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Biomedical subjects

D M Cohen

Publications and source records attributed to D M Cohen.

At least 37 records · Page 2Linked to original sources
PubMed1999

Severe anaphylactic reaction after primary exposure to aprotinin.

Aprotinin is widely used to prevent bleeding and reduce blood transfusions after open heart surgical procedures. Because it is a foreign protein, aprotinin has allergenic potential. We report a case of near-fatal anaphylactic reaction to primary aprotinin exposure in a child successfully treated using cardiopulmonary bypass support. The possibility of an allergic reaction must be considered whenever this drug is used.

Anaphylaxis↗
PubMed1999

Pulmonary homograft repair of a mycotic aortic aneurysm in an infant.

Thoracic aortic aneurysms are rare in children and even more unusual in infants. The vast majority are mycotic. Frequently, those with mycotic thoracic aortic aneurysm do not survive and the diagnosis is made at autopsy. We present the case of an asymptomatic infant found to have a mycotic thoracic aortic aneurysm. The clinical course, diagnosis, and surgical repair of the aneurysm with pulmonary homograft are discussed.

Aneurysm, Infected↗
PubMed1999

Metastatic neuroblastoma with ganglioneuromatous differentiation and mandibular involvement.

Neuroblastic tumors comprise neuroblastoma (NB), ganglioneuroblastoma, and ganglioneuroma (GN). NBs have shown remarkable differentiation capabilities, which include spontaneous regression. In the last 3 decades, the prognosis for metastatic NB has improved significantly. The ability to distinguish prognostic subtypes based on clinical and biologic features allows for understanding of this disease process and development of management procedures. NBs are often asymptomatic and remain undetected until a large abdominal mass or metastasis is found. GN, the most differentiated variant, is a benign neoplasm with significant growth potential and ability to cause clinical complications. GN of the mandible has seldom been reported in the literature in English. We present a case of NB metastatic to the mandible exhibiting ganglioneuromatous differentiation. We discuss the current understanding of the biology, grading, classification, and prognostic implications of NB.

Abdominal Neoplasms↗
PubMed1999

Linear IgA disease histopathologically and clinically masquerading as lichen planus.

In each of 2 cases reported, the patient presented with features of erosive lichen planus or lichenoid drug eruptions and an incisional biopsy taken from the patient was diagnosed histologically as lichen planus. Subsequent recurrences or exacerbations were associated with vesiculobullous lesions. Simultaneous or subsequent direct immunofluorescence studies--from the same tissue sample in one case and from a similar site in the other case--demonstrated classic features of linear IgA disease. Both patients were originally treated for lichen planus with systemic and/or topical corticosteroids with limited success. One patient was treated with sulfapyridine with minimal improvement. Both patients were subsequently treated with dapsone and demonstrated significant clinical improvement. We propose that linear IgA disease may be more common than reported in the oral cavity, inasmuch as many cases of recalcitrant lichen planus, erosive lichen planus, and lichenoid drug eruptions, especially those with a vesiculobullous component, may in reality represent linear IgA disease. We recommend that direct immunofluorescence be done in any case in which bullous lichen planus is suspected.

Aged↗
PubMed1999

Signalling and gene regulation by urea and NaCl in the renal medulla.

1. Cells of the mammalian renal medulla are routinely subjected to an enormously elevated and labile ambient osmolality as a consequence of the renal concentrating mechanism. The present review focuses on the most recent advances in hyperosmotic solute-mediated signal transduction and regulation of gene transcription in cells of the kidney medulla. 2. On the basis of osmolality alone, NaCl and urea are the principal renal medullary solutes. 3. Urea, which is membrane permeant, activates transcription of immediate-early genes via an extracellular signal-regulated kinase (ERK)/Elk-1-dependent pathway. Urea also activates multiple effectors characteristic of a receptor tyrosine kinase-like signalling cascade. 4. In contrast, the functionally impermeant solute NaCl activates transcription of tonicity responsive genes (principally genes encoding proteins essential for osmolyte uptake or synthesis) via a unique consensus element contained within their 5' flanking sequences. 5. An activity exhibiting tonicity inducible sequence-specific interaction with this DNA element has been identified. 6. Hypertonicity, like thermal stress, activates transcription of genes encoding heat shock proteins. The relationship between signalling events leading to tonicity mediated and heat shock-mediated gene transcription remains to be established.

