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Results for “Pathologic response”

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PubMed1988

Evaluation of angiogenesis in chronic inflammation by laser-Doppler flowmetry.

1. A non-invasive method is described for the assessment of angiogenesis in chronic inflammation using laser-Doppler flowmetry. 2. Significant increases in capillary blood flow were seen on days 5 and 7 after induction of subcutaneous granulomatous lesions, as compared with control skin. 3. Changes in blood flow were accompanied by changes in pulsatile flow pattern and by an intense angiogenic response observed by light microscopy. 4. The potential application of laser-Doppler flowmetry to quantitative and qualitative studies of evolving angiogenesis in pathological responses is discussed.

Animals↗

PubMed1982

Atypical histopathologic features in sympathetic ophthalmia. A study of a hundred cases.

One hundred cases of clinically acceptable sympathetic ophthalmia (SO) were evaluated histologically to determine the incidence of atypical features and correlate them with the severity of choroidal inflammation. The inflammatory response in the choroid varied from a focal non-granulomatous to a diffuse non-necrotizing granulomatous process. The choriocapillaris was focally involved rather frequently (in 40% of the cases). This was associated with severe inflammation. Chorioretinal adhesions were noted in 7% of the cases. Retinal detachment was observed in 50% of the cases, and this was associated with severe uveal inflammation. Fifty percent of the cases showed retinal perivasculitis and 18% a mild inflammatory infiltrate of the retina. Involvement of the meninges (a finding present in 22% of the cases) and severe inflammation in the scleral canals were both related to the severity of choroidal inflammation. Lens-induced endophthalmitis was observed in 14 cases and was not associated with the severity of the choroidal inflammation. Our observations indicate that the changes interpreted as atypical in SO are usually associated with severe choroidal inflammation, suggesting that these features may be the response to high doses of antigenic agent. The classical histopathologic description of SO may represent only one manifestation of the pathologic response of this disease.

Adolescent↗

PubMed2001

Second-look laparotomy for epithelial ovarian cancer: a reappraisal.

Although second-look laparotomy (SSL) has been used in the management of ovarian cancer for over three decades, its current clinical use is limited. On average, over 50% of patients with a clinical complete response are noted to have disease at the time of SLL, emphasizing our lack of accurate noninvasive methods for determining pathologic response. Although findings at SLL have some prognostic significance, there is no definitive evidence that those patients undergoing SLL have improved survival, and even 50% of patients with negative findings at SLL have recurrences. The lack of survival advantage for patients enduring SLL highlights the need to identify consistently effective salvage and consolidation regimens. Few published studies provide definitive evidence regarding efficacy of treatment. Prospective, randomized, controlled trials are needed to evaluate the various therapies available. In general, the performance of SLL should be confined to those patients enrolled in clinical trials.

Adult↗

PubMed1994

Absence of immunohistochemical metallothionein staining in bladder tumor specimens predicts response to neoadjuvant cisplatin, methotrexate and vinblastine chemotherapy.

Pre-chemotherapy bladder tumor tissue was retrospectively analyzed in 21 patients treated with neoadjuvant cisplatin, methrotrexate and vinblastine. Immunohistochemical staining for 2 proposed mediators of drug resistance, p-glycoprotein and metallothionein, was performed and compared to chemotherapeutic response and survival. There was no significant relationship between staining for p-glycoprotein and the response to chemotherapy or survival. Patients with no detectable staining for metallothionein were statistically more likely to sustain a complete pathological response (p = 0.029) after chemotherapy than those with any detectable staining. No relationship between metallothionein immunostaining and survival was apparent. This study offers further evidence linking metallothionein in tumor resistance to cisplatin containing chemotherapy regimens.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2000

Optimal treatment for localized esophageal cancer still uncertain.

