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1.  High-dosage short-term corticotrophin therapy in acute asthma 
Thorax  1969;24(4):415-420.
The effect of corticotrophin suspended in gelatin in doses varying from 40 to 400 i.u. on the plasma 11-hydroxycorticosteroid response has been investigated in volunteer subjects in order to determine the optimum dose required to produce prolonged and continuous adrenocortical stimulation using this preparation. Increasing the dose of corticotrophin beyond 200 i.u. did not produce a greater intensity or prolongation of adrenocortical stimulation; 300 i.u. corticotrophin in 7·5 ml. of gelatin produced the same effect as 310 i.u. in 1 ml. gelatin. In order to achieve prolonged and continuous adrenal stimulation the optimum dose of corticotrophin would appear to be 200 i.u., which could be suspended in 1 ml. of gelatin for ease of administration, and which produced adrenal stimulation for approximately 36 hours. The effect of the administration of a single large dose of corticotrophin has been investigated in 13 asthmatic patients during an exacerbation. All had failed to respond to conventional therapy but responded to corticotrophin with one exception. Five patients required no more than two injections for a sustained remission. Seven were discharged needing prolonged corticotrophin in conventional doses. The advatage of using this form of corticotrophin therapy over a short course of high-dosage corticosteroid therapy is discussed.
PMCID: PMC472004  PMID: 4307610
2.  Effect of ethylene glycol dinitrate on metabolism of catecholamines and on blood pressure reaction to re-exposure 
Minami, M., Okada, A., Takizawa, A., and Kubota, J. (1972).Brit. J. industr. Med.,29, 321-327. Effect of ethylene glycol dinitrate on metabolism of catecholamines and on blood pressure reaction to re-exposure. Male Donryu rats were divided into two groups. One group was given 65 mg/kg per day of ethylene glycol dinitrate (EGDN) subcutaneously for five days and the other group received the same for 10 days. On the first, second, third, fourth, and fifth days after the last injection of EGDN catecholamines were estimated in the heart, brain, and adrenals and plasma 11-hydroxycorticosteroids and haemoglobin were estimated in blood. Urine samples were collected for 24 hours every other day before, during, and after the period of EGDN injection.
After five successive doses of EGDN the concentration of catecholamines in the organs increased and urinary catecholamine excretion was a little greater than from the controls. Reinjection of EGDN caused prolonged irreversible depression of the blood pressure.
After 10 successive doses of EGDN the concentrations of catecholamines in the organs were normal, but noradrenaline excretion in the urine was increased for three days. Reinjection of EGDN on the first day caused prolonged depression of blood pressure, but by five days the response had returned to the more transient depression observed in the controls.
The probability of coronary spasm is considered to be greater in the condition found after five than in that after 10 successive injections because more noradrenaline was available in the cardiac muscle as well as adrenaline in the adrenals.
After 10 successive injections the increased noradrenaline concentration in the urine reflected the raised noradrenaline level in the blood which could alleviate the depressant action of EGDN reinjection.
The clinical significance of these findings is discussed.
PMCID: PMC1009431  PMID: 5044604
3.  Islet-cell Carcinoma (Zollinger—Ellison Syndrome) with Fulminating Adrenocortical Hyperfunction and Hypokalemia 
The production of ACTH-like material by tumours arising in non-endocrine tissue may initiate severe adrenocortical hyperfunction. The pathogenesis and clinical and laboratory features of Cushing's syndrome associated with such tumours are characteristic. The autonomous production by the tumour of ACTH-like material cannot be suppressed by exogenous corticoids. The onset of clinical symptoms is rapid; muscle wasting, general weakness, thirst and peripheral edema predominate, and the classical signs of Cushing's syndrome may be absent. High levels of plasma 17-hydroxycorticosteroids and urinary 17-hydroxycorticosteroids and 17-ketosteroids, usually with normal levels of urinary aldosterone, commonly occur. Hypokalemic alkalosis unresponsive to replacement therapy may cause death. In the case reported herein, the intriguing possibility exists that two hormone-like substances were produced by the primary growth and its metastases: one, ACTH-like, to account for the adrenal hyperplasia and Cushing's syndrome; and another, gastrin-like, giving rise to the ulcerogenic diathesis.
