Energy expenditure in patients with chronic obstructive pulmonary disease

Energy expenditure was studied in ten patients with chronic obstructive pulmonary disease (COPD) and weight loss, and in five malnourished patients without clinical evidence of COPD (control group) prior to and after a two-week refeeding regimen. Patients received 5 percent dextrose solution (plus electrolytes) for 36 hours to establish standard baseline conditions and were then randomly assigned to either a carbohydrate-based (CB; 53 percent of calories) or fat-based (FB; 55 percent of calories) diet for the first week. The alternate diet was given the following week. Total calorie intake was set at 70 percent above the energy expenditure measured prior to institution of nutritional support. During energy repletion, energy expenditure was greater than predicted (116 percent) in patients with COPD and less than predicted (90 percent) in the control patients. Thermic effect of nutrients during administration of either regimen was significantly greater (p less than .05) in patients with COPD than in those without COPD during both diets. The difference between the two groups was enhanced during the CB regimen. These observations suggest that malnourished patients with COPD have an elevated resting energy expenditure, and an enhanced thermic response to nutrients as compared to malnourished patients without COPD. Increased diet-induced thermogenesis may contribute to weight loss in patients with COPD, in addition to factors previously described such as decreased caloric intake and increased resting energy expenditure.     

Reversal of diet-induced catabolism by infusion of recombinant insulin-like growth factor-I in humans.

Treatment of catabolic conditions with insulin-like growth factor I (IGF-I), the peptide that mediates some of the anabolic growth-promoting effects of GH, offers potential advantages of avoiding the hyperglycemia caused by treatment with GH. A state of moderate catabolism was produced in six normal, young adult volunteers by restricting their daily dietary intake to 20 kilocalories/kg/day. During the last 6 days of two 2-week diet-study periods, they received either IGF-I (12 micrograms/kg/h by i.v. infusion over 16 h) or GH (0.05 mg/kg/day by sc injection). IGF-I improved nitrogen balance from -236 +/- 45 mmol/day (+/- SE) during diet alone, to -65 +/- 40 mmol/day (P less than 0.001) during the last 4 days of IGF-I infusion. A similar effect was produced by GH. IGF-I infusion decreased fasting blood glucose from 4.94 +/- 0.91 mmol/L to 3.13 +/- 0.44 mmol/L (P less than 0.001), while GH raised blood glucose values (4.75 +/- 1.01 mmol/L on diet alone, to 5.48 +/- 1.00 during the period of GH treatment; P less than 0.05). Despite these differences in blood glucose, IGF-I infusions decreased serum insulin (74.9 +/- 26.8 pmol/L on diet alone, to 16.7 +/- 1.5 pmol/L during IGF-I) and serum connecting-peptide concentrations (2.14 +/- 0.89 mmol/L on diet alone, to 0.97 +/- 0.14 during IGF-I), while GH raised insulin (109.4 +/- 31.3 pmol/L, P less than 0.05 during GH) and connecting-peptide (3.12 +/- 0.59 mmol/L, P less than 0.02). At the dose of each hormone used, the attenuation of nitrogen wasting produced by infusions of IGF-I was similar in magnitude and timing to that produced by injections of GH. The reduction in serum glucose concentrations produced by IGF-I compared with the increase in glucose noted during GH treatment, could benefit hyperglycemic catabolic patients.     

Correction of severe malnutrition by cyclic enteral feeding]

This study was designed to evaluate the efficacy and tolerance of cyclic (nocturnal) enteral nutrition in ambulatory malnourished patients. A ternary polymeric diet was administered to a total of 28 women and 23 men (mean age: 58 years) for a nocturnal period of 12-14 hours during 24.5 +/- 1.1 days. This diet provided an average of 28.3 +/- 0.6 kcal/kg ideal body weight/day. The nutritional program was administered as planned and well tolerated in 50 of the 51 patients. Voluntary oral caloric intake improved significantly during the treatment period (18.2 +/- 1.4 kcal/kg ideal body weight/day during the first week of enteral nutrition and 22.7 +/- 1.6 kcal/kg ideal body weight/day during the last week). The global nutritional deficit based on 10 anthropometric and biological parameters improved by an average of 36.8 +/- 2.2 percent. Overall, 71 percent of the patients exhibited a favorable nutritional course. Results were identical regardless of the pathology responsible for malnutrition. The main advantages of cyclic enteral nutrition include the possibility for patients to engage in physical activities and to eat normally during the day.     

