Pap smears: quality, not only quantity.
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Biomedical subjects
Publications and source records attributed to A Farnsworth.
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The provision of a truly-representative cellular sample is the major prerequisite for reliable cervical cytology. We performed a trial with a cervical-sampling implement of innovative design, the Cervex Sampler. By means of the parameters of patient and doctor acceptability, the quality of the smear, the presence of endocervical cells, and the rate of squamous-cell atypia, the Cervex Sampler was compared with a modified Ayre spatula. One hundred samplers were distributed to each of 10 doctors. The parameters were assessed before, during and after the trial period. The consensus was that the Cervex Sampler was easier to use and did not cause patients any problems. Assessment of the smears that were made with the Cervex Sampler showed a significant improvement in the quantity and evenness of the distribution of the cellular sample. During the trial, statistically-significant increases occurred in the percentage of smears that contained endocervical cells (P = 0.0001) and atypical squamous cells (P = 0.028). At the end of the trial, when the doctors again used the modified Ayre spatula, these rates reverted to the same levels as before.
Over recent years, the association between human papillomavirus (HPV) and squamous cell carcinoma of the cervix and its precursors has been well established, largely as a result of advances in the techniques of molecular biology. A similar association between HPV and invasive adenocarcinoma of the cervix has also been recently demonstrated; however, little work has been published on the relationship between the precursor lesion, adenocarcinoma in situ (ACIS), and HPV. We have therefore undertaken an in situ hybridization study of 22 cases of known cervical ACIS using probes for HPV messenger RNA expression. Seventeen of these had residual ACIS in the blocks studied, 15 of which (88.6%) expressed HPV messenger RNA. Five cases were positive for HPV 16 and 10 cases for HPV 18. Early invasive adenocarcinoma was present with ACIS in three cases and one case had early invasion plus cervical intraepithelial neoplasia (CIN III). These invasive lesions showed a similar type and degree of HPV expression as the in situ component. One section had only residual CIN III, which was positive for HPV type 18. Four cases had only minor glandular atypias (less than ACIS) in the studied sections, and all four of these were negative for HPV expression. None of the normal endocervical epithelia in any of the sections were positive by this technique. In summary, the finding of HPV messenger RNA expression in nearly 90% of cervical ACIS supports a possible role for these viruses in the pathogenesis of glandular neoplasms of the uterine cervix.
Whole-body irradiation has been extensively used to ablate immune responsiveness in rodent recipients in adoptive allograft assays. This study was undertaken to determine the relative radioresistance and the tempo of regeneration, following whole-body irradiation, of cells involved in the allograft response. Six distinct cell populations have been identified in the lymphoid tissues of rats subjected to sublethal whole-body irradiation. The relative representation of these subpopulations was significantly different from that in nonirradiated controls. NK cells, macrophages, and plasma cells, which are present in very low numbers in cell suspensions prepared from normal lymphoid tissues, made up a significant proportion of the residual/regenerating population in the tissues of rats recovering from whole-body irradiation. More significantly perhaps, the mature T cell populations showed a significant increase in the T cytotoxic/suppressor to T helper cell ratio. These observations support the suggestion that a number of the cell types within the mixed cell population observed in the rejecting indicator grafts of irradiated recipients in adoptive allograft assays are host derived. The finding that the T cytotoxic/suppressor population is apparently more radioresistant than the T helper population supports a conclusion that graft rejection in irradiated recipients, restored with pure populations of T helper cells, may not be directly mediated by the injected cells but may be the result of collaboration between these and host-derived cytotoxic cell populations.