PMCID: PMC1928544  PMID: 14323654
4.  Expérience clinique avec une épreuve de réserve hypophysaire 
A test of pituitary reserve was used in the investigation of 14 children with retarded growth and 15 adults with endocrine disorders. Mepyrapone (Metopiron), 500 mg. every four hours, was administered orally for 48 hours. The pituitary response was determined by the amount of 17-hydroxycorticosteroid in a 24-hour urine sample (by a modification by Peterson of the Porter-Silber method). Pituitary reserve was decreased in four patients who were pituitary dwarfs, one who had retarded growth, two patients with Sheehan's syndrome, three with pituitary tumours, one who had panhypopituitarism without a tumour, and one case of limited adrenal reserve (confirmed by a negative response to ACTH stimulation). The pituitary reserve was normal in three patients with gonadal dysgenesis, three who exhibited retarded growth, one case of diabetes insipidus, one cretin, one patient treated by steroids, three with psychogenic amenorrhea, and five normal controls. It is concluded that this test of pituitary reserve is useful in the assessment of children with growth retardation and in establishing the diagnosis of pituitary insufficiency in adults.
PMCID: PMC1921739  PMID: 14016287
5.  Circadian rhythms in plasma concentration of 11-hydroxycorticosteroids in men working on night shift and in permanent night workers 
Conroy, R. T. W. L., Elliott, Ann L., and Mills, J. N. (1970).Brit. J. industr. Med.,27, 170-174. Circadian rhythms in plasma concentration of 11-hydroxycorticosteroids in men working on night shift and in permanent night workers. Blood samples have been collected for estimation of plasma 11-hydroxycorticosteroids from three groups of workers - day and night shift workers in a light engineering factory, and night workers in a newspaper printing works. Up to five samples were collected over 24 hr, or two samples per 24 hr were collected for three days. In conformity with the observations of others, day workers showed maximal concentrations in the morning around the time when they started work. In the newspaper workers maximal concentrations were found when they awoke around 14·00 hr. Night shift workers in the engineering works showed a greater variety of pattern, some showing the pattern usual in a day worker, some showing a maximum concentration about midnight and a minimum around 06·00 hr and a large proportion showing no clear circadian rhythm.
In the newspaper workers the rhythm was thus well adapted to their pattern of nocturnal work, whereas relatively few of the night shift workers in the engineering works showed such adaptation. It appears that the adrenal cortical rhythm can be adapted to night work in a community in which this is universal, accepted and lifelong, but that such adjustment is unusual in men on night shift work for limited periods, and whose associates are mainly following a usual nycthemeral existence.
PMCID: PMC1009093  PMID: 5428635
6.  Central venous catheter related infections: Risk factors and the effect of glycopeptide antibiotics 
We undertook a prospective study of all new central venous catheters inserted into patients in the intensive care units, in order to identify the risk factors and to determine the effect of glycopeptide antibiotics on catheter – related infections.
During the study period 300 patients with central venous catheters were prospectively studied. The catheters used were nontunneled, noncuffed, triple lumen and made of polyurethane material. Catheters were cultured by semiquantitative method and blood cultures done when indicated. Data were obtained on patient age, gender, unit, primary diagnosis on admission, catheter insertion site, duration of catheterization, whether it was the first or a subsequent catheter and glycopeptide antibiotic usage.
Ninety-one (30.3%) of the catheters were colonized and infection was found with 50 (16.7%) catheters. Infection was diagnosed with higher rate in catheters inserted via jugular vein in comparison with subclavian vein (95% CI: 1.32–4.81, p = 0.005). The incidence of infection was higher in catheters which were kept in place for more than seven days (95% CI 1.05–3.87, p = 0.03). The incidence of infection was lower in patients who were using glycopeptide antibiotic during catheterization (95% CI: 1.49–5.51, p = 0.005). The rate of infection with Gram positive cocci was significantly lower in glycopeptide antibiotic using patients (p = 0.01). The most commonly isolated organism was Staphylococcus aureus (n = 52, 37.1%).
Duration of catheterization and catheter insertion site were independent risk factors for catheter related infection. Use of glycopeptide antibiotic during catheterization seems to have protective effect against catheter related infection.
