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Biomedical subjects

R W Carlson

Publications and source records attributed to R W Carlson.

At least 163 records · Page 9Linked to original sources

Relationship between the apparent dissociation constant of blood carbonic acid and severity of illness.

The Henderson-Hasselbalch equation is commonly used to calculate plasma bicarbonate and CO2 content (tCO2) from blood gas measurements and an assumed constant value of the apparent dissociation constant of blood carbonic acid (pK'). Several studies have reported pK' to be variable in critically ill patients. We prospectively compared the pK' of patients in an intensive care unit to their severity of illness. Blood specimens were analyzed for pH, Pco2, and tCO2, and the results were used to calculate pK'. The tCO2 was also calculated from this equation by means of the measured pH and Pco2 and from an assumed constant pK'. Severity of illness was evaluated with the acute physiology score and the Therapeutic Intervention Scoring System. A total of 2004 specimens were analyzed; they had a mean pK' of 6.126. A strong correlation was shown between calculated and measured tCO2; however, there was essentially no correlation between disease severity and pK'. We conclude that bicarbonate and tCO2 can be accurately calculated in critically ill patients.

Blood Gas Analysis↗

Impact of critical care physician staffing on patients with septic shock in a university hospital medical intensive care unit.

To evaluate the effects of reorganizing physician resources in a medical intensive care unit (MICU), we studied the impact of these changes in patients with septic shock. Patients were compared during two consecutive 12-month periods: (1) an interval in which faculty without critical care medicine (CCM) training supervised the MICU (before CCM, n = 100) and (2) following staffing with physicians formally trained in CCM (after CCM, n = 112). Acute Physiology and Chronic Health Evaluation scores were utilized to compare severity of illness and were similar for each group (29 +/- 11 before CCM vs 28 +/- 10 after CCM). However, mortality was significantly lower during the post-CCM interval (74% vs 57%, respectively). There was no significant difference in the frequency of use of mechanical ventilation (83% vs 87%), although pulmonary artery catheters (48% vs 64%) and arterial catheters (24% vs 73%) were employed more frequently after CCM. The number of subspecialty consultations and MICU and hospital length of stay were similar for both intervals. We conclude that the implementation of dedicated staffing by CCM physicians in a university hospital MICU was associated with a favorable impact on patients with septic shock.

Critical Care↗

Enhancement of the clinical activity of melphalan by the hypoxic cell sensitizer misonidazole.

One hundred patients with non-small cell lung cancer were entered by members of the Northern California Oncology Group into a randomized Phase II trial of i.v. melphalan versus i.v. melphalan with concomitant oral misonidazole. The patients had not received prior chemotherapy. Eighty-five patients were evaluable for assessment of response and 89 were evaluable for toxicity analysis. The melphalan/misonidazole group had a superior response rate (two complete and four partial responses among 42 patients or 14%) compared to the melphalan group in which there were no responses among 43 patients (p = 0.024, two-sided Fisher exact test). Since hematological toxicity was equivalent in the two groups, there was an improvement in therapeutic index. Data from 12 patients undergoing pharmacological studies demonstrated that the plasma concentration of melphalan was 25% higher in the misonidazole group, a difference that is not statistically significant. Although the mechanism of interaction has not been fully established, this randomized trial demonstrates that a chemosensitizer can enhance the clinical antitumor activity of an alkylating agent and suggests that chemosensitizers in combination with alkylating agents should be investigated in further clinical trials.

Adult↗

A core oligosaccharide component from the lipopolysaccharide of Rhizobium trifolii ANU843.

The major oligosaccharide from the core region of the lipopolysaccharide from R. trifolii ANU843 was isolated and its structure determined. It is a trisaccharide consisting of two galacturonic acid residues and one 3-deoxy-D-manno-2-octulosonic acid (KDO) residue. The two galacturonic acid residues are terminally linked alpha to the C-4 and C-7 atoms of KDO. This structure was determined through use of 1H- and 13C-n.m.r. spectroscopy, f.a.b.-m.s., and g.l.c.-m.s. techniques. This oligosaccharide had not previously been reported to be present in the lipopolysaccharides from Gram-negative bacteria.

