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Biomedical subjects

S Katz

Publications and source records attributed to S Katz.

At least 109 records · Page 6Linked to original sources

Pernicious anemia and adenocarcinoma of the stomach in an adolescent: clinical presentation and histopathology.

Primary gastric-carcinoma accounts for only 0.05% of pediatric gastrointestinal malignancies. Although elderly patients who have pernicious anemia are at greater risk of the development of atrophic gastritis and gastric carcinoma, pernicious anemia caused by vitamin B12 deficiency is extremely rare in otherwise healthy adolescents. The authors present a 14.5-year-old boy who had dimorphic anemia caused by vitamin B12 and iron deficiencies in whom atrophic gastritis and gastric carcinoma developed. To the best of our knowledge, this association has not been previously reported in children or adolescents.

Adenocarcinoma↗

Safety of calcium antagonists in patients with congestive heart failure.

Continuing high morbidity and mortality have spurred an ongoing search for new therapeutic agents for patients with congestive heart failure. Calcium antagonists (CAs) have been under active investigation in patients with heart failure since their introduction into clinical medicine, because their anti-ischemic and vasodilator properties were thought to be of potential benefit in this patient population. However, review of published clinical trials of CAs in patients with heart failure reveals that some of these drugs are associated with detrimental effects, including acute hemodynamic deterioration, increased symptoms of heart failure, and increased mortality. The adverse effects of short-acting CAs in patients with heart failure include negative inotropic effects and neurohormonal activation. Long-acting CAs, such as amlodipine and felodipine, had fewer negative inotropic effects, showed less evidence of neurohormonal activation, and were better tolerated in clinical trials. Amlodipine, in combination with an angiotensin-converting enzyme inhibitor, had a neutral effect in patients with ischemic heart failure and an unexplained benefit in a subgroup of patients with non-ischemic cardiomyopathy. Although the preliminary experience with long-acting dihydropyridine CAs in heart failure has been encouraging, safety concerns raised by past trials dictate that no CA can be recommended for the treatment of heart failure at this time.

Benzimidazoles↗

Glucocorticoids regulate both phorbol ester and calcium ionophore-induced endothelial prostacyclin synthesis.

The respective roles of protein kinase C (PKC) and intracellular calcium concentration ([Ca2+]i) in glucocorticoid (GC) action on prostacyclin (PGl2) production by bovine aortic endothelial cells (BAEC) were investigated. Twenty-four hours' pretreatment with dexamethasone (DEX, 10(-6) diminished the response of BAEC to calcium ionophore A23187 (0.001-1 micrograms/ml) and ionomycin (3 microM) by about 50%, as assessed by both PGl2 release and [Ca2+]i elevation. Contrary to control cells, in DEX-penetrated cells short treatment with 12-O-tetradecanoyl phorbol 13-acetate (100 nM) significantly decreased PGl2 production without affecting cyclooxygenase activity. The data suggest that the mechanism of action of GC involves both pathways of intracellular signal transduction, namely the rises in both [Ca2+]i and PKC activity. These actions of DEX may be attributed to a phospholipase A2-inhibiting protein, such as lipocortin, which accumulates during exposure to DEX. Binding of a sufficient fraction of calcium ions and phosphorylation by PKC might be the events needed fro lipocortin activation.

6-Ketoprostaglandin F1 alpha↗

Stomal ulcer after gastric bypass.

BACKGROUND: Stomal ulcer is a serious complication of gastrogastric fistula following Roux-en-Y gastric bypass for obesity. STUDY DESIGN: A 1-8 year continuous followup of 499 patients with gastric bypass in continuity (GB) and isolated gastric bypass (IGB) documented the incidence of fistula formation, development of stomal ulcer, stimulation of acid production within the gastric pouch, and response to treatment. RESULTS: In 123 GB patients, staple line disruption occurred in 36 (29%) and stomal ulcer occurred in 20 (16%). Gastrogastric fistula with stomal ulcer was significantly lower in 376 patients who underwent IGB, (ie, 11 patients [3%]). Significantly larger amounts of acid, a lower pH, and a greater time with a pH less than 2 were found in the gastric pouches of patients who developed stomal ulcer after Roux-en-Y gastric bypass. All patients had a perforated staple line. Successful closure of the staple line significantly decreased acid production and pH in the gastric pouch when tested before and after remedial operation with healing of stomal ulcers. CONCLUSIONS: Stomal ulcer after gastric bypass is the result of acid production in the bypassed stomach in the presence of a gastrogastric fistula. Separation of the gastric pouch from the main stomach decreases the incidence of fistula formation and stomal ulcer but does not eliminate it. Interposition of a well vascularized organ, the jejunum between the pouch and main stomach, is an attractive solution for patients who require remedial operations on the stomach and possibly for primary operations as well.

