Plateletpheresis in the management of thrombocytosis

Acute thrombotic and hemorrhagic manifestations of thrombocytosis associated with myeloproliferative disorders may be life threatening. Conventional therapy with radioisotopes and/or cytotoxic drugs may require weeks for effective control of platelet counts. In five patients, plateletpheresis by discontinuous-flow (Haemonetics) or continuous-flow (Aminco Celltrifuge) centrifugation was used as a means of reducing platelet counts acutely. With each procedure, approximately 2-9 X 10(12) platelets were removed, resulting in decrements in platelet counts and relief of symptoms. Plateletpheresis is a useful and safe acute means of controlling platelet counts in myeloproliferative disorders.     

Acute small bowel obstruction secondary to intestinal endometriosis,an elusive condition: a case report

Background  

Endometriosis is a benign condition affecting females of reproductive age. Although intestinal endometriosis is common it is rare for the condition to manifest as an acute bowel obstruction secondary to ileocaecal and appendicular endometriosis. This case is important to report as it highlights the diagnostic difficulty this particular condition presents to an emergency surgeon.     

Anti-nociceptive properties of the xanthine oxidase inhibitor allopurinol in mice: role of A1 adenosine receptors

Background and purpose

Allopurinol is a potent inhibitor of the enzyme xanthine oxidase, used primarily in the treatment of hyperuricemia and gout. It is well known that purines exert multiple effects on pain transmission. We hypothesized that the inhibition of xanthine oxidase by allopurinol, thereby reducing purine degradation, could be a valid strategy to enhance purinergic activity. The aim of this study was to investigate the anti-nociceptive profile of allopurinol on chemical and thermal pain models in mice.

Experimental approach

Mice received an intraperitoneal (i.p.) injection of vehicle (Tween 10%) or allopurinol (10–400 mg kg⁻¹). Anti-nociceptive effects were measured with intraplantar capsaicin, intraplantar glutamate, tail-flick or hot-plate tests.

Key results

Allopurinol presented dose-dependent anti-nociceptive effects in all models. The opioid antagonist naloxone did not affect these anti-nociceptive effects. The non-selective adenosine-receptor antagonist caffeine and the selective A₁ adenosine-receptor antagonist, DPCPX, but not the selective A_2A adenosine-receptor antagonist, {"type":"entrez-protein","attrs":{"text":"SCH58261","term_id":"1052882304","term_text":"SCH58261"}}SCH58261, completely prevented allopurinol-induced anti-nociception. No obvious motor deficits were produced by allopurinol, at doses up to 200 mg kg⁻¹. Allopurinol also caused an increase in cerebrospinal fluid levels of purines, including the nucleosides adenosine and guanosine, and decreased cerebrospinal fluid concentration of uric acid.

Conclusions and implications

Allopurinol-induced anti-nociception may be related to adenosine accumulation. Allopurinol is an old and extensively used compound and seems to be well tolerated with no obvious central nervous system toxic effects at high doses. This drug may be useful to treat pain syndromes in humans.     

Paroxysmal disorders in infancy and their risk factors in a population‐based cohort: the Generation R Study

Aim To examine the incidence of paroxysmal epileptic and non‐epileptic disorders and the associated prenatal and perinatal factors that might predict them in the first year of life in a population‐based cohort. Method This study was embedded in the Generation R Study, a population‐based prospective cohort study from early fetal life onwards. Information about the occurrence of paroxysmal events, defined as suddenly occurring episodes with an altered consciousness, altered behaviour, involuntary movements, altered muscle tone, and/or a changed breathing pattern, was collected by questionnaires at the ages of 2, 6, and 12 months. Information on possible prenatal and perinatal determinants was obtained by measurements and questionnaires during pregnancy and after birth. Results Information about paroxysmal events in the first year of life was available in 2860 participants (1410 males, 1450 females). We found an incidence of paroxysmal disorders of 8.9% (n=255) in the first year of life. Of these participants, 17 were diagnosed with febrile seizures and two with epilepsy. Non‐epileptic events included physiological events, apnoeic spells, loss of consciousness by causes other than epileptic seizures or apnoeic spells, parasomnias, and other events. Preterm birth (p<0.001) and low Apgar score at 1 minute (p<0.05) were significantly associated with paroxysmal disorders in the first year of life. Continued maternal smoking during pregnancy and preterm birth were significantly associated with febrile seizures in the first year of life (p<0.05). Interpretation Paroxysmal disorders are frequent in infancy. They are associated with preterm birth and a low Apgar score. Epileptic seizures only form a minority of the paroxysmal events in infancy. In this study, children whose mothers continued smoking during pregnancy had a higher reported incidence of febrile seizures in the first year of life. These findings may generate various hypotheses for further investigations.     

Dedifferentiation of adult monkey Sertoli cells through activation of extracellularly regulated kinase 1/2 induced by heat treatment

Sertoli cells play a key role in triggering and regulating the process of spermatogenesis. Failure of a Sertoli cell to mature functionally will presumably render it incapable of supporting germ cell survival and development that appeared after puberty. Expression of cytokeratin 18 (ck-18) intermediate filaments indicates a state of undifferentiation usually observed in Sertoli cells of prepubertal testis. In this study we demonstrated that local testicular heat treatment of adult monkey with water at 43 C for 30 min once daily for 2 consecutive days was capable of activating reexpression of ck-18 in Sertoli cells, which was coincident with activation of ERK1/2 and Akt kinases. Using primary Sertoli cell culture isolated from adult monkey testis, we further confirmed that the heat treatment of the cells at 43 C could also induce ck-18 reexpression, which was similar to the in vivo treatment. ERK MAPK was also induced by the heat treatment in a time- and protein kinase A (PKA)-dependent manner. After blocking the ERK MAPK signaling pathway, an inhibition of ck-18 expression in the cultured Sertoli cells was observed, and this inhibitory effect was also detected by blocking the PKA activation. However, ck-18 activation in Sertoli cells remained unaltered when the phosphatidylinositol 3-kinase/Akt pathway was blocked. In conclusion, the heat treatment of adult monkey Sertoli cells are capable of inducing a reversible change in the Sertoli cells from an adult differentiated state to an immature-like dedifferentiated state through PKA-ERK MAPK-dependent pathways but not via the phosphatidylinositol 3-kinase/Akt pathway.     