Carbohydrate Conformation↗

Development of a comprehensive supportive care team for the hopelessly ill on a university hospital medical service.

We developed a supportive care service for a university hospital medical service that serves a socially and medically disadvantaged urban population. The team includes a faculty physician and a clinical nurse specialist who provide primary medical care, family support, and in-service guidance to hospital staff about ethical issues. A multidisciplinary approach incorporates nursing, pastoral care, social work, and other hospital services. We report our experience from November 1985 through May 1987, during which time 222 patients were referred to the team; 212 patients were accepted. The goals and operation of the service are described. The most common (n = 62, 29%) diagnosis on referral was global central nervous system anoxia following cardiopulmonary arrest. Other severe neurological conditions accounted for an additional 79 patients (37%). Comparison of patients on the service with a similar group revealed no difference in survival rate, although hospital length of stay and charges were progressively reduced after implementation of the service. This approach to the care of hopelessly ill patients may serve as an alternative method of treatment in similar hospital settings.

Brain Diseases↗

Prevalence and clinical implications of hypocalcemia in acutely ill patients in a medical intensive care setting.

The incidence and the clinical implications of hypocalcemia were evaluated in acutely ill patients admitted to the Medical Intensive Care Unit of the Detroit Receiving Hospital. Total and ionized calcium levels were prospectively evaluated upon admission for all patients over a three-month interval. A high proportion of patients (62 of 88, 70 percent) were found to have decreased levels of both total and ionized calcium. Known causes of hypocalcemia could be identified in only 28 patients (45 percent). These included hypomagnesemia (17, 28 percent), renal insufficiency (five, 8 percent), alkalosis (four, 6 percent), and acute pancreatitis (two, 3 percent). In the remaining 34 patients (55 percent), no readily identifiable cause could be found. These 34 patients had a lower mean albumin level than did the 23 normocalcemic patients (p less than 0.01), but there were no differences in age, pH, serum creatinine, magnesium, or phosphate between the two groups. Serum albumin correlated directly with ionized calcium levels (n = 82, r = 0.33, p less than 0.01), as well as with total calcium levels (n = 76, r = 0.70, p less than 0.01). There was a strong association between sepsis and hypocalcemia. Patients who survived the hospitalization had higher mean ionized calcium, total calcium, and albumin values than did nonsurvivors, but there were no differences in age, serum creatinine, magnesium, and phosphate between the two groups. The mortality of the hypocalcemic patients (44 percent) was significantly greater (p less than 0.05) than the mortality of the normocalcemic patients (17 percent). These findings suggest that hypocalcemia is a very common abnormality in acutely ill patients and is associated with a poor prognosis.

Acute Disease↗

Enzyme-linked immunosorbant assay (ELISA) of size-selected crotalid venom antigens by Wyeth's polyvalent antivenom.

The binding of Antivenom (Crotalidae) Polyvalent to fractions from crude venoms of eight crotalid and one viperid snake, obtained by high performance size-exclusion chromatography, was determined with an indirect enzyme-linked immunosorbent assay (ELISA). Most of the large (greater than 30,000 mol. wt) molecular mass crotalid venom fractions were associated with high (greater than 0.7 absorbance units) ELISA values. Similarly, the medium (13,000-30,000 mol. wt) and small (less than 14,000 mol. wt) molecular mass crotalid venom fractions were coincident with moderate (0.3-0.7 absorbance units) and low (less than 0.3 absorbance units) ELISA levels. Some variability in this pattern was seen with individual venom fractions. A distinctly different pattern of ELISA values were observed with two rattlesnake venoms: the South American (Crotalus durissus terrificus) and Mojave desert (Crotalus scutulatus scutulatus) rattlesnakes. The elution profile from these venoms showed a progression of low to moderate ELISA values within the large molecular mass fractions. This pattern was followed by a decline to low ELISA values throughout the remainder of the elution profile. When saw scaled viper (Echis carinatus leucogaster) venom fractions were tested, only background ELISA values were detected with antivenom. Similarly, background ELISA values were associated with the small molecular mass fractions of all venoms tested. In addition, the elution position for the basic peptides of southern Pacific (Crotalus viridis helleri) and timber (Crotalus h. horridus) rattlesnake venoms showed minimal ELISA values. These data support the view that except for the venom of C. durissus terrificus and C. s. scutulatus, most antivenom antibodies bind large (greater than 30,000 mol. wt) venom fractions. Thus, antivenom contains minimal levels of antibodies to the basic peptides in these venoms.