Follow-Up Studies↗

Characterization of calcium-dependent forms of protein kinase C in adult rat ventricular myocytes.

The presence and subcellular localization of the Ca2+-dependent protein kinase C (PKC) isoforms alpha and beta were investigated in freshly isolated adult rat cardiac ventricular myocytes. PKC activity was measured in cytosolic and particulate fractions prepared from control myocytes and those treated with either phorbol ester (phorbol 12-myristate 13-acetate, PMA) or a permeant synthetic diacylglycerol analog (1-oleoyl-2-acetylglycerol, OAG) in the absence or presence of an inhibitor of diacylglycerol kinase activity, compound R59022. Preliminary studies detected no Ca2+-/phospholipid-dependent histone kinase activity in either subcellular fraction. To reproducibly observe Ca2+-/phospholipid-dependent protein kinase activity, partial purification using a MonoQ HR 5/5 column and the presence of the peptide inhibitor of the cAMP-dependent protein kinase were essential. MonoQ chromatography of cytosolic and particulate fractions resulted in three peaks of Ca2+/phospholipid-dependent protein kinase activity. In the cytosolic fraction a large peak of activity eluted at 230-300 mM NaCl. Isoform-specific antisera indicated both PKC alpha and PKC beta were present. In the particulate fraction two peaks of Ca2+-/phospholipid-dependent protein kinase activity, both containing PKCa immunoreactivity, were observed. The larger peak eluted at 230-300 mM NaCl. In addition, a peak eluting at lower salt concentrations contained a Ca2+-/phospholipid-independent histone kinase activity. This peak of kinase activity contained PKC alpha immunoreactive bands of 80- and 50-kDa. The 80-kDa band was the holoenzyme of PKC alpha whereas the band of lower molecular mass was likely a proteolytic fragment. In both cytosolic and particulate fractions, the peak of kinase activity eluting at 230-300 mM NaCl contained PKC alpha in the form of an 80-kDa doublet; this suggested the presence of autophosphorylated PKC. Incubation of the myocytes with PMA, but not OAG, resulted in translocation of PKC from the cytosolic to the particulate fraction. Curiously, a transient decrease in PKC activity was observed in both subcellular fractions following treatment with either OAG or ethanol (1%). Results from this study show that freshly isolated adult rat cardiac ventricular myocytes contain both PKC alpha and PKC beta, and that these isoforms translocate to the particulate fraction in response to treatment with PMA, but not OAG.

Animals↗

Comparison of two regimens of feeding and oral electrolyte solutions in infants with diarrhea.

BACKGROUND: Glucose-based oral rehydration solutions (ORS) available in the United States do not appear to reduce the severity or duration of diarrhea. The use of cereal-derived ORS and cereal-based feedings appears to diminish the severity of illness in studies conducted in the developing world. To our knowledge, no controlled trials of cereal-derived ORS or cereal-based feedings have been performed in the United States. METHODS: We performed a randomized, double-blind trial of two ORS feeding regimens in outpatients with diarrhea. Patients aged 2-13 months with acute watery diarrhea were enrolled. Subjects received standard glucose-based ORS in alternation with soy-based, lactose-free infant formula (Group 1) or rice syrup solid containing ORS in alternation with rice-based, lactose-free infant formula (Group 2). Subjects were visited at home daily to determine the severity of illness and characteristics of the stool. RESULTS: After the first 2 days, significantly more Group 1 subjects continued to have diarrhea than did Group 2 subjects (median duration of diarrhea 3 vs. 2 days) as demonstrated by Kaplan-Meier survival curves (p = 0.04). CONCLUSION: We conclude that infants fed a regimen consisting of rice syrup solid containing ORS and rice formula resolved their diarrhea sooner than did infants fed a regimen of standard glucose-based ORS and formula. The relative contributions of ORS and formula to this more rapid recovery can be elucidated by further studies.

Diarrhea, Infantile↗

Index of affective suffering. Linking a classification of depressed mood to impairment in quality of life.

The authors report on development and validation of their Index of Affective Suffering (IAS), an explicit measure of subjective symptom severity, constructed as a typological system, rather than a multifactorial scoring system, with combinations of "intensity" (degrees of distress per given time) and "extensity" (duration and frequency of episodes, and number and variety of life events and activities that are pervaded by distress) item rankings. Seven levels of severity appeared to have both face value and empirical justification. Further conceptual and methodological advances would enhance the development and evaluation of treatments for geriatric mental disorders and chronic diseases in general.

