The effect of long-term thyroxine on bone mineral density and serum cholesterol

The effect of thyrotrophin suppression on bone mineral density (BMD) and serum cholesterol concentration was assessed in 31 treated hypothyroid women. Measurements of the BMD of the lumbar spine and femoral neck were repeated in seven of those with the lowest value after an average period of 22.7 months. Final cholesterol concentrations were compared with values before thyroxine was started. The dose of thyroxine was based on clinical assessment, serum triiodothyronine concentrations kept within the normal range, and thyrotrophin values within the normal range or suppressed. The patients had taken thyroxine replacement for a mean of 12.7 years. Two-thirds (21 subjects) had suppressed thyrotrophin concentrations, and it was normal in one-third (10). Fifteen subjects had a past history of thyrotoxicosis. BMD and cholesterol concentrations were compared between those with suppressed and normal thyrotrophin concentrations and between those with and without a past history of thyrotoxicosis. No patient had a pathological fracture. One had a Z value for the femoral neck of -1.6, denoting early but definite osteoporosis, and five had borderline osteoporosis with Z values for one or other site between -1.1 and -1.5. None of the seven with the lowest BMDs had any significant change when measurements were repeated. The difference in Z values between subjects with suppressed and normal thyrotrophin concentrations was not significant for either the lumbar spine (p = 0.68) or the femoral neck (p = 0.28). A past history of thyrotoxicosis had a greater effect on BMD for both sites than thyrotrophin suppression, but again the difference between those with and without a past history of thyrotoxicosis was significant neither for the lumbar spine (p = 0.18) nor for the femoral neck (p = 0.34). The combination of thyrotrophin suppression and a past history of thyrotoxicosis also failed significantly to reduce the BMD of the lumbar spine (p = 0.38) or femoral neck (p = 0.30) in comparison with those who had neither thyrotrophin suppression nor a past history of thyrotoxicosis. The mean fall in serum cholesterol concentration was 2.1 mmol/l (SD 1.78) (p = 0.001) in those with a suppressed thyrotrophin concentration taking a mean daily dose of thyroxine of 171 micrograms (SD: 34.7), compared with a fall of 0.89 mmol/l (SD: 1.04) (p = 0.065) in those whose thyrotrophin concentration was not suppressed on a mean daily thyroxine dose of 140 micrograms (SD: 50). No patient had atrial fibrillation or cardiographic evidence of coronary artery disease (CAD). The serum cholesterol concentration should play at least as important a part in influencing the dose of thyroxine as a fear of osteoporosis. Fractures are not a feature in the natural history of treated hypothyroidism, whereas CAD is a common cause of death in these patients.     

Effects of thyroxine as compared with thyroxine plus triiodothyronine in patients with hypothyroidism

BACKGROUND: Patients with hypothyroidism are usually treated with thyroxine (levothyroxine) only, although both thyroxine and triiodothyronine are secreted by the normal thyroid gland. Whether thyroid secretion of triiodothyronine is physiologically important is unknown. METHODS: We compared the effects of thyroxine alone with those of thyroxine plus triiodothyronine (liothyronine) in 33 patients with hypothyroidism. Each patient was studied for two five-week periods. During one period, the patient received his or her usual dose of thyroxine. During the other, the patient received a regimen in which 50 microg of the usual dose of thyroxine was replaced by 12.5 microg of triiodothyronine. The order in which each patient received the two treatments was randomized. Biochemical, physiologic, and psychological tests were performed at the end of each treatment period. RESULTS: The patients had lower serum free and total thyroxine concentrations and higher serum total triiodothyronine concentrations after treatment with thyroxine plus triiodothyronine than after thyroxine alone, whereas the serum thyrotropin concentrations were similar after both treatments. Among 17 scores on tests of cognitive performance and assessments of mood, 6 were better or closer to normal after treatment with thyroxine plus triiodothyronine. Similarly, among 15 visual-analogue scales used to indicate mood and physical status, the results for 10 were significantly better after treatment with thyroxine plus triiodothyronine. The pulse rate and serum sex hormone-binding globulin concentrations were slightly higher after treatment with thyroxine plus triiodothyronine, but blood pressure, serum lipid concentrations, and the results of neurophysiologic tests were similar after the two treatments. CONCLUSIONS: In patients with hypothyroidism, partial substitution of triiodothyronine for thyroxine may improve mood and neuropsychological function; this finding suggests a specific effect of the triiodothyronine normally secreted by the thyroid gland.     