Animals↗

A direct relationship between ionized calcium and arterial pressure among patients in an intensive care unit.

Serum ionized calcium (Ca+2), creatinine, magnesium, phosphate, and arterial pH were measured in patients on admission to the medical ICU (MICU). Patients were classified into three groups: a) hypotensive (n = 38), those who received vasopressor support for frank hypotension; b) hypertensive (n = 21), those who required vasodilator therapy; and c) normotensive (n = 53), those who required neither vasopressor nor vasodilator therapy. Analysis of variance revealed that only Ca+2, creatinine, and arterial pH differed among the three groups. The difference in Ca+2 persisted when analysis of variance was repeated with creatinine as a covariate. Hypotensive patients had a significantly (p less than .05) lower mean Ca+2 (1.04 +/- 0.13 mmol/L) than normotensive patients (1.13 +/- 0.10 mmol/L), who in turn had a significantly (p less than .05) lower Ca+2 than hypertensive patients (1.18 +/- 0.09 mmol/L). Ca+2 correlated with mean arterial pressure at the time of serum collection (n = 118; r = .43; p less than .01), independent of any other variable. Vasopressor support was required in 41% of hypocalcemic patients in comparison to 14% of normocalcemic patients (p less than .01). Vasodilator therapy was required for 34% of normocalcemic patients, compared to 7.5% of hypocalcemic patients (p less than .01). There appears to be a clinically significant association between hypotension and hypocalcemia. This association may or may not be causal.

Adult↗

The clinical biology of breast cancer.

Breast cancers present as a spectrum of neoplasms. The natural histories of the neoplasms are tied to the biological properties of the neoplastic cells that compose them. We review the histological, cytological, kinetic, and other parameters that best characterize the clinical biology of breast cancer.

Breast↗

Constancy of blood carbonic acid pK' in patients during cardiopulmonary resuscitation.

Previous studies have suggested that the apparent dissociation constant of blood carbonic acid (pK') may actually vary in acutely ill patients. We prospectively compared the pK' of healthy control subjects to that of patients undergoing cardiopulmonary resuscitation (CPR). Arterial blood obtained from 20 patients undergoing CPR and from 30 healthy volunteers was analyzed for Na+, pH, PCO2, and total CO2 content (tCO2). pK' was calculated from this data, using the Henderson-Hasselbalch equation. Total CO2 was then calculated in the CPR patients, using this equation and the control pK'. Mean pK' was 6.109 +/- 0.004 (SEM) for the control group and 6.123 +/- 0.007 for the CPR group (p = NS). In the CPR group, calculated tCO2 was not significantly different from measured from tCO2, and the correlation between calculated and measured tCO2 was 0.99. In patients undergoing CPR, pK' does not differ significantly from normal, and tCO2 can be accurately estimated with the Henderson-Hasselbalch equation.

Adult↗

Post-infectious ARDS: mechanisms of lung injury and repair.

