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Biomedical subjects

S Lakhanpal

Publications and source records attributed to S Lakhanpal.

At least 19 recordsLinked to original sources
PubMed2001

Phase II study of 4-ipomeanol, a naturally occurring alkylating furan, in patients with advanced hepatocellular carcinoma.

BACKGROUND/PURPOSE: 4-Ipomeanol (IPO; NSC 394438), a naturally occurring furan isolated from common sweet potatoes (Ipomoea batatas) infected with the fungus Fusarium solani was the first agent to be developed by the National Cancer Institute based on a biochemical-biological rationale as an anticancer agent targeted specifically against lung cancer. Prior to clinical development, IPO was shown to induce pulmonary toxicity in the lungs of several mammalian species because the agent is metabolized to a highly reactive furan epoxide by specific cytochrome P450 monooxygenases found in pulmonary Clara cells and type II pneumocytes, which share biochemical features with bronchogenic carcinoma. However, instead of inducing the anticipated lung toxicity in patients with lung cancer in disease-directed phase I studies, hepatotoxicity was the principal toxic effect of IPO in humans. Based on the presumption that IPO may be preferentially activated by cytochrome P450 monooxygenases in liver cells and biochemically-related hepatic malignancies, a phase II study was conducted to determine the activity and evaluate the toxicity of IPO in patients with advanced hepatocellular carcinoma. PATIENTS AND METHODS: Nineteen patients with advanced measurable hepatocellular carcinoma were enrolled on the phase II trial. All patients had an Eastern Cooperative Oncology Group performance status of at least two, no evidence of pulmonary dysfunction, and had either no prior treatment or minimal prior therapy. Patients were treated with IPO at a dose of either 1032 mg/m2, which was the maximum tolerated and recommended phase II dose previously derived for patients with normal hepatic function (15 patients) or 826 mg/m2 if they had serum bilirubin concentrations in the range of 2.0 to 3.0 mg/dL (four patients). Treatment was repeated every three weeks. Objective tumor response, the primary endpoint of the study, was assessed after every two courses of treatment, and both pulmonary function and lung density were rigorously monitored using successive pulmonary function testing and computerized tomography. RESULTS: All nineteen patients were evaluable for both response and toxicity. No major objective responses were observed. One patient had a minor, brief reduction in lung metastases. Although marker lesions and overall disease remained stable for at least 12 and 24 months in three and two patients, respectively, the median time to progression was three months and the median survival was five months for all patients. The principal toxicity was reversible elevations in hepatic transaminases, which occasionally resulted in dose reduction. No clinically-significant pulmonary toxicity was noted. CONCLUSION: IPO at a dose of either 826 or 1032 mg/m2 administered every three weeks did not demonstrate a relevant degree of clinical activity against advanced hepatocellular carcinoma. Further evaluations of TO is not recommended for this disease.

Adult↗
PubMed1998

Post-kala-azar dermal leishmaniasis--an unusual presentation.

Post-kala-azar dermal leishmaniasis can present as hypopigmented macules, erythematous to skin-coloured papules, nodules and photosensitive butterfly erythema on the face. We present a patient with disseminated annular lesions of post-kala-azar dermal leishamaniasis. The patient was treated with daily intravenous injections of sodium antimony gluconate for 120 days at a dose of 20 mg/kg body weight with complete clearance of lesions.

Adult↗
PubMed1994

Diagnostic value of C-reactive protein in acute appendicitis.

Serum C-reactive protein was measured in 56 patients hospitalized with a suspected diagnosis of acute appendicitis. Based on these determinations, four groups of patients were defined: Group A = 26 patients with acute appendicitis who had a C-reactive protein level higher than 2.5 mg/dl. Group B = 4 patients with a C-reactive protein level lower than 2.5 mg/dl who, after surgery based on a presumed diagnosis of acute appendicitis, were found to have a normal appendix. Group C = 22 patients with nonspecific abdominal pain, 18 (72 percent) of whom had an elevated C-reactive protein level, although in only 4 (7.1 percent) were these levels higher than 2.5 percent mg/dl. Group D = 4 patients who had diseases other than acute appendicitis. It is concluded that an increase in C-reactive protein levels to more than 2.5 mg/dl is not a definite indicator of acute appendicitis. However, if the C-reactive protein level in blood drawn 12 hours after the onset of symptoms is less than 2.5 mg/dl, acute appendicitis can be excluded.

