Function and form of the shoulder in congenital and untreated growth hormone deficiency.

OBJECTIVES: The shoulder is the most mobile joint in the entire human body. During arm elevation, it requires the integrity of a set of muscles, bones, and tendons. Individuals with short stature often need to raise their arms above the shoulder girdle and may have functional restriction or shoulder injuries. The impact of isolated GH deficiency (IGHD) on joints remains not well defined. The purpose of this work is to evaluate the function and structure of the shoulder in short-statured adult individuals with untreated IGHD due to the same homozygous mutation in the GHRH receptor gene. METHODS: A cross-sectional study (evidence 3) was carried out in 20 GH-naive IGHD subjects and 20 age-matched controls. They completed the disabilities of the arm, shoulder, and hand (DASH) questionnaire and shoulder ultrasound (US). Thickness of the anterior, medial, and posterior portions of the supraspinatus tendon and of subacromial space was measured, and the number of individuals with tendinosis or tearing of the supraspinatus tendon was registered. RESULTS: DASH score was similar between IGHD and controls, but IGHD subjects complained less of symptoms (p = 0.002). The number of individual with tears was higher in the controls (p = 0.02). As expected, the absolute US measurements were lower in IGHD, but the magnitude of the reduction was most pronounced in the thickness of the anterior portion of the supraspinatus tendon. CONCLUSION: Adults with lifetime IGHD do not have functional shoulder restrictions, complain less of problems in performing upper extremity activities, and have fewer tendinous injuries than controls.

Quantitative measures of the vascular and neural components of the retina in adult individuals with congenital and untreated growth hormone deficiency.

BACKGROUND: The somatotrophic axis, including hypothalamic growth hormone (GH)-releasing hormone (GHRH), pituitary GH and circulating IGF-I, is critical for body size. However, the local production of GH/IGF-I (and IGF-II) and other peptides is relevant for other body functions, such as vascular, brain, and retinal function. The consequences of GH deficiency (GHD) on the retinal structure are still unclear, possibly reflecting the heterogeneity of patients and the different types of assessment in previous publications. Our purpose was to assess quantitative measures of the vascular and neural components of the retina in subjects with severe congenital isolated GHD (IGHD). METHODS: A cross-sectional study was carried out in 25 adult IGHD subjects and 25 age- and gender-matched controls. Interview, physical examination, laboratory data, optical coherence tomography (OCT) and OCT angiography (OCTA) were performed. RESULTS: OCT revealed no difference in the areas of the nerve fiber layer average, nor in the areas of superior, inferior, or nasal quadrants, between the two groups. However, areas of the temporal quadrant (p = 0.041), the optical disc (p = 0.042), the cup (p < 0.0001), as well as the cup/disc ratio (p < 0.0001), were higher in IGHD subjects than controls. The rim area was smaller (p = 0.002), although still normal. In OCTA, there was no difference in the minimum foveal thickness, central fovea, foveal avascular zone, and retinal density in any assessed area. CONCLUSIONS: In conclusion, congenital IGHD does not affect quantitative measures of the vascular and neural retina, and it is associated with increased optical disc in this genetically homogeneous cohort.

Individuals with isolated congenital GH deficiency due to a GHRH receptor gene mutation appear to cope better with SARS-CoV-2 infection than controls.

PURPOSE: Several interactions exist between the GH/IGF axis and the immune system, including effects on innate immunity and humoral and cellular response. Acquired GH deficiency (GHD) has been recently proposed as a risk factor for severity of COVID-19 infections. However, acquired GHD is often associated to other factors, including pituitary tumors, surgery, radiotherapy, and additional pituitary hormones deficits and their replacements, which, together, may hinder an accurate analysis of the relationship between GHD and COVID-19. Therefore, we decided to assess the seroprevalence of SARS-CoV-2 antibodies and the frequency of symptomatic cases of COVID-19 in adults subjects with untreated isolated GHD (IGHD) due to a homozygous null mutation in the GHRH receptor gene. METHODS: A cross-sectional study was carried out in 27 adult IGHD subjects and 27 age- and gender-matched local controls. Interview, physical examination, bio-impedance, hematological and SARS-CoV-2 IgM and IgG antibodies were analyzed. RESULTS: There was no difference in the prevalence of positivity of anti-SARS-CoV-2 IgM and IgG antibodies between the two groups. Conversely, no IGHD individual had a previous clinical diagnosis of COVID-19 infection, while 6 control subjects did (p = 0.023). CONCLUSION: The production of anti-SARS-CoV-2 antibodies was similar between IGHD subjects due to a GHRH receptor gene mutation and controls, but the evolution to symptomatic stages of the infection and the frequency of confirmed cases was lower in IGHD subjects than in GH sufficient individuals.