Dietary carbohydrate content determines responsiveness to growth hormone in energy-restricted humans

To determine if diet composition influences responses to GH, we fed 11 obese women diets containing 12 Cal/kg ideal BW (IBW) for 2 5-week study intervals. Nonprotein calories were supplied to 6 subjects as 72% carbohydrate (high carbohydrate diet), and 5 subjects received 80% of their nonprotein calories as lipid (high lipid diet). Protein intake was constant (1.0 g/kg IBW) in both groups. During 1 study interval we gave injections of GH (0.1 mg/kg IBW) every other day for 3 weeks (weeks 2-4), and in the other interval injections of vehicle were given. Subjects ingesting the high carbohydrate diet excreted significantly less urinary nitrogen [660.2 +/- 124.1 mmol/day (mean +/- SD)] than those who received high lipid (794.2 +/- 198.5 mmol/day; P less than 0.001), and GH injections reduced nitrogen excretion in the high carbohydrate subjects (532.8 +/- 123.8 mmol/day), but not in the high lipid subjects (743.7 +/- 126.6 mmol/day). The subjects receiving the high carbohydrate diet had a significant increase in serum insulin-like growth factor-I (IGF-I; from 36.2 +/- 9.7 to 55.9 +/- 6.6 nmol/L) and urinary C-peptide excretion (from 43.9 +/- 25.6 to 60.8 +/- 29.4 nmol/day) in response to GH. The IGF-I response attenuated slowly over the 3-week treatment interval. On the other hand, the high lipid group had lesser increases in IGF-I (from 31.0 +/- 6.5 to 41.7 +/- 8.8 nmol/L) and C-peptide excretion (from 24.3 +/- 28.9 to 29.8 +/- 32.8 nmol/day), and IGF-I concentrations declined to control values after only 5 days of GH injection. We believe that this initial IGF-I response was due to an antecedent 35-Cal balanced diet. The mean increment in serum FFA 4 h after GH injection was significantly less in subjects fed the high lipid diet (0.53 +/- 0.40 meq/L) than in those fed the high carbohydrate diet (0.83 +/- 0.43 meq/L). GH injections produced more body fat loss than injections of vehicle whether expressed as percent body fat lost (GH, 3.7 +/- 1.0%; vehicle, 2.8 +/- 0.7%, P less than 0.05) or as the fraction of weight lost as fat (fat loss/weight loss; GH, 0.81 +/- 0.13; vehicle, 0.64 +/- 0.08; P less than 0.005). There was an inverse correlation between the percentage of body fat lost and mean urinary C-peptide excretion during GH injections (r = -0.70; P less than 0.05), suggesting that stimulation of insulin secretion by GH might antagonize the tendency of GH to promote fat loss.(ABSTRACT TRUNCATED AT 400 WORDS)     

Oxygen consumption of the respiratory muscles in normal and in malnourished patients with chronic obstructive pulmonary disease

Patients with severe chronic obstructive pulmonary disease (COPD) commonly experience weight loss. An increased energy expenditure for respiration might explain the increased caloric requirements and weight loss seen in this patient population. We measured the oxygen cost of augmenting ventilation (O2 cost) using an open circuit technique with dead-space stimulation of ventilation in nine normally nourished (greater than 90% ideal body weight) and in 10 malnourished (less than 90% ideal body weight) patients with COPD as well as in seven normal control subjects. O2 cost was significantly elevated in the malnourished patients with COPD (4.28 +/- 0.98 ml O2/L ventilation) relative to the normally nourished group (2.61 +/- 1.07) and the normal control subjects (1.23 +/- 0.51) (p less than 0.001). The measured resting energy expenditure (REEmeas) was also increased compared with predicted values (REEpred) in the malnourished population (REEmeas/REEpred = 94.57 +/- 6.21% for control subjects, 105.5 +/- 19.66% for normally nourished patients with COPD, and 119.4 +/- 11.69% for malnourished patients with COPD) (p less than 0.005). The malnourished population was characterized by a greater degree of hyperinflation (RV/TLC = 0.55 +/- 0.09 for normally nourished versus 0.69 +/- 0.06 for malnourished patients) and inspiratory muscle weakness (PImax = 51 +/- 16.5 for the normally nourished and 34 +/- 12.2 for the malnourished population). We conclude that malnourished patients with COPD are characterized by a relative increase in resting energy requirements and, specifically, increased energy requirements for augmenting ventilation. This increase in energy requirements may result from the increased mechanical work load associated with severe COPD and/or a reduced ventilatory muscle efficiency.     

Treatment of obese, diet-restricted subjects with growth hormone for 11 weeks: effects on anabolism, lipolysis, and body composition

