Atomic layer deposition ultrathin film origami using focused ion beams.

Focused ion beam (FIB) micromachining is a powerful tool for maskless lithography and in recent years FIB has been explored as a tool for strain engineering. Ion beam induced deformation can be utilized as a means for folding freestanding thin films into complex 3D structures. FIB of high energy gallium (Ga+) ions induces stress by generation of dislocations and ion implantation within material layers, which create creases or folds upon mechanical relaxation enabled by motion of the material layers. One limitation on such processing is the ability to fabricate flat freestanding thin film structures. This capability is limited by the residual stresses formed during processing and fabrication of the films, which can result in initial curvature and deformation of films upon release from a sacrificial fabrication layer. This paper demonstrates folding in freestanding ultrathin films (<40 nm thin) of heterogeneous composition (metal, insulator, semiconductor, etc) with large lateral dimension structures (aspect ratio >1:1000) by ion-induced stress relaxation. The ultrathin flat structures are fabricated using atomic layer deposition on sacrificial polyimide. We have demonstrated vertical folding with 30 keV Ga+ ions in structures with lateral dimensions varying from 10 to 50 µm.

Ultrathin thermoacoustic nanobridge loudspeakers from ALD on polyimide.

The recent development of low-temperature (<200 °C) atomic layer deposition (ALD) for fabrication of freestanding nanostructures has enabled consideration of active device design based on engineered ultrathin films. This paper explores audible sound production from thermoacoustic loudspeakers fabricated from suspended tungsten nanobridges formed by ALD. Additionally, this paper develops an approach to lumped-element modeling for design of thermoacoustic nanodevices and relates the near-field plane wave model of individual transducer beams to the far-field spherical wave sound pressure that can be measured with standard experimental techniques. Arrays of suspended nanobridges with 25.8 nm thickness and sizes as small as 17 µm × 2 µm have been fabricated and demonstrated to produce audible sound using the thermoacoustic effect. The nanobridges were fabricated by ALD of 6.5 nm Al2O3 and 19.3 nm tungsten on sacrificial polyimide, with ALD performed at 130 °C and patterned by standard photolithography. The maximum observed loudspeaker sound pressure level (SPL) is 104 dB, measured at 20 kHz, 9.71 W input power, and 1 cm measurement distance, providing a loudspeaker sensitivity value of ∼64.6 dB SPL/1 mW. Sound production efficiency was measured to vary proportional to frequency f 3 and was directly proportional to input power. The devices in this paper demonstrate industrially feasible nanofabrication of thermoacoustic transducers and a sound production mechanism pertinent to submicron-scale device engineering.

Laparoscopic adjustable gastric band survival in a high-volume bariatric unit.

BACKGROUND: Although laparoscopic adjustable gastric bands (LAGBs) have been shown to be efficacious, their long-term usefulness has been questioned. This study examined the fate of LAGBs in a unit with over a decade of experience in their use. Patient factors related to the need for, and timing of, band removal were investigated. METHODS: A prospectively maintained database was used to identify all patients with a LAGB. Patient demographics, need for band removal and band survival were examined. Logistic regression modelling was done and Kaplan-Meier curves were calculated for band survival. RESULTS: Between 2000 and 2012, 674 bands were placed in 665 patients. Of these, 143 (21.2 per cent) were removed. There was no difference in rates of removal by sex (P = 0.910). The highest rates of removal were in patients aged less than 40 years (26.7 per cent), and those with a BMI greater than 60 kg/m2 (28.6 per cent). Earlier band removal was seen in younger patients (P = 0.002). Rates of removal increased linearly by earlier year of placement. Of bands placed 4 or more years previously, 35.0 per cent required removal. Eighty-three patients (58.0 per cent) who had a LAGB removed went on to have a further bariatric procedure (band to bypass, 66; band to sleeve, 17). CONCLUSION: Even in experienced hands LAGB does not appear to be a definitive solution. In a large number of patients there appears to be a finite 'band life', with the majority of patients requiring conversion to a further bariatric procedure.

