Preceding Control Period Research Articles

Impacts of medication adherence and home healthcare on the associations between polypharmacy and the risk of severe hypoglycemia among elderly diabetic patients in Taiwan from 2002 to 2012: A nationwide case-crossover study

AimTo assess how medication adherence and home healthcare support influence the role of polypharmacy in induced hypoglycemia events among elderly diabetic patients. MethodsThis case-crossover study retrieved records on diabetic patients >=65 years with severe hypoglycemia from 2002 to 2012 in Taiwan. Case period defined as 1–3 days before severe hypoglycemia was compared with a preceding control period of the same length, with an all-washout period of 30 days. Moreover, the modifiable effects of medication adherence and home healthcare service use were evaluated by stratified analysis. ResultsTotally 2,237 patients were identified. Polypharmacy use was associated with the risk of severe hypoglycemia. Patients receiving polypharmacy without home healthcare services (aOR: 1.34; 95 % CI: 1.16–1.54) and those with poor adherence to anti-diabetic medications (aOR: 1.48; 95 % CI: 1.24–1.77) were significantly associated with an elevated risk of severe hypoglycemia. In patients with good adherence, non-home healthcare users being prescribed with polypharmacy had a higher risk of severe hypoglycemia. In the group that received home healthcare services, patients with poor adherence using polypharmacy had a higher risk of severe hypoglycemia. ConclusionsGood adherence and receiving home healthcare services were associated with a decreased odds of severe hypoglycemic events in elderly diabetic patients, regardless of the fact whether they were prescribed with polypharmacy.

Estimating Patient Satisfaction Through a Language Processing Model: Model Development and Evaluation.

Measuring patient satisfaction is a crucial aspect of medical care. Advanced natural language processing (NLP) techniques enable the extraction and analysis of high-level insights from textual data; nonetheless, data obtained from patients are often limited. This study aimed to create a model that quantifies patient satisfaction based on diverse patient-written textual data. We constructed a neural network-based NLP model for this cross-sectional study using the textual content from disease blogs written in Japanese on the Internet between 1994 and 2020. We extracted approximately 20 million sentences from 56,357 patient-authored disease blogs and constructed a model to predict the patient satisfaction index (PSI) using a regression approach. After evaluating the model's effectiveness, PSI was predicted before and after cancer notification to examine the emotional impact of cancer diagnoses on 48 patients with breast cancer. We assessed the correlation between the predicted and actual PSI values, labeled by humans, using the test set of 169 sentences. The model successfully quantified patient satisfaction by detecting nuances in sentences with excellent effectiveness (Spearman correlation coefficient [ρ]=0.832; root-mean-squared error [RMSE]=0.166; P<.001). Furthermore, the PSI was significantly lower in the cancer notification period than in the preceding control period (-0.057 and -0.012, respectively; 2-tailed t47=5.392, P<.001), indicating that the model quantifies the psychological and emotional changes associated with the cancer diagnosis notification. Our model demonstrates the ability to quantify patient dissatisfaction and identify significant emotional changes during the disease course. This approach may also help detect issues in routine medical practice.

Judicious ending of isolation based on reverse transcription–polymerase chain reaction (RT-PCR) cycle threshold only for patients with coronavirus disease 2019 (COVID-19) requiring in-hospital therapy for longer than 20 days after symptom onset

