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Biomedical subjects

R D Gordon

Publications and source records attributed to R D Gordon.

At least 37 records · Page 2Linked to original sources
PubMed2000

Treatment of familial hyperaldosteronism type I: only partial suppression of adrenocorticotropin required to correct hypertension.

In familial hyperaldosteronism type I, inheritance of a hybrid 11beta-hydroxylase/aldosterone synthase gene leads to ACTH-regulated overproduction of aldosterone (causing hypertension) and of "hybrid" steroids, 18-hydroxy- and 18-oxo-cortisol. To determine whether complete suppression of the hybrid gene is necessary to normalize blood pressure, we sought evidence of persisting expression in eight patients who were rendered normotensive for 1.3-4.5 yr by glucocorticoid treatment. At the time of the study, six patients were receiving dexamethasone (0.125-0.25 mg/day) and two patients were taking prednisolone (2.5 or 5 mg/day). Urinary 18-oxo-cortisol levels during treatment demonstrated close correlation with mean "day curve" (blood collected every 2 h for 24 h) cortisol (r = 0.74), consistent with regulation by ACTH. Although urinary 18-oxo-cortisol levels were lower during than before treatment (mean 12.6 +/- 2.4 SEM vs. 35.0 +/- 5.6 nmol/mmol creatinine; P < 0.01), they remained above normal (0.8-5.2 nmol/mmol creatinine) in all eight patients. Although mean upright plasma potassium levels during treatment were higher, aldosterone levels lower, PRA levels higher, and aldosterone to PRA ratios lower than before treatment, PRA levels were uncorrected (< 13 pmol/L x min) and aldosterone to PRA ratios were uncorrected (>65) during treatment in four patients. For each of the eight patients, day curve aldosterone levels during treatment correlated more tightly with cortisol (mean r for the eight patients, 0.87 +/- 0.05 SEM) than with PRA (mean r = 0.36 +/- 0.10 SEM). Hence, control of hypertension by glucocorticoid treatment was associated, in all patients, with only partial suppression of ACTH-regulated hybrid steroid and aldosterone production. Normalization of urinary hybrid steroid levels and abolition of ACTH-regulated aldosterone production is not a requisite for hypertension control and, if used as a treatment goal, may unnecessarily increase the risk of Cushingoid side effects.

Adolescent↗
PubMed1999

Expression of 11beta-hydroxysteroid dehydrogenase type 2 (11betaHSD-2) in the developing human adrenal gland and human adrenal cortical carcinoma and adenoma.

The aim of this study was to investigate the ontogeny of localization of 11betaHSD-2 protein in the human adrenal gland. In addition, we have investigated the effects of abnormal adrenal function on 11betaHSD-2 by determining the pattern of localization of 11betaHSD-2 protein, and the amount and level of expression of 11betaHSD-2 mRNA and protein in human adrenal cortical carcinoma and adenoma. In the human foetal adrenal gland 11betaHSD-2 immunoreactivity (11betaHSD-2-ir) was detected in the foetal zone, whereas in normal adult adrenal glands 11betaHSD-2-ir was not detected by immunocytochemistry. In adrenal cortical carcinoma and adenoma, 11betaHSD-2-ir was detectable in specific regions, which have been identified as steroid synthesizing cells using 3betaHSD-ir as a marker. In adrenal cortical carcinoma and adenoma, 11betaHSD-2 mRNA and 11betaHSD-2 protein were detected by nuclease protection analysis and by western blot analysis, respectively. In summary, 11betaHSD-2-ir was detected in the foetal zone of the mid-gestation human foetal adrenal, whereas, 11betaHSD-2-ir was not detectable in the postnatal or normal adult adrenal gland. 11BetaHSD-2 protein and mRNA was induced in adult human adrenal cortical carcinoma and adenoma. The induction of expression of 11betaHSD-2 in the adrenal cortex suggests a possible role in regulating abnormal adrenal steroidogenic function in these patients.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1999

Isolation and expression of novel human glutamate carboxypeptidases with N-acetylated alpha-linked acidic dipeptidase and dipeptidyl peptidase IV activity.

