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Hemoglobin-Strumica or alpha 2 112(G19) His replaced by Arg beta 2. (With an addendum: hemoglobin-J-Paris-I, alpha 2 12(A10) Ala replaced by Asp beta 2, in the same population).

Hemoglobin-Strumica has been observed in five members of a Macedonian family. Histidyl residue in position 112 of the alpha chain of this variant is replaced by an arginyl residue. Two other variants (hemoglobin-Dakar and hemoglobin-Hopkins-2) in which this histidyl residue has been replaced by a glutaminyl and by an aspartyl residue, respectively, have been described (Rosa et al. (1968) 12 thCongr. Int. Soc. Haematol. New York, abstract, p. 73 and Charache, S. and Osterag, W. (1970) Bloodt 36, 852). The hemoglobin-Strumica heterozygotes have minimal hematological changes although this may not necessarily be associated with the hemoglobinopathy. Subjects heterozygous for hemoglobin-Dakar have a mild hemolytic anemia and hemoglobin-Hopkins-2 heterozygotes exhibit minimal hematological changes.

Adolescent↗

The differentiation of murine thymocytes in vivo and in vitro.

The differentiation of lymphoid cells in the early foetal mouse thymus was studied in vivo and in organ culture. The lymphoid precursors found in the 13 and 14 day foetal thymus constituted about 50% of the total thymus cell population. These T precursors were large blast-like cells which already expressed the Thy-1 antigen but were mostly TL negative. Both in vivo and in vitro the blasts were rapidly replaced by a population of typical small lymphocytes which were strongly Thy-1 and TL positive but Ig negative. In organ cultures grown under optimal conditions, large bimodal increases in cell numbers occurred. An initial population of about 2 x 10(4) T precursors per thymus lobe gave rise to nearly 10(6) predominantly Thy-1 and TL positive small lymphocytes by the 6--8th day in vitro. After this time lymphocyte numbers decreased until about the 10th day when they again increased to form a second peak of small lymphocytes on the 12--13th day. These cells were also predominantly Thy-1 positive but the majority were now TL negative. No Ig positive B lymphocytes were detected either by immunofluorescence or by autoradiography using polyvalent anti-MIg sera and no plasma cells were detected by electronmicroscopy. At all times however, minor subpopulations of Thy-1 negative small cells were present. The production of small lymphocytes during the 1st week of culture was critically dependent on culture conditions and particularly on the batch of FCS used. The population developing during the 2nd week required less stringent conditions and was less dependent on FCS. The culture systems described should prove useful in the study of T-lymphocyte differentiation.

Animals↗

Hormone replacement therapy and WONCA/COOP functional status: a cross-sectional population-based study of women in Israel.

BACKGROUND: Current indications for hormone replacement therapy (HRT) for menopausal women include symptom relief, but recent studies have raised concerns about the safety of HRT. Little data are available on the effect of HRT on functional status of women taking hormonal preparations after menopause. OBJECTIVE: To assess the association between hormonal replacement therapy and functional status in menopausal women. METHODS: A cross-sectional survey, population-based study of 682 menopausal women between the ages of 50 and 70 years registered with six family physicians in central Israel. The main outcome measure was the functional status measured by the WONCA/COOP charts. RESULTS: A total of 587 women (86%) completed questionnaires. Univariate analysis showed an association between current use of HRT and improved functional status. However this association was diminished in a regression analysis which controlled for sociodemographic status and health variables. The contribution of HRT to functional status was small but was found to be significant in the domains of general health status (1.9%, p<0.002), sleep (0.9%, p<0.044), physical activities (2.1%, p<0.001) and feelings (1.0%, p<0.033). The contribution of HRT to daily activities, social activities, change in health status and pain was not significant. CONCLUSIONS: HRT use had a small contribution to improved functional status in half of the domains measured by the WONCA/COOP charts.

Aged↗

Different effects of oral and transdermal hormone replacement therapies on factor IX, APC resistance, t-PA, PAI and C-reactive protein--a cross-sectional population survey.