BackgroundFor patients with coronavirus disease 2019 (COVID-19) requiring hospitalization, extending isolation is warranted. As a cautious protocol, ending isolation based on polymerase chain reaction cycle threshold (Ct) value was introduced for patients requiring therapy for >20 days after symptom onset. MethodWe compared a Ct-based strategy using Smart Gene® between March 2022 and January 2023 with a preceding control period (March 2021 to February 2022) when two consecutive negative reverse transcription–polymerase chain reaction tests using FilmArray® were required for ending isolation. Ct was evaluated on day 21, and ending isolation was permitted in patients with Ct ≥ 38. Although patients with Ct 35–37 were transferred to a non-COVID-19 ward, isolation was continued. ResultsThe duration of stay on a COVID-19 ward in the Ct group was 9.7 days shorter than that in controls. The cumulative number of tests was 3.7 in controls and 1.2 in the Ct group. There was no nosocomial transmission after ending isolation in either group. The number of days from symptom onset to testing was 20.7 ± 2.1 in Ct group, and five patients had Ct < 35, nine Ct 35–37, and 71 Ct ≥ 38. No patients were moderately or severely immunocompromised. Steroid use was an independent risk factor for prolonged low Ct (odds ratio 9.40, 95% confidence interval 2.31–38.15, p = 0.002) ConclusionsThe efficacy of ending isolation based on Ct values could improve bed utilization without the risk of transmission among patients with COVID-19 requiring therapy for >20 days after symptom onset.

COVID-19 PANDEMIC INDUCED DISRUPTIONS IN TROPONIN AND LOW-DENSITY LIPOPROTEIN CHOLESTEROL LABORATORY TEST VOLUMES ACROSS ALBERTA

BACKGROUNDAtherosclerotic cardiovascular disease (ASCVD) is a leading cause of morbidity and mortality in Canada and worldwide. Laboratory tests, including troponin and low-density lipoprotein cholesterol (LDL-C), are important biomarkers of ASCVD risk. The objective of this study was to investigate patterns of testing for troponin and LDL-C test volumes among Alberta residents during the coronavirus disease 2019 (COVID-19) pandemic.METHODS AND RESULTSA repeated cross-sectional study design captured population-level laboratory test volumes between March 15, 2019 and December 14, 2020. Three-month cross-sections were derived to report laboratory test volumes by different COVID-19 restriction periods during 2020-2021 and using 2019-2020 as a preceding control period. Percent change for troponin and LDL-C test volumes were calculated for both control and COVID-19 periods among adult (≥18 years of age) Alberta residents, and stratified by age (18-49, 50-65, 66-79, and ≥80 years), sex, and geographic zones (urban, rural). This preliminary data is part of an ongoing study for which further troponin and LDL-C test volumes will be available up until March 14, 2021 (representing one year of data throughout the COVID-19 pandemic). Among the Alberta population, 292,836 troponin and 794,789 LDL-C tests were captured between March 15, 2020 and December 14, 2020 (Figure 1). Testing patterns during the COVID-19 restriction period showed marked reduction in test volumes from the previous year. The initial cross-section of the COVID-19 period (March-June 2020) was characterized by the largest overall reduction with troponin test volumes decreasing 18% and LDL-C test volumes decreasing 63%, compared to the year prior. As restrictions eased in the summer months of 2020, testing volumes rebounded to near pre-pandemic volumes for both tests. However, in the fall of 2020, troponin tests decreased again (-15%). Within these drops in utilization, slightly larger relative declines were observed for troponin test volumes in women (-20%) and patients ≥80 years-old (-25%) and for LDL-C test volumes among urban residents (-64%), women (-67%) and patients aged 18-49 (-66%) and 50-65 (-65%) years (Table 1).CONCLUSIONThis study describes declines in troponin and LDL-C test volumes in the initial and second COVID-19 lockdown periods. Women had overall smaller total troponin and LDL-C test volumes and larger relative declines during the pandemic compared to men. The decrease in these ASCVD-related laboratory test volumes during the pandemic may have been accompanied by other important changes in indicators of healthcare utilization and associated clinical outcomes. Ongoing analyses will further explore the impact of the pandemic.