These articles both report the results of multi-institutional, randomized, phase 3 trials for the treatment of patients with localized (T1-3 N0-1 M0) esophageal squamous cell carcinoma (SCC) or esophageal adenocarcinoma. Both studies were initiated and coordinated by the Radiation Therapy Oncology Group (RTOG) but included patients enrolled by other study groups as well. Cooper et al. report late follow-up results for the RTOG 85-01 trial that was conducted between 1986 and 1990. This trial randomized patients to either radiation therapy (RT) alone (RT, 64 Gy in 32 fractions over 6.4 wk, n = 62) or combined RT and chemotherapy (50 Gy in 25 fractions over 5 wk, plus cisplatin 75 mg/m2 i.v. on first day of wk 1, 5, 8, and 11, and continuous infusion fluorouracil (5FU) 1 g/m2 per day on the first 4 days of the same weeks, n = 61). Most (82%) of the patients had SCC. Eight percent of the cohort randomly assigned to combined modality therapy experienced acute life-threatening toxic effects, and an additional 2% died as a direct consequence of treatment. The randomized trial was halted in 1990 when an interim analysis found a highly significant difference in survival favoring the combined therapy group, after which 73 consecutive patients were enrolled into a nonrandomized study offering only the combined therapy regimen. At 5-yr of follow-up, the overall survival rate for the combined therapy group in the randomized study was 26% (95% CI, 15-37%) compared with 0% for RT alone. In the nonrandomized study, the 5-yr overall survival rate was 14% (95% CI, 6-23%). The histopathological type of tumor did not significantly influence survival. Cooper et al. now report that 22% of the randomized combined modality group survived at least 8 yr after treatment, and that there were no deaths caused by esophageal cancer after 5 yr post-treatment. The study reported by Kelsen et al. included 440 patients with esophageal adenocarcinoma (n = 236) or SCC (n = 204) randomized to either preoperative chemotherapy plus esophagectomy or to esophagectomy alone. The chemotherapy regimen consisted of three cycles of preoperative cisplatin and 5FU and two cycles after operation for responding patients. Doses were higher than those used in the RTOG 85-01 trial. Although radiation therapy was not part of the treatment plan, it could be given in some circumstances. There was no significant difference in median survival (14.9 months for chemotherapy plus surgery compared with 16.1 months for surgery alone), and there were also no significant differences in 1-yr, 2-yr, 3-yr, or disease-free survival rates. There were no significant differences in survival between patients with adenocarcinoma and those with SCC. A clinical response to chemotherapy, as assessed by barium contrast radiography, was found in 19% of patients who received chemotherapy. A complete pathological response was found in 2.5% of patients. There was no significant increase in operative complications in the chemotherapy treated group.

Adenocarcinoma↗

PubMedDate not supplied

Biological diversity among serotype 2 Marek's disease viruses.

Selected biological characteristics were determined for 14 low-passage serotype 2 Marek's disease virus (MDV) isolates. Four of these isolates were also tested after extensive serial passage in chicken embryo fibroblast cultures. Observations were made on replication in vitro and in vivo, pathogenicity by in ovo inoculation, antigenicity, and protection against virulent MDV challenge. Among the low-passage isolates, there were some differences in pathogenicity after in ovo inoculation but relatively little difference in other characteristics, with the exception of the HN-1 strain, which replicated more rapidly in cell culture but produced generally lower in vivo responses than other isolates. After extended in vitro passage, isolates replicated much more readily in cell culture and produced lower pathologic responses in vivo than low-passage isolates, as has been reported for serotype 1 isolates. No antigenic differences among isolates were detected, but high-passage isolates induced lower levels of precipitating antibodies than low-passage isolates, indicating a possible reduction in A antigen production. The observed diversity associated with strain and passage level may be of value in the selection of optimum vaccine strains.

Animals↗

PubMed1995

Rectal cancer: the influence of tumor proliferation on response to preoperative irradiation.

