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Biomedical subjects

K F Fairley

Publications and source records attributed to K F Fairley.

At least 19 recordsLinked to original sources

Randomized controlled trial of cyclophosphamide, warfarin and dipyridamole in idiopathic membranous glomerulonephritis.

40 patients with idiopathic membranous glomerulonephritis were randomized to receive either no treatment or a regime of cyclophosphamide for 6 months, and warfarin and dipyridamole for two years. During the two years of the trial there was no significant deterioration in renal function in either group. A significantly greater improvement in urinary protein excretion was, however, observed at all time points in the treatment group. Plasma albumin was also significantly higher in the treatment group at 18 and 24 months. As progressive deterioration in renal function in membranous glomerulonephritis is associated with persistent heavy proteinuria these results suggest a beneficial effect of treatment.

Cyclophosphamide

Lupus nephritis and pregnancy.

Sixty-four pregnancies in 41 women with biopsy proven lupus nephritis between 1965 and 1991 were analysed to record fetal and maternal outcome and identify risk factors for poor outcome. Of 65 fetuses, 22 (34 per cent) were lost (including therapeutic abortions), 19 (30 per cent) were live born but premature (less than or equal to 36 weeks gestation) and 24 (37 per cent) were term. Fetal loss after 20 weeks gestation was 19 per cent. Twelve per cent of 25 fetuses whose birthweight was recorded were small for gestational age. Maternal renal function deteriorated in 19 per cent of pregnancies but was irreversible post-partum in only one woman (2 per cent). Hypertension was recorded in 44 per cent of pregnancies, developed early (less than or equal to 32 weeks gestation) in 28 per cent and was severe in 13 per cent. Treated hypertension predated 17 per cent of pregnancies and in 6 per cent (included in the overall incidence of hypertension) exacerbation occurred during pregnancy despite continued anti-hypertensive medication. Nine women (22 per cent) who developed de novo hypertension in pregnancy had permanent hypertension post-partum. Increased proteinuria was recorded in 48 per cent of pregnancies and was irreversible post partum in 5 per cent. Comparison of pregnancies occurring before or after diagnosis was made by renal biopsy failed to show any significant difference in fetal outcome. Pregnancies occurring after the diagnosis of glomerulonephritis were associated with a significantly lower incidence of maternal hypertension, early hypertension, severe hypertension and increased proteinuria. The presence of the circulating lupus anticoagulant was clearly associated with a significantly high fetal loss rate although the incidence of maternal complications did not differ significantly between mothers positive or negative for lupus anticoagulant.

Abortion, Spontaneous

Sterile pyuria.

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Bacteria

Mesangiocapillary glomerulonephritis type II (dense-deposit disease): clinical features of progressive disease.

Twenty-seven patients presenting to the Royal Melbourne Hospital between 1968 and 1988 with mesangiocapillary glomerulonephritis type II with intramembranous dense deposits (dense-deposit disease, DDD) are analyzed. Patients were divided into two groups on the basis of whether renal function deteriorated (14 patients) or remained stable (13 patients). At presentation or during the course of the disease, heavy proteinuria, macroscopic hematuria, and high quantitative urinary red cell or white cell counts characterized patients with progressive disease. Patients with crescents on their initial renal biopsy or with large numbers of polymorphs in glomerular capillaries corresponding with sterile pyuria were more likely to have deterioration of renal function. The average time from onset of symptoms to development of end-stage renal disease was over 16 years. The patient's clinical course could not be anticipated by serum complement profiles, the presence of C3 nephritic factor, or partial lipodystrophy. Pregnancy did not affect the course of the disease. Six patients underwent renal transplantation and the disease recurred on renal biopsy in four. However, only two individuals lost renal allografts due to recurrent DDD.

Adolescent

Detection of bladder bacteriuria in patients with acute urinary symptoms.

Quantitative culture of midstream urine fails to yield a significant microorganism in many patients with acute urinary symptoms. We cultured bladder urine, obtained by aspiration, from symptomatic adults with equivocal findings on standard testing of midstream urine for low numbers of conventional uropathogens and fastidious bacteria. We found 561 (31%) of 1817 women and 36 (12%) of 300 men to be culture positive. Five hundred eighty-one (70%) of 830 isolates were fastidious bacteria; 191 (34%) of 561 culture positive women and 0 of 36 culture-positive men had polymicrobic bacteriuria. Bacterial counts were less than 10(5) colony-forming units/mL in 67% of samples; 204 of 406 patients with single-species infections had increased leukocyte counts in urine. Patients with symptoms of urinary tract infection who are culture negative on standard testing may harbor fastidious bacteria or low numbers of conventional uropathogens in the bladder. In these patients, culture of bladder aspiration urine for low counts and fastidious species is necessary to diagnose bacteriuria.

