Ki-67 labeling indices in non-small cell lung cancer: comparison between image cytometry and flow cytometry

Expression of the proliferation-associated nuclear antigen Ki-67 was studied in 27 human non-small cell lung cancers (NSCLCs). We measured immunohistochemical Ki-67 labeling indices using image cytometry (ICM) and flow cytometry (FCM) and compared the indices determined with the two methods. Ki-67 labeling indices of tumor cells ranged from 2% to 59% with ICM, and from 3% to 56% with FCM, varying from case to case. There was a linear correlation of values between the two methods (r = 0.77, P < 0.05). To examine whether Ki-67 labeling indices represent tumor proliferative activity, we studied the relationship between the Ki-67 labeling index and the S-phase fraction determined by FCM. There was a positive correlation between the Ki-67 labeling index and the S-phase fraction (r = 0.91, P < 0.01). Comparison of Ki-67 labeling indices and clinicopathological parameters showed lower Ki-67 labeling indices in well-differentiated tumors than in moderate and poorly differentiated tumors (P < 0.05). No correlation was observed between Ki-67 labeling indices and p53 expression. It was concluded that the Ki-67 labeling index was in fact measured with both ICM and FCM, and that it represents tumor proliferative activity of NSCLCs.     

Immunohistochemical analysis of progesterone receptor and Ki-67 labeling index in astrocytic tumors

BACKGROUND: Intracranial tumors such as meningiomas express steroid hormone receptors but little is known regarding progesterone receptor (PR) in astrocytic tumors. The authors evaluated expression of PR in 86 astrocytic tumors in relation to tumor proliferative potential. METHODS: Paraffin embedded tumor sections were stained with polyclonal antiprogesterone antibody by the peroxidase-antiperoxidase method and with monoclonal MIB-1-Ki-67 antibody by avidin-biotin complex immunohistochemistry. RESULTS: Sixty-three of the 86 astrocytic tumors (73%) showed positive PR immunoreactivity. PR expression was observed in 4 of 9 pilocytic astrocytomas, 13 of 24 Grade 2 astrocytomas, 15 of 20 anaplastic astrocytomas, and 31 of 33 glioblastomas. In addition to the tumor cells, cells of microvascular endothelial proliferation and the smooth muscle of tumor vessel walls were frequently PR positive. Glioblastomas had a significantly higher percentage of PR positive cells compared with anaplastic (P < 0.0008) and low grade (P < 0.0001) astrocytomas. Patients with PR positive astrocytomas were of an older age than patients with PR negative astrocytomas (48.71 +/- 21.95 years vs. 37.09 +/- 24.69 years; P < 0.04). The mean Ki-67 labeling index (LI) was significantly higher in the high grade (3-4) astrocytomas compared with low grade (1-2) astrocytomas (P < 0.0001). PR positive astrocytic tumors had higher Ki-67 LI than PR negative tumors. PR expression was not correlated with tumor recurrence and patient survival. CONCLUSIONS: The current study suggests that PR in the astrocytic tumors correlates with histologic grade and PR may participate in the growth of these tumors and tumor angiogenesis. The measurement of PR in these tumors may indirectly represent tumor growth potential.     

The correlation of Ki-67 staining indices with tumour doubling times in regrowing non-functioning pituitary adenomas

In order to improve our ability to predict the regrowth of nonfunctioning pituitary adenomas, we tried to assess the correlation between growth fractions with Ki-67 and PCNA (proliferating cell nuclear antigen) and tumour doubling times in regrowing tumours, and also to find out any difference of growth fractions between the regrowing and the cured cases. In 33 patients with non-functioning pituitary adenomas, 14 cases including 11 with cavernous sinus invasion showed residual tumour on MRI after the operation (regrowing group) and 19 cases had no tumour regrowth on MRI within 5 years after the operation (cured group). Immunocytochemical studies were done with monoclonal antibodies (anti-PCNA, anti-Ki-67: MIB-1). The growth fraction of each tumour was estimated by calculating the ratio of the positive nuclei to the total number of tumour cells with the aid of an image analyser (Mac SCOPE). The tumour doubling times were estimated from serial CT or MRI with the aid of the image analyser (NIH image). Ki-67 staining indices ranged from 0.2% to 1.5% (n = 14, 0.86 +/- 0.10%; mean +/- SEM) in the regrowing group, and from 0.1% to 0.5% (n = 19, 0.23 +/- 0.03%) in the cured group. PCNA staining indices of the regrowing group ranged from 0.6% to 24% (n = 14, 3.7 +/- 1.6%). In the regrowing group, the tumour doubling times ranged from 200 to 2550 days (930 +/- 180 days), and showed a significant inverse correlation with Ki-67 staining indices, but no correlation with PCNA staining indices. The regrowing group showed a significantly higher Ki-67 staining index (n = 14, 0.86 +/- 0.10%) than the cured group (n = 19, 0.23 +/- 0.03%) (p < 0.01). These results indicate that immunocytochemical studies using MIB-1 may be better than those with PCNA for the prediction of regrowth in non-functioning pituitary adenomas. Immunocytochemical study with MIB-1 could lead to the accurate prediction of the rapid regrowing lesions in non-functioning adenomas.     