PMCID: PMC151687  PMID: 12643811
Central venous catheter; infection; risk; glycopeptide
7.  Ethanol Causes Protein Precipitation—New Safety Issues for Catheter Locking Techniques 
PLoS ONE  2013;8(12):e84869.
The ethanol lock technique has shown great potential to eradicate organisms in biofilms and to treat or prevent central venous catheter related infections. Following instillation of ethanol lock solution, however, the inherent density gradient between blood and ethanol causes gravity induced seepage of ethanol out of the catheter and blood influx into the catheter. Plasma proteins so are exposed to highly concentrated ethanol, which is a classic agent for protein precipitation. We aimed to investigate the precipitating effect of ethanol locks on plasma proteins as a possible cause for reported catheter occlusions.
Plasma samples were exposed in-vitro to ethanol (concentrations ranging from 7 to 70 v/v%) and heparin lock solutions. In catheter studies designed to mimic different in-vivo situations, the catheter tip was placed in a plasma reservoir and the material contained within the catheter was analyzed after ethanol lock instillation. The samples underwent standardized investigation for protein precipitation.
Protein precipitation was observed in plasma samples containing ethanol solutions above a concentration of 28%, as well as in material retrieved from vertically positioned femoral catheters and jugular (subclavian) catheters simulating recumbent or head down tilt body positions. Precipitates could not be re-dissolved by dilution with plasma, urokinase or alteplase. Plasma samples containing heparin lock solutions showed no signs of precipitation.
Our in-vitro results demonstrate that ethanol locks may be associated with plasma protein precipitation in central venous catheters. This phenomenon could be related to occlusion of vascular access devices locked with ethanol, as has been reported. Concerns should be raised regarding possible complications upon injection or spontaneous gravity induced leakage of such irreversibly precipitated protein particles into the systemic circulation. We suggest limiting the maximum advisable concentration of ethanol to 28 v/v% in catheter lock solutions.
PMCID: PMC3877335  PMID: 24391979
8.  Quantitative relations between avoidance behavior and pituitary-adrenal cortical activity1 
The rate at which monkeys pressed a lever and avoided shocks was manipulated in several ways. Measurements were also made of their plasma levels of 17-hydroxycorticosteroids. The rate at which the animals pressed the lever and the frequency with which they received shocks were both implicated as determiners of the steroid levels.
PMCID: PMC1404087  PMID: 13912548
9.  Structural and Functional Alterations in The Zona Fasciculata of The Rat Adrenal Cortex in Obstructive Jaundice 
HPB Surgery  1989;1(4):271-281.
This study investigated the effect of experimentally-induced cholestasis in the rat on the structure and function of the zona fasciculata, the glucocorticoid secretory region of the adrenal cortex. Wistar-Furth rats (200-250g) were assigned to three groups: bile duct ligated (BDL), Sham operated (Sham) and unmodified normal control (NC). On day 14, serum bilirubin and liver histology were performed to confirm cholestasis in BDL animals together with basal 24 hour 17-hydroxycorti-costeroid excretion, adrenal histology and zona fasciculata ultrastructure in all experimental groups. Following this laparotomy, structural and functional studies were repeated on day 15 to evaluate the response of the gland to surgically induced stress. Basal 24 hr. 17-hydroxycorticoid steroid excretion was elevated in BDL animals (26.9 ±3.2 μ g/24 hr) with respect to Sham (10.4 ± 2.3) and NC groups (13.5 ± 3.2) (p <0.05). Adrenal histology and ultrastructural studies demonstrated excessive accumulation of vesicles laden with glucocorticoid biogenic precursors. Following surgical stress 24 hr 17 OH corticosteroid excretion increased in all groups: BDL (31.0 ± 3.0 μg/24 hr) vs Sham (15.6 ± 1.8) and NC (14.5 ± 2.4) Moderate alterations in zona fasciculata architecture were seen following surgery in all groups. Cholestasis induces overactivity of the zona fasciculata of the adrenal cortex, and may modify the normal metabolic responses to surgical and other stresses.
PMCID: PMC2423546  PMID: 2487067
10.  Plasma 11-Hydroxycorticosteroid and Growth Hormone Levels in Acute Medical Illnesses 
British Medical Journal  1969;2(5657):595-598.