We found in a previous study that injections of GH for 3 weeks caused nitrogen conservation despite restriction of intake to 24 Cal (100 kJ)/kg ideal BW (IBW). To determine the effects of longer periods of treatment and further caloric restriction on nitrogen balance, lipolysis, and body composition, 20 obese (30-67% over IBW) subjects (16 women and 4 men; 20-54 yr old) were fed a diet of 18 Cal (75 kJ)/kg IBW with 1.2 g protein/kg IBW daily for 13 weeks. During weeks 2-12, 10 subjects received injections of recombinant methionyl GH (0.1 mg/kg IBW every other day), and the other 10 sex-, age-, and weight-matched subjects were given injections of saline. There were no significant differences between the two groups in total weight loss [GH, 13.9 +/- 3.0 (+/- SD) kg; saline, 15.2 +/- 3.8 kg ) or the percentage of body fat lost (GH, 8.1 +/- 2.4%; saline, 7.5 +/- 1.5%), although GH injection caused a significant acute increment in serum FFA concentrations (GH, 0.53 +/- 0.37 mmol/L; saline, 0.08 +/- 0.22 mmol/L; P less than 0.001) throughout the study. This acute lipolytic response to GH decreased significantly, from 0.86 +/- 0.32 mmol/L on day 1 of GH treatment to 0.35 +/- 0.41 mmol/L by day 35 of GH injection (P less than 0.01). Nitrogen balance was significantly more positive in the group receiving GH during the first 33 days of the GH injection period [GH, +0.07 +/- 1.82 g/day (+5.0 +/- 130.0 mmol/day); saline, -1.91 +/- 1.10 g/day (-136.3 +/- 78.5 mmol/day); P less than 0.001]. During the last 44 days of GH injection, however, the nitrogen balance in the two groups was similar [GH, -0.90 +/- 1.65 g/day (-64.2 +/- 117.8 mmol/day); saline, -1.08 +/- 0.95 g/day (-77.1 +/- 67.8 mmol/day); P = NS]. Mean plasma insulin-like growth factor I (IGF-I) concentrations rose from a basal value of 1.6 +/- 0.8 to 2.9 +/- 1.2 U/mL by 48 h after the first GH injection and ranged subsequently from 3.2 +/- 1.3 to 4.9 +/- 3.3 U/mL during GH injection (P less than 0.001). In contrast, the mean IGF-I concentration did not change in the group that received saline. Dietary restriction during the first week of study caused serum T3 concentrations to decline in both groups.(ABSTRACT TRUNCATED AT 400 WORDS)     

Relationship between plasma somatomedin-C and liver somatogenic binding sites in neonatal rats during malnutrition and after short and long term refeeding

To determine the mechanism(s) for the growth retardation associated with malnutrition early in life, the relationships among plasma somatomedin-C (SM-C), plasma GH, and hepatic bovine GH-binding sites were assessed in rat pups that were milk-deprived from birth until weaning (21 days). After this period of malnutrition, body weight, tail length, plasma SM-C, and liver GH-binding capacity of the malnourished animals were significantly (P less than 0.001) reduced below those of control, well fed rats [SM-C at 21 days, 0.06 +/- 0.01 vs. 0.30 +/- 0.04 U/ml (mean +/- SE); GH binding, 2.96 +/- 0.39 vs. 7.19 +/- 0.80 pmol/liver]. The number of GH-binding sites per mg DNA was also reduced (0.59 +/- 0.06 vs. 1.08 +/- 0.11 pmol/mg DNA; P less than 0.001). After 1 week of ad libitum refeeding (days 21-28), body weight and tail length of malnourished pups increased significantly but showed no signs of catching up with that of control pups. Plasma SM-C and liver GH-binding capacity in the malnourished rats also rose significantly (P less than 0.005) after refeeding, but remained as far below controls as at 21 days [SM-C on day 28, 0.19 +/- 0.02 vs. 0.53 +/- 0.02 U/ml (P less than 0.001); GH binding, 6.59 +/- 0.99 vs. 12.94 +/- 1.60 pmol/liver (P less than 0.005)]. After 7 weeks of refeeding (days 21-70), tail length but not body weight recovered, while plasma SM-C levels were normalized. The mean number of GH binding sites per mg DNA in the malnourished rats was not significantly different from that in controls and reached for the males and the females, respectively, 79% and 86% of control binding. When expressed per liver, GH binding followed a similar pattern; for the males, binding capacity returned to 73% of the control value (20.45 +/- 1.82 vs. 27.93 +/- 3.49 pmol/liver; P = NS), and for the females, it returned to 77% of the control value (36.42 +/- 1.76 vs. 47.42 +/- 4.13 pmol/liver; P less than 0.01). In the young rats up to day 28, liver GH-binding capacities correlated with plasma SM-C concentrations (r = 0.81; P less than 0.01), while in the adult rats no correlation was present. During malnutrition and refeeding, there were no changes in the affinity constants of the hepatic GH-binding sites or in plasma GH concentrations.(ABSTRACT TRUNCATED AT 400 WORDS)     

Recombinant human growth hormone enhances the metabolic efficacy of parenteral nutrition: a double-blind, randomized controlled study.

