Search

Rationale: Although we and others have recently shown that mast cells play an important role in plaque progression and destabilization, the nature of the actual trigger for (peri)vascular mast cell activation during atherosclerosis is still unresolved., Objective: In this study, we confirm that perivascular mast cell content correlates with the number of nerve fibers in the adventitia of human coronary atherosclerotic plaque specimen. Because peripheral C-type nerve fibers secrete, among others, substance P, a potent mast cell activator, we set out to study effects of adventitial administration of this neuropeptide on mast cell dependent destabilization of carotid artery plaques in apolipoprotein E-deficient (apoE(-/-)) mice., Methods and Results: Substance P treatment significantly enhanced the number and activation status of adventitial mast cells compared to controls and promoted intraplaque hemorrhages. These phenomena could be prevented by coadministration of the neurokinin-1 receptor antagonist spantide I and did not occur in mast cell deficient apoE(-/-) mice, establishing the critical involvement of mast cells in substance P-elicited plaque destabilization., Conclusions: Our data suggest that neurotransmitters such as substance P are capable of promoting mast cell dependent plaque destabilization and provide a new, direct link between neural factors and vascular inflammation.

Unlabelled: BACKGROUND, AIMS OF THE STUDY: The objective of the study was to relate the progress of coronary artery remodeling to the earliest stages of the atherosclerotic process. For this purpose, a mathematical model for description of dimensional change of the coronary artery wall and its constituent components was developed and applied., Materials and Methods: The study used coronary artery samples randomly taken from each of 83 consecutive, unselected postmortems. All samples were routinely fixed and processed to paraffin for the preparation of right-angled, 5-micron sections, routinely stained and mounted for subsequent analysis. Computer assisted image analysis, using 32 systematic random, radial sampling lines, was used for interactive measurements of distance from centre of lumen to points defining intima, media and adventitia thickness along the radial intercept, which were subsequently tabled for analysis of variance, calculations of (group-vessel) means, and related to stage of pathology., Results: Pre-atherosclerotic changes, before any localised changes in especially intima dimensions, are found, consisting of a process of gradual vascular widening, associated with temporally at least partly dissociated increases in width, which as a fraction of total vessel radius show a phased process. In these, the intima first increases, subsequently remains stable, and finally reduces in width proportionally to the increasing diameter. The media shows a similar initial increase, on average stabilising in the third phase after reaching a plateau value in the second. The adventitia, already increasing in phase 1, continues to increase in phase 2, accelerating in phase 3. The complex process, as found, occurs systematically in all vessels, is distributed circumferentially, and precedes the development of localised lesions of the intima., Conclusions: The findings suggest the existence of a diffuse complex of changes, consisting of a gradual vascular widening followed by narrowing, with associated mural changes reflecting the atherosclerotic process.

Background: In this study the MIB-1 immunostaining pattern as an index of cellular proliferation was analyzed in smears diagnosed as borderline dyskaryosis in order to establish whether the combination of human papillomavirus testing and MIB-1 staining could resolve equivocal cytology., Methods: Conventional Pap smears of 108 women diagnosed as borderline dyskaryosis were stained with MIB-1 and the proliferation index was assessed. These women were evaluated by colposcopy, histological sampling, and human papillomavirus, semi-quantitative evaluated by hybrid Capture II test., Results: All 64 human papillomavirus- and MIB-1-negative women had no underlying high-grade cervical intraepithelial neoplasia or cervical cancer. Forty of the 104 women with normal histology or cervical intraepithelial neoplasia I were positive for human papillomavirus, compared to only one positive MIB-1 test (i.e. proliferation index of more than 35%)., Conclusions: Adding a MIB-1-test in human papillomavirus-positive women with equivocal cytology might reduce the number of colposcopies needed to predict > or = cervical intraepithelial neoplasia II. With this approach only four instead of 43 human papillomavirus-positive women would have been referred for colposcopy.

