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Biomedical subjects

P Chu

Publications and source records attributed to P Chu.

At least 37 records · Page 2Linked to original sources

Acute correction of metabolic acidosis increases serum procollagen type I carboxyterminal propeptide in patients with chronic renal failure.

BACKGROUND AND PURPOSE: Previous in vitro study has shown that an acidic medium increases osteoclastic and inhibits osteoblastic activity. The present study sought to determine the role of alkali therapy in osteoblast function in patients with chronic renal failure by assessing the serum concentration of procollagen type I carboxyterminal propeptide (PICP), a marker of bone formation, before and after bicarbonate infusion. PATIENTS AND METHODS: Eighteen patients with chronic renal failure (creatinine clearance 12 +/- 6.6 mL/min) associated with mild to moderate metabolic acidosis were enrolled in this study. None had undergone dialysis. Metabolic acidosis was corrected by continuous bicarbonate infusion while plasma ionized calcium was clamped at the preinfusion level by calcium gluconate infusion throughout the procedure. RESULTS: After bicarbonate infusion, there were significant increases in plasma pH (7.31 +/- 0.04 to 7.40 +/- 0.03, p < 0.001), bicarbonate concentration (18.46 +/- 2.49 to 23.66 +/- 2.72, p < 0.001), serum total calcium concentration (2.01 +/- 0.24 to 2.12 +/- 0.24 mmol/L, p < 0.001), and PICP concentration (137.3 +/- 56.25 to 159.6 +/- 57.30 micrograms/L, p < 0.05), whereas serum parathyroid hormone concentrations assessed by radioimmunoassay decreased significantly (153.7 +/- 88.6 to 111.5 +/- 78.7, p < 0.001). Serum ionized calcium concentrations showed no significant difference before and after bicarbonate infusion. CONCLUSION: These results suggest that acute correction of metabolic acidosis improves osteoblast function and appear to underline the importance of maintaining normal acid-base homeostasis in chronic renal failure.

Acidosis↗

CD40 activation does not protect chronic lymphocytic leukemia B cells from apoptosis induced by cytotoxic T lymphocytes.

Cytotoxic T lymphocytes (CTLs) can kill target cells by the granule/exocytosis pathway or the Fas-mediated apoptosis pathway. The sensitivity of chronic lymphocytic leukemia (CLL) B cells to CTL-mediated apoptosis before and after CD40 activation was examined. Resting or CD40-activated CLL cells were found to be equally sensitive to class I-restricted CTL-mediated killing. Despite expressing CD95, the CD40-activated CLL target cells were found to be resistant to apoptosis induced by CH11, an IgM CD95 monoclonal antibody (mAb). Consistent with this, inhibitors of caspases, which are involved in the Fas-induced apoptotic pathway (eg, N-carbobenzoxy-Val-Ala-Asp fluoromethyl ketone [z-VAD-fmk]), were unable to block destruction of CLL target cells by CTL. In addition, preincubation of the effector T cells with the anti-Fas ligand mAb NOK-2 failed to inhibit their subsequent ability to kill CLL target cells. On the other hand, CTL activity was blocked by inhibitors of the granule exocytosis pathway such as ethylene-glyco-tetra-acetic acid or concanamycin A. These results indicate that CD40 activation does not impair the sensitivity of CLL cells to Fas-independent CTL-mediated apoptosis. (Blood. 2000;95:3853-3858)

Anti-Bacterial Agents↗

Multiple infundibulocystic basal cell carcinomas in association with human immunodeficiency virus.

Infundibulocystic basal cell carcinoma (IBCC) is a relatively recently described variant of basal cell carcinoma that is controversial and not universally accepted. Excluding cases of nevoid basal cell carcinoma syndrome, IBCC usually presents as a small, solitary, superficial lesion on the face of older persons. There have been previous reports of diffusely distributed, multiple similar lesions, but there is disagreement about the diagnosis in these cases. We present a case of a 43-year-old man with multiple papular lesions which we believe represent IBCC in the setting of infection with the human immunodeficiency virus (HIV).

Adult↗

Cytokeratin 7 and cytokeratin 20 expression in epithelial neoplasms: a survey of 435 cases.