Ki-67 and apoptosis in a embryologic model

A 67-year-old man developed slowly progressive muscular weakness in the bilateral upper extremities (C5- 7 regions) without signs of sensory deficit following the cervical radiation therapy (70.5Gy) for right laryngeal cancer 4 years before. These clinical signs resembled those of lower motor neuron disease. MRI with gadolinium-DTPA, however, showed enhancement in the bilateral C5 and C6 anterior roots, suggesting the cervical radiculopathy due to radiotherapy. It is known that radiation to the spinal cord can lead to "selective anterior horn cell injury". This is the first case report of the cervical radiation radiculopathy, which, if without MRI, might be classified into selective anterior horn cell injury. Suggestion is made for the hypothesis that the spinal motoneuron loss in radiation myelopathy would be caused by retrograde degeneration due to anterior root damages.     

Ki-67 immunostaining and prognosis in laryngeal cancer

A 7-year-old male Husky dog developed atrophy of the right masseter muscle and pruritus of the right side of the face. A myogenic origin was excluded using muscular biopsy. Electrophysiologically, there was involvement of the motor and sensory fibers of the trigeminal nerve, suggesting a lesion located between the brainstem and the trigeminal ganglion. On MRI examination, a nodular mass was detected in the right caudal fossa. This mass was characterized by intense enhancement after injection of contrast medium. Because of the progressive clinical signs, electrophysiology, and MRI results, a presumptive diagnosis of a trigeminal nerve schwannoma was made. The animal's condition improved slightly with corticosteroids. The dog underwent euthanasia 3 months after initial presentation. Necropsy was not performed.     

The extent of proliferative and apoptotic activity in intraductal and invasive ductal breast carcinomas detected by Ki-67 labeling and terminal deoxynucleotidyl transferase-mediated digoxigenin-11-dUTP nick end labeling

BACKGROUND: The balance among cell proliferation, cell differentiation, and cell death determines the cell number in a population as well as the size or even the stage of a tumor. Thus, to improve our understanding of the pathogenesis of neoplasms, it is important to investigate the regulation of both cell proliferation and cell death. METHODS: This study examined the occurrence of apoptosis and proliferative capacity in 46 breast carcinomas: 20 intraductal carcinomas (ductal carcinomas in situ [DCIS]) and 26 infiltrative ductal carcinomas (IDC). Terminal deoxynucleotidyl transferase-mediated digoxigenin-11-dUTP nick end labeling (TUNEL) and immunostaining with the Ki-67 antibody were used in the examination. A ladder of DNA fragments induced by apoptosis was demonstrated by means of DNA agarose gel electrophoresis in 10 of the available TUNEL positive and negative samples. RESULTS: The results were correlated with p53, bcl-2, estrogen receptor (ER), and progesterone receptor (PR) protein expression, which would suggest association with apoptosis by immunohistochemistry. The apoptosis and proliferation of each cancer were expressed as the number of tumor cells undergoing apoptosis and proliferation per 1000 tumor cells. The extent of apoptosis was more frequently observed in DCIS than in IDC (21.9+/-6.8 vs. 4.0+/-0.9, P < 0.001), and the proliferation activity was significantly higher in IDC than in DCIS (16.8+/-6.5 vs. 3.5+/-0.8, P < 0.006). Apoptosis associated with MIB-1 positive cells and TUNEL labeling was significantly higher in IDC than in DCIS (3.26 vs. 0.42, P=0.001). In DCIS, apoptosis was correlated with p53 (r=0.663, P=0.005), and p53 had a reverse correlation with bcl-2 (r=0.620, P= 0.018). Moreover, bcl-2 expression was associated with ER (P=0.028) and PR (P= 0.005) expression in both DCIS and IDC. CONCLUSIONS: The results of this study show that a higher degree of apoptosis and lower proliferation activity in intraductal carcinoma result in a steady-state, self-renewing condition in which net growth of the tumor is rare. The results also indicate that apoptosis was altered by the expression of p53, bcl-2, ER, and PR.     