Objective: 1) To assess the regression to normal cytology in women with cervical smears diagnosed as atypical squamous or glandular cells of undetermined significance (ASCUS/AGUS) and absence or clearance of human papillomavirus (HPV) infection; 2) To evaluate the association between viral load, semi-quantitatively evaluated, and cytological or histological outcome., Material and Methods: In this cohort study HPV test and biopsy was taken in 148 women with ASCUS/AGUS cytology. After 12-18 months a HPV test and cervical smear were repeated in 121 women., Results: Absence or clearance of HPV showed significantly more regression to normal cytology than persistent or newly acquired infected women, odds ratio 27 (95% confidence interval; 7-103). The viral load of the HPV test at enrollment was not correlated with the follow-up cytological outcome (Spearman correlation coefficient 0.2, p = 0.2). A marked association between viral load and histological outcome at enrollment was shown (Spearman correlation coefficient 0.43, p < 0.0001)., Conclusion: Absence or clearance of HPV can predict regression to normal cytology. Viral load at enrollment cannot predict cytological regression. There was a marked association between viral load and the underlying CIN at enrollment. However, there was large overlapping of viral loads among the grades of CIN. Therefore, viral load is not a useful parameter to predict high-grade lesions in women with ASCUS/AGUS cytology.

We studied the fixation of the Mecron cementless titanium screw cup radiographically and histologically in 20 dwarf-goats after periods of 0, 6, 26 and 52 weeks. In only 3 goats did histology show good bone-implant contact, whereas in the other 17 goats a fibrous membrane interface was seen. This high failure rate is caused by the poor primary fixation and should be a warning against the use of this implant.

Background: To determine the degree of specificity of the cellular immune response in cervical carcinoma, that is known to be human papillomavirus-related, we investigated the exact relationship between in situ tumor-infiltrating immune cells and the monomorphic/allele-specific HLA expression on the tumor cells., Experimental Design: Attention was focussed on the type, location and number of in situ immunocompetent cells in malignant cervical tissue (N = 30). Immune cell distribution was quantitatively assessed by morphometry for stromal and tumor tissue separately. These results were related to the degree of expression of monomorphic- and allele-specific HLA I and II antigens on the cervical tumor cells., Results: In monomorphic HLA class I downregulated cervical tumors, a significant decrease in tumor-infiltrating CD8+ T cells was observed. However, allele-specific downregulation of respectively HLA-A2, HLA-A3, HLA-Bw4, and HLA-Bw6, did not correlate significantly with a decrease in tumor-infiltrating immune cells. For HLA class II-positive cervical tumors, HLA-DR expression significantly correlated with an increase in the presence of tumor-infiltrating CD3+/CD4+/CD8+ T cells, CD56+ natural killer cells and CD16+ macrophages. No significant correlations were found between alterations in HLA class I or II expression on the tumor cells and stromal infiltrating immune cells., Conclusions: Our observations provide in situ immunomorphologic evidence that in cervical carcinoma, de novo expression of HLA class II antigens on the tumor cells resulted in an increase of tumor-infiltrating immune cells. In addition, the tumor-infiltrating CD8+ T lymphocytes correlated with monomorphic HLA class I expression on the tumor cells, which stresses the existence of a HLA-restricted immune response of T lymphocytes in cervical carcinoma. These findings might have implications for the biologic behavior of this disease and have to be taken into account in strategies concerning immunotherapy of cervical carcinoma.

The clinical value and limitations of a previously described cytomorphometric method, based on nuclear size and anisonucleosis, for evaluation of routine fine-needle aspiration of the breast were assessed in a series of 313 histologically investigated primary breast lesions. Limitations were analyzed by histomorphometry and DNA flow cytometry in 116 consecutive cases of histologically confirmed breast carcinoma. Eighty per cent of histologically proven malignant tumours were classified cytomorphometrically as malignant and no false-positive results were encountered. For benign lesions a benign cytomorphometric classification was reached in 66% of the cases. Histomorphometry showed that on the whole the assignment of histologically malignant tumours to a non-malignant cytomorphometric classification was determined by smaller nuclei and not by sampling error. Tumours assigned to a malignant cytomorphometric classification had on average significantly higher DNA indices than did tumours not assigned to a malignant cytomorphometric classification (P less than 0.001). The mean-nuclear areas in cytomorphometry and histomorphometry were strongly correlated with DNA indices indicated by DNA flow cytometry (P less than 0.001 for both). The present findings show that this cytomorphometric method is appropriate for routine quality control of a cytological diagnosis of malignancy in FNA of the breast. However, an inconclusive result in 15-25% of the tumours is inevitable.