Hydrolysis of the neuropeptide N-acetyl-L-aspartyl-L-glutamate (NAAG) by N-acetylated alpha-linked acidic dipeptidase (NAALADase) to release glutamate may be important in a number of neurodegenerative disorders in which excitotoxic mechanisms are implicated. The gene coding for human prostate-specific membrane antigen, a marker of prostatic carcinomas, and its rat homologue glutamate carboxypeptidase II have recently been shown to possess such NAALADase activity. In contrast, a closely related member of this gene family, rat ileal 100-kDa protein, possesses a dipeptidyl peptidase IV activity. Here, we describe the cloning of human ileal 100-kDa protein, which we have called a NAALADase- "like" (NAALADase L) peptidase based on its sequence similarity to other members of this gene family, and its inability to hydrolyze NAAG in transient transfection experiments. Furthermore, we describe the cloning of a third novel member of this gene family, NAALADase II, which codes for a type II integral membrane protein and which we have localized to chromosome 11 by fluorescent in situ hybridization analysis. Transient transfection of NAALADase II cDNA confers both NAALADase and dipeptidyl peptidase IV activity to COS cells. Expression studies using reverse transcription-polymerase chain reaction and Northern blot hybridization show that NAALADase II is highly expressed in ovary and testis as well as within discrete brain areas.

Alternative Splicing↗
PubMed1999

Enovin, a member of the glial cell-line-derived neurotrophic factor (GDNF) family with growth promoting activity on neuronal cells. Existence and tissue-specific expression of different splice variants.

Glial cell-line-derived neurotrophic factor (GDNF), neurturin and persephin are neurotrophic factors involved in neuroneal differentiation, development and maintenance. They act on different types of neuroneal cells and signal through a receptor complex composed of a specific ligand-binding subunit of the GDNF family receptor alpha (GFRalpha) family together with a common signaling partner, the cRET protein tyrosine kinase. We describe the molecular cloning, expression, chromosomal localization and functional characterization of enovin, a fourth GDNF family member almost identical to the recently described artemin. We show the occurence in most tissues of several differently spliced mRNA variants for enovin, of which only two are able to translate into functional enovin protein. Some tissues seem to express only nonfunctional transcripts. These observations may underlie a complex transcriptional regulation pattern. Enovin mRNA expression is detectable in all adult and fetal human tissues examined, but expression levels are highest in peripheral tissues including prostate, placenta, pancreas, heart and kidney. This tissue distribution pattern is in accordance with that of GFRalpha-3, which here is shown to be the preferred ligand-binding receptor for enovin (Kd = 3.1 nM). The human enovin gene is localized on chromosome 1, region p31.3-p32. In vitro, enovin stimulates neurite outgrowth and counteracts taxol-induced neurotoxicity in staurosporine-differentiated SH-SY5Y human neuroblastoma cells. The peripheral expression pattern of enovin and its receptor together with its effects on neuroneal cells suggest that enovin might be useful for the treatment of neurodegenerative diseases in general and peripheral neuropathies in particular.

Adult↗
PubMed1999

Leptin levels are suppressed in primary aldosteronism.

Primary aldosteronism is associated with hypertension secondary to salt and water retention, hypokalemia and impaired insulin secretion with glucose intolerance in some patients. The secretion of leptin, a hormone produced by adipocytes, may be altered by reduced insulin secretion in primary aldosteronism. We measured plasma leptin approximately 3 months before and 3 months after curing of primary aldosteronism in 18 patients (12 male, 6 female, body mass index 29.1+/-4.4, mean +/- SD). Patients were treated by unilateral laparoscopic adrenalectomy to remove an aldosterone-producing adenoma. There was a 46% postoperative increase in plasma leptin concentrations from 6.65+/-0.81 to 9.68+/-1.50 ng/ml (P=0.004), despite a non-significant fall in body mass index. Plasma leptin was noted to increase after adrenalectomy in 16 of the 18 patients. The patients also had improved blood pressure and a significant increase in plasma potassium post-operatively. It is proposed that increased insulin secretory capacity associated with correction of negative potassium balance may account for the increase in plasma leptin after curing primary aldosteronism. Further studies are indicated to identify the mechanism of plasma leptin suppression in primary aldosteronism.