Adrenal cortical response in acute medical illness has been studied by measuring the plasma 11-hydroxycorticosteroid (11-OHCS) concentration in 178 patients. Those with unbalanced diabetes, acute infections, and severe myocardial infarction had high levels. The results obtained suggest that in a patient with a severe infection and hypotension a plasma 11-OHCS level of less than 15 μg./100 ml. indicates an inadequate adrenal cortical response, and one patient with septicaemia and temporary adrenal cortical insufficiency is described. Growth hormone levels were increased in patients with severe diabetic ketosis but not in those with hyperosmolar non-ketotic diabetic coma.
PMCID: PMC1983596  PMID: 5798469
11.  Endocrinopathy in thalassaemia major. 
Archives of Disease in Childhood  1976;51(3):195-201.
Pituitary, adrenal, and pancreatic functions were investigated in 9 patients with thalassaemia major. 9 a.m. plasma ACTH values were 148-480 pg/ml (normal range 15-70 pg/ml). Cortisol and growth hormone response to insulin-induced hypoglycaemia was normal in all. 24-hour urinary excretions of 17-ketosteroids and 17-hydroxycorticosteroids were normal. There was normal cortisol response to intramuscular injection of ACTH. In a physiological adrenal stimulation test there was a significantly smaller response to each physiological dose of tetracosactrin. 4 patients had diabetic glucose tolerance tests--none are clinically diabetic. The mean plasma glucose utilization constant (Kgl=2-02) is significantly smaller than normal. Plasma insulin response both in the oral and the intravenous glucose tolerance test was significantly smaller than normal. The data were consistent with severe and widespread impairment of endocrine function and a plausible explanation would be iron deposition in endocrine organs. It is suggested that pituitary hyperfunction of ACTH secretion is due to target organ unresponsiveness which can be shown in its early stages only by a physiological test of the adrenal cortex. Skin pigmentation in thalassaemia seems to be due to the melanophore-stimulating effect of this raised plasma ACTH.
PMCID: PMC1545930  PMID: 182088
12.  Primary hyperaldosteronism due to an adrenal adenoma in a 14-year-old boy. 
Postgraduate Medical Journal  1995;71(832):104-106.
Conn's syndrome due to an adrenal adenoma is very rare in children. This paper reports a 14-year-old boy with primary hyperaldosteronism due to an adrenal adenoma. His biochemistry data were compatible with either bilateral adrenal hyperplasia or an adrenal adenoma. A dexamethasone test did not suppress aldosterone levels. Venous catheter sampling and 75Se-selenomethylcholesterol scanning suggested that the hyperaldosteronism originated at the right adrenal. Computed tomography showed an 8-mm low-density nodule in the right adrenal gland and magnetic resonance imaging confirmed the nodule which had high signal intensity on T2-weighted images consistent with a functioning adenoma. Surgery confirmed the right adrenal adenoma, and the patient was cured by right adrenalectomy. This case illustrates the difficulty of defining the aetiology of primary hyperaldosteronism and we review the biochemical and scanning techniques available to aid in diagnosis. Hypertension is unusual in children and endocrine causes are very rare, but Conn's syndrome should always be considered in the differential diagnosis.
PMCID: PMC2397950  PMID: 7724419
13.  17-Ketosteroid and 17-hydroxycorticosteroid excretion in patients with duodenal ulceration 
Gut  1962;3(4):327-332.
The 24-hour excretion of 17-ketosteroids and 17-hydroxycorticosteroids has been estimated in a series of male duodenal ulcer subjects and compared with that of 56 normal male controls. It has been found that both 17-ketosteroid and 17-hydroxycorticosteroid excretion is less in ulcer subjects than in the control group; these differences are not large but in the case of 17-hydroxycorticosteroids they are statistically significant. For active ulcers (107 men) 17-hydroxycorticosteroid excretion is approximately 78% of normal and 17-ketosteroid excretion 93% of normal; in the quiescent phase (50 men) the differences are rather larger, being respectively 71% and 86% of normal. This reduced excretion persists after operation in both the short term, six months after operation (53 men), and the long term, 10 years and more after gastric resection (39 men).