The case is described of a patient with fulminant hepatic failure attributed to intake of glafenine 400 mg daily for 15 days. The first symptoms appeared two weeks after discontinuation of glafenine. Other causes of hepatic necrosis could be excluded. Approximately five weeks after the onset of symptoms the patient died of hepatic failure. At autopsy massive hepatic necrosis and massive pancreatic necrosis were demonstrated.

Material collected by fine needle aspiration (FNA) in 321 histologically examined primary breast lesions of previously untreated patients was analyzed by morphometry. The mean nuclear area (MNA) and its standard deviation (SD) were calculated for 50 cells in each case. Four subclasses were defined on the basis of the MNA and SD: benign (less than 10% probability of malignancy), doubtful benign (10% to 49%), doubtful malignant (50% to 90%) and malignant (greater than 90% probability of malignancy). FNA samples showing signs of acute inflammation or only apocrine metaplastic cells were not suitable for analysis by this morphometric method and were excluded. In 274 (85.4%) of the cases, the measurements allowed a definite morphometric conclusion, with predictive values of 99.5% and 100% for the histologically malignant and benign aspirates, respectively. The probability of malignancy in the doubtful malignant group was almost 86%. The morphometric method described is quick, easy to perform and well suited for use in routine daily practice; furthermore, it does not require expensive equipment. The ease of the technique and its high predictive value make this method appropriate for use as a quality control procedure in FNA cytology.

The fibrinolytic system of the peritoneum is important in the pathogenesis of adhesions. Plasminogen activator activity is depressed by serosal types of injury, which cause ischemia. Ischemic peritoneum induces fibrinous adhesions. When local fibrinolytic activity is impaired, persistence of fibrin and organisation of the fibrinous adhesions may occur. Peritoneal adhesion in rabbits were created by drying the serosa of the uterine horns and by introducing a small amount of blood intraperitoneally. In one group of rabbits tissue-type plasminogen activator (t-PA) was given intraperitoneally at the end of the operation: another group served as controls. 48 rabbits were operated on. The animals were killed 3 h, 1, 3 and 7 days postoperatively for evaluation of adhesions. All animals of the control group had adhesions. The animals of the t-PA group had less adhesions than the animals of the control group.

Melanin production by two medullary carcinomas of the thyroid is reported and discussed. In both tumours, melanin and calcitonin could be detected in the same cells.

The influence of age and sex on the lymphocyte count and numbers of E and EAC rosette-forming cells (RFC) was investigated using peripheral blood of healthy donors. In the female donors we found a lower total lymphocyte count and percentage of EAC RFC than in male donors. The percentage and total number of E RFC appeared to be low in younger donors. Total lymphocyte count and numbers of E and EAC RFC were investigated in untreated and treated patients with advanced solid tumors and in patients with untreated malignant lymphomas. The lymphocyte count in all these groups was decreased, but the E/EAC RFC ratio was normal, except in the group with untreated solid tumors, where we found an increased percentage of E RFC. It is suggested that in these patients a nonspecific impairment of bone marrow function might be expressed in numbers of peripheral T and B cells.

Guinea pigs were immunized intracutaneously into the ears with sheep red blood cells (SRBC). Application of a sensitizing dose of the contact allergen dinitrochlorobenzene (DNCB) onto the same ears was shown to suppress or enhance the humoral response to SRBC depending on the time of application. When guinea pigs were sensitized to a contact allergen, application of a sensitizing dose of a non-related allergen on the same ears either had no effect or caused a clear enhancement of the development of delayed type hypersensitivity (DTH). Strongest enhancement was found when both sensitizations were performed on the same day. Further experiments on the effects of a concomitant DTH reaction elicited at the site of application of a contact allergen showed a strong potentiation of DTH when B-cell suppression was minimized by pretreatment with cyclophosphamide (CY). It was considered that CY-DTH-immunopotentiation might be a useful tool for achieving a higher level of sensitivity after epicutaneous sensitization.