Animals↗
PubMed1999

Urea-associated oxidative stress and Gadd153/CHOP induction.

Urea treatment (100-300 mM) increased expression of the oxidative stress-responsive transcription factor, Gadd153/CHOP, at the mRNA and protein levels (at >/=4 h) in renal medullary mIMCD3 cells in culture, whereas other solutes did not. Expression of the related protein, CCAAT/enhancer-binding protein (C/EBP-beta), was not affected, nor was expression of the sensor of endoplasmic reticulum stress, grp78. Urea modestly increased Gadd153 transcription by reporter gene analysis but failed to influence Gadd153 mRNA stability. Importantly, upregulation of Gadd153 mRNA and protein expression by urea was antioxidant sensitive. Accordingly, urea treatment was associated with oxidative stress, as quantitated by intracellular reduced glutathione content in mIMCD3 cells. In addition, antioxidant treatment partially inhibited the ability of urea to activate transcription of an Egr-1 luciferase reporter gene. Therefore oxidative stress represents a novel solute-signaling pathway in the kidney medulla and, potentially, in other tissues.

Animals↗
PubMed1999

ERK activation by urea in the renal inner medullary mIMCD3 cell line.

Urea- and NaCl-inducible extracellular signal-regulated kinase (ERK) phosphorylation exhibited dissimilar kinetics. Among cell lines examined, the effect of urea was unique to mIMCD3 inner medullary collecting duct cells and MDCK cells. Urea-inducible ERK activation was approximately 10-fold less sensitive to the MEK inhibitor, PD-98059, than was that of NaCl. This difference did not appear to be accounted for by differential activation of MEK isoforms. Interestingly, the inhibitor of p38 activation, SB-203580, abrogated the effect of both urea and NaCl upon both ERK and MEK activation; however, the former was much less sensitive to the inhibitor. Consistent with this observation, NaCl was much more effective than urea at inducing p38 phosphorylation. The effect of hypertonic stress (e.g., sorbitol 100 mM) could be blocked by appropriate medium dilution such that isotonicity was maintained. In marked contrast, the effect of hyperosmotic urea could not be blocked in this fashion, implying the absence of dependence upon cell volume. Together, these data suggest that cells of the renal inner medulla are potentially uniquely responsive to urea and that urea and hypertonic stressors induce ERK activation through distinct mechanisms.

Animals↗
PubMed1999

Recalcitrant oral ulcers caused by calcium channel blockers: diagnosis and treatment considerations.

BACKGROUND: Oral ulcers often pose a dilemma in diagnosis and treatment. Patients seen routinely in dental practices are frequently receiving multiple medications. The authors discuss the pathogenesis, clinical appearance and treatment of drug-induced oral ulcers. CASE DESCRIPTIONS: Two patients with recalcitrant painful oral ulcers caused by calcium channel blockers are described. These ulcers failed to heal despite repeated interventions, including surgery, laser ablation, and topical and systemic steroid therapy. Results of the histopathologic examinations were nonspecific. The patients were in a great deal of pain because of the initial failure to recognize the cause of these ulcers. CLINICAL IMPLICATIONS: A careful medical history, including a detailed list of medications received, is critical in identifying drug-induced oral ulcerations, especially when the ulcer is resistant to treatment and of indeterminate cause. To date, calcium channel blockers have not been reported to cause oral ulcerations.

Aged↗
PubMed1999

Cerebral blood flow responses to somatosensory stimulation are unaffected by scopolamine in unanesthetized rat.