Major histocompatibility complex diversity in the endangered Ethiopian wolf (Canis simensis).

The major histocompatibility complex (MHC) influences immune response to infection and vaccination. In most species, MHC genes are highly polymorphic, but few wild canid populations have been investigated. In Ethiopian wolves, we identified four DLA (dog leucocyte antigen)-DRB1, two DLA-DQA1 and five DQB1 alleles. Ethiopian wolves, the world's rarest canids with fewer than 500 animals worldwide, are further endangered and threatened by rabies. Major rabies outbreaks in the Bale Mountains of southern Ethiopia (where over half of the Ethiopian wolf population is located) have killed over 75% of wolves in the affected sub-populations. In 2004, following a rabies outbreak, 77 wolves were vaccinated, and 19 were subsequently recaptured to monitor the effectiveness of the intervention. Pre- and post-vaccination rabies antibody titres were available for 18 animals, and all of the animals sero-converted after vaccination. We compared the haplotype frequencies of this group of 18 with the post-vaccination antibody titre, and showed that one haplotype was associated with a lower response (uncorrected P < 0.03). In general, Ethiopian wolves probably have an adequate amount of MHC variation to ensure the survival of the species. However, we sampled only the largest Ethiopian wolf population in Bale, and did not take the smaller populations further north into consideration.

Artemisia annua extracts, artemisinin and 1,8-cineole, prevent fruit infestation by a major, cosmopolitan pest of apples.

CONTEXT: Extracts of Artemisia annua (L.) (Asteraceae) and artemisinins are used for treatment of malaria, parasitic infections and have potent anticancer properties in cell lines. Eucalyptus oil and 1,8-cineole have antimicrobial, immune-stimulatory, anti-inflammatory, antioxidant, analgesic, and spasmolytic effects. Codling moth, Cydia pomonella, (L.) (Tortricidae), is a major cosmopolitan pest of the apple, potentially causing damage translating to 40 billion US dollars per year, globally. Currently used control measures are either hazardous to agricultural workers and harmful to environment, or ineffective. The potential of plant-derived semiochemicals for codling moth control is heavily understudied. OBJECTIVE: This study evaluated the potential of A. annua extracts, and two chemicals that this plant contains, artemisinin and 1,8-cineole, for preventing apple feeding and infestation by neonate Cydia pomonella larvae. METHODS: We studied effects of A. annua extracts, artemisinin and 1,8-cineole on apple infestation by neonate codling moth larvae using fruit choice assay in laboratory experiments. Preference of fruit treated with test solutions versus fruit treated with solvent was recorded and analyzed. RESULTS: Crude A. annua extracts prevented fruit feeding at 1, 3, and 10 mg/ml. Artemisinin had feeding deterrent effects at 10 and 30 mg/ml, and 1,8-cineole at 100 and 300 mg/ml. DISCUSSION AND CONCLUSIONS: A. annua contains chemicals that prevent apple infestation by codling moth neonates. Artemisinin and 1,8-cineole are among them, but there are other, polar constituents of A. annua, which have similar effects. There is a potential of using our findings in codling moth control and production of codling moth-resistant apples.

Association of HLA-DRB1* and keloid disease in an Afro-Caribbean population.

BACKGROUND: Keloid disease (KD) is a fibroproliferative dermal tumour of unknown aetiology. The high incidence of familial clustering in KD, its prevalence in certain races and its concordance in identical twins suggest a strong genetic predisposition to keloid formation. The highest incidence of keloids is found in black populations, where the incidence has been estimated to be up to 16%. The most polymorphic genetic system in vertebrates is the major histocompatibility complex (MHC) also known as the human leucocyte antigen (HLA) system. The MHC has been shown to be strongly associated with numerous conditions. Of particular relevance is the association of DR2 with dermal fibrotic diseases including sarcoidosis and systemic sclerosis. AIMS: To investigate the aetiology of KD and the potential involvement of the MHC. METHODS: We compared the HLA-DRB1 phenotype frequencies of Afro-Caribbean patients of Jamaican origin with keloid scars against those seen in a control population of the same ethnicity (n = 121; mean age 34.8 years, range 14-88). In total, 180 keloid cases of Afro-Caribbean origin, recruited from Kingston, Jamaica, were evaluated in the study (mean age 29.7 years, range 2-90 years). HLA-DRB1 alleles were determined in all participants using a semiautomated typing system of reverse hybridization PCR with sequence-specific oligonucleotide probes. HLA-DRB1* phenotype frequencies were established in the Jamaican Afro-Caribbean population and comparisons made between cases and controls. Furthermore, the influence of multiple vs. single lesions, patient gender and family history were also investigated. RESULTS: Differences were observed between the disease and control cohorts although none was significant. CONCLUSIONS: This study does not support an association between HLA-DRB1* alleles and susceptibility to keloid in people of Afro-Caribbean origin.