PURPOSE: Regression of rectal carcinoma after preoperative irradiation is variable, likely reflecting differences in the physical and biologic properties of these tumors. This study examines the association between the pathologic response of rectal cancer after irradiation and its pretreatment proliferative state as assayed by the activity of the proliferative dependent antigens (Ki-67, PCNA) and mitotic counts. METHODS AND MATERIALS: One hundred and twenty-two patients with locally advanced rectal cancer received preoperative irradiation followed by surgery. Pretreatment tumor biopsies were scored for the extent of Ki-67 and PCNA immunostaining and the number of mitoses per 10 high-powered fields. Postirradiation surgical specimens were examined for extent of residual disease. RESULTS: The tumors of 38 of 122 patients (31%) exhibited marked pathologic downstaging (no residual tumor or cancer confined to the rectal wall) after preoperative irradiation. Two features were associated with the likelihood of marked pathologic regression after preoperative irradiation: tumor proliferative activity and lesion size. When stratified by lesion size, marked tumor regression occurred most frequently in smaller tumors with high Ki-67, PCNA, and mitotic activity compared to larger tumors with lower Ki-67, PCNA, and mitotic activity. Intermediate downstaging rates were seen for small or large tumors with moderate Ki-67, PCNA, and mitotic activity. CONCLUSION: Tumor Ki-67, PCNA, and mitotic activity predicts the likelihood of response to irradiation, which may aid in formulating treatment policies for patients with rectal cancer.

Adult↗

PubMed1976

The value of electrostimulation in epileptic focus localization.

The ES is a non-physiological stimulus of the brain. However it represents an important and indispensable part of stero-EEG investigation since it is an easily adjustable method, capable of inducing typical electro-clinical seizures. From the clinical and electrical responses elicited by ES and from the data of the stimulation tresh-old, we are in agreement with other authors, we feel we can also distinguish several different reacting zones in the epileptic brain: 1. The epileptogenic zone from which the complete or almost complete electro-clinical seizure is reproducible immediately by ES or with short latency. These pathological responses show the severe dysfunction of the given structures. 2. The irritative zones from which seizure elements can be evoked, but the complete electro-clinical seizure does not. "Physiological" clinical responses can also be elicited, but by a very low threshold stimulus pointing to the pathological excitability of this zone. 3. The area reacting to "normal" stimulus threshold with a physiological response. 4. The silent area without any electro-clinical response in the functional state of the nervous system. One of the practical values of ES is that makes possible to separate these zones from each other in a given patient within certain limits, and it may help to reveal the localization, the multiplicity and the degree of the "seizure disposition" in epilepsy.

Brain Mapping↗

PubMed1997

Virulent and avirulent Rhodococcus equi infection in T-cell deficient athymic nude mice: pathologic, bacteriologic and immunologic responses.

We investigated the pathologic, bacteriologic and immunologic responses of BALB/c-nu/nu mice (nude mice) and BALB/c mice (euthymic mice) infected intravenously with virulent and avirulent Rhodococcus equi ATCC 33701, and its plasmid-cured derivative ATCC 33701P-, to evaluate the role of T lymphocytes. Adaptive transfer of immune and normal spleen cells into nude mice was also investigated. Nude and euthymic mice were inoculated with 10(6) ATCC 33701 or 10(6) ATCC 33701P- intravenously (i.v.) and killed at 0, 7, 14, 21, 28 and 35 days post-inoculation, except dead cases. In athymic nude mice infected with ATCC 33701, deteriorating systemic inflammatory responses developed during the experimental period and multiplication of the bacteria continued until the end of the experiment. Nude mice developed splenomegaly and multifocal gross hepatic necrosis with some mortality. Splenomegaly was caused by diffuse proliferation of bacteria-laden macrophages and epithelioid cells, and gross hepatic necrosis was caused by the formation of thromboses and granulomatous lesions. Infection of euthymic mice with a sublethal dose of ATCC 33701 resulted in transient granuloma formation in the liver and spleen, production of specific antibodies against the virulent bacteria and gradual elimination thereof. In contrast, infection with ATCC 33701P- produced few lesions after rapid elimination and no antibody production against bacteria in either normal or athymic nude mice. In nude mice given normal and immune spleen cells, histopathological lesions and granulomas formed only in the liver and spleen, in addition to specific antibodies against 15- to 17-kDa antigens. The pathological lesions observed in the nude mice given immune spleen cells were similar to those seen in the mice given normal spleen cells, but they were less severe than those in mice given normal spleen cells. Mice given immune spleen cells showed a significantly higher elevation of antibody production than mice given normal spleen cells. These results suggested that protection against virulent R. equi in mice depends mainly on cell-mediated immune responses, whereas avirulent R. equi in mice are cleared by innate immune responses.

