Influence of Genetic Variation in the C-Reactive Protein Gene on the Inflammatory Response During and After Acute Coronary Ischemia

The aim of this research was to assess whether common genetic variants within the C-reactive protein gene ( CRP ) are related to the degree of acute rise in plasma C-reactive protein (CRP) levels following an acute coronary syndrome (ACS). While polymorphisms within CRP are associated with basal CRP levels in healthy men and women, less is known about the relationship of such genetic variants and the degree of CRP rise during and after acute ischemia. Plasma CRP is associated with increased rates of recurrent coronary events. We evaluated seven common genetic variants within CRP and assessed their relationship to the degree of rise in CRP levels immediately following an acute coronary syndrome in 1827 European American patients. Variants in the putative promoter region, −757T > C and −286C > T > A, were associated with the highest CRP elevations after ACS. Patients with two copies of the A allele of SNP −286C > T > A had median CRP values of 76.6 mg/L, compared to 11.1 mg/L in patients with no copies of the rare variant (p-value <0.0001), post ACS. The lowest CRP values were found for patients with minor alleles of the exonic 1059G > C and the 3'untranslated region 1846G > A SNPs. For example, patients homozygous for the minor allele of 1059G > C had 71% lower median CRP values than those homozygous for the major allele [3.5 vs 12.0 mg/L, p < 0.0001]. These trends persisted in the chronic stable phase after ischemia had resolved, and after adjustment for infarct size by peak creatinine kinase levels and clinical status by Killip class. Assessment of CRP genetic variants identified patients with higher and lower CRP elevation after acute coronary syndrome.     

Effect of age and diet on cyclic nucleotide concentrations in the intestinal mucosa of developing rats

Mucosa isolated from the proximal third of the small intestine of infant rats had much lower cyclic nucleotide concentrations (expressed both per unit wet weight and per unit DNA content) than those determined in the intestinal wall. The steady-state concentrations of both cyclic AMP and cyclic GMP in jejunum showed dramatic increases during the first 5 d post partum. Another increase in cyclic nucleotide concentrations was observed in the isolated mucosa between d 15 and 21. Starvation for 24 h always resulted in lower intestinal cyclic nucleotide concentrations than those of the fed littermates. This effect was more pronounced in younger animals and more evident for cyclic AMP values. Three-week-old rats fed a high carbohydrate diet for 24-48 h exhibited more pronounced elevations in the concentrations of cyclic nucleotides from the jejunal mucosa than did rats fed a high fat diet.     

Sleep spindles in epilepsy

Spindles are a ubiquitous phenomenon in sleep, but their physiology and the effects of neurologic disorder on their frequency and amplitude are incompletely understood. We compared the incidence of three commonly defined spindle types (14-15 Hz, 12-13 Hz, and 10 Hz) and the frequency and amplitude of spindles during Stage II sleep in 50 patients with complex partial, partial and secondarily generalized, and primary generalized seizures, with and without interictal behavioral symptoms. All patients had 12-13 Hz and 14-15 Hz spindles of symmetric character in C3-A1 and C4-A2 derivations during prolonged sleep-deprived EEG recordings, which were normal except for partial or generalized epileptiform activity. Seventy-one per cent of complex partial seizure patients had 10 Hz spindles, and they occurred in 50% of the other two groups, predominating among those with interictal behavioral symptoms in all groups. Spindle frequency was significantly less in patients with generalized epilepsy than with partial seizures, and patients with complex partial seizures and partial seizures with secondary generalization differed significantly in spindle frequency. Spindle frequency was significantly lower with polypharmacy than with monotherapy. Patients whose regimens included phenobarbital had significantly lower spindle frequencies and spindle frequencies differed significantly between phenytoin and carbamazepine. Differences in spindle frequency may be due to residual medication effects, underlying encephalopathy or physiological differences between partial and generalized epilepsy.     

