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Michael D Hughson

Publications and source records attributed to Michael D Hughson.

17 recordsLinked to original sources
PubMed2006

A comparison of pathomolecular markers of fibrosis and morphology in kidney from autopsies of African Americans and whites.

African Americans have an increased incidence of chronic kidney disease (CKD) due to hypertension and arteriosclerosis and increased death due to coronary artery disease, compared with whites. The pathogenesis of CKD involves the increased presence and activation of myofibroblasts and macrophages, promotion of tubulointerstitial fibrosis, and effects of tubulointerstitial cell mitosis and apoptosis. We hypothesized that increased risk of hypertensive vascular disease may be identified by renal pathomolecular markers that are associated with progressive CKD. Renal sections were available from 50 autopsies of 33 African Americans (55% males) and 17 whites (76% males) undergoing forensic autopsy for unexpected death. Sclerotic glomeruli, severity of cortical fibrosis, and renal arteriolosclerosis, total glomerular number (N (glom)), average glomerular volume (V (glom)), birth weights, and blood pressure were known. Presence and locality of markers for myofibroblasts (alpha-SMA), macrophages (CD68), collagen, pro-fibrotic transforming growth factor-beta1 were scored in renal autopsies, and tubulointerstitial apoptosis was recorded. The results demonstrated a strong positive correlation between age, cortical fibrosis and alpha-SMA (p<0.05), and between CD68 and hypertension and coronary artery disease (p<0.05). The findings confirm the role of myofibroblasts and macrophages in pathogenesis of human CKD. However, the markers showed no significant relationships to V (glom), N (glom), birth weight, or race.

Actins↗
PubMed2006

N-Acetylcysteine improves renal dysfunction, ameliorates kidney damage and decreases blood pressure in salt-sensitive hypertension.

BACKGROUND: Salt-sensitive hypertension in humans and experimental animals causes progressive increases in renal damage and dysfunction. The Dahl salt-sensitive (S) rat closely mimics human salt-sensitive hypertension. AIM: Our goal was to test the hypothesis that enhancing the glutathione system with dietary N-acetylcysteine administration in Dahl S rats on a high sodium intake for 5 weeks will attenuate the increases in arterial pressure, the decreases in renal hemodynamics and the increases in renal damage that normally occur in S rats on high sodium. METHODS: Forty-four 7- to 8-week-old Dahl S/Rapp strain rats were maintained on a high sodium (8%), high sodium + N-acetylcysteine (4 g/kg per day), or low sodium (0.3%) diet for 5 weeks. Rats had arterial and venous catheters implanted at day 21. RESULTS: By day 35 in the high-sodium rats, N-acetylcysteine treatment significantly increased the renal reduced-to-oxidized glutathione ratio, glomerular filtration rate, and renal plasma flow, and decreased renal cortical and medullary O2 release, urinary protein excretion, renal tubulointerstitial damage and glomerular necrosis. At this time, mean arterial pressure increased to 183 +/- 1 mmHg, and N-acetylcysteine reduced this arterial pressure to 121 +/- 4 mmHg. By day 35 in S high-sodium rats, N-acetylcysteine had caused a 91% decrease in glomerular necrosis and an 83% decrease in tubulointerstitial damage. CONCLUSIONS: In Dahl S rats on high sodium intake, arterial pressure increases significantly and renal injury is pronounced. Treatment with N-acetylcysteine enhances the renal glutathione system, improves renal dysfunction and markedly decreases arterial pressure and renal injury in Dahl salt-sensitive hypertension.

Acetylcysteine↗
PubMed2006

How many glomerular profiles must be measured to obtain reliable estimates of mean glomerular areas in human renal biopsies?

The objective of this study was to investigate the number of glomerular profiles that are required for accurate estimates of mean profile area in a renal biopsy series. Slides from 384 renal biopsies from one center were reviewed. They contained a median of seven glomerular profiles or of four profiles without sclerosis. Profile areas were measured using stereologic point counting. The "true individual mean" for each biopsy was calculated and the "true population mean" for groups of biopsies derived. Individual and population "random sample means" then were calculated from a random sampling of profiles in each biopsy and were compared with true means for the same biopsies. The effect on the true population means of the entire group of biopsies was also assessed, as the minimum number of glomerular profiles that were required for inclusion was changed. In a single biopsy, random sampling of > or =10 profiles without exclusions and of eight profiles or more without sclerosis reliably estimated the true mean areas. In a group of 30 biopsies, random sampling of five or more glomeruli per biopsy reliably estimated the true population mean. In the aggregate series, inclusion of all 384 biopsies produced the most robust true population mean; the reliability of the estimates decreased as the numbers of eligible biopsies diminished with increasing requisite minimum numbers of profiles per biopsy. We conclude that, while > or =10 profiles might be needed for reliable area estimates in a single biopsy, far fewer profiles per biopsy can suffice when groups of biopsies are studied. In analyses of groups of biopsies, all available biopsies should be used without consideration of the number of glomerular profiles in each. Stipulation of a specific minimum number of glomeruli in each biopsy for inclusion reduces the power of analyses because fewer biopsies are available for evaluation.