Thyroid hormones and thyrotropin in liver and kidney insufficiency

In 22 patients with hepatic or renal insufficiency the serum concentrations of trijodothyronin, thyroxine and thyrotropin and also the T4-binding capacity of TBG were determined. The mean serum T3 concentration was found to be significantly lower in patients with hepatic coma when compared with euthyroid subjects. In the cases of renal insufficiency the serum T3 concentrations were in the normal range. Due to hormone loss through dialysis however, the mean value of the T3 concentrations was slightly lower than the average concentration of normal subjects. The obtained results agree with those of our earlier studies which showed that there are significant differences between liver artery and vein T3 concentrations in serum, whereas no such differences could be ascertained between serum concentrations in renal artery and vein. On the basis of these findings it is assumed that conversion of T4 into T3 occurs predominantly in the liver.     

Influence of metabolic acidosis on serum 1,25(OH)2D3 levels in chronic renal failure

Metabolic acidosis has been shown to alter vitamin D metabolism. There is also evidence that calcium may modulate 1,25(OH)2D3 by a parathyroid hormone (PTH)-independent mechanism. To investigate the effect of rapid correction of chronic metabolic acidosis on serum 1,25(OH)2D3 levels by free calcium clamp in chronic renal failure, 20 patients with mild to moderate metabolic acidosis (mean pH 7.31 +/- 0.04) and secondary hyperparathyroidism (mean intact PTH 156.47 +/- 84.20 ng/l) were enrolled in this study. None had yet received any dialysis therapy. Metabolic acidosis was corrected by continuous bicarbonate infusion for 3-4 h until plasma pH was around 7.4, while plasma ionized calcium was held at the preinfusion level by calcium solution infusion during the entire procedure. The plasma pH, bicarbonate, total CO2, sodium, and serum total calcium levels were significantly increased while serum concentrations of alkaline phosphatase and albumin were significantly decreased after bicarbonate infusion. The plasma ionized calcium, potassium, serum magnesium, inorganic phosphorus, and 25(OH)D levels showed no significant change before and after bicarbonate infusion. The serum 1,25(OH)2D3 levels were significantly increased (38.66 +/- 11.77 vs. 47.04 +/- 16.56 pmol/l, p < 0.05) after correction of metabolic acidosis. These results demonstrate that rapid correction of metabolic acidosis raises serum 1,25(OH)2D3 levels in vitamin D-deficient chronic renal failure patients, and may underline the importance of maintaining normal acid-base homeostasis in the presence of secondary hyperparathyroidism in chronic renal failure.     

Tetanus immunization and its association to hepatitis B vaccination in patients with chronic renal failure

A defect in the immune response of patients with chronic renal failure leads to low response rates and insufficient antibody concentrations following a number of highly recommended vaccinations. This has been shown before for immunization against hepatitis B and influenza. Few data are available concerning the efficacy of vaccination with tetanus toxoid in these patients. In a prospective, controlled study we vaccinated seronegative patients with chronic renal failure not on dialysis, patients on chronic intermittent hemodialysis, and patients after kidney transplantation with tetanus toxoid. The results were compared with those of a control group consisting of 13 age-matched patients with mild essential hypertension and normal kidney function. Only 11 of 20 (55%) patients in the chronic renal failure group and 16 of 23 (69%) in the dialysis group had a protective antibody response after triple vaccination. In contrast, all the patients in the control group and six of seven transplant patients seroconverted. The response to tetanus toxoid was highly associated with the response to a previously administered vaccination against hepatitis B. Responders to this vaccination also had a better response rate to tetanus toxoid. The antibody concentrations after vaccination were lower in all patient groups compared with the controls; the lowest titers were found in the transplant patients. Therefore, renal patients will need revaccination much earlier, and tetanus toxoid antibody levels should be checked if a patient is injured and potentially requires vaccination.     