PMCID: PMC1413375  PMID: 13950054
14.  Stability of Trisodium Citrate and Gentamicin Solution for Catheter Locks after Storage in Plastic Syringes at Room Temperature 
Catheter-related infections are a major problem for hemodialysis patients with central venous catheters for vascular access. Catheter lock solutions containing an anticoagulant are used to maintain the patency of the catheter between hemodialysis sessions. There is evidence that the use of lock solutions containing an antibiotic is associated with lower rates of infection but also that these solutions can kill microbes in colonized catheters and thus avoid the risks and costs associated with replacing the catheter.
This stability study was conducted to determine whether an extemporaneously prepared gentamicin–citrate catheter lock solution would retain its potency over time, thus allowing for advance preparation of the solution.
Catheter lock solutions containing gentamicin alone, citrate alone, and the combination of gentamicin and citrate were prepared aseptically and packaged in polyethylene syringes. The syringes were stored at room temperature. At timed intervals over 112 days, samples were withdrawn for analysis by means of validated high-performance liquid chromatography.
None of the 3 lock solutions showed any evidence of degradation during the 112-day observation period. In the formulation containing both gentamicin 2.5 mg/mL and sodium citrate 40 mg/mL (4%), there was no change in the concentration of either gentamicin (p = 0.34) or citrate (p = 0.55). Linear regression analysis of the concentration–time data for the combined formulation showed that 99.97% of the labelled amount of gentamicin and 101.30% of the labelled amount of citrate remained at day 112. The lower limit of the 95% confidence intervals indicated that more than 98.17% of the gentamicin and more than 99.57% of the citrate remained on day 112.
The results of this study will allow pharmacies to extemporaneously compound the combined gentamicin–citrate catheter lock solution in advance of use. The method described here will yield a stable product for use in clinical applications.
PMCID: PMC2932495  PMID: 22478993
gentamicin; citrate; stability; catheter lock solution; hemodialysis; high-performance liquid chromatography; gentamicine; citrate; stabilité; solution pour verrou de cathéter; hémodialyse; chromatographie liquide haute performance
15.  Use of the Tego needlefree connector is associated with reduced incidence of catheter-related bloodstream infections in hemodialysis patients 
Background and objectives
Catheter-related bloodstream infections (CRBSIs) are common in hemodialysis patients using central venous catheters, and catheter occlusion also occurs frequently. The Tego needlefree connector was developed to reduce the incidence of these complications; however, existing studies of its effectiveness and safety are limited.
Materials and methods
This retrospective analysis compared outcomes among patients of a large dialysis organization receiving in-center hemodialysis using a central venous catheter with either the Tego connector or standard catheter caps between October 1 and June 30, 2013. Incidence rates for intravenous (IV) antibiotic starts, receipt of an IV antibiotic course, positive blood cultures, mortality, and missed dialysis treatments were calculated, and incidence-rate ratios (IRRs) were estimated using Poisson regression models. Utilization of erythropoiesis-stimulating agents (ESAs) and thrombolytics was described for each patient-month and compared using mixed linear models. Models were run without adjustment, adjusted for covariates that were imbalanced between cohorts, or fully adjusted for all potential confounders.
The analysis comprised 10,652 Tego patients and 6,493 controls. Tego use was independently associated with decreased risk of CRBSI, defined by initiation of IV antibiotics (adjusted IRR 0.92, 95% confidence interval [CI] 0.87–0.97) or initiation of IV antibiotic course (adjusted IRR 0.89, 95% CI 0.84–0.95). Tego use was independently associated with decreased rate of missed dialysis treatments (adjusted IRR 0.98, 95% CI 0.97–1.00); no significant difference between Tego and control cohorts was observed with respect to mortality. Tego use was associated with decreased likelihood of thrombolytic use (adjusted per-month probability of 5.6% versus 6.2% for controls) and lower utilization of ESAs in study months 7–9.
Use of the Tego connector may reduce the risk of CRBSI and result in lower utilization of thrombolytics, antibiotics, and ESAs, as well as fewer missed dialysis treatments.