This multicenter, randomized, double-blind study was performed to investigate whether recombinant GH improves the efficacy of total parenteral nutrition (TPN). Fifteen stable patients requiring parenteral feeding due to gastrointestinal/pancreatic disease were studied. Constant maintenance TPN providing approximately 30 kcal/kg day and approximately 1.6 g protein/kg.day was administered during an initial 7-day baseline period. After randomization, daily sc injections of saline (control, n = 9) or GH (10 mg/day, n = 6) were administered a 14-day treatment period as nutrient intake remained constant. Elemental balances for nitrogen (N), potassium (K), phosphorus (P), and sodium (Na) were determined daily and serial blood indices, vital signs, and other clinical parameters were monitored. Nutrient balances approached equilibrium during the baseline week in both groups. With GH administration, a significant increase in N, K, and P balance occurred; in contrast, nutrient balances did not change significantly from baseline values in control patients. The cumulative change (delta) in nutrient balances from the baseline week was also significantly greater in the GH-treated patients (delta N: control+2 +/- 7 g vs. GH+36 +/- 6. g, P less than 0.005; delta K:+57 +/- 45 mmol vs.+199 +/- 19 mmol, P less than 0.03; delta P: -27 +/- 30 mmol vs. +91 +/- 69 mmol, P less than 0.02). Plasma insulin-like growth factor-I concentrations rose 5-fold and serum cholesterol rose slightly with GH; no other significant change in group mean blood values occurred. One patient receiving GH and chronic prednisone therapy developed moderate hyperglycemia and mild peripheral edema; no other deleterious effects attributable to GH were observed. GH was well tolerated and significantly enhanced nutrient retention compared to standard parenteral feeding alone. GH improves the efficacy of parenteral nutrient utilization in patients requiring TPN.     

Adult height in short normal girls treated with gonadotropin-releasing hormone analogs and growth hormone

Combined treatment with GH and GnRH analogs (GnRHa) has been proposed to improve final adult height in true precocious puberty, GH deficiency, and short normal subjects with early or normal timing of puberty with still controversial results. We treated 12 girls with idiopathic short stature and normal or early puberty with GH and GnRHa and followed them to adult height; 12 girls comparable for auxological and laboratory characteristics treated with GH alone served to better evaluate the efficacy of addition of GnRHa. At the start of combined treatment, the chronological age of the girls (CA; mean +/- SD) was 10.2 +/- 0.9 yr, bone age (BA) was 10.6 +/- 1.9 yr, height SD score for BA was - 1.81 +/- 0.8, PAH was 146.3 +/- 5.0 cm. PAH was significantly lower than target height (TH 152.7 +/- 3.6 cm; P < 0.005). GH was given at a dose of 0.3 mg/kg x week, sc, 6 days weekly, and GnRHa (depot-triptorelin) was given at a dose of 100 microg/kg every 21 days, im. The 12 girls were treated with GH alone at the same dose; at the start of therapy their CA was 10.7 +/- 1.0, BA was 10.1 +/- 1.4 yr, height SD score for BA was - 1.65 +/- 0.8, PAH was 145.6 +/- 4.4 cm, and TH was 155.8 +/- 4.6 cm. Pubertal Tanner stage in both groups was B2P2 or B3P3. LHRH test and pelvic ultrasound showed the beginning of puberty. The GH response to standard provocative tests was 10 g/L or more. The mean period of treatment was 4.6 +/- 1.7 yr in the group treated with GH plus GnRHa and 4.9 +/- 1.4 yr in the group treated with GH alone; both groups discontinued treatment at comparable CA and BA. Adult height was considered to be attained when growth during the preceding year was less than 1 cm, with a BA of over 15 yr. Patients in the group treated with GH plus GnRHa showed an adult height significantly higher (P < 0.001) than the pretreatment PAH (156.3 +/- 5.9 vs. 146.3 +/- 5 cm); the gain in centimeters calculated between pretreatment PAH and adult height was 10 +/- 2.9 cm, and 7 of 12 girls had a gain over 10 cm. Target height was significantly exceeded. Height SD score for BA increased from - 1.81 +/-0.8 to -0.85 +/- 1.0. The GH alone group reached an adult height higher than the pretreatment PAH (151.7 +/- 2.7 vs. 145.6 +/- 4.4 cm); the gain in final height vs. pretreatment PAH was 6.1 +/- 4.4 cm, and 5 of 12 girls did not gain more than 4 cm. TH was even not reached. The height SD score did not significantly change. No adverse effects were observed in either group. All of the girls showed good compliance and were satisfied with the results. Our experience suggests that the combination of GH and GnRHa is significantly more effective in improving adult height than GH alone in girls with idiopathic short stature, early or normal onset of puberty, and low PAH well below the third percentile and TH. As the cost-benefit of such invasive treatment must be seriously considered, further studies are needed due to the small sample of our patients as well as in other studies reported to date.     

