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Biomedical subjects

S M Cohn

Publications and source records attributed to S M Cohn.

87 records · Page 5Linked to original sources
PubMed1990

Are low tidal volumes safe?

High airway pressure may be injurious to lung parenchyma, but lowering airway pressure using conventional mechanical ventilation necessitates lowering tidal volume (VT). Intubated patients in the surgical intensive care unit (SICU) were randomly assigned to group 1 (VT = 12 ml/kg, n = 56) or group 2 (VT = 6 ml/kg, n = 47). Variables recorded included acute physiology and chronic health evaluation (APACHE II) score, mean peak airway pressure (MPAP), mean PaO2/FIO2, incidence of pulmonary infectious complications (PIC), duration of intubation (DOI), and duration of SICU stay (DOS). Results in the table are means +/- SE. (table; see text) The incidence of pulmonary infection tended to be lower and DOI and DOS tended to be shorter for nonneurosurgical and noncardiac surgical patients randomized to low VT, suggesting that morbidity may be decreased. The use of low VT was associated with a statistically significant but clinically irrelevant decrease in oxygenation. The routine use of low VT appeared to be safe in a selected population of patients in the SICU.

Female↗
PubMed1989

Effect of lipopolysaccharide on intestinal intramucosal hydrogen ion concentration in pigs: evidence of gut ischemia in a normodynamic model of septic shock.

We tested the hypothesis that lipopolysaccharide (LPS) leads to an imbalance between mesenteric oxygen delivery (DO2) and gut metabolic demand for oxygen, even when cardiac index (CI) is within the normal range. Two groups of pentobarbital-anesthetized pigs (13 to 17 kg) were studied. The first group (LPS; n = 9) was infused over 20 min with Escherichia coli LPS (100 micrograms/kg) and resuscitated with normal saline (1.2 ml/kg.min). The second group (NS; n = 5) was not infused with LPS, but was resuscitated in the same way as the LPS group. Superior mesenteric arterial (SMA) blood flow and ileal intramucosal hydrogen ion concentration, [H+], were determined using a Doppler-shift probe and a tonometric catheter, respectively. Infusing LPS did not affect CI, although mean arterial pressure and systemic vascular resistance were significantly reduced. SMA flow and mesenteric DO2 decreased significantly in the LPS group. Although mesenteric oxygen utilization was well preserved in both groups, ileal intramucosal [H+] was significantly higher in endotoxic animals. These data support the idea that mesenteric oxygen consumption is flow-limited in this clinically relevant porcine model of septic shock.

Animals↗
PubMed1989

Complement depletion with Naje haje cobra venom factor limits prostaglandin release and improves visceral perfusion in porcine endotoxic shock.

We tested the hypothesis that complement (C')-dependent release of prostaglandin (PG) I2 is an important factor contributing to the development of hypotension and low systemic vascular resistance index (SVRI) in endotoxic shock. Two groups (n = 7) of pentobarbital-anesthetized pigs (12-15 kg) were infused over 40 min with Escherichia coli lipopolysaccharide (LPS; 200 micrograms/kg) and continuously resuscitated with normal saline (1 ml/kg min): LPS-Control (no pretreatment) and LPS-Decomplemented (pretreatment 18 hr before study with 500-1,500 units of Naje haje cobra venom factor, CVF). Prior treatment with CVF: i) decreased the mean titer of total hemolytic C' to 15.9% of pretreatment levels; ii) significantly decreased post-LPS plasma concentrations of immunoreactive TxB2 (TxA2 metabolite) and 6-keto-PGF1 alpha (PGI2 metabolite); iii) abrogated the early transient decrease in cardiac index observed in the LPS-Control group; iv) tended to improve post-LPS visceral perfusion assessed using radioactive microspheres; and v) had no discernible effect on the late sustained decrease in SVRI observed following infusion of LPS. We conclude that C' activation is a major determinant of LPS-induced prostanoid release in vivo, although our results do not support the view that C'-dependent release of PGI2 is an important factor contributing to low SVRI in resuscitated endotoxic shock.

6-Ketoprostaglandin F1 alpha↗
PubMed1989

Systemic and mesenteric O2 metabolism in endotoxic pigs: effect of ibuprofen and meclofenamate.