The effects of hormone replacement therapy (HRT) on thrombosis risk, thrombotic variables, and the inflammatory marker C-reactive protein (CRP) may vary by route of administration (oral versus transdermal). We studied the relationships of 14 thrombotic variables (previously related to cardiovascular risk) and CRP to menopausal status and to use of HRT subtypes in a cross-sectional study of 975 women aged 40-59 years. Our study confirmed previously-reported associations between thrombotic variables and menopausal status. Oral HRT use was associated with increased plasma levels of Factor IX, activated protein C (APC) resistance, and CRP; and with decreased levels of tissue plasminogen activator (t-PA) antigen and plasminogen activator inhibitor (PAI) activity. Factor VII levels were higher in women taking unopposed oral oestrogen HRT. The foregoing associations were not observed in users of transdermal HRT; hence they may be consequences of the "first-pass" effect of oral oestrogens on hepatic protein synthesis. We conclude that different effects of oral and transdermal HRT on thrombotic and inflammatory variables may be relevant to their relative thrombotic risk; and suggest that this hypothesis should be tested in prospective, randomised studies.

Activated Protein C Resistance↗

Hormone replacement therapy with estradiol and risk of venous thromboembolism--a population-based case-control study.

Recent epidemiological studies on hormone replacement therapy (HRT) containing mainly conjugated equine estrogens indicate increased risk for venous thromboembolism (VTE). The purpose of the present epidemiological study was to evaluate the effect of HRT containing natural estrogens, i.e., estradiol, on the risk of VTE. HRT formulations containing estradiol are commonly used in Scandinavia. The study was a population-based case-control study. Cases were consecutive females, aged 44-70 years, discharged from Ullevål University Hospital with the diagnosis of deep venous thrombosis or pulmonary embolism during 1990-1996. Fifty-one women with cancer-associated thrombosis were excluded from the study. Controls were randomly collected from the same source population and matched by age. The material comprised 176 cases and 352 controls, i.e., 2 controls for each case. Only formulations containing estradiol were used. The frequency of HRT use was 28% (50/176) in cases and 26% (93/352) in controls. The estimated matched crude odds ratio with 95% confidence interval was 1.13 (0.71-1.78), which indicates no significant association of overall use of HRT and VTE. The estimated adjusted odds ratio was 1.22 (0.76-1.94) performing multi-confounder adjustment using the conditional logistic model and adjusting for hypertension, coronary heart disease, diabetes mellitus, smoking habit, BMI, and the presence of previous VTE. Stratification for time of exposure indicated an increased risk of VTE during the first year of use with a crude odds ratio of 3.54 (1.54-8.2). This effect was reduced by extended use to a crude odds ratio of 0.66 (0.39-1.10) after the first year of use. We conclude that use of HRT containing estradiol was associated with a threefold increased risk of VTE, but this increased risk was restricted to the first year of use.

Aged↗

Huge progression of diabetes prevalence and incidence among dialysed patients in mainland France and overseas French territories. A second national survey six years apart. (UREMIDIAB 2 study).

In 1989, we conducted a survey (UREMIDIAB) on the prevalence of diabetes among the population on Renal Replacement Therapy (RRT) in Mainland France (MF), the lowest of the developed countries (6.9%) with a North-South gradient (higher prevalence in the North). This highlighted a possible (genetical or nutritional) "new french paradox" in mainland France populations. In 1992 we conducted a similar study in the french (mainly non caucasian) overseas territories (OT) hosting 3.2% of the total french population, and observed a prevalence of diabetes in RRT of 22.9%. The frequency of diabetes mellitus as a cause of ESRD increasing worldwide, we conducted a second survey in year 1995, in MF and the OT. This study, UREMIDIAB 2, included all of the 244 french dialysis centers. A "Center file" allowed us to determine the prevalence and incidence of diabetes in the french RRT population, (response rate 73%). Then a "Patient medical file" (response rate 64.8% for MF and 91% for the OT) provided detailed informations: type of diabetes (type 1 or 2), etiology of nephropathy, status of diabetic complications, family's geographic origin of the patient. In MF the prevalence of diabetics in RRT doubled within 6 years: 13.04% vs 6.9%, the incidence reached 15.7%. In the OT the prevalence and the incidence reached 25.7% and 35.6%, respectively. Type 2 diabetes represented 87% and 93% of the RRT diabetics in MF and the OT, respectively. Diabetic nephropathy was considered as the cause of renal failure in 91.3% of type 1 and 57.5% of type 2 diabetics under dialysis. We found: 14.7% of myocardial infarction, 12.7% of cerebral strokes, 17.6% of amputations (extreme 37% in some OT centers) among this diabetic RRT population. A North-East (higher prevalence) South-West (lower) gradient was confirmed. We conclude that, while an unusual low prevalence (< or = 13%) of diabetics under dialysis persists in some parts of Mainland France, the total prevalence has been doubled within 6 years (1989/95) and that in Overseas Territories, hosting similar mixed blood populations than USA (afro-caribbeans, asians, indians, micronesians and metis), the high incidence of diabetes in RRT has reached the US levels during the same period.