Ki-67 and p53 in T2 laryngeal cancer

OBJECTIVE: To study the relationship between the proliferative capacity, represented by the immunohistochemical labeling index (LI) of proliferation marker Ki-67, and the p53 status, as in theory an intact p53 cell cycle checkpoint system should result in a lower proliferative capacity. STUDY DESIGN: From a group of 128 patients with a T2 laryngeal carcinoma, presented from 1989 to 1993 at the University Hospital Utrecht, 20 patients with recurrent disease and 16 patients without recurrent disease were randomly selected. All patients received primary irradiation. METHODS: Denaturing gradient gel electrophoresis and immunohistochemistry determined the p53 status. MIB-1 staining was used to determine the Ki-67 LI. RESULTS: In 36% of specimens we found a p53 mutation with overexpression (LI, 31%). In 8% a p53 mutation without p53 overexpression was found (LI, 18%). Forty-two percent showed no mutation but, nevertheless, overexpression (LI, 35%). Neither mutation nor overexpression was found in 14% (LI, 38%). No correlation exists between p53 status and proliferative capacity of tumors (analysis of variance [ANOVA]; P = .104). The proliferation rate as established with Ki-67 LI positively correlates with response to radiotherapy (P = .006). CONCLUSIONS: 1. Overexpression of wild-type p53 protein does not result in cell cycle arrest measurable by a lower Ki-67 LI in comparison with cases overexpressing mutant type p53 protein. 2. A high Ki-67 LI correlates with a favorable response to radiotherapy.     

Proliferative potential of recurrent intracranial meningiomas as evaluated by labelling indices of BUdR and Ki-67, and tumour doubling time

BACKGROUND: Saphenous vein harvested with a traditional longitudinal technique often results in leg wound complications. An alternative endoscopic harvest technique may decrease these complications. METHODS: One hundred twelve patients scheduled for elective coronary artery bypass grafting were prospectively randomized to have vein harvested using either an endoscopic (group A, n = 54) or traditional technique (group B, n = 58). Groups A and B, respectively, were similar with regard to length of vein harvested (41 +/- 8 cm versus 40 +/- 14 cm), bypasses done (4.1 +/- 1.1 versus 4.2 +/- 1.4), age, preoperative risk stratification, and risks for wound complication (diabetes, sex, obesity, preoperative anemia, hypoalbuminemia, and peripheral vascular disease). RESULTS: Leg wound complications were significantly (p < or = 0.02) reduced in group A (4% [2 of 51] versus 19% [11 of 58]). Univariate analysis identified traditional incision (p < or = 0.02) and diabetes (p < or = 0.05) as wound complication risk factors. Multiple logistic regression analysis identified only the traditional harvest technique as a risk factor for leg wound complications with no significant interaction between harvest technique and any preoperative risk factor (p < or = 0.03). Harvest rate (0.9 +/- 0.4 cm/min versus 1.2 +/- 0.5 cm/min) was slower for group A (p < or = 0.02) and conversion from endoscopic to a traditional harvest occurred in 5.6% (3 of 54) of patients. CONCLUSIONS: In a prospective, randomized trial, saphenous vein harvested endoscopically was associated with fewer wound complications than the traditional longitudinal method.     

Prognosis value of the expression of Ki-67 for squamous cell carcinoma of the oral cavity

A single dose of either cyclosporin-A (CsA) or lobenzarit (CCA) given with an arthrogenic adjuvant completely prevented expression of experimental adjuvant arthritis in rats. The aim of this study was to understand how these drugs prevented the arthritis expression by studying the popliteal lymph nodes draining the arthritic joints at various times after adjuvant injection. Neither drug affected the proliferation in popliteal lymph nodes at the time arthritis was normally expressed, however, there was a marked change in the types of cells present. Immunofluorescence assays showed a reduction in the proportion of CD4+ cells, while the proportion of B-lymphocytes was almost doubled. This coincided with a marked elevation in the ability of these cells to produce interleukin (IL)-6. At the same time production of other cytokines (IL-2, tumour necrosis factor (TNF) and interferon (IFN)-gamma) was not greatly affected. However, one day after adjuvant injection IL-2 and IFN-gamma production was reduced. In vitro experiments showed that IL-6 production by lymphoid cells was relatively unaffected by CsA and CCA but IL-2, TNF and IFN-gamma were suppressed by CsA. The results indicate that CsA and CCA may modify the response to the arthritic adjuvant by specifically inhibiting IL-2, TNF and IFN-gamma production at the time of adjuvant injection. The lack of inhibition of IL-6 by these drugs reveals it may not play a key role in the initiation of this model of chronic inflammation.     