The effect of two chemically dissimilar cyclooxygenase inhibitors was studied in pentobarbital-anesthetized endotoxic pigs. Animals in groups II-IV were infused with Escherichia coli lipopolysaccharide (LPS, 150 micrograms/kg) and resuscitated with normal saline (1.2 ml.kg-1.min-1). Animals in group I (n = 4) were resuscitated as above but were not infused with LPS. Animals in group II (n = 7) served as endotoxic controls. Pigs in groups III (n = 6) and IV (n = 5) were pre- and posttreated with ibuprofen (10 mg/kg bolus then 10 mg.kg-1.h-1 and meclofenamate (5 mg/kg then 5 mg.kg-1.h-1, respectively. Ileal intramucosal hydrogen ion concentration [( H+]) was estimated tonometrically. In group I, cardiac index (CI), mean arterial pressure (MAP), superior mesenteric arterial perfusion (QSMA), and mesenteric O2 delivery (DO2) increased significantly, but other variables were unchanged. After infusion of LPS in group II, MAP and systemic vascular resistance index were markedly diminished but CI was well preserved. In this group, QSMA, systemic DO2, and mesenteric DO2 decreased, whereas systemic O2 uptake (VO2) and gut [H+] increased; mesenteric VO2 was unchanged. Compared with pigs in group II, pigs treated with ibuprofen or meclofenamate manifested improved systemic and mesenteric DO2. In groups III and IV, QSMA remained normal, increased systemic VO2 was not observed, and gut intramucosal acidosis was ameliorated. Increased intramucosal [H+] in group II suggests that QSMA was inadequate. The salutary effects of ibuprofen and meclofenamate suggest that inadequate mesenteric perfusion was mediated, at least in part, by cyclooxygenase-derived metabolites or arachidonic acid.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

Pyogenic sacroiliitis: another imitator of the acute abdomen.

Acute suppurative infection of the sacroiliac joint can mimic the acute abdomen. Experience with a patient who had exploratory laparotomy for acute appendicitis prompted a review of the literature, which indicated that 12.6% of patients with pyogenic sacroiliitis have acute abdominal pain. A high index of suspicion is necessary to establish this diagnosis.

Abdomen, Acute↗
PubMed1984

The use of antibodies to 5-bromo-2'-deoxyuridine for the isolation of DNA sequences containing excision-repair sites.

We have developed an immunological method for isolation and identification of DNA sequences containing 5-bromo-2'-deoxyuridine (BrdUrd) incorporated during UV-induced excision-repair synthesis. DNA fragments containing BrdUrd incorporated during repair synthesis were incubated with goat anti-BrdUrd and rabbit anti-goat IgG, and the antibody-DNA complexes were separated from bulk DNA by nitrocellulose filter binding. With this method, 80% of DNA sequences containing BrdUrd-labeled excision-repair sites were recovered, contaminated with less than 1% of DNA fragments devoid of excision-repair sites. Recovery of DNA fragments containing repair sites was independent of size from 2 to 20 kilobases. We have used this method in conjunction with blot hybridization to demonstrate that repair synthesis occurs in human ribosomal gene sequences in cells treated with UV.

Antibodies↗
PubMed1984

The distribution of DNA excision-repair sites in human diploid fibroblasts following ultraviolet irradiation.

Using the technique for separating DNA fragments containing excision-repair sites from total genomic DNA as described in the previous paper (Cohn, S. M., and Lieberman, M. W. (1984) J. Biol. Chem. 259, 12456-12462), we have developed a method for directly determining the distribution of excision-repair sites in the genome. DNA was prepared from confluent, diploid human fibroblasts which had been irradiated with ultraviolet light and incubated in the presence of 5-bromo-2'-deoxyuridine (BrdUrd), repaired fragments were isolated, and the dependence of the fraction of total DNA fragments containing excision-repair sites on DNA fragment length was determined by electrophoretic analysis. The observed dependence was compared to the relationship expected for a random distribution of repair sites. At 36 h following 3 J/m2 UV, the distribution of repair sites was indistinguishable from a random distribution; however, at doses of UV above 6 J/m2, the observed dependence indicated that the distribution of repair sites was nonrandom. A time course of the distribution of repair sites following 12 J/m2 UV was clearly nonrandom from 4 h after irradiation until at least 36 h following irradiation. By 72 h, however, the distribution had become random. In cells treated with hydroxyurea, a reduced number of excision-repair sites were present, but the distribution of repair sites was also nonrandom. Autoradiographic analysis of the amount of unscheduled DNA synthesis in individual nuclei suggested that the nonrandom distribution of repair sites did not result from variable extents of repair synthesis in different cell populations or from cell death.

Bromodeoxyuridine↗
PubMed1984

Induction of replicative DNA synthesis in quiescent human fibroblasts by DNA damaging agents.

