Granulomatous Pneumocystis carinii pneumonia in patients with low-grade lymphoid malignancies: a diagnostic dilemma.
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Aged↗
Biomedical subjects
J C Byrd
Publications and source records attributed to J C Byrd.
Coxsackievirus-associated pancreatitis mimicking metastatic carcinoma.
The origin of idiopathic acute pancreatitis has not been well defined. Several enteroviruses, including coxsackievirus, have been implicated. We report the case of a 21-year-old woman with severe, acute pancreatitis with no classic risk factors. Initial evaluation failed to show choledocholithiasis. Her condition improved with conservative treatment, but symptoms recurred after resumption of oral intake. Computed tomography (CT) of the abdomen revealed an atypical pseudocyst and omental nodules suggestive of a metastatic malignancy. An acute coxsackievirus B5 titer delayed CT-guided omental biopsy. The patient showed improvement, but progression of the omental nodules prompted open laparotomy. No malignant or inflammatory process was identified. This is the first reported case of presumed viral pancreatitis causing reactive omental nodules. This case shows a benign process mimicking malignancy, requiring an extensive, potentially dangerous workup. It also emphasizes the need to consider viral causes for unusual presentations of common problems.
Acute Disease↗
Hearing loss in former prisoners of war of the Japanese.
OBJECTIVE: To describe the prevalence, degree, and types of hearing loss present in a group of older American veterans who had been prisoners of war of the Japanese. DESIGN: A descriptive study. SETTING: A Veterans Affairs university hospital. PARTICIPANTS: Seventy-five male veterans, mean age 68 (+/- 3.6) years. INTERVENTIONS: Hearing aids were prescribed for eight veterans. MEASUREMENTS: Subjects were examined, and pure tone air and bone conduction, speech reception threshold, and speech discrimination were determined. Results were compared with age- and sex-matched controls from the largest recent American population study of hearing loss. RESULTS: 95% of subjects had been imprisoned longer than 33 months. Starvation conditions (100%), head trauma (85%), and trauma-related loss of consciousness (23%) were commonly reported. A total of 73% complained of hearing loss, and 29% (22/75) dated its onset to captivity. Most of those with the worst losses in hearing and speech discrimination were found in this subgroup. When the entire group was compared with published age- and sex-matched controls from the Framingham Study, no significant differences were found. CONCLUSIONS: We advocate screening examinations and long-term follow-up of populations with similar histories of starvation, head trauma, and torture.
Aged↗
Extramedullary myeloid cell tumors in myelodysplastic-syndromes: not a true indication of impending acute myeloid leukemia.
The purpose of this report is to record a patient with myelodysplastic syndrome (MDS) associated acute myelogenous leukemia (AML) and leukemia cutis who had blast expression of the neural cell adhesion molecule (NCAM) and to review the world literature on prognostic implications of extramedullary myeloid cell tumors (granulocytic sarcoma, myeloblastoma, chloroma and leukemia cutis) in MDS and MDS associated AML. Case report and world literature from January 1965-January 1994 for all cases of MDS-associated extramedullary myeloid cell tumors (EMT) is reviewed, and the first patient with EMT, MDS associated AML and blast expression of NCAM is described. There have been 46 cases of MDS associated EMT previously reported. 32 cases occurred in the absence of AML. AML developed in 47% of these patients at a mean of 38 weeks from initial EMT. Of the patients not developing AML, median survival from initial EMT was 11 weeks. Nine patients received chemotherapy at the time of EMT and had a median survival of 36 weeks. The median survival for patients receiving conservative therapy for EMT was 48 weeks. Patients (n = 15) with EMT and MDS associated AML had a poor outcome regardless of therapy with a median survival of 11 weeks. Unlike other forms of isolated EMT, MDS associated EMT is not always a forerunner of AML. Premature induction therapy for MDS associated EMT does not appear to prolong survival. EMT in the setting of MDS associated AML is associated with a poor prognosis despite aggressive chemotherapy. Blast expression of NCAM may prove to be a risk factor for EMT in MDS associated AML.
Adult↗
Opportunistic pulmonary infections with fludarabine in previously treated patients with low-grade lymphoid malignancies: a role for Pneumocystis carinii pneumonia prophylaxis.