Aged↗

Lack of association of catechol-O-methyltransferase (COMT) functional polymorphism in bipolar affective disorder.

Abnormal catecholamine transmission has been implicated in the pathogenesis of mood disorders. Consequently, alterations in genes that are involved in catecholamine metabolism could be potential candidates for bipolar affective disorder (BPD) vulnerability. One such candidate is catechol-O-methyltransferase (COMT). A functional polymorphism has recently been characterized that is responsible for substantial variability in COMT enzymatic activity. A relatively low activity allele is associated with a methionine residue at amino acid 158 of membrane bound COMT whereas a high activity variant has a valine at this site. We have now screened 63 unrelated patients with BPD for this functional polymorphism. However, no significant association was detected. This suggests that the codon 158 COMT polymorphism is not a susceptibility gene in BPD.

Alleles↗

Intracellular calcium responses in CF/T43 cells: calcium pools and influx pathways.

We studied the intracellular free Ca2+ concentration ([Ca2+]i) response to histamine in a cystic fibrosis airway epithelial cell line (CF/T43). Histamine (100 microM; duration approximately 10 min) biphasically increased [Ca2+]i, with a rapid initial peak (30-45 s) followed by a smaller second peak that lasted for several minutes before returning to baseline. Neither peak specifically depended on Ca2+ influx. Exposure to bradykinin (10 microM) elicited a single peak that lasted 3-3.5 min before returning to baseline. Bradykinin increased intracellular inositol 1,4,5-trisphosphate (IP3), which peaked and returned to baseline within 150 s. Histamine also increased IP3 monophasically, but the peak was brief (< 20 s). Both phases of the Ca2+ response to histamine exhibited similar responsiveness to histamine concentration and sensitivity to antagonists. Cimetidine or thioperamide (1 mM) had no effect on the second peak. Pyrilamine blocked the second peak at concentrations similar to those required to block the initial peak. Activation of the second peak was observed at a threshold concentration of 1 microM comparable with the threshold of the initial peak. Neither adenosine 3',5'-cyclic monophosphate, guanosine 3',5'-cyclic monophosphate, nor cyclic ADP (cADP)-ribose altered the second phase of the histamine response.

Bradykinin↗

Premalignant lesions of the vocal cords. A retrospective study of 62 cases treated with CO2 laser.

A series of 62 patients treated by (repeated) CO2 laser excision and/or vaporization for premalignant lesions of the vocal cords was analysed retrospectively. Of the 54 patients available for follow-up (ranging from 1 to 15 years), five patients (9%) developed an invasive glottic carcinoma and needed radiotherapy. Only two patients (4%) needed extensive surgery (total laryngectomy). One patient (2%) died of a recurrent carcinoma despite radiotherapy and laryngectomy, and six patients (11%) died of a metachronic lung carcinoma. The therapeutic results of (repeated) laser therapy were comparable to those in other reports regarding radiotherapy or stripping. The subjective functional results were satisfactory and tended to improve along with refinement of laser surgery techniques. Follow-up of patients who once had a premalignant laryngeal lesion is mandatory ad vitam, regardless of the grade of the lesion. For the screening of lung cancer, there is still no consensus on a standard-of-care. The classical chest X-ray remains the most accessible and comfortable screening procedure.

Carcinoma in Situ↗

Posterior epistaxis: our experience with transantral ligation and embolisation.

Transantral ligation of the arteria maxillares internae (AMI) (with or without ligation of the arteria ethmoidalis) and percutaneous embolisation of AMI in cases of intractable epistaxis (i.e. epistaxis not responding to classical posterior packing) are compared. Except when ethmoidal bleeding is suspected, we recommend embolisation for epistaxis not responding to classical measures as it leads to fewer complications and recurrences, to shorter hospital stay and to improved postoperative comfort.

Adolescent↗

Differences in risk of Crohn's disease in offspring of mothers and fathers with inflammatory bowel disease.

OBJECTIVE: To determine whether there are any unusual patterns of transmission of susceptibility to inflammatory bowel disease (IBD) within multiplex families. METHODS: Individuals with IBD were recruited for genome-wide screening of susceptibility genes. The extent of familial aggregation and blood relationships in multiplex families were determined by questionnaires given to participants followed up by confirmation of disease diagnosis by participants' physicians. RESULTS: Of 135 families identified in which both a parent and a child had IBD, 93 involved transmission of susceptibility to disease from mother to child versus 42 examples of transmission from father to child (p = 0.00001, exact two-tailed binomial test). This distortion in transmission on the basis of the sex of the parent was observed only among non-Jewish pairs with Crohn's disease (CD), in which, of 33 parent-child pairs with CD, disease susceptibility was transmitted from the mother 28 times (p = 0.00007). CONCLUSION: Susceptibility to CD in a subset of patients may involve a gene that is imprinted.