Genetic susceptibility to raised dermal scarring.

Raised skin scars, such as keloid and hypertrophic scars mostly occur post-wounding in the human dermis. There is compelling evidence for a genetic component to these conditions, given the familial predisposition, varied incidence in different ethnic populations and the presence in twins. The aim of this study was to perform a systematic review of the literature regarding genetic susceptibility to raised dermal scarring. We identified relevant articles by a systematic search of relevant search engines. Key search terms included: keloid disease, hypertrophic scarring, fibrosis, linkage analysis, gene expression, human leucocyte antigen system (HLA), twins, families, case-control association study and congenital syndromes. Numerous candidate genes have been identified, along with potential linkage regions on different chromosomes. Recent data also suggest that carriers of specific major histocompatibility complex (MHC) alleles, in particular HLA-DRB1*15, HLA-DQA1*0104, DQB1*0501 and DQB1*0503, are at increased risk of developing keloid scarring. In addition, distinct immunophenotypical profiles can distinguish between keloid and hypertrophic scars. Keloid and hypertrophic scars are multifaceted aberrations of the healing process with as yet incompletely understood aetiologies. Current data suggest a genetic susceptibility with a strong immunogenic component to dermal fibrosis with MHC genes being implicated. It appears unlikely that a single gene is responsible for the development of raised dermal scars. A likely scenario may involve the interaction of several gene pathways in addition to environmental factors. The ability to assess accurately an individual's potential genetic susceptibility to raised scarring may lead to a more personalized approach to their management in the future.

Appendicitis in pregnancy: an ongoing diagnostic dilemma.

INTRODUCTION: Appendicitis in pregnancy (AIP) is the most common nonobstetric cause of an acute abdomen requiring surgical intervention. Diagnostic difficulties arising from gestational symptoms compound the risk of foetal loss after negative appendicectomy and exponentially increase the risk to mother and foetus with delay in genuine cases. In this article, we investigate the symptoms and signs of AIP and attempt to identify consistent clinical features and review the role of imaging in diagnosis. METHOD: MEDLINE and PubMed were searched for case-control studies recording preoperative symptoms/signs suggestive of AIP, as well as appendiceal pathology. Combined likelihood and odds ratios (OR) were created for clinical features across homogenous papers. Papers examining the use of laparoscopy, ultrasound (US), computerized tomography (CT) and magnetic resonance imaging (MRI) were assessed qualitatively. RESULTS: Seven papers met the inclusion criteria for the analysis of consistent clinical features (450 patients). The only symptoms or signs significantly associated with a diagnosis of appendicitis were nausea (OR: 2.21, 95%CI: 1.34-3.66), vomiting (OR: 0.82-15.6 range) and peritonism (OR: 1.80, 95%CI: 1.06-3.04). US, CT and MRI have all been used to successfully diagnose AIP. Laparoscopic appendicectomy has been safely undertaken in pregnancy. CONCLUSION: Appendicitis will continue to challenge the diagnostic acumen of surgeons. Whilst useful, consensus regarding the safety of laparoscopy, CT and MRI in pregnancy is yet to be achieved.

Safety and efficacy of intravenous zoledronic acid in paediatric osteoporosis.