The high incidence of opportunistic pulmonary infections in fludarabine-treated patients at Walter Reed Army Medical Center (WRAMC) and in the literature are described. A CancerLit search of fludarabine from June 1983-April 1994 with subsequent cross referencing and a retrospective review of all patients receiving fludarabine at WRAMC was performed. A total of 2,269 patients with low-grade lymphoid malignancies who received 7,547 + cycles of fludarabine were identified from the literature. Seventy-three (3.2%) of these patients developed opportunistic infections. Seventy-one (97%) of these infections occurred in patients who were pretreated with alkylator regimens or corticosteroids. Forty-five (2%) of these were of respiratory origin and associated with a 56% mortality rate. In contrast, 6 of the 21 patients (29%) treated with fludarabine at WRAMC developed opportunistic pulmonary infections which included three Pneumocystis carinii (PCP), one PCP/disseminated Candidiasis, one Mycobacterium avium intracellulare, and one Aspergillus niger pneumonia. These infections developed during and after treatment with fludarabine in alkylator-resistant patients who had received corticosteroids before (n = 6), during (n = 1), or after (n = 4) fludarabine therapy. Lack of PCP prophylaxis was the only significant (P = .018) variable that differentiated patients who developed opportunistic pulmonary infections. Corticosteroid treatment before, during, or after fludarabine treatment in patients with alkylator-resistant, low-grade lymphoid malignancies who have not received PCP prophylaxis is associated with an increased risk of opportunistic pulmonary infections. Aggressive work-up of pulmonary syndromes and PCP prophylaxis in these patients should be considered during and after treatment with fludarabine.
Antineoplastic Agents↗
Successful treatment of invasive aspergillosis complicating prolonged treatment-related neutropenia in acute myelogenous leukemia with amphotericin B lipid complex.
Herein we report the successful treatment of invasive aspergillosis with the liposomal amphotericin B (AMB) formulation, Amphotericin B Lipid Complex (ABLC). This investigational compound was employed in a 50-year-old patient with acute myelomonocytic leukemia complicated by prolonged, treatment-induced granulocytopenia and documented Aspergillus flavus sinusitis with signs of disseminated aspergillosis. The patient demonstrated radiographic signs of pulmonary aspergillosis and biochemical signs of hepatic involvement that were resistant to a 23 day course of conventional AMB (Fungizone) therapy. Following therapy with ABLC her fever abated, her chest X-ray findings improved, and her hepatic function tests improved with eventual resolution.
Adult↗
Inhibition of mucin synthesis by benzyl-alpha-GalNAc in KATO III gastric cancer and Caco-2 colon cancer cells.
Previous studies from our laboratory have shown that benzyl-alpha-GalNAc inhibits the glycosylation of mucin in colon cancer cells. In this study, we determined whether benzyl-alpha-GalNAc inhibits mucin glycosylation in KATO III gastric cancer cells. We also examined its effects on expression of mucin antigens, and compared the mucins made by KATO III with those of a colonic cancer cell line, Caco-2. Results of these experiments suggest that benzyl-alpha-GalNAc (2 mM) inhibited [3H]glucosamine labelling of mucins by 82% in KATO III and by 70% in Caco-2. For both cell lines, the mucin secreted in the presence of benzyl-alpha-GalNAc was less acidic. Both cell lines secreted benzyl-oligosaccharides, but those from KATO III (8-9 sugars) were larger than those from Caco-2 (6-7 sugars). In mucins purified from the medium of treated cells, peripheral carbohydrate antigens (sialyl Lex in KATO III and terminal fucose in Caco-2) were decreased (compared with control), while core carbohydrate antigens (T antigen in both cell lines and sialyl Tn in Caco-2) were increased. Western blots of cell homogenates showed differences between KATO III and Caco-2 in MUC 1 apomucin protein antigens, in sialyl Lex and in sialyl Tn antigens. We conclude that benzyl-alpha-GalNAc does inhibit the glycosylation of mucin in KATO III gastric cancer cells as in human colon cancer cells, but that alterations in mucin antigens occur in a cell line-specific manner.
Acetylgalactosamine↗
Fatal recurrence of autoimmune hemolytic anemia following pentostatin therapy in a patient with a history of fludarabine-associated hemolytic anemia.
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Anemia, Hemolytic↗
Extramedullary myeloid cell tumors in acute nonlymphocytic leukemia: a clinical review.