Acute Disease

Urine cytologic profile in renal allograft recipients determined by monoclonal antibodies. Diagnosis of allograft rejection.

Controversy exists as to the type of cells present in the urine during renal allograft rejection. In order to resolve this controversy as well as to evaluate the value of urine sediment examination as a means of detecting AR, we quantitated the different cells present in urine during AR using an immunoperoxidase technique and monoclonal antibodies reactive with lymphocytes, monocytes, granulocytes, glomerular epithelial, tubular, and urothelial cells. Urine sediment (n = 176) was examined serially over 3 months in 15 transplant recipients. There were 12 episodes of early posttransplant acute tubular necrosis and 21 episodes of AR. It was possible to detect AR as well as to distinguish AR from ATN. Lymphocyte and tubular cell excretions were increased significantly during AR. Excretion of urothelial cells was also significantly increased during most episodes of AR suggesting that rejection of ureters occurs concomitantly with rejection of the kidneys.

Antibodies, Monoclonal

Primary glomerulonephritis and pregnancy.

Three hundred and ninety-five pregnancies undertaken by 238 women with primary glomerulonephritis between 1962 and 1987 were analysed to record fetal and maternal outcome and identify risk factors for a poor outcome. Of 398 fetuses, 26 per cent were lost (including therapeutic abortions), 24 per cent surviving infants were premature (less than or equal to 36 weeks gestation) and 51 per cent were term. Excluding therapeutic abortions, 20 per cent of fetuses were lost, 15 per cent after 20 weeks gestation. Fifteen per cent of 237 fetuses whose birth weight was recorded were small for gestational age: Deterioration in maternal renal function was seen in 15 per cent of pregnancies and in 5 per cent of women failed to resolve post partum. Only four women had impaired renal function recorded in the first-trimester and two of these were known to have renal impairment before pregnancy. Hypertension was recorded in 52 per cent of pregnancies, developed early (less than or equal to 32 weeks gestation) in 26 per cent and was severe in 18 per cent. Treated hypertension pre-dated 12 per cent of pregnancies and in 7 per cent (included in the overall incidence of hypertension) exacerbation occurred during pregnancy despite continued antihypertensive medication. Forty-four women (18 per cent) who developed de novo hypertension in pregnancy had permanent hypertension postpartum. Increased proteinuria was recorded in 59 per cent of pregnancies and was irreversible in 15 per cent of women. Comparison of pregnancies which occurred before or after renal biopsy revealed a significantly higher fetal loss rate after 20 weeks gestation in those pregnancies undertaken before the diagnosis of renal disease, and a significantly higher incidence of hypertension and increased proteinuria. Impaired renal function, early or severe hypertension or nephrotic range proteinuria was significantly associated with increased fetal loss, prematurity and fewer full-term infants. There was no significant difference in fetal outcome or maternal complications in pregnancy in patients with treated hypertension before pregnancy and those who were normotensive in the first-trimester. The highest incidence of fetal and maternal complications occurred in patients with primary focal and segmental hyalinosis and sclerosis and the lowest in non-IgA diffuse mesangial proliferative glomerulonephritis. The presence of severe vessel lesions on renal biopsy was associated with a significantly higher total fetal loss and fetal loss after 20 weeks gestation.

Female

Immunoperoxidase identification of nucleated cells in urine in glomerular and acute tubular disorders.

Nucleated nonsquamous cells in urine of patients with crescentic glomerulonephritis (CN), noncrescentic glomerulonephritis (NCN), acute tubular necrosis (ATN) and drug related acute interstitial nephritis (AIN) were identified using monoclonal antibodies and immunoperoxidase stain. Cell viability was determined by trypan blue permeability. CN was distinguishable from NCN by total cell numbers exceeding 30,000/ml (p less than 0.001) and counts of granulocytes exceeding 10,000/ml (p less than 0.05), monocytes exceeding 3,000/ml (p less than 0.001), T4 lymphocytes exceeding 1,500/ml (p less than 0.001), T8 lymphocytes exceeding 1,500/ml (p less than 0.001), glomerular epithelial cells exceeding 4,000/ml (p less than 0.001), proximal tubular cells exceeding 8,000/ml (p less than 0.001), loop of Henle cells exceeding 1,500/ml (p less than 0.01) and urothelial cells exceeding 1,500/ml (p less than 0.05). AIN was distinguishable from ATN by total cell numbers exceeding 75,000/ml (p less than 0.001) and counts of granulocytes exceeding 150,000/ml (p less than 0.001), monocytes exceeding 5000/ml (p less than 0.001), T4 lymphocytes exceeding 3,000/ml (p less than 0.01), T8 lymphocytes exceeding 2,500/ml (p less than 0.01) and cell viability exceeding 60% (p less than 0.05). Proximal tubular, loop of Henle, distal tubular/collecting duct and urothelial cells were present in high numbers in CN, ATN and AIN. CN can be distinguished from NCN, and ATN can be distinguished from AIN by identifying and quantifying the nucleated cells present in the urine.