Adult↗
PubMed1999

Biochemical evidence of aldosterone overproduction and abnormal regulation in normotensive individuals with familial hyperaldosteronism type I.

We examined in detail biochemical characteristics of 10 normotensive individuals (6 females; age range, 11-43 yr) with glucocorticoid-suppressible hyperaldosteronism (familial hyperaldosteronism type I) in an attempt to understand the development of hypertension in this disorder. All were normokalemic (median plasma potassium, 3.7 +/- 0.4 mmol/L SD), and upright plasma aldosterone levels (478 +/- 333 pmol/L) were within the normal range (140-1110 pmol/L) in nine subjects. However, upright PRA levels (3.3 +/- 30.5 pmol/L x min) were suppressed (<13 pmol/L x min), and the aldosterone to PRA ratio (169.0 +/- 308.3) was elevated (>65) in all but one subject. All subjects had elevated 24-h urinary levels of 18-oxo-cortisol (34.3 +/- 11.2 nmol/mmol creatinine; normal range, 0.8-6.5 nmol/mmol creatinine). Plasma aldosterone failed to rise by at least 50% during 2 h of upright posture in five of seven subjects, or during a 1-h infusion of angiotensin II (2 ng/kg x min) in each of six subjects so studied. Serial, second-hourly (day-curve) aldosterone levels correlated tightly with cortisol (r = 0.79-0.97, P < 0.01 to 0.001), but not with PRA (r = 0.13-0.40, not significant) levels in each of six subjects, and plasma aldosterone suppressed to less than 110 pmol/L during 4 days of dexamethasone administration (0.5 mg 6 hourly) in each of two studied, consistent with ACTH-regulated aldosterone production. In conclusion, biochemical evidence of excessive, abnormally regulated aldosterone production is present not only in hypertensive individuals with familial hyperaldosteronism type I, but also in those who are normotensive. The absence of hypertension in such individuals, therefore, cannot be attributed to lack of biochemical expression of the hybrid gene.

Adolescent↗
PubMed1998

Molecular cloning, expression and tissue distribution of glial-cell-line-derived neurotrophic factor family receptor alpha-3 (GFRalpha-3).

Neurturin and glial-cell-line-derived neurotrophic factor (GDNF) promote the survival and maintenance of different types of neuronal cells and signal through a receptor complex composed of a ligand binding subunit, either GDNF family receptor alpha-1 (GFRalpha-1) or alpha-2 (GFRalpha-2), together with the cRET membrane-bound protein tyrosine kinase. We have cloned GFRalpha-3, a novel receptor belonging to the GFRalpha family, that is 35% identical by amino acid sequence to both GFRalpha-1 and GFRalpha-2. GFRalpha-3 is a protein composed of 400 amino acid residues with three potential N-linked glycosylation sites together with the features characteristic of a glycosyl-phosphatidylinositol-anchored membrane protein. The heterologous expression of a FLAG-tagged GFRalpha-3 in human embryonic kidney cells showed that the protein is bound to the cell surface via a glycosyl-PtdIns anchor and is glycosylated, with different glycoforms migrating on SDS/PAGE with apparent molecular masses ranging over 43-62 kDa. The gene for GFRalpha-3 was mapped to human chromosome 5 in a region (q31.1-q31.3) where several disease loci, growth factor and growth factor receptor genes have been localized. Using northern blot analysis or reverse-transcription PCR, GFRalpha-3 was shown to be expressed within the nervous system predominantly in the cerebellum and the spinal cord while in peripheral tissues GFRalpha-3 was found to be expressed mostly in the colon, small intestine, pancreas, heart, testis and prostate. Using a GFRalpha-3-specific [35S]cRNA[gammaS] probe, in situ hybridization histochemistry experiments confirmed the expression in the cerebellum.

Amino Acid Sequence↗
PubMed1998

Diastolic ventricular interaction in chronic heart failure: relation to heart rate variability and neurohumoral status.