PURPOSE: To discuss the predisposing risk factor for all forms of extramedullary leukemia (EML) and to review the clinical features, prognostic significance, and treatment strategies for primary EML and leukemia cutis (LC)/granulocytic sarcomas (GS) in the setting of acute nonlymphocytic leukemia (ANLL). METHODS: A review of all reports published since 1965 related to all forms of extramedullary leukemia (LC, GS, gingival hypertrophy, and meningeal leukemia [ML]). RESULTS: Several factors, including chromosomal abnormalities [t(8;21), inv(16)], cell-surface markers (CD56, CD2, CD4, CD7), French-American-British (FAB) subtype (M2, M4, M5), blast differentiation and maturation, patient nutritional status, age, cellular immune dysfunction, high presenting leukocyte count, and decreased blast Auer rods, have been associated with a higher incidence of EML. Of 154 published cases of primary EML identified, 71 (46%) were initially misdiagnosed. The addition of immunohistochemical stains can assist in preventing such misdiagnoses and should be included in all atypical lymphoma/carcinoma cases. Only one of the patients (3%) with primary EML did not progress to ANLL in the absence of chemotherapy. In contrast, 66% of patients who received chemotherapy for the primary EML never developed ANLL. The prognostic significance of EML at presentation and medullary relapse of ANLL is uncertain. Isolated extramedullary recurrence of ANLL always heralds bone marrow relapse and should be treated with reinduction chemotherapy. Close clinical follow-up observation is necessary to insure resolution of EML. Radiation therapy is an effective local treatment for resistant or symptomatic EML. CONCLUSION: Many advances in diagnoses and treatment of EML have been made. Future investigations are needed to define the clinical significance of EML in patients with ANLL treated with modern chemotherapy or bone marrow transplantation.
Age Factors↗
Equilibration of hemoglobin concentration after transfusion in medical inpatients not actively bleeding.
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Adult↗
Recurrent granulocytic sarcoma. An unusual variation of acute myelogenous leukemia associated with 8;21 chromosomal translocation and blast expression of the neural cell adhesion molecule.
This study reports on a patient with acute myelogenous leukemia (AML) in remission who had a series of 11 granulocytic sarcomas (chloromas or myeloblastomas) appearing periodically over a 29-month interval in a variety of anatomic sites without evidence of bone marrow recurrence. This isolated extramedullary recurrence of AML is distinctly unusual with only 24 cases described previously. This patient had the greatest number and longest reported interval of recurrent granulocytic sarcomas (GS) before bone marrow relapse. Furthermore, he represents the first case of a patient with GS presenting with both an 8;21 chromosomal translocation and neural cell adhesion molecule (CD56) expression. The authors hypothesize that these two abnormalities identified previously as predisposing factors to GS may, in fact, be synergistic for this phenomenon. His case and the review of the literature demonstrate some of the important clinical and management features of a patient who develops GS while in complete marrow remission from previous AML. Although highly sensitive to radiation therapy, the onset of granulocytic sarcomas is almost always followed by bone marrow relapse and should be treated with aggressive reinduction chemotherapy and local irradiation. Such therapy is associated with the longest interval of disease-free survival.
Adult↗
Biosynthesis of two distinct types of mucin in HM3 human colon cancer cells.
Mucins, high-M(r) glycoproteins with a large amount of O-glycosidically linked carbohydrate, protect the colonic epithelial surface and are altered in ulcerative colitis and colon cancer. At least two mucin genes, MUC2 and MUC3, are expressed at high levels in the human intestine. As an experimental model for studying the biosynthesis of human intestinal mucins, we used HM3 colon cancer cells. When mature mucins labelled with [3H]glucosamine or [3H]threonine were analysed by gel filtration, it was found that secreted mucins (M(r) > 10(8) were larger than soluble cellular mucins (M(r) approx. 5 x 10(6)). Only secreted mucin was sensitive to reduction. Both MUC2 and MUC3 proteins, identified by labelling with [3H]threonine or [35S]cysteine and immunoprecipitation with antibodies to synthetic mucin peptides, were already of large size (M(r) > 180,000) by the earliest labelling time (5 min). The MUC3 precursor was completely degraded by trypsin, but the MUC2 precursor had a trypsin-resistant fragment of M(r) approx. 240,000 containing threonine and cysteine. The trypsin-resistant MUC2 fragment contained N-linked carbohydrate, as indicated by a decrease in size as a result of peptidyl N-glycosidase digestion or tunicamycin treatment of HM3 cells. These results show that HM3 colon cancer cells produce at least two distinct human intestinal mucins. They also indicate that the mechanisms of biosynthesis of intestinal mucins differ from those of other mucin-like glycoproteins that have been studied.