A marked induction of DNA replication was observed in confluent human diploid fibroblast cultures treated with low relatively nontoxic doses of UV radiation, N-methyl-N-nitrosourea (MNU), and N-acetoxy-2-acetylaminofluorene (AAAF). Isopycnic CsCl density gradient analysis of newly synthesized DNA labeled with BrdUrd indicated that most of the synthesis was semiconservative. The rate of semiconservative DNA synthesis was maximal 24 hr after damage. This induction of DNA replication was greatest at approximately equal to 3 J/m2 UV, 0.5 mM MNU, or 1.0 microM AAAF; was inhibited by hydroxyurea and aphidicolin; and also occurred in repair-deficient xeroderma pigmentosum fibroblasts. Autoradiographic examination of both confluent cultures and serum-arrested cultures showed a large increase in the fraction of densely labeled (S phase) cells after UV treatment. These densely labeled cells retain the capacity for cell division and subsequent proliferation. We conclude that low doses of at least three different DNA damaging agents are capable of recruiting quiescent cells into a state of DNA replication similar to that observed in the normal cell cycle.

Acetoxyacetylaminofluorene↗
PubMed1982

Reevaluation of a DNA binding activity with specificity for chemically modified DNA.

A DNA binding activity which appeared in direct filter binding assays to show specificity for DNA modified by N-acetoxy-2-acetylaminofluorene (AAF), N-methyl-N-nitrosourea and methylmethanesulfonate (Moranelli and Lieberman, Proc. Natl. Acad. Sci. USA 77, 3201, 1980) has been further purified and characterized. Equilibrium competition binding experiments indicate this activity shows little, or no, preferential binding of AAF-modified DNA compared to single-stranded DNA and only a small preference compared to u.v.-irradiated DNA or double-stranded DNA. These findings demonstrate the difficulty of using direct filter binding assays when purifying proteins with a desired biological function and the need to perform competition assays when evaluating specificity.

2-Acetylaminofluorene↗
PubMedDate not supplied

Maxillary sinusitis in the surgical intensive care unit: a study using bedside sinus ultrasound.

PURPOSE: This study investigates the incidence of acute maxillary sinusitis (AMS) in the surgical intensive care unit (SICU). METHODS: One hundred consecutive patients admitted to the SICU were examined in a prospective observational mode. Bedside sinus ultrasound (SUS) was performed on admission and every 48 hours. Patients with sinus fluid by SUS and unexplained sepsis underwent confirmatory sinus aspiration. RESULTS: The development of fluid in the maxillary sinus was identified in 15 patients by SUS. Acute maxillary sinus occurred in only 1 (1%). CONCLUSION: This study shows SUS to be a simple, efficient method for determining the presence of maxillary sinus fluid in the SICU. Acute maxillary sinus was an unusual finding. Our policy of avoidance of nasal instrumentation may have contributed to the low incidence of AMS in this high-risk patient population.

Acute Disease↗
PubMedDate not supplied

The mouse intestinal fatty acid binding protein gene: nucleotide sequence, pattern of developmental and regional expression, and proposed structure of its protein product.

The rat intestinal fatty acid binding protein (I-FABP) gene has been used as a model to study temporal and spatial differentiation of the gut epithelium while its protein product has been used as a model for examining the atomic details of noncovalent fatty acid-protein interactions. We have isolated the mouse I-FABP gene (Fabpi) and determined its nucleotide sequence. Comparisons of the orthologous mouse, rat, and human I-FABP genes revealed three conserved domains in their otherwise divergent 5' nontranscribed sequences. RNA blot hybridization and multilabel immunocytochemical methods were used to compare the developmental stage-specific patterns of activation of the rat and mouse genes. In addition, Fabpi expression in enterocytes was examined as a function of their differentiation along the crypto-to-villus and duodenal-to-colonic axes of the small intestine. Based on the similar temporal and geographic patterns of mouse and rat I-FABP expression described here and the results of our earlier studies of transgenic mice containing rat Fabpi/human growth hormone fusion genes, we propose that one of the conserved domains, spanning nucleotides -500 to -419 in mouse Fabpi, and/or a 14-bp element, are necessary for establishing and maintaining its region-specific expression along the duodenal-to-colonic axis of the perpetually renewing gut epithelium. Finally, predictions of the structure of mouse I-FABP using the refined 2.0 A model of rat I-FABP, suggest that a proline found at position 69 of the mouse, but not rat, protein may affect its ligand binding properties.

Amino Acid Sequence↗
PubMedDate not supplied

Comparison of MRI with postcontrast CT for the evaluation of acute abdominal trauma.