Relationship of admission thyroid function tests to outcome in critical illness

One hundred and eighty patients had serum thyrotropin, total triiodothyronine and free thyroxine concentrations measured within 3 h of admission to the Intensive Therapy Unit to assess whether thyroid function tests could predict outcome in critical illness. Overall mortality was 30.6%. Nonsurvivors were older (p = 0.001), and had higher APACHE II scores (p < 0.001) and predicted mortalities (p < 0.001). There was no difference in the median values of thyrotropin, total triiodothyronine and free thyroxine concentrations between survivors and nonsurvivors. Thyrotropin concentration was subnormal in 15 patients, normal in 152 and elevated in 13 patients. In contrast, 80 patients had subnormal triiodothyronine concentration. Free thyroxine was subnormal in five patients. Thyrotropin, total triiodothyronine and free thyroxine concentrations were not related to outcome (p = 0.360, p = 0.622, p = 0.726, respectively). No variable independently predicted death. Total triiodothyronine concentrations were lower in patients who received dopamine before admission to the intensive therapy unit than those who did not (p = 0.008); thyrotropin and free thyroxine concentrations were not influenced by dopamine administration. Serum concentrations of thyrotropin, total triiodothyronine and free thyroxine measured within 3 h of admission to the intensive therapy unit are not predictive of outcome.     

Role of the kidney in regulating plasma immunoreactive beta-melanocyte-stimulating hormone

An analysis of the factors that influence the increase in plasma immunoreactive beta-melanocyte-stimulating hormone (beta-MSH) concentration in chronic renal failure showed that: (a) the increase correlated with the increase in serum creatinine concentrations; (b) beta-MSH was not cleared from the plasma by haemodialysis; (c) beta-MSH concentrations increased with length of time on dialysis and increased further after bilateral nephrectomy but there was no further increase with time; (d) beta-MSH levels decreased to normal after renal transplantation; and (e) beta-MSH was excreted in urine only when plasma levels rose to well above those of chronic renal failure (in Nelson's syndrome). These findings suggest that the kidney regulated plasma beta-MSH by a non-excretory mechanism and is the major site of beta-MSH metabolism.     

Thyroid status in patients with chronic renal failure

Serum thyroid hormone concentrations have been measured in 21 patients with chronic renal failure, treated conservatively and compared with values from 19 control subjects. Many patients had serum total T3 and T4 concentrations below the reference ranges. The concentrations of free T4 and free T3 and the free thyroxine index were significantly lower in patients with abnormal total concentrations of the thyroid hormones than in the controls. Both the free and the total concentrations of T4 correlated inversely with the degree of renal failure. The concentration of thyroxine binding globulin (TBG), fell within the reference range in each of the patients, but was significantly lower in the patient group when compared with the controls. These TBG concentrations, however, were not sufficiently decreased to explain the low total thyroid hormone concentrations found in the patients. The affinity of TBG for T4 and T3 in the patient and control groups was not significantly different. The TSH response to TRH was diminished in many of the patients, but the measurement of other pituitary hormones indicated that pituitary function was normal in these patients. The possible mechanisms responsible for the changes observed in thyroid and pituitary hormones are discussed.     

Acute effect of inorganic iodide after 131I therapy for hyperthyroidism

Patients treated with inorganic iodide weeks to years following 131I therapy for hyperthyroidism do not adapt to its antithyroid effect. To determine whether such adaptation occurs soon after 131I therapy, serum thyroxine (T4) and triiodothyronine (T3) concentrations were measured daily for 9-14 days following 131I therapy in seventeen hyperthyroid patients. Nine patients received 150 mg KI daily starting 48 h after 131I administration; eight received only 131I. Serum T4 and T3 concentrations did not change significantly in the patients who received only 131I. In the patients who received 131I and KI, serum T4 and T3 concentrations fell promptly, reaching nadir values 2-10 days after initiation of iodide, and then increased despite continuation of KI therapy. The mean maximal fall in serum T4 was 34% and in serum T3 42%. These results show that "escape" from the acute anti-thyroid effect of iodide occurs when it is given immediately after 131I therapy, thus limiting the utility of iodide as a therapeutic agent at this time.     