Effect of educational programs, rigid sharps containers, and universal precautions on reported needlestick injuries in healthcare workers

OBJECTIVE: To evaluate the effect of infection control programs on reported needlestick injuries in a general hospital. DESIGN: Surveillance of all reported needlestick injuries at the University of Cincinnati Hospital was maintained by the infection control department for five years, from 1985 through 1989. Data on individual workers were collected, tabulated on a monthly basis, and reviewed continually to monitor trends in injuries. During this time, the effects of each of three new infection control programs on reported injuries were evaluated sequentially. SETTING: A 700-bed general hospital that serves as the main teaching hospital of the University of Cincinnati. PARTICIPANTS: All employees of University Hospital who reported to personnel health for management of needlestick injuries. INTERVENTIONS: In 1986, an educational program to prevent injuries was initiated and continued throughout the surveillance period. In 1987, rigid sharps disposal containers were placed in all hospital rooms. In 1988, universal precautions were introduced with an intensive inservice. RESULTS: Surveillance identified 1,602 needlestick injuries (320/year) or 104/1,000/year. After the educational program began, reported injuries increased rather than decreased, and this was attributed to increased reporting. Subsequently, after installation of the new disposal containers, reported injuries returned to the levels seen prior to the educational program, but recapping injuries showed a significant decrease from 63/year to 30, or 20/1,000/year to 10. This decrease was observed in nurses but not in other healthcare workers. After universal precautions were instituted, total injuries increased slightly, but recapping injuries remained at 50% of the levels reported prior to the use of rigid sharps disposal containers. CONCLUSIONS: The three infection control programs failed to produce a major reduction in reported needlestick injuries, except for a decrease in recapping injuries associated with the placement of rigid sharps disposal containers in all patient rooms. These observations indicate that new approaches are needed to reduce needlestick injuries.     

Regional extraction of circulating norepinephrine, DOPA, and dihydroxyphenylglycol in humans

Dihydroxyphenylglycol (DHPG) is the main intraneuronal metabolite of the sympathetic neurotransmitter, norepinephrine (NE), and dihydroxyphenylalanine (DOPA) the immediate product of the rate-limiting step in catecholamine biosynthesis. Simultaneous measurements of regional rates of appearance (spillovers) of NE, DOPA, and DHPG in plasma have the potential to provide unique information about aspects of sympathoneural function but have not actually been measured in humans. In the present study, spillovers of DHPG, DOPA, and NE in the heart, head, leg, and lungs, were estimated from regional extraction fractions of infused [3H]-1-NE, DHPG, and [13C6]DOPA or unlabelled DOPA in humans during cardiac catheterization. There was little cardiac extraction of DHPG (7 +/- SEM 2%) or DOPA (8 +/- 4%) but substantial extraction of NE (69 +/- 4%). Values for cardiac spillover of DHPG and DOPA therefore were similar to values for the arteriovenous increment times plasma flow (arteriovenous production rate), whereas the cardiac spillover of NE averaged about 7-times the NE arteriovenous production rate. Cardiac DHPG spillover (28 +/- 3 ng/min) exceeded the spillovers of NE (9 +/- 2 ng/min) and DOPA (15 +/- 4 ng/min). In contrast, cranial DOPA spillover (159 ng/min) exceeded those of NE and DHPG by 8- and 2-fold and accounted for about 1/10 of the total spillover of DOPA into arterial plasma. In the femoral vascular bed, arteriovenous production rates of NE and DHPG were unrelated to femoral spillovers of NE and DHPG. Arterial and regional clearances of [13C6]DOPA were similar to those of unlabelled DOPA. The results suggest that (1) endogenous NE, DOPA, and DHPG all are released into the bloodstream by the heart, head, and limbs of humans; (2) DHPG and DOPA are not co-released with NE; (3) cardiac arteriovenous production rates of DOPA and DHPG can be used to indicate cardiac spillover of these catechols, whereas the cardiac NE arteriovenous production rate substantially underestimates cardiac NE spillover; and (4) estimates of limb spillover of NE and DHPG require concurrent measurements of the corresponding regional clearances.     

