Prevention of acquired transient defect in platelet plug formation by infused prostacyclin

Cardiopulmonary bypass in baboons produced transient severe platelet dysfunction (bleeding times prolonged to 27.8 +/- 1.4 min compared with 3.9 +/- 0.7 baseline) that was associated with a parallel release of platelet alpha-granule proteins into plasma (platelet factor 4 and beta- thromboglobulin levels of 28.8 +/- 9.3 and 20.0 +/- 1.8 ng/ml, respectively) and their clearance into urine with a reciprocal depletion from circulating platelets. In contrast, platelet-dense granules did not undergo significant release. The bleeding times normalized rapidly following bypass (8.5 +/- 1.4 min at 1 hr). The infusion of prostacyclin (PGI2) into the bubble oxygenator during bypass (40--80 ng/kg/min) prevented the prolongation in bleeding time (p less than 0.01 compared with untreated control values) but did not block the release of alpha-granule proteins. Dosages outside this range were associated with prolonged bleeding times. These results show that transient platelet dysfunction occurring during cardiopulmonary bypass represents activation of platelets independent of alpha or dense granule release and is blocked by potent short-acting inhibition of platelet function using PGI2 infused into the oxygenator apparatus at optimal therapeutic doses.     

Systemic use of non‐biologics in orofacial diseases: 2. Purine synthesis inhibitors

Systemic non‐biological agents (NBAs) have been extensively used for immunosuppression in clinical medicine, often with considerable efficacy, although sometimes accompanied with adverse effects as with all medicines. With the advent of biological agents, all of which currently are restricted to systemic use, there is a rising need to identify which agents have the better therapeutic ratio. The NBAs include a range of agents, most especially the corticosteroids (corticosteroids). This article reviews the purine synthesis inhibitors (azathioprine and mycophenolate), which are currently the most commonly used systemically immunosuppressive agents in the management of orofacial mucocutaneous diseases. Subsequent articles discuss other corticosteroid‐sparing agents used in the management of orofacial disease, such as calcineurin inhibitors, and the cytotoxic and other immunomodulatory agents.     

Pelvic emergency management: the first 24 hours

Pelvic ring injuries are a major cause of morbidity and mortality in the polytrauma patient. Mortality rates from pelvic ring injuries have declined, unrelated to injury severity. This is due to an improved understanding of trauma as a disease, initial and subsequent management options. There are a number of guidelines pertaining to these injuries. These have been brought together to provide an overview of the current guidance on the emergent management of these complex injuries. The foundations of treatment for these injuries includes the following: recognition of the high energy involved, rapid assessment, resuscitation and temporary stabilization of bony and soft tissue injuries. It is important to involve a multidisciplinary team prior to definitive management. By following the guidance set out by this article, the orthopaedic trauma team in the receiving hospital can optimize the patient and prepare them for transfer to the regional major trauma centre. This will improve patient morbidity and mortality and ensure standardization of pelvic trauma management in the first 24 hours.     

Prevalence of caries and salivary levels of mutans streptococci in 5-year-old children in relation to duration of breast feeding

144 children with a known breast feeding history were studied for their caries prevalence and level of salivary mutans streptococci. 19% of the children were exclusively breast-fed for more than 9 months and 38% of the children were weaned after the age of 12 months (max. 34 months). The results of the study showed an equal caries prevalence at the age of 5 among children with a longer or shorter period of exclusive breast-feeding (chi 2 = 3.68, 9 df, NS). Exclusive breast-feeding also did not affect the levels of salivary mutans streptococci (chi 2 = 4.87, 9 df, NS). Children who were weaned late did not differ from those who were weaned early with respect to caries experience (chi 2 = 6.12, 9 df, NS), level of salivary mutans streptococci (chi 2 = 5.49, 9 df, NS) or presence of mutans streptococci (chi 2 = 1.53, 4 df, NS). On the basis of our sample we concluded that breast feeding alone cannot be connected with an increased or lowered caries prevalence.     

Marginal fracture of dental amalgams.

The purpose of this study was to determine the marginal fracture of different amalgams, using a semiclinical method which facilitates standardization and minimizes the observation time, in 10 patients receiving complete dentures. Cavities were cut occlusally in acrylic premolars and molars. The margin was then beveled to 45 degrees with a cone-shaped diamond. Two dispersion-strengthened amalgams and one conventional amalgam were used in each mouth. The cavities of each quadrant were filled with the same amalgam. Thus, conventional amalgam fillings were always placed in opposing quadrants to those filled with a dispersion-strengthened amalgam. The degree of marginal fracture was evaluated from the prints (magnification X 5-7) by five dentists separately and blindly. After 6 months' service, severe marginal fracturing was frequently seen.     

Parent-reported food allergy requiring an avoidance diet in children starting elementary school

Aim: To evaluate the prevalence of parent‐reported food allergies requiring avoidance diet at early school age. Methods: The school health nurses interviewed, by using a structured questionnaire on the required diet at school, the parents of all the 1542 children starting elementary school in a Finnish town with 210 000 inhabitants. Results: An allergy to basic foods was found in 41 (2.7%) children: 1.5% to milk, 1.1% to eggs and 1.0% to grains. An allergy to nuts was present in 3.1% and to fruits and vegetables in 5.8%, both with known cross‐sensitization to pollens. In all, 9.2% of the children reported some allergy. Milk, egg and grain allergies were associated with soy, nut and spice allergies. Conclusion: Over 2% of the 1542 Finnish first‐graders reported allergies to basic foods (milk, eggs or grains) requiring special avoidance diets at school. The figure suggests that avoidance diets started in the first years of life still unnecessarily continued.     