Child↗

Coupling of hemodynamic measurements with oxygen consumption during exercise does not improve risk stratification in patients with heart failure.

BACKGROUND: Measurement of peak Vo2 has become an accepted method to select patients for cardiac transplantation. Some investigators have suggested that the addition of exercise hemodynamic measurements can further enhance risk stratification because these measurements may identify patients with a noncardiac limitation to exercise. METHODS AND RESULTS: Accordingly, we performed maximal bicycle exercise with respiratory gas analysis and hemodynamic measurements in 65 patients (47 men, 18 women) 53 +/- 10 years old (mean +/- SD) who underwent a transplant evaluation at Columbia Presbyterian Medical Center. Skeletal muscle oxygenation of the vastus lateralis during exercise was assessed with near-infrared spectroscopy. Exercise hemodynamic, ventilatory, and muscle oxygenation measurements were obtained in all patients. For each subject, a linear correlation was derived between Vo2 and pulmonary artery saturation (PA Sao2). The slope of this relationship and a theoretical Vo2max at a PA Sao2 of 0% (Vo2 intercept) was derived. Baseline measurements were left ventricular ejection fraction, 22 +/- 9%; pulmonary capillary wedge pressure (PCWP), 16 +/- 10 mm Hg; cardiac index (CI), 2.1 +/- 0.5 L. min-1. m-2; and PA Sao2, 53 +/- 8%. The cardiac output response to exercise was categorized as normal or abnormal by comparison to the linear equation of peak Vo2 versus peak cardiac output as described by Higginbotham. Exercise measurements were peak Vo2, 12.1 +/- 3.0 mL.kg-1.min-1; Vo2 intercept, 19.1 +/- 5.5 mL. kg-1.min-1; PCWP, 31 +/- 11 mm Hg; CI, 3.8 +/- 1.3 L.min-1.m-2; and PA Sao2, 27 +/- 9%. Only 6% of patients exhibited a normal cardiac output response to exercise. Multivariate analysis was performed with peak Vo2, Vo2 intercept, skeletal muscle oxygenation at end exercise, and peak exercise hemodynamic variables. Only left ventricular stroke work and left ventricular stroke work index were shown to be predictive of survival. CONCLUSIONS: Addition of exercise hemodynamic measurements to noninvasive metabolic stress testing minimally improves risk prognostication in patients with severe heart failure.

Adult↗

Phosphorylation of cardiac junctional and free sarcoplasmic reticulum by PKC alpha, PKC beta, PKA and the Ca2+/calmodulin-dependent protein kinase.

Phosphorylation of cardiac junctional and free sarcoplasmic reticulum (SR) by protein kinase C (PKC) isoforms alpha and beta was investigated. Both SR and PKC were isolated from canine heart. Junctional and free SR vesicles were prepared by calcium-phosphate-loading. The substrate specificities of PKC alpha and PKC beta were found to be similar in both SR fractions. A high molecular weight junctionally-associated protein was phosphorylated by PKA, PKC and an endogenous Ca2+/calmodulin-dependent protein kinase activity: the highest levels of phosphate incorporation being catalysed by the latter kinase. In addition to this high molecular weight junctionally-associated protein, PKC induced phosphorylation of 45, 96 kDa and several proteins of greater than 200 kDa in junctional SR. A protein of 96 kDa was phosphorylated by both isoforms in junctional and free SR. The major substrate for PKA, PKC alpha, PKC beta and the Ca2+/calmodulin-dependent protein kinase, in both junctional and free SR, was phospholamban. Although the phosphorylation of phospholamban by PKC was activated by Ca2+, a component of this activity appeared to be independent of Ca2+. PKC-mediated phosphorylation of phospholamban was fully activated by 1 microM Ca2+ whereas the Ca2+/calmodulin dependent kinase required concentrations in excess of 5 microM Ca2+. In the in vitro system employed in these studies, the concentrations of either PKC alpha or the catalytic subunit of PKA required to phosphorylate phospholamban were found to be similar. In addition, in the presence of a 15 kDa sarcolemmal-associated protein, which becomes phosphorylated upon activation of PKC in vivo, phosphorylation of phospholamban by PKC was unaffected. These results demonstrate that, although substrates for both subtypes are found in both junctional and free SR, PKC alpha and PKC beta do not show differences in selectivity towards these substrates.

Animals↗