Adult height in girls with central precocious puberty treated with gonadotropin-releasing hormone analogues and growth hormone

GnRH analogues (GnRHa) represent the treatment of choice in central precocious puberty (CPP), because arresting pubertal development and reducing either growth velocity (GV) or bone maturation (BA) should improve adult height. However, in some patients, GV decrease is so remarkable that it impairs predicted adult height (PAH); and therefore, the addition of GH is suggested. Out of twenty subjects with idiopathic CPP (treated with GnRHa depot-triptorelin, at a dose of 100 microg/kg im every 21 days, for at least 2-3 yr), whose GV fall below the 25th percentile for chronological age, 10 received, in addition to GnRHa, GH at a dose of 0.3 mg/kg x week s.c., 6 days weekly, for 2-4 yr; and 10 matched for BA, chronological age, and duration of GnRHa treatment, who showed the same growth pattern but refused GH treatment, served to evaluate the efficacy of GH addition. No patient showed classical GH deficiency. Both groups discontinued treatment at a comparable BA (mean +/- SEM): 13.2 +/- 0.2 in GnRHa plus GH vs. 13.0 +/- 0.1 yr in the control group. At the conclusion of the study, all the patients had achieved adult height. Adult height was considered to be attained when the growth during the preceding year was less than 1 cm, with a BA of over 15 yr. Patients of the group treated with GH plus GnRHa showed an adult height significantly higher (P < 0.001) than pretreatment PAH (160.6 +/- 1.3 vs. 152.7 +/- 1.7 cm). Target height (TH) was significantly exceeded. The group treated with GnRH alone reached an adult height not significantly higher than pretreatment PAH (157.1 +/- 2.5 vs. 155.5 +/- 1.9 cm). TH was just reached but not significantly exceeded. The gain in centimeters obtained, calculated between pretreatment PAH and final height, was 7.9 +/- 1.1 cm in patients treated with GH combined with GnRHa; whereas in patients treated with GnRHa alone, the gain was just 1.6 +/- 1.2 cm (P = 0.001). Furthermore, no side effects have been observed either on bone age progression or ovarian cyst appearance and the gynecological follow-up in the GH-treated patients (in comparison with those treated with GnRHa alone). In conclusion, a gain of 7.9 cm in adult height represents a significant improvement, which justifies the addition of GH for 2-3 yr during the conventional treatment with GnRHa, especially in patients with CPP, and a decrease in GV so marked as to impair PAH, not allowing it to reach even the third centile.     

Concurrent nitroglycerin administration decreases thrombolytic potential of tissue-type plasminogen activator

Dynamic coronary vasoconstriction may play a role in coronary artery reocclusion after successful thrombolysis. The effect of nitroglycerin on the thrombolytic effects of recombinant tissue-type plasminogen activator (rt-PA) was examined in dogs with an electrically induced occlusive coronary artery thrombus. Eleven dogs were randomly given rt-PA alone and seven rt-PA with nitroglycerin. The dose of rt-PA was 0.75 mg/kg body weight given over 20 min and the dose of nitroglycerin was 125 micrograms/min for 40 min. The reperfusion rate in the dogs given rt-PA alone was 73% (8 of 11 dogs) and that in the rt-PA plus nitroglycerin group was 57% (four of seven dogs) (p = NS). The time to thrombolysis (or reperfusion) in dogs receiving rt-PA plus nitroglycerin was 70% greater than in those receiving rt-PA alone (means +/- SD/29.8 +/- 9.9 versus 17.6 +/- 5.9 min, p less than 0.02), and the duration of reperfusion much shorter (11 +/- 17 versus 42 +/- 16 min, p less than 0.02). Peak coronary blood flow after reperfusion in dogs receiving rt-PA plus nitroglycerin was also less than in those receiving rt-PA alone (36 +/- 52 versus 63 +/- 20 ml/min, p less than 0.02). Reocclusion occurred in all dogs given rt-PA with nitroglycerin and in six of eight given rt-PA alone (p = NS). Plasma concentrations of rt-PA were lower when nitroglycerin was given with rt-PA alone (427 +/- 279 versus 1,471 +/- 600 ng/ml, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Transcutaneous oxygen saturation and carbon dioxide tension during meals in patients with chronic obstructive pulmonary disease

The effect on transcutaneous SaO2 and transcutaneous carbon dioxide tension (PtCO2) of eating was assessed in 44 patients with severe COPD (FEV1 less than 50 percent). The SaO2, PtCO2, and heart rate (HR) were measured every minute before, during, and until 30 minutes after a standardized meal (445 kcal) was consumed. All patients were measured twice on the same day, while eating a meal with high (80 percent) and low (28 percent) carbohydrate content, respectively. The mean meal desaturation (delta SaO2) was less than 1 percent in normoxemic patients but was -3.2 +/- 0.7 percent (p less than 0.001) in hypoxemic (PaO2 less than 7.3 kPa) patients. Significant differences between hypoxemic patients with a delta SaO2 greater than 4 percent and less than or equal to 4 percent, respectively, were found in FEV1 (16 +/- 3 percent and 29 +/- 8 percent; p less than 0.001), respiratory muscle strength (3.9 +/- 1.2 kPa and 5.9 +/- 1.2 kPa; p less than 0.01), HR (112 +/- 12 beats per minute and 90 +/- 18 beats per minute; p less than 0.001), body weight (54.9 +/- 7.5 kg and 74.7 +/- 10.4 kg; p less than 0.001), and fat-free mass (42.0 +/- 6.6 kg and 52.6 +/- 5.8 kg; p less than 0.005) but not in baseline SaO2 and PtCO2. The decrease in SaO2 and the increase in HR were less during the carbohydrate-rich meal. No significant fluctuations in PtCO2 were found after either meal. Meal-related oxygen desaturation cannot explain weight loss in normoxemic patients with COPD but may contribute to a limited dietary intake in a subgroup of hypoxemic patients exhibiting marked oxygen desaturation during meals. A single carbohydrate-rich meal does not have an immediate impact on PtCO2 in stable COPD.     