The qualitative features of the intracytoplasmic vacuoles occurring in the cells of pleural malignant mesothelioma and of metastatic carcinoma exfoliated in pleural fluid were studied. There were important differences in the two types of vacuoles. In mesotheliomas, the vacuoles were centrally situated, small and regular in size; these vacuoles stained positively with fat stains and always negatively with the periodic acid-Schiff stain. In routine cytology, these lipid-containing vacuoles can best be seen in air-dried May-Grünwald-Giemsa-stained smears and are almost invisible in wet-fixed Papanicolaou-stained smears. In metastatic carcinoma, the vacuoles were irregular in size, noncentral in location and often positive with mucin stains. Electron microscopy was used in one case to further elucidate the staining patterns of the vacuoles. This study proves that the analysis of the qualitative features of vacuoles of malignant cells exfoliated in pleural fluid can be of great value in the distinction between metastatic carcinoma and mesothelioma.

Rabbit erythrocyte (RRBC) and EAC rosette formation, for detection of T and B lymphocytes respectively, was studied in thymus, lymph nodes and peripheral blood of guinea-pigs. Using two different methods for preparation of RRBC rosette-forming cells (RFC) it was found that, without an incubation period at 37 degrees, a smaller part of the pool of T cells is detected which is particularly sensitive to cyclophosphamide (cy). RRBC rosette formation was studied for 2 weeks after treatment with one high dose of cy and appeared to be minimal in the thymus after 1 week and maximal in the lymph nodes at about day 3. EAC rosette formation was completely blocked by cy treatment. Four days after contact sensitization with 2,4-dinitrochlorobenzene (DNCB) no percentual increase was found in RRBC-RFC, suggesting a parallel increase of B and T cells in stimulated lymph nodes. Cytological screening of the rosettes at day 4 after DNCB showed that of the RRBC-RFC approximately 17 per cent were blast cells, while no difference was detected in the number of blast cells participating in EAC rosette formation as compared to the unstimulated lymph nodes. In contrast to RRBC-RFC the percentage of EAC-RFC in draining lymph nodes is increased after contact sensitization. The mechanism of this increase is discussed.

An important question in the effective use of quantitation in cytology is how to make the link between mathematical parameters and the cytologist. As an example, an investigation is discussed in which cell images from benign mesothelial proliferations were distinguished by quantitative characteristics from those of malignant mesotheliomas originating in the pleura and peritoneum. The significant differences between the three groups in nuclear size, cytoplasmic size and nuclear-cytoplasmic (N/C) ratio could partly be explained by the vacuolation patterns of the exfoliated mesothelial cells in each. Moreover, the primary site of the tumor could be predicted by the quantitative cell parameters. The characteristics of cytologic images, once known to be important, are easily incorporated into standard diagnosis. Thus it now seems possible for the cytologist to differentiate between the three groups by using the cytomorphologic features that relate to the computed parameters. This shows the value of translating computerized parameters into cytomorphologic criteria.

Cells exfoliated from primary pleural mesotheliomas differ significantly from those from primary peritoneal tumors. In a quantitative study, it was shown that the pleural cells have larger nuclei, a more pronounced anisokaryosis and a higher nuclear-cytoplasmic ratio and, therefore, appear more malignant than the peritoneal cells, which have abundant cytoplasma and small nuclei. The differences in quantitative parameters were due to a more extensive vacuolization and consequent cytoplasmic distension, combined with nuclear compression in the case of peritoneal mesotheliomas. The morphometric parameters and the vacuolization patterns of cell populations in cases with both pleural and peritoneal involvement correlated with the data of the primary tumor regardless of the fluid in which the cells were found. This finding indicates the transcoelomic metastatic properties of malignant mesothelioma.

