A lectin horseradish peroxidase study of the origin of ascending fibers in the medial forebrain bundle of the rat. The lower brainstem

The origins of projections within the medial forebrain bundle from the lower brainstem were examined with the horseradish peroxidase technique. Labeled cells were found in at least 15 lower brainstem nuclei following injections of a conjugate or horseradish peroxidase and wheat germ agglutinin at various levels of the medial forebrain bundle. Dense labeling was observed in the following cell groups (from caudal to rostral): A1 (above the lateral reticular nucleus); A2 (mainly within the nucleus of the solitary tract); a distinct group of cell trailing ventrolaterally from the medial longitudinal fasciculus at the level of the rostral pole of the inferior olive; raphe magnus; nucleus incertus; dorsolateral tegmental nucleus (of Castaldi); locus coeruleus; nucleus subcoeruleus; caudal part of the dorsal (lateral) parabrachial nucleus; and raphe pontis. Distinct but light labeling was seen in raphe pallidus and obscurus, nucleus prepositus hypoglossi, nucleus gigantocellularis pars ventralis, and the ventral (medial) parabrachial nucleus. Sparse labeling was observed throughout the medullary and caudal pontine reticular formation. Several lower brainstem nuclei were found to send strong projections along the medial forebrain bundle to very anterior levels of the forebrain. They were: A1, A2, raphe magnus (rostral part), nucleus incertus, dorsolateral tegmental nucleus, raphe pontis and locus coeruleus. With the exception of the locus coeruleus, attention has only recently been directed to the ascending projections of most of the nuclei mentioned above. Evidence was reviewed indicating that fibers from lower brainstem nuclei with ascending medial forebrain bundle projections distribute to widespread regions of the forebrain.It is concluded from the present findings that several medullary cell groups are capable of exerting a direct effect on the forebrain and that the medial forebrain bundle is the major ascending link between the lower brainstem and the forebrain.     

Excretion of porphyrins and porphyrin precursors during neuromuscular paralysis produced by dithiobiuret

Urinary excretion of porphyrin precursors delta-aminolevulinic acid (ALA) and porphobilinogen (PBG) and total porphyrins was measured during intoxication of rats with 2,4-dithiobiuret (DTB), a chemical which produces delayed-onset neuromuscular weakness, in an attempt to ascertain whether or not DTB poisoning in the rat would serve as an animal model of the neurologic symptoms of acute intermittent porphyria. Daily administration of DTB (1 mg/kg/day, i.p.) produced flaccid skeletal muscle weakness first detected after 4 to 5 days of treatment. Onset of skeletal muscle weakness was associated with a significant increase in urinary excretion of ALA. The excretion of PBG and total porphyrin was also increased; however, the increase was not significant. The increase in porphyrins and porphyrin precursors was due to increased urine output which coincided with the onset of neuromuscular weakness; urinary concentrations of ALA, PBG, and porphyrins were not increased by DTB. Measurements of free-erythrocyte protoporphyrin, taken after 7 days of DTB treatment, indicated a significant elevation of free erythrocyte protoporphyrin concentration. The pattern of alterations in the heme precursors associated with DTB-induced paralysis in rats is quite different from that observed in humans afflicted with acute intermittent porphyria. Therefore, we conclude that DTB-induced paralysis in the rat does not represent an accurate animal model of acute intermittent porphyria.     

An electrocardiogram technician improves in-hospital first medical contact-to-electrocardiogram times: a cluster randomized controlled interventional trial

Background

In the case of chest pain, the current guidelines require electrocardiogram (ECG) recording and patient assessment within 10 minutes upon arrival in the emergency department.

Methods

We investigated the effect of an ECG technician (ECG-T) on in-hospital first medical contact-to-ECG times (iFMC-to-ECG) investigated in a cluster randomized, controlled trial. Allocation of intervention was concealed. Staff satisfaction and feasibility was defined as a secondary outcome. Delays between ECG and the availability of an emergency physician and the assessment of ECG were additionally evaluated.

Results

A total of 163 (44 clusters) and 191 (47 clusters) patients were allocated to control and intervention, respectively. Twenty-seven (17%) of 163 patients in the control group vs 110 (58%) of 191 patients in the intervention group received ECG registration within 10 minutes (risk ratio, 3.40 [2.24-5.15]; P < .001). The iFMC-to-ECG time was 23 (95% confidence interval [CI], 20-27) minutes for the control group vs 9 (95% CI, 8-11) minutes for the intervention group (P < .001). Nursing staff judged the feasibility of intervention with a median of 1 (interquartile range [IQR], 1-1 (on a scale of 1 [best] to 5 [worst]), perceived workload alleviation with a median of 1 (IQR, 1-1), and improvement of quality of care with a median of 1 (IQR, 1-2). The ECG-to-EP time was 78 (95% CI, 64-92) seconds, and diagnosis was made within 17 (95% CI, 16-18) seconds.

Conclusions

Delays of iFMC-to-ECG can be effectively addressed by implementation of an ECG-T. The service of an ECG-T is feasible and improves staff satisfaction. Both ECG-to-EP time and ECG assessment constitute no relevant delay.     

Prolonged door-to-balloon time: is treatment delayed always treatment denied?

Rapid reperfusion following the onset of ST-segment elevation myocardial infarction has been shown to provide life-saving benefit. Both systemic fibrinolytic therapy and percutaneous coronary intervention have been shown to be effective in reducing mortality, and their effectiveness is greater the sooner they are applied. Percutaneous coronary intervention has become the dominant method of reperfusion and may offer benefit over systemic fibrinolysis in some patients. Accordingly, physicians, hospitals, and professional organizations have developed guidelines and algorithms to both speed and standardize care. In addition, the institutional rapidity of therapy—the mean or median door-to-balloon time—is often publically reported providing further impetus to rapid triage and treatment of ST-segment elevation myocardial infarction. However, some patients do not receive reperfusion within the time guidelines set out by professional organizations. In many instances, this delay relates to medical issues that exist in addition to the patient's myocardial infarction. These data raise the question of whether the most rapid reperfusion is always superior to more delayed but potentially more comprehensive therapy.