Assessment of bioequivalence after subcutaneous and intramuscular administration of urinary gonadotrophins

The objective was to demonstrate bioequivalence between s.c. and i.m. administration of Humegon (FSH/LH ratio 1:1) and Normegon (FSH/LH ratio 3:1). In two randomized, single-centre, cross-over studies, 18 healthy volunteers on each formulation were assigned to one of the two administration sequences. Subjects were given single doses of one of the above gonadotrophins after endogenous gonadotrophin production had first been suppressed using high-dose oral contraceptive. Subsequently, rate (Cmax, tmax) and extent (AUC) of absorption of follicle stimulating hormone (FSH) and luteinizing hormone (LH) were determined for 14 days. For Cmax and AUC, analysis of variance (ANOVA) was performed on log-transformed data and for tmax ANOVA was performed on ranks. Intramuscular and s.c. injections of Humegon were bioequivalent with respect to the main pharmacokinetic parameters, being AUC and Cmax of FSH absorption. Intramuscular and s.c. injections of Normegon were bioequivalent with respect to the AUC of FSH and not bioequivalent with respect to the Cmax of FSH. For tmax of FSH as well as for most LH variables of both preparations, bioequivalence could not be proven due to the high intra- and interindividual variability and/or concentrations being close to the detection limit. Thus, the main pharmacokinetic FSH variables after i.m. and s.c. administration of Humegon and Normegon were bioequivalent.      

Regulation of heme metabolism during senescence: activity of several heme-containing enzymes and heme oxygenase in the liver and kidney of aging rats

The activities of several heme-containing enzymes plus succinate dehydrogenase, the content of mitochondrial cytochromes, the amount of microsomal cytochrome P-450, and the activity of heme oxygenase, the major enzyme of heme degradation, have been compared in young, mature and senescent rats. Measurements were made in liver, a tissue previously reported to have an age-related decrease in δ-aminolevulinic acid synthetase, and in kidney, a tissue previously reported to have no age-related change in this enzyme, the rate-limiting enzyme of heme biosynthesis (Paterniti, Lin and Beattie, Arch. Biochem. Biophys., 191 (1978) 792–797). The activity of cytochrome oxidase in liver mitochondria did not decrease with age while this activity in kidney mitochondria was highest in animals one year old and decreased in the two-year-olds. By contrast, succinate dehydrogenase of both kidney and liver mitochondria decreased markedly in the aging rats. No age-related change in the content of cytochromes b, c or aa₃ was observed in liver mitochondria; however, a marked age-related decrease in cytochrome aa₃ was observed in kidney mitochondria. Similarly no change in cytochrome P-450 levels was observed in either tissue obtained from aging animals. In the liver, catalase activity increased while in the kidney it decreased in senescent as compared to mature animals. Heme degradation does not decrease with age as the activity of heme oxygenase increased in both liver and kidney of two-year-old rats as compared to one-year-olds. These results suggest that the lower activity of δ-aminolevulinic acid synthetase observed in the aging rat may not be correlated with a decrease in the activity of heme-containing proteins and that the regulation of the heme pool used for the synthesis of various intracellular hemo-proteins may be complex.     

Food intake of institutionalized women over 80 years of age

Food intake of 30 women over 80 years of age and residing in a long-term care facility was determined for a five-day period using the weighed intake method. Purposes of the study were to examine the contribution to nutrient intake of foods from eight major food groups; to characterize intake by time of day; and to examine the effect of age on nutrient intake. The results indicated that intakes of calcium, thiamin, vitamin A, zinc, and protein were below recommended levels. Analysis of intake by food group revealed that the grain group was the primary source of energy and many nutrients. Percentage consumption of foods in this group was significantly higher than that of vegetables or meat and alternates. Analysis of intake by time of day indicated that more energy was consumed at breakfast than at dinner. Advanced age was negatively correlated with overall dietary adequacy, although the distribution of energy intake from the eight food groups did not change with age. Implications of the results, for these subjects and similar groups of elderly, are discussed.     

Halothane alters the oxygen consumption-oxygen delivery relationship compared with conscious state