Lung infections are considered the most common causes of ARDS. Additionally, superimposed secondary lung infections may occur in the setting of ARDS and further aggravate lung damage. Substances released by neutrophils are the major mediators of lung injury, although other factors, such as endotoxin, exotoxins, macrophages, and immune mechanisms, are significant contributors. Neutrophil-induced lung injury results from the production of oxygen radicals, the release of products of arachidonate metabolism, and the activation of lysosomal enzymes. The development of ARDS is associated with high mortality. Although a large proportion of survivors eventually recover adequate lung function, some patients progress to severe fibrosis. Experimental evidence suggests that the development of fibrosis results from increased synthesis of ECM components by lung fibroblasts. Fibroblast synthesis of ECM components is normally influenced by alveolar cells, by circulating growth factors, by the external milieu, and by the extent of gene expression of the specific ECM components. These factors undergo significant alterations during the evolution of experimental lung fibrosis. Growth factors are more abundant, alveolar cells are activated, and gene expression is enhanced. These factors, which play a crucial role in promoting experimental lung fibrosis, are likely to be involved in the pathogenesis of fibrosis in post-infectious ARDS.

Animals↗

Significance of blood lactate levels in critically ill patients with liver disease.

Lactic acidosis unrelated to tissue hypoxia has been described in patients with liver disease. This raises questions regarding the utility of the arterial lactate level as an indicator of tissue hypoperfusion in critically ill patients with hepatic dysfunction. The incidence of hyperlactatemia in a group of critically ill patients with liver disease and its association with clinical indicators of circulatory shock as well as hospital mortality were examined. The medical records of all patients admitted to the medical intensive care unit of Detroit Receiving Hospital between July 1, 1984, and June 30, 1985, with parenchymal liver disease and a total bilirubin level of more than 2 mg/dl were reviewed. Patients were excluded if lactate was not assayed. The severity of liver disease was assessed by Child's classification. Shock was defined as a systolic blood pressure of less than 90 mm Hg and at least two of the following: urine output of less than 20 ml/hour, evidence of decreased skin perfusion, or acutely altered mentation. These criteria were met in 35 patients; three patients had two medical intensive care unit admissions separated by more than one week. There were two patients in Child's class A, three in class B, and 30 in class C. Shock was identified in 27 of the 38 medical intensive care unit admissions. In the group with shock, the maximal lactate level ranged from 1.2 to 30 mM (mean, 9.6). The lactate level was significantly lower (p less than 0.0005) in the group without shock, ranging from 0.6 to 2.0 mM (mean, 1.3). The mean bilirubin level was significantly higher in the group without shock (16.7 mg/dl) than in the group with shock (8.5 mg/dl). A maximal arterial lactate concentration of more than 2.2 mM was significantly associated with hospital mortality. Thus, lactic acidosis in critically ill patients with liver disease is associated with clinical evidence of shock and with increased hospital mortality.

Acidosis, Lactic↗

Pulmonary fibrin deposition and increased microvascular permeability to protein following fibrin microembolism in dogs: a structure-function relationship.