Cerebral vasoreactivity, a surrogate marker of cerebrovascular disease, is not impaired in subjects with lifetime, untreated, congenital isolated GH deficiency.

OBJECTIVES: Cerebrovascular disease (CeVD) is a major cause of death and disability. The role of the GH/IGF-I axis on CeVD risk is controversial. Patients with GH deficiency (GHD) in the setting of hypopituitarism often exhibit CeVD predisposing factors, like low nitric oxide generation, endothelial dysfunction, increased visceral fat mass, increased levels of LDL cholesterol, and increased intima-media thickness, a surrogate marker of atherosclerosis. However, several confounders such as the primary hypothalamic-pituitary lesion, hormonal replacement therapies, consequences of surgery and radiotherapy, may influence this relationship. Therefore, we decided to assess cerebral vasoreactivity, a surrogate marker of CeVD, in adult subjects with untreated isolated GHD (IGHD) due to the same homozygous null mutation in the GHRH receptor gene. METHODS: A cross-sectional study was carried out in 25 adult IGHD subjects and 25 age- and gender-matched controls. Interview, physical examination, laboratory data, intima-media thickness measurement, and transcranial Doppler were performed. The intracranial hemodynamics (mean flow velocity, pulsatility and resistance indexes) were measured, and the response to the vasodilatory stimulus by breath-holding maneuver (breath-holding index) was calculated. RESULTS: IGHD and control groups were similar in Framingham risk score and intima-media thickness. Similarly, there was no difference in mean flow velocity, pulsatility, resistance, and breath-holding index. CONCLUSIONS: Lifetime, untreated IGHD does not cause impaired cerebral vasoreactivity.

A study of vaccine-induced immune pressure on breakthrough infections in the Phambili phase 2b HIV-1 vaccine efficacy trial.

INTRODUCTION: The Merck Adenovirus-5 Gag/Pol/Nef HIV-1 subtype-B vaccine evaluated in predominately subtype B epidemic regions (Step Study), while not preventing infection, exerted vaccine-induced immune pressure on HIV-1 breakthrough infections. Here we investigated if the same vaccine exerted immune pressure when tested in the Phambili Phase 2b study in a subtype C epidemic. MATERIALS AND METHODS: A sieve analysis, which compares breakthrough viruses from placebo and vaccine arms, was performed on 277 near full-length genomes generated from 23 vaccine and 20 placebo recipients. Vaccine coverage was estimated by computing the percentage of 9-mers that were exact matches to the vaccine insert. RESULTS: There was significantly greater protein distances from the vaccine immunogen sequence in Gag (p=0.045) and Nef (p=0.021) in viruses infecting vaccine recipients compared to placebo recipients. Twenty-seven putative sites of vaccine-induced pressure were identified (p<0.05) in Gag (n=10), Pol (n=7) and Nef (n=10), although they did not remain significant after adjustment for multiple comparisons. We found the epitope sieve effect in Step was driven by HLA A∗02:01; an allele which was found in low frequency in Phambili participants compared to Step participants. Furthermore, the coverage of the vaccine against subtype C Phambili viruses was 31%, 46% and 14% for Gag, Pol and Nef, respectively, compared to subtype B Step virus coverage of 56%, 61% and 26%, respectively. DISCUSSION: This study presents evidence of sieve effects in Gag and Nef; however could not confirm effects on specific amino acid sites. We propose that this weaker signal of vaccine immune pressure detected in the Phambili study compared to the Step study may have been influenced by differences in host genetics (HLA allele frequency) and reduced impact of vaccine-induced immune responses due to mismatch between the viral subtype in the vaccine and infecting subtypes.