The introduction of a simple one-stage silver nitrate stain as a method of displaying nucleolar organizer regions (NOR's) in formalin-fixed tissue has made it possible to examine the significance of these structures in tumour pathology. In the current study argyrophilic proteins of the NOR's were studied in 39 consecutive patients with bladder tumours. The results indicate that the counting of silver staining particles is only of limited value in grading bladder tumours and that this method is not superior to other additional grading techniques such as histo-morphometry and flow cytometry.

Morphological changes are described in pelvic lymph nodes excised 10 days after C. parvum (CP) treatment of patients with cervical carcinoma. Guinea-pig popliteal and inguinal lymph nodes were investigated from Days 1 to 10 after an injection of 70 micrograms CP into the footpad. Eosinophils were detected from the first few hours after stimulation, initially in the marginal sinus, then in the medullary sinuses and subsequently in the efferent lymphatics. From Day 2 to Day 6, histiocyte accumulations with the appearance of epithelioid cells were found mainly in subcapsular and interfollicular areas, and small granulomas were also seen in the paracortex. The granuloma formation in the lymph node was considered as an indication of the activation of histiocytes. Besides small granulomas in the paracortex, activated interdigitating cells, surrounded by scattered lymphoblasts and eosinophils, were also present. We considered this lymphoblastic response and eosinophilic accumulation as likely to be due to blastogenic factor and eosinophil stimulation promotor. Eight to 10 days after CP stimulation, the macrophage lymphoblast eosinophil response was replaced by a B-cell reaction: germinal-centre activation and medullary plasma cells. Such a B-cell reaction was also found in the human pelvic nodes removed at operation, but this reaction could not be attributed to CP treatment alone, since cervical-carcinoma patients not treated with CP also showed such reactions. In contrast, pelvic lymph nodes removed at necropsy from females killed in traffic accidents showed no predominance of either B- or T-cell stimulation.

Only 3% of patients with T1 bladder tumours die of bladder carcinoma within 5 years (Williams, Hammonds & Saunders 1977), therefore these patients are initially treated conservatively. There would however be benefits from being able to predict which patients should be treated more aggressively. Morphometry was applied to quantitate characteristic microscopical features of the removed T1 tumours in 16 patients who had survived for five years and in seven patients dead from the tumour, in order to evaluate the prognostic value of this method. The measurements of nuclear and cytoplasmic areas were made on routine H & E sections with a graphic tablet (ASM, Leitz). Statistical analysis of the obtained data revealed that there were significant differences between the two groups. It indicated that morphometric parameters of T1 bladder tumours can have prognostic as well as therapeutic significance which will be further tested in a prospective study.

In a detailed study of granulomas in lymph nodes of 19 patients with Sarcoidosis we assessed and correlated a number of features, with size, development and radiographic staging of the disease. Except with the epithelioid cells the number of constituent cells (lymphocytes, giant cells and polymorphs), size, confluency and degree of necrosis of the granulomas were found to be very variable within a single gland. This indicates that the granulomas are in different stages of activity at a given time. All the features studied showed little or no correlation with the radiographic staging, which suggests that the latter is not a good index of the extent of the disease.

The chemotactic responsiveness of peripheral monocytes and the acid-phosphatase activity of tumor-infiltrating macrophages, as well as the ultrastructural appearance, were studied in 40 patients with squamous cell carcinoma of the head and neck. The chemotactic responsiveness was found to be decreased in carcinoma patients, and this value appeared to be positively correlated in individual patients with the number of tumor-infiltrating macrophages, as well as with the histologic grade of the tumor. Patients with poorly differentiated malignancies showed impaired monocyte chemotactic responsiveness and low numbers of tumor-infiltrating macrophages. Macrophages present in the parenchyma of the tumor showed a weak and diffuse pattern of acid phosphatase activity. The acid phosphatase activity of stromal macrophages was much stronger and distributed in foci. Electron microscopic examination of the parenchymal macrophages revealed low numbers of lysosomes and the presence of tumor cell debris in the cytoplasm of the cell, without any sign of a surrounding phagosomal membrane. Together with the weak cytochemical reactivity, this probably indicates the poor functional state of the phagocyte when infiltrated in the parenchyma of the tumor. Low molecular weight factors derived from the tumor are known to decrease chemotactic responsiveness of peripheral monocytes. The poor functional state of the macrophages infiltrated within tumor parenchyma might be explained by assuming that a high concentration of such factors in the near vicinity of malignant cells causes toxic effects in macrophages.