Studies with positron-emission tomography have indicated that muscarinic acetylcholine receptors may be involved in the mechanism of enhancement of cerebral blood flow (CBF) by neuronal functional activation. We examined the effects of muscarinic receptor blockade by scopolamine on the local CBF responses to vibrissal stimulation in the whisker-to-barrel cortex sensory pathway in unanesthetized rats. Local CBF was measured by the quantitative autoradiographic [(14)C]iodoantipyrine method. Scopolamine (0.4 or 0.8 mg/kg) was injected i.v. 30 min before measurement of local CBF; control rats received equivalent volumes of physiological saline. Vibrissae on the left side of the face were stroked continuously throughout the 1-min period of measurement of CBF. Local CBF was determined bilaterally in four structures of the pathway, i.e., spinal and principal sensory trigeminal nuclei, ventral posteromedial thalamic nucleus, and barrel field of the sensory cortex, as well as in four representative structures unrelated to the pathway. The higher dose of scopolamine raised baseline CBF in the two trigeminal nuclei, but neither dose diminished the percentage of increases in local CBF because of vibrissal stimulation in any of the stations of the pathway. These results do not support involvement of muscarinic receptors in the mechanism of enhancement of local CBF by functional neuronal activation, at least not in the whisker-barrel cortex sensory pathway in the unanesthetized rat.

Animals↗
PubMed1998

Multidimensional flow-cytometric analysis of dendritic cells in peripheral blood of normal donors and cancer patients.

We studied the potential of multidimensional flow cytometry to evaluate the frequency and maturation/activation status of dendritic cells in minimally manipulated peripheral blood mononuclear cell preparations (i.e., only separated on Ficoll-Hypaque) of normal donors and cancer patients. A rare subset of HLA-DR+ leukocytes (less than 1% mononuclear cells) was detected in blood of normal donors that displayed all the features of dendritic cells: these cells had high forward-light-scatter characteristics and coexpressed CD4, CD86 and CD54 surface antigens, but lacked the lineage-associated surface markers of T cells, B cells, monocytes, granulocytes or NK i.e. they were CD3-, CD19-, CD20-, CD14-, CD11b-, CD16-, CD56-). These physical and phenotypic properties were virtually identical to those of immunomagnetically sorted leukocytes characterized as dendritic-cells on the basis of morphology, phenotype and high stimulatory activity in allogeneic mixed-lymphocyte cultures. Using this flow-cytometric approach we observed that the frequency of dendritic cell-like cells in peripheral blood mononuclear cell specimens of cancer patients receiving chemotherapy alone or those recovering from stem cell transplantation was significantly lower than that of normal individuals (mean +/- SE: 0.36 +/- 0.05%, 0.14 +/- 0.06%, and 0.75 +/- 0.04% respectively). Multidimensional flow-cytometric analysis of dendritic cells might represent an important new tool for assessing immunocompetence, and for monitoring the effects of therapeutic regimens on the immune system.

Dendritic Cells↗
PubMed1998

Pediatric bronchioloalveolar carcinoma: a favorable pediatric malignancy?

Primary pulmonary tumors are infrequent in children. Bronchioloalveolar carcinoma has been documented rarely in the pediatric population. Before this report, there have been only three cases of bronchioloalveolar carcinoma in patients less than 16 years of age. Our two cases represent two of the youngest cases (ages 6 and 15 years) reported with bronchioloalveolar carcinoma. They illustrate many of the typical findings of this disease including clinical presentation, diagnostic difficulty, and better prognosis compared with other pulmonary malignancies. This neoplasm appears to have a favorable outcome in childhood.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed1998

Prilocaine-phenylephrine and bupivacaine-phenylephrine topical anesthetics compared with tetracaine-adrenaline-cocaine during repair of lacerations.

The effectiveness of two new topical anesthetics that do not contain cocaine (prilocaine-phenylephrine and bupivacaine-phenylephrine) was compared with that of tetracaine-adrenaline-cocaine (TAC) during laceration repair in children. This study was a prospective, randomized, double-blind trial conducted in the emergency department of a large children's hospital. Participants were 180 children 1 year of age or older with a laceration 5 cm or less in length that required suturing. Pain felt during suturing was scored by suture technicians, research assistants, parents, and patients 5 years of age and older using a visual analogue scale (VAS). There was no statistical difference demonstrated between the effectiveness of prilocaine-phenylephrine and that of TAC for any of the observer groups. A statistically significant difference was seen among anesthetics when comparing VAS scores of research assistants (P = .002), suture technicians (P = .006), and parents (P = .03), but not when comparing VAS ratings of patients (P = .07). Based on Tukey's post hoc test, these statistically significant differences were between TAC and bupivacaine-phenylephrine. When power analyses were performed using alpha = 0.05 and beta = 0.20, it was possible to detect a difference of 1.3 VAS units for each rater group. In conclusion, this study demonstrated the effectiveness and safety of prilocaine-phenylephrine and bupivacaine-phenylephrine. Prilocaine-phenylephrine statistically outperformed bupivacaine-phenylephrine and offers an effective alternative to TAC during laceration repair in children.