It is likely that abnormal baroreflex control mechanisms are at least partially responsible for autonomic dysfunction in chronic heart failure. We recently demonstrated that diastolic ventricular interaction is associated with impaired baroreflex control of vascular resistance in heart failure. We reasoned that by constraining left ventricular filling, such interaction would decrease baroreflex activity and, thereby, increase sympathetic and decrease parasympathetic outflow. We hypothesized, therefore, that diastolic ventricular interaction in chronic heart failure patients would be associated with autonomic dysfunction. We used radionuclide ventriculography to measure changes in left and right ventricular end-diastolic volumes during acute volume unloading achieved by -30 mm Hg lower-body negative pressure in 30 patients with chronic heart failure. An increase in left ventricular volume in association with a reduction in right ventricular volume indicates diastolic ventricular interaction (a larger increase indicating a greater degree of interaction). We also measured heart rate variability (n = 23) and resting venous plasma norepinephrine (n = 24), epinephrine (n = 24), and atrial natriuretic peptide (ANP) (n = 14). During lower-body negative pressure, while right ventricular volume decreased in all patients (P < 0.001), left ventricular end-diastolic volume increased (from 152 +/- 25 to 157 +/- 36 ml/m2, P = 0.01). The change in left ventricular volume was positively correlated with resting plasma norepinephrine (P < 0.01) and ANP (P < 0.005), and negatively correlated with the standard deviation of normal to normal R-R intervals (P < 0.005), the root-mean-square of differences between successive normal to normal R-R intervals (P < 0.05), total power (P < 0.01), low-frequency power (P < 0.01), and high-frequency power (P < 0.05). Diastolic ventricular interaction in patients with chronic heart failure is associated with sympathetic nervous system activation evidenced by increased plasma norepinephrine and reduced heart rate variability.

Atrial Natriuretic Factor↗
PubMed1998

Success of surgery for primary aldosteronism judged by residual autonomous aldosterone production.

Since February 1996 we have prospectively assessed residual adrenal autonomy by the fludrocortisone suppression test (FST) in 23 patients 3 months after unilateral adrenalectomy for Conn syndrome and in 45 patients after a longer interval. In regard to blood pressure, 36 (53%) patients were cured of hypertension and the remaining 32 (47%) patients had improved hypertension control at the time of their latest postoperative clinical assessment. In regard to the outcome of surgery, patients who achieved normal suppressibility of aldosterone were regarded as cured, and those who had greater suppressibility after surgery were considered improved. Time since surgery for the whole group averaged 26 months. By these biochemical criteria, 42 patients (62%) were cured by surgery, and the rest improved; 16 (76%) of 21 women were cured, and 26 (55%) of 47 men. The women (mean +/- SD age 47 +/- 11 years) were significantly (p < 0.05) younger than the men (52 +/- 9 years). Preoperative aldosterone levels before and after FST were similar in the cured and improved groups and fell significantly (p < 0.01) in both groups following surgery. After surgical reduction of autonomous aldosterone production, mean plasma renin activity levels increased sixfold in the cured group and threefold in the improved group. Surgical mortality in this group of 68 patients with Conn syndrome was zero.

Adult↗
PubMed1998

Linkage of Gordon's syndrome to the long arm of chromosome 17 in a region recently linked to familial essential hypertension.

Gordon's syndrome (GS) is a salt-sensitive, hyperkalaemic, familial hypertension syndrome which may masquerade in milder forms as essential hypertension. The response of hyperakalaemia to dietary salt restriction and to mineralocorticoids is heterogeneous, suggesting genetic heterogeneity. In a recently published study using small pedigrees, possible linkage of GS to chromosomes 1 and 17 was described. Studying the largest pedigree so far reported with GS, and using fluorescent-labelled microsatellite markers, we sought evidence of linkage to chromosomes 1 and 17. In this family there was no segregation of GS with any of the markers for chromosome 1. On chromosome 17, however, evidence of linkage was found with a maximum multipoint LOD score of 2.4 (the maximum LOD possible from the pedigree) over markers D17S250 and D17S934. This represents strong evidence in this pedigree for a responsible gene mutation on the long arm of chromosome 17. Recent reports of linkage for essential hypertension and, especially, familial essential hypertension within the same area of chromosome 17 containing the D17S934 marker raise the possibility that the same gene may be responsible for familial essential hypertension and for Gordon's syndrome.