The authors describe the results of the grading of bladder tumors using morphometry and then compare these with results of histologic grading of the same tumors by different pathologists. Nuclear sizes of cells obtained from superficial and deep cell layers of each carcinoma and from giant cells were measured in 27 cases in which histologic tumor grading by different pathologists was unequivocal. In cells from all three areas, nuclear area increased with higher tumor grade. However, tumors of grades I and II showed significant differences in the size only of the large cells. It is concluded that morphometry is a valuable tool in the objective grading of bladder tumors, with the exception of carcinoma in situ lining the bladder lumen.

In 1926, Abrikossoff described a tumor, usually benign, which only rarely appears in the esophagus. In a 40-year-old woman, the authors found a multicentric granular cell tumor which was localized in the cervical esophagus and in the subcutaneous tissues over the right scapula; it was removed surgically. Granular cell tumors causing stenosis of the upper esophagus have been described only four times in the literature. Characteristics and treatment are discussed.

The histopathological diagnosis of squamous cell hyperplasia of the larynx is very subjective. Since morphometry is highly reproducible, this method was applied to routine processed slides of 45 such lesions to assess objectively the epithelial characteristics. In each case measurements of nuclei of 50 cells in the basal, intermediate, and superficial cell layers were carried out. The data were analysed statistically. The findings suggest that quantitative morphometry may be helpful for the histopathological classification of squamous cell hyperplasia of the laryngeal mucosa.

Acetylsalicylic acid (ASA) given simultaneously with paracetamol decreased paracetamol-induced hepatotoxicity (measured by plasma transaminase activities as well as histology) without any effect on glutathione depletion, indicating that ASA prevents a process (or processes) subsequent to the metabolic activation of paracetamol. Delayed treatment with ASA also reduced paracetamol-induced liver toxicity, suggesting that reduction of the absorption rate of paracetamol does not contribute essentially to the protection by ASA. Combinations of paracetamol and ASA may have potential use in the development of safer analgesic combinations containing paracetamol (or ASA).

The results of cholecystectomy have been studied in a series of 43 patients with pain suggestive of biliary origin in the absence of gallstones. The most probable diagnosis in these cases is cholecystosis of the gallbladder usually to be ascertained by careful scrutiny of the gallbladder periphery on a good cholecystogram. Based on the present results and those reported in the literature, cholecystectomy can be advocated as treatment of patients with adenomyomatosis and other forms of cholecystosis of the gallbladder.

In order to test the reproducibility of a histomorphometrical grading system of bladder tumours, 15 tumours were twice measured independently by three pathologists. The data obtained were then analysed and compared with that of histological grading only. The way in which these morphometrical results are presented to the clinician in a computerized report is described. The need for a satisfactory reliable reproducibility test of every histomorphometrical grading system before introduction in diagnostic pathology is discussed.

Thirty men and 7 women with malignant mesothelioma seen at the Free University Hospital from 1st January 1960 until 1st July 1981 were reviewed. The histological, histochemical and morphometrical findings are reported. These findings are compared with 25 cases of pleural metastatic carcinoma and 25 cases of reactive pleural lesions. Fourty-nine percent of malignant mesotheliomas produced hyaluronic acid, however all cases of pleural metastatic carcinomas failed to produce this substance. All cases of malignant mesothelioma were D-PAS negative while 15 cases of pleural metastatic carcinoma showed reactivity to D-PAS. All cases of malignant mesothelioma and 9 cases of metastases were CEA negative. To distinguish malignant mesothelioma from metastases it is advisable to perform the D-PAS staining first. If it is negative mesothelioma can be confirmed by showing hyaluronic acid activity. A positive CEA staining rules out mesothelioma. In our study it was shown that with these methods 18 of 37 mesotheliomas could be identified with certainty, and 22 of the 25 carcinoma metastases. Morphometrically the malignant mesotheliomas could not be distinguished from the metastases, however the reactive pleural lesions had smaller nuclei than the malignant cells with mean values below 30 mu2. In the malignant cases these values had a range from 36 to 101 mu2. In distinguishing between reactive pleural lesions and malignant mesothelioma the production of hyaluronic acid points to the malignant character of the lesion. Thus histochemistry and immunostaining are important in the distinction of malignant mesothelioma from metastases, while the value of morphometry lies mainly in the seperation of reactive lesions from malignant mesothelioma.

