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K Kaul

Publications and source records attributed to K Kaul.

At least 19 recordsLinked to original sources
PubMed2001

Tumor-infiltrating lymphocytes are a marker for microsatellite instability in colorectal carcinoma.

BACKGROUND: Cells with deficient DNA mismatch repair develop microsatellite instability. Extensive microsatellite instability (MSI-high) is characteristic of colorectal carcinomas in hereditary nonpolyposis colorectal carcinoma (HNPCC) and in 10-% 15% of sporadic colorectal carcinomas. Microsatellite instability-high colorectal carcinomas differ from others in important clinical and pathologic features. However, MSI typing is expensive and not widely available. Microsatellite instability type may be predicted by tumor-infiltrating lymphocytes (TILs), which can be evaluated with ordinary light microscopy. METHODS: The authors evaluated TILs as a pathology screen for MSI-high status in 138 colorectal carcinomas that had been evaluated for MSI in a variety of studies. This case series was systematically enriched with HNPCC and other MSI-high cases to allow accurate sensitivity and specificity estimation. Tumor-infiltrating lymphocytes were quantitated as TILs per 10 high-power microscopic fields by an observer blinded to MSI status. RESULTS: Of the 138 carcinomas studied, 67 (48.6%) were MSI-high, 22 (15.9%) were MSI-low, and 49 (35.5%) were MSI-stable. All 25 HNPCC colorectal carcinomas were MSI-high. Tumor-infiltrating lymphocytes counts ranged from 0 to 300, with a markedly skewed distribution (median, 11; mean, 36). Sensitivity and specificity for selected cut points of TIL count were computed. Using a TIL count of 5 as a cut point yields a sensitivity of 93% and specificity of 62%. In a population in which 12% were MSI-high, consideration of TIL could reduce the number of colorectal carcinomas referred for MSI testing by greater than one-half, and still 93% of the MSI-high carcinomas would be identified. CONCLUSIONS: The presence of MSI defines a subset of colorectal carcinomas with special molecular etiology and characteristic clinical, pathologic features, inclusive of increased survival. The authors conclude that quantification of TILs may provide a simple, single criterion for choosing which colorectal carcinomas are candidates for MSI testing.

Colorectal Neoplasms↗
PubMed2000

Gastric stromal tumor.

Gastric stromal tumors display a bewildering array of immunohistological and ultrastructural features as well as variable biological behavior. These tumors are rare as compared with ones that arise from the gastric epithelium. Moreover, they have been the subjects of controversy because of their uncertain histogenesis. We report the pathological features of gastric stromal tumors we recently encountered in three patients.

Humans↗
PubMed1999

A new polymerase chain reaction-based method for the detection of T-cell clonality in patients with possible cutaneous T-cell lymphoma.

OBJECTIVE: To evaluate a new, rapid, and sensitive method for the detection of T-cell clonality in patients with lesions suggestive of cutaneous T-cell lymphoma (CTCL). DESIGNS: Skin specimens were obtained from 48 patients with possible CTCL. Polymerase chain reaction amplification of the T-cell receptor gamma (TCRG) gene was performed using consensus primers to the V and J regions. Clonal populations having identical N-region sequences are detected by single-strand conformation polymorphism analysis using a semiautomated electrophoresis system with a silver-staining method for gel visualization. The results of clinicopathological assessment were compared with those of immunohistochemistry and polymerase chain reaction analysis. SETTING: Cutaneous lymphoma clinic at a university medical center. PATIENTS: Forty-eight patients with skin lesions suggestive of CTCL. RESULTS: Based on the clinicopathological assessment, 26 patients were diagnosed as having CTCL. Of them, clonality was detected in 19 patients (73%) and an abnormal phenotype in 17 (68%) of 25 patients. Combining both tests, abnormal results were noted in 24 (92%) of 26 patients with CTCL. Clonality was also identified in 2 (12%) of 17 patients with presumably benign lesions on clinicopathological assessment. CONCLUSIONS: Polymerase chain reaction and single-strand conformation polymorphism analysis of the TCRG gene is a rapid and sensitive method that can contribute to the diagnosis of CTCL. The new method is especially useful when used in conjunction with immunophenotyping.