Adult↗
PubMed2006

Does nephron number matter in the development of kidney disease?

The total number of nephrons in normal human kidneys varies over a 10-fold range. This variation in total nephron number leads us to question whether low nephron number increases the risk of renal disease in adulthood. This review considers the available evidence in humans linking low nephron number/reduced nephron endowment and the susceptibility to renal disease. Total nephron number in humans has been directly correlated with birth weight and inversely correlated with age, mean glomerular volume, and hypertension. Low nephron number may be the result of suboptimal nephrogenesis during kidney development and/or loss of nephrons once nephrogenesis has been completed. Low nephron number is frequently, but not always, associated with hypertrophy of remaining glomeruli. This compensatory hypertrophy has also been associated with a greater susceptibility for kidney disease. Three human studies have reported reduced nephron number in subjects with a history of hypertension. This correlation has been observed in White Europeans, White Americans (but not African Americans) and Australian Aborigines. Studies in additional populations are required, as well as a greater understanding of the fetal environmental and genetic determinants of low nephron number.

Black or African American↗
PubMed2005

Determinants of glomerular volume in different cortical zones of the human kidney.

Enlarged glomerular size is a feature of focal segmental glomerulosclerosis, obesity-related glomerulopathy, diabetic nephropathy, and hypertension. The distribution of glomerular volumes within different cortical zones and glomerular volume alterations with age and obesity may contribute to understanding the evolution of these diseases. We analyzed the distributions of volumes of individual glomeruli in the superficial, middle, and juxtamedullary cortex of normal human kidneys using the disector/Cavalieri method. Volumes (V(glom)) of 720 nonsclerotic glomeruli (30 per kidney, 10 per zone) were estimated in autopsy kidneys of 24 American men, 12 aged 20 to 30 yr and 12 aged 51 to 69 yr. Black and white individuals were represented equally. The range of individual V(glom) within subjects varied from two- to eight-fold. There were no significant zonal differences in V(glom) in the young or those with body surface area (BSA) < or = 2.11 m(2). In contrast, superficial glomeruli in the older age group, in those with BSA > 2.11 m(2), and in white subjects were significantly larger than juxtamedullary glomeruli. Black subjects tended toward larger V(glom) than white subjects, and this difference was significant and most marked in the juxtamedullary zone and independent of age, BSA, and glomerular number. There is a wide range in individual V(glom) in adults. BSA, race, and age independently influence V(glom) in different zones of the renal cortex. These findings might reflect processes of aging and susceptibility factors to renal disease.

Adult↗
PubMed2005

Antioxidant treatment prevents renal damage and dysfunction and reduces arterial pressure in salt-sensitive hypertension.

The goal of this study was to test the hypothesis that oxidative stress in Dahl salt-sensitive (SS) rats on a high-sodium intake contributes to the progression of renal damage, the decreases in renal hemodynamics, and the development of hypertension. We specifically studied whether antioxidant therapy, using vitamins C and E, could help prevent renal damage and glomerular filtration rate (GFR) and renal plasma flow reductions and attenuate the increases in arterial pressure. Thirty-three 7- to 8-week old Dahl SS/Rapp strain rats were placed on either a high-sodium (8%) or a low-sodium (0.3%) diet with or without vitamin E (111 IU/d) in the food and 98 mg/d vitamin C in the drinking water for 5 weeks. Rats were equipped with indwelling arterial and venous catheters at day 21. By day 35 in the rats with high-sodium diet, vitamin C and E treatment significantly decreased renal cortical and medullary O2*- release, mean arterial pressure, urinary protein excretion, glomerular necrosis, and renal tubulointerstitial damage. At this time, GFR significantly decreased in the high-sodium diet group (1.6+/-0.2 mL/min) when compared with either the high-sodium plus vitamins C and E (2.9+/-0.2 mL/min) or the low-sodium diet group (2.9+/-0.3 mL/min). In SS rats on high-sodium diet, renal plasma flow decreased 40%, and this reduced flow was restored by vitamin treatment. In Dahl salt-sensitive hypertension, increased oxidative stress plays an important role in the renal damage, decreases in renal hemodynamics, and increases in arterial pressure that occur. Antioxidant treatment with vitamins C and E improves renal dysfunction, lessens renal injury, and decreases arterial pressure in Dahl salt-sensitive hypertension.