Amino Acid Sequence↗
Alterations of O-glycan biosynthesis in human colon cancer tissues.
Human colon cancer is associated with antigenic and structural changes in mucin-type carbohydrate chains (O-glycans). To elucidate the control of the biosynthesis of these O-glycans is colon cancer, we have studied glycosyltransferase and sulphotransferase activities involved in the assembly of elongated O-glycan structures. We analysed homogenates prepared from cancer tissue, adjacent normal and distal normal tissue from 20 patients. Several transferase activities showed pronounced changes in cancer tissue. The changes correlate with previous findings of a loss of O-glycans in cancer mucins, but did not always correlate with levels of Tn, sialyl-Tn, T and Lex antigens in homogenates or with the differentiation status and Duke's stages of the cancer tissue or the patient's blood type, sex and age. UDP-GlcNAc: Gal NAc-R beta 3-N-acetylglucosaminyltransferase (where GlcNAc is N-acetyl-D-glucosamine and GalNAc is N-acetyl-D-galactosamine) synthesizing O-glycan core 3, GlcNAc beta 1-3GalNAc-, CMP-sialic acid: GalNAc-peptide alpha 6-sialyltransferase synthesizing the sialyl-Tn antigen and sulphotransferase activities towards O-glycan core 1, Gal beta 1-3GalNAc-, were found to be decreased in cancer. UDP-GlcNAc: Gal beta 1-3GalNAc beta 6-N-acetylglucosaminyltransferase was also decreased in cancer concomitant with a loss of the ability to synthesize the I antigen and core 4, GlcNAc beta 1-6(GlcNAc beta 1-3) GalNAc-, CMP-sialic acid: Gal beta 1-3GalNAc-R alpha 3-sialyltransferase and GDP-fucose: Gal beta-R alpha 2-fucosyltransferase, synthesizing the blood group H determinant, were found to be 4- and 3- to 8-fold increased, respectively, in cancer compared to normal tissue. The data suggest that the biosynthesis of antigens and mucin-bound O-glycan structures in colon cancer is subject to complex control mechanisms.
Adult↗
Laryngeal carcinoma presenting as platypnea.
Platypnea, or dyspnea in the upright position relieved by recumbency, is most commonly associated with cardiac or pulmonary disease. We describe a patient who presented to the emergency department with platypnea due to a laryngeal carcinoma. A tumor of the upper airway should be considered in any patient presenting with platypnea.
Aged↗
Monoclonal antibody directed against colon cancer mucin has high specificity for malignancy.
Exposure of core carbohydrate structures such as NeuAc alpha2-6GalNAc-Ser/Thr (sialosyl-Tn) in mucus glycoproteins is often associated with malignant transformation in a number of different tissues. Reagents that specifically identify such structures would be useful in the diagnosis of cancer. Monoclonal antibody JT10e has been produced against mucins from xenografts of LS174T colon cancer cells but also reacts with mucins of pancreatic cancer xenografts. The following data suggest that JT10e reacts with sialosyl-Tn: (I) reactivity with bovine and ovine submaxillary mucins; (2) reactivity sensitive to neuraminidase or mild acid; (3) inhibition of reactivity by NeuAc and NeuAc alpha2-6 lactose; and (4) lack of reactivity with other glycoproteins with related carbohydrate structures but no sialosyl-Tn. JT10e is distinguishable from 2 other antibodies which react with sialosyl-Tn, B72.3 and TKH2 because JT10e: (a) did not react with normal gastric tissue while B72.3 and TKH2 did; (b) was only partially inhibited by TKH2 and not at all by B72.3; (c) did not react with Tn antigen while B72.3 did; and (d) bound more strongly to pancreatic cancer mucins than did either B72.3 or TKH2. JT10e reacted with a high percentage of malignant colonic, pancreatic, gastric and mammary tissues but not with the corresponding normal tissues. A high percentage of patients with colonic, pancreatic, gastric, mammary and lung cancers had elevated blood levels of JT10e antigen. A number of colonic cancer patients had elevated JT10e antigen levels without corresponding elevations in CA19-9 levels. These results suggest that JT10e antibody could be used in conjunction with other mucin markers to improve the identification of malignancy in colon, and to study the structure of oligosaccharides in cancer mucins.
Animals↗
Human gastric mucin. Identification of a unique species by expression cloning.