Actinomycetales Infections↗

PubMed1983

Tissue response to carbon-reinforced polyethylene.

There has been clinical concern about the gray discoloration in synovial tissue adjacent to carbon-reinforced polyethylene total joint implants. To evaluate the pathologic response of the synovium to this material, synovial specimens from 11 total ankle cases with carbon-reinforced tibial components and two synovial specimens from cases with standard polyethylene tibial components were studied by gross and histologic techniques. Polyethylene debris was found to produce a significant synovial reaction with histiocytes and foreign body giant cells. This was found in both the carbon-reinforced cases and in those cases without carbon-reinforced components. This reaction is also seen in revisions of total hips and total knees in which standard polyethylene components have been implanted. In contrast with this, carbon particles produced only a minimal reaction in the synovial tissue. Carbon appears to be an extremely benign implant material, and synovial discoloration from shed carbon fibrils does not appear to present a significant clinical problem.

Adult↗

PubMed1993

The regulation by light of retinal necrosis and the immune response following anterior chamber inoculation of herpes simplex virus type-1.

Following anterior chamber injection of the KOS strain of herpes simplex virus type 1 into Balb/c mice a characteristic pathologic response occurs. When examined 10-14 days later there is intense anterior segment inflammation of the injected eye, but the retina is spared. In contrast, the contralateral eye undergoes intense and destructive retinitis with little or no involvement of the anterior segment. Coincident with these observations is the induction of ACAID (for anterior chamber associated immune deviation) which is characterized by a suppressed DTH response, normal antibody titers, and normal cytolytic T-cell responses to HSV antigens. Since we have recently demonstrated that ACAID does not take place in the absence of light (i.e., is light dependent), we have examined the effect of light on the HSV-retinitis model. When Balb/c mice are either dark-reared or dark-adapted prior to AC injection of HSV-1, contralateral retinitis is abolished. Concurrent with the abrogation of retinitis, is the elimination of ACAID to HSV-1 antigens. In addition, although contralateral retinitis and ACAID do not develop in dark-reared mice if they are placed in the light immediately following injection, both can be re-established in dark-reared animals following a 2 week period of re-adaptation to light. Our results demonstrate that the entrance of light into the eye is not only important for ACAID, but also for the development of contralateral HSV-induced retinitis.

Animals↗

PubMed2006

Pre-treatment haemoglobin levels and the prediction of response to neoadjuvant chemotherapy in breast cancer.

AIMS: A low pre-treatment haemoglobin level has been shown to negatively influence outcome in the treatment of tumours of the cervix, bladder and head and neck by radiotherapy. The purpose of this study was to assess the influence of baseline haemoglobin levels on the response to neoadjuvant chemotherapy for breast cancer. MATERIALS AND METHODS: One hundred and thirty-nine women receiving neoadjuvant chemotherapy for operable breast tumours (T2-4, N0-1, M0) were accessed from our prospective database. Women were treated between March 1999 and June 2004. The median age was 47 years (range 25-70). Most women were treated with 5-fluorouracil, epirubicin and cyclophosphamide chemotherapy (122/139 patients). Baseline haemoglobin levels were compared for clinical responders (partial or complete) and non-responders (stable or progressive disease) using Student's t test and logistic regression. The analysis was adjusted for nodal status, tumour size, tumour grade and menopausal status. RESULTS: The overall response rate was 84.9% (118/139), with a complete clinical response in 24.5% (34/139). Mean haemoglobin levels were 13.3 g/dl in responders and 13.4 g/dl in non-responders (range 7.9-15.8). The distributions of haemoglobin levels were not significantly different when comparing either responders with non-responders or 'good' responders with 'poor' responders (P = 0.70 and P = 0.32, respectively). If haemoglobin is treated as a binary variable using 12.0 g/dl as the threshold, there is a non-significant trend towards a reduction in the probability of achieving a good response if baseline haemoglobin is below 12.0 g/dl (odds ratio = 0.26, confidence interval = 0.06-1.21; P = 0.086). The rate of complete pathological response was 4.3% (6/139). The mean haemoglobin level in these patients was 14.2 g/dl (range = 12.8-15.7), but the small numbers precluded further analysis. CONCLUSIONS: There is no evidence for an influence of pre-treatment haemoglobin levels on the clinical response to neoadjuvant chemotherapy in breast cancer. It is unlikely that correction of anaemia above that which is warranted clinically will improve outcomes.