Locally recurrent prostate tumors following either radiation therapy or radical prostatectomy have changes in Ki-67 labeling index, p53 and bcl-2 immunoreactivity

Mast cells participate in the host defense against parasites. Mast cells release leukotrienes (LTs), potent 5-lipoxygenase (LO) products of arachidonic acid well-known to be involved in the inflammatory process. After incubation with Toxoplasma gondii, mast cells were found to degranulate and release LTB4; this interaction damages the tachyzoites. This mast cell activity against the tachyzoites was inhibited by the 5-LO inhibitor A-63162 and the 5-LO-activating protein inhibitor MK-886 but not by the cyclooxygenase inhibitor indomethacin. Reactive oxygen species were not implicated in the mast cell-mediated toxoplasmacidal activity. The generation of LTs is important for mast cell secretion, and LTB4 released by mast cells and other inflammatory cells may be a key factor in the host defense against T. gondii.     

Spindle cell carcinoma of the breast: a case report and an immunohistochemical study including p53 and Ki-67 expression

A rare case of spindle cell carcinoma (SpCC) of the breast occurring in a 51-year-old Japanese woman is reported. A firm and well-circumscribed tumor, measuring 9 x 8.5 x 8.5 cm, was located on the upper lateral region of the right breast. Microscopically, the tumor consisted of sheets of both malignant spindle cells and poorly differentiated ductal carcinoma containing squamoid islands with gradual transition to the spindle cell component. The immunocytochemical expression of epithelial markers was recognized in the spindle cells, as well as in the carcinomatous cells. Moreover, the spindle cell component expressed vimentin, alpha-smooth muscle actin and S-100 protein. Ultrastructurally, in addition to the features of adenocarcinoma, squamous or myoepithelial differentiation was confirmed in the spindle cell component. These findings thus suggest an epithelial origin with squamous differentiation and myoepithelial participation in the genesis of SpCC. In a comparative study, the expression of p53 protein and Ki-67 as a proliferation marker in each component of this tumor was also investigated. The mean p53 labeling index (LI) in both the carcinomatous and spindle cell area was similar, however the mean MIB-1 LI in the spindle cell area was significantly higher than that in the carcinomatous area. The results indicate that p53 overexpression is involved in the tumorigenesis of both components in the SpCC, and the spindle cell component shows a higher degree of proliferative activity than the carcinomatous component.     

DNA topoisomerase II alpha and Ki-67 in human adrenocortical neoplasms: a possible marker of differentiation between adenomas and carcinomas

Cell kinetic information is valuable in evaluating the diagnosis and/or biologic behavior of various human neoplasms. Monoclonal antibody Ki-67 recognizes the cells other than G0 of the cell cycle. A cell cycle-related intranuclear protein, topoisomerase II alpha (topoII alpha), separates chromosomes at the end of mitosis. Its expression is mostly limited to the S to G2/M phases of the cell cycle. We studied cell proliferative activity in adrenocortical adenomas (n = 28), carcinomas (n = 17), and normal adrenal glands (n = 6) by immunohistochemical analysis of Ki-67 and topoII alpha to evaluate their value in the diagnosis of adrenocortical malignancy. We detected Ki-67 and topoII alpha immunohistoreactivity in the nuclei of each case we examined. There was a significant positive correlation (r = 0.927) between the Ki-67 and topoII alpha labeling indexes (LIs), the percentage of positive cells. In normal adrenal cortex and adenoma, the LIs for Ki-67 and topoII alpha were 0.48 +/- 0.16 and 0.44 +/- 0.15 for normal and 0.64 +/- 0.11 and 0.72 +/- 0.12 for adenoma, respectively, with no significant differences in the LIs of adenomas and normal adrenals. The Ki-67 and topoII alpha LIs in the carcinomas were 5.84 +/- 1.33 and 6.13 +/0 1.65, respectively; these LIs were significantly higher than the LIs of adenomas. Eleven of 17 carcinomas demonstrated topoII alpha and Ki-67 LIs of more than 2.5, whereas none of the adenomas did. The topoII alpha and Ki-67 LIs in carcinomas with metastasis (11.21 +/- 3.15 and 9.75 +/- 2.31 respectively; n = 7) were significantly higher than in those without metastasis (2.58 +/- 0.61 and 3.12 +/- 0.90, respectively; n = 10). This indicates that immunohistochemical analysis of Ki-67 and topoII alpha could help to differentiate carcinoma from adenoma in resected adrenocortical neoplasms and might predict aggressive biologic behavior in carcinomas.     