Diabetes Mellitus, Type 1↗

Is the somatopause an indication for growth hormone replacement?

In the normal population, a gradual and progressive fall in spontaneous growth hormone (GH) secretion occurs with increasing age and is reflected in a parallel fall in circulating insulin-like growth factor (IGF)-I, reduction in lean body mass, increase in body fat and rise in low-density lipoprotein (LDL) cholesterol. Aging is also associated with a progressive failure of body functions and particularly with an increasing lack of physical strength and mobility. Many problems of aging are attributable to the progressive loss of lean tissues and to catabolic events. This can be and often is associated with a progressive decline in independence and quality of life, leading eventually to a prolonged dependence on others, followed by a distressing process of death. By analogy with the fall in ovarian function that inevitably eventually occurs in women with increasing age, this fall in GH secretion has been termed the somatopause. In cross-sectional studies on elderly people, the amount of GH secreted spontaneously correlates well with "good risk factors" such as body composition, mobility, lipid profiles and blood pressure. The important question that these scientific facts raises is whether this fall in GH secretion with increasing years is an important physiological safety event of the normal aging process, or whether it marks the development of GH deficiency which would benefit from GH replacement. It is established that a number of the clinical features of the somatopause are shared with the syndrome of adult-onset GH deficiency and Rudman first proposed the importance of GH in maintaining health and vitality with increasing age many years ago. In 1989, GH replacement was shown to be beneficial in adults with GH deficiency, and in 1990 Rudman showed remarkably similar beneficial effects in a group of elderly men with low plasma IGF-I values, but no underlying pituitary pathology, who were administered GH. In these adults, low doses of GH increased lean body mass and bone mineral density, decreased body fat and lowered LDL cholesterol. Sleep and exercise are the two major stimuli for secretion of GH in normal people and there is evidence to indicate that the GH response to exercise is essential for developing and maintaining physical fitness. There is also some evidence to suggest that adults who continue to exercise with increasing age better maintain lean body mass and physiological GH secretion. So, is the somatopause due to lifestyle changes consequent upon indolence, too much TV and modern living? Is it better to chase our patients (and colleagues?) down to the gym three times a week or should we give them an injection of GH before they sit down with a can of lager to watch the World Cup? Should the fact that elite athletes in virtually all sports have decided from their own "clinical trials" that GH is a performance-enhancing drug, when combined with exercise, have any influence on our strategy? The long-term safety of GH replacement is clearly a matter for concern but we do now know that life without GH is poor both in quantity and quality. Is there a safe therapeutic window that allows GH replacement in the somatopause to add years to life, quality to these years, and maybe even improves the quality of death?

Adult↗

Features of medullary thymic epithelium implicate postnatal development in maintaining epithelial heterogeneity and tissue-restricted antigen expression.

Although putative thymic epithelial progenitor cells have been identified, the developmental potential of these cells, the extent of medullary thymic epithelium (mTEC) heterogeneity, and the mechanisms that mediate the expression of a wide range of peripheral tissue-restricted Ags (TRAs) by mTECs remain poorly defined. Here we have defined several basic properties of the mTEC population that refine our understanding of these cells and impose important constraints for any model of mTEC differentiation and function. We report here that mTECs from adult mice are mitotically active, implying continual turnover, differentiation, and replacement of mTEC populations in the adult thymus. The mTEC population in adult thymus expresses transcription factors implicated in the maintenance of multipotential progenitor cell populations, suggesting that epithelial progenitors in the adult thymus may not be restricted to a thymic fate. mTECs also express multiple transcription factors required for the specification of multiple epithelial lineages in peripheral tissues. Thus, expression of some TRAs by mTECs may represent coordinated gene expression that reflects alternate programs of epithelial differentiation among mTECs. Analysis of TRA expression in individual and small pools of sorted mTECs show that mTECs are highly heterogeneous; each individual mTEC expresses a limited spectrum of TRAs, and the frequency of mTECs that express any individual TRA is quite low (>0.4-2%). Collectively, these findings suggest that the differentiation of mTECs can involve some of the developmental programs used by other epithelial lineages and that expression of some TRAs by mTECs may reflect this activity.

