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Transcatheter pulmonary valve replacement (tPVR) is an accepted therapy for treatment of dysfunctional right ventricular outflow tract (RVOT) conduits. At present, the majority of Fallot patients who undergo transannular patch (TAP) repair are not candidates for tPVR due to the large irregular nature of their RVOT. Herein, we describe a novel approach to assessing the RVOT in this group, which may then be used to design, test, and carry out hybrid RVOT modification and transcatheter valve implantation in this population.A retrospective analysis of TAP patients who underwent 3D modeling of the RVOT which was then used to develop individualized hybrid procedures designed to modify the RVOT, thereby rendering patients suitable for transcatheter valve implantation.Eight consecutive patients underwent 3D RVOT modeling followed by hybrid implantation of a transcatheter valve via a perventricular approach. A landing zone stent was placed in all and four required additional intravascular geometric remodeling of the RVOT prior to valve implant. Transcatheter valves were successfully implanted in all. There were no instances of valve malposition, embolization, or death. There was one minor procedural complication. No patient had more than trivial pulmonary regurgitation at follow-up.Using a hybrid approach to remodel the RVOT in TAP patients supported by preprocedural 3D-model planning allows for successful tPVR implantation in this population. A larger cohort and longer follow-up will be needed to determine the ultimate utility of this approach.

Background. Few studies have evaluated the prevalence of severe hyperkalaemia in unselected\ud patient populations.We identified all episodes of severe hyperkalaemia occurring in 1 year, and described\ud patient demographics, clinical response and outcome. We also assessed junior doctor\ud knowledge of its causes and significance.\ud Materials and methods. A retrospective interrogation of the database of the regional biochemical\ud laboratory identified all episodes of severe hyperkalaemia (K ≥ 6.5 mmol/L) occurring in 2011. The\ud understanding of trainee doctors of the importance, causes and treatment of severe hyperkalaemia\ud was assessed by structured questionnaire.\ud Results. Severe hyperkalaemia was recorded in 433 samples (365 patients) giving a prevalence of\ud 0.11%. Thirty-six per cent of episodes occurred in patients under the care of a nephrologist, who\ud were significantly younger than those not under the care of a nephrologist. In the nephrology\ud cohort, 86% occurred in patients with chronic kidney disease (CKD), the majority of which had CKD\ud Stage 5. In the non-nephrology cohort, only 65% occurred in the context of CKD, which was\ud equally distributed between Stages 3 and 5 CKD. In both patient groups, roughly 50% of episodes\ud occurred in association with acute kidney injury (AKI). Acute mortality (death within 48 h of documented\ud severe hyperkalaemia) was higher in the non-nephrology compared with the nephrology\ud cohort. Time to repeat serum potassium was influenced by the clinical setting with shorter time to\ud repeat for acute care compared with ward settings. Assessment of trainee doctor’s knowledge\ud suggested significant deficiencies in relation to severe hyperkalaemia.\ud Conclusions. The prevalence of severe hyperkalaemia was low and occurred predominantly in the\ud context of CKD and/or AKI. The majority of episodes occurred in patients not under the care of a\ud nephrologist. Variability in time to repeat serum potassium levels suggested deficiencies in care,\ud and assessment of trainee doctor’s knowledge suggests the need for further educational initiatives\ud to highlight its importance.

A combination of toxicity tests, chemical analyses, and Toxicity Identification Evaluations (TIEs) were used to investigate receiving water toxicity in the Calleguas Creek watershed of southern California. Studies were conducted from 1995 through 1999 at various sites to investigate causes of temporal variability of toxicity throughout this system. Causes of receiving water toxicity varied by site and species tested. Investigations in the lower watershed (Revolon Slough, Santa Clara Drain, Beardsley Wash) indicated that toxicity of samples to the cladoceran Ceriodaphnia dubia was due to elevated concentrations of the organophosphate pesticide chlorpyrifos, while causes of intermittent toxicity to fathead minnows (Pimephales promelas) and the alga Selanastrum capricornutum were less clear. Investigations at sites in the middle and upper reaches of the watershed (Arroyo Simi and Conejo Creek) indicated that the pesticide diazinon was the probable cause of receiving water toxicity to Ceriodaphnia. Elevated ammonia was the cause of toxicity to fathead minnows in the upper watershed sites. Results of these and previous studies suggest that biota are impacted by degraded stream quality from a variety of point and non-point pollution sources in the Calleguas Creek watershed. Water quality resource manager's efforts to identify contaminant inputs and implement source control will be improved with the findings of this study.