Chromosomes, Human, Pair 1↗
PubMed1998

Familial hyperaldosteronism type II: description of a large kindred and exclusion of the aldosterone synthase (CYP11B2) gene.

Familial hyperaldosteronism type II (FH-II) is characterized by autosomal dominant inheritance and hypersecretion of aldosterone due to adrenocortical hyperplasia or an aldosterone-producing adenoma; unlike FH type I (FH-I), hyperaldosteronism in FH-II is not suppressible by dexamethasone. Of a total of 17 FH-II families with 44 affected members, we studied a large kindred with 7 affected members that was informative for linkage analysis. Family members were screened with the aldosterone/PRA ratio test; patients with aldosterone/PRA ratio greater than 25 underwent fludrocortisone/salt suppression testing for confirmation of autonomous aldosterone secretion. Postural testing, adrenal gland imaging, and adrenal venous sampling were also performed. Individuals affected by FH-II demonstrated lack of suppression of plasma A levels after 4 days of dexamethasone treatment (0.5 mg every 6 h). All patients had negative genetic testing for the defect associated with FH-I, the CYP11B1/CYP11B2 hybrid gene. Genetic linkage was then examined between FH-II and aldosterone synthase (the CYP11B2 gene) on chromosome 8q. A polyadenylase repeat within the 5'-region of the CYP11B2 gene and 9 other markers covering an approximately 80-centimorgan area on chromosome 8q21-8qtel were genotyped and analyzed for linkage. Two-point logarithm of odds scores were negative and ranged from -12.6 for the CYP11B2 polymorphic marker to -0.98 for the D8S527 marker at a recombination distance (theta) of 0. Multipoint logarithm of odds score analysis confirmed the exclusion of the chromosome 8q21-8qtel area as a region harboring the candidate gene for FH-II in this family. We conclude that FH-II shares autosomal dominant inheritance and hyperaldosteronism with FH-I, but, as demonstrated by the large kindred investigated in this report, it is clinically and genetically distinct. Linkage analysis demonstrated that the CYP11B2 gene is not responsible for FH-II in this family; furthermore, chromosome 8q21-8qtel most likely does not harbor the genetic defect in this kindred.

Aldosterone↗
PubMed1997

A simple solution to a technical complication in "piggyback" liver transplantation.

"Piggyback" orthotopic liver transplantation is a technical modification of the standard technique that has found favor with a number of surgeons. One possible complication is that of venous outflow obstruction, which presents as an acute Budd-Chiari syndrome. If not rapidly corrected, it is almost inevitable that the newly implanted graft will fail. Additionally, severe portal hypertension and general infradiaphragmatic venous stasis may compound the damage. We find that anastomosing the donor infrahepatic vena cava to the recipient suprarenal vena cava in an end-to-side fashion is an excellent way to correct the problem.

Budd-Chiari Syndrome↗
PubMed1997

Efficacy of tacrolimus as rescue therapy for chronic rejection in orthotopic liver transplantation: a report of the U.S. Multicenter Liver Study Group.