We compared the ability of MRI and CT to detect and characterize abdominal visceral injury. Seven patients with contrast-enhanced abdominal CT interpreted as showing definite (five patients) or possible (two) solid organ injury following blunt abdominal trauma were referred for abdominal MRI with a mean interval of 3 days between modalities. T1-weighted and T2-weighted spin echo sequences were obtained in all patients. Gradient-recalled echo (GRE) sequences (22-25/12-13/60 degrees flip angle) were obtained in five cases. Both CT and MR allowed detection of complex splenic lacerations in two patients and complex hepatic injuries in three other patients. A sixth patient had subtle periportal hypodensity noted on CT which was not detected prospectively on MRI. One patient had a right adrenal hematoma detected on MRI but not on CT. Relative lesion conspicuity and extent were judged equal on CT and T2-weighted imaging. The T1-weighted and GRE imaging were judged inferior to CT. We conclude that MRI offers no significant advantage over CT for the routine evaluation of acute abdominal trauma.

Abdominal Injuries↗
PubMedDate not supplied

A safety assessment of diaspirin cross-linked hemoglobin (DCLHb) in the treatment of hemorrhagic, hypovolemic shock.

OBJECTIVE: To determine the safety and possible efficacy of diaspirin cross-linked hemoglobin (DCLHb) in the treatment of patients in Class II-IV hemorrhagic, hypovolemic shock. DESIGN: Multicenter, randomized, normal saline-controlled, dose-escalation study. SETTING: Eleven hospitals in the U.S. and Belgium. SUBJECTS: One hundred and thirty-nine (139) hospitalized patients with Class II-IV hemorrhagic, hypovolemic shock within the previous 4 hours who still were requiring therapy for shock. INTERVENTIONS: Beginning with the lowest dose, patients were randomized to receive 50, 100, or 200 mL of either 10% DCLHb or normal saline infused intravenously over 15 minutes. Following infusion of either treatment, further fluid resuscitation could be given, as necessary, to maintain perfusion. Vital signs, laboratory assessments, blood and fluid administration, complications, and adverse events were recorded at various times from the end of infusion through 72 hours after infusion. RESULTS: A total of 29 (13 DCLHb- and 16 saline-treated) patients died during the study period. Adverse events were experienced by 61% of patients in the DCLHb group and 53% of patients in the saline group; serious adverse events occurred in 28% of DCLHb-treated patients and 30% of saline-treated patients. The incidence of prospectively defined, clinical complications, including renal insufficiency and renal failure, was similar between the treatment groups except for the occurrence of dysrhythmias/conduction disorders, which occurred significantly more frequently in the saline-treated patients than the DCLHb-treated patients (p = 0.041). At the highest dose level (200 mL), statistically significant between-group differences were observed with greater increases in serum amylase, LDH, the isoenzymes LD1,2,4 and 5, and CK-MB in the DCLHb group compared to the control group; none were of clinical significance. The volume of blood administered did not differ between the groups. Overall 24- and 72-hour survival rates were similar between treatment groups, although the hospital discharge rate was slightly higher in the DCLHb-treated patients (80%) compared with the saline-treated patients (74%). CONCLUSION: Administration of 50 to 200 mL of DCLHb to patients in hemorrhagic, hypovolemic shock was not associated with evidence of end organ toxicity or significant adverse events. Further studies involving larger doses and, perhaps, earlier administration of DCLHb are warranted.

Adult↗
PubMedDate not supplied

Fibrin glue eliminates the need for packing after complex liver injuries.

Hemostasis after traumatic liver injury can be extremely difficult to obtain, particularly in coagulopathic patients who have suffered extensive liver damage. We determined the ability of a fibrin glue preparation (FG) to terminate ongoing bleeding using a new, clinically relevant porcine model of complex hepatic injury. Anesthetized swine (n = 6, 18 to 19 kg) received an external blast to the right upper abdomen and were immediately anticoagulated with intravenous heparin (200 u/kg). Uncontrolled hemorrhage from blast continued from time of injury (t = 0 minutes) to t = 15 minutes. Lactated Ringer's solution was infused to keep mean arterial pressure (MAP) > 80 mm Hg until the end of experiment (t = 90 minutes). Animals underwent routine surgical techniques to control bleeding, and FG was employed in the event these measures failed. Estimated blood loss and fluid resuscitation volume were measured. Serial MAP, arterial base excess, and temperature were recorded. Animals were severely injured with significant blood loss prior to laparotomy (26 +/- 6 cc/kg) and during routine surgical efforts to arrest hemorrhage (11 +/- 2 cc/kg). Bleeding could not be controlled with standard techniques in any animal. FG rapidly controlled hemorrhage and eliminated the need for packing. Re-bleeding was noted in only one animal (portal vein injury). FG can control severe hepatic hemorrhage when surgical techniques fail. Further work in the clinical arena is warranted to determine the potential benefits of FG in arresting hemorrhage in hemodynamically unstable coagulopathic patients with complex hepatic injuries.

Animals↗