Adolescent↗
PubMed1998

Clinical criteria for using radiography for children with acute knee injuries.

OBJECTIVE: To evaluate clinical criteria for selective radiography for knee injuries in children. DESIGN: Retrospective chart review. SETTING: Emergency department (ED) of a children's hospital. PARTICIPANTS: All patients evaluated by radiography for an isolated, acute knee injury during 12 months. Patients were excluded for injuries: >1 week; isolated to superficial lacerations/abrasions; with prior knee surgery; being reassessed. RESULTS: Two hundred fifty-four patients (60% male; 12.7 years median age) were included. Twelve patients (4.7%) sustained a fracture. Evaluated criteria were point tenderness, inability to bear weight in the ED, and inability to flex the knee to 90 degrees. Point tenderness was not statistically associated with fracture, P = 0.7. Inability to bear weight in the ED (37% fracture rate, P = 0.001) and inability to flex to 90 degrees (52% fracture rate, P < 0.001) were associated with the presence of fracture.[table in text] Applying a rule combining nobearwt and noflex90 would decrease the number of x-rays by 73%, with no missed fractures. CONCLUSIONS: Point tenderness was not a good predictor of knee fracture in children. Using the clinical criteria to select patients requiring knee radiography may greatly reduce the number of unnecessary x-rays.

Acute Disease↗
PubMed1998

Hypotonicity activates transcription through ERK-dependent and -independent pathways in renal cells.

Acute hypotonic shock (50% dilution of medium with sterile water, but not with isotonic NaCl) activated the extracellular signal response kinase (ERK) mitogen-activated protein (MAP) kinases in renal medullary cells, as measured by Western analysis with a phospho-ERK-specific antibody and by in vitro kinase assay of epitope-tagged ERKs immunoprecipitated from stable HA-ERK transfectants. Hypotonicity also activated the transcription factor and ERK substrate Elk-1 in a partially PD-98059-sensitive fashion, as assessed by chimeric reporter gene assay. Consistent with these data, hypotonic stress activated transcription of the immediate-early gene transcription factor Egr-1 in a partially PD-98059-sensitive fashion. Hypotonicity-inducible Egr-1 transcription was mediated in part through 5'-flanking regions containing serum response elements and in part through the minimal Egr-1 promoter. Elimination of the Ets motifs adjacent to key regulatory serum response elements in the Egr-1 promoter diminished the effect of hypotonicity but failed to abolish it. Interestingly, hypotonicity also transiently activated p38 and c-Jun NH2-terminal kinase 1, as determined by immunoblotting with anti-phospho-MAP kinase antibodies. Taken together, these data strongly suggest that hypotonicity activates immediate-early gene transcription in renal medullary cells via MAP kinase kinase-dependent and -independent mechanisms.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed1998

Urea activates ribosomal S6 kinase (RSK) in a MEK-dependent fashion in renal mIMCD3 cells.

Urea activates a characteristic subset of signaling pathways in a tissue-specific fashion, including transcription of immediate early genes through activation of the mitogen-activated protein kinase (MAPK), ERK (extracellular signal-regulated kinase), and activation of its transcription factor substrate, Elk-1. The ability of urea to activate the ERK effector and pivotal regulatory kinase, ribosomal S6 kinase (RSK), was investigated in mIMCD3 renal inner medullary collecting duct cells. Urea upregulated RSK activity in a time-dependent fashion in serum-deprived mIMCD3 cells; the effect was maximal at 5 min. Activation by hypertonic NaCl, in contrast, was negligible at 5 min and peaked at 15 min. Both stimuli induced the nuclear translocation of cytosolic RSK, as determined via immunofluorescence. Importantly, activation of RSK by both solutes was MAPK/ERK kinase (MEK) dependent, as determined by the ability of the specific MEK inhibitor, PD-98059, to abrogate the response. Taken together, these data indicate that urea activates the ERK effector, RSK, in cells of the renal medulla in an ERK-dependent fashion, further emphasizing the functional significance of urea signaling through ERK activation in renal medullary cells.