Cytokeratin 7 (CK 7) and cytokeratin 20 (CK 20) are low molecular weight cytokeratins. Their anatomic distribution is generally restricted to epithelia and their neoplasms. We surveyed 435 epithelial neoplasms from various organ systems by immunohistochemistry using CK 7 and CK 20 monoclonal antibodies. Expression of CK 7 was seen in the majority of cases of carcinoma, with the exception of those carcinomas arising from the colon, prostate, kidney, and thymus; carcinoid tumors of the lung and gastrointestinal tract origin; and Merkel cell tumor of the skin. The majority of cases of squamous cell carcinoma of various origins were negative for CK 7, except cervical squamous cell carcinoma, in which 87% of cases were positive. Approximately two thirds of cases of malignant mesothelioma were CK 7-positive. CK 20 positivity was seen in virtually all cases of colorectal carcinomas and Merkel cell tumors. CK 20-positive staining was also observed in cases of pancreatic carcinomas (62%), gastric carcinoma (50%), cholangiocarcinomas (43%), and transitional cell carcinomas (29%). The expression of CK 20 was virtually absent in carcinomas from other organ systems and in malignant mesothelioma. CK 7- and CK 20-negative epithelial neoplasms included adrenal cortical carcinoma, germ cell tumor, prostate carcinoma, renal cell carcinoma, and hepatocellular carcinoma.

Biomarkers, Tumor↗

Pedunculated malignant melanoma.

BACKGROUND: The pedunculated melanoma is an unusual variant of nodular melanoma that presents a challenge in staging and management. OBJECTIVE: We discuss the clinical and histopathologic characteristics of a case of pedunculated melanoma and present a brief review of the literature. METHODS: Routine stain with hematoxylin and eosin was performed on tissue specimens. RESULTS: The pedunculated melanoma was excised. Sentinel lymph node dissection was performed and was negative for the presence of melanoma. CONCLUSIONS: Pedunculated melanoma is a rare type of melanoma. Conventional staging methods for melanoma may not be reliable in this type of tumor. Complete workup, possibly including sentinel lymph node dissection, should be performed in all patients with pedunculated melanomas.

Adult↗

Post-transfusion HIV infection despite donor screening: a report of three cases.

In August 1996, a blood donation was collected which subsequently infected three patients post-transfusion with HIV 1. The donation itself was originally screened as negative for anti-HIV 1/2 using a sensitive EIA method, but subsequently was shown to contain p24 Ag and HIV RNA by an amplification technique. The proposed introduction of nucleic acid testing of all blood donations in the UK for hepatitis C, hepatitis B and HIV may further reduce the remote risk of further episodes of post-transfusion infection. The infection in the index recipient was detected on routine pre-transplant virological screening but proved difficult to confirm, at a time when she had recently received myeloablative treatment for a haematological malignancy which impaired the immune response. There is a need for continued vigilance in such patients to exclude post-transfusion infection, at a time when natural immunological responses have been impaired by their disease or treatment.

Aged↗

Paraffin-section detection of CD10 in 505 nonhematopoietic neoplasms. Frequent expression in renal cell carcinoma and endometrial stromal sarcoma.

We tested 505 cases of nonhematopoietic neoplasms by immunohistochemistry using a newly characterized monoclonal antibody (clone 56C6) against the CD10 antigen. CD10 was expressed widely in neoplasms of the genitourinary tract, including 41 (89%) of 46 cases of renal cell carcinoma, 13 (54%) of 24 cases of transitional cell carcinoma, and 11 (61%) of 18 cases of prostatic adenocarcinoma. In addition, 5 (100%) of 5 endometrial stromal sarcomas, 3 (60%) of 5 rhabdomyosarcomas, 7 (50%) of 14 pancreatic adenocarcinomas, 5 (45%) of 11 cases of schwannoma, and 12 (40%) of 30 cases of malignant melanoma also were positive for CD10. Similar to normal tissue, CD10 positivity was restricted to the apical surface of malignant glandular cells of well-differentiated colonic, pancreatic, and prostatic adenocarcinoma, whereas in poorly differentiated adenocarcinoma and other tumors, such as melanoma, transitional cell carcinoma, renal cell carcinoma, and endometrial stromal sarcoma, the CD10 positivity showed diffuse cytoplasmic or membranous/Golgi patterns. The monoclonal antibody clone 56C6 is a reliable marker for CD10 in paraffin immunohistochemistry after heat-induced epitope retrieval. CD10 expression in renal cell carcinoma and endometrial stromal sarcoma may be a useful marker in the differential diagnoses of these tumors because both tumors otherwise lack specific markers.