Dose-dependent benefits of quercetin on tumorigenesis in the C3(1)/SV40Tag transgenic mouse model of breast cancer

Breast cancer is the leading cause of cancer related death in women. Quercetin is a flavonol shown to have anti-carcinogenic actions. However, few studies have investigated the dose-dependent effects of quercetin on tumorigenesis and none have used the C3(1)/SV40 Tag breast cancer mouse model. At 4 weeks of age female C3(1)/SV40 Tag mice were randomized to one of four dietary treatments (n = 15–16/group): control (no quercetin), low-dose quercetin (0.02% diet), moderate-dose quercetin (0.2% diet), or high-dose quercetin (2% diet). Tumor number and volume was assessed twice a week and at sacrifice (20 wks). Results showed an inverted ‘U’ dose-dependent effect of dietary quercetin on tumor number and volume; at sacrifice the moderate dose was most efficacious and reduced tumor number 20% and tumor volume 78% compared to control mice (C3-Con: 9.0 ± 0.9; C3-0.2%: 7.3 ± 0.9) and (C3-Con: 2061.8 ± 977.0 mm³; and C3-0.2%: 462.9 ± 75.9 mm³). Tumor volume at sacrifice was also reduced by the moderate dose compared to the high and low doses (C3-2%: 1163.2 ± 305.9 mm³; C3-0.02%: 1401.5 ± 555.6 mm³), as was tumor number (C3-2%: 10.7 ± 1.3 mm³; C3-0.02%: 8.1 ± 1.1 mm³). Gene expression microarray analysis performed on mammary glands from C3-Con and C3-0.2% mice determined that 31 genes were down-regulated and 9 genes were up-regulated more than 2-fold (P < 0.05) by quercetin treatment. We report the novel finding that there is a distinct dose-dependent effect of quercetin on tumor number and volume in a transgenic mouse model of human breast cancer, which is associated with a specific gene expression signature related to quercetin treatment.     

Autonomic cardiac regulation during spontaneous nocturnal hypoglycemia in patients with type 1 diabetes

OBJECTIVE

Experimental clamp studies have suggested that hypoglycemia evokes a reduction of cardiac vagal control in patients with type 1 diabetes. However, there are limited data on the influence of spontaneous nocturnal hypoglycemia on cardiac autonomic regulation.

RESEARCH DESIGN AND METHODS

Adults with type 1 diabetes (n = 37) underwent continuous glucose monitoring via a subcutaneous sensor as well as recording of R-R interval or electrocardiogram for 3 nights. Heart rate (HR) variability was analyzed during periods of hypoglycemia (glucose <3.5 mmol/L) (minimum length of 20 min) and a control nonhypoglycemic period (glucose >3.9 mmol/L) of equal duration and at the same time of night.

RESULTS

The duration of hypoglycemic and control episodes (n = 18) ranged from 20 to 190 min (mean 71 min). HR (62 ± 7 vs. 63 ± 9 beats per min; P = 0.30) or the high-frequency component of HR power spectrum (2,002 ± 1,965 vs. 1,336 ± 1,506 ms²; P = 0.26) did not change during hypoglycemia. Hypoglycemia resulted in a significant decrease in the low-frequency component of HR variability (2,134 ± 1,635 vs. 1,169 ± 1,029 ms², respectively; P = 0.006). The decline in the glucose concentration displayed a significant positive correlation with the decrease of the low-frequency component of HR variability (r = 0.48; P = 0.04). The latter was closely related to an increase in muscle sympathetic nerve activity recorded in 10 subjects during controlled sympathetic activation.

CONCLUSIONS

Spontaneous nocturnal hypoglycemia in patients with type 1 diabetes results in a reduction of the low-frequency component of HR, which is best explained by excessive sympathetic activation without a concomitant withdrawal of vagal outflow.Individuals with type 1 diabetes adhering to strict glycemic control are prone to suffer severe hypoglycemia. Other well-established risk factors for hypoglycemia include a history of severe hypoglycemia and impaired awareness of hypoglycemia (1–3). Despite advanced technology and new insulin analogs, the fear of hypoglycemia is still a major problem complicating the management of diabetes (4,5).Since 1991, when Tattersall and Gill (6) introduced the term “dead in bed syndrome,” the role of hypoglycemia as a factor predisposing young adults to sudden arrhythmic death has been hypothesized (7,8). According to earlier studies, ~2–4% of deaths of type 1 diabetic subjects have been attributed to hypoglycemia (9). However, more recent reports have indicated that as many as 6–10% of deaths in individuals with type 1 diabetes were the result of hypoglycemia (10–12).Heart rate (HR) variability has been used to detect autonomic dysfunction in various clinical settings. A dysfunction of autonomic nervous system has been associated with increased mortality after myocardial infarction (13,14) in patients with diabetes (15,16) and in the general population (17). Nonetheless, very little is known about changes in the parameters of HR variability during hypoglycemia. In our previous clamp study, controlled hypoglycemia resulted in progressive reductions of the high-frequency spectral component and beat-to-beat HR variability (SD1) in patients with type 1 diabetes and their healthy counterparts—evidence of reduced cardiac vagal outflow during hypoglycemia (18). Since symptoms at the time of hypoglycemia induced by clamp technique in the awake state may contribute to autonomic responses, it was decided to assess the effects of spontaneous hypoglycemia on HR variability during sleep in type 1 diabetic subjects.