Acute Disease↗
PubMed1994

Angiocentric T cell lymphoma masquerading as cutaneous vasculitis.

Angiocentric T cell lymphoma may present with cutaneous inflammatory lesions masquerading as cutaneous vasculitis both clinically and pathologically. We describe a case of angiocentric T cell lymphoma. Although initial biopsies in this patient resembled polyarteritis nodosa, subsequent biopsies exhibited more characteristic changes and immunohistochemical stains confirmed the diagnosis of large cell angiocentric cutaneous T cell lymphoma. It is important to differentiate these diseases as treatment and prognostic implications are very different.

Adult↗
PubMed1991

Priapism as a manifestation of isolated genital vasculitis.

Vasculitis may affect virtually any organ system in the body. We describe a patient who presented with priapism due to isolated genital vasculitis. This responded promptly to oral corticosteroids. In patients presenting with priapism, a possible underlying vasculitis should be considered in the differential diagnosis; the treatment for this may be nonsurgical.

Adrenal Cortex Hormones↗
PubMed1989

Lymphoreticular disorders masquerading as rheumatic disease syndromes.

We describe four cases, each with a distinct rheumatologic presentation. Three had lymphoma, and the fourth, though initially suggestive of lymphoma, had a tuberculous infection. Clinicians should be alert for diseases masquerading as diverse clinical syndromes. It is important to establish rheumatic, lymphoproliferative, or infectious etiology because of major differences in therapeutic and prognostic implications.

Adult↗
PubMed1988

Eosinophilic fasciitis: clinical spectrum and therapeutic response in 52 cases.

The clinical course of 52 cases with eosinophilic fasciitis observed at the Mayo Clinic has been described. Cutaneous changes included pitting edema, peau d'orange, and induration, and may affect virtually any body surface area. In addition, localized morphea was present in 15 cases. Arthritis was observed in 21 patients; 29 patients had flexion contractures and 12 had carpal tunnel syndrome. Associated hematologic diseases were found in five patients; thrombocytopenia in two, myeloproliferative disorder in one, myelomonocytic leukemia in one, and chronic lymphocytic leukemia in one. Peripheral blood eosinophilia was noted in 33 of 52 patients, hypergammaglobulinemia was noted in 17 of 49, and elevated sedimentation rate was noted in 15 of 52. Nonspecific EMG changes were seen in 11 of 15 patients. None had clinical involvement of the kidneys, lungs, or heart. No significant association between any HLA-A, -B, or -DR and eosinophilic fasciitis was seen. Prednisone and hydroxychloroquine seemed equally beneficial in treatment; however, some cases showed spontaneous recovery, making evaluation of therapeutic efficacy difficult. Relapses occurred in some cases.

Adolescent↗
PubMed1988

Eosinophilia associated with perimyositis and pneumonitis.

We describe a patient who had severe myalgias, bronchial asthma, pulmonary infiltrates, and eosinophilia. The findings on physical examination and the erythrocyte sedimentation rate were normal; there was no elevation of the serum creatine kinase. Muscle biopsy demonstrated an inflammatory exudate that contained eosinophils, localized primarily to the perimysium. Pulmonary and muscle manifestations responded to corticosteroids. Systemic eosinophilic disease associated with perimyositis or myositis has not been reported previously. In addition, we review the spectrum of eosinophilic muscle diseases--eosinophilic perimyositis, eosinophilic polymyositis, and focal eosinophilic myositis.

Biopsy↗
PubMed1988

Evidence for linkage of IgA deficiency with the major histocompatibility complex.

A 57-year-old woman with IgA deficiency and Still's disease was the proband in a 20-member, three-generation kindred in which we studied the possible linkage of IgA deficiency with her HLA-A1-B8 haplotype. The presence of paternal A1-B8 haplotype complicated the analysis. Known maternal HLA-A1-B8 haplotype, present in three of the children of the proband, was associated with IgA deficiency, whereas all five family members with exclusively paternal A1-B8 had normal IgA. Of three third-generation family members whose A1-B8 haplotype was of indeterminate origin--that is, potentially either maternally or paternally derived--two had IgA deficiency and one did not.

