The consequences of growth hormone deficiency in adulthood, and the effects of growth hormone replacement

The availability of recombinant human growth hormone (GH) has resulted in investigation of the role of GH in adulthood and the effects of GH replacement in the GH-deficient adult. These studies have led to the recognition of a specific syndrome of GH-deficiency, characterized by symptoms, signs and investigative findings. Adults with long-standing growth hormone deficiency are often overweight, have altered body composition, with reduced lean body mass (LBM), increased fat mass (FM), reduced total body water and reduced bone mass. In addition, there is reduced physical and cardiac performance, altered substrate metabolism and an abnormal lipid profile predisposing to the development of cardiovascular disease. Adults with GH deficiency report reduced psychological well-being and quality of life. These changes may contribute to the morbidity and premature mortality observed in hypopituitary adults on conventional replacement therapy. GH treatment restores LBM, reduces FM, increases total body water and increases bone mass. Following GH therapy, increases are recorded in exercise capacity and protein synthesis, and "favourable" alterations occur in plasma lipids. In addition, psychological well-being and quality of life improve with replacement therapy. GH is well tolerated; adverse effects are largely related to fluid retention and respond to dose adjustment. It is likely that GH replacement will become standard therapy for the hypopituitary adult in the near future. The benefits of GH replacement in the GH-deficient adult have been unequivocally demonstrated in studies lasting up to 3 years. The results of longer term studies are awaited to determine whether these benefits are sustained over a lifetime.

Bone mineral density in young women with long-standing amenorrhea: limited effect of hormone replacement therapy with ethinylestradiol and desogestrel

To assess bone mineral density (BMD) at different skeletal sites in women with hypothalamic or ovarian amenorrhea and the effect of estrogen-gestagen substitution on BMD we compared BMD of 21 amenorrheic patients with hypothalamic or ovarian amenorrhea with that of a control population of 123 healthy women. All amenorrheic patients were recruited from the outpatient clinic of the Division of Gynecological Endocrinology at the University of Berne, a public University Hospital. One hundred and twenty-three healthy, regularly menstruating women recruited in the Berne area served as a control group. BMD was measured using dual-energy X-ray absorptiometry (DXA). At each site where it was measured, mean BMD was lower in the amenorrheic group than in the control group. Compared with the control group, average BMD in the amenorrheic group was 85% at lumbar spine (p < 0.0001), 92% at femoral neck (p < 0.02), 90% at Ward's triangle (p < 0.03), 92% at tibial diaphysis (p < 0.0001) and 92% at tibial epiphysis (p < 0.03). Fifteen amenorrheic women received estrogen-gestagen replacement therapy (0.03 mg ethinylestradiol and 0.15 mg desogestrel daily for 21 days per month), bone densitometry being repeated within 12-24 months. An annual increase in BMD of 0.2% to 2.9% was noted at all measured sites, the level of significance being reached at the lumbar spine (p < 0.0012) and Ward's triangle (p < 0.033). In conclusion BMD is lower in amenorrheic young women than in a population of normally menstruating, age-matched women in both mainly trabecular (lumbar spine, Ward's triangle, tibial epiphysis) and mainly cortical bone (femoral neck, tibial diaphysis).(ABSTRACT TRUNCATED AT 250 WORDS)

Differential impact of conventional oral or transdermal hormone replacement therapy or tibolone on body composition in postmenopausal women

To compare the effects on body composition and body weight of tibolone vs two different sequential oral or transdermal oestrogen-progestogen hormone replacement therapies versus no therapy.

Long-term influence of different postmenopausal hormone replacement regimens on serum lipids and lipoprotein(a): a randomised study

To assess the influence of three different postmenopausal hormone replacement therapies on levels of serum lipids and lipoprotein(a) [Lp(a)].

Prevention of postmenopausal bone loss using tibolone or conventional peroral or transdermal hormone replacement therapy with 17beta-estradiol and dydrogesterone

