Whole-body SPECT/CT for bone scintigraphy: diagnostic value and effect on patient management in oncological patients.

PURPOSE: This study was designed to assess the additional value of SPECT/CT of the trunk used in conjunction with conventional nuclear imaging and its effects on patient management in a large patient series. METHODS: In 353 patients, whole-body scintigraphy (WBS), SPECT, and SPECT/CT were prospectively performed for staging and restaging. SPECT/CT of the trunk was performed in all patients. In the 308 evaluable patients (211 with breast cancer, 97 with prostate cancer), clinical follow-up was used as the gold standard. Bone metastases were confirmed in 72 patients and excluded in 236. Multistep analyses per lesion and per patient were performed. Clinical relevance was expressed in terms of downstaging and upstaging rates on a per-patient basis. RESULTS: In the total patient group, sensitivities, specificities, and negative and positive predictive values on a per-patient basis were 93 %, 78 %, 95 % and 59 % for WBS, 94 %, 71 %, 97 % and 53 % for SPECT, and 97 %, 94 %, 97 % and 88 % for SPECT/CT, respectively. In all subgroups, specificity and positive predictive value were significantly (p<0.01) better with SPECT/CT. Downstaging of metastatic disease in the total, breast cancer and prostate cancer groups using SPECT/CT was possible in 32.1 %, 33.8 % and 29.5 % of patients, respectively. Upstaging in previously negative patients by additional SPECT/CT was observed in three breast cancer patients (2.1 %). Further diagnostic imaging procedures for unclear scintigraphic findings were necessary in only 2.5 % of patients. SPECT/CT improved diagnostic accuracy for defining the extent of multifocal metastatic disease in 34.6 % of these patients. CONCLUSIONS: SPECT/CT significantly improved the specificity and positive predictive value of bone scintigraphy in cancer patients. In breast cancer patients, we found a slight increase in sensitivity. SPECT/CT had a significant effect on clinical management because of correct downstaging and upstaging, better definition of the extent of metastases, and a reduction in further diagnostic procedures.

Moving Beyond Referrals: Addressing Multilevel Barriers to Substance Use Treatment Engagement Through Police-Led Recovery Management Check-Ups.

The opioid epidemic in the United States (US) has prompted innovative responses from law enforcement agencies including specialized units to refer overdose survivors to substance use treatment following an overdose. However, traditional law enforcement outreach does not address the multilevel barriers to treatment engagement that lead to repeat overdose-related calls for service. The current evaluation explored the process components and outcomes of a Comprehensive Opioid Abuse Program (COAP) initiative within a local law enforcement agency in the Southeast US. COAP funding supported a police-led recovery management team (RMT) to connect overdose survivors to substance use treatment. The RMT also utilized recovery management check-ups (RMCs) to provide sustained support to enhance substance use treatment engagement beyond the initial treatment referral. A mixed-methods approach was employed to examine participant demographic, substance use, mental health, treatment, and criminal justice characteristics (N = 65) and explore perceptions of programmatic strengths and potential areas for improvement (N = 15). The quantitative and qualitative analyses were informed by the Recovery Capital Model. Quantitative analysis revealed that the RMT connected many participants with various support services, notably including housing assistance and health insurance. Qualitative findings highlight program effectiveness in improving social, community, and personal recovery capital. These findings contribute to expanding research on police-led post-overdose initiatives and suggest that police-led RMCs can address multilevel barriers to treatment engagement and minimize law enforcement stigma.

Feasibility and safety of long-term photodynamic therapy (PDT) in the palliative treatment of patients with hilar cholangiocarcinoma.