Antigens, Neoplasm↗

A case of meningeal myeloma presenting as obstructive hydrocephalus--a therapeutic challenge.

Meningeal involvement in myeloma is a rare though recognised complication, and previous treatment strategies have included radiotherapy, intra-thecal and systemic chemotherapy to which there is almost universally a poor response. We report a case of a 60-year-old lady in serological remission with IgG lambda myeloma, presenting with obstructive hydrocephalus due to meningeal infiltration treated with neurosurgical decompression. Such presentation and the treatment strategies are previously unreported, though in view of the ultimate resistance to treatment the prognosis remains poor.

Combined Modality Therapy↗

Immunogenetic therapy for B-cell malignancies.

Neoplastic B cells are stealthlike in their ability to evade immune detection, even by allogeneic T cells of normal healthy donors. This stealthlike phenotype can be reversed by activating neoplastic B cells through ligation of CD40, a cell surface molecule that can interact with a ligand expressed on activated T cells. The gene encoding this ligand, CD154, can be transferred into neoplastic B cells ex vivo through infection with a modified adenovirus vector called Ad-CD154. This results in a dramatic change in the phenotype and function of the neoplastic B cells. Infected malignant B cells can stimulate T cells reactive with potential tumor antigens and induce autologous cytotoxic T cells capable of destroying the neoplastic B cells in vitro. This formed the basis for an immune gene therapy protocol in which patients were infused with Ad-CD154-transduced leukemic B cells. Treatment was well tolerated, without apparent long-term toxicity, and without a maximum tolerated dose. Biologic and clinical responses were observed, including significant reductions in leukemia cell counts and lymph node sizes after a single one-time infusion. Furthermore, preliminary data suggest that this approach can enhance antibody-dependent cellular cytotoxicity and thereby augment the activity of antitumor monoclonal antibody therapy. Development of such strategies may allow for effective immunogenetic therapy for B-cell malignancies.

Antibodies, Monoclonal↗

Granuloma annulare and human immunodeficiency virus infection.

OBJECTIVES: To characterize human immunodeficiency virus (HIV)-associated granuloma annulare (GA) by clinical, microscopic, and molecular methods and to investigate the role of Epstein-Barr virus infection in the pathogenesis of GA. DESIGN: Patients were evaluated clinically, and biopsy specimens of lesional skin were examined by light microscopy. Polymerase chain reaction and in situ hybridization for Epstein-Barr virus were performed on 4 and 12 biopsy specimens, respectively. SETTING: Academic referral center. PATIENTS: Thirty-four consecutive HIV-positive patients who have a clinical and histological diagnosis of GA. OUTCOME MEASURES: Clinical distribution of lesions, light-microscopic features, and the presence of Epstein-Barr virus DNA and RNA in biopsy specimens. RESULTS: Granuloma annulare was generalized in 20 patients and localized in 14. Twenty patients (59%) presented with acquired immunodeficiency syndrome. Unusual features were the presence of oral lesions in 1 patient, perforating lesions in 2 patients, and the coexistence of GA and Kaposi sarcoma in 1 biopsy specimen. Microscopic examination of 34 biopsy specimens showed a granulomatous pattern that was interstitial in 8, palisaded in 18, perforating in 2, and mixed interstitial and palisaded in 6. Special staining of all specimens was negative for organisms. Epstein-Barr virus infection was not detected by either polymerase chain reaction or in situ hybridization. CONCLUSIONS: Generalized GA is the most common clinical pattern in HIV infection. Granuloma annulare associated with HIV can present at all stages of HIV infection, but it is slightly more common in patients with acquired immunodeficiency syndrome. Epstein-Barr virus is an unlikely causative agent of HIV-associated GA. Granuloma annulare may be a manifestation of increasing immune dysregulation.