AIM: To study the safety and efficacy of zoledronic acid treatment in children with osteoporotic bone disorders. STUDY DESIGN: Observational study in 22 patients with osteogenesis imperfecta and related conditions who were treated at our institution with zoledronic acid. These patients had initial treatment with pamidronate. Lumbar spine z-scores, annual change in areal bone mineral density, bone mineral adjusted density, fracture number and linear growth before and after zoledronic acid treatment was commenced were compared. RESULTS: Patients were treated for a mean of 3.4 years with zoledronic acid after a mean of 3.75 years of pamidronate therapy. There was no difference in areal bone mineral density accrual in the first year of zoledronic acid treatment compared to the preceding year of pamidronate treatment. Lumbar spine z-scores and bone mineral adjusted density continued to increase with zoledronic acid. Number of fractures during treatment was significantly reduced compared to baseline with either bisphosphonate, with no difference between treatments. Linear growth was not affected. CONCLUSIONS: Zoledronic acid is at least as effective as pamidronate as treatment for paediatric osteoporosis, and has a similar safety profile.

Bisphosphonate-associated osteonecrosis of the jaw: does it occur in children?

BACKGROUND: Bisphosphonate use in adult patients has been linked to osteonecrosis of the jaw (ONJ). This complication has not been systematically assessed in a paediatric population receiving bisphosphonates. OBJECTIVE: To assess our cohort of paediatric patients treated with intravenous bisphosphonate for occurrence of ONJ. DESIGN: Observational study at a tertiary children's hospital. PATIENTS: A total of 42 paediatric patients with osteoporosis who received bisphosphonate infusions for a mean of 6.5 years (SD 2.7 years) were assessed clinically and radiographically for possible ONJ. Among 42, 37 patients had received disodium pamidronate 1 mg/kg/dose at a mean cumulative dose of 19.8 mg/kg and zoledronic acid (ZA) 0.05 mg/kg/dose at a mean cumulative dose of 0.49 mg/kg; four had received ZA and one received pamidronate alone. Invasive dental treatment during bisphosphonate treatment, a known risk factor for osteonecrosis, was specifically assessed. RESULTS: In all patients assessed, including 11 who had invasive dental treatment, there were no cases of osteonecrosis. CONCLUSION: ONJ has so far not been demonstrated in this patient group.

Positive association of HLA-DRB1*15 with keloid disease in Caucasians.

Keloid disease (KD) is a fibroproliferative dermal tumour of unknown aetiology. The increased familial clustering in KD, its increased prevalence in certain races and concordance in identical twins suggest a strong genetic predisposition to keloid formation. The most polymorphic genetic system in all vertebrates is the major histocompatibility complex (MHC) also known as the human leucocyte antigens (HLA) system. The MHC has been shown to be strongly associated with numerous conditions. Of particular interest is the association of DR2 with dermal fibrotic diseases such as sarcoidosis. To investigate the aetiology of KD, we compared the HLA-DRB1 phenotype frequencies of Caucasoid patients with keloid scars against those observed in a control population (n = 537). A total number of 67 keloid cases were evaluated in the study. HLA-DRB1 alleles were determined in all cases and controls using a commercially available semiautomated reverse hybridization polymerase chain reaction sequence-specific oligonucleotide probes typing system. HLA-DRB1*15 phenotype frequency was higher in KD-positive Caucasians (38.8%) when compared with controls (20.9%) (corrected P = 0.017). We conclude that in Caucasians of Northern European origin, HLA-DRB1*15 is associated with risk of developing KD following injury. We have demonstrated for the first time that a genetic association exists between HLA-DRB1*15 status and the risk of developing keloid scarring in Caucasians. Our data suggest the possible involvement of an immunogenic component to KD although the exact mechanisms involved in MHC-driven abnormal fibrosis will require further investigation.

Cyclic AMP-dependent protein kinase (PKA) gene expression is developmentally regulated in fetal lung.