Cofactor infections and HIV epidemics in developing countries: implications for treatment.

This article shows that the burden of certain tropical disease infections, after controlling for other factors, is positively correlated with HIV prevalence. Using cross-national data and multivariate linear regression analysis, we investigate the determinants of HIV prevalence in low- and middle-income countries. We begin with social and economic variables used in other cross-national studies and then incorporate data on parasitic and infectious diseases endemic in poor populations, which are found to be strongly and significantly correlated with--and are potent predictors of--HIV prevalence. The paper concludes by arguing that treating tropical diseases may be a cost-effective add-on to HIV-prevention and -treatment programs, thus slowing the spread of HIV in disease-burdened populations.

Evidence for ionic samarium(II) species in THF/HMPA solution and investigation of their electron-donating properties

The fundamental nature of samarium(II) complexes in THF/HMPA (HMPA = hexamethylphosphoramide) solutions containing SmI2 has been clarified by means of cyclic voltammetry, conductivity measurements, UV spectroscopy, and kinetic measurements. The principal species is not [SmI2(hmpa)4] as previously suggested, but either the ionic cluster [Sm(hmpa)4(thf)2+2I- if four equivalents of HMPA is present in the THF solution or [Sm(hmpa)6]2+ 2I- in the presence of at least 10 equivalents of HMPA. The formal potential of the [Sm(hmpa)4(thf)2]3+ 2I-/[Sm(hmpa)4(thf)2]2- 2I- redox couple determined by cyclic voltammetry was -1.79 +/- 0.08 V versus SCE. The order of reactivity of the samarium(II) complexes was found to be [Sm(hmpa)6]2+2I- > [Sm(hmpa)4(thf)2]2+2I- > SmI2 in their respective reactions with 1-iodobutane and with benzyl chloride. Very high rate enhancements, of the order of 1,000-15,000-fold, were observed upon addition of HMPA to the THF solution containing SmI2, Comparison of these rate constants with the corresponding rate constants for electron transfer (ET) reactions involving aromatic radical anions revealed that none of the reactions studied can be classified as outer-sphere ET processes and that the inner-sphere electron-donating abilities of the [Sm(hmpa)4(thf)2]2+ 2I- and SmI2 complexes are comparable. The inner-sphere ET character of the transition state increases on going from 1-iodobutane and benzyl bromide to benzyl chloride and acetophenone.

Using administratively collected hospital discharge data for AIDS surveillance.

The objectives of this study were twofold: to improve methods of identifying possible and acquired immunodeficiency syndrome (AIDS)-related hospital discharges in administrative databases and to measure AIDS-reporting completeness in Massachusetts both overall and by subgroup. We used fiscal year 1988 discharge data from the Massachusetts Rate Setting Commission (RSC) and data from the Massachusetts AIDS Reporting System (ARS). We identified 3362 discharges of adult patients (> 12 years old) from the RSC file that had diagnosis codes which are human immunodeficiency virus (HIV)-specific (042.x, 043.x, 044.x, or 795.8) or pertain to AIDS-defining "manifestations." Medical records of 650 patients apparently not reported to the ARS were reviewed. THe best set of codes overall consisted of either (a) the 042.x code or (b) the 043.x, 044.x, or 795.8 code plus selected manifestation codes (sensitivity, 93%; specificity, 86%; predictive value positive, 71%). Of the 927 AIDS cases identified from the 3362 discharges, only 36 had not been reported. AIDS cases among women (odds ratio (OR) = 2.9; 95% confidence interval (CI): 1.33 to 6.33), intravenous drug users (OR = 4.2; 95% CI: 2.20 to 8.02), and persons residing outside the Boston metropolitan area (OR = 2.3; 95% CI: 1.18 to 4.57) were more likely to be unreported than those among comparison groups.

