renal function. In other diseases, eg primary malignant hypertension, analgesic nephropathy, function frequently improves in both the short and long term with appropriate management. Thus knowledge of the nature of the underlying disease is essential in assessing progression. The value of diet in preserving renal function has been debated, particularly the relative roles of protein and phosphate control. In our own unit, a prospective randomized study showed a benefit of protein restriction. Development of accelerated hypertension is an important cause of progression of renal disease and clinical and experimental evidence supports the view that non-accelerated hypertension is also a factor in progression, amenable to treatment. Various intercurrent events may accelerate progression and function may be lost permanently following sepsis, urinary tract obstruction, renal arterial or venous obstruction, hypotension and in some cases pregnancy. Numerous drugs can have deleterious effects on the kidney. The possibility that converting enzyme inhibitors might preserve renal function is attracting attention but in view of their side effects their place in therapy should be determined by prospective controlled studies in which the above factors are carefully considered.
We performed a prospective randomized trial, comparing the incidence of peritonitis between a flush-disconnect (O-System, Baxter, Deerfield, IL) (OS) and a conventional (System II, Baxter) (CS) continuous ambulatory peritoneal dialysis (CAPD) method. Sixty consenting patients with no significant physical disabilities who commenced CAPD after May 1987 were entered and followed for a minimum of 12 months. Thirty were placed on the OS system and 30 were placed on CS. Age, gender, and time for training did not differ significantly. The period of observation for OS was 375 months; CS was observed for 430 months. OS patients experienced 28 episodes of peritonitis (13.4 months/patient/episode) compared with 88 (4.9 months/patient/episode) in CS (p less than 0.005). By 6 months, 32% of OS patients had had at least one episode of peritonitis, compared with 62% of CS patients; at 12 months, these figures rose to 48% for OS and 91% for CS (p less than 0.01) patients (Life Table Analysis). The median survival time to first peritonitis episode was 5.1 months in CS and 9.7 months in OS (p less than 0.01). Exit-site infections occurred in 14/30 (46%) of patients on OS and in 13/30 (43%) of CS patients. We conclude that the OS was associated with a significant reduction in the incidence of peritonitis.
OBJECTIVE: --To determine the effectiveness of the Palmaz balloon expandable stent for the creation of a transjugular intrahepatic portosystemic shunt. The device is designed to achieve portal decompression in patients with variceal hemorrhage secondary to portal hypertension. DESIGN: --Transjugular intrahepatic portosystemic shunting was performed in eight patients during a 9-month period. Mean follow-up was 5 months. PATIENTS: --All patients had cirrhosis with portal hypertension and varices. Bleeding occurred in seven patients from esophageal varices and in one patient from hemorrhoids. MAIN OUTCOME MEASURES: --Shunt patency and recurrent variceal hemorrhage. RESULTS: --Shunts created from a transjugular approach between a hepatic and a portal vein (diameters of 8 to 12 mm) lowered the average portosystemic pressure gradient from 36 to 11 mm Hg. Mean postoperative hospital stay was 7.7 days. Complete variceal decompression after transjugular intrahepatic portosystemic shunt placement was identified endoscopically in all eight patients. The patient treated for hemorrhoids rebled and was treated successfully by transfemoral balloon expansion of the shunt diameter from 8 to 12 mm. All shunts were patent at 1 to 9 months (mean, 5 months) of follow-up. CONCLUSION: --Initial results suggest that transjugular intrahepatic portosystemic shunt is a safe and effective method of portal decompression for the treatment of variceal hemorrhage.
Primary sarcomas of the aorta are rare vascular tumors. About 26 cases have been reported between 1973 and 1989. They are seldom diagnosed antemortem. The present report describes a patient with a myxoid malignant fibrous histiocytoma arising in the intima of the lower thoracic aorta, which was diagnosed premortem in metastatic peripheral emboli. The clinical and pathologic features of this patient along with a summary of the 29 primary aortic tumors previously reported (26 malignant and 3 benign) are discussed. Although few of these tumors have been described histologically as benign, all of them behave as malignant tumors.