Animals↗
PubMed2005

Human papillomavirus genotyping and p16INK4a expression in cervical intraepithelial neoplasia of adolescents.

Adolescents have high rates of human papillomavirus (HPV) infection, and persistent high-risk HPV infection can lead to the development of cervical cancer. The cyclin-dependent kinase inhibitor, p16(INK4a) is overexpressed in cervical intraepithelial neoplasia (CIN), probably due to a persistent and integrated HPV infection. This study investigated p16(INK4a) expression, grades of CIN, and high-risk HPV infection in adolescent cervical biopsies. Biopsies were immunohistochemically stained for p16(INK4a). The presence of wide-spectrum, low-risk, or high-risk HPV was determined by amplifying DNA extracted from the cervical biopsies. Biopsies were classified as cervicitis, 15 cases; CIN 1, 48 cases; CIN 2, 46 cases, and CIN 3, 52 cases. The distribution of p16(INK4a) staining was graded as patchy, diffuse basal, and diffuse full thickness. Pearson's chi(2) tests analyzed the relationships between p16(INK4a) staining, HPV infection, and CIN. Biopsies of cervicitis were negative for HPV and for p16(INK4a) expression. High-risk HPV 16, 18, and 31 increased from 18% in CIN 1 to 66% in CIN 2/3 (P<0.001). In CIN 1, p16(INK4a) was positive in 44% of biopsies with 35% showing patchy, 7% diffuse basal, and one case (2%) showing diffuse full thickness staining. In CIN 2/3, p16(INK4a) was positive in 97% of biopsies with 23% showing patchy, 21% diffuse basal, and 53% diffuse full thickness staining. The difference in the proportions of biopsies showing patchy p16(INK4a) staining in CIN 1 and diffuse full thickness staining in CIN 2/3 was significant (P<0.001). In CIN 1, 61% of high-risk HPV-positive biopsies were p16(INK4a) negative, while all high-risk HPV-positive CIN 2/3 biopsies were p16(INK4a) positive. Diffuse, full thickness p16(INK4a) expression discriminated low-grade from high-grade CIN and appears to be a marker of persistent high-risk HPV infection.

Adolescent↗
PubMed2004

Expression of fibronectin and HIF-1alpha in renal cell carcinomas: relationship to von Hippel-Lindau gene inactivation.

The von Hippel-Lindau (VHL) tumor suppressor gene (TSG) at 3p25 is mutated in approximately 50% of conventional (clear cell) renal cell carcinomas (cRCC). VHL normally regulates the ubiquitin-mediated proteolysis of hypoxia-inducible factor 1alpha (HIF-1alpha), and VHL inactivation results in increased cellular HIF-1alpha expression. VHL protein (pVHL) also interacts with fibronectin (Fn) and VHL inactivation results in defective Fn extracellular matrix assembly. The present study investigated the immunohistochemical (IHC) staining for Fn and HIF-1alpha in 11 cRCC and the relationship of the staining to VHL inactivation by gene deletion, mutation, or hypermethylation. Evidence for VHL inactivation by 3p deletions and VHL mutations were found in six tumors. Fn-positive IHC staining of tumor cells and negative to weak staining of extracellular stroma was found in five cases having exon 1 or exon 2 mutations. In contrast, Fn staining was absent in tumor cells and positive in the stroma of five tumors without VHL inactivation and in one tumor with a C-terminal exon 3 mutation. HIF-1alpha tumor cell staining was present in the cRCC with VHL inactivation but was also present in two tumors having 3p deletions but neither mutation nor hypermethylation of VHL. These two cRCC showed a tumor cell-negative and stroma-positive pattern of Fn staining. The findings indicate that VHL inactivation plays a role in the development of some cRCC by altering Fn cell--stroma relationships. They also suggest that some C-terminal mutations may not interfere with Fn assembly and that a 3p TSG in addition to VHL influences HIF-1alpha degradation.

Carcinoma, Renal Cell↗
PubMed2004

The predictive value of p16(INK4a) and hybrid capture 2 human papillomavirus testing for high-grade cervical intraepithelial neoplasia.