Low-frequency sound exposure causes reversible long-term changes of cochlear transfer characteristics

Intense, low-frequency sound presented to the mammalian cochlea induces temporary changes of cochlear sensitivity, for which the term ‘Bounce’ phenomenon has been coined. Typical manifestations are slow oscillations of hearing thresholds or the level of otoacoustic emissions. It has been suggested that these alterations are caused by changes of the mechano-electrical transducer transfer function of outer hair cells (OHCs). Shape estimates of this transfer function can be derived from low-frequency-biased distortion product otoacoustic emissions (DPOAE).Here, we tracked the transfer function estimates before and after triggering a cochlear Bounce. Specifically, cubic DPOAEs, modulated by a low-frequency biasing tone, were followed over time before and after induction of the cochlear Bounce. Most subjects showed slow, biphasic changes of the transfer function estimates after low-frequency sound exposure relative to the preceding control period. Our data show that the operating point changes biphasically on the transfer function with an initial shift away from the inflection point followed by a shift towards the inflection point before returning to baseline values. Changes in transfer function and operating point lasted for about 180 s. Our results are consistent with the hypothesis that intense, low-frequency sound disturbs regulatory mechanisms in OHCs. The homeostatic readjustment of these mechanisms after low-frequency offset is reflected in slow oscillations of the estimated transfer functions.

A novel multidimensional geriatric screening tool in the ED: evaluation of feasibility and clinical relevance

PurposesGeriatric problems frequently go undetected in older patients in emergency departments (EDs), thus increasing their risk of adverse outcomes. We evaluated a novel emergency geriatric screening (EGS) tool designed to detect geriatric problems. Basic proceduresThe EGS tool consisted of short validated instruments used to screen 4 domains (cognition, falls, mobility, and activities of daily living). Emergency geriatric screening was introduced for ED patients 75 years or older throughout a 4-month period. We analyzed the prevalence of abnormal EGS and whether EGS increased the number of EGS-related diagnoses in the ED during the screening, as compared with a preceding control period. Main findingsEmergency geriatric screening was performed on 338 (42.5%) of 795 patients presenting during screening. Emergency geriatric screening was unfeasible in 175 patients (22.0%) because of life-threatening conditions and was not performed in 282 (35.5%) for logistical reasons. Emergency geriatric screening took less than 5 minutes to perform in most (85.8%) cases. Among screened patients, 285 (84.3%) had at least 1 abnormal EGS finding. In 270 of these patients, at least 1 abnormal EGS finding did not result in a diagnosis in the ED and was reported for further workup to subsequent care. During screening, 142 patients (42.0%) had at least 1 diagnosis listed within the 4 EGS domains, significantly more than the 29.3% in the control period (odds ratio 1.75; 95% confidence interval, 1.34-2.29; P < .001). Emergency geriatric screening predicted nursing home admission after the in-hospital stay (odds ratio for ≥3 vs <3 abnormal domains 12.13; 95% confidence interval, 2.79-52.72; P = .001). Principal conclusionsThe novel EGS is feasible, identifies previously undetected geriatric problems, and predicts determinants of subsequent care.

Speed of molecular detection techniques for meticillin-resistant Staphylococcus aureus admission screening in an acute care hospital

Active surveillance for methicillin-resistant Staphylococcus aureus (MRSA) carriers is considered an essential component of MRSA control strategies in acute care hospitals. Recently, molecular assays for MRSA screening have been proposed with significant reduction of the sample processing time. Using a time analysis model, we investigated the time gain after the introduction of a molecular assay and compared this with a preceding control period, using culture-based techniques. During a four-month period all high risk patients (N=44) and all known MRSA-positive patients readmitted to the hospital (N=41) were screened for MRSA upon admission. In both groups the long pre-analytical phase - time from admission to sampling and transportation of samples to the laboratory - was the determining factor in the entire process. A substantial reduction of the sample processing time was achieved using molecular assays, compared with conventional culture. Due to the long pre-analytical phase, in addition to the high costs associated with polymerase chain reaction (PCR) testing, molecular techniques were not introduced for the admission screenings. In the group of the readmission screenings, however, a fast test result could save a substantial number of unnecessary isolation days, resulting in an economic benefit for the hospital. PCR testing might be of interest for the readmission screenings. In conclusion, local policies for MRSA screening should be investigated before introducing expensive PCR technology.