PMCID: PMC3979783  PMID: 24729725
catheter; dialysis; end-stage renal disease; ESA; infection; mortality
16.  Urinary 17-KS and 17-OHCS as markers of endocrine disruption by air pollution in primary school children 
The present study was undertaken to determine the effects of air pollution on urinary excretion of 17-ketosteroids (17-KS) and 17-hydroxycorticosteroids (17-OHCS), which are markers of adrenal cortex functions, in primary school children from five schools with different levels of air pollution. One hundred and twentynine fourth-grade children were included in the study. Urinary excretion of 17-KS and 17-OHCS were significantly lower in male children living in polluted areas than in children living in clean areas. We conclude that adrenal cortex functions before puberty can serve as practical markers of endocrine disruption by environmental factors in epidemiological studies.
PMCID: PMC2723600  PMID: 21432489
air pollution; 17-ketosteroids; 17-hydroxycorticosteroids; school children; endocrine disruption
17.  Assessment of Long-acting Synthetic Corticotrophin in Hypersensitive Asthmatics and Normal Subjects 
British Medical Journal  1968;3(5619):653-655.
The synthetic polypeptide depot-tetracosactrin (Synacthen-Depot) was given to nine steroid-treated asthmatic patients hypersensitive to animal corticotrophin. Eight had a satisfactory increase in plasma and urinary 17-hydroxycorticosteroids (17-OHCS). The remaining patient had been shown previously to have adrenal suppression. None of the patients developed allergic reactions to depot-tetracosactrin, and seven have been receiving regular injections of the polypeptide twice weekly for the past eight months.
In 13 normal subjects intramuscular injections of 1 mg. and 0.5 mg. of depot-tetracosactrin and 40 units of corticotrophin-gel were equally potent in raising the plasma 17-OHCS, but depot-tetracosactrin had a significantly longer action than corticotrophin-gel.
PMCID: PMC1986530  PMID: 4299775
18.  Adrenocortical Hyperfunction Associated with Bronchogenic Carcinoma 
Canadian Medical Association Journal  1965;93(24):1243-1249.
Five patients with bronchogenic carcinoma associated with adrenocortical hyperfunction are described. The clinical features, laboratory studies and autopsy findings are discussed and compared with previously reported cases. Four patients presented most of the typical features of this disorder as previously described, whereas the fifth was atypical in some respects. Typical features included: acute onset of adrenocortical hyperfunction in a middle-aged male, rapid downhill course, slight or absent physical signs of Cushing's syndrome, frequently impaired glucose tolerance, markedly elevated plasma and urinary 17-hydroxycorticosteroids not suppressed by exogenous steroids, absent diurnal variation of plasma corticoids, hypokalemic alkalosis with normal aldosterone excretion, and tumour histology of the oat cell variety. The adrenal glands of two patients were of normal or slightly increased weight, and mean 17-ketosteroid excretion values were normal in three; this contrasts with the marked increase in adrenal weight and 17-ketosteroid excretion in most reported cases.
PMCID: PMC1935096  PMID: 5839222
19.  Lipid Cell Tumor of the Ovary 
A 32-year-old nulligravida, with a history of abdominal hysterectomy for multiple leiomyomas of the uterus, was seen initially with signs of masculinization. Normal values for 17-ketosteroids, 17-hydroxycorticosteroids, and plasma cortisol eliminated the adrenal as the source of the excess androgen as well as Cushing syndrome. Increased plasma testosterone and androstenedione levels in the peripheral blood as well as in the right ovarian vein sampling implicated the right ovary, which revealed a lipid cell tumor (0.5 to 1.3 cm in maximum dimension).
PMCID: PMC2552544  PMID: 7420444
20.  Central venous catheter-related bloodstream infections in the intensive care unit 
Central venous catheter-related bloodstream infection (CRBSI) is associated with high rates of morbidity and mortality in critically ill patients.
This study was conducted to determine the incidence of central venous catheter-related infections (CRIs) and to identify the factors influencing it. So far, there are very few studies that have been conducted on CRBSI in the intensive care unit in India.
Settings and Design:
This was a prospective, observational study carried out in the medical intensive care unit (MICU) over a period of 1 year from January to December 2004.
Materials and Methods:
A total of 54 patients with indwelling central venous catheters of age group between 20 and 75 years were included. The catheters were cultured using the standard semiquantitative culture (SQC) method. Statistical analysis used SPSS-10 version statistical software.