Pentoxifylline improves pulmonary gas exchange

Pentoxifylline is a xanthine derivative with hemorrheologic and vascular properties that may improve gas exchange in patients with chronic obstructive pulmonary disease (COPD). We tested this hypothesis in 12 patients with COPD (mean FEV1 = 40 percent predicted; mean DCO, 8.6 ml/min/mm Hg) randomly divided into a treatment and control group and six healthy volunteers. Following establishment of baseline DCO and maximum expiratory flow volume (MEFV) curve values, each subject in the treatment and healthy groups took 400 mg of pentoxifylline three times a day for 12 weeks. Weekly DCO and MEFV curves were measured before treadmill exercise in both COPD groups and before and after exercise in the healthy group. The MEFV curve parameters from the final three weeks of therapy did not differ significantly from baseline values. During this time, however, the treatment COPD group's resting DCO rose by 8.2 +/- 2.4 percent over baseline level (p less than 0.01). Treadmill walk time increased from 17.7 +/- 2.9 minutes to 23.2 +/- 2.9 minutes (p less than 0.02). This was accompanied by improved exercise oxygen saturation measured by oximetry (SoxiO2). Premedication SoxiO2 fell from 92.8 +/- 1.2 percent to 88.6 +/- 2.5 percent during exercise, and from 94.4 +/- 1.1 percent to only 91.8 +/- 1.0 percent after 12 weeks of medication (p less than 0.05). No such improvement was noted in the control COPD group. Although the healthy group's resting SoxiO2 and DCO did not change during treatment, their exercise DCO increased significantly from 36.3 +/- 3.1 ml/min/mm Hg to 41.8 +/- 3.5 ml/min/mm Hg (p less than 0.001). These data demonstrate that pentoxifylline improves gas exchange, possibly by increasing cardiac output, and/or by raising mixed venous PO2, and/or by improving blood flow to underperfused alveoli.     

Pyridostigmine potentiates L-dopa- but not arginine- and galanin-induced growth hormone secretion in children.

The coadministration of growth hormone (GH) secretagogues can provide insight into the neuroregulation of GH secretion. The GH response to L-dopa (125, 250 and 500 mg orally for body weights less than 15 kg, between 15 and 30 kg and greater than 30 kg, respectively), arginine (Arg; 0.5 g/kg infused intravenously over 30 min) and galanin (GAL; 15 micrograms/kg infused intravenously over 60 min) when administered alone or combined with pyridostigmine (PD; 60 mg orally), a cholinergic agonist that likely acts via inhibition of endogenous somatostatin secretion, was studied in children with familial short stature. The GH-releasing effect of PD was also evaluated. In 8 children, PD and L-dopa when administered alone induced an equivalent GH rise (area under the response curve, mean +/- SEM: 241.4 +/- 31.1 vs. 202.9 +/- 38.6 micrograms/l/h) while their coadministration had an additive effect (435.4 +/- 41.4 micrograms/l/h; p less than 0.02 vs. PD and L-dopa alone). On the contrary, in other 8 children, PD and Arg induced similar GH increases either when administered alone (394.2 +/- 68.5 vs. 405.8 +/- 103.9 micrograms/l/h) or in combination (535.8 +/- 97.3 micrograms/l/h). GH increases almost superimposable were also observed when PD and GAL were administered alone (405.2 +/- 72.3 vs. 412.6 +/- 94.1 micrograms/l/h) or in combination (537.9 +/- 139.0 micrograms/l/h) in other 7 children. These data show that the enhancement of the cholinergic activity by PD increases the L-dopa-induced GH release but fails to modify both Arg- and GAL-induced GH release in short children.(ABSTRACT TRUNCATED AT 250 WORDS)     

The hemodynamic effects of sympathetic stimulation combined with parasympathetic blockade in man