Approximate entropy of motoneuron firing patterns during a motor preparation task

The aim of this study was to test whether approximate entropy (ApEn) analysis provides a suitable method of detecting differences induced by a motor preparation task in time-ordered inter-spike intervals (ISIs) recorded in tonically firing motoneurons. Unlike classical methods of analyzing neuronal discharge variability, in which serial order is no taken into account, the approximate entropy (ApEn) was proposed by Pincus [Pincus SM. Approximate entropy as a measure of system complexity. Proc Natl Acad Sci USA 1991;88:2297–301] to analyze ordered series. ApEn statistic is a number assigned to an ordered series, where higher values correspond to greater serial irregularity. In the present study, the activity of 31 single motor units (SMUs) was recorded in human extensor carpi radialis muscles and the ISI durations were analyzed during the performance of a pre-cueing reaction time motor task involving a 3-s preparatory period. ApEn values were computed for each SMU during three steps of the preparatory period and during the preceding control period. Lower ApEn values, were found during preparatory period. The decrease in ApEn values, i.e., the increase in serial regularity, was monotonic from the control to the end of the preparatory period. These results show that ApEn model-independent statistics are a relevant means of detecting changes related to motor preparation in the regularity of time-ordered inter-spike intervals (ISIs).

New strategy to attenuate pulse wave velocity in haemodialysis patients

Pulse wave velocity (PWV) is commonly elevated in haemodialysis (HD) patients having cardiovascular diseases. Disturbances in calcium-phosphate metabolism are among the established cardiovascular risk factors in HD patients. The present study was performed to assess the effect of sevelamer on PWV in HD patients. Fifteen patients, who had been treated with calcium carbonate as a phosphate binder, were entered into the study. Changes in PWV during the 6 months before sevelamer administration were compared with PWV changes during 6 months of receiving sevelamer. Serum biochemistry parameters were also assessed. Compared with the preceding control period, the sevelamer period resulted in decreased serum calcium (9.9+/-0.1 to 9.6+/-0.1 mg/dl, n = 15; P<0.01) in association with reductions in oral calcium load (4.3+/-0.4 to 2.3+/-0.6 g/day; P<0.001). Serum phosphorus and whole parathyroid hormone remained unchanged. Sevelamer reduced serum total cholesterol (167+/-7 to 148+/-6 mg/dl; P<0.001) and LDL-cholesterol (85+/-8 to 65+/-7 mg/dl; P<0.001), without modifying HDL-cholesterol or triglycerides. Finally, sevelamer reversed the increase in PWV observed during the control period (from 46+/-16 to -20+/-9 cm/s/month; P<0.01). In chronic HD patients, sevelamer decreased serum total- and LDL-cholesterol as well as calcium. Moreover, our findings suggest that treatment with sevelamer attenuates the progressive increase in PWV observed during calcium carbonate treatment.

Amiloride blocks the inhibition of fetal lung liquid secretion caused by AVP but not by asphyxia