A total of 54 CVC catheters with 319 catheter days were included in this study. Of 54 patients with CVCs studied for bacteriology, 39 (72.22%) catheters showed negative SQCs and also negative blood cultures. A total of 15 (27.77%) catheters were positive on SQC, of which 10 (18.52%) were with catheter-associated infection and four (7.41%) were with catheter-associated bacteremia; the remaining one was a probable catheter-associated bacteremia. CRIs were high among catheters that were kept in situ for more than 3 days and emergency procedures where two or more attempts were required for catheterization (P < 0.05). In multivariate analysis of covariance duration of catheter in situ for >3 days, inexperienced venupucturist, more number of attempts and emergency CVC were associated with more incidence of CVCBSIs, with P <0.02. The duration of catheter in situ was negatively correlated (-0.53) and number of attempts required to put CVC was positively correlated (+0.39) with incidence of CVCBSIs. Sixty-five percent of the isolates belonged to the CONS group (13/20). Staphylococcus epidermidis showed maximum susceptibility to amikacin, doxycycline and amoxycillin with clavulanic acid and was susceptible to vancomycin (100%). Klebsiella pneumoniae was 100% susceptible to amikacin and ciprofloxacin. Escherichia coli was susceptible to amikacin and cefotaxime.
The overall incidence of CRI was 27.77% (15/54). Catheter-associated BSIs were 47.31 per 1000 catheter-days. CRI was low in the catheters inserted by the experienced venipuncturists, elective procedure and CVC kept in situ for ≤3 days. S. epidermidis was the most common isolate.
PMCID: PMC3271557  PMID: 22346032
Catheter-related infection; catheter-associated infection; semiquantitative culture
21.  Comparison of the Roll Plate Method to the Sonication Method To Diagnose Catheter Colonization and Bacteremia in Patients with Long-Term Tunnelled Catheters: a Randomized Prospective Study▿  
Journal of Clinical Microbiology  2009;47(4):885-888.
Diagnosing catheter-related bloodstream infection (CRBSI) still often involves tip culture. The conventional method is the semiquantitative roll plate method. However, the use of a quantitative sonication technique could have additional value, as it may detect endoluminal microorganisms more easily. Because endoluminal infection tends to occur in long-term central venous catheters, we compared both techniques for patients with long-term tunnelled catheters. For 313 consecutive Hickman catheter tips from 279 hematological patients, colonization detection rates were compared by performing both techniques in a random order, using conventional detection cutoffs. Additionally, for the subgroup of patients with clinical suspicion of CRBSI (n = 89), the diagnostic values of both techniques were compared. The overall tip colonization rate was 25%. For each technique, the detection rate tended to be better if that technique was performed first. The diagnostic performance for the subgroup of patients with clinical suspicion of CRBSI was limited and not different for both methods. Sensitivity and specificity were 45% and 84%, respectively, for sonication versus 35% and 90%, respectively, for the roll plate technique. The fact that 35 of 40 patients with CRBSI received antimicrobial therapy before catheter removal and tip culture, in an attempt to salvage the catheter, may partly explain this poor performance. No differences were observed when catheters were stratified according to in situ time below or above the median of 4 weeks. The sonication culture technique was not better than the roll plate method to diagnose tip colonization or CRBSI in patients with long-term tunnelled catheters.
PMCID: PMC2668323  PMID: 19171682
22.  Excretion of individual adrenocortical steroids in obese children 
Archives of Disease in Childhood  1974;49(12):946-954.
The excretion of 13 individual adrenocortical metabolites in the urine of 21 obese children aged 7 months to 16 years is reported. Fractionation of the steroids was carried out on 24-hour samples of urine by paper chromatography using Bush systems and incorporating a radioactive steroid recovery technique. The excretion of the 17-hydroxycorticosteroids and of the α-ketolic metabolites of cortisol and corticosterone exceeded that of normal children studied in the same manner. These differences persisted when the results were corrected for surface area but were eliminated by correction for body weight. The raised corticosteroid excretion in obese children is therefore related to the increased weight. In addition the excessive calorie intake enhances the hepatic metabolism of cortisol leading to an increased corticosteroid excretion.