BACKGROUND: A study was performed by 17 different U.S. liver transplantation centers to determine the safety and efficacy of conversion from cyclosporine to tacrolimus for chronic allograft rejection. METHODS: Ninety-one patients were converted to tacrolimus a mean of 319 days after liver transplantation. The indication for conversion was ongoing chronic rejection confirmed by biochemical and histologic criteria. Patients were followed for a mean of 251 days until the end of the study. RESULTS: Sixty-four patients (70.3%) were alive with their initial hepatic allograft at the conclusion of the study period and were defined as the responder group. Twenty-seven patients (29.7%) failed to respond to treatment, and 20 of them required a second liver graft. The actuarial graft survival for the total patient group was 69.9% and 48.5% at 1 and 2 years, respectively. The actuarial patient survival at 1 and 2 years was 84.4% and 81.2%, respectively. Two significant positive prognostic factors were identified. Patients with a total bilirubin of < or = 10 mg/dl at the time of conversion had a significantly better graft and patient survival than patients converted with a total bilirubin > 10 mg/dl (P=0.00002 and P=0.00125, respectively). The time between liver transplantation and conversion also affected graft and patient survival. Patients converted to tacrolimus < or = 90 days after transplantation had a 1-year actuarial graft and patient survival of 51.9% and 65.9%, respectively, compared with 73.2% and 87.7% for those converted > 90 days after transplantation. The mean total bilirubin level for the responder group was 7.1 mg/dl at the time of conversion and decreased significantly to a mean of 3.4 mg/dl at the end of the study (P=0.0018). Thirteen patients (14.3%) died during the study. Sepsis was the major contributing cause of death in most of these patients. CONCLUSIONS: Our results suggest that conversion to tacrolimus for chronic rejection after orthotopic liver transplantation represents an effective therapeutic option. Conversion to tacrolimus before development of elevated total bilirubin levels showed a significant impact on long-term outcome.

Adolescent↗
PubMed1997

Hepatitis G virus co-infection in liver transplantation recipients with chronic hepatitis C and nonviral chronic liver disease.

Hepatitis G virus (HGV) is a newly described RNA virus that is parenterally transmitted and has been found frequently in patients with chronic hepatitis C infection. To determine the impact of hepatitis G virus co-infection on morbidity and mortality following liver transplantation, we measured HGV RNA by polymerase chain reaction in pre and posttransplantation sera from a cohort of patients transplanted for chronic hepatitis C and a control group of patients transplanted for nonviral causes who were negative for hepatitis C virus (HCV) RNA in serum. The overall prevalence rate of HGV RNA in transplanted patients with chronic hepatitis C was 20.7%. HGV infection was present before transplantation in 13% while it appeared to have been acquired at the time of transplantation in 7.4%. Mean serum alanine aminotransferase activity, hepatic histological activity, and patient and graft survival were similar between HGV-positive and HGV-negative patients. The prevalence rate of HGV RNA in transplanted controls was 64% (P < .01) with a significantly higher rate of acquisition of HGV infection following transplantation (53%, P < .001) when compared with patients with chronic hepatitis C. Mean serum alanine aminotransferase activity was significantly lower in the control patients with HGV infection alone following transplantation than in patients co-infected with hepatitis C (37 +/- 9 vs. 70 +/- 33 U/L, P < .01). Thus, HGV is frequently found in transplantation patients co-infected with hepatitis C although it appears to have minimal clinical impact. In patients transplanted for nonviral causes of end-stage liver disease, a high rate of hepatitis G acquisition at the time of transplantation may occur but does not appear to predispose to chronic hepatitis.

Adult↗
PubMed1997

Evidence for persistent dysfunction of wild-type aldosterone synthase gene in glucocorticoid-treated familial hyperaldosteronism type I.

BACKGROUND: In familial hyperaldosteronism type I (FH-I), glucocorticoid treatment suppresses adrenocorticotrophic hormone-regulated hybrid gene expression and corrects hyperaldosteronism. OBJECTIVE: To determine whether the wild-type aldosterone synthase genes, thereby released from chronic suppression, are capable of functioning normally. METHODS: We compared mid-morning levels of plasma potassium, plasma aldosterone, plasma renin activity (PRA) and aldosterone: PRA ratios, measured with patients in an upright position, and responsiveness of aldosterone levels to infusion of angiotensin II (AII), for 11 patients with FH-I before and during long-term (0.8-14.3 years) treatment with 0.25-0.75 mg/day dexamethasone or 2.5-10 mg/day prednisolone. RESULTS: During glucocorticoid treatment, hypertension was corrected in all. Potassium levels, which had been low (< 3.5 mmol/l) in two patients before treatment, were normal in all during treatment (mean 4.0+/-0.1 mmol/l, range 3.5-4.6). Aldosterone levels during treatment [13.2+/-2.1 ng/100 ml (mean+/-SEM)] were lower than those before treatment (20.1+/-2.5 ng/100 ml, P< 0.05). PRA levels, which had been suppressed before treatment (0.5+/-0.2 ng/ml per h), were unsuppressed during treatment (5.1+/-1.5 ng/ml per h, P< 0.01) and elevated (> 4 ng/ml per h) in six patients. Aldosterone: PRA ratios, which had been elevated (> 30) before treatment (101.1+/-25.9), were much lower during treatment (4.1+/-1.0, P< 0.005) and below normal (< 5) in eight patients. Surprisingly, aldosterone level, which had not been responsive (< 50% rise) to infusion of AII for all 11 patients before treatment, remained unresponsive for 10 during treatment. CONCLUSIONS: Apparently regardless of duration of glucocorticoid treatment in FH-I, aldosterone level remains poorly responsive to AII, with a higher than normal PRA and a low aldosterone: PRA ratio. This is consistent with there being a persistent defect in functioning of wild-type aldosterone synthase gene.