We characterized the ontogeny of cAMP-dependent protein kinase (PKA) enzymatic activity and PKA subunit mRNA expression in developing lung. The lungs of fetal Sprague-Dawley rat pups were removed after 16, 18, or 20 days of gestation and at term. PKA activity was greatest in the 18- and 20-day gestation lungs. Tissue cAMP levels were lowest in the 16-day lungs and increased with lung maturity. We were able to detect only low levels of mRNA for the C beta subunit of PKA by northern blot analysis of total lung RNA and we were able to detect mRNA for the RI beta and RII beta subunits only by RT-PCR. Therefore, we limited our analysis of PKA subunit mRNA levels to those for C alpha, RI alpha and RII alpha. The mRNA levels for C alpha, were highest in the 16-day lung, decreased at 18 and 20 days, were lower in the newborn and lowest in the adult lung. RI alpha mRNA levels were also highest at 16 days and lowest in the adult lung. However, RII alpha mRNA levels were similar in the 18-day, 20-day and newborn lungs. Dexamethasone treatment of fetal lung explants resulted in a small decrease in RI alpha mRNA levels but was not associated with a change in PKA activity. We conclude that PKA activity and PKA subunit mRNA expression are developmentally regulated in fetal lung. Such regulation results in optimal PKA activity at the time of type II alveolar cell differentiation, presumably in preparation for air breathing. The absence of an effect of glucocorticoid on PKA activity suggests that glucocorticoids are not responsible for the increase in PKA activity which accompanies this critical time in lung maturation.

Effects of transient coronary ischemia and reperfusion on myocardial edema formation and in vitro magnetic relaxation times.

The effects of transient ischemia and reperfusion on regional myocardial function, salvage and swelling have been systematically analyzed in experimental canine preparations. The results of these interventions on myocardial in vitro measurements of magnetic relaxation times (T1 = magnetization recovery, T2 = spin echo) are of significant importance with respect to future nuclear magnetic resonance tomographic imaging. Thus, using a pulsed magnetic resonance spectrometer (10.7 MHz), myocardial tissue samples from two groups of dogs were evaluated. In group 1 (n = six dogs), the left anterior descending artery was occluded for 3 hours before sacrifice; in group 2 (six dogs), 3 hours of occlusion was followed by 1 hour of reperfusion. Multiple tissue samples from normal and ischemic (or ischemic and reperfused) myocardium were obtained for measurement of T1, T2 and % water content (wet weight--dry weight/wet weight). Water content increased with ischemia (78 +/- 4%) and reperfusion (81 +/- 4%) (both p less than 0.01 versus control values). Values for T1 increased with ischemia (598 +/- 39 versus 487 +/- 23 ms in normal tissue from the same heart, p less than 0.01). Even greater T1 changes occurred in the animals with reperfusion (654 +/- 52 ms, p less than 0.01 versus the intra-animal control values). Changes in T2 were similar but less marked (ischemic zone 43.9 +/- 1.0 versus 41.2 +/- 1.0 ms in nonischemic tissue in the corresponding heart, p less than 0.05; reperfusion zone 48.3 +/- 3.5 versus 41.9 +/- 2.3 ms in the normal zone, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Phylogenetic analysis of T-Box genes demonstrates the importance of amphioxus for understanding evolution of the vertebrate genome.

The duplication of preexisting genes has played a major role in evolution. To understand the evolution of genetic complexity it is important to reconstruct the phylogenetic history of the genome. A widely held view suggests that the vertebrate genome evolved via two successive rounds of whole-genome duplication. To test this model we have isolated seven new T-box genes from the primitive chordate amphioxus. We find that each amphioxus gene generally corresponds to two or three vertebrate counterparts. A phylogenetic analysis of these genes supports the idea that a single whole-genome duplication took place early in vertebrate evolution, but cannot exclude the possibility that a second duplication later took place. The origin of additional paralogs evident in this and other gene families could be the result of subsequent, smaller-scale chromosomal duplications. Our findings highlight the importance of amphioxus as a key organism for understanding evolution of the vertebrate genome.

Expression of T-box genes Tbx2-Tbx5 during chick organogenesis.