Preoperative naproxen sodium reduces postoperative pain following arthroscopic knee surgery.

This study was undertaken to assess the efficacy of a single preoperative dose of naproxen sodium in reducing postoperative pain and length of day surgery stay in patients undergoing arthroscopic knee surgery. A randomized, double-blind clinical trial was carried out on 66 ASA I and ASA II patients scheduled for arthroscopic knee surgery. The treatment group (n = 26) received two capsules containing 275 mg of naproxen sodium each, and the control group (n = 40) received placebo. Preoperative and postoperative visual analogue pain scores, postoperative analgesic requirements in hospital as well as 24 hr after discharge, and length of day surgery stay were studied. There was a decrease in postoperative pain, both in hospital (naproxen 0.7 +/- 1.2 vs placebo 2.2 +/- 2.3) and at 24 hr after discharge (naproxen 0.8 +/- 1.9 vs placebo 3.8 +/- 3.2) (P = 0.0001). There was no difference in the need for in-hospital postoperative analgesics or in the time to discharge. However, there was a difference in the use of analgesics after discharge (naproxen group 30.4% vs placebo group 71.4%) (P < 0.01). The results of this study suggest that a single preoperative dose of 550 mg naproxen sodium is effective in reducing postoperative pain in arthroscopic knee surgery, both in the immediate postoperative period and for up to 24 hr after the completion of surgery.

[Angioarchitecture of the ulna and radius and their practical relevance]. / Angioarchitektur von Ulna und Radius und ihre praktische Relevanz.

The periosteal and endosteal blood supply of the human ulna and radius was investigated by anatomical dissection. The main artery concerned is the anterior interosseous artery. It supplies the diaphysis of ulna and radius; its branches feed the distal one-fourths of both the ulna and the radius. The proximal one-fourth of the ulna is supplied by the ulnar artery, the ulnar recurrent artery and the recurrent interosseous artery. Periosteal branches of the common interosseous artery, the ulnar artery and the recurrent interosseous artery supply the proximal one-fourth of the radius. In both bones the main branch of the nutrient artery has an ascending course. The anterior interosseous artery, as the main artery of the periosteal and endosteal supply of the human ulna and radius, is important in transplantation and reconstruction, especially with a view to reducing the rate of pseudarthrosis. When osteosynthesis is planned so-called LC-DC plates should be chosen to preserve the periosteal branches. When a vascularized bone graft is taken from the forearm the vascularization of the remaining bones has to be considered. The vascularity of this area allows various options in grafting.

The effects of intravenous drug use and gender on the cost of hospitalization for patients with AIDS.

At present limited data exist describing the hospital use patterns of intravenous drug users (IVDUs) and women with AIDS. Our objective was to determine if frequency of hospitalization, length of stay (LOS), and cost per hospitalization varied by risk status and gender, controlling for a variety of confounders, including severity of illness as measured by the Turner-Kelly-Ball and Justice AIDS severity of illness systems. We performed a population-based cohort study that compared all women (n = 69) and male IVDUs (n = 74) with AIDS diagnosed in Massachusetts in 1987 with a random sample of all male, nonintravenous drug-using patients diagnosed in that year (n = 148). Frequency of hospitalization, LOS, and cost of hospital care were obtained from hospital billing records for 1987 and 1988. Regression analysis showed 42% longer lengths of stay (p < or = 0.001) and 38% higher cost (p < or = 0.001) per hospitalization for IVDUs with AIDS compared with non-IVDU homosexual AIDS patients. No statistically significant differences by gender were observed. Our results suggest that hospital care for IVDUs is likely to be more expensive. Policymakers should incorporate these data when planning for AIDS care. In addition, instruments to assess severity of illness should incorporate information on intravenous drug use.

The relation between hospital experience and mortality for patients with AIDS.