Postmenopausal bone loss can be prevented by continuous or intermittent estradiol (E2) administration. Concomitant progestogen therapy is mandatory in nonhysterectomized women to curtail the risk of endometrial hyperplasia or cancer. However, the recurrence of vaginal bleeding induced by sequential progestogen therapy in addition to continuous estrogen administration is one of the reasons for noncompliance to hormone replacement therapy (HRT). Tibolone, a synthetic steroid with simultaneous weak estrogenic, androgenic, and progestational activity, which does not stimulate endometrial proliferation, has recently been proposed for the treatment of climacteric symptoms. To compare the efficacy of conventional oral and transdermal HRT with that of tibolone in the prevention of postmenopausal bone loss, 140 postmenopausal women (age, 52 +/- 0.6 years; median duration of menopause, 3 years) were enrolled in an open 2-year study. Volunteers had been offered a choice between HRT and no therapy (control group, CO). Patients selecting HRT were randomly allocated to one of the following three treatment groups: TIB, tibolone, 2.5 mg/day continuously, orally; PO, peroral E2, 2 mg/day continuously, plus sequential oral dydrogesterone (DYD), 10 mg/day, for 14 days of a 28-day cycle; TTS, transdermal E2 by patch releasing 50 microg/day, plus DYD as above. Bone densitometry of the lumbar spine, upper femur, and whole body was performed using dual-energy X-ray absorptiometry at baseline, and then 6, 12, 18, and 24 months after initiation of therapy. One hundred and fifteen women (82%) completed the 2 years of the study. The dropout rate was similar in each group. Over 2 years, bone preservation was observed in all three treatment groups as compared with controls, without significant differences among treatment regimens. In conclusion, tibolone can be regarded as an alternative to conventional HRT to prevent postmenopausal bone loss.

Prosthetic valve endocarditis caused by a Pasteurella dagmatis-like isolate originating from a patient's cat

Pasteurella species are part of the oral flora of cats and dogs. In humans, they are frequently found in infected animal bite wounds, but invasive infections are rare. This is the first report of prosthetic-valve endocarditis with a Pasteurella dagmatis-like species, which originated from the patient's cat.

Evaluation of a Mixture of Corn Steep Liquor and Distillers Solubles as a Replacement for Corn and Supplement in Cattle Finishing Diets

Finishing yearling steers fed a corn-based diet containing steep liquor had statistically similar live performance as steers fed the control diet. Numerically steers fed the steep containing diet were 6% more efficient. Steers fed steep liquor tended to contain less carcass fat (as measured by intramuscular marbling) less kidney, heart and pelvic fat, and less backfat thickness. When priced at $50/ton adding steep liquor at 10% of diet dry matter reduced feed cost for gain 9%.

Impact of B-type natriuretic peptide on short-term clinical outcomes following transcatheter aortic valve implantation

Aims: We aimed to assess the impact of B-type natriuretic peptide (BNP) on short-term outcomes in patients undergoing transcatheter aortic valve implantation (TAVI). Methods and results: Of 500 consecutive patients with severe aortic stenosis undergoing TAVI at our institution, we studied 340 patients who had a BNP assessment prior to TAVI. Patients were divided into tertiles - low: BNP ≤201 pg/mL (n=114), mid: BNP 202-595 pg/mL (n=113) and high: BNP ≥596 pg/mL (n=113). The primary endpoint was all-cause mortality, cardiac death and major adverse cardiac and cerebrovascular events (MACCE; death, major stroke and myocardial infarction) at 30 days. Compared with low tertile, high tertile patients were at higher baseline surgical risk (STS score 5.5±3.0 vs. 7.4±4.1, p=0.002). On echocardiography, high tertile patients had smaller valve areas (0.74±0.21 vs. 0.66±0.23 cm2, p=0.008), higher left ventricular (LV) mass indices (123.40±33.66 vs. 168.22±47.96 g/m2, p<0.001) and lower LV ejection fractions (61.59±7.18 vs. 42.65±15.41%, p<0.001) as compared with low tertile patients. At 30 days, a significantly higher incidence of death (hazard ratio [HR] 7.41, p=0.001) cardiac death (HR 5.82, p=0.006) and MACCE (HR 9.04, p<0.001) was observed among high as compared to low tertile patients. Conclusions: In TAVI patients, higher BNP values at baseline are associated with an increased risk for an adverse event periprocedurally and after 30 days, respectively.

The 2011-12 pilot European Sentinel Registry of Transcatheter Aortic Valve Implantation: in-hospital results in 4,571 patients

AIMS The aim of this prospective multinational registry is to assess and identify predictors of in-hospital outcome and complications of contemporary TAVI practice. METHODS AND RESULTS The Transcatheter Valve Treatment Sentinel Pilot Registry is a prospective independent consecutive collection of individual patient data entered into a web-based case record form (CRF) or transferred from compatible national registries. A total of 4,571 patients underwent TAVI between January 2011 and May 2012 in 137 centres of 10 European countries. Average age was 81.4±7.1 years with equal representation of the two sexes. Logistic EuroSCORE (20.2±13.3), access site (femoral approach: 74.2%), type of anaesthesia and duration of hospital stay (9.3±8.1 days) showed wide variations among the participating countries. In-hospital mortality (7.4%), stroke (1.8%), myocardial infarction (0.9%), major vascular complications (3.1%) were similar in the SAPIEN XT and CoreValve (p=0.15). Mortality was lower in transfemoral (5.9%) than in transapical (12.8%) and other access routes (9.7%; p<0.01). Advanced age, high logistic EuroSCORE, pre-procedural ≥grade 2 mitral regurgitation and deployment failure predicted higher mortality at multivariate analysis. CONCLUSIONS Increased operator experience and the refinement of valve types and delivery catheters may explain the lower rate of mortality, stroke and vascular complications than in historical studies and registries.