T-box genes encode putative transcription factors implicated in diverse developmental processes (Papaioannou, V.E. and Silver, L.M., 1998. BioEssays 20, 9-19). We have previously reported the embryonic expression patterns of T-box genes in mice (Chapman, D.L., Garvey, N., Hancock, S., Alexiou, M., Agulnik, S.I., Gibson-Brown, J.J., Cebra-Thomas, J., Bollag, R.J., Silver, L.M., Papaioannou, V.E., 1996. Dev. Dyn. 206, 379-390; Chapman, D.L., Agulnik, I., Hancock, S., Silver, L.M. and Papaioannou, V.E., 1996. Dev. Biol. 180, 534-542; Gibson-Brown, J.J., Agulnik, S.I., Chapman, D.L., Alexiou, M., Garvey, N., Silver, L.M., Papaioannou, V.E., 1996. Mech. Dev. 56, 93-101). Four of these genes (Tbx2-Tbx5) are represented in the mouse genome as two cognate, linked gene pairs (Agulnik, S.I., Garvey, N., Hancock, S., Ruvinsky, I., Chapman, D.L., Agulnik, I., Bollag, R., Papaioannou, V.E., Silver, L.M., 1996. Genetics 144, 249-254), and have all been implicated in playing important roles in limb development (Gibson-Brown, J.J., Agulnik, S.I., Chapman, D.L., Alexiou, M., Garvey, N., Silver, L.M., Papaioannou, V.E., 1996. Mech. Dev. 56, 93-101). To investigate the role of these genes in limb development, we cloned the chicken orthologs and report functional studies, as well as patterns of expression in the developing limbs, elsewhere (Gibson-Brown, J.J., Agulnik, S.I., Silver, L.M., Niswander, L., Papaioannou, V.E., Development, in press). This report details the patterns of expression of Tbx2-Tbx5 in chick embryonic tissues other than the limbs.

Evidence of a role for T-box genes in the evolution of limb morphogenesis and the specification of forelimb/hindlimb identity.

Tetrapod fore-and hindlimbs have evolved from the pectoral and pelvic fins of an ancient vertebrate ancestor. In this ancestor, the pectoral fin appears to have arisen following the rostral homeotic recapitulation of an existing pelvic appendage (Tabin and Laufer (1993), Nature 361, 692-693). Thus the basic appendage outgrowth program is reiterated in both tetrapod fore- and hindlimbs and the pectoral and pelvic fins of extant teleost fishes (Sordino et al. (1995) Nature 375, 678-681). Recently a novel family of putative transcription factors, which includes the T (Brachyury) locus, has been identified and dubbed the "T-box' family. In mice, all of these genes have expression patterns indicative of involvement in embryonic induction (Chapman et al. (1996) Dev. Dyn., in press), and four (Tbx2-Tbx5) are represented as two cognate, linked gene pairs (Agulnik et al., (1996), Genetics, in press). We now report that, whereas Tbx2 and Tbx3 are expressed in similar spatiotemporal patterns in both limbs, Tbx5 and Tbx4 expression is primarily restricted to the developing fore- and hindlimb buds, respectively. These observations suggest that T-box genes have played a role in the evolution of fin and limb morphogenesis, and that Tbx5 and Tbx4 may have been divergently selected to play a role in the differential specification of fore- (pectoral) versus hind- (pelvic) limb (fin) identity.

Angiotensin II/aldosterone dose-response curves in the dog: effect of changes in sodium balance.

The possibility that the responsiveness of plasma aldosterone concentration to angiotensin II alters with changes in sodium balance was investigated in male beagle dogs under conditions of controlled sodium and potassium intake. Angiotensin II was infused at four different rates (usually 3, 6, 12, and 24 ng/kg/min), each for 1 h, 1) after periods of normal sodium diet (32 mEq/day), 2) after moderate sodium depletion (negative cumulative sodium balance 25-58 mEq), 3) after severe sodium depletion (65-116 mEq negative cumulative sodium balance), and 4) after sodium loading (150-212 mEq positive sodium balance), daily potassium intake remaining constant (26 mEq/day) throughout. Angiotensin II/aldosterone dose-response curves after moderate sodium depletion were both elevated and steepened in comparison with those found during normal sodium intake. Severe sodium depletion was associated with even greater elevation of dose-response curves, but individual aldosterone responses to angiotensin II were irregular and unpredictable. Sodium loading significantly diminished aldosterone responsiveness to angiotensin II. Blood pressure increments during angiotensin II infusion were attenuated by sodium depletion.