We performed p16(INK4a) immunocytochemical analysis and Hybrid Capture 2 (HC2; Digene, Gaithersburg, MD) high-risk HPV testing on 210 abnormal SurePath (TriPath Imaging, Burlington, NC) Papanicolaou specimens diagnosed as low-grade squamous intraepithelial lesion (LSIL) or high grade squamous intraepithelial lesion (HSIL). The results were compared with 121 follow-up biopsy specimens. p16(INK4a) was positive in 57.9% of women with LSIL compared with 97.1% of women with HSIL. In contrast, HC2 testing was positive in 85.0% of women with LSIL and 86.4% of women with HSIL. The differences in the positive rates for16(INK4a) between LSIL and HSIL was significant (P < .001), whereas, for HC2, it was not (P = .264). In patients who had cervical biopsies following a cytologic diagnosis of LSIL, the positive predictive value (PPV) of p16(INK4a) for a biopsy of cervical intraepithelial neoplasia grade 2 or 3 (CIN2/3; 33.3%) was significantly higher than the PPV of HC2 results (21.2%) (P < .001). Using liquid-based cytology specimens, p16(INK4a) immunocytochemical analysis has a higher PPV than reflex HC2 HPV testing for identifying CIN2/3 among patients with LSIL and might be useful for selecting patients with LSIL for colposcopy.

Cyclin-Dependent Kinase Inhibitor p16↗
PubMed2003

Regulation of 11 beta-hydroxysteroid dehydrogenase enzymes in the rat kidney by estradiol.

The 11beta-hydroxysteroid dehydrogenase (11betaHSD) type 1 (11betaHSD1) enzyme is an NADP+-dependent oxidoreductase, usually reductase, of major glucocorticoids. The NAD+-dependent type 2 (11betaHSD2) enzyme is an oxidase that inactivates cortisol and corticosterone, conferring extrinsic specificity of the mineralocorticoid receptor for aldosterone. We reported that addition of a reducing agent to renal homogenates results in the monomerization of 11betaHSD2 dimers and a significant increase in NAD+-dependent corticosterone conversion. Estrogenic effects on expression, dimerization, and activity of the kidney 11betaHSD1 and -2 enzymes are described herein. Renal 11betaHSD1 mRNA and protein expressions were decreased to very low levels by estradiol (E2) treatment of both intact and castrated male rats; testosterone had no effect. NADP+-dependent enzymatic activity of renal homogenates from E2-treated rats measured under nonreducing conditions was less than that of homogenates from intact animals. Addition of 10 mM DTT to aliquots from these same homogenates abrogated the difference in NADP+-dependent activity between E2-treated and control rats. In contrast, 11betaHSD2 mRNA and protein expressions were significantly increased by E2 treatment. There was a marked increase in the number of juxtamedullary proximal tubules stained by the antibody against 11betaHSD2 after the administration of E2. Notwithstanding, neither the total corticosterone and 11-dehydrocorticosterone excreted in the urine nor their ratio differed between E2- and vehicle-treated rats. NAD+-dependent enzymatic activity in the absence or presence of a reducing agent demonstrated that the increase in 11betaHSD2 protein was not associated with an increase in in vitro activity unless the dimers were reduced to monomers.

11-beta-Hydroxysteroid Dehydrogenase Type 1↗
PubMed2003

Expression of HIF-1 and ubiquitin in conventional renal cell carcinoma: relationship to mutations of the von Hippel-Lindau tumor suppressor gene.

Conventional clear cell renal cell carcinomas (cRCC) have mutations of the von Hippel-Lindau (VHL) tumor suppressor gene at 3p25 in approximately 50% of cases. The VHL gene normally regulates ubiquitin-mediated proteolysis of hypoxia-inducible factor 1alpha (HIF-1alpha); in cell lines, VHL inactivation blocks HIF-1alpha proteolysis, resulting in increased HIF-1 expression. This study was undertaken to investigate the relationship between VHL mutations and the expression of ubiquitin and HIF-1alpha in cRCC. Eleven cRCC were studied with microsatellite analysis for 3p deletions and with sequencing for VHL mutations. Immunohistochemistry was performed for HIF-1alpha and ubiquitin. Deletions at 3p25 were found in 10 tumors, and VHL mutations were identified in 6 of these cases. There was staining for ubiquitin and HIF-1alpha in all tumors with VHL mutations. Among the five cases without VHL mutations, staining for ubiquitin or HIF-1alpha was not present in three cases but was present in two tumors, both of which had 3p deletions. The findings support a role for VHL mutations promoting cRCC development by an impairment of HIF-1alpha proteolysis. The findings also suggest that a 3p tumor suppressor gene other than VHL may also influence HIF-1alpha degradation and that there is an additional tumorigenic pathway for cRCC that does not involve VHL or HIF-1.