OBJECTIVE: To determine whether there is an association between mortality and hospital acquired immune deficiency syndrome (AIDS) experience for all AIDS-related diagnoses, and to determine whether the association is explained by differences in severity of illness, earlier discharge of terminally ill patients, or differences in resource use. DESIGN AND SETTING: Population-based statewide cohort study. All hospitalizations identified for a cohort of AIDS patients diagnosed during 1987 in 40 Massachusetts hospitals were included. PATIENTS: All women and all male intravenous drug users (n = 151), and a random sample of all male non-intravenous drug users diagnosed with AIDS during 1987 in Massachusetts (n = 149). MAIN OUTCOME MEASURES: Primary end points studied were (1) inpatient mortality and (2) 30-day mortality. Length of stay, cost, and intensive care unit use were also examined. RESULTS: In 806 hospitalizations at 40 hospitals inpatient mortality was 13.2%. Relative risk of mortality at low AIDS experience hospitals was 2.16 (95% confidence interval, 1.43 to 3.26) compared with high AIDS experience hospitals. When logistic regression was used to control for age, sex, race, human immunodeficiency virus transmission mode, severity, payer, admission type, hospital ownership, and teaching status, low hospital experience with AIDS remained a significant predictor of inpatient mortality (relative risk, 2.92; 95% confidence interval, 1.37 to 6.22). Comparisons of 30-day mortality by hospital AIDS experience yielded similar results. Length of stay and intensive care unit use were also significantly higher at low-experience hospitals after controlling for severity of illness (P < .05). CONCLUSIONS: We conclude that mortality of AIDS patients is higher at hospitals with less AIDS experience. This finding is not because of greater severity of illness, differences in discharge patterns of the terminally ill, or less intensive use of resources.

Transport of siderotic Kupffer cells to the lung and bronchial excretion of iron in experimental iron-overload.

In 3,5,5-trimethylhexanoylferrocene-induced iron overload of rats, three different types of iron-loaded macrophages and derivatives thereof were found in the lungs. On the basis of their localization and of their pattern of iron load it was possible to distinguish: (1) Resident macrophages, showing an alveolar localization and a moderate iron content represented by lysosomal ferritin and haemosiderin. (2) Liver-derived macrophages and giant cells, as well as fragments of them. They showed an exclusive localization in capillaries and alveolar septa, and high concentrations of free ferritin molecules in addition to polymorphous ferritin- and haemosiderin-containing siderosomes. (3) Monocyte-derived intravascular pulmonary macrophages. Initially, they contained iron only as lysosomal aggregates of ferritin and haemosiderin, as a result of phagocytosis of liver-derived macrophageal cell fragments. Later in iron overload, they also showed free ferritin molecules in the cytosol and fused intrapulmonarily to giant cells. The resident as well as the liver-derived siderotic pulmonary macrophages provide a way for iron excretion through the airways.

On the mechanism of kidney stone disintegration by acoustic shock waves.

In the present study we have, by theoretical and experimental investigations, especially concentrated on the importance of acoustic streaming, transient cavitation and microstreaming in the fluid close to the stone. Artificial stones, round stones 20 mm in diameter made of Plaster of Paris or rectangular flat stones, 25 x 25 x 15 mm, were suspended in a water bath at the focus of an EDAP LT01 lithotripter. "Unprotected" stones were disintegrated while stones surrounded by a layer of silicone showed no or very small disintegration. For successful destruction of the calculus, it seems to be essential that the stones are surrounded by a liquid, i.e., water.

A new ultrasonic method for fluid property measurements.

A new ultrasonic method for fluid property measurements is described. The method uses ultrasound to generate acoustic streaming in a fluid. The resulting flow velocity will vary due to several viscous parameters of the fluid. If there are acoustic scatterers in the fluid, it will be possible to monitor the resulting flow velocity with an ultrasound Doppler device. The same acoustic energy is then utilized both to generate the acoustic streaming in the medium and to measure the resulting flow. The method seems to be very well suited for monitoring biological processes. Of special interest, for measurements on contaminated blood or on fluids in a fermentation process, is the method's ability to investigate liquids in a completely closed vessel.