Levels of cadmium in serum of patients with chronic renal failure

The aim of the study was obtain answers the following questions: 1. Are serum cadmium concentrations in patients with chronic renal failure (CRF) different from levels in healthy subjects? 2. Are serum concentrations of above mentioned metal different between haemodialysed and non-haemodialysed patients. 3. Are serum cadmium concentrations changing during haemodialysis? 66 patients with chronic renal failure (42 patients treated with haemodialysis and 24 non-haemodialysed patients) and 16 healthy subjects were observed. The blood samples in non-haemodialysed patients and healthy subjects were withdrawn only after cannula had been inserted into the antebrachial vein. The blood samples in haemodialysed patients were withdrawn four times: just before dialysis, during haemodialysis (in one hour of dialysis just in front of dialyser and just behind one) and after haemodialysis. Cadmium concentrations in serum in all examined group and cadmium concentrations in dialysis fluid and in demineralised water were measured by flame atomic absorption spectrophotometry. No significant changes were observed in serum cadmium concentration between patients with CRF and healthy subjects. Cadmium-concentration in non-haemodialysed patients was significantly higher than in haemodialysed patients. During haemodialysis a significant increase of serum cadmium level was observed. Conclusions: 1. Serum cadmium concentration in patients with CRF and in healthy subjects are not statistically different; 2. No significant changes in cadmium concentration between uraemic group patients were found; 3. Haemodialysis influences significantly on cadmium concentration.     

Astrocytic pathology in progressive supranuclear palsy: significance for neuropathological diagnosis

It has been shown that hepatitis C virus (HCV) infection is closely associated with mixed type cryoglobulinaemia. It is also known that HCV infection is rampant among chronic haemodialysis patients. We studied 531 renal failure patients on maintenance dialysis including 170 with positive HCV antibodies for cryoglobulinaemia, and its incidence was compared with controls which consisted of 242 chronic hepatitis C patients without renal failure and 183 healthy adults. Cryoglobulinaemia was present in 30.6% of dialysis patients with HCV infection, 10.8% of dialysis patients without HCV infection, 29.8% of patients with chronic hepatitis C without renal failure, and 0% of healthy adults. Among the 30 new renal failure patients who were started on dialysis within 6 months, four were positive for HCV antibodies, and one of them had cryoglobulinaemia; of the 26 HCV-negative patients, four (15%) were cryoglobulinaemic. The cryocrit values among dialysis patients were much lower than those of the control cases and other reports on non-dialysis cases. Patients with cryoglobulinaemia were generally younger compared with patients negative for this condition. There was no correlation between cryoglobulinaemia and past blood transfusion, underlying disease or length of dialysis. Cryoglobulinaemic patients seem to develop renal failure at relatively young ages and a considerable proportion of cryoglobulinaemic dialysis patients may have already had cryoglobulinaemia at the time of the start of haemodialysis. There was no indication that the presence of cryoglobulin in serum adversely affects the liver disease nor increases serum virus load in HCV-infected dialysis patients. Thus, it was concluded that although HCV infection has a certain role in the development of cryoglobulinaemia in dialysis patients, they develop cryoglobulinaemia less frequently and produce cryoglobulin to a lesser degree in the presence of HCV infection as compared with non-dialysis patients.     