A spectrum of changes precedes clinical invasive adenocarcinoma of the cervix. Cytological and histological criteria for the diagnosis of adenocarcinoma in situ (ACIS) are becoming more clearly defined. A 5-year prospective study was undertaken to test the accuracy of a cytological prediction of ACIS. From a total of 290,000 cervical smears 54 predictions of ACIS were made: 33 (61%) alone and 21 (39%) with associated squamous carcinoma in situ (SCIS). The rate of reporting ACIS was compared to the rates for intraepithelial and invasive squamous lesions and for frank invasive adenocarcinoma. The findings suggest that ACIS is being underdiagnosed. Forty-seven patients were adequately investigated; 46 had intraepithelial or invasive malignancy. There were 10 cases of ACIS, 10 ACIS with SCIS, 9 microinvasive adenocarcinoma, 5 invasive adenocarcinoma, 2 microinvasive adenosquamous carcinomas, 1 invasive adenosquamous carcinoma, 8 SCIS and 1 endometrial carcinoma. There was one true false positive report. Thus cervical glandular neoplasia was confirmed in 37 patients (79%), 13 of these having adenosquamous tumours. Because 98% of patients had in situ or invasive malignancy and because 36% of cases were invasive (though mostly microinvasive) prompt investigation, by cone biopsy, must follow a cytological report of ACIS.
Of 16 patients with normal preoperative left ventricular (LV) function studied by simultaneous two-dimensional and M-mode echocardiography before and after uncomplicated cardiac surgery, M-mode interventricular septal motion remained normal in seven (group I) and was paradoxical in nine (group II) 7 to 13 days postoperatively, but was normal in all 12 patients (7 group II) studied 3 to 18 months later. An abnormal systolic increase in normalized septal curvature, the essential feature of truly paradoxical septal motion, was not observed in either group during any study period (mean = 0.92 +/- 0.08), nor were significant differences found in septal thickening, LV fractional shortening, or fractional area change. In contrast, systolic anterior motion of the LV center increased from -0.1 +/- 1.6 mm preoperatively to 4.8 +/- 2.5 mm postoperatively in group II (p less than 0.001), and the LV posterior wall motion:thickening ratio increased from 1.10 +/- 0.33 to 2.16 +/- 0.45 (p less than 0.01), but both parameters had returned to preoperative levels at the follow-up study. Both parameters remained stable in group I during all study periods. In addition, direct intraoperative M-mode recordings (n = 14) demonstrated normal septal motion in both groups before chest closure, but esophageal echocardiograms (n = 10) demonstrated exaggerated anterior systolic LV motion within 2 hours of surgery in those from group II. Thus, early after uncomplicated cardiac surgery, apparently paradoxical septal motion relative to a fixed reference point is an artifact due to exaggerated cardiac mobility that resolves with the progressive restraining effect of postoperative adhesions.
The outcome of patients with acute renal failure following cadaveric renal transplant has been evaluated in a prospective, controlled trial, comparing treatment with cyclosporine (CSA) to prednisone, azathioprine, and antilymphocyte globulin (AZA). There was a high incidence of acute post-transplant renal failure in both groups: 37 of 51 CSA and 31 of 45 AZA patients, due to the long exposure of kidneys to warm and cold ischemia. Onset of adequate renal function was delayed for three or more weeks in 27 (53%) CSA and only nine (20%) AZA patients, and the only predisposing factor found was donor hypotension. All nine AZA and 18 of the 27 CSA patients with prolonged oliguria subsequently had a spontaneous diuresis. Nine of the CSA patients were changed to azathioprine and prednisone because of suspected CSA toxicity, and eight of these kidneys began functioning within days, even though they had been oliguric for 21 to 83 days. Of these nine patients, five had adequate long-term function on AZA, three developed CMV infections that were fatal to two individuals, and two rejected their grafts. Plasma CSA levels fluctuated widely in all patients, but were not higher in any group, including those with prolonged oliguria. During the oliguric period, biopsy specimens proved rejection was more common in the nine patients who had their CSA stopped than in the other CSA patients, and seven of these nine developed a diffuse interstitial fibrosis that was thought to be a manifestation of CSA toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)