The effects of fibrin microembolism were examined using an infusion of a prothrombin activator (Echis carinatus venom, ECV; 30 min, 0.5 NIH thrombin equivalent units/kg) in acute mongrel dogs prepared with a pulmonary lymph cannula (n = 6, 12.3-21.5 kg). Lymph flow increased approximately 2.5-fold after 1-1.5 hr of elevated left atrial pressure (Pla = 20 cm H2O; 26 +/- 7 to 63 +/- 16 microliter/min, P less than 0.01) and the plasma to lymph protein concentration ratio (CP/CL) declined from 0.66 +/- .04 to 0.54 +/- .16 (P less than 0.01, x +/- SE). After Pla was reduced to control levels, the initiation of fibrin microembolism was associated with an approximate 2.7-fold elevation of lymph flow (62 +/- 8 microliters/min, P less than 0.01) and the CP/CL was not changed (0.56 +/- 0.04, P = ns). When Pla was increased following microembolism, lymph flow more than doubled to 117 +/- 24 microliter/min (P less than 0.01) and the CP/CL remained unaltered (0.56 +/- 0.03, P = ns). These changes were associated with afibrinogenemia and the appearance of fibrin degradation products (FDP) in plasma (150 +/- 50 micrograms/ml) and lymph (80 micrograms/ml) in three of the animals tested. No consistent pattern was seen in the CL/CP of separate endogenous plasma proteins after each intervention. These data support the view that pulmonary fibrin microembolism without inhibition of the fibrinolytic system was associated with an early increased pulmonary microvascular permeability to protein. In a separate group of similarly prepared animals (n = 8, 13-21.5 kg) without a lymph catheter, scanning electron microscopic observations showed branching fibrin microemboli to partially occlude some pulmonary arterioles. Mixed thrombus formations in larger precapillary blood vessels were also seen. Ultrastructural observations revealed the deposition of fibrin strands (periodicity = 220-230 A) within the pulmonary capillaries. Some of these deposits were overlaid by lamellar pseudopodia from endothelial cells and the fibrin appeared to be within these cells. Although plasmalemmal vesicles seemed to be more numerous in the endothelial cells with adjacent fibrin deposits, no gaps or breaks were seen in the densely stained interendothelial cell junctions and/or the endothelial cell membrane of the affected lung capillaries. Activated neutrophils and platelets were more numerous in the pulmonary capillaries following EVC. These data suggest that the presence of FDP and/or fibrin deposits within the pulmonary microvasculature may influence the early functional integrity of pulmonary endothelial cells at sites of fibrin accumulation.

Animals↗

Effects of colloid or crystalloid solutions on edemagenesis in normal and thrombomicroembolized lungs.

We studied the effects of crystalloid (75 ml/kg of Ringer's lactate) or colloid (6% dextran-70, 6% hydroxyethyl starch, or 25 ml/kg of 5% human serum albumin) fluid infusions or no treatment (control) on the calculated lung capillary (Pc)-plasma oncotic pressure (pi c) gradient and pulmonary edema. Two sets of mongrel dogs were studied: uninjured (n = 25; 14 to 22 kg) and pulmonary fibrin-microembolized (n = 25; 15 to 23 kg). In both sets of experiments, left atrial pressure was controlled (15 mm Hg) throughout the 4-h plus experimental period. In the uninjured set, the Pc-pi c gradient averaged +1.0 and -0.2 mm Hg in the hydroxyethyl starch and dextran groups, +0.7 and +2.3 mm Hg in the human serum albumin and control groups, and +6.2 mm Hg in the Ringer's lactate group. In the fibrin-microembolized group, this gradient averaged 2.6, 2.4, 3.0, 5.3, and 9.5, respectively. The extravascular lung water to bloodless dry lung wet weight ratios in the no-fluid treatment group of the uninjured and microembolism groups with increased pressure (3.8 +/- 0.3 to 4.1 +/- 0.4 [SEM]; NS) are consistent with interstitial or perivascular edema. There were, however, no significant differences noted between the respective control groups or any fluid treatment group in either set of experiments. These data support the view that infusion of either colloid or crystalloid solutions in normal or pulmonary fibrin-microembolized lungs does not produce sufficient change in the Pc-pi c gradient to elevate edemagenesis when pulmonary capillary pressure is limited to 22 mm Hg in dogs.

Animals↗

The Isolation and Partial Characterization of the Lipopolysaccharides from Several Rhizobium trifolii Mutants Affected in Root Hair Infection.