Adult↗

PubMed1994

Dietary supplementation with L-arginine in patients with breast cancer (> 4 cm) receiving multimodality treatment: report of a feasibility study.

L-Arginine has been shown, in human breast cancers, to increase protein synthesis and the number of cells in the growth phase of the cell cycle. L-Arginine, therefore, may potentiate the response of breast cancers to cell cycle-specific cytotoxic agents. This phase II pilot study assessed the clinical, radiological and pathological responses in 44 patients with breast cancers > 4 cm in diameter (46 tumours: T2, n = 6; T3, n = 22; T4, n = 19), who received oral L-arginine 30 g day-1 for 3 days prior to each cycle of CHOP chemotherapy, followed after 4-6 cycles by radiotherapy. Following this treatment, 95% of patients had a clinical response: complete response in 30% and partial response in 65%. Imaging, ultrasound and mammography revealed response rates of 91% and 76% respectively. Surgery was performed in 43 patients. Histological examination revealed that in 18% of cases there was no residual evidence of tumour. Furthermore, if residual tumour was identified, the degree of destruction was graded as 'severe' in 36% and 'moderate' in 30% of cases. Further studies are now required to evaluate the potential beneficial use of nutritional pharmacology in combination with existing treatment regimens.

Adult↗

PubMed1996

Isolated limb perfusion with tumor necrosis factor and melphalan for limb salvage in 186 patients with locally advanced soft tissue extremity sarcomas. The cumulative multicenter European experience.

OBJECTIVE: The objective of the study was to achieve limb salvage in patients with locally advanced soft tissue sarcomas that can only be treated by amputation or functionally mutilating surgery by performing an isolated limb perfusion (ILP) with tumor necrosis factor (TNF) + melphalan (M) as induction biochemotherapy to obtain local control and make limb-sparing surgery possible. SUMMARY BACKGROUND DATA: To increase the number of limb-sparing resections in the treatment of locally advanced extremity soft tissue sarcoma, preoperative radiation therapy or chemotherapy or a combination of the two often are applied. The ILP with cytostatic agents alone is another option but rarely is used because of rather poor results. The efficacy of the application of TNF in ILP markedly has changed this situation. METHODS: In 8 cancer centers, 186 patients were treated over a period of almost 4.5 years. There were 107 (57%) primary and 79 (43%) recurrent sarcomas, mostly high grade (110 grade III; 51 grade II; and 25 very large, recurrent, or multiple grade I sarcomas). The composition of this series of patients is unusual: 42 patients (23%) had multifocal primary or multiple recurrent tumors; median tumor size was very large (16 cm); 25 patients (13%) had known systemic metastases at the time of the ILP. Patients underwent a 90-minute ILP at 39 to 40 C with TNF + melphalan. The first 55 patients also received interferon-tau. A delayed marginal resection of the tumor remnant was done 2 to 4 months after ILP. RESULTS: A major tumor response was seen in 82% of the patients rendering these large sarcomas resectable in most cases. Clinical response rates were: 33 complete response (CR) (18%), 106 partial response (PR) (57%), 42 no change (NC) (22%), and 5 progressive disease (PD) (3%). Final outcome was defined by clinical and pathologic response: 54 CR (29%), 99 PR (53%), 29 NC (16%), and 4 PD (2%). At a median follow-up of almost 2 years (22 months; range, 6-58 months), limb salvage was achieved in 82%. Regional toxicity was limited and systemic toxicity minimal to moderate, easily managed, with no toxic deaths. CONCLUSIONS: In the setting of isolated limb perfusion, TNF is an active anticancer drug in patients. The ILP with TNF + melphalan can be performed safely in many centers and is an effective induction treatment with a high response rate that can achieve limb salvage in patients with locally advanced extremity soft tissue sarcoma.

Adolescent↗

PubMed1993

Pathogenesis of multiple sclerosis--the immune diathesis and the role of viruses.