Adult↗
PubMed1987

Interleukin 2 induces proliferation of normal "resting" human T cells in the absence of other known external stimulation.

Interleukin 2(IL-2) is known to stimulate the progression of activated T cells from G1 through the rest of the cell cycle. We have demonstrated that addition of purified recombinant human IL-2 (rIL-2) to fresh normal human peripheral blood mononuclear cells (PBM), which were IL-2 receptor (Tac) negative by FACS analysis, stimulated marked proliferation of the PBM. IL-2-induced proliferation was also observed with umbilical cord blood mononuclear cells. Monocyte depletion of PBM resulted in a marked reduction of rIL-2-induced proliferative response which could be restored by adding back autologous irradiated monocytes but not by interleukin 1. The T cells preincubated with rIL-2 showed a five to six times enhanced autologous mixed-lymphocyte reaction (AMLR) compared to controls. The rIL-2-induced proliferative response of PBM was inhibited in a concentration-dependent fashion by preincubation of PBM with an anti-HLA-DR framework monoclonal antibody. The proliferating cells were shown by two-color flow cytometric analysis to be primarily Leu-1+ and Leu-4+ T cells (both leu-3+ and Leu-2+ subsets); however, 6 to 19% of responding cells had surface markers for B cells or NK cells. The data demonstrate that rIL-2 can induce proliferation of "resting" human T cells. The phenomenon may be related to a monocyte-dependent AMLR which induces IL-2 receptors and IL-2 responsiveness in a subset of T cells.

Adult↗
PubMed1987

A flow cytofluorometric double staining technique for simultaneous determination of human mononuclear cell surface phenotype and cell cycle phase.

A double staining technique for the simultaneous determination by flow cytofluorometry of cell surface phenotype and cell cycle phase is described. Peripheral blood mononuclear cells were stained with fluorescein-conjugated monoclonal antibodies for cell surface phenotype, fixed serially with 2% paraformaldehyde and 71.25% ethanol, and stained with propidium iodide to label cellular DNA. The cells were then analyzed by flow cytofluorometry for both green and red fluorescence. A variety of cells, including T cells and their subsets, B cells, NK cells and monocyte/macrophages, can be identified by this technique with simultaneous determination of cell cycle phase.

Antibodies, Monoclonal↗
PubMed1987

Synovial fluid analysis for diagnosis of amyloid arthropathy.

To detect the presence of amyloid, we studied synovial fluid samples from 7 patients who had biopsy-proven amyloidosis and clinical arthropathy and from 98 patients who had other forms of arthritis. Centrifuged sediments from synovial fluids of all 7 patients with amyloid and clinical arthropathy were positive on staining with Congo red, whereas the 98 others were negative. Under polarized microscopy, the amyloid appeared as an amorphous material with strong Congo red uptake and typical apple-green birefringence. These findings indicate that analysis of synovial fluid sediments with Congo red may represent a simple, yet sensitive, test for the diagnosis of amyloid arthropathy.

Aged↗
PubMed1987

Interleukin 2 receptors and responsiveness to recombinant human interleukin 2 in patients with systemic lupus erythematosus.

Defects in interleukin 2 (IL2) responsiveness may contribute to immunologic abnormalities in systemic lupus erythematosus (SLE). We studied the acquisition of IL2 receptors and responsiveness to recombinant human IL2 (rIL2) in the peripheral blood mononuclear cells (PBM) of patients with SLE and matched control subjects. Peak rIL2-induced proliferation was significantly decreased (mean reduction of 58%) in 5 of the 10 patients with SLE. Five of six patients with SLE studied for phytohemagglutinin-induced IL2 receptors had acquisition of IL2 receptors comparable to that of the control subjects. Some patients with SLE have a defect in rIL2-induced proliferation of their "resting" PBM that seems unrelated to a concomitant defect in phytohemagglutinin-induced IL2 receptor acquisition. This finding suggests that the defect in rIL2-induced proliferation may be due to either an abnormality in postreceptor signaling or an impairment in induction of high-affinity IL2 receptors.

Adult↗