We have examined whether the activation of Na+ channels, located on the luminal surface of pulmonary epithelial cells, mediates the inhibitory effects of both arginine vasopressin (AVP) and moderate asphyxia on fetal lung liquid secretion. Lung liquid secretion rates were measured in chronically catheterized fetal sheep during AVP infusions and during periods of asphyxia with and without an Na+ transport blocker (amiloride; 10(-4) M) present in lung liquid. Lung liquid secretion rates were also measured during epinephrine infusions with amiloride present in lung liquid. These secretion rates were compared with measurements made during a preceding control period. Both asphyxia and an infusion of AVP significantly reduced the rate of secretion of fetal lung liquid from 8.4 +/- 1.5 and 18.0 +/- 3.7 to 3.6 +/- 1.0 (P < 0.01) and 5.5 +/- 2.1 ml/h (P < 0.01), respectively. The addition of amiloride to lung liquid did not reverse the inhibitory effects of asphyxia on lung liquid secretion (8.6 +/- 0.8 vs. 0.7 +/- 0.4 ml/h) but did block the inhibitory effects of both epinephrine (14.8 +/- 4.4 vs. 13.8 +/- 3.1 ml/h) and AVP (18.0 +/- 3.7 vs. 19.5 +/- 5.0 ml/h). The addition of amiloride to lung liquid during fetal normoxia did not significantly affect fetal lung liquid secretion rates (8.2 +/- 1.1 vs. 7.4 +/- 0.7 ml/h). We conclude that the inhibitory effect of AVP on fetal lung liquid secretion, like that of epinephrine, involves the activation of luminal surface Na+ channels, whereas the inhibitory effect of asphyxia does not.

Short-term effects of alterations in dietary fat on metabolic control in IDDM.

Two experimental diets were evaluated to investigate the hypothesis that dietary fat has an independent influence on metabolic control in IDDM. The diets had similar CHO contents (26 and 22% of energy intake) but differed markedly in fat (53 vs. 16% energy) and protein (20 vs. 62% energy). We had 10 subjects follow the low-CHO, high-fat diet, and 8 subjects follow the low-CHO, low-fat, high-protein diet. In each case, markers of glycemic and lipid control obtained after adherence to the experimental diet for 2 wk were compared with corresponding data from a preceding control period during which subjects had followed their usual diet (protein 18-19%, CHO 41-46%, fat 33-37%). Despite the low CHO content of the high-fat diet, insulin requirements were unchanged relative to the control diet. Moreover, the glycemic response to a standard breakfast was elevated significantly (P < 0.001), suggesting that insulin resistance had either been induced or exacerbated. The small rise in total cholesterol concentration in response to the high-fat diet was accounted for by a rise in HDL cholesterol. Glycemic control and lipid metabolism were unchanged after the low-CHO, low-fat diet, although insulin requirements fell by an average of 6 U/day (P < 0.05) relative to those recorded during the 2-wk control period. Diets high in fat are deleterious to glycemic control in IDDM, but general applicability is limited by the small sample size and short duration of this study.

The effects of maternal hyperoxia on fetal breathing movements, body movements and heart rate variation in growth retarded fetuses

In hypoxemic intrauterine growth-retarded fetuses (IUGR) there is a reduction in the incidence of fetal movements and in fetal heart rate variation. A causal relationship with the impairment of fetal oxygenation has been suggested. In 16 IUGR fetuses and in 13 normally grown fetuses maternal hyperoxygenation was applied for 40 min to increase fetal P O 2 levels. All IUGR fetuses had abnormal Doppler blood velocity waveforms of the umbilical artery suggesting an impaired uteroplacental exchange. The effect of hyperoxygenation on fetal breathing and body movements and on fetal heart rate was evaluated. In the IUGR fetuses there was a significant increase in fetal breathing and body movements and in heart rate variation during hyperoxygenation as compared to the preceding control period of 40 min. No significant changes in fetal breathing and body movements were found in the normally grown control fetuses. A surprising observation was the increase of the number of heart rate decelerations after discontinuation of the maternal hyperoxygenation. It is concluded that in IUGR fetuses the increase in fetal heart rate variation and the increase in the incidence of breathing and body movements during maternal hyperoxygenation substantiates the relationship between these variables and the oxygenation status of the fetus.