Adult↗
PubMed1998

Diagnosis of pulmonary tuberculosis using PCR assays on sputum collected within 24 hours of hospital admission.

There have been few studies evaluating the efficacy of polymerase chain reaction (PCR) testing in front-line clinical practice. We assessed the diagnostic yield of PCR prospectively in a blinded study of patients admitted to rule out tuberculosis and compared PCR results to a culture and clinical diagnosis of tuberculosis. Specimens were sent for routine smear, culture, and PCR analysis. Sputum sediments were submitted for PCR amplification of IS6110 sequences by an in-house assay and also the Roche Amplicor PCR assay targeting 16s ribosomal RNA genes. Eighty-five patients were enrolled: 27 patients had cultures positive for tuberculosis; 12 were smear-positive. PCR by both assays on the first specimen picked up all patients smear-positive on any specimen. A positive PCR on at least one of two specimens collected in the first 24 h was 85 and 74% sensitive and 88 and 93% specific for tuberculosis by the in-house and Roche techniques, respectively. Sensitivity in smear-negative patients was 73 and 53%, respectively. The in-house PCR detected 100% and Roche detected 95% of patients with more than paucibacillary (greater than 20 colonies) tuberculosis. We conclude that PCR may be a useful tool to evaluate patients for tuberculosis within the first hospital day.

Female↗
PubMed1998

Detection of Breast Cancer Cells in Blood Using Immunomagnetic Bead Selection and Reverse Transcription-Polymerase Chain Reaction.

Background: A sensitive and specific method for the detection of occult breast cancer cells may prove clinically useful. The purpose of this study was to investi gate cytokeratin-19 (CK-19) and gross cystic disease fluid protein (GCDFP) as potential reverse transcription-polymerase chain reaction (RT-PCR) targets for the detection of breast micrometastases. Through positive selection of breast epithelial cells by immunomagnetic bead separation, two RT-PCR assays were developed. Methods and Results: Positive selection of breast epithelial cells was performed using Ber-EP4 monoclonal antibody bound to magnetic beads. RNA was isolated and RT-PCR performed using CK-19 and GCDFP as targets. Detection sensitivity was five T47D cells spiked into 10 mL of normal blood for either target. In all, 100% (3 9/39) of normal bloods were negative for CK-19, whereas only 87% (34/39) were negative with GCDFP. In 15 patients with metastatic disease including 3 without treatment and 12 on either tamoxifen or chemotherapy, CK-19 was positive in 67% (10/15) of patients and GCDFP yielded positives in 27% (4/15) of patients tested. Conclusions: The detection of CK-19 and GCDFP in bloods from patients with metastatic breast cancer may be beneficial in determining the course of therapy, as well as having potential prognostic and diagnostic applications. Although CK-19 appears to be the more sensitive and specific marker, further investigation with both targets is warranted.

Journal Article↗
PubMed1997

Mycobacterium tuberculosis DNA Not Detected by Polymerase Chain Reaction In Air Samples From Hospital Rooms of Tuberculosis Patients.

Background: As the incidence of tuberculosis (TB) increased in the United States, the risk of occupational and nosocomial TB also increased. Airborne Mycobacterium tuberculosis (MTB) is difficult to measure directly. Quantifying MTB DNA by polymerase chain reaction in air samples obtained from isolation rooms of patients with TB would provide a measure of the number of airborne organisms produced by a patient and the efficacy of ventilation, and might predict when an individual patient is no longer infectious. Methods and Results: The air was sampled through cellulose ester filters from the isolation room of a patient with newly diagnosed pulmonary TB, from a patient on therapy for 14 days, and from adjacent offices, and an attempt was made to detect MTB DNA; however, MTB DNA was detected only on positive control filters. Conclusions: Mycobacterium tuberculosis was not detected by polymerase chain reaction in air samples from the rooms of two patients with pulmonary TB. This may have been due to the large number of room air changes with resultant rapid clearance of airborne droplet nuclei or to the limited air volume sampled. A sensitive molecular assay of airborne MTB could be used to monitor the efficacy of infection control measures by sampling a sufficient volume of isolation room air and could aid in determining when an individual patient was no longer infectious.