Mean sediment quality guideline quotients (mean SQGQs) were developed to represent the presence of chemical mixtures in sediments and are derived by normalizing a suite of chemicals to their respective numerical sediment quality guidelines (SQGs). Mean SQGQs incorporate the number of SQGs exceeded and the degree to which they are exceeded and are used for comparison with observed biological effects in the laboratory or field. The current research makes it clear, however, that the number and type of SQGs used in the derivation of these mean quotients can influence the ability of mean SQGQ values to correctly predict acute toxicity to marine amphipods in laboratory toxicity tests. To determine the optimal predictive ability of mean SQGQs, a total of 18 different chemical combinations were developed and compared. The ability of each set of mean SQGQs to correctly predict the presence and absence of acute toxicity to amphipods was determined using three independent databases (n = 605, 2753, 226). Calculated mean SQGQ values for all chemical combinations ranged from 0.002 to 100. The mean SQGQ that was most predictive of acute toxicity to amphipods is calculated as SQGQ1 = ((sigma ([cadmium]/4.21 )([copper]/270)([lead]/ 12.18)([silver]/1.77)([zinc]/ 410)([total chlordane]/6)([dieldrin]/8)([total PAHoc]/1,800)([total PCB]/400))/9). Both the incidence and magnitude of acute toxicity to amphipods increased with increasing SQGQI values. To provide better comparability between regions and national surveys, SQGQ1 is recommended to serve as the standard method for combination of chemicals and respective SQGs when calculating mean SQGQs.

Sediment quality was assessed in San Francisco Bay, California, USA, using a two-tiered approach in which 111 sites were initially screened for sediment toxicity. Sites exhibiting toxicity were then resampled and analyzed for chemical contamination, recurrent toxicity, and, in some cases, benthic community impacts. Resulting data were compared with newly derived threshold values for each of the metrics in a triad-based weight-of-evidence evaluation. Sediment toxicity test results were compared with tolerance limits derived from reference site data, benthic community data were compared with threshold values for a relative benthic index based on the presence and abundance of pollution-tolerant and -sensitive taxa, and concentrations of chemicals and chemical mixtures were compared with sediment quality guideline-based thresholds. A total of 57 sites exceeded threshold values for at least one metric, and each site was categorized based on triad inferences. Nine sites were found to exhibit recurrent sediment toxicity associated with elevated contaminant concentrations, conditions that met program criteria for regulatory attention. Benthic community impacts were also observed at three of these sites, providing triad evidence of pollution-induced degradation. Multi- and univariate correlations indicated that chemical mixtures, heavy metals, chlordanes, and other organic compounds were associated with measured biological impacts in the Bay. Toxicity identification evaluations indicated that metals were responsible for pore-water toxicity to sea urchin larvae at two sites. Gradient studies indicated that the toxicity tests and benthic community metrics employed in the study predictably tracked concentrations of chemical mixtures in Bay sediments.

A number of methods have been employed to determine the statistical significance of sediment toxicity test results. To allow consistency among comparisons, regardless of among-replicate variability, a protocol-specific approach has been used that considers protocol performance over a large number of comparisons. Ninetieth-percentile minimum significant difference (MSD) values were calculated to determine a critical threshold for statistically significant sample toxicity. Significant toxicity threshold values (as a percentage of laboratory control values) are presented for six species and nine endpoints based on data from as many as 720 stations. These threshold values are useful for interpreting sediment toxicity data from large studies and in eliminating cases where statistical significance is assigned in individual cases because among-replicate variability is small.