New concepts on the pathogenesis of fever

For more than 50 years, experimental studies on fever have focused on a substance from leukocytes called leukocytic or endogenous pyrogen. Various investigators concluded that changes associated with infection--such as numbers of circulating leukocytes; levels of trace metals, amino acids, and hepatic proteins; and altered lymphocyte function--were also caused by endogenous leukocyte mediators. There was reasonable evidence that fever and these other changes were brought about through the action of a single endogenous pyrogen, now known as interleukin 1 (IL-1). Two forms of IL-1 have been cloned (IL-1 beta and IL-1 alpha), and studies of recombinant IL-1 preparations have confirmed that fever and the broad spectrum of host responses to infection and injury are indeed mediated by this substance. However, IL-1 is not the only leukocyte product that induces fever: tumor necrosis factor (cachectin) and interferon produce fever in humans and animals. Accordingly, the concept of a single endogenous pyrogen now requires modification. Nature has conferred the ability to produce fever on no fewer than three structurally distinct molecules. Investigators trying to determine what triggers the hypothalamus to initiate fever in a particular disease must now consider these three endogenous pyrogens, either alone or together, as mediators of fever.     

Management of pressure ulcers.

PURPOSE: Wound healing, the epidemiology and staging of pressure ulcers, and pressure ulcer prevention and treatment are discussed. SUMMARY: The principal event leading to the formation of pressure ulcers appears to be a consistent interruption in blood supply to the skin. Several known risk factors exist and can be attributed to patient-specific variables and wound-specific conditions. Initial management should include removal of the source of pressure, a comprehensive assessment of the patient, and proper staging of the ulcer. Preparation of the wound for treatment is essential and can have a significant impact on healing. While the patient's nutritional status is thought to affect wound healing, only an increased protein content in the diet has been demonstrated to have a benefit. Specialized wound dressings are available for pressure ulcers of all stages and drainage characteristics. With wide variation in cost and in application regimens, a direct cost-effectiveness comparison of commercially available dressing products is difficult. Many of the growth factors commonly present in healing wounds have been synthesized and evaluated as treatments. Although topical platelet-derived growth factor has demonstrated benefit in some studies, its use remains controversial. To date, no topical growth factors carry FDA-approved labeling for use in the treatment of pressure ulcers. Human skin equivalents mark the latest advancement in therapy. Certain species of bacteria have been associated with poorly healing ulcers and may warrant intervention with either local or systemic antibiotic therapy. CONCLUSION: No pharmacologic intervention has been conclusively shown to be effective for pressure ulcers. The cornerstones of therapy remain elimination of the source of pressure or friction and appropriate wound care. usa.     

Coronary bypass surgery early after thrombolytic therapy for acute myocardial infarction

The safety of coronary bypass operations after coronary reperfusion with streptokinase for acute myocardial infarction is not well documented. Therefore we studied 23 consecutive patients (mean age, 59.5 years; 22 men) undergoing bypass operations a median of 5 days (range, 1 to 23 days) after thrombolysis (streptokinase). The control group consisted of 169 concurrent patients of similar mean age (58.8 years) having bypass operations for standard indications. The preoperative angiographic ejection fraction was 68 +/- 14% in the control patients and 61 +/- 14% in the streptokinase group (p less than 0.05). The number of diseased vessels (70% stenosis or greater) averaged 2.6 in control and 2.3 in streptokinase patients. A previous myocardial infarction had occurred in 42% of the controls and all of the streptokinase patients. Aortic cross-clamp times did not differ between the two groups (80 +/- 35 minutes for the controls and 68 +/- 25 minutes for the streptokinase group). Cardiopulmonary bypass times were similar: 108 +/- 45 minutes in the controls versus 109 +/- 28 minutes in the streptokinase group. Grafts per patient averaged 3.7 +/- 1.5 for the controls versus 2.8 +/- 1.1 for the streptokinase patients (p less than 0.01). Difficult operative hemostasis was noted in 4% of both groups. Inotropic support was given postoperatively to 11% of the control and 13% of the streptokinase patients (p = not significant). Measured blood loss during the first 48 hours postoperatively was similar, averaging 809 ml in controls and 776 ml in the streptokinase group. Blood product replacement was also comparable: mean, 713 ml in the control group versus 759 ml in the streptokinase group.(ABSTRACT TRUNCATED AT 250 WORDS)