The excretion of the 17-oxosteroids and 11-deoxygenated-17-oxosteroids exceeded that of normal children. Before puberty these steroids represent the adrenal androgens, and the raised excretion in the obese children was associated with an advanced bone age. The early onset of puberty in obesity may be related to the increased body weight, but it is suggested that the increased adrenal androgen secretion may stimulate early maturation of the hypothalamic centre controlling the onset of puberty.
PMCID: PMC1649107  PMID: 4374898
23.  The incidence of complications of central venous catheters at an intensive care unit 
Annals of Thoracic Medicine  2007;2(2):61-63.
Central venous catheter (CVC) placement in the intensive care unit (ICU) is a common practice and is being increasingly used also in general wards. Its use is associated with both mechanical and infectious complications.
To determine the infectious and mechanical complication rate of central venous catheterization in an ICU.
A retrospective study about complications of 1319 central venous catheter placements.
An 11-bed adult medical, surgical, neuro-trauma ICU at salmaniya medical complex, Bahrain.
This was a retrospective review of all central venous catheter inserted over 4 year's period from October 2002 to December 2006.
There were 12 mechanical complications and 128 infectious complications total of 1319 CVCs placed.
The CVC can be performed safely in an ICU if done by a competent physician with all aseptic precautions.
PMCID: PMC2732078  PMID: 19727348
Central venous catheter; complications; infections; intensive care unit
24.  Endocrinological and clinical evaluation of two doses of formestane in advanced breast cancer. 
British Journal of Cancer  1994;70(1):145-150.
Formestane is a selective inhibitor of oestrogen synthesis by aromatase enzymes and induces disease regression in breast cancer patients. This phase II randomised study was carried out to determine whether there were any differences in the effects of two different doses of formestane on oestradiol (E2) serum levels and to evaluate the corresponding clinical activity in post-menopausal patients with positive or unknown oestrogen receptor status pretreated or not for advanced disease. Furthermore, possible drug interference with adrenal steroidogenesis was assessed by measuring 17-hydroxycorticosteroid (17-OHCS) urinary levels. A total of 143 patients entered the study and were randomly assigned to receive formestane 250 mg (72 patients) or formestane 500 mg (71 patients), both given i.m. every 2 weeks. In comparison with baseline, E2 serum levels decreased by an average of 40% after only 15 days and remained unchanged thereafter, with no difference being observed between the two doses. The values of 17-OHCS remained unchanged during treatment in both groups. Objective responses were 28% (19/69) in the 250 mg and 46% (31/68) in the 500 mg group. In conclusion, the two formestane doses were equally effective in reducing E2 levels without affecting adrenal function, and in inducing a considerable percentage of clinical responses.
PMCID: PMC2033308  PMID: 8018527
25.  Adrenocortical Atrophy and Diffuse Cerebral Sclerosis 
Archives of Disease in Childhood  1971;46(247):273-284.
A boy, diagnosed as having Addison's disease due to idiopathic atrophy of the adrenal glands at the age of 7 years, developed the first evidence of what was originally thought to be `Schilder's disease' at 8 years and 10 months. He died at 9 years and 11 months. There was a very striking family history of autoimmune disorders on the mother's side. The clinical and pathological aspects of his case are outlined. Detailed studies of adrenal function during life showed a diminution in excretion of adrenal androgens and corticosteroids before therapy which was not evident from the 17-oxosteroid and 17-hydroxycorticosteroid assays in the resting state, though the initial diagnosis was based on the failure of ACTH to produce a rise in the 17-hydroxycorticosteroid excretion. No unusual or abnormal steroids were detected nor was there any disproportion between the androgen and corticosteroid excretion to suggest an adrenal enzyme deficiency. The biochemistry of the brain at necropsy revealed the changes expected in a demyelinating disorder, but the detection of abnormalities in the grey matter distinguished the condition from `Schilder's disease' in which the biochemistry of the grey matter is normal. There are 12 fully documented reports of boys with adrenocortical atrophy and diffuse cerebral sclerosis, and it is thought that this rare entity is inherited as an X-linked recessive characteristic. The two likely theories of causation involve either an error of metabolism common to the adrenal cortex and the brain, or the possibility that both the adrenal and brain pathology are due to an autoimmune disorder.
PMCID: PMC1647695  PMID: 4326280

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