Sediment quality in the Los Angeles and Long Beach Harbor area of southern California, USA, was assessed from 1992 to 1997 as part of the California State Water Resources Control Board's Bay Protection and Toxic Cleanup Program and the National Oceanic and Atmospheric Administration's National Status and Trends Program. The assessment strategy relied on application of various components of the sediment quality triad, combined with bioaccumulation measures, in a weight-of-evidence approach to sediment quality investigations. Results of bulk-phase chemical measurements, solid-phase amphipod toxicity tests, pore-water toxicity tests with invertebrate embryos, benthic community analyses (presented as a relative benthic index), and bioaccumulation measures indicated that inner harbor areas of this system are polluted by high concentrations of a mixture of sediment-associated contaminants and that this pollution is highly correlated with toxicity in laboratory experiments and degradation of benthic community structure. While 29% of sediment samples from this system were toxic to amphipods (Rhepoxynius abronius or Eohaustorius estuarius), 79% were toxic to abalone embryos (Haliotis rufescens) exposed to 100% pore-water concentrations. Statistical analyses indicated that amphipod survival in laboratory toxicity tests was significantly correlated with the number of crustacean species and the total number of species measured in the benthos at these stations. Triad measures were incorporated into a decision matrix designed to classify stations based on degree of sediment pollution, toxicity, benthic community degradation, and, where applicable, tissue concentrations in laboratory-exposed bivalves and feral fish.

Summary The incidence of sudden infant death syndrome or cot death has decreased by 60 to 70% in the last 10 years. The largest decrease has been following the Back to sleep campaign in 1991. The epidemiology of cot death now emphasises its association with poverty and smoking in the home. The compassionate reception of the ‘cot death’ baby and his family in the Accident and Emergency department is the first step in enabling families to come to terms with the grief that the death produces. Accident and Emergency staff can facilitate the early grieving process by an understanding of the family’s needs and the provision of appropriate information.

The effects of acute and repeated increasing oral doses of 1-methyl-3-keto-4-phenylquinuclidinium bromide (MA540) and guanethidine in the rat and dog have been described. On repeated oral administration guanethidine produced histopathological changes in cervical ganglia of rats and dogs which were clearly dose-dependent and reproduced lesions reported in the literature. Repeated oral administration of MA540 resulted in no histopathological changes in either species. The maximum tolerated oral dose for guanethidine was estimated to be 515 mg/kg in the rat and 26 mg/kg in the dog compared with an estimated maximum tolerated oral dose for MA540 of 1750 mg/kg in the rat and 460 mg/kg in the dog. On the basis of these findings it is suggested that subchronic studies with MA540 in the rat and dog should provide evidence which would justify the use of MA540 in man at daily oral doses as high as 9 mg/kg.

In recent years the use of the oral contraceptive preparations has provoked a considerable amount of discussion in the medical literature along with a vigorous reaction in the lay Press. Various side effects have been described and these have been in the main attributed to the oestrogen content of these preparations and, in particular, an increase in the incidence of venous and arterial thromboembolism in women taking oral contraceptives. (Inman, Vessey, Westerholm and Engelund, 1970; A Statement by the Committee on Safety of Drugs, 1970.) As a result of these findings the low oestrogen dosage is now being used as theincidence of serious thromboembolic phenomena is thereby significantly reduced. In addition to occlusive vascular lesions, there are numerous other complications, which in many instances require withdrawal of the drug, (Grant, 1968) and mood changes (Grant and Pryse-Davies, 1968) being two of the commoner troublesome features.

Two cases of anticonvulsant megaloblastic anaemia are described, showing features of unusual interest. Though both cases were apparently deficient in folic acid, the Figlu tests were negative. One patient had an extremely low serum B 12 concentration apparently associated with defective B 12 absorption due to deficiency of intrinsic factor, and both showed impaired intestinal absorption of D-xylose. There was, however, no evidence of permanent gastro-intestinal dysfunction, and the absorptive defects disappeared completely after treatment with folic acid. Possible reasons for the findings are discussed. It is suggested that absorptive defects produced by the drugs may play some part in initiating anticonvulsant megaloblastic anaemia, and that once deficiencies of haemopoietic factors are established, a vicious circle may be set up owing to the effects of these deficiencies on the gastro-intestinal tract.

A 2 1/2-year-old girl recently arrived from eastern Nigeria presented with a soft tissue swelling of the infraclavicular region. Subsequent investigation revealed a cavity in the left lung associated with a small pleural effusion and leucocytosis with pronounced eosinophilia. Clinical and serological findings were compatible with the diagnosis of paragonimiasis. After a course of Bitin-S the chest x-ray returned to normal, the soft tissue changes disappeared, and the eosinophil count fell.