BACKGROUND AND AIM: PDT is an important palliative option for patients with unresectable extrahepatic cholangiocarcinoma (CC). However, the results published to date reported on studies with no more than 6 (mostly up to 4) PDT procedures. Furthermore, the clinical experience of PDT in combination with chemotherapy is limited. The purpose of this retrospective analysis was to evaluate the feasibility and safety of multiple (4 to 14) settings of PDT, combined with biliary drainage, and (in some cases) with chemotherapy. - METHODS: Ten patients with unresectable extrahepatic CC were treated with biliary stenting and at least 4 PDT procedures in our department between 10/2005 and 08/2010. - RESULTS: Ten patients (male/female = 5/5), mean age 68.8 years (range, 54 - 81 years) who received at least 4 PDT procedures were analyzed. All patients underwent endoscopic biliary drainage. Nine patients received metallic stents and one patient a plastic stent. In 4 patients (40%) bilateral metal stenting (JoStent SelfX®) was performed. The mean number of PDT sessions was 7.9 ± 3.9 (range: 4 - 14). Eight patients had elevated bilirubin levels with a mean bilirubin at admission of 9.9 ± 11.3 mg/dL, which had decreased to an average minimum of 1.2 ± 0.9 mg/dL after 3 months. No severe toxicity was noted. Two patients received concomitant chemotherapy (GEMCIS as 1st line, GEMOX plus cetuximab as 2nd line). The median overall survival has not been reached, whereas the estimated survival of all patients was 47.6 months, 95% CI 25.9 - 48.1. - CONCLUSION: Long-term PDT in patients with extrahepatic CC is feasible and effective and is accompanied - at least in this cohort- by a survival time of more than 2 years.

Combination of bilateral metal stenting and trans-stent photodynamic therapy for palliative treatment of hilar cholangiocarcinoma.

Endoscopic biliary drainage is the mainstay of palliative treatment in patients with unresectable malignant hilar biliary obstruction. While self-expandable metal stents have shown significant advantages in distal tumors, bilateral hilar stenting is technically demanding. Moreover, ingrowth is a significant problem in uncovered stents. We evaluated the feasibility and efficacy of endoscopic bilateral JoStent SelfX deployment in patients with proximal malignant biliary obstruction in combination with photodynamic therapy (PDT) and/or chemotherapy. Twenty-one consecutive patients with malignant hilar biliary strictures were treated with transpapillary bilateral insertion of JoStentSelfX metal stents. Additional PDT was applied in 8 patients (PDT plus chemotherapy n = 4, only PDT n = 4). Solely chemotherapy was performed in 5 patients. Mean (+/- SD) stent patency was 173.9 +/- 201.8 days. The median estimated survival was 12.3 months (95 % CI: 8.5; 15.9). PDT was safely and efficaciously performed after endoscopic stent deployment (1.8 +/- 1.1 sessions/patient). There was a trend towards a longer stent patency in patients receiving additional therapy (202.2 +/- 197.6 vs. 128 vs. 213.2 days; p = 0.38). Furthermore, we observed a significantly longer survival in this cohort (16.5 [12.2; 20.1] vs. 12.3 [1.9; 8.5] months, p < 0.005). Additional therapy had no significant impact on cumulative hospitalization time (16.3 +/- 15.8 vs. 14.4 +/- 22.5 days; p = 0.54). Bilateral insertion of Jostent SelfX in patients with proximal cholangiocarcinoma is feasible and effective and can be safely combined with trans-stent photodynamic therapy.

Beta-trace protein-based equations for calculation of GFR in renal transplant recipients.

Recently, we showed that serum beta-trace protein (BTP) is an alternative marker of glomerular filtration rate (GFR) in renal transplant recipients (RTR). We have now developed three BTP-based GFR formulae derived by multiple regression analyses from the patients who had participated in that study. Currently, we validated the diagnostic performance of these BTP-formulae in 102 consecutive RTR who underwent a technetium diethylenetriamine pentaacetic acid (DTPA) clearance for GFR measurement in comparison to the re-expressed Modification of Diet in Renal Disease (MDRD) equation and a recently proposed BTP-based equation (referred to as 'White equation'). The best-performing BTP formula was found to be: GFR = 89.85 x BTP(-0.5541)x urea(-0.3018). This equation estimated true GFR virtually without bias (+0.43 mL/min/1.73 m(2), not significant [NS]), while a small, but significant, overestimation was seen for the MDRD formula (+3.43 mL/min/1.73 m(2), p = 0.003). Precision and accuracies within 50% of true GFR (93.1% and 88.2%, respectively) tended to be higher for the BTP formula, but the differences did not reach significance. The White equation overestimated the true GFR by 9.43 mL/min/1.73 m(2)(p = 0.001), and was inferior with respect to precision and 50% accuracy (79.4%). BTP-based GFR calculations are reliable, and may serve as an alternative to the re-expressed MDRD equation.