To define the effects of circulating norepinephrine and epinephrine on cardiac function and to determine whether left ventricular function is influenced by parasympathetic mechanisms during catecholamine stimulation, hemodynamic changes were investigated in healthy young human subjects who were supine and awake during infusion of intravenous norepinephrine alone (125 ng/kg/min) (n = 6), norepinephrine (125 ng/kg/min) plus epinephrine (50 ng/kg/min) (n = 6), and norepinephrine plus epinephrine plus parasympathetic blockade induced by atropine (2 mg intravenously) (n = 5). Ejection fraction and changes in cardiac volumes were measured by radionuclide ventriculography. During the infusion of norepinephrine plus epinephrine, plasma norepinephrine increased from 358 +/- 35 to 1782 +/- 123 pg/ml (mean +/- SE) and plasma epinephrine increased from 31 +/- 5 to 355 +/- 90 pg/ml (both p less than .01 vs baseline). These increases in plasma catecholamines were associated with increases in the heart rate (58 +/- 3 to 67 +/- 2 beats/min, p = NS), systolic blood pressure (113 +/- 3 to 140 +/- 6 mm Hg, p less than .01), ejection fraction (0.64 +/- 0.02 to 0.72 +/- 0.02 ejection fraction units, p less than .01), stroke volume (+41 +/- 5%, p less than .01), and cardiac output (+54 +/- 8%, p less than .01), and a decrease in systemic vascular resistance (-31 +/- 3%, p less than .01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Growth hormone administration conserves lean body mass during dietary restriction in obese subjects

Because weight-reducing diets result in loss of lean body tissue as well as fat, we sought to determine whether injections of GH might facilitate the preservation of nitrogen and accelerate the loss of body fat during dietary restriction. The dietary intake of 8 obese subjects was restricted to 24 Cal/kg ideal BW and 1 g protein/kg for 11 weeks. During weeks 3-5, 4 subjects were given a total of 10 im injections of recombinant methionyl human GH, 1 morning injection every 48 h in a dosage of 0.1 mg/kg ideal BW. The other 4 subjects were given injections of vehicle. During weeks 8-10, the subjects who had received GH previously were given vehicle and vice versa. While receiving GH injections the mean daily nitrogen deficit [0.35 +/- 2.14 (+/- SD) g/day] was significantly less than the loss during injection of vehicle (2.21 +/- 1.45 g/day; P less than 0.001). Although three of six subjects lost 190% more fat (as determined by hydrostatic weighing) while receiving GH, the difference in group mean fat loss during GH injection was not significantly greater than that during injection of vehicle (3.06 +/- 1.39 kg lost with GH vs. 2.64 +/- 1.08 kg lost with vehicle; P = NS). In parallel with the changes in nitrogen balance, GH produced a significant increase in the mean plasma somatomedin-C/insulin-like growth factor I concentration. From a mean pretreatment value of 1.06 +/- 0.28 U/mL, a maximal value of 3.20 +/- 1.60 U/mL was achieved after 12 days of GH injection (P less than 0.001). Somatomedin-C/insulin-like growth factor I concentrations did not change during injection of vehicle. During GH injection weight loss was attenuated because of fluid retention. If weight loss was determined 1 week after the end of GH administration, however, the total weight loss (3.42 +/- 1.73 kg) was not significantly different from that during the 3 weeks of vehicle administration and the following week (4.16 +/- 1.30 kg). Fasting blood glucose and serum insulin concentrations did not change during GH administration, and no glycosuria was detected in morning urine samples. Short term GH administration is effective in decreasing the loss of lean body mass in individuals ingesting restricted diets. However, fat loss was not accelerated.     

Beneficial effect of vegetable protein diet supplemented with psyllium plantago in patients with hepatic encephalopathy and diabetes mellitus

A controlled crossover study was performed in 8 diabetic patients with chronic portal-systemic encephalopathy. After a basal period the patients were treated during periods A and B. During period A, a meat protein diet (0.8 g/kg body wt, approximately 1800 kcal/day) was consumed and neomycin plus laxatives were given. During period B patients received vegetable protein (0.8 g/kg body wt, 1800 kcal/day). This diet was supplemented with psyllium fiber to reach 35 g of fiber per day. Four patients were randomly assigned to receive the treatments in the order A-B and the other 4 patients in the order B-A. At the end of the first experimental period, fasting glucose levels were 204 +/- 86 mg% in the meat protein diet group and 127 +/- 8 mg% in the vegetable protein diet group (p less than 0.014). The patients were receiving 2.5 +/- 0.2 g/day and 2.1 +/- 0.5 g/day of tolbutamide at the end of the meat protein diet and vegetable protein diet, respectively. In all cases, fasting glucose levels decreased at the end of the vegetable diet period regardless of the previous treatment. An improvement of greater than or equal to 25 mg% of fasting glucose levels was observed in 7 of the 8 patients after the vegetable protein diet and in no case after the meat protein diet (p less than 0.0078). The parameters of encephalopathy were comparable at the end of both the meat protein diet and the vegetable protein diet. A significant increase in the number of bowel movements was noticed after the vegetable diet plus fiber (p less than 0.01). We propose the use of vegetable diet plus fiber to facilitate the treatment of patients with both diabetes and hepatic encephalopathy.     