The authors' objectives were as follows: 1) to characterize for the first time the relationship between whole body O2 delivery (DO2) and O2 consumption (VO2) in adult conscious dogs; and 2) to asses the effects of the inhalational anesthetic, halothane, on that relationship. DO2 was varied over a wide range in chronically instrumented dogs by gradual inflation and deflation of a hydraulic occluder implanted around the thoracic inferior vena cava to alter venous return and cardiac output. VO2 was measured at different values of DO2 in dogs in the fully conscious state and again during halothane anesthesia. A "binning" technique indicated that halothane decreased VO2 (P less than 0.01) at any given value of DO2 over a broad range of VO2. A two-line piecewise linear regression analysis technique indicated that halothane decreased (P less than 0.01) the critical O2 delivery (COD) from 20 +/- 3 to 10 +/- 1 ml.kg-1.min-1 and increased (P less than 0.01) O2 extraction at COD from 31 +/- 3 to 40 +/- 2%. However, the DO2-VO2 plots measured in both conscious and halothane-anesthetized dogs did not exhibit a discrete discontinuity but rather were closely fit (correlation coefficient = 0.98) by an exponential equation of the following form: O2 extraction = B1.(1 - exp (-DO2/B2))/DO2, where B1 is the delivery-independent estimate of VO2 and B2 is the "delivery constant," i.e., the DO2 associated with a VO2 equal to 63% of B1. Halothane decreased B1 (P less than 0.01) from 5.3 +/- 0.1 to 3.9 +/- 0.1 ml.kg-1.min-1 and decreased B2 (P less than 0.01) from 5.6 +/- 0.3 to 3.6 +/- 0.3 ml.kg-1.min-1 compared with that measured in conscious dogs. Thus, compared with the conscious state, halothane anesthesia alters the fundamental relationship between DO2 and VO2 and may have a beneficial effect on tissue oxygenation at low values of DO2.     

Effects of pre- and post-mating nutritional status on hepatic function, progesterone concentration, uterine protein secretion and embryo survival in Meishan pigs

This experiment examined whether the pre- or the post-mating diet had greater impact on embryo survival in Meishan gilts. Gilts received either a maintenance (1.15 kg day(-1); n = 12) or a high (3.5 kg day(-1); n = 12) diet during the oestrous cycle preceding mating. After mating, half the animals in each group received either the maintenance or the high diet until slaughter on Day 12. Gilts fed the high pre-mating diet had more corpora lutea (22.7 v. 19.0, SED = 0.98; P<0.001), increased embryo survival (95.5% v. 74.8%, SED = 7.58; P<0.01) and heavier corpora lutea (-0.71 log g v. -0.90 log g, SED = 0.09; P = 0.07) compared with gilts fed the maintenance diet prior to mating. The post-mating diet had no effect on embryo survival. There were no treatment effects on blastocyst developmental stage, luteal surface area or progesterone release. Gilts receiving the high post-mating diet had heavier livers than those fed the maintenance post-mating diet (1.45 v 1.08% of total bodyweight, SED = 0.07; P<0.001), suggesting that these gilts have a greater capacity to metabolize progesterone. Pre-mating nutritional status therefore appears to be a greater determinant of embryo numbers and survival than the post-mating diet.     

Hospital consolidation. Applying stakeholder analysis to merger life-cycle

Nearly three of every five hospitals in the United States have been involved in some form of consolidation during the past 5 years. Within this turbulent hospital merger environment, nurse executives are confronted with organizational, professional, and personal decisions. Stakeholder analysis is offered as one strategy to facilitate effectiveness throughout the hospitals' merger life-cycle.     

Influence of systemic factors on pre-existing intimal hyperplasia and their effect on the outcome of infrainguinal arterial reconstruction with vein

BACKGROUND: The association between raised levels of homocysteine, fibrinogen and lipoprotein (a), and the presence of pre-existing intimal hyperplasia (IH) in vein has not been assessed. The positive association between such hyperplasia and graft failure following infrainguinal arterial reconstruction, and between lipoprotein (a) and graft failure, is disputed. The influence of homocysteine on outcome has not been investigated prospectively. METHODS: Fifty-seven patients (63 grafts) undergoing infrainguinal arterial reconstruction with saphenous vein were studied. Homocysteine, fibrinogen and lipoprotein (a) levels were measured, and a vein biopsy was taken at operation. Patients underwent graft surveillance and outcome at 12 months was determined. RESULTS: Fifty-seven per cent of patients had hyperhomocysteinaemia. Patients with pre-existing IH had significantly higher homocysteine levels. There was no association between homocysteine and outcome, or between fibrinogen and pre-existing IH or outcome. Lipoprotein (a) levels were significantly lower in patients with pre-existing disease, and were lower, but not significantly, in those whose grafts failed. The correlation between pre-existing IH and vein graft failure was highly significant. CONCLUSION: Hyperhomocysteinaemia is associated with peripheral vascular disease and the development of pre-existing IH in vein, which itself is associated with vein graft failure.     

The limping child: epidemiology, assessment and outcome

We investigated the epidemiology, assessment and outcome of acute atraumatic limp in 243 children under the age of 14 years presenting to a paediatric accident and emergency department (AED) over a period of six months. Data were collected at presentation and medical notes were re-examined after 18 to 21 months. The incidence of limp was 1.8 per thousand. The male:female ratio was 1.7:1 and the median age 4.35 years. Limp was mainly right-sided (54%) and painful (80%); 33.7% of the children had localised pain in the hip. A preceding illness was found in 40%. The main diagnosis was 'irritable hip'/transient synovitis (39.5%); Perthes' disease accounted for 2%. Most patients (77%) were managed entirely in the AED. Acute atraumatic limp is a common problem in children presenting to the AED. Most can be safely managed there if guidelines are followed and will have a benign outcome. Further studies are needed to identify the role of preceding illness in the aetiology of acute atraumatic limp.