Kidney's nightshift, kidney's nightmare? Comparison of daylight and nighttime kidney transplantation: impact on complications and graft survival.

BACKGROUND: Organ distribution and internal procedures often delay kidney transplantation into nighttime. Consequently, surgeons start the operation at a time different from normal working hours, and nighttime work is accompanied by higher incidence of complications. Surgical complications in kidney transplantation often require reoperation, and graft survival can be affected. The aim of our study was to evaluate the impact of the time starting transplantation had on complications and graft survival. METHODS: Between 1994 and 2004, a total of 260 patients underwent kidney transplantation. Of these, 166 of 260 (64%) operations were initiated between 8 a.m. and 8 p.m. (day-kidney) and 94 of 260 operations (36%) between 8 p.m. and 8 a.m. (night-kidney). Mean follow-up was 43 months (range, 0-121 months). RESULTS: Overall graft failure rate was 8.1% 12 months and 12.7% 60 months after engraftment, respectively. Nighttime operation was associated with a higher risk of graft failure. Twenty-four of 260 patients (9.1%) underwent reoperation within 30 days after transplantation. Reoperation rates (night-kidney: 16 of 94 patients [16.8%], day-kidney: 8 of 166 patients [6.4%]) differed significantly between both groups. Reoperation was associated with risk of graft failure (P < .05, Cox proportional hazard). CONCLUSIONS: Nighttime surgery enhances the risk for complications and graft failure. Delaying kidney transplantation of a night-kidney to the following day may be worthwhile, even risking prolonged cold ischemia time.

Alcohol use following liver transplantation for alcoholic cirrhosis.

Due to the significant increase in the number of patients with alcoholic liver cirrhosis being referred for liver transplantation, studies to determine recidivism rates and influential factors affecting those rates have become increasingly crucial. Between 12/85 and 12/91, 67 patients diagnosed with alcohol related end-stage liver disease underwent orthotopic liver transplantation at Baylor University Medical Center. A 3-8 year follow-up study was conducted wherein surviving patients were contacted by phone to evaluate subsequent alcohol consumption following transplantation (with the exception of two patients whose primary physicians were contacted). Of the 67 patients transplanted, 18 had expired, 7 were alive but unavailable, and 1 had been lost to follow-up. Of the remaining 41 patients interviewed, 21 had remained abstinent, while the other 20 had returned to some form of drinking. Of patients with less than 6 months of pretransplant abstinence, only 30% remained abstinent, while the other 70% had resumed drinking. Regarding patients with at least 6 months of pretransplant abstinence, 58% had remained abstinent, while the other 42% had resumed drinking. In both groups, nearly 1/3 of those who had admitted to posttransplant drinking reported themselves as again abstinent and recommitted to sobriety when interviewed. In conclusion, 49% of patients interviewed had resumed some type of drinking following transplantation-- however, this appears not to have affected compliance or survival potential. Only 2 (4.8%) of the 41 patients interviewed had returned to excessive drinking. Thus, our findings support the use of orthotopic liver transplantation for patients with alcohol related end-stage liver disease.

Apnea of prematurity: II. Respiratory reflexes.

Airway obstruction is a cause of apnea in preterm infants. The activity of protective respiratory reflexes was determined in 18 preterm infants with apnea (mean of 32 episodes of more than 20 seconds duration per day) and in 18 neonates without apnea used as control subjects. This was done in order to elucidate the role of respiratory reflexes in apnea of prematurity. The infants were matched for birth weight (1,068 g v 1,065 g), gestational age (30.2 weeks v 30.2 weeks), and postnatal age (8.6 days v 8.3 days). The airway occlusion technique was used to determine the inspiratory prolongation of the occluded breath and the effective elastance of the respiratory system. Inspiratory prolongation is a measure for the reflex influence on inspiratory duration, and effective elastance reflects load compensating ability. Inspiratory prolongation was 7.3% +/- 33.5% in infants with apnea and 30.6% +/- 22.7% in the control group (P less than .025). Effective elastance was 1.1 +/- 0.5 cm H2O/mL in the apneic group and 1.5 +/- 0.5 cm H2O/mL in the infants without apnea (P less than .025). The results indicate that during exposure to respiratory loads, the infants with apnea maintained inspiratory effort poorly and had a decreased ability for load compensation. Their respiratory reflexes were significantly more immature than the reflex activity of the infants without apnea. This functional immaturity of respiratory reflexes may be a contributing factor in the etiology of apnea of prematurity.

