Rheologic predictors of the severity of the painful sickle cell crisis

Deformable sickle erythrocytes have been reported by Mohandas and Evans to be more adherent to vascular endothelium than rigid irreversibly sickled cells (ISC). To define the clinical implications of this finding we have determined genetic, hematological, clinical, and rheological characteristics of sickle erythrocytes obtained from 65 patients with sickle cell anemia and fetal hemoglobin (Hb F) levels less than 15%. The alpha-globin gene number had a significant effect on the hematological parameters, the percentage of dense cells, ISC number, and HB A2 levels. The presence or absence of alpha thalassemia, however, had no effect on the frequency and severity of the sickle cell painful crisis (r = 0.06, P greater than .05). RBC deformability, determined by an ektacytometer, showed great heterogeneity among patients with three or four alpha-globin genes. Linear regression analyses of the data showed significant positive correlation of the frequency and severity of the painful crisis with RBC deformability (r = 0.49, P less than .001), and negative correlations with the percentage of dense cells (r = -0.37, P = .002), and the percentage of ISC (r = -0.46, P less than .001). We propose that the more deformable the sickle RBC are, the greater their adherence to vascular endothelium, and the more they cause vaso-occlusive crises, RBC deformability and the percentage of dense cells (or ISC) seem to have a predictive value of the frequency and severity of painful crises in sickle cell anemia.     

Electrical and contractile consequences of Na+ or Ca2+ gradient reduction in cultured heart cells

The normal electrical and contractile activity of cultured neonatal rat ventricular cells is characterized and compared to activity seen in low [Ca²⁺]₀ and low [Na⁺]₀ solutions. In 0 Ca²⁺/0.5 mm EGTA solutions electrical activity is altered: the maximum diastolic potential (m.d.p.), maximum rate of rise ($\text{+}\text{V}\text{?}{}_{\mathrm{<mtext>max</mtext>}}$), and overshoot (o.s.) are reduced, while duration is increased. Low [Ca²⁺]₀ activity is insensitive to TTX and blocked by La³⁺. In low [Na⁺]₀ solutions electrical activity is generally absent; when present $\text{+}\text{V}\text{?}{}_{\mathrm{<mtext>max</mtext>}}$ and o.s. are decreased while duration is increased. Low [Na⁺]₀ activity is blocked by La³⁺. These data suggest the presence of one La³⁺-sensitive slow inward current channel. The absence of spontaneous electrical activity in low [Na⁺]₀ solutions suggests an inhibition of automaticity. To determine if this inhibition is due to a reduction of the Na⁺ gradient, drugs which raise [Na⁺]_i were examined. Both monensin (a Na⁺ ionophore) and ouabain inhibit the occurrence of spontaneous action potentials (cells respond to stimulation) indicating a dependence of pacemaker activity on a normal Na⁺ gradient. During Na⁺ gradient reduction, asynchronous subcellular contractile activity occurs independent of membrane potential fluctuation. This asynchronous activity is inhibited by La³⁺ or when Ca²⁺₀ is absent, but continues in the presence of verapamil (normal activity is blocked by all three conditions). The Na⁺Ca²⁺ exchange system is unaffected by verapamil but blocked by La³⁺, while both these drugs block the slow inward current. These data indicate that the Na⁺Ca²⁺ exchange system can directly supply Ca²⁺ (independent of electrical activity at the membrane) to intracellular sites that support contractile activity.     

Risk of Second Cancers in Patients with Colorectal Carcinoids

INTRODUCTION: It is often stated that patients with colorectal carcinoid tumors have an increased risk of developing other malignancies. However, this risk has not been conclusively documented. A comprehensive evaluation is needed to more thoroughly assess the risk of second cancers in patients with colorectal carcinoids. METHODS: A search of the National Cancer Institute Surveillance, Epidemiology, and End Result database from 1973 to 1996 revealed 2,086 patients with colorectal carcinoids. This subset of patients was examined for occurrence of second cancers. The observed incidence of cancer for each site was compared with the expected incidence based on the gender-adjusted and age-adjusted cancer rates in the remaining Surveillance, Epidemiology, and End Result file. A Poisson distribution probability was used to determine the significance of these comparisons. RESULTS: Patients with colorectal carcinoids had an increased rate of cancer in the colon and rectum (P < 0.001), small bowel (P < 0.001), esophagus/stomach (P = 0.02), lung/bronchus (P < 0.001), urinary tract (P = 0.005), and prostate (P < 0.001), when compared with a control population. Most of the gastrointestinal tract cancers were synchronous cancers, whereas lesions outside the gastrointestinal tract were most commonly metachronous tumors. CONCLUSIONS: A significantly increased risk of synchronous colorectal, small-bowel, gastric, and esophageal cancers and metachronous lung, prostate, and urinary tract neoplasms is clearly demonstrated. After the diagnosis of colorectal carcinoid tumors, patients should undergo appropriate screening and surveillance for cancer at these sites.     

Hematopoietic stem cell transplantation for severe rheumatoid arthritis

The substantial morbidity and mortality associated with rheumatoid arthritis (RA), while not widely appreciated, provide adequate justification for consideration of high-dose immunoablative therapy followed by hematopoietic stem cell transplantation. While some patients with RA follow a benign course, selected subsets of patients have been identified with 5-year survival rates of 40-70%. A number of factors that can be easily determined serve as useful prognostic indicators for poor outcome. These include the presence of many involved joints (total joint count), the degree of functional disability as measured by the health assessment questionnaire and the presence of rheumatoid factor. This article summarises the present status of hematopoietic stem cell transplantation for rheumatoid arthritis and proposes future directions for research.     

Quantification of experimental myocardial infarction using nuclear magnetic resonance imaging and paramagnetic ion contrast enhancement in excised canine hearts

Determination of myocardial infarct size is important for clinical management of patients with ischemic heart disease and for research on limiting infarct size. Nuclear magnetic resonance (NMR) imaging permits tomographic depiction of the distribution of mobile tissue protons. NMR images have demonstrated high spatial resolution and contrast. To evaluate the potential of this technique in measuring myocardial infarct size, NMR imaging was performed in six canine hearts excised 24 hours after circumflex coronary artery ligation. Before sacrifice, the dogs received i.v. manganous chloride (0.05 mmol/kg). After NMR imaging, the heart were sectioned and the myocardial slices were stained with triphenyl tetrazolium chloride. The pathologically determined infarct size was compared with the infarct size measured by NMR imaging. The correlation was good (regression line slope 1.06; r = 0.94). We conclude that NMR imaging with paramagnetic contrast agents can be used to determine infarct size in excised hearts.