Journal Article↗
PubMed1996

Detection of Clonal Rearrangement of the T-cell Receptor Gamma Gene by Polymerase Chain Reaction and Single-strand Conformation Polymorphism (PCR-SSCP).

Background: Diagnosis of T-lymphoid neoplasms frequently requires molecular studies of T-cell receptor (TCR) gene rearrangements. The Southern blot technique traditionally used for these analyses lacks the sensitivity and speed necessary for the routine clinical laboratory. The authors have developed a method using polymerase chain reaction (PCR) amplification with single-strand conformation polymorphism (SSCP) analysis that is rapid, sensitive, and semiautomated. Methods and Results: Polymerase chain reaction of the TCR gamma gene is done with consensus primers to the V and J regions. Amplicons thus include the N region, which serves as a marker of clonal T-cell population. Clonal populations having identical N-region sequences are identified by SSCP analysis, using a semiautomated electrophoresis system with silver staining for gel visualization. A series of 46 DNA samples from normal controls and various hematopoietic malignancies was comparatively analyzed by both Southern blot of the TCR beta locus and PCR-SSCP of the of the TCR gamma gene. The PCR-SSCP technique was rapid and reproducible, and detected clonal T-cell populations constituting 1% of the cell sample: The PCR-SSCP technique detected clones in eight cases that were negative by Southern blot. Conclusions: PCR-SSCP analysis of the TCR gamma gene is a rapid and sensitive method for the detection of clonal T-cell populations.

Journal Article↗
PubMed1996

Amplification of residual DNA sequences in sterile bronchoscopes leading to false-positive PCR results.

PCR has been used successfully for the direct detection of Mycobacterium tuberculosis in uncultured patient samples. Its potential is hindered by the risk of false-positive results as a result of either amplicon carryover of cross-contamination between patient samples. In the present study, we investigated whether residual amplifiable human or M. tuberculosis DNA could remain in sterile bronchoscopes and potentially be a cause of false-positive PCR results in subsequent patient samples. Sterilized bronchoscopes were flushed with sterile saline, and the collected eluate was submitted for PCR amplification of IS6110 sequences and exon 8 of the human p53 gene. Of a total of 55 washes of sterile bronchoscopes from two institutions, 2 (3.6%) contained amplifiable M. tuberculosis DNA and 11 (20%) contained residual human DNA. These findings indicate that residual DNA can remain in sterilized bronchoscopes and can be a source of false-positive PCR results.

Bronchoscopes↗
PubMed1996

Molecular detection of prostate epithelial cells from the surgical field and peripheral circulation during radical prostatectomy.

PURPOSE: Prostate cancer progression despite organ confined pathological assessment has been reported in a variable number of men after radical retropubic prostatectomy. To study this phenomenon, we used the prostate specific antigen (PSA) reverse transcriptase-polymerase chain reaction assay. MATERIALS AND METHODS: We prospectively assayed the peripheral venous blood before, during and after surgical manipulation as well as the intraoperative field blood for PSA reverse transcriptase-polymerase chain reaction-positive cells in 22 men undergoing radical retropubic prostatectomy. RESULTS: PSA reverse transcriptase-polymerase chain reaction-positive cells were identified in 20 of the 22 operative field samples (91%) and 4 of 16 (25%) had evidence of intraoperative hematogenous dissemination (p = 0.046). No significant association was identified among Gleason score, pathological stage and the PSA reverse transcriptase-polymerase chain reaction result. CONCLUSIONS: Our results suggest that tumor cell spillage and less frequently hematogenous dissemination may be associated with operative manipulation of the prostate during radical retropubic prostatectomy and may potentially represent mechanisms of failure after radical retropubic prostatectomy.

Adenocarcinoma↗
PubMed1993

Correlation of clinical responses with immunologic and morphologic characteristics in patients with cutaneous T-cell lymphoma treated with interferon alfa-2a.