Preclinical studies were performed in mice, rats and dogs of cis-diamminedichloroplatinum(II) (CDDP) and its derivatives cis-1,1-di(aminomethyl) cyclohexane platinum(II) sulphate (TNO-6), cis-diammine-1,1-cyclobutanedicarboxylate platinum(II) (CBDCA) and cis-dichloro, trans-dihydroxybis-isopropylamine platinum(IV) (CHIP). In mice toxicity and antitumour activity were determined. All three derivatives were at least as toxic as CDDP for haemopoietic stem cells and were less active than CDDP against the mouse tumours leukaemia L1210 and osteosarcoma C22LR. Toxicology studies in rats revealed no renal toxicity after a single dose of TNO-6. Fractionated doses of TNO-6 and CBDCA did cause renal toxicity but less than CDDP. CHIP produced little or no kidney damage. In dogs, TNO-6 (1.5 mg/kg) produced more severe kidney damage--although this was reversible--than CDDP (2 mg/kg). Half-lives of distribution were 4.0-5.1 min for TNO-6 and 9.7 min for CDDP, while half-lives of elimination were 3.6-6.6 days and 5.9 days respectively. Plasma levels, normalized for the dose, were at least two times higher after TNO-6 than after CDDP. Twelve weeks after drug administration, plasma levels were undetectable, while tissue concentrations could still be measured. The platinum concentration in kidney cortex was higher after CDDP than after TNO-6.

Cervical microglandular hyperplasia is an unusual lesion that may confused with malignancy, by both macroscopic and colposcopic examinations. Even the cytologic and histologic characteristics may mimic an adenocarcinoma. When, in addition, the simultaneous occurrence of an area of cervical intraepithelial neoplasia is found, it could complicate the correct diagnosis. The clinical implications are discussed on the basis of a single case and the available literature survey. We suggest an in-depth colposcopic and histopathologic examination prior to making a definite diagnosis.

Three patients with multiple focal extraovarian serous carcinoma are discussed. The disease is characterized by carcinomatosis peritonei of papillary adenocarcinoma type without an evident primary tumor. The clinical aspect is that of ovarian carcinoma. It is proposed that these tumors might originate from the extragenital Müllerian epithelium.

Fifty-seven transurethrally resected bladder tumors were analyzed to determine whether different pathologists, using the World Health Organization grading system, graded the same bladder tumor differently (interindividual consistency) and whether the same pathologist graded a bladder tumor differently at different times (intraindividual consistency). Disturbingly high inter- and intraindividual inconsistency in the grading of bladder tumors was found. All pathologists showed essentially the same degree of intraindividual inconsistency: In almost 50 per cent of cases the tumor was graded differently at different times by the same pathologist. The inconsistencies might invalidate the usefulness of bladder tumor grading in clinical decision-making.

Quantitative as well as qualitative cellular parameters were investigated in 20 cases of reactive mesothelial proliferations and 40 cases of primary pleural mesotheliomas. The two groups showed statistically significant differences in the nuclear areas, cytoplasmic areas and standard deviations. In the mesotheliomas, the mean nuclear area and the mean cytoplasmic area were larger than in the reactive proliferations. Nine cases could not be properly classified with these quantitative parameters alone. Qualitative analysis revealed highly characteristic features in the mesotheliomas. Morula formation as well as irregular and coarse reticular chromatin patterns were strongly indicative of mesothelioma. The location and shape of the nucleus and the type and amount of cytoplasmic vacuolization gave additional information for distinguishing between the two groups.