Nutritional supplementation in ambulatory patients with chronic obstructive pulmonary disease

We examined the effect of nutritional supplementation for 8 wk on respiratory muscle function (RMF) in 21 malnourished patients with COPD. Patients were randomized to a fed group or to a control group. Patients in the fed group were provided with an enteral formula in addition to their usual diet. Daily calorie and protein intake and weekly anthropometric measures were made. Pulmonary function tests were measured on Weeks 1, 4, and 8. Respiratory muscle strength was measured by means of maximal inspiratory and expiratory pressures (MIP), (MEP), and respiratory muscle endurance was measured by the maximal sustained ventilatory capacity (MSVC). The mean weight of the fed group increased from 52.2 +/- 6.4 to 53.3 +/- 6.9 kg (NS). The mean daily caloric intake of the fed group was significantly increased during the study (p less than 0.02). The mean calorie intake during the study of the fed group was 174 +/- 17% of the estimated basal energy expenditure. During the study period, no change was observed in anthropometric measures, pulmonary function studies, or RMF. Because patients tend to decrease their own food intake while receiving enteral formulas, it is difficult to provide sufficient calories and protein needed to effect changes in nutritional status and RMF in an outpatient COPD population. In addition, we compared RMF in 12 poorly nourished male patients (87.6 +/- 6.1% of ideal body weight) and 13 well-nourished male patients with severe COPD. Both groups had comparable degrees of air-flow limitation and hyperinflation. No difference was noted between the groups in either MIP, MEP, or MSVC.(ABSTRACT TRUNCATED AT 250 WORDS)     

Growth hormone affects both adiposity and voluntary food intake in old and obese female rats.

OBJECTIVE: To investigate whether the promotion of breakdown of body fat and the increased energy expenditure associated with growth hormone (GH) affect the voluntary food intake of an obese organism. DESIGN: Wistar rats (15 months old) were first fed either a high-fat (HF) or a low-fat (LF) diet for 10 weeks. In the subsequent treatment period, two saline groups continued with either the HF or the LF diet, and rats of three other groups had their diet shifted from HF to LF and were treated with saline, human GH (hGH) or rat GH (rGH). hGH and rGH were given in a dose of 4 mg/kg per day. After 21 days of treatment and registration of food intake, rats were killed, blood was collected and tissues were excised. RESULTS: The HF diet produced a significant (P<0.05) increase in weight of fat pads compared with the LF diet: 69+/-5 g compared with 48+/-2 g. The switch from HF to LF diet combined with injections of saline alone decreased the intake of metabolizable energy, but fat pad weight did not decrease significantly (69+/-5 g compared with 63+/-6 g). The latter value was significantly (P<0.05) decreased (to 37+/-3 g) in groups treated with either hGH or rGH. Both GH treatments increased serum IGF-I and muscle weight, whereas the activity of adipose tissue lipoprotein lipase decreased significantly (P<0.01). During the first 9 days of treatment, food intake was significantly (P<0.01) depressed, from 27+/-1 g/kg per day in control rats to 14+/-2 and 16+/-4 g/kg per day in the hGH and rGH groups respectively. CONCLUSION: This study demonstrates that breakdown of adipose tissue and a transient decrease in voluntary food intake are parallel consequences of GH treatment in old and obese rats, and that the actions of hGH and rGH are very similar.     

Beneficial effects of dietary carbohydrate restriction in chronic cor pulmonale

To explore the effects of moderate and severe reductions in carbohydrate intake on abnormal pulmonary physiology in chronic hypercapneic respiratory failure, spirometric, metabolic, arterial blood gas tension, and oximetric studies were carried out in eight patients who took, in random order daily for a week, either 50 g or 200 g of carbohydrate in an isocaloric diet. At the end of a week's daily intake of an isocaloric diet containing 200 g of carbohydrate, all patients experienced a subjective improvement; the mean body weight was 55.5 +/- 15.4 kg (1 SD) compared with 56.0 +/- 16.0 kg during the control dietary period, the arterial carbon dioxide tension decreased from a mean of 56.9 +/- 6.7 to 50.9 +/- 6.2 mm Hg (p less than 0.005), and the arterial oxygen tension increased from a mean of 50.6 +/- 7.3 to 62.0 +/- 14.5 mm Hg (p less than 0.02). After a week's intake of 50 g of carbohydrate in an isocaloric diet, the body weight and arterial oxygen tension did not change significantly, but the arterial carbon dioxide tension decreased still further to 48.0 +/- 7.8 mm Hg (p less than 0.05). Mouth pressure at 100 msec after the start of inspiration, as a measure of respiratory center output, was significantly higher during both the low carbohydrate intakes compared with the control dietary period. The spirometric data, ventilation-perfusion distribution measurements, oxygen consumption, and carbon dioxide production did not change significantly during various dietary periods. It is concluded that, under these short-term, hospital-controlled conditions, a reduction in the carbohydrate intake to 200 g a day improves the general well-being of patients with chronic hypercapneic respiratory failure, increases arterial oxygen tension, and decreases arterial carbon dioxide tension. A further reduction in the carbohydrate intake to 50 g a day provides further beneficial effects, and such a diet may be used in patients with intractable respiratory failure.