BACKGROUND: Immunophenotyping may aid in distinguishing more aggressive forms of cutaneous T-cell lymphoma (CTCL), thereby improving classification and treatment. OBJECTIVE: Our purpose was to investigate the relations between clinical, histologic, and immunophenotypic profiles in determining variables with respect to outcome. METHODS: Thirty-seven cases of histologically proven CTCL were analyzed in relation to clinical responses to treatment with interferon alfa alone or in combination with PUVA. Clinical stage, immunophenotyping, and histologic features were noted. RESULTS: All patients with no response to therapy had deletion of T-cell CD7 antigen. In contrast, only 21% of patients with a complete response had CD7 deletion. Deletion of the CD5 antigen occurred in 50% of patients with no response and in no patients with complete response. Large cell histologic features were found in 16% of patients with a complete response, 42% with a partial response, and 83% with no response. The presence or absence of other T-cell antigens and the clinical stage of disease did not correlate with outcome. CONCLUSION: Immunophenotypic analysis may be of greatest value in identifying a subset of high-risk CTCL patients, including those previously classified as low risk on the basis of clinical stage.

Antigens, CD↗
PubMed1993

Phase I trial of the diphtheria toxin/interleukin-2 fusion protein DAB486IL-2: efficacy in mycosis fungoides and other non-Hodgkin's lymphomas.

The purpose of this study was to investigate the biologic activity of DAB486IL-2 when administered three times daily, in terms of toxicity, pharmacokinetics, and anti-tumor effects in patients with IL-2R expressing hematologic malignancies, especially mycosis fungoides. 20 patients were enrolled in this dose escalation phase I trial. Patient cohorts were treated at levels of 0.03 mg/kg, 0.05 mg/kg, 0.07 mg/kg and 0.09 mg/kg every 8 hours for a total of 12 doses, every 21 days as toxicity and response warranted. Eight patients experienced transient fevers associated with DAB486IL-2 administration. One patient experienced grade 3 hypotension, and a second developed fluid retention manifested as weight gain/pedal edema. Dose limiting toxicity consisted of one episode of transient grade 4 hepatic transaminase elevation, and 8 episodes of transient asymptomatic grade 3 hepatic transaminase elevation. At the maximum tolerated dose DAB486IL-2 exhibited biphasic clearance kinetics; transient receptor saturation may be one mechanism for this observation. Initial serum concentration and apparent steady state level (plateau) directly correlated with the dose administered, but no difference in area under the concentration curve with greater dose was observed. Biologic activity was noted in patients with mycosis fungoides with skin lesion clearing and relief of pruritus. One patient with mycosis fungoides, and one patient with a relapsed intermediate grade non-Hodgkin's lymphoma achieved partial responses. The novel mechanism of action, toxicity profile, and evidence of biologic activity in refractory cancer patients, support development of more active constructs of this agent; such trials are underway.

Adult↗
PubMed1993

Systemic T-cell lymphoma presenting with isolated neurological dysfunction and intraparenchymal brain lesions. Case report.

Secondary non-Hodgkin's lymphoma of the central nervous system is typically a late manifestation of systemic T-cell lymphoma, with a 2-month median survival time after the development of neurological disease. Of the reported patients with this late complication, only 1% manifest spread of the disease to the brain parenchyma. The authors report a patient with an unusual initial neurological presentation of systemic T-cell lymphoproliferative disorder and associated space-occupying lesions of the brain parenchyma. The diagnosis was supported by extensive molecular, immunological, and histopathological analysis. Neurological symptoms appeared early in the course of systemic disease and were characterized by spontaneous exacerbations and remissions. The patient has survived for more than 5 years since the onset of his neurological symptoms. Histopathological characterization including immunoperoxidase staining for T-cell markers, DNA content, and cell-cycle analysis of brain tissue obtained at stereotactic biopsy were compared to those of atypical lymphoid cells of peripheral blood, bone marrow, and liver. The neurological manifestations and possible etiologies of T-cell lymphoma are discussed.

Adult↗
PubMed1992

A single cycle of 2-chlorodeoxyadenosine results in complete remission in the majority of patients with hairy cell leukemia.

