SUMMARY Sections from 100 cervical biopsy specimens were studied by 12 consultant histopathologists to determine the robustness of the existing pathology terminology and classification. Analysis by K statistics showed good agreement in the diagnosis of CIN 3 and squamous carcinoma but an inability to distinguish accurately between the lesser grades of CIN.It is recommended that the classification be changed to low grade (present CIN 1 and 2) and high grade (present CIN 3) categories alone. There was very poor agreement in the identification ofcellular changes associated with human papilloma virus (HPV) infection.Several novel analytical methods of assessing the severity of uterine cervical intraepithelial neoplasia (CIN) have been proposed,'2 but histological assessment remains the basis for determination oftreatment, clinical management, and subsequent follow up of patients. Although clear criteria for the diagnosis and grading of CIN have been described,3 such assessments are subjective and prone to intra-and interobserver variation.45 The problems of histological assessment have been further complicated by the increasing recognition of human papilloma virus (HPV) infection"7 which may be an aetiological factor in the development of CIN.89 HPV infection may be indicated by koilocytosis and other changes that distort cellular appearances and so may apparently exaggerate the severity of the premalignant appearances ofthe cervical epithelium, particularly in the higher layers-making grading more difficult.It is reasonable that efforts should be made to establish the degree of confidence which can be given to the histological reporting of cervical biopsy lesions by pathologists and to determine the robustness of the existing terminology and classification. We describe the findings of a study of cervical biopsy specimens conducted by a group of 12 pathologists, all of consultant grade, but with varying degrees of experience.Accepted for publication 1 September 1988 Material and methods COMPOSITION OF PANELTwelve histopathologists were invited to join the study with a deliberate attempt by the organisers to obtain a composition representative of Scottish pathology as a whole. The members came from pathology laboratories in Aberdeen (n = 2), Dundee (n = 2), Edinburgh (n = 2), Airdrie (n = 1), Perth (n = 1), Stirling (n = 1) and Glasgow (n = 3) and varied in years of consultant experience (five to 25 years) and nature ofsubstantive post (university staffn = 5: NHS staff n = 7). All the members of the group had undertaken their postgraduate training in Scotland. CLASSIFICATION OF CERVICAL HISTOPATHOLOGYAt the initial meeting current cervical pathology terminology was reviewed and following discussion a proforma was designed for completion after examination of each slide in the circulation. This was modified in a minor way after the first circulation and the final form is shown in the figure. It was decided to keep the classification simple, but to relate it as closely as possible to everyday practice. The following ...

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We have determined the effect of pulsatile flow on segmental vascular resistance in lungs from 29 adult rabbits. In group I (n = 4), II (n = 8), and III (n = 8) lungs were isolated. In group IV (n = 9) rabbits were anesthetized, their chests were opened, and lungs were studied in vivo. Group I and II lungs had steady-flow perfusion: group I with intact vasotonus and group II with papaverine treatment. Group III lungs (papaverine treated) were perfused for two consecutive 45-min periods with steady and pulsatile flow. In all isolated lungs and in lungs of five anesthetized rabbits, we measured pressures in subpleural 20- to 50-microns-diam arterioles and venules by use of the micropipette servo-nulling method. Measurement of distribution of blood flow in lungs of four anesthetized rabbits by use of radiolabeled microspheres revealed no abnormality of blood flow to the micropunctured lobe. We found that total and segmental vascular resistances were similar in group I and II lungs, with microvessels representing 55% of total resistance. In group III lungs, total resistance was 30% lower during pulsatile flow than during steady flow because of a lower microvascular resistance. Lungs in vivo (group IV) had a significantly lower total vascular resistance than isolated lungs and had a low fractional resistance in microvessels (approximately 28%). We conclude that, in isolated perfused adult rabbit lungs, vascular resistance is very high, particularly in the microvascular segment, and that pulsatile flow decreases microvascular resistance.

We have determined the sites of hypoxic vasoconstriction in ferret lungs. Lungs of five 3- to 5-wk-old and five adult ferrets were isolated and perfused with blood. Blood flow was adjusted initially to keep pulmonary arterial pressure at 20 cmH2O and left atrial and airway pressures at 6 and 8 cmH2O, respectively (zone 3). Once adjusted, flow was kept constant throughout the experiment. In each lung, pressures were measured in subpleural 20- to 50-microns-diam arterioles and venules with the micropipette servo-nulling method during normoxia (PO2 approximately 100 Torr) and hypoxia (PO2 less than 50 Torr). In normoxic adult ferret lungs, approximately 40% of total vascular resistance was in arteries, approximately 40% was in microvessels, and approximately 20% was in veins. With hypoxia, the total arteriovenous pressure drop increased by 68%. Arterial and venous pressure drops increased by 92 and 132%, respectively, with no change in microvascular pressure drop. In 3- to 5-wk-old ferret lungs, the vascular pressure profile during normoxia and the response to hypoxia were similar to those in adult lungs. We conclude that, in ferret lungs, arterial and venous resistances increase equally during hypoxia, resulting in increased microvascular pressures for fluid filtration.

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Objective.\p=m-\To assess pairwise differences between placebo, unopposed estrogen, and each of three estrogen/progestin regimens on selected heart disease risk factors in healthy postmenopausal women.Design.\p=m-\A3-year, multicenter, randomized, double-blind, placebo-controlled trial.Participants.\p=m-\A total of 875 healthy postmenopausal women aged 45 to 64 years who had no known contraindication to hormone therapy.Intervention.\p=m-\Participants were randomly assigned in equal numbers to the following groups: (1) placebo; (2) conjugated equine estrogen (CEE), 0.625 mg/d;(3) CEE, 0.625 mg/d plus cyclic medroxyprogesterone acetate (MPA), 10 mg/d for 12 d/mo; (4) CEE, 0.625 mg/d plus consecutive MPA, 2.5 mg/d; or (5) CEE, 0.625

We have determined the sites of action of endothelin-1 (ET) in the lamb pulmonary circulation. The influence of cyclooxygenase inhibition and baseline vasomotor tone on ET effects was also studied. Lungs of 14 lambs (6-9 wk of age, 12.1 +/- 0.6 kg body wt) were isolated and perfused with blood. Group I lungs (n = 5) were untreated, group II lungs (n = 5) were treated with indomethacin to inhibit cyclooxygenase, and group III lungs (n = 4) were treated with indomethacin and a thromboxane A2 analogue, U-46619, to elevate vasomotor tone. All lungs were perfused with constant flow in zone 3, with left atrial and airway pressures being 8 and 6 cmH2O, respectively. We measured pulmonary arterial pressure and, by the micropuncture servo-null method, pressures in 20- to 50-microns diameter subpleural venules, both before and after each dose of ET was infused (50, 100, 250, and 500 ng/kg). Group I lungs, with high baseline vasomotor tone, exhibited a biphasic response to ET; 50-100 ng/kg of ET dilated both arteries and veins, whereas 500 ng/kg of ET constricted both arteries and veins. In group II lungs with low vasomotor tone, all doses of ET caused constriction of arteries only. In group III lungs (indomethacin treated with elevated vasomotor tone), 50-100 ng/kg of ET caused dilation of arteries and veins, whereas 500 ng/kg of ET induced constriction, this time only in arteries. We conclude that ET has both dilator and constrictor effects in arteries and veins of isolated, perfused lamb lungs. ET-induced arterial and venous dilation is dependent on initial vasomotor tone but not on cyclooxygenase metabolites.(ABSTRACT TRUNCATED AT 250 WORDS)

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