Adolescent↗
PubMed1997

Hormonal, immunological, and hematological responses to intensified training in elite swimmers.

The purpose of this study was to compare the responses of selected hormonal, immunological, and hematological variables in athletes showing symptoms of overreaching with these variables in well-trained athletes during intensified training. Training volume was progressively increased over 4 wk in 24 elite swimmers (8 male, 16 female); symptoms of overreaching were identified in eight swimmers based on decrements in swim performance, persistent high ratings of fatigue, and comments in log books indicating poor adaptation to the increased training. Urinary excretion of norepinephrine was significantly lower (P < 0.05, post hoc analysis) in overreached (OR) compared with well-trained (WT) swimmers throughout the 4 wk. There were no significant differences between OR and WT swimmers for other variables including: concentrations of plasma norepinephrine, cortisol, and testosterone, and the testosterone/cortisol ratio; peripheral blood leukocyte and differential counts, neutrophil/lymphocyte ratio, and CD4/CD8 cell ratio; serum ferritin and blood hemoglobin concentrations, erythrocyte number, hematocrit, and mean red cell volume (MCV). MCV increased significantly over the 4 wk in both groups, suggesting increased red blood cell turnover. These data show that, of the 16 hormonal, immunological, and hematological variables measured, urinary norepinephrine excretion appears to be the only one to distinguish OR from WT swimmers during short-term intensified training. Low urinary norepinephrine excretion was observed 2 to 4 wk before the appearance of symptoms of overreaching, suggesting the possibility that neuroendocrine changes may precede, and possibly contribute to, development of the overreaching/overtraining syndromes.

Adolescent↗
PubMed1997

A PCR-based method of screening individuals of all ages, from neonates to the elderly, for familial hyperaldosteronism type I.

AIM: Unless specifically treated (glucocorticoids in low doses), Familial Hyperaldosteronism Type I (FH-I) may result in early death from stroke. We report the successful application of a rapid, polymerase chain reaction (PCR)-based method of detecting the 'hybrid' 11 beta-hydroxylase (11 beta-OHase)/aldosterone synthase (AS) gene as a screening test for FH-I. METHODS: 'Long-PCR' was used to amplify, concurrently, a 4 kb fragment of AS gene (both primers AS-specific) and a 4 kb fragment of the hybrid gene (5' primer 11 beta-OHase-specific, 3' primer AS-specific) from DNA extracted from blood either collected locally or transported from elsewhere. Sample collection and transport were straightforward. This 4 kb fragment contains all the currently recognised hybrid gene 'crossover' points. RESULTS: Within a single family, long-PCR identified all 21 individuals known to have FH-I. Hypertension was corrected in all 11 treated with glucocorticoids. Nine with normal blood pressure are being closely followed for development of hypertension. Long-PCR cord blood analysis excluded FH-I in three neonates born to affected individuals. Long-PCR newly identified two other affected families: (1) a female (60 years) with a personal and family history of stroke and her normotensive daughter (40 years), and (2) a female (51 years) previously treated for primary aldosteronism with amiloride, her two hypertensive sons (14 and 16 years) and her hypertensive mother (78 years). No false negative or false positive results have yet been encountered. At least seven other centres have successfully performed this test. CONCLUSION: Long-PCR is a reliable method of screening individuals of all ages for FH-I.

Adolescent↗