Transcatheter aortic valve implantation and bleeding: incidence, predictors and prognosis

Peri-procedural bleeding complications are feared adverse events in patients undergoing transcatheter aortic valve implantation (TAVI). Little is known about the implications of peri-procedural bleeding on clinical outcome. In a prospective single-center registry of consecutive patients undergoing TAVI, we investigated incidence, predictors and clinical consequences of life-threatening and major bleeding as defined by the Valve Academic Research Consortium. Among 389 consecutive patients undergoing TAVI by a transfemoral (79.2%), transapical (19.6%) or trans-subclavian (1.3%) approach between July 2007 and October 2011, life-threatening or major peri-procedural bleeding events occurred in 64 (16.4%) and 125 patients (32.1%), respectively. Patients with peri-procedural bleeding events had a higher logistic EuroSCORE, more advanced renal disease, and were more symptomatic as assessed by New York Heart Association functional class at baseline as compared to patients with no bleeding. Life-threatening bleeding was associated with a higher all-cause (17.2 vs. 5.6 vs. 3.0%, p < 0.001) and cardiovascular mortality (10.9 vs. 5.6 vs. 2.5%, p = 0.02) at 30 days compared to patients with major bleeding or no bleeding. Multivariate analysis identified transapical access (OR 2.6, 95% CI 1.4-4.8; p = 0.002), glomerular filtration rate <30 ml/min (OR 2.3, 95% CI 1.1-4.7, p = 0.031), and diabetes (OR 1.8, 95% CI 1.001-3.2, p = 0.049) as independent predictors of life-threatening, peri-procedural bleeding. Life-threatening bleeding complications in patients undergoing TAVI are associated with increased mortality. Renal impairment, diabetes, and transapical approach were identified as independent risk factors for life-threatening bleeding events.

Clinical outcomes of patients with low-flow, low-gradient, severe aortic stenosis and either preserved or reduced ejection fraction undergoing transcatheter aortic valve implantation

AIMS Our aim was to evaluate the invasive haemodynamic indices of high-risk symptomatic patients presenting with 'paradoxical' low-flow, low-gradient, severe aortic stenosis (AS) (PLF-LG) and low-flow, low-gradient severe AS (LEF-LG) and to compare clinical outcomes following transcatheter aortic valve implantation (TAVI) among these challenging AS subgroups. METHODS AND RESULTS Of 534 symptomatic patients undergoing TAVI, 385 had a full pre-procedural right and left heart catheterization. A total of 208 patients had high-gradient severe AS [HGAS; mean gradient (MG) ≥40 mmHg], 85 had PLF-LG [MG ≤ 40 mmHg, indexed aortic valve area [iAVA] ≤0.6 cm(2) m(-2), stroke volume index ≤35 mL/m(2), ejection fraction (EF) ≥50%], and 61 had LEF-LG (MG ≤ 40 mmHg, iAVA ≤0.6 cm(2) m(-2), EF ≤40%). Compared with HGAS, PLF-LG and LEF-LG had higher systemic vascular resistances (HGAS: 1912 ± 654 vs. PLF-LG 2006 ± 586 vs. LEF-LG 2216 ± 765 dyne s m(-5), P = 0.007) but lower valvulo-arterial impedances (HGAS: 7.8 ± 2.7 vs. PLF-LG 6.9 ± 1.9 vs. LEF-LG 7.7 ± 2.5 mmHg mL(-1) m(-2), P = 0.027). At 30 days, no differences in cardiac death (6.5 vs. 4.9 vs. 6.6%, P = 0.90) or death (8.4 vs. 6.1 vs. 6.6%, P = 0.88) were observed among HGAS, PLF-LG, and LEF-LG groups, respectively. At 1 year, New York Heart Association functional improvement occurred in most surviving patients (HGAS: 69.2% vs. PLF-LG 71.7% vs. LEF-LG 89.3%, P = 0.09) and no significant differences in overall mortality were observed (17.6 vs. 20.5 vs. 24.5%, P = 0.67). Compared with HGAS, LEF-LG had a higher 1 year cardiac mortality (adjusted hazard ratio 2.45, 95% confidence interval 1.04-5.75, P = 0.04). CONCLUSION TAVI in PLF-LG or LEF-LG patients is associated with overall mortality rates comparable with HGAS patients and all groups profit symptomatically to a similar extent.

Emergency transcatheter aortic valve implantation for decompensated aortic stenosis

We report the case of an 84-year-old male presenting with syncope and dynamic ST-T wave changes due to decompensated severe valvular aortic stenosis undergoing successful emergency transcatheter aortic valve implantation.