Although the evidence of involvement of viruses in the pathogenesis of MS is largely circumstantial, the pattern of association is constant, with little evidence for direct viral infection of the CNS but with a consistent immune response to several common viruses. In parallel with these studies, epidemiological studies, while indicating genetic predisposition, favor an environmental pathogenetic factor and experimental models indicate that viruses can induce demyelination either by oligodendrolysis or by a variety of immune mechanisms with or without persistence in the CNS. In elucidating the pathogenesis of MS, the challenge is to understand the basis of the immune abnormalities, with intrathecal synthesis of viral antibodies and abnormal immune responses to some viruses, and to relate these to the MRI abnormalities which indicate periodic BBB breakdown. There is strong evidence that the breakdown is associated with inflammation. and that cytokines, particularly TNF, may play a role in demyelination. In conclusion, therefore, several factors are probably key in our understanding of MS. These include: (i) the genetic control of the immune system and its interaction with viral antigen; (ii) related effects on cerebral endothelium including cytokine and adhesion molecule regulation; and (iii) associated glial and axonal responses. Such an approach to the pathogenesis of MS may not identify a specific cause. It may, however, indicate that a pathological cascade can be "triggered" by several common viral infections and that therapy can be used to intervene at several points in the pathological response.

Animals↗

PubMed1993

Total sleep deprivation in the rat transiently abolishes the delta amplitude response to darkness: implications for the mechanism of the "negative delta rebound".

1. The homeostatic model of delta sleep has provided a useful framework for basic sleep research. This model is based on the relation of delta EEG to the duration of prior waking in man, a relation highlighted by the marked increase (rebound) in the delta EEG of nonrapid eye movement (NREM) sleep that follows total sleep deprivation (TSD). The generality of this model is severely challenged by the response to TSD in the rat. In the 12-h light period (LP) that immediately follows TSD, the rat shows a massive increase in REM sleep but only a modest increase in NREM delta EEG. Although this initial delta increase does not nearly compensate for the delta lost during deprivation, the rat then exhibits a depressed rate of delta production (the "negative delta rebound"). This robust and reproducible reaction worsens the delta deficit. 2. Using rats with chronic electrode implantations, we deprived them of all sleep for 24 h by handling them gently when they became inactive. We found that the negative delta rebound entails a transient, near-total failure of delta amplitude to increase normally in response to the onset of darkness. This loss of the rat's EEG response to darkness suggests a disruption of basic sleep physiology and raises the possibility that the negative rebound is also a pathological response. 3. We hypothesize that the negative rebound is maladaptive, and is caused by the massive increase in REM sleep that precedes it; this hypothesis can be tested experimentally.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

Neurophysiological studies of patients with classical phenylketonuria: evaluation of results of IQ scores, EEG and evoked potentials.

Neurophysiological studies were conducted in 42 patients with classical phenylketonuria. The results of the intelligence quotient scores, electroencephalogram, visual evoked potentials and brain-stem auditory evoked potentials were evaluated. When compared with the controls, the subjects demonstrated a significant prolongation in VEP P1 and BAEP I-V interpeak latencies and an increase in VEP N1P1 amplitudes. No relationship was found between these pathological responses and metabolic control. However, the observation of normal intelligence quotient scores in 14 out of 18 patients who displayed a pathological prolongation in P1 latencies led us to the conclusion that evoked potentials may have a significant role in the determination of neurophysiological defects and that even cases with good metabolic control may have some obscure neurophysiological dysfunction which should be evaluated more carefully.

Brain Stem↗

PubMed1976

Histopathology of spontaneous regression in virus-induced murine leukemia.

The histopathology of the spontaneous regression of murine leukemia induced by a particular strain of Friend leukemia virus was studied in Swiss ICR/Ha mice. Animals inoculated with the regressing strain of Friend virus exhibited an initial pathologic response identical to that induced by conventional strains of Friend virus. Unlike the fatal leukemia produced by conventional Friend virus, the pathology of the disease induced by the regressing strain of Friend virus appeared to be self-limiting. The histopathology of the two diseases is compared in this report.

Animals↗