The effects of serotonergic drugs on the locomotor pattern and on cutaneous reflexes of the adult chronic spinal cat

The effects of serotonergic substances on the locomotor pattern and cutaneous reflexes were studied in 3 adult chronic spinal cats trained for 1–3 months to walk with their hindlimbs on a treadmill. The 5-hydroxytryptamine (5-HT) precursor, 5-hydroxytryptophan (5-HTP), and two 5-HT agonists, 5-methoxy- N, N-dimethyltryptamine and quipazine, were found to generally increase the step length and augment the amplitude of hindlimb extensors and flexors as well as axial muscles. Correspondingly, the excursion of the hip, the knee and the ankle joints was increased, mainly in the flexion direction. Cyproheptadine, a 5-HT antagonist, partially or completely antagonised these effects. The threshold current needed to elicit a flexion reflex by stimulating the dorsum of the paw through implanted wires, was lower after the injection of 5-HT agonists than in the immediately preceding control period. Fast paw shaking initiated by dipping the paw in water was unchanged after quipazine and was not abolished by cyproheptadine. In accordance with others, our results suggest that serotonergic drugs may increase the excitability of several types of spinal neurones, including motoneurones, and consequently influence the locomotor pattern as well as the reflex responsiveness. The changes observed with serotonergic agonists were different in many respects from those obtained with noradrenergic agonists and these differences are discussed. This may indicate specific roles for these classes of substances on locomotor function and reflex activity and also provide a basis for further clinical investigations.

Shortening velocity, myosin light chain phosphorylation and Ca2+ dependence of force during metabolic inhibition in smooth muscle of rat portal vein.

The concentration-response relation for Ca2+ (0.2-5.0 mM) of high-K+ contractures (40 mM) in the rat portal vein during respiratory inhibition by 0.2 mM cyanide was investigated. A reduction of force in the presence of cyanide to about 30% of control was associated with a leftward shift of the normalized concentration-response relation. When force at the plateau of high-K+ contractures (at about 2 min) was reduced to 65 +/- 2% due to the addition of cyanide, the maximal shortening velocity (Vmax) was 94 +/- 5% of control (n = 6). In electrically (AC) stimulated preparations giving short tetanic contractions, a reduction of active force to 58 +/- 2% of control in the presence of cyanide was associated with a reduction of Vmax to 83 +/- 5% (n = 7). Phosphorylation of the 20-kDa regulatory light chains (LC20) of the myosin molecule was studied in the relaxed state and at the plateau of high-K+ contractures for comparison with the mechanical data. Both control and cyanide-treated preparations showed 9% LC20 phosphorylation in nominally Ca2+-free solution (n = 6). After activation the level of phosphorylation increased to 30 +/- 3% (n = 9) in the control veins. In cyanide-treated veins, where force was reduced to 42 +/- 6% compared to a preceding control period, the phosphorylation level was 17 +/- 2% (n = 7). The study suggests that the mechanical changes caused by inhibition of cellular respiration may involve the combined effect of several metabolic alterations, including decreased LC20 phosphorylation during contraction, but apparently not decreased intracellular Ca2+ concentration or sensitivity of the contractile system to Ca2+.

Reduction in the body content of DDE in the mongolian gerbil treated with sucrose polyester and caloric restriction

It has previously been shown that oral administration to rats of sucrose polyester (SPE 4 4 SPE, sucrose polyester; the term, “olestra” also has been proposed for sucrose esterified with more than six fatty acids per molecule. ), a nonabsorbable lipophilic binding agent, greatly stimulates the fecal excretion of coorally administered DDT 5 5 DDT, 2,2-bis( p-chlorophenyl)-1,1,1-trichloroethane. ( R. J. Jandacek, 1982, Drug Metab. Rev., 13, 695–714). To determine whether this agent would stimulate the excretion of persistent metabolites of DDT stored in body tissues, we treated a group of gerbils with [ 14C]-DDT and monitored the fecal excretion of radioactivity for several months until a terminal, log-linear phase of excretion was observed. At this point, when > 75% of the fecal radioactivity was identified as [ 14C]DDE, we fed the animals diets containing up to 10% sucrose polyester and found that the rate of excretion of radioactivity in the stool promptly increased two to three times as compared to the rate in the preceding control period. Some rats were subjected to a 25–50% restriction in total food allotment, but this produced no significant change in fecal excretion of total radioactivity. However, when food restriction was combined with administration of sucrose polyester, there was a dramatic, eightfold average increase in excretion of fecal radioactivity. This synergistic effect was reversed (within 24 hr) when the animals were transferred to a normal diet. Measurement of total body radioactivity confirmed that food restriction plus sucrose polyester treatment reduced the body content of the pesticide. We conclude that stimulation of intestinal excretion may offer a new approach to treatment of patients exposed to lipophilic environmental contaminants.