Acute Kidney Injury

Morphologic changes in the renal glomerulus and the juxtaglomerular apparatus in human preeclampsia.

The renal biopsies of ten women with preeclampsia without other underlying renal disease were examined in detail using light and electron microscopy and immunofluorescence. Characteristic preeclamptic glomerular lesions with endocapillary cell swelling, subendothelial and mesangial deposits, and mesangial interposition were detected in each patient. Juxtaglomerular regions were not prominent and were poorly granulated on light microscopy; ultrastructurally, they showed myoepithelioid cells with sparse renin granulation and considerable heterogeneity of granule size and density in association with relatively meagre granular endoplasmic reticulum and Golgi profiles. These morphologic findings suggest that, in patients with clinical and renal biopsy evidence of preeclampsia, there is no significant stimulation of the renin-angiotensin system.

Adolescent

Morphometric analysis of pre-eclampsia in women biopsied in pregnancy and post-partum.

The importance of endothelial cell swelling and subepithelial deposits in producing capillary wall thickening in women with pre-eclampsia is controversial. In this study renal biopsy tissue from 16 women with a diagnosis of pre-eclampsia was analyzed morphometrically. Women biopsied during pregnancy (N = 6) showed substantial, electron-dense subendothelial deposits in capillary loops, but these were rare or absent in women (N = 10) biopsied post-partum (P less than 0.01). Endothelial cell swelling was present in both groups of patients to an equal degree. Mesangial cell interposition occurred but was not the dominant feature, and was similar in both pregnancy and post-partum biopsies. The median percentage per patient occupied by basement membrane was similar for both groups. Subendothelial deposits appear to resolve early in the post-partum period.

Adult

Immunocytologic dissection of the urine sediment using monoclonal antibodies.

A method to identify nucleated nonsquamous cells in urine using monoclonal antibodies and immunoperoxidase stain is described. Cells from washed deposits of midstream urine samples were transferred to gelatinized slides in a cytocentrifuge, air-dried, acetone fixed, and subjected to microwave irradiation. Slide preparations were then treated with monoclonal antibodies with the use of a four-layer peroxidase-antiperoxidase technique. It was possible to identify granulocytes, monocytes, lymphocytes, and renal epithelial and urothelial cells. This method was found to be helpful in determining the profiles of cells in urine in acute tubular necrosis, drug-related acute interstitial nephritis, and crescentic glomerulonephritis.

Acute Kidney Injury

Prevalence of Gardnerella vaginalis in the urinary tract.

Midstream urine samples from 106 patients presenting to the Casualty Department of The Royal Melbourne Hospital with frequency or dysuria were cultured for Gardnerella vaginalis and conventional uropathogens. Urine samples collected via an open-end catheter from 70 healthy pregnant women were examined similarly. Midstream urine and other samples, including the seminal fluids and swabs of the mouths, throats, rectums, and vaginas of 33 healthy subjects, were cultured for G. vaginalis. Another 15 female patients with proven G. vaginalis bacteriuria were given a bladder washout localization test to determine the site of infection in the urinary tract. G. vaginalis in counts greater than 10(3) CFU/ml was recovered from the midstream urine of 27 of 106 patients (25%), 7 of whom also harbored conventional pathogens in counts greater than 10(4) CFU/ml. Another 11 patients with cultures negative for G. vaginalis yielded greater than 10(4) CFU of conventional pathogens per ml. G. vaginalis was cultured (greater than 10(3) CFU/ml) from catheter samples of 19 of 70 healthy pregnant women (27%), 6 of whom also harbored greater than 10(3) CFU of conventional uropathogens per ml. Two women yielded growths of conventional pathogens only. Midstream urine samples from 13 of 13 healthy males were free of G. vaginalis, whereas 5 of 20 healthy nonpregnant females yielded greater than 10(3) CFU of G. vaginalis per ml from midstream urine samples. G. vaginalis was recovered from 4 of 12 semen samples and from urethral samples from four of seven males and four of eight females. All four culture-positive females also harbored G. vaginalis in their vaginas. There was no evidence of oral or rectal carriage of G. vaginalis in 15 healthy subjects. Localization studies with 15 female patients having underlying renal disease showed that 11 patients harbored G. vaginalis in their kidneys. The result suggest that colonization or infection of the bladder and upper urinary tract by G. vaginalis is very largely a phenomenon of females, with the highest frequency in pregnant women. The prevalence of G. vaginalis in the urinary tracts of healthy females is similar to that of symptomatic subjects. However, G. vaginalis in counts greater than 10(5) CFU/ml is more likely to be associated with urinary tract symptoms. In males, this bacterial species infects the genital tract rather than the urinary tract.