Apnea of prematurity: I. Lung function and regulation of breathing.

It has been suggested that apnea of prematurity may be caused by "immaturity" of central control of breathing. To test the validity of this hypothesis tidal volume (VT), alveolar ventilation (VA), alveolar Pco2 (Paco2), esophageal pressure change, and the slope of the CO2 response curve (delta Ve [minute ventilation]/delta Paco2) were determined in 18 infants with apnea (mean of 32 episodes of more than 20 seconds duration per day) and in 18 healthy newborns used as control subjects. The infants were matched for birth weight (1,068 g v 1,065 g), gestational age (30.2 weeks v 30.2 weeks), and postnatal age (8.6 days v 8.3 days). The results were as follows: Vt (4.4 +/- 1.0 mL/kg v 5.3 +/- 1.6 mL/kg), Va (96 +/- 21 mL/kg/min v 129 +/- 33 mL/kg/min), Paco2 (45.4 +/- 8.5 mm Hg v 35.6 +/- 4.7 mm Hg), esophageal pressure change (4.5 +/- 0.9 cm H2O v 6.0 +/- 1.8 cm H2O), delta Ve/delta Paco2 (20.2 +/- 10.6 mL/min/kg/mm Hg CO2 v 40.7 +/- 19.9 mL/min/kg/mm Hg CO2). There was a significant difference between infants with and without apnea for all measurements. The results indicate a decreased respiratory center output and a depressed ventilatory response to CO2 in infants with apnea. As there was no difference between the two groups in pulmonary mechanics or oxygenation, the findings support the hypothesis that a central disturbance in regulation of breathing is the cause of apnea in these infants.

Aminophylline therapy for idiopathic apnea in premature infants: effects on lung function.

The effect of aminophylline on lung function was studied in 14 premature infants with apnea (gestational age, 30.2 weeks; birth weight, 1.052 gm). The infants showed compromised pulmonary function with a large difference in alveolar-arterial PO2 gradient (83.9 mm Hg), a low normal lung compliance of 1.1 ml/cm H2O . kg, and a normal inspiratory resistance of 45.3 cm H2O/liter/sec. Aminophylline therapy did not change these functions significantly, but it decreased the incidence of apneic episodes from 29.7 to 4.4 per day. The effectiveness of aminophylline in treating apnea in premature infants must be related to its central stimulating effect and not to an improvement in lung function and oxygenation.

Blood transfusion effect on the respiratory pattern of preterm infants.

Anemia may increase the risk of tissue hypoxia in preterm infants. This could lead to respiratory center depression and an increased risk for apnea. Heart rate and breathing pattern were recorded in 30 preterm infants (gestational age 30.0 +/- 2.3 weeks, postnatal age 46.6 +/- 20.8 days, and weight 1,438 +/- 266 g) before and after a transfusion of 10 mL/kg of packed RBCs. All infants were stable clinically, breathing room air, and free of prolonged apneic episodes. After transfusion, hematocrit levels increased from 27.0% +/- 2.5% to 35.8% +/- 4.7%. Heart rate decreased from 157.2 +/- 13.6 beats per minute to 148.4 +/- 13.9 beats per minute. There was no change in respiratory rate or BP. The duration of periodic breathing decreased significantly, as did the duration of the longest periodic breathing episode (P less than .01). The number of respiratory pauses lasting 5 to 10 seconds and the number of pauses lasting 11 to 20 seconds also decreased significantly (P less than .05). The total duration of respiratory pauses, excluding pauses during periodic breathing, were significantly lower after transfusion (P less than .05), as was the number of episodes of bradycardia. These results indicate that preterm infants have a more irregular breathing pattern while anemic than after correction of the anemia. The irregular breathing pattern is probably caused by mild hypoxic respiratory center depression.

Extrathoracic airway stability during resistive loading in preterm infants.