Upper airway stability and apnea during nasal occlusion in newborn infants.

Brief end-expiratory airway occlusions were performed in 22 preterm babies, 17 with and 5 without clinical apnea, and 4 full-term babies, 1 with Pierre-Robin syndrome. Airway stability was evaluated by comparing pressures measured simultaneously in the chest and nasal passages during occluded inspiratory efforts. The airway remained patent throughout all 301 trials in 20 babies during rapid-eye-movement (REM) and quiet sleep. Airway closure occurred during 31/102 trials in 6 babies (5 preterm and 1 term with Pierre-Robin syndrome), more commonly in quiet than in REM sleep. Overall and within individuals, mean closing pressures were significantly lower than the mean maximum falls in airway pressure recorded during occlusions without closure. Mixed-obstructive and obstructive apnea was significantly more frequent in babies with airway closure than in those without (5.3 +/- 4.0 vs. 0.4 +/- 0.8 episodes/h). Pauses in breathing greater than or equal to 3 s occurred during 28% of occlusions in preterm infants and 2% of occlusions in full-term babies. There was no significant difference between the mean frequency of pauses during occlusion and during the preceding control period or in the incidence of pauses in occlusions with vs. those without closure. It is concluded that the airway of most preterm and full-term babies is remarkably stable under load. Intermittent closure occurs in certain infants and may be related to airway muscle dysfunction.

Effects of low oxygen on the release of dopamine from the rabbit carotid body in vitro.

1. Rabbit carotid bodies were pre-loaded with [(3)H]dopamine (DA) synthesized from [(3)H]tyrosine and then mounted in a vertical drop-type superfusion chamber which permitted simultaneous collection of released [(3)H]DA and recording of chemoreceptor discharge from the carotid sinus nerve.2. The time course of the spontaneous release of [(3)H]DA (superfusion with media equilibrated with 100% O(2)) in the presence of monoamine oxidase inhibitors exhibited two linear components, an initial steep phase followed after 3-4 hr by a later slower phase of release.3. When a 5 min low O(2) stimulus was delivered during the initial steep linear component of resting [(3)H]DA release, there was an abrupt increase in release, the magnitude of which was stimulus-dependent.4. The efflux of total radioactivity from the preparation declined exponentially with time; under resting conditions it was principally non-metabolized [(3)H]tyrosine. During stimulation, however the efflux increased, and 60-80% of the radioactivity could be attributed to [(3)H]DA.5. For a given low O(2) stimulus, the ratio of [(3)H]DA release during the stimulus period over that in the preceding control period remained approximately the same throughout a single experiment. Ratios for different low O(2) stimuli (50, 40, 30, 20, 10 and 0% O(2) in N(2)) yielded a parabolic relationship when plotted against stimulus intensity.6. Transection of the carotid sinus nerve or removal of the superior cervical ganglion 12-15 days prior to the experiment did not affect the release of [(3)H]DA at moderate stimulus intensities (superfusion with media equilibrated with 30% or 10% O(2) in N(2)) but both procedures significantly depressed release at the highest stimulus intensity (100% N(2)).7. Chemoreceptor discharge and [(3)H]DA release were simultaneously monitored in experiments using superfusion media free of monoamine oxidase inhibitors. In these experiments, the efflux of [(3)H]dihydroxyphenyl acetic acid (DOPAC) was also measured. The increase in peak chemosensory discharge was closely correlated with the increase in total release ([(3)H]DA + [(3)H]DOPAC) during stimulation with a series of low O(2) stimuli.8. Release of [(3)H]DA was almost completely abolished during superfusion with Ca(2+)-free, high Mg(2+) (2.1 mM) media, and the stimulus-related efflux of [(3)H]DOPAC was significantly reduced. However, chemoreceptor discharge was diminished by only 55%. These data are discussed with respect to their implications for DA as a chemosensory transmitter in rabbit carotid body.