Animals↗
PubMed1998

Urea and NaCl differentially regulate FAK and RAFTK/PYK2 in mIMCD3 renal medullary cells.

Two cytosolic tyrosine kinases, focal adhesion kinase (FAK) and the newly described FAK homolog, related adhesion focal tyrosine kinase (RAFTK, also called PYK2 and CAKbeta), have been implicated in signaling to multiple mitogen-activated protein kinase (MAPK) pathways. Therefore, the ability of NaCl and urea to activate these kinases was investigated by in vitro kinase assay and anti-phosphotyrosine immunoblotting. RAFTK was promptly but only transiently activated by urea (within 1 min; 45%), whereas NaCl activated this kinase at 1, 5, 15, and 30 min of treatment (35-60%). In contrast, FAK exhibited only subtle regulation by the two solutes; however, the time course of induction was distinct for each solute. NaCl activated FAK at 1, 5, and 15 min (25-40%), whereas urea-inducible FAK activation (30%) was not evident until fully 15 min of treatment. At 5 min of treatment with increasing concentrations of solute, both urea and NaCl activated RAFTK in a dose-dependent and comparable fashion, culminating in an approximately twofold activation at 800 mosmol/kgH2O solute. Consistent with these data, solute treatment also enhanced tyrosine phosphorylation of RAFTK.

Animals↗
PubMed1998

Tetracaine-lidocaine-phenylephrine topical anesthesia compared with lidocaine infiltration during repair of mucous membrane lacerations in children.

This study compared the effectiveness of a new topical anesthetic, tetracaine-lidocaine-phenylephrine (TetraLidoPhen), with that of lidocaine infiltration during repair of mucous membrane lacerations in children. It was conducted in the emergency department of an urban children's hospital with use of a prospective, randomized, blinded study design. Participants were 90 children 1 year of age or older with a laceration 5 cm or less in length on or near a mucous membrane that required suturing. They were randomly assigned to one of two treatment groups, with 45 patients in each group. Pain felt during suturing was scored by suture technicians, research assistants, a videotape reviewer, parents, and patients 5 years of age and older using a Visual Analogue Scale (VAS). Suture technicians, research assistants, a videotape reviewer, and parents also scored pain using a seven-point Likert scale. In addition, suture technicians completed an Anesthesia Effectiveness scale and a Wound Blanching scale. The laceration was located near the eyes in 71 patients (79%), and on or near the lips in 19 (21%). Lidocaine infiltration performed significantly better than topical TetraLidoPhen in comparisons of Likert scores of suture technicians (P = 0.007), research assistants (P = 0.005), the videotape reviewer (P = 0.003), and parents (P = 0.03); Anesthetic Effectiveness scale scores of suture technicians (P = 0.00002; relative risk (RR) = 1.83, 95% confidence interval 1.36 < RR < 2.46); and VAS scores of suture technicians (P = 0.002), research assistants (P = 0.001), and the videotape reviewer (P = 0.005). No significant difference in performance was detected between lidocaine and TetraLidoPhen in comparing VAS scores of parents and patients. There was a 4.4% wound complication rate, including two (2.2%) wound infections. The authors conclude that TetraLidoPhen is a new topical anesthetic that appears to be safe when applied on or near mucous membranes. Its performance among study participants was statistically inferior to that of lidocaine infiltration; however, the differences in pain scores were small and may not be clinically significant. Also, comparisons of pain scores in this study did not take into account the pain associated with the initial injection of lidocaine. Therefore, study findings may underestimate the comparative performance of TetraLidoPhen. Further investigation of this new topical anesthetic is warranted.

Anesthesia, Local↗