Extrathoracic airway (ETA) stability was tested in 10 preterm infants during sleep with a drop in intraluminal pressure produced by the application of an external inspiratory flow-resistive load (IRL, 125 cmH2O.1-1.s at 1 l/min). An increase in total pulmonary resistance was sought as the measure of airway narrowing. The role of the ETA in the increased pulmonary resistance with loading was examined by testing the same infants while endotracheally intubated and after extubation. Total pulmonary resistance decreased with loading during the intubated studies (102.5 +/- 41.2 to 82.4 +/- 33.3 cmH2O.1-1.s, P less than 0.05), whereas a significant increase in pulmonary resistance was seen with loading in the extubated studies (101 +/- 58.1 to 128 +/- 68.6 cmH2O.1-1.s, P less than 0.01). Intraluminal pressure in the ETA, measured by the lowest proximal airway pressure, fell significantly with loading in both conditions, with values changing from -0.7 +/- 0.3 to -4.7 +/- 2.7 cmH2O in the intubated infants and from -0.9 +/- 0.3 to -4.6 +/- 0.9 cmH2O) in the extubated infants (P less than 0.01). The results suggest ETA narrowing with loading in extubated infants despite the absence of overt obstructive apnea. Measurements of total pulmonary resistance with IRL can be used as a simple test of ETA stability.

Assessment of airway resistance in preterm infants during incremental inspiratory flow-resistive loading.

Extrathoracic airway (ETA) stability was tested by inspiratory flow-resistive loading in 10 preterm infants to determine whether ETA collapsibility was directly related to the size of the added load. A fall in intraluminal pressure was produced by applying two inspiratory flow-resistive loads of lower (L1) and higher (L2) magnitudes. An increase in intrinsic resistance was used as an index of upper airway collapsibility. Total pulmonary resistance did not change from baseline with L1 (73 +/- 26 to 71 +/- 25 cmH2O.l-1.s) but increased significantly with L2 (72 +/- 21 to 99 +/- 34 cmH2O.l-1.s, P less than 0.02) secondary to a rise in inspiratory resistance (55 +/- 21 to 109 +/- 55 cmH2O.l-1.s, P less than 0.05). Expiratory resistance did not change significantly with either load. Proximal airway pressure was more negative with L2 than with L1 in every infant (mean -4.5 +/- 0.6 vs. -3.6 +/- 0.9 cmH2O, P less than 0.05). This study shows that the ETA of preterm infants is pressure passive at high but not at low collapsing pressures, and possible explanations include limited "active" compensation by upper airway dilator muscles and an overwhelming of the "passive" defense offered by the intrinsic rigidity of the ETA to large changes in transmural pressure.

Metabolic, hemodynamic, and ventilatory responses to respiratory load in sedated neonatal piglets.

Some neonatal species fail to develop the expected degree of hypercapnia during hypoventilation with mechanical loads. We studied 13 spontaneously breathing, sedated piglets (1-9 days old), grouped by age as young (< or = 3 day old) or old (> 3 day old). Baseline measurements of minute ventilation, arterial blood pressure (BP), cardiac output, and O2 consumption were repeated after continuous (inspiratory and expiratory) flow-resistive loading of 330 cmH2O.l-1 x s for 10 min. Older animals [n = 6, age 6.6 +/- 1.9 (SD) days, wt 1.99 +/- 0.5 kg] increased metabolic rate (9.8 +/- 1.4 to 10.5 +/- 1.3 ml.min-1 x kg-1, P < 0.01), whereas younger animals (n = 7, 2.6 +/- 0.6 days, 1.37 +2- 0.3 kg) invariably decreased metabolic rate with loading (9.7 +/- 1.6 to 7.9 +/- 2.6 ml.min-1 x kg-1); changes were different between groups (P < 0.02). Although ventilation decreased with loading in both groups (P < 0.01), younger animals showed a relatively greater fall from baseline values (38 vs. 27%). Despite differences in the degree of hypoventilation, arterial CO2 tension increased similarly in both groups (21%). BP increased (P < 0.01) with loading in older but not younger animals. We conclude that the decreased metabolic rate and limited hemodynamic response in younger piglets reflect an accomodative response to hypoventilation in contrast to that of older animals, which display an adult pattern of increased metabolic rate and BP with loaded breathing.

Effect of maturation on the extrathoracic airway stability of infants.

