Forty-six patients with surgical sepsis were studied prospectively until death or survival to evaluate the effect of exogenous metabolic support on the observed plasma substrate levels and on the differential endogenous utilization of branch chain amino acids. There were no effects of administered glucose or colloid load. The administered amino acid load had little effect on substrate levels in patients who died; but significantly effected the observed levels of glycine, isoleucine, and methionine in patients who survived. Evidence is presented which suggests that fatal sepsis is associated with an increased release of endogenous valine and isoleucine into plasma, as well as increased plasma levels of tyrosine, proline, and methionine. These abnormalities are highly correlated with the increased levels of plasma alanine and occur at a time when the nonsurviving septic patient manifests a tendency toward reduced oxygen consumption and abnormal vascular tone relations--the septic B state. These data are consistent with the hypothesis that increased muscle protein catabolism is occurring with a differential utilization of branch chain amino acids and increased use of leucine and isoleucine and reduced use of valine. This autocannibalism of muscle mass appears to be the source of the increased plasma alanine and is little influenced by administered amino acid support in the absence of control of the septic process.
HIV Treatment as Prevention (TasP) initiatives promote antiretroviral therapy (ART) access and optimal adherence (≥95 %) to produce viral suppression among people living with HIV (PLHIV) and prevent the onward transmission of HIV. ART treatment interruptions are common among PLHIV who use drugs and undermine the effectiveness of TasP. Semi-structured interviews were conducted with 39 PLHIV who use drugs who had experienced treatment ART interruptions in a setting with a community-wide TasP initiative (Vancouver, Canada) to examine influences on these outcomes. While study participants attributed ART interruptions to “treatment fatigue,” our analysis revealed individual, social, and structural influences on these events, including: (1) prior adverse ART-related experiences among those with long-term treatment histories; (2) experiences of social isolation; and, (3) breakdowns in the continuity of HIV care following disruptive events (e.g., eviction, incarceration). Findings reconceptualise ‘treatment fatigue’ by focusing attention on its underlying mechanisms, while demonstrating the need for comprehensive structural reforms and targeted interventions to optimize TasP among drug-using PLHIV.
Proliferation of epithelial cells in the fetal trachea was studied in hamsters, beginning on the 10th gestational day and ending on the 16th day, shortly after birth. The mean mitotic index (MI) was highest on day 10, with no statistical confirmation of a change between days 10 and 11. The MI fell to about 2% on days 12 and 13, and declined thereafter to about 0.3% on day 16. The MIs for dorsal and ventral surfaces were compared and values were similar except on day 10, when ventral exceeded dorsal, and on day 12, when dorsal exceeded ventral, 2.56% and 1.3%, respectively. On days 10, 11, and 12 the epithelium was simple, composed of poorly differentiated columnar cells that proliferated. On day 13 the epithelium was pseudostratified owing to the presence of a few short cells that did not reach to the lumen. Throughout the fetal period, proliferation of columnar cells predominated but division of short (basal) cells increased from 8% to 40% of the total mitotic activity between day 13 and day 15. Proliferation of basal cells then declined, so that on day 16, 84% of all cells in mitosis were columnar. If basal cells divide to make more of themselves they must proliferate rapidly between day 13 and day 15, because they were virtually absent on day 12 but accounted for about 36% of the ventral and 23% of the dorsal epithelial cells on day 16. Based on the results, a hypothetical model is proposed for the formation of pseudostratified mucociliary epithelium.(ABSTRACT TRUNCATED AT 250 WORDS)
The development of the tracheal epithelium was studied in hamsters, beginning on fetal day 10 and ending on fetal day 16, shortly after birth. The epithelial morphology was characterized and as soon as the cells could be recognized by type (day 14) their proportions were quantified along dorsal and ventral surfaces from larynx to carina. At all times, columnar cells of the dorsal surface were taller than those of the ventral surface. On days 10 and 11 the simple epithelium was composed of poorly differentiated columnar cells, but on day 12 organoid clusters, consistent with the morphology of neuroepithelial bodies, were observed; four clusters were seen along the dorsal epithelium in one section. The epithelium was pseudostratified on day 13, composed of short and columnar cells. Most columnar cells were poorly differentiated but a few preciliated and ciliated cells were recognizable dorsally, especially at the tracheal poles. Hemidesmosomes were seen at the base of some short cells on day 14, and rough endoplasmic reticulum was moderately developed in some columnar cells, suggesting that these cells were prebasal and presecretory cells, respectively. Preciliated and ciliated cells, which were most prevalent caudally, accounted for about 14% of all dorsal epithelial cells on day 14, but they were rare in the ventral surface, about 0.1%. The epithelial cells were sufficiently specialized by days 15 and 16 to allow quantification by type. Proportions of basal, presecretory, and preciliated-ciliated cells were similar on both days but the cellular makeup of dorsal and ventral surfaces was significantly different. There were more basal cells ventrally (36-40%) than dorsally (22-23%), and more preciliated-ciliated cells dorsally (18-21%) than ventrally (about 1%). On days 15 and 16 differences also existed along both surfaces between cranial and caudal parts of the trachea. Basal cells were more prevalent cranially and preciliated-ciliated cells were more prevalent caudally.
In an environment of resource rationing there are numerous patients who are unable to be admitted to a highdependency unit (HDU) postoperatively despite the belief that this is the optimal discharge destination for them from the recovery room. It is unknown if this is associated with an increase in adverse outcomes. We performed an observational study, over a two-month period, comparing outcomes between patients who were admitted to HDU postoperatively and patients who, although an HDU bed was preferred, were discharged from the recovery room to the general ward due to an unavailability of HDU beds. Our primary outcome variable was hospital length-of-stay. We found an almost twofold increase in hospital length-of-stay in the group of patients admitted to the HDU. ASA IV patients were more likely to be admitted to HDU. However, the increased length-of-stay in the HDU group persisted even after stratifying patients according to ASA status. There was no difference between groups in all other baseline demographic variables, including POSSUM score, which is used as a predictor of postoperative morbidity and mortality. We believe that the most likely explanation for our findings is that the baseline risk between groups is, in fact, subtly different. This is not detected by preoperative scoring systems. However, clinical judgement in the recovery room appears to select a group of patients for HDU admission who subsequently have a slower postoperative recovery, despite no measurable increase in complication rate. That there was no increase in adverse events in the group of patients unable to be admitted to HDU due to a lack of bed availability suggests that current clinical judgement in a resource-rationed environment is functioning adequately, but the study was not powered to detect such a difference.
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