Aging↗

Evidence for positive selection in the capsid protein-coding region of the foot-and-mouth disease virus (FMDV) subjected to experimental passage regimens.

We present sequence data from two genomic regions of foot-and-mouth disease virus (FMDV) subjected to several experimental passage regimens. Maximum-likelihood estimates of the nonsynonymous-to-synonymous rate ratio parameter (d(N)/d(S)) suggested the action of positive selection on some antigenic sites of the FMDV capsid during some experimental passages. These antigenic sites showed an accumulation of convergent amino acid replacements during massive serial cytolytic passages and also in persistent infections of FMDV in cell culture. This accumulation was most significant at the antigenic site A (the G-H loop of capsid VP1), which includes an Arg-Gly-Asp (RGD) cellular recognition motif. Our analyses also identified a subregion of VP3, part of the fivefold axis of FMDV particles, that also appeared to be subjected to positive selection of amino acid replacements. From these results, we can conclude that under the restrictive conditions imposed either by the presence of the monoclonal antibodies, by the persistent infections, or by the competition processes established between different variants of the viral population, amino acid replacement in some capsid-coding regions can be positively selected toward an increase of those mutants with a higher capability to infect the cell.

Aphthovirus↗

Ten-year clinical laboratory follow-up after application of a symptom-based therapeutic strategy to patients with severe chronic aortic regurgitation of predominant rheumatic etiology.

OBJECTIVES: This study was designed to assess the feasibility and the long-term results of a symptom-based strategy of aortic valve replacement in a Brazilian population with predominant rheumatic etiology. BACKGROUND: Optimal criteria for valve replacement in aortic regurgitation (AR) are still not entirely clear. The appearance of symptoms is an indication for surgery, but may be associated with myocardial damage. Although cardiac imaging data have provided a safer guide for such decisions, the use of symptom-based surgical indication has not been validated and might conceivably be better in populations with predominant rheumatic etiology and younger age. METHODS: Echocardiography and rest-exercise radionuclide ventriculography were performed in 75 patients with severe AR, age 28 +/- 9 years, over a period of 10 +/- 0.69 years. Thirty-seven patients developed symptoms and underwent aortic valve replacement surgery within six months. Thirty-eight patients remained asymptomatic and were managed medically. RESULTS: Survival was 100% in asymptomatic patients and 82% in symptomatic. Surgical treatment caused marked ventricular remodeling, with ventricular diameter involution and an improvement of rest-exercise ejection fraction percent variation. Multivariate analysis showed that the probability of developing symptoms within 10 years was 58% for a patient with a left ventricular end-diastolic diameter > or =70 mm and 76% for a patient with left ventricular end-systolic (LVESD) > or =50 mm. Logistic regression identified LVESD and age as the most predictive and specific, but not sensitive, indicators of symptom development. CONCLUSIONS: Application of a standardized therapeutic strategy to patients with severe AR and predominant rheumatic etiology resulted in 90.6% survival after 10 years of follow-up.

Adult↗

Hormone replacement therapy and symptom reporting in menopausal women: a population-based study of 35-65-year-old women in mid-Sweden.

OBJECTIVE: To measure the prevalence rate of hormone replacement therapy (HRT) in the general population and to see whether HRT users report less symptoms, better general health and less use of other palliative than non-users and previous users. METHODS: The study was performed in 1995 as a cross-sectional postal questionnaire study in seven counties in mid-Sweden. The questionnaire was sent to a random sample of 4200 35-64-year-old women of whom 2991 responded. The age distribution of responders and non-responders was similar 49.6+/-8.5 and 49.8+/-8.7 years, respectively. The main outcome measures were vasomotor and general symptoms in relation to menstrual status and HRT. RESULTS: Fifteen percent were on HRT and 2.3% had stopped treatment during the past year. Thirteen percent used other palliatives. Twenty-five percent of premenopausal women experienced any vasomotor symptoms, as compared with 51% of menopausal and 40% of postmenopausal women. Those on HRT reported higher frequencies than non-users of all symptoms except for sweating during the daytime. In addition, menopausal women experienced more of other symptoms, usually not associated with the menopause, than premenopausal and postmenopausal women. HRT users reported a significantly worse perceived health and they took other palliatives drugs to a larger extent than HRT non-users. CONCLUSION: HRT seemed to be effective in relieving some vasomotor symptoms but did not affect the prevalence of other symptoms or perceived health, in spite of the fact that women on HRT supplemented their therapy with palliative drugs to a larger extent than other women.