Twenty-six patients with hairy cell leukemia (HCL) were treated with 2-chlorodeoxyadenosine (2-CdA), a purine analogue resistant to adenosine deaminase, at 0.1 mg/kg/d for 7 days by continuous intravenous infusion. Fifteen patients were previously untreated, while 11 patients had received prior treatment with splenectomy alone (three patients), interferon alpha alone (four), splenectomy, then interferon alpha (two), or splenectomy, interferon alpha, then 2-deoxycoformycin (2-DCF) (two). Sixteen (80%) of 20 patients evaluable at 3 months achieved complete remission (CR), and four (20%) achieved partial remission (PR) following a single cycle of therapy. All four patients in PR had complete recovery of their peripheral blood counts (except one patient whose platelet count remained 84,000/microL), but had residual HCL in the bone marrow (three patients) or residual splenomegaly (one). Patients with bulky adenopathy, massive splenomegaly, and severe pancytopenia responded as well as those with only modest marrow involvement. The three patients with residual marrow disease received a second cycle of 2-CdA, and two have attained CR. Therefore, 18 of 20 (90%) achieved CR with either one or two cycles of therapy. No patient achieving CR has relapsed at a median follow-up of 12 (+/- 2.1) months. Toxicities included myelosuppression and culture-negative fever. A community-acquired pneumonia was the only infectious complication. Since a single cycle of 2-CdA induces sustained CR in the vast majority of patients with minimal toxicity, this agent is emerging as the treatment of choice for all patients with HCL.

Bone Marrow↗
PubMed1990

Interferon alfa-2a combined with phototherapy in the treatment of cutaneous T-cell lymphoma.

Escalating doses of recombinant interferon alfa-2a (Roferon-A), administered intramuscularly three times weekly, combined with psoralen plus ultraviolet light irradiation (PUVA), were tested in a phase I trial for the therapy of patients with cutaneous T-cell lymphomas (CTCL). Interferon doses were escalated in groups of three patients from 6 million to 30 million IUs three times weekly. Disease stages ranged from IB to IVB. Eighty percent of the patients entered in this trial had failed at least one prior therapy. Complete remissions were obtained in 12 of 15 patients, and partial responses were seen in two of 15 patients, for an overall response rate of 93%. The median duration of response exceeded 13 months (range, 3-15+). All patients who responded have been maintained on therapy. The dose-limiting toxic effects were constitutional symptoms such as fevers and malaise (93.3%), leukopenias (40.0%), mental status changes consisting of depression and confusion (33.3%), and photosensitivity (26.6%). These side effects were reversible with a decrement in dose or discontinuation of the interferon. No patient tolerated 30 million IU of the interferon for extended periods; the maximally tolerated dose was 18 million IU. Interferon plus PUVA appears to be a highly effective regimen for the treatment of patients with CTCL. Phase II studies investigating this combination, using 18 million IU of interferon alfa-2a three times weekly, should be undertaken to expand these findings, and to attempt to reduce the toxic effects associated with this therapy.

Combined Modality Therapy↗
PubMed1990

Photochemotherapy alone or combined with interferon alpha-2a in the treatment of cutaneous T-cell lymphoma.

Eighty-two patients with either mycosis fungoides (MF) or parapsoriasis en plaques were treated with psoralens ultraviolet A light (PUVA). Clinical and histologic parameters were followed for a period from 6 months to 10 years. Complete clinical clearing of lesions was observed in 51 patients (62%) and most of them were in limited-plaque MF group or parapsoriasis en plaque. The mean total dose of PUVA for complete clearing was less for early MF. Thirty-one patients (38%) relapsed and responded to additional PUVA. Patients in early stages of the disease remained clear for up to 68 months after the first course of PUVA. Post-treatment skin biopsies with early MF showed histologic clearing. A new combination therapy for MF is presented in 15 patients. Recombinant interferon alpha-2a (Roferon-A), administered intramuscularly combined with PUVA were tested in a phase I trial. Interferon doses were from 6-30 million units three times weekly. Disease stages ranged from I-B to IV-B. Complete responses were obtained in 12 of 15 patients, and partial responses seen in 2 of 15 patients, for an overall response rate of 93%. The median duration of response exceeded 23 months (range, 3 to 25 months). All responding patients have been maintained on therapy. The dose-limiting toxicities were constitutional symptoms such as fevers and malaise (93.3%), leukopenias (40.0%), mental status changes consisting of depression and confusion (33.3%), and photosensitivity (26.6%). Interferon plus PUVA appear to be highly effective regimens for the treatment of patients with cutaneous T-cell lymphomas.

Adult↗