The preoperative value of target ultrasonic mammography (TUSM) and cytopathology, combined with clinical examination and mammography, was studied in 146 mammographically demonstrated round-shaped breast lesions. All lesions were biopsied and histology was performed. Advantages of combining TUSM with cytology are the possibility to have a more precise puncture aspiration with TUSM and a subsequently higher predictive value, compared to each technique alone.

In view of the discouraging results that have been obtained so far with the use of cytotoxic chemotherapy as an adjunct to surgery, a double-blind placebo-controlled evaluation of the adjuvant use of levamisole was conducted in 211 resectable lung cancer patients, following these patients for 2 years after their operation. Levamisole (or the placebo) was given for 3 days every 2 weeks and the dose level ranged 1.1--3.8 mg/kg per day (a fixed dose of 3 x 50 mg was given to all patients). It appeared that recurrences and carcinomatous deaths had occurred significantly less often in patients who had received a high dose (i.e., 2.1--3,8 mg/kg: patients weighing 70 kg or less) but not in the patients who received a lower dose. Patients who had more advanced cancers at the time of surgery seemed to have profited more from the treatment, but the results did not seem to depend upon the histologic type of the tumor or on the immune status of the patients as estimated from the skin test reactivity at the start. There was also suggestive evidence that levamisole may be more effective in preventing hematogenous dissemination than in inhibiting recurrences in the lung or the mediastinal tissues. Levamisole, if dosed adequately, appears to be a very suitable adjuvant treatment in resectable lung cancer patients as judged from its efficacy and its lack of troublesome side-effects.

The stromal characteristics in papillary and non-papillary tumours of the urinary bladder were investigated in an attempt to improve the accuracy of histopathological diagnosis. It appeared to be possible to differentiate true papillary tumours from pseudopapillary structures lined by carcinoma in situ. Stromal differences were not found in cases of carcinoma in situ accompanied by denuding cystitis and cystitis due to other aetiological factors. It is concluded that histopathological examination of the stroma of bladder tumours improves diagnostic accuracy.

A quantitative analysis of the lipid vacuoles in benign hypertrophic and neoplastic mesothelial cells, using a size-independent distribution index, showed that computer-assisted image analysis for distribution patterns of cytoplasmic components can aid in distinguishing benign from malignant cells. Benign mesothelial cells had fewer lipid vacuoles, which were smaller and predominantly found around the nuclei. It is argued that, due to the high surface tension in the lipid vacuoles, the largest vacuoles are found in the center of the cells, which is the least flattened part of the air-dried mesothelial cells. It seems likely that the distribution pattern of rigid substructures, such as lipid vacuoles, varies between histologic and cytologic material as well as between cells processed by different cytologic methods with various cell-flattening artifacts. The study of the distribution of cytoplasmic components that differ in size was enhanced by using the defined size-independent distribution index, which incorporates the radius of the cell, the radius of the vacuoles and their respective centers of gravity.

In three of 52 consecutive patients with a painful mass in the right lower quadrant, ultrasound (US) disclosed severe mural thickening of the terminal ileum and cecum and moderate mural thickening of the appendix. In all three, the tentative diagnosis of Crohn disease was subsequently confirmed. If these US features are found in a patient with a suspected appendiceal mass, the diagnosis of Crohn disease must be seriously considered, and further evaluation is imperative.

Because of the rise in incidence of upper urinary tract tumors, there is a need for a simple and reliable method for diagnosing these tumors, especially in people in a "high-risk" group. This retrospective study showed the usefulness of cytology and cytomorphometry in making the diagnosis of transitional-cell carcinoma of the upper urinary tract. The study also emphasized that the methods of collection and processing are of the utmost importance: the cytologic evaluation of ureteral catheterized urine specimens gave 100% accuracy as compared with a 40% false-negative rate in the cytologic diagnosis of voided urine specimens. A higher accuracy of urinary cytology for the diagnosis of upper urinary tract lesions clearly requires selective catheterization of the ureter. Objective cytomorphologic grading of the urinary cytology specimens was shown to compare favorably with histologic grading. Cytomorphologic grading not only can offer important information in determining the prognosis and in planning treatment but can also assist in quality control of other diagnostic methods and can help to resolve apparent diagnostic discrepancies.