Base Sequence↗
PubMed2003

A stereological study of glomerular number and volume: preliminary findings in a multiracial study of kidneys at autopsy.

BACKGROUND: This report describes preliminary results of a study of glomerular number and volume and their associations, in kidneys of people coming to autopsy. METHODS: Both kidneys were weighed at autopsy and the right kidney was perfusion-fixed and sub-sampled for stereological estimation of total glomerular number, and of mean renal corpuscle volume, using the physical disector/fractionator combination. RESULTS: The 78 kidneys studied so far were from Australian Aborigines, Australian non-Aborigines, US blacks and US whites, ages newborn to 84 years. Glomerular number ranged almost ninefold (from 210,332 to 1,825,380), with mean (SD) of 784,909 (314,686); it decreased throughout adult life (r=-0.32, P=0.009). Mean renal corpuscle volume varied 5.6-fold in adults and was inversely correlated with glomerular number (r=-0.38, P=0.001). Total renal corpuscle volume varied in adults by a factor of 15.8. Kidney weight correlated with body surface area (BSA) at all ages (r=0.76, P < 0.001); it varied 3.4-fold among adults, while kidney weight/m2 varied 3.7-fold. The percentage of sclerosed glomeruli varied from 0 to 23%, and it correlated strongly with age (r=0.58, P < 0.001). Females had smaller kidneys than males, and, marginally, fewer glomeruli. There were no significant variations by ethnic group. CONCLUSIONS: These extraordinary ranges of glomerular number and size among ostensibly "normal" people, and their inverse relationship, probably have important implications for susceptibility to renal insufficiency. People with low glomerular (nephron) numbers are likely to be particularly predisposed, with the process marked by compensatory hypertrophy of residual nephrons, which, in turn, accelerates their obsolescence. Much, however, remains to be done, including evaluation of history, clinical features, accompanying pathology, detailed renal morphology, and further pursuit of potentially defining characteristics in high risk groups.

Adolescent↗
PubMed2003

Glomerular calcification in hypercalcemic nephropathy.

Hypercalcemic nephropathy has been classified as a tubulointerstitial renal disease. The presence of glomerular pathologic findings attributable to hypercalcemia has been observed in only a few patients and therefore has been considered an unusual finding. In the current study, calcium deposition within glomeruli was investigated in 2 patients with extreme elevations in serum calcium levels and hypercalcemic nephropathy. The study material consisted of a renal biopsy specimen from a 31-year-old woman (patient 1) who had T-cell lymphoma/leukemia and a serum calcium level of 20.2 mg/dL (5.0 mmol/L) and autopsy kidney specimens from a 19-year-old woman (patient 2) who was being evaluated for primary hyperparathyroidism and a calcium level of 18.4 mg/dL (4.6 mmol/L). The renal biopsy specimen for patient 1 exhibited calcium deposits present in the glomerular capillary basement membranes, where they were associated with segmental sclerosing lesions (21% of glomeruli). Nine percent of the cortical tubules contained calcifications. In patient 2, calcium was found in the mesangial areas in 95% of glomeruli, filling the Bowman space in 7% of glomeruli, or associated with capillary basement membranes and segmental sclerosing lesions (12% of glomeruli). Fifteen percent of cortical tubules, 4% of outer medullary tubules, and 40% of inner medullary tubules were calcified. In neither case was there immunofluorescence or electron microscopic evidence of primary glomerular disease. Thus, glomerular calcification may exceed that occurring in the cortical and outer medullary tubules and may play a significant role in the loss of renal function in hypercalcemic nephropathy. Glomerular calcinosis may also be recognized as an additional cause of segmental glomerulosclerosis and nephrotic range proteinuria in patients with extremely high levels of serum calcium.

Adult↗
PubMed2002

Fatal enteritis necroticans (pigbel) in a diabetic adult.