Long-term effects of a new ketoacid–amino acid supplement in patients with chronic renal failure

Nine patients with severe chronic renal failure (mean glomerular filtration rate 4.8 ml/min; mean serum creatinine 11.3 mg/dl) who were previously on a protein-restricted diet were treated with a diet containing an average of 33 kcal/kg and 22.5 g/day of mixed quality protein, supplemented by a combination of amino acids and mixed salts formed between basic amino acids and keto-analogues of essential amino acids. The supplement was designed to minimize or reverse the amino acid abnormalities of chronic renal failure rather than to meet the normal requirements for the essential amino acids; it contained tyrosine, ornithine, and a high proportion of branched-chain ketoacids, but no phenylalanine or tryptophan and very little methionine. Within one month, serum urea nitrogen fell and serum albumin and transferrin rose significantly; serum creatinine fell slightly. Hyperphosphatemia (present in three patients) was corrected. Nitrogen balance, measured in seven of the nine patients, on the average was neutral, as it was in a preceding control period on a 40 to 50 g/day protein diet. Plasma tyrosine and threonine, which were subnormal before therapy, rose to normal or high normal levels. Branched-chain amino acids did not change. During a total of 63 patient-months of therapy, no side effects or toxicity were observed, and serum albumin and transferrin did not change further. It is concluded that this specially designed supplement added to a 20 to 25 g/d protein diet is an acceptable regimen which can improve or maintain protein nutrition in patients with severe chronic renal failure who would otherwise require dialysis.

Sodium- and calcium-dependent somatostatin release from dissociated cerebral cortical cells in culture.

The influence of membrane depolarization on somatostatin release from cerebral cortical neurons was examined. Fetal rat telencephalic cells, obtained by mechanoenzymatic dispersal, were maintained as organotypic monolayer cultures for 12 days before experimental studies. The immunoreactive somatostatin (IRS) released into the medium during a treatment epoch was compared to the amount released from the same cells during an immediately preceding control period. Potassium (60 mM) induced an increase in IRS secretion which was dependent on extracellular calcium concentration and could be prevented by the addition of the calcium channel blockers, cobalt or verapamil. Depolarization by veratridine, a sodium ionophore, also stimulated IRS release. The effect of veratridine was reversed by simultaneous exposure of the cells to either tetrodotoxin, a sodium channel blocker, or verapamil, a calcium channel blocker. These findings indicate that IRS release by cerebral cortical cells is stimulated by membrane depolarization and is dependent on both Na+ and Ca++ entry into the cells.

Divascan in migraine prophylaxis. Open trial with three different doses.

SYNOPSISIn an open trial 26 patients with severe migraine were treated with 3 different doses of Divascan (1‐isopropyl‐noradrenochrome‐5‐monosemicarbazone) ‐ 15, 30 and 40 mg a day. During treatment with Divascan there was a significant reduction in the number of migraine attacks and in the headache index compared with a preceding control period. The prophylactic effect of 30 and 40 mg Divascan a day seemed better than that of 15 mg a day. The headache frequency was significantly lower with 40 mg a day than with 15 mg a day. A good or very good effect of the treatment was reported by 24 per cent of the patients on 15 mg a day, by 48 per cent on 30 mg a day and by 57 per cent on 40 mg a day. No serious side‐effects were noted. Divascan seems to be a promising drug in the prophylactic treatment of migraine but further studies are needed to establish what doses are optimal in migraine prophylaxis.