Adult↗

Results of up to 9 years of high-temperature-fixed valvular bioprostheses in a young population.

BACKGROUND: Bioprosthetic valve replacement in young patients remains a controversial issue due to a high rate of early calcification. Previous studies in our laboratory have shown that high-temperature fixation of glutaraldehyde preserved bioprosthesis (HTF) mitigates calcification. The first clinical application of this technique was started in 1991. METHODS: From January 1991 to September 1998, 50 patients in whom anticoagulants were contraindicated underwent single aortic valve replacement (n = 33) or mitral valve replacement (n = 17) using HTF bioprostheses. The age of the patients ranged from 7 months to 35 years (mean 22.7+/-6.8 years). The mean New York Heart Association status was 2.4. Mean follow-up 4 years +/- 1.8 for a total follow-up of 196 patient-years. RESULTS: There were no operative deaths and but there were two late deaths, one valve related. Structural failure occured in 4 patients (2%/patient-year) requiring a reoperation in 3 patients (1.5%/patient-year). No endocarditis or thromboembolic episodes were observed. At late examination (June 2000), 46 patients (92%) were in New York Heart Association class I or II, with a well functioning valve. CONCLUSIONS: Replacement with HTF bioprostheses in young patients has demonstrated encouraging midterm results with a low incidence of structural failure

Adolescent↗

Archaic African and Asian lineages in the genetic ancestry of modern humans.

A 3-kb region encompassing the beta-globin gene has been analyzed for allelic sequence polymorphism in nine populations from Africa, Asia, and Europe. A unique gene tree was constructed from 326 sequences of 349 in the total sample. New maximum-likelihood methods for analyzing gene trees on the basis of coalescence theory have been used. The most recent common ancestor of the beta-globin gene tree is a sequence found only in Africa and estimated to have arisen approximately 800,000 years ago. There is no evidence for an exponential expansion out of a bottlenecked founding population, and an effective population size of approximately 10,000 has been maintained. Modest differences in levels of beta-globin diversity between Africa and Asia are better explained by greater African effective population size than by greater time depth. There may have been a reduction of Asian effective population size in recent evolutionary history. Characteristically Asian ancestry is estimated to be older than 200,000 years, suggesting that the ancestral hominid population at this time was widely dispersed across Africa and Asia. Patterns of beta-globin diversity suggest extensive worldwide late Pleistocene gene flow and are not easily reconciled with a unidirectional migration out of Africa 100,000 years ago and total replacement of archaic populations in Asia.

Africa↗

Quantitative genetics of doubled haploid populations and application to the theory of line development.

The line value of a genotype is defined as the expected value of all lines that can be derived from this genotype. Specific genetic effects are defined for this value: only additive and additive by additive epistatic effects are necessary. There is no dominance effect for such a value. A general expression for the covariances between related lines is given. From a design with several lines per haplodiploidized plant taken at random from a population it is possible to estimate the additive variance for line value and the variance of additive by additive epistasis for line value. Variances of higher order epistasis can be estimated with a two-factor mating design in which a cross is replaced by the population of lines that can be derived from it. With a diallel or a factorial design a direct test for the presence of homozygous by homozygous epistasis is possible. The application of the concept of line value to the theory of line development leads to simple expressions of genetic advance in one cycle of recurrent selection according to the testing system. A brief consideration of these expressions leads to the conclusion that single doubled haploid descent recurrent selection will be one of the most efficient methods for low heritabilities and with a rapid development of doubled haploid lines.

Alleles↗

The effect of Wolbachia-induced cytoplasmic incompatibility on host population size in natural and manipulated systems.