Expression of bcl-2, p53 and Ki-67 in arsenical skin cancers

To investigate the regulation of apoptosis and proliferation in arsenic-induced skin cancers, we examined the expression of bcl-2, p53, and Ki-67 using immunohistochemical staining. Thirty patients with Bowen's disease (BD), ten with basal cell carcinoma (BCC), eight with squamous cell carcinoma (SCC) and eleven of perilesional normal skin (PLN) of the non-sun exposure sites from endemic area were examined. The results showed that: 1) bcl-2 was expressed in all of the BCC homogeneously, in none of the SCC, and in 12/30 of the BD focally or homogeneously; 2) p53 was expressed in all of the arsenical skin cancers with a labelling index of 75 +/- 14% of BD, 50 +/- 17% of BCC, 61 +/- 15% of SCC, and also in all of the perilesional normal skin with a labelling index of 55 +/- 24%; 3) Ki-67 was expressed in all of the skin cancers with labelling index of 58 +/- 17% of BD, 12 +/- 7% of BCC, 47 +/- 21% of SCC, and in 9/11 of PLN with a labelling index of 41 +/- 24%. Expression of bcl-2 in BCC or BD is related to the phenotype of germinative basal cell. The constant expression of bcl-2 i early dysplastic cells of BD and the earliest expression of P53 in the basal cells of perilesional normal skin indicate that the initial step of arsenic-induced carcinogenesis is from the basal germinative cells. There is no mutual relationship between bcl-2, p53 or Ki-67 expression in any type of the arsenical skin cancers, but there is a positive correlation between p53 and Ki-67 expression identified in perilesional normal skin. BD had the highest labelling index of p53 and Ki-67.     

Distinction of basaloid carcinoma of the prostate from benign basal cell lesions by using immunohistochemistry for bcl-2 and Ki-67

The distinction of rare basaloid carcinomas (BC) of the prostate from more common basal cell hyperplasia may be difficult, because basal cell hyperplasia (BCH) may have prominent nucleoli and may appear infiltrative. Using immunohistochemistry, we studied bcl-2 and p53 expression and Ki-67 proliferation index in eight cases of typical BCH, eight cases of BCH with nucleoli, and six cases of BC. Bcl-2 expression (P < .0001) and Ki-67 index (P=.005) were elevated in BC compared with typical BCH or BCH with nucleoli, whereas there was no significant difference between typical BCH and BCH with nucleoli. P53 was not discriminative in separating benign from malignant basal cell lesions of the prostate. Bcl-2 may play a role in the pathogenesis of basal cell lesions of the prostate. Elevated expression of bcl-2 and higher Ki-67 index may aid in the diagnosis of basal cell proliferative lesions of the prostate.     

Correlation between p53 mutations and antibody staining in breast carcinoma

Abnormalities of the p53 gene and protein were examined in 81 primary breast carcinoma samples. Using a polymerase chain reaction-single-strand conformational polymorphism (PCR-SSCP) analysis, mutations in p53 exons 5-8 were identified in 13 of 81 tumours (16 per cent) and confirmed by DNA sequencing. Positive staining for p53 protein was detected in ten of 77 (13 per cent) of these tumours using polyclonal CM1 antibody on formalin-fixed tissue. Mutations detected by PCR-SSCP analysis were more common in grade III tumours (P = 0.015), but no correlation was found with tumour size, node status or level of epidermal growth factor receptor expression. A p53 mutation was associated with positive antibody staining in only two patients. Positive immunohistochemical staining using a p53 antibody may detect p53 protein expression, but this may not correlate directly with an underlying mutation in the hot spot region examined.     