Enteritis necroticans is a segmental necrotizing infection of the jejunum and ileum caused by Clostridium perfringens, Type C. The disease occurs sporadically in parts of Asia, Africa, and the South Pacific, where it primarily affects children with severe protein malnutrition. The disease is extremely rare in developed countries, where it has been seen primarily in diabetics. Two cases have previously been reported in the United States, one in a child with poorly controlled Type 1 diabetes. A 66-year-old woman with a 12-year history of Type 2 diabetes mellitus developed severe abdominal pain and bloody diarrhea after eating a meal of turkey sausage. She died unattended at home. An autopsy showed peritonitis and segmental necrosis of the jejunum and ileum. Microscopic examination showed Gram-positive club-shaped bacilli consistent with Clostridia coating a necrotic mucosa. Products of cpa and cpb genes of C. perfringens, Type C were identified in the necrotic jejunum by polymerase chain reaction amplification.

Aged↗
PubMed2002

Glomerular size and glomerulosclerosis: relationships to disease categories, glomerular solidification, and ischemic obsolescence.

In focal segmental glomerulosclerosis (FSGS), a biphasic change in glomerular size is described in which glomeruli are enlarged with early glomerulosclerosis. Hyperperfusion of larger glomeruli is believed to contribute to progressive glomerular injury. This study was undertaken to investigate whether similar alterations in glomerular size can be found in other renal diseases. Volumes of sclerotic and nonsclerotic glomeruli were estimated in renal biopsy specimens using the Weibel and Gomez method (1962). Glomerulosclerosis was graded on individual glomeruli from 0 to 4, with 0 as no sclerosis and 4 as 76% to 100% sclerosis. Primary and secondary FSGS showed a biphasic change in which grade 2 glomeruli were 50% larger than grade 0 glomeruli and grades 3 and 4 glomeruli were solidified and smaller than grade 0 glomeruli. In essential hypertension, no increase in glomerular size was seen with early glomerulosclerosis, and the latter stages consisted of ischemic obsolescence in which collapsed tufts were 50% smaller than solidified glomeruli of FSGS. Grade 0 glomeruli of membranous glomerulonephritis (MGN) were significantly larger than grade 0 glomeruli of FSGS, and no significant difference in size was seen between grades 0 and 2 glomerulosclerosis. Solidified diabetic glomeruli maintained a large size with grades 3 and 4 sclerosis. Glomeruloscleroses of FSGS, hypertension, MGN, and diabetes have stereologically distinct features. A biphasic change in glomerular size is characteristic of primary and secondary FSGS, but not hypertension, in which tuft collapse supports reduced rather than increased perfusion in the pathogenesis of its glomerular obsolescence.

Adult↗
PubMedDate not supplied

Accuracy of liquid-based Pap tests: comparison of concurrent liquid-based tests and cervical biopsies on 782 women with previously abnormal Pap smears.

OBJECTIVE: To evaluate the diagnostic performance of a liquid-based Pap test, the ThinPrep Pap test (TP) (Cytyc Corp., Boxborough, Massachusetts, U.S.A.), by comparing concurrent TP and cervical biopsy results on 782 patients who were referred for colposcopy because of previously abnormal conventional Pap smears (CPs). STUDY DESIGN: The ability of TP diagnoses of atypical cells of undetermined significance (ASC-US) and squamous intraepithelial lesions (SILs) to predict biopsy diagnoses of cervical intraepithelial neoplasia (CIN) was analyzed using chi2 and McNemar tests. RESULTS: The rate of agreement between diagnoses of SIL by TP and CIN by biopsy was 74.7%. ASC-US accounted for 16.0% of TP diagnoses. ASC-US had biopsy diagnoses of CIN 1 in 60% and CIN 2/3 in 12.8% of cases. For TP diagnosis of low grade SIL, biopsy diagnoses of CIN 2/3 were found in 13.5% of cases. For TP diagnoses of ASC-US and higher, the proportions of TP and cervical biopsies in comparable diagnostic categories were statistically significant (p < 0.001), with TP having sensitivity of 89.4% and positive predictive value of 89.7% for the detection of CIN. The false positive rate for TP was 8.1%, but rescreening confirmed the presence of abnormal cells in 51 of 63 (81.0%) cases of ASC-US or higher having negative biopsies. TP had a false negative rate of 8.3% and negative predictive value of 61.3%. Rescreening showed that most (77.6%) of the false negative TP specimens failed to have abnormal cells on the slides. CONCLUSION: For patients having previously detected cervical abnormalities by CP, concurrent TP demonstrated the following: (1) that it has high diagnostic accuracy for SIL, (2) that ASC-US was diagnostically equivalent to LSIL, and (3) that false negative TP for SIL can be attributed primarily to sampling rather than cytotechnologists' screening errors.

Adolescent↗