Gastric mucin is a large glycoprotein which is thought to play a major role in the protection of the gastrointestinal tract from acid, proteases, pathogenic microorganisms, and mechanical trauma. In this paper we describe the isolation by expression cloning and characterization of cDNAs which code for human gastric mucin. The cDNA sequence is characterized by a tandem repeat region whose individual repeat unit is 507 base pairs (169 amino acids) long. The translated sequence is rich in threonine, serine, and proline (31, 18, and 15%, respectively) and contains a relatively large amount of histidine (7.1%) and alanine (5.6%). RNA blot analysis shows a polydisperse pattern which is characteristic of mucins. Expression of this gene is highest in the stomach and gall bladder, with weaker expression in the terminal ileum and right colon. This expression pattern is different from other human mucins and indicates that this gene codes for a unique mucin. Fluorescence in situ hybridization techniques have localized this gene to chromosome 11p15.4-11p15.5. This is the third mucin to be localized to the 11p15 region and suggests a clustering of secretory mucin genes. We propose that this gene for human gastric mucin be called MUC6.
Amino Acid Sequence↗
Mucin synthesis and secretion in various human epithelial cancer cell lines that express the MUC-1 mucin gene.
Previous studies have suggested that mucin gene expression is tissue-specific; however, the relationship between unique mucin gene products and the biochemical properties of mucins is unknown. The purpose of this study was to determine the biochemical and molecular characteristics of mucin synthesized by adenocarcinoma cell lines derived from breast (ZR-75-1), stomach (MGC-803), pancreas (Capan-2), and lung (Chago K-1). Mucin was quantitated by [3H]glucosamine labeling and Sepharose CL-4B chromatography. The mucinous nature of the labeled high molecular weight glycoproteins (HMG) was verified by alkaline borohydride treatment, cesium chloride density gradient ultracentrifugation, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Specific mucin gene expression was determined using cDNA probes for 2 distinct intestinal mucins (MUC-2 and MUC-3) and one breast cancer mucin (MUC-1). Specific core mucin proteins were confirmed by immunoblots using antibodies that recognize MUC-1, MUC-2, and MUC-3 core peptides. These experiments demonstrate that all cell lines contained HMG in the medium, cytosol, and membrane fractions. The HMG was mucinous in breast, pancreatic, and lung cell lines. In contrast, most of the HMG secreted by the gastric cell line was proteoglycan-like, due to its susceptibility to hyaluronidase, heparinase, and chondroitinase avidin-biotin complex. Ion-exchange (DEAE-Sephacel) chromatography of [3H]glucosamine-labeled HMG demonstrated that the acidic or basic nature of the mucin was different in all cancer cell lines tested. Despite these differences, mRNA and immunoblot analysis suggest that all cell lines predominantly express MUC-1 apomucin, small amounts of MUC-2 apomucin, and no MUC-3. Immunoprecipitation of MUC-1-type mucin using the 139H2 monoclonal antibody demonstrated that different sizes of mucin peptides were present in all cell lines, corresponding to the known length polymorphism of this mucin. The amount and nature of carbohydrate epitopes were analyzed by immunoblots using anti-T (peanut lectin), anti-Tn (91S8 monoclonal antibody), and anti-sialosyl Tn (JT10e monoclonal antibody). T and Tn antigens were significantly higher in breast and pancreatic cells as compared with lung and gastric cell lines. These findings correlated with increased activities of polypeptidyl N-acetylgalactosaminyl transferase and beta-1,3-galactosyltransferase.(ABSTRACT TRUNCATED AT 400 WORDS)
Adenocarcinoma↗
The impact of educational loan burden on housestaff career decisions.
The past decade has seen declining interest in primary care medicine and a dramatic increase in the cost of a medical degree. Seventy-nine percent of housestaff in an internal medicine residency program responded to a survey to determine whether medical school loan burden was related to career choice in a primary care field or specialty area. Overall mean indebtedness was $45,185 (median $40,000). Thirty-eight percent of residents with debts < $40,000 chose a career in primary care, compared with 10% with debts > $40,000 (chi square = 9.44, p < 0.01). Fourteen percent of those with debts < 40,000 and 59% with debts > $40,000 stated that financial conditions had a moderate to marked impact on their career decision making. Excessive loan burden has a significant influence on residents' career decision making and a negative influence on choosing careers in primary care internal medicine.
Adult↗