Low blood pressure in Down's syndrome, A link with Alzheimer's disease?

Low blood pressure is reported in Down's syndrome (DS). To assess this and determine whether low pressure results from the disease or from long-term residence in hospital, we measured blood pressure with a random-zero sphygmomanometer in three groups of patients: 52 DS inpatients, 62 DS outpatients, and 60 outpatients with other forms of mental handicap. Relative to normal reference populations, blood pressure was low in both DS inpatients (systolic, score -33 mm Hg, P < .0001) and DS outpatients (-25 mm Hg, P < .0001). It was normal in non-DS outpatients (-4.0 mm Hg, P = .3). Blood pressure rose normally with age in the non-DS group but not in the DS group. We conclude that blood pressure is low in DS and that this is a feature of the disease rather than of the protected environment in which patients live. A mechanism related to trisomy 21 is likely, and there may be a link with Alzheimer's disease (AD) because blood pressure is also low in Alzheimer's and a high proportion of Ds patients develop this disease. If, as is likely, blood pressure is lowered in Alzheimer's by the neuropathy, the same neuropathy developing early in DS may also reduce blood pressure.

Renal artery stenosis with normal angiotensin II values. Relationship between angiotensin II and body sodium and potassium on correction of hypertension by captopril and subsequent surgery.

The case is reported of a young woman with severe hypertension, unilateral renal artery stenosis, variously normal or marginally high plasma concentrations of active renin, angiotensin II, aldosterone, sodium, and potassium; and normal total exchangeable and total body sodium and potassium. Arteriograms and ureter catheterization showed the stenosis to be severe, but the unstimulated renal vein renin and angiotensin II differential to be modest. Captopril caused an initial fall in angiotensin II and arterial pressure. During prolonged captopril treatment, plasma angiotensin II and aldosterone remained depressed; exchangeable and total body sodium and potassium were unaltered. Blood pressure fell further to normal levels during prolonged captopril treatment, while subsequent surgical correction of the renal artery stenosis was curative; absolute values of blood pressure and plasma angiotensin II were similar in both situations. The findings support, without proving, the concept that chronic modest elevation of angiotensin II may be responsible for sustained hypertension in unilateral renal artery stenosis. Patients of this type contrast sharply with those, also with severe renal artery stenosis or occlusion, who have gross elevation of renin, angiotensin II, and aldosterone, with sodium and potassium deficiency. Captopril or surgery are effective in both syndromes, but the manner of response to treatment differs markedly.

Response of aldosterone and 18-hydroxycorticosterone to angiotensin II in normal subjects and patients with essential hypertension, Conn's syndrome, and nontumorous hyperaldosteronism.

Dose-response curves relating plasma angiotensin II (AII) concentration during AII infusion to blood pressure (BP), to plasma aldosterone, and to plasma 18-hydroxycorticosterone were compared in normal subjects and in patients with essential hypertension, Conn's syndrome, and nontumorous hyperaldosteronism. The BP response was steeper than normal in patients with Conn's syndrome and essential hypertension. Before infusion, mean plasma aldosterone concentration was approximately four-fold higher in Conn's syndrome than in the normal group, while that of 18-hydroxycorticosterone was ninefold higher. Neither increased significantly during AII infusion. In essential hypertension, both corticosteroids were within the normal range, but their responses to AII infusion were greater than normal. In the three subjects with non-tumorous hyperaldosteronism, plasma aldosterone and 18-hydroxycorticosterone concentrations were raised, and their responses to AII infusion resembled those found in essential hypertension and were different from those found in Conn's syndrome. This suggests that nontumorous hyperaldosteronism is not a variant of Conn's syndrome. In the response to AII and in other ways, it is indistinguishable from essential hypertension.