Acquired Immunodeficiency Syndrome↗

Radiographic changes after colonoscopic decompression for acute pseudo-obstruction.

PURPOSE: Colonoscopy has been the principal tool for decompression in acute colonic pseudo-obstruction, known as Ogilvie's syndrome. The objectives of this study were to determine the immediate effect of colonoscopy on the cecal diameter (measured on supine radiographs) and to delineate possible correlations in the diameters of dilated segments of the colon. METHODS: The charts and radiographs of 24 patients who had colonoscopic decompression for acute colonic pseudo-obstruction between 1992 and 1997 at the San Diego Veterans Affairs Medical Center and the University of California, San Diego Hospitals were reviewed. We measured cecal, transverse, descending, and sigmoid colon diameters on serial radiographs up to the point of clinical resolution. RESULTS: Mean +/- standard deviation cecal diameter change (between initial and post-decompression films) was -2+/-3.4 cm at four hours and -2.2+/-3.3 cm one day after decompression. On the daily radiographs between colonoscopic decompression and clinical resolution, there was a close correlation between the diameter of the cecum and that of the transverse colon (P<0.05). There was no correlation between the cecal diameter and that of the descending or sigmoid colon. CONCLUSIONS: Colonoscopic decompression only causes a small decrease in cecal size in the patient with acute colonic pseudo-obstruction. Dilation patterns of the cecum and transverse colon are significantly correlated in acute colonic pseudo-obstruction. This correlation provides additional support to the contention that the same pathophysiology affects these two segments of the colon.

Acute Disease↗

Functional dissociation of mu opioid receptor signaling and endocytosis: implications for the biology of opiate tolerance and addiction.

Opiate analgesia, tolerance, and addiction are mediated by drug-induced activation of the mu opioid receptor. A fundamental question in addiction biology is why exogenous opiate drugs have a high liability for inducing tolerance and addiction while native ligands do not. Studies indicate that highly addictive opiate drugs such as morphine are deficient in their ability to induce the desensitization and endocytosis of receptors. Here, we demonstrate that this regulatory mechanism reveals an independent functional property of opiate drugs that can be distinguished from previously established agonist properties. Moreover, this property correlates with agonist propensity to promote physiological tolerance, suggesting a fundamental revision of our understanding of the role of receptor endocytosis in the biology of opiate drug action and addiction.

Arrestin↗

Pili bigeminy induced by low fluence therapy with hair removal alexandrite and ruby lasers.

BACKGROUND: Lasers are being widely used for the hair removal. Several complications including hyperpigmentation, erythma, hypopigmentation, and burns have been reported. OBJECTIVE: To study laser hair removal complications. METHODS: Pubic hairs were treated with alexandrite and ruby lasers. RESULTS: Pili Bigeminy can be induced by low fluence therapy with hair removal Alexandrite and Ruby lasers as a complication. CONCLUSION: To our knowledge, this is the first report of pili bigminy as a complication of laser-assisted hair removal.

Adult↗

Traumatic abdominal wall hernia caused by persistent cough.

We report a rare case of traumatic abdominal wall hernia caused by persistent and severe cough. We believe this is the first reported case of such an entity. We present computed tomography findings and a pertinent review of the literature.

Aged↗

Severe hypercalcaemia in B-cell lymphoma: combined effects of PTH-rP, IL-6 and TNF.

Hypercalcaemia as the only manifestation of B-cell lymphoma is seen very rarely. Its pathophysiology is heterogenous and not well understood. We report a 73-year-old man who presented with severe hypercalcaemia before any signs of malignancy became evident. He was diagnosed with a B-cell lymphoma on bone marrow trephine biopsy. The hypercalcaemia was associated with high plasma concentrations of parathyroid-hormone-related protein, interleukin-6 and tumour necrosis factor. Our patient had markedly increased osteoclast and osteoblast activity as a result of synergistic effects between these factors, with consequent severe hypercalcaemia. This is the first reported example of such combined effects of these factors in humans.

Aged↗