Female

Monoclonal antibodies: use in urine sediment examination.

Accurate identification of nucleated cells in urine can be difficult with conventional methods of microscopic urinalysis. Monoclonal antibodies were used with an immunoperoxidase technique to identify nucleated cells in urine. This new development in urinalysis is in its early stages, but it has helped to circumvent the difficulties associated with standard microscopy. The monoclonal antibody technique allowed for the identification of granulocytes, monocytes, lymphocytes, glomerular epithelial, proximal tubular, loop of Henle, distal tubule/collecting duct, and urothelial cells in urine, and by quantifying these cells it was possible to determine the urine cell profiles in various renal diseases as well as in allograft rejection and early post-transplant acute tubular necrosis in renal allograft recipients. The cell profiles are useful in aiding the diagnosis of these conditions.

Antibodies, Monoclonal

Lupus anticoagulant associated with renal thrombotic microangiopathy and pregnancy-related renal failure.

The clinical features in 12 women with a circulating coagulation inhibitor (lupus 'anticoagulant') were studied and correlated with findings in 22 renal biopsies in these patients. Four of 12 women had serological evidence of systemic lupus. Only two of 23 pregnancies in these women were successful. Lesions in all biopsies were remarkably similar. Seven biopsies taken during or soon after pregnancy showed acute fibrinoid lesions. 'Acute' lesions consisted of fibrin thrombi in glomeruli arterioles and arteries and double contours in glomerular capillary walls. Biopsies carried out remote from pregnancy in these seven patients showed persisting double contours in glomeruli together with narrowing of arteries due to recanalizing thrombi and cellular intimal proliferation. All other biopsies showed similar lesions. The lesions were essentially the same as those of thrombotic microangiopathy and those described previously in post-partum renal failure. Renal function was severely impaired in four patients and showed moderate impairment in two patients at the time that acute thrombotic lesions were demonstrated in glomeruli. Renal function in two patients improved during plasma exchange therapy. Because all biopsies showed either acute, healing or healed, thrombotic lesions, it is proposed that these lesions are characteristic of the renal findings in patients with a lupus 'anticoagulant'. In all but two cases the acute lesions were seen during or soon after pregnancy.

Abortion, Habitual

Pregnancy in women with primary focal and segmental hyalinosis and sclerosis.

Thirty-one pregnancies and post partum clinical course of 21 women with a diagnosis of primary focal and segmental hyalinosis and sclerosis have been analyzed. Forty-five percent (14) of pregnancies resulted in fetal loss, 39% (12) in premature delivery and 16% (5) in a term infant. Of 17 fetuses for whom birthweight was recorded, 29% (5) were small for gestational age. Maternal renal function deteriorated in 49% (15) of pregnancies, in 13% (4) irreversibly. Three of these patients (15%) subsequently progressed to end-stage renal failure, and one to progressive chronic renal impairment, by the end of follow-up (median 4 years, range 1-25 years). In 74% (23) of pregnancies hypertension was recorded and this frequently developed early (61%) and was severe (45%). Nephrotic range proteinuria developed in 42% (13) of pregnancies. Increased proteinuria was recorded in 22 (17%) pregnancies. It is concluded that pregnancy in women with primary focal and segmental hyalinosis and sclerosis is associated with increased fetal loss and maternal complications.

Adult

IgA glomerulonephritis and pregnancy.

One hundred and sixteen pregnancies in 70 women with a biopsy-proven diagnosis of IgA glomerulonephritis have been analysed. Thirty percent (35) of the fetuses died, 22% (26) were premature and 44% (52) were full term. Maternal renal function declined during pregnancy in 26% (30) and in 2% (2) this was irreversible post-partum. Hypertension developed in 52% (61) of the pregnancies and in 13% (15) this was irreversible. Increased proteinuria was recorded in 62% (74) of the pregnancies. Fetal loss in pregnancies taking place after biopsy diagnosis was lower (16%) than those in which biopsy was performed either during or following the pregnancy (36%).

Abortion, Habitual