The lipopolysaccharides (LPSs) from Rhizobium trifolii ANU843 and several transposon (Tn5) symbiotic mutants derived from ANU843 were isolated and partially characterized. The mutant strains are unable to induce normal root hair curling (Hac- phenotype) or nodulation (Nod-phenotype) in clover plants. The LPSs from the parent and mutants are very similar in composition. Analysis by PAGE shows that the LPSs consist of higher and lower molecular weight forms. The higher molecular weight form of the LPSs exists in several aggregation states when PAGE is done in 0.1% SDS but collapses into a single band when PAGE is done in 0.5% SDS. Mild acid hydrolysis of all the LPSs releases two polysaccharides, PS1 and PS2. Immunoblots of the PAGE gels and enzyme linked immunosorbant assay inhibition assays show that the PS1 fractions contain the immunodominant sites of the LPSs and that these sites are present in the higher molecular weight form of the LPSs. All the PS1 fractions contain methylated sugars, 2-amino-2,6-dideoxyhexose, heptose, glucuronic acid, and 2-keto-3-deoxyoctonic acid (KDO). All the PS2 fractions contain galacturonic acid, mannose, galactose, and KDO. The PS2 fractions have a molecular weight of about 700. The KDO is present at the reducing end of both the PS1 and the PS2 fractions. The PS1 and PS2 fractions from the mutants contain more glucose than these fractions from the parent. The LPS from a deletion mutant contains less acyl groups than the other LPSs. Immunoblots of the LPSs show that the parent and nod A mutant LPSs contain an additional antigenic band which is not observed in the other LPSs.

Journal Article↗

Characterization of the lipopolysaccharide from a Rhizobium phaseoli mutant that is defective in infection thread development.

The lipopolysaccharide (LPS) from a Rhizobium phaseoli mutant, CE109, was isolated and compared with that of its wild-type parent, CE3. A previous report has shown that the mutant is defective in infection thread development, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis shows that it has an altered LPS (K. D. Noel, K. A. VandenBosch, and B. Kulpaca, J. Bacteriol. 168:1392-1462, 1986). Mild acid hydrolysis of the CE3 LPS released a polysaccharide and an oligosaccharide, PS1 and PS2, respectively. Mild acid hydrolysis of CE109 LPS released only an oligosaccharide. Chemical and immunochemical analyses showed that CE3-PS1 is the antigenic O chain of this strain and that CE109 LPS does not contain any of the major sugar components of CE3-PS1. CE109 oligosaccharide was identical in composition to CE3-PS2. The lipid A's from both strains were very similar in composition, with only minor quantitative variations. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of CE3 and CE109 LPSs showed that CE3 LPS separated into two bands, LPS I and LPS II, while CE109 had two bands which migrated to positions similar to that of LPS II. Immunoblotting with anti-CE3 antiserum showed that LPS I contains the antigenic O chain of CE3, PS1. Anti-CE109 antiserum interacted strongly with both CE109 LPS bands and CE3 LPS II and interacted weakly with CE3 LPS I. Mild-acid hydrolysis of CE3 LPS I, extracted from the polyacrylamide gel, showed that it contained both PS1 and PS2. The results in this report showed that CE109 LPS consists of only the lipid A core and is missing the antigenic O chain.

Carbohydrates↗

Esophageal carcinoma: modest benefits from combined modality therapy.

Between 1969 and 1986, 109 consecutive patients with esophageal carcinoma were studied. Of the 77 patients who had squamous cell carcinoma, 62 received definitive treatment for disease confined to the esophagus and regional nodes. Survival was equivalent whether they were treated with radiation alone (n = 18), preoperative radiation and esophagectomy (n = 19), postoperative radiation (n = 5), or a combination of chemotherapy and radiation with or without esophagectomy (n = 20). Fifteen patients had significantly poorer survival after palliative irradiation for overt metastatic disease or severe debility. The pathologic specimens from four of the nine patients who underwent resection showed no histologic evidence of residual tumor; however, tumor recurred in three in the mediastinum, and only one remains alive and free of disease. Four of the 11 patients who received chemotherapy and radiation therapy without resection remain alive and free of disease after further mediastinal irradiation, suggesting a benefit from additional regional therapy. Chemotherapy improved median survival duration and complete response rate but did not produce a significant improvement in survival, as reported in other recent series.

Adenocarcinoma↗