Fetal growth from mid‐ to late pregnancy is associated with infant development: the Generation R Study

Aim The aim of this study was to investigate within a population‐based cohort of 4384 infants (2182 males, 2202 females) whether fetal growth from early pregnancy onwards is related to infant development and whether this potential relationship is independent of postnatal growth. Method Ultrasound measurements were performed in early, mid‐, and late pregnancy. Estimated fetal weight was calculated using head and abdominal circumference and femur length. Infant development was measured with the Minnesota Infant Development Inventory at 12 months (SD 1.1mo, range 10–17mo). Information on postnatal head size and body weight at 7 months was obtained from medical records. Results After adjusting for potential confounders and for postnatal growth, faster fetal weight gain from mid‐ to late pregnancy predicted a reduced risk of delayed social development (odds ratio [OR] 0.82; 95% confidence interval [CI] 0.71–0.95, p=0.008), self‐help abilities (OR 0.84; 95% CI 0.73–0.98, p=0.023), and overall infant development (OR 0.65; 95% CI 0.49–0.87, p=0.003). Similar findings were observed for fetal head growth from mid‐ to late pregnancy. Interpretation Faster fetal growth predicts a lower risk of delayed infant development independent of postnatal growth. These results suggest that reduced fetal growth between mid‐ and late pregnancy may determine subsequent developmental outcomes.     

Economic burden of comorbidities in patients with psoriasis is substantial

Background Psoriasis is frequently associated with comorbidities. Objective To estimate the incremental economic burden associated with comorbidities in patients with psoriasis, accounting for psoriasis severity. Methods Patients continuously enrolled ≥ 6 months after a randomly selected psoriasis diagnosis date were selected from the Ingenix Impact National Managed Care Database (1999–2004). Comorbidities identified during the 6‐month study included: psoriatic arthritis, cardiovascular disease, depression, diabetes, hyperlipidemia, hypertension, obesity, cerebrovascular diseases and peripheral vascular disease. Resource utilization and costs during the 6‐month follow‐up period were compared for patients with ≥ 1 comorbidity vs. those without and for patients with a specific comorbidity vs. those without. Adjusted incidence rate ratios (IRRs) and odds ratios (ORs) were estimated for resource utilization using negative binomial and logistic regression models, respectively. Adjusted incremental costs associated with comorbidities were reported using general linear models with log‐link and gamma distributions or two‐part models. Models controlled for age, sex and psoriasis severity. Results A total of 114 512 patients were included; 51% had ≥ 1 comorbidity. Hyperlipidemia (27%) and hypertension (25%) were most prevalent. Patients with comorbidities were more likely to experience urgent care [OR (95% confidence interval (CI)) = 1.58 (1.51–1.65)] than patients without comorbidities. They also had significantly greater hospitalization rates [IRR (95% CI) = 2.27 (2.13–2.42)] and outpatient visits [IRR (95% CI) = 1.53 (1.52–1.55)]. Compared with patients who did not have comorbidities, patients with comorbidities incurred $2184 (P < 0.001) greater total costs. Conclusion Comorbidities present a significant economic burden in patients with psoriasis.     

Antidiarrhoeal Activity of an Ethanol Extract of the Stem Bark of Piliostigma Reticulatum (Caesalpiniaceae) in Rats

Piliostigma reticulatum (Caesalpiniaceae) is used in Africa as a traditional medicine for the treatment of many diseases, such as malaria, tuberculosis and diarrhoea. We investigated the antidiarrhoeal properties of a crude ethanol extract from the stem bark of Piliostigma reticulatum (EEPR) in Wistar albino rats to substantiate its traditional use and to determine its phytochemical constituents. The antidiarrhoeal activity of the plant extract was evaluated in a castor oil-induced diarrhoea model in rats and compared with loperamide. The effect of the extract on gastrointestinal motility was also determined by the oral administration of charcoal meal and castor oil-induced intestinal fluid accumulation (enteropooling). EEPR showed remarkable dose-dependent antidiarrhoeal activity evidenced by a reduction of defecation frequency and change in consistency. Extracts at 250, 500 and 1000 mg/kg body weight significantly reduced diarrhoeal faeces. EEPR also significantly inhibited gastrointestinal motility and castor oil-induced enteropooling at 500 and 1000 mg/kg, similar to the inhibition obtained in control rats treated by atropine. Phytochemical screening revealed the presence of tannins, flavonoids, polyphenols and reducing sugars in the stem bark of P. reticulatum. No mortality or visible signs of general weakness were observed in the rats following administration of the crude extract in doses up to 6000 mg/kg body weight in an acute toxicity study. Our results show that the stem bark of P. reticulatum possesses antidiarrhoeal activity and strongly suggest that its use in traditional medicine practice could be justified.