Acute renal failure in the immediate postoperative period remains a significant complication of renal transplantation. A major factor in the pathogenesis may be warm ischaemia (WI). Recent evidence implicates a calcium mediated mechanism as a final common pathway in certain models of acute renal failure. This study was undertaken to evaluate the effects of Verapamil, a calcium antagonist, in the prevention of warm ischaemia-induced acute renal failure following renal autotransplantation in the dog. Twenty-one mongrel dogs were randomly allocated to three groups. Group 1 (control, 8 dogs) received 20 ml normal saline before a standardized 60 min warm ischaemic insult to the left kidney. Group 2 (6 dogs) received Verapamil (0.3 mg/kg) by intravenous injection and Group 3 (7 dogs) received Verapamil (0.3 mg/kg) by intra-arterial injection into the left renal artery prior to the same ischaemic insult. The left kidney was heterotopically grafted to the right iliac fossa in the warm ischaemic period. Contralateral nephrectomy was performed. The dogs were followed up to 7 days after operation by serial creatinine estimation. Histological examination of some autografts was performed. Of the eight controls, six showed marked renal impairment (serum creatinine greater than 800, or death in renal failure). Three of the six dogs given intravenous Verapamil showed marked renal impairment. None of the seven dogs receiving intra-arterial Verapamil showed marked renal impairment (P = 0.013, chi 2 test). The mean rate of serum creatinine rise for each group was analysed by multivariate analyses of variance.(ABSTRACT TRUNCATED AT 250 WORDS)
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In the rejection response against renal allografts, the relative importance of helper/inducer T cells mediating a delayed-type hypersensitivity response and of T cells with direct cytotoxicity has not been defined. These subpopulations were identified with commercially available monoclonal antibodies and an indirect immunoperoxidase technique in 31 renal biopsies from patients undergoing acute rejection episodes and in 9 rejected nephrectomy specimens. T lymphocytes were the predominant cell population in all biopsies and in 8 of 9 nephrectomies. The T4 helper/inducer subset was equal to, or greater than, the T8 cytotoxic/suppressor subset in 28 of the 31 biopsies and in the 8 nephrectomy specimens that had histological evidence of cellular rejection. T4 lymphocytes were found predominantly in large areas of cellular infiltrate. T8 lymphocytes had a more diffuse interstitial distribution and were a minority of the cells in the large areas of cellular infiltration. These results show that helper/inducer T lymphocytes are often more frequent than cytotoxic/suppressor cells in acute renal allograft rejection in humans and they suggest that helper/inducer T cells may play an important role in the mediation of graft destruction.
Nephrotoxicity is a major side effect of cyclosporin A (CSA) when used in renal transplantation, and the distinction between nephrotoxicity and rejection is important in patient management. One hundred twenty-five renal biopsies were examined from 56 patients entered into a controlled clinical trial aimed at comparing the efficacy of CSA therapy alone to a combination of prednisone, azathioprine, and antilymphocyte globulin (AZA). In order to define the histopathology of rejection and nephrotoxicity, all the biopsies were evaluated in a semiquantitative manner by an observer unaware of the clinical state of the patient. Comparison of the morphological appearances of 32 biopsies from patients on CSA, and 22 biopsies from AZA-treated patients performed during clinically apparent rejection episodes showed that the histological patterns of rejection were the same in both treatment groups. Comparison of the morphological features of 34 biopsies from patients receiving CSA and 13 from patients receiving AZA, performed during prolonged periods of post-transplant renal failure, who eventually recovered on continuation of original therapy, showed that there were no morphological features specific to the CSA-treated group. Five patients on CSA had oliguria which was prolonged by CSA nephrotoxicity. Thirteen biopsies from all five patients showed a diffuse interstitial fibrosis that was peculiar to this group of patients.
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A group of 71 patients with myasthenia gravis is reviewed. All were initially managed medically, and 18 underwent thymectomy. Twenty-three responded poorly to drug treatment, and seven died from respiratory failure. In contrast, thymectomy was beneficial in 16 of the 18 who were subjected to operation. Seven patients had significant postoperative respiratory complications, and nine required a tracheostomy. Thymectomy appears to be effective and safe and to be indicated in young patients with early disease, and in patients who do not respond to drug treatment. The transcervical approach to thymectomy was satisfactory on two occasions.
The clinical histories of two patients with angiosarcoma of the pericardium are described. Both were previously well young men who presented with cardiac tamponade caused by haemorrhagic pericardial effusions. If a pericardiectomy is undertaken for diagnosis, wide excision of the pericardium is recommended. This will provide a large specimen for histological examination and may prevent subsequent development of constriction.
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