No abstract

The OEIS complex comprises a combination of defects including omphalocele, exstrophy of the cloaca, imperforate anus, and spinal defects. It may represent the most severe manifestation of a spectrum of birth defects, the exstrophyepispadias sequence. The OEIS complex affects 1 in 200 000 to 400 000 pregnancies and is of unknown cause. The purpose of the current report is to document the occurrence of OEIS in sibs from separate pregnancies and suggest that some cases may have a genetic basis.

Although ischaemic stroke is associated with accentuated platelet function, it remains unclear whether this applies to all sub-types, especially lacunar infarcts, which differ from cortical infarction in their patho-aetiology. Similarly, conflicting evidence suggests that haemorrhagic stroke may, or may not, be associated with a hypothrombotic state. Levels of von Willebrand factor (vWF), fibrinogen, and P-selectin were measured within 48 h of ictus in 163 patients with acute ischaemic stroke and 40 patients with acute primary intracerebral haemorrhage, and 33 age, gender and race matched-controls. vW F (IU/dl) was significantly increased in both cortical and lacunar ischaemic stroke, and haemorrhagic stroke, as compared with controls, median (semiquartile range): 158 (25) vs 144 (19) vs 147 (24) vs 114 (16), respectively. Similarly, fibrinogen (g/litre) was increased: 4.80 (0.90) vs 4.65 (0.70) vs 4.35 (0.83) vs 3.70 (0.70). In contrast, soluble P-selectin (ng/ml) was increased in cortical stroke as compared with lacunar infraction patients or controls: 408 (101) vs 300 (108) vs 324 (121), respectively; P-selectin was not increased in haemorrhagic stroke, 360 (153). Both vW F and fibrinogen correlated with 3-month functional outcome (modified Rankin score): r = 0.371 (2 P = 0.0006), and r = 0.195 (2 P = 0.042), respectively; however, P-selectin was not associated with outcome: r = 0.188 (2 P = 0.084). The results suggest that increases in vW F and fibrinogen in all types of stroke reflect an acute phase response; in contrast, increased soluble P-selectin levels in cortical stroke, but not lacunar infarction, suggest that platelets contribute to the patho-aetiology of some subtypes of ischaemic stroke.

Acinetobacter baumannii is emerging with resistance to polymyxins. In 24-h time-kill experiments, high-dose ampicillin-sulbactam in combination with meropenem and polymyxin B achieved additivity or synergy against 10 8 CFU/ml of two clinical A. baumannii isolates resistant to all three drugs (maximum reductions, 1.6 and 3.1 logs). In a 14-day hollow-fiber infection model, high-dose ampicillinsulbactam (8/4 g every 8 h, respectively) in combination with meropenem (2 g every 8 h) and polymyxin B (1.43 mg/kg of body weight every 12 h with loading dose) resulted in rapid (96 h) eradication of A. baumannii. KEYWORDS Acinetobacter, antibiotic resistance, antimicrobial combinations, meropenem, polymyxins, sulbactam, synergism A cinetobacter baumannii is a troubling nosocomial pathogen with an exceptional propensity for acquiring resistance mechanisms against commonly used antimicrobials (1). Although carbapenems have traditionally been the drug of choice for treating A. baumannii infection, enzyme-mediated hydrolysis of carbapenems has forced clinicians to utilize polymyxins as a drug of last resort against extensively drug-resistant A. baumannii (2, 3). Unfortunately, the emergence of A. baumannii strains resistant to polymyxins has prompted the search for novel dosing schemes and combination regimens that overcome such extreme levels of drug resistance (4-6).One proposed strategy for combating drug resistance in A. baumannii is the use of high-dose ampicillin-sulbactam regimens that have been evaluated in exploratory clinical studies (7,8). The combination of ampicillin-sulbactam with a carbapenem and a polymyxin has also demonstrated a promising mortality benefit against colistinresistant A. baumannii (9); however, the pharmacodynamics of high-dose ampicillinsulbactam alone and in combination with other agents has yet to be fully defined. In the present study, time-kill experiments were utilized to investigate the level of killing by high-dose ampicillin-sulbactam, meropenem, and polymyxin B alone and in double/ triple combinations against A. baumannii resistant to each of these antibiotics based on MIC testing. A hollow-fiber infection model (HFIM) was subsequently used to fully define the time course of A. baumannii killing over 14 days.

Platelets are anucleate cells with little or no capacity for de novo protein synthesis. Their potential haemostatic reactivity is established at or before thrombopoiesis by their precursor cell, the bone marrow megakaryocyte. In some pathologic conditions, the megakaryocyte-platelet-haemostatic axis (MPHA) becomes perturbed, resulting in the formation of hyperfunctional platelets which may contribute to the development of vascular disease or an acute thrombotic event such as ischaemic stroke or myocardial infarction. Laboratory measurements of platelet function have established that platelet reactivity is accentuated in acute ischaemic stroke, particularly following cortical rather than lacunar infarction. Whether accentuated platelet function is a cause or a consequence of stroke is not yet clear, but it is likely that patients with certain risk factor profiles have some degree of platelet activation preceding the stroke. Further work into the MPHA is required to establish whether enhanced post-stroke platelet reactivity can be referred to the megakaryocyte. The antiplatelet agents tested to date are effective in secondary but not primary prevention of stroke. This probably reflects the diverse pathophysiology of stroke: accentuated platelet function is only likely to be a significant factor in cortical stroke.