Obligate, intracellular bacteria of the genus Wolbachia often behave as reproductive parasites by manipulating host reproduction to enhance their vertical transmission. One of these reproductive manipulations, cytoplasmic incompatibility, causes a reduction in egg-hatch rate in crosses between individuals with differing infections. Applied strategies based upon cytoplasmic incompatibility have been proposed for both the suppression and replacement of host populations. As Wolbachia infections occur within a broad range of invertebrates, these strategies are potentially applicable to a variety of medically and economically important insects. Here, we examine the interaction between Wolbachia infection frequency and host population size. We use a model to describe natural invasions of Wolbachia infections, artificial releases of infected hosts and releases of sterile males, as part of a traditional sterile insect technique programme. Model simulations demonstrate the importance of understanding the reproductive rate and intraspecific competition type of the targeted population, showing that releases of sterile or incompatible individuals may cause an undesired increase in the adult number. In addition, the model suggests a novel applied strategy that employs Wolbachia infections to suppress host populations. Releases of Wolbachia-infected hosts can be used to sustain artificially an unstable coexistence of multiple incompatible infections within a host population, allowing the host population size to be reduced, maintained at low levels, or eliminated.

Animals↗

Standardized incidence rates of total hip replacement for primary hip osteoarthritis in the 5 Nordic countries: similarities and differences.

BACKGROUND: The national hip registers of the Nordic countries provide an opportunity to compare age- and sex-standardized annual incidence of primary total hip replacement (THR) and types of implants used for primary hip osteoarthritis (OA) in Denmark, Finland, Iceland, Norway and Sweden. METHODS: The data on THR were from the national total hip replacement registries, and population data were from the national statistics agencies. Annual incidence density per 100,000 was calculated for each 5-year age group and it was age-standardized using the WHO European standard population. RESULTS: Crude country-specific annual incidence (all ages) for 1996-2000 varied between 73 and 90. WHO age-standardized annual incidence (all ages) varied between 61 (Finland) and 84 (Iceland). For the ages 50-89, comprising 94-98% of all THRs for OA, annual incidence varied between 217 (Finland) and 309 (Iceland). For Norway, the sex incidence ratio (women/men) was 2, and for the other countries it was between 1.1 and 1.3. The use of uncemented and hybrid replacements was considerably higher in Finland and Denmark than in the other countries. INTERPRETATION: We found overall similarity in THR incidence between the 5 Nordic countries, but substantial differences between women and men, and in the use of different types of implant. Population-based, age-standardized and disease-specific information on THR incidence is required in order to properly explore the causes of differences in provision and practice of THR in different countries, regions and groups, and it will aid in projecting future needs.

Aged↗

Demographic scope and economic magnitude of contemporary organ replacement therapies.

This analysis draws upon a variety of sources to provide a tally of the number of patients receiving organ replacement therapies and the costs associated with the provision of such therapies. Constituent data were available from treatment-specific patient registries, peer reviewed reports in scientific literature, business publications, and industry sources. The magnitude and economic scope of the contemporary organ replacement enterprise were found to be much larger than is generally recognized. In the year 2000, the lives of over 20 million patients will be sustained, supported, or significantly improved by functional organ replacement. The impacted population grows at over 10% per year. Worldwide, first year and follow-up costs of organ prosthesis exceeds $300 billion US dollars per year and represents between 7 and 8% of total worldwide health care spending. Remarkably, in the United States, the costs of therapies enabled by organ replacement technology exceed 1% of the Gross Domestic Product. These findings constitute an incontestable tribute to the scientific significance and medical impact of the still nascent field of substitutive medicine. At the same time, the enormous magnitude of resources dedicated to organ replacement raises several issues related to overall cost effectiveness of current modalities and raises challenges and opportunities for future technical developments.

Arthroplasty, Replacement↗

Growth hormone replacement for adult growth hormone deficiency.

Growth hormone deficiency (GHD) in childhood causes growth retardation, short stature and significant impairment of adult height. Growth hormone (GH) has been given successfully to these children for > 40 years but only since the introduction of recombinant DNA technology, has enough GH been available for paediatric needs and also for other indications. Adults with pituitary disease and hypopituitarism commonly develop GHD. Adult GHD is associated with an array of body composition alterations and metabolic abnormalities, as well as impaired physical performance and psychological well-being. None of these abnormalities are pathogenic for GHD but they constitute a characteristic clinical syndrome. GH substitution for adult GHD has been approved since 1996 in the US and most Western countries and since then, the clinical experience with this novel therapeutic modality is exponentially increased. GH replacement in this population has resulted in considerable clinical benefits. This article reviews the therapeutic principles, available GH formulations and current treatment guidelines for adult patients with GHD.

Body Composition↗