Monoclonal antibodies detecting components of the bovine immune system in formaldehyde-fixed paraffin-embedded tissue specimens

Although the use of monoclonal antibodies in the diagnosis of fixed human material is a daily routine, the lack of suitable reagents recognizing epitopes resistant to formaldehyde fixation is an obvious limit to extending this approach to veterinary research and practice. To find reagents that retain their binding capacity to the recognized epitopes in formaldehyde-fixed samples, bovine lymphoid tissue sections were immunostained using various antigen retrieval procedures with monoclonal antibodies raised against ruminant leukocyte cell surface molecules. As a results, a set of antibodies could be established that allowed the identification of different immune cell types including all or a distinct subpopulation of B and T lymphocytes, monocytes, macrophages, granulocytes, red blood cells, and vascular endothelial cells.     

Bcl-2 oncoprotein positivity and high MIB-1 (Ki-67) proliferative rate are independent predictive markers for recurrence in prostate carcinoma

The incidence of transfusion-associated hepatitis in the United States has fallen dramatically since the late 1960s. Where once the risks were so great that as many as one in three transfused patients contracted hepatitis, now they are infinitesimal. Many factors share responsibility for this accomplishment; however, two stand above the rest: (i) improved donor selection and screening criteria, especially elimination of paid blood donations; and (ii) major advances in testing for viral hepatitis carriers. Currently, four tests are used for the prevention of transfusion-associated hepatitis: (i) hepatitis B surface antigen; (ii) hepatitis C virus antibody; (iii) hepatitis B core antibody; and (iv) alanine aminotransferase. The first two tests are largely responsible for the current low risks of transfusion-associated hepatitis due to hepatitis B virus and hepatitis C virus of 1 in 63,000 and 1 in 125,000, per unit, respectively. To further reduce the risks of transfusion-associated hepatitis will require the enhanced sensitivity provided by nucleic acid amplification techniques (e.g. polymerase chain reaction). Currently, however, no such tests are licensed and practical, automated, or inexpensive enough for individual blood donor screening. We have made such great strides in the prevention of transfusion-transmitted hepatitis that background rates of viral hepatitis now greatly exceed the risk of transmission via transfusion. For this reason, while it may still be reasonable to consider a transfusion as a possible cause for hepatitis, it is imperative that many other possibilities (e.g., iatrogenic and other risk factors) be ruled out.     

Value of Ki-67 immunostaining in preoperative biopsies of carcinomas of the lung

The mechanism of the dimensional increase in demineralized dentine crystals was investigated using a high-resolution transmission electron microscope. Lattice fringes were observed even in the demineralized crystals. The characteristics of demineralized dentine crystals mainly consisted of a partial disappearance of their lattice fringes along their lateral surface. High-resolution transmission electron microscopy also revealed that an intricate association between partially demineralized crystals occurred at the interface where incoherent or coherent tilt boundary, the dislocation of lattice fringes appeared. The present findings suggest that the dimensional increase in carious dentine could be brought by a crystal fusion.     

Ki-67 immunolabelling index is a prognostic indicator in childhood posterior fossa ependymomas

Treatments with once-daily trovafloxacin (200 or 100 mg) and amoxicillin/clavulanic acid (500/125 mg three times daily) were compared in adults with acute exacerbations of chronic obstructive bronchitis. At end of treatment, 95% (113/119) of clinically evaluable patients receiving trovafloxacin 200 mg, 98% (113/115) of patients treated with trovafloxacin 100 mg and 97% (113/117) of patients receiving amoxicillin/clavulanic acid were cured or improved. At study end, 91%, 87% and 88%, respectively, were cured or improved. At end of treatment, trovafloxacin 200 mg eradicated Haemophilus influenzae in 97% of patients, Streptococcus pneumoniae in 90% and Chlamydia pneumoniae in 100%. The respective eradication rates for trovafloxacin 100 mg were 84%, 100% and 100%; those for amoxicillin/clavulanic acid were 92%, 100% and 100%. At study end, trovafloxacin 200 mg totally eradicated all three pathogens. Trovafloxacin 100 mg eradicated Haemophilus influenzae in 91% of patients, Streptococcus pneumoniae in 100% and Chlamydia pneumoniae in 80%. Respective eradication rates for amoxicillin/clavulanic acid were 78%, 100% and 80%. Only 7% (10/144) of patients receiving trovafloxacin 200 mg reported treatment-related adverse events, as did 7% (10/135) of patients given trovafloxacin 100 mg and 12% (17/140) of patients given amoxicillin/clavulanic acid.