The influence of maturation on extrathoracic airway (ETA) stability during quiet sleep was determined in 13 normal preterm infants of 1.41 +/- 0.14 (SD) kg birth weight and 32 +/- 2 wk estimated gestational age. Studies began in the first week of life and were performed three times at weekly intervals. A drop in intraluminal pressure within the ETA was produced by external inspiratory flow-resistive loading (60 cmH2O.l-1 x s at 1 l/min); an increase in intrinsic resistance, indicating airway narrowing, was sought as a measure of ETA instability. Baseline total pulmonary resistance was not significantly different between weeks 1, 2, and 3 (88 +/- 35, 65 +/- 24, and 61 +/- 17 cmH2O.l-1 x s, respectively) but increased markedly above baseline with loading to 144 +/- 45 cmH2O.l-1.s during week 1 (P < 0.001), 89 +/- 28 cmH2O.l-1 x s at week 2 (P < 0.01), and 74 +/- 25 cmH2O.l-1 x s at week 3 (n = 10). The increment with loading was significantly greater during week 1 than during weeks 2 or 3 (P < 0.02). Similar studies were also done in seven full-term infants in the first week of life to evaluate the influence of gestational maturity on ETA stability. Despite a relatively greater drop in intraluminal pressure within the ETA of term vs. preterm infants with loading (P < 0.001), total pulmonary resistance failed to increase (68 +/- 21 to 71 +/- 32 cmH2O.l-1.s). These data reveal that ETA instability is present in preterm infants at birth and decreases with increasing postnatal age. Full-term neonates, by comparison, display markedly greater ETA stability in the immediate neonatal period.

Metabolic and respiratory effects of flow-resistive loading in preterm infants.

Oxygen consumption (VO2) was measured during hypoventilation induced by moderate-sized flow-resistive loading in 12 preterm infants, and the results were compared with those obtained under basal conditions immediately before and after the loaded run, each of which lasted for 7-10 min. Loading was performed with a continuous flow-resistive load (inspiratory and expiratory), which was approximately threefold greater in magnitude than the intrinsic resistance of preterm infants. VO2, minute ventilation (VE), transcutaneous oxygen tension (PtCO2), and transcutaneous carbon dioxide tension (PtcCO2) were continuously monitored. Results revealed that VE decreased significantly with loading, from 336 +/- 103 to 231 +/- 58 (SD) ml.min-1.kg-1 (P less than 0.001), while returning to basal levels of 342 +/- 59 ml.min-1.kg-1 after discontinuation of the load. VO2 decreased from 7.2 +/- 1.2 to 5.9 +/- 0.9 ml.min-1.kg-1 with loading (P less than 0.001) and returned to 7.2 +/- 1.2 ml.min-1.kg-1 at the second basal measurement. PtcCO2 remained unchanged with loading, and PtcCO2 only increased from 39 +/- 8 to 41 +/- 9 Torr (P less than 0.05) with loading, while returning to 40 +/- 9 Torr at the second basal measurement. Results indicate a decrease in the metabolic rate and ventilation with loading, with relatively little increase in PtcCO2. These data can explain prior observations that minimal disturbances in oxygen and carbon dioxide tensions occur with hypoventilation during flow-resistive loading in neonates, although the precise mechanism for this reduction remains to be determined.

Effects of nisoldipine on stress-induced changes in haemodynamics and plasma catecholamines in normotensives and hypertensives.

In a double-blind, placebo-controlled crossover study 10 mg nisoldipine was given orally twice daily for 3.5 days to 12 normotensives and 12 essential hypertensives. In each study period, subjects were exposed to 6 min of physical exercise and 3 min of mental stress following the morning dose on day 3 and 4, respectively. Blood pressure, heart rate, systolic time intervals (day 3 only) and plasma levels of noradrenaline, adrenaline, dopamine as well as dihydroxyphenylglycol (DOPEG; the main presynaptic metabolite of noradrenaline) were determined at rest and at the end of both tests. Nisoldipine increased resting heart rate in normotensives and hypertensives, but reduced resting BP and BP during mental stress in hypertensives only. It also increased plasma concentrations of noradrenaline and DOPEG at rest and plasma noradrenaline concentrations during mental stress in both groups. However, nisoldipine affected neither exercise- nor stress-induced changes in any of the parameters monitored here. There was a correlation between the drug-induced percentage fall in resting BP and the height of BP during placebo treatment. While the resting values of plasma DOPEG were higher in hypertensives than in normotensives, those of plasma noradrenaline were not. Consequently, the linear relationship that existed between the resting plasma concentrations of DOPEG and noradrenaline in both groups was shifted to higher DOPEG levels in hypertensives when compared with normotensives. In conclusion, the effectiveness of nisoldipine in lowering BP was the more pronounced the higher the BP to begin with. Nisoldipine did not attenuate exercise- or stress-induced increases in plasma catecholamines. Essential hypertension may be associated with an enhanced presynaptic formation of DOPEG.

Assay of catecholamines and dihydroxyphenylethyleneglycol in human plasma and its application in orthostasis and mental stress.

A high performance liquid chromatographic method involving electrochemical detection is described which permits the assay of noradrenaline (NA), adrenaline (A), dopamine (DA), and dihydroxyphenylethyleneglycol (DOPEG) in human plasma and brings about analytical recoveries of 70% and more. This method was used to assess the effects of graded orthostasis and mental stress on the plasma levels of these catechols. Orthostasis elicited increases in plasma NA and DOPEG, but did not cause any change in plasma A and DA. The increases in NA and DOPEG were dependent on the degree of orthostasis and correlated closely (rs = 0.724; n = 30, P less than 0.001). Pretreatment with desipramine abolished the DOPEG response to standing, indicating that orthostasis - induced increases in plasma DOPEG are presynaptic in origin. Mental stress evoked pronounced increases in plasma A, less pronounced increases in plasma NA and no changes in plasma DA and DOPEG. Hence, the simultaneous measurement of plasma NA and DOPEG may help to distinguish between various types of activation of the sympathetic nervous system.

Nonlinear pressure/volume relationship and measurements of lung mechanics in infants.

We examined the effects of within-breath changes in compliance (C) upon the accuracy of measurements of compliance and resistance (R) by linear regression analysis and by Mead and Wittenberger's method. These effects were illustrated by a computer model and by lung models with linear and nonlinear pressure/volume relationships, and were also studied in 14 normal spontaneously breathing premature infants (mean +/- SD, BW 1,290 +/- 200 g, GA 29.9 +/- 2.7 weeks, age 7.4 +/- 2.1 days). Flow was measured by pneumotachography and tidal volume was derived as digitally integrated flow, and transpulmonary pressure as airway minus esophageal pressure. We found that C and R calculated from the equation of motion is accurate only if C and R remain constant throughout the respiratory cycle. Calculated compliance depends more on C at the end than at the beginning of inspiration. A decreasing C leads to underestimation or R, while an increasing C leads to an overestimation of inspiratory R. Calculated total R may be accurate, but with low r values for measurement points. Mead and Wittenberger's method and the regression method are similarly affected by changing C; however, since the regression method is based on many more measurement points and therefore allows the detection and analysis of within-breath changes of C and R, it is less prone to erroneous results secondary to signal artifacts than Mead and Wittenberger's method.

Pulmonary mechanics in normal infants and young children during first 5 years of life.

To characterize lung function in young children we measured lung compliance and pulmonary conductance in 40 normal infants and children ranging in age from the newborn period to 5 years. Inspiratory and expiratory flow was measured by a pneumotachograph, esophageal pressure through a water-filled feeding tube, and functional residual capacity (FRC) by a N2 washout technique. The esophageal pressure change per breath [(mean +/- SD) 7.3 +/- 1.4 cm H2O] and specific compliance (75 +/- 13 ml/cm H2O/L-FRC) did not change with growth. Specific conductance was high (0.60 L/s/cm H2O/L-FRC) in preterm infants, decreasing rapidly with initial growth but minimally beyond 10 kg of body weight, and stabilizing at 0.10 L/s/cm H2O/L-FRC. During the age period studied, compliance increased approximately x 25 whereas conductance only rose five-fold. The changes in compliance and conductance were well correlated to FRC, body weight, and length. These findings suggest that in the last trimester of pregnancy the airways are already well developed and postnatal lung growth occurs mainly by formation of new alveoli, leading to a proportional increase in FRC and lung compliance. Postnatally, conductance increases much more slowly than FRC, resulting in a rapid drop in specific conductance.