Pharmacokinetics of gentamicin during peritoneal dialysis in children

The pharmacokinetics of gentamicin were examined on two occasions using intravenous and intraperitoneal routes in five children undergoing intermittent peritoneal dialysis for chronic renal failure. Serum, urine and dialysis fluid (DF) were assayed microbiologically for gentamicin and the data were subjected to computer analysis using equations evolved for a two-compartment model which considered the bi-directional flux of the drug. Following i.v. injection of 1 mg/kg of gentamicin, the apparent volume of distribution averaged 23% (range, 13 to 36%) of body wt (similar to normal), the mean half-life was 21 hr (range 9 to 37 hr; normal, 2 hr) and the peritoneal clearance averaged 4.0 ml/min/m2 (range, 1.2 to 7.0 ml/min/m2). During peritoneal administration of gentamicin (15 mg/liter of DF, 0.7 liters/m2 administered in each cycle over 9 to 12 cycles), serum concentrations increased towards extrapolated steady-state levels which averaged 42% (range, 25 to 68%) of DF concentrations. The mean renal clearance of gentamicin was only 1.6 ml/min/m2 while total body clearance ranged from 2.3 to 8.0 ml/min/m2 mostly occurring by a variable degree of dialysance. Peritoneal clearances and half-lives of gentamicin were similar in each patient following either treatment mode. The appreciable variability in gentamicin pharmacokinetics among adolescent patients with renal insufficiency necessitates dosage adjustments based on measurements of serum concentrations.     

Pharmacokinetics of cefamandole in patients undergoing hemodialysis and peritoneal dialysis

The pharmacokinetics of cefamandole nafate, a new parenteral cephalosporin derivative, were evaluated in 11 patients with chronic renal failure (creatinine clearance less than 5 ml/min), including five patients during hemodialysis, four patients during routine peritoneal dialysis, and two patients during the interdialytic period. Peak serum levels of cefamandole were comparable to those observed in patients with normal renal function. Clearance of the drug during the interdialytic period and during hemodialysis and peritoneal dialysis was minimal, with a resultant significant prolongation of serum half-life. The nondialyzability of cefamandole is in contrast with reported studies of cephalothin, where significant reduction of the serum half-life was achieved during hemodialysis but not peritoneal dialysis. The concentration of cefamandole in the peritoneal dialysate after parenteral administration was observed to be bactericidal for many gram-negative pathogens and, with the exception of Streptococcus faecalis, most gram-positive organisms found in bacterial peritonitis in patients with severe renal failure. The present data suggest that if stable bactericidal serum levels of cefamandole are to be maintained during hemodialysis and peritoneal dialysis, a parenteral loading dose must be administered followed by one-half the loading dose every half-life.     

Serum immunoreactive leptin concentration and its relation to the body fat content in chronic renal failure

Leptin, secreted from fat cells, functions as a lipostat mechanism through modulation of satiety signals. The role of leptin in humans has been only partly revealed. However, obese patients have markedly elevated levels of this hormone, and in both normal-weight and obese subjects there is a direct correlation between serum leptin levels and the percentage of body fat. The aim of the present study was to investigate the role of leptin and its relation to body fat content in chronic renal failure (CRF), a disorder associated with decreased appetite. Serum leptin levels and body composition (dual-energy x-ray absorptiometry) were measured in a cohort of 59 patients with terminal CRF (creatinine clearance rate, 8 +/- 1 ml/min). Sixteen of the patients were re-evaluated after 12 mo of peritoneal dialysis treatment, and eight patients were re-evaluated after 12 mo of hemodialysis treatment. The mean serum leptin concentrations were markedly higher (mean +/- SEM) in patients with CRF than in healthy control subjects matched for gender and body mass index (25.7 +/- 5.2 ng/ml versus 8.4 +/- 0.9 ng/ml; P < 0.001). Patients with ongoing signs of inflammation (C-reactive protein > 10 mg/L) demonstrated higher serum leptin levels (41.9 +/- 13.7 ng/ml versus 18.6 +/- 4.2 ng/ml; P < 0.05) than patients with normal C-reactive protein. A strong positive correlation (rho = 0.83; P < 0.0001) was found between serum leptin concentrations and the percentage of body fat. After 12 mo of peritoneal dialysis, the amount of body fat increased markedly (19.0 +/- 1.5 to 25.1 +/- 2.2 kg; P < 0.001), and the changes in serum leptin concentrations correlated significantly (rho = 0.69; P < 0.01) to the changes in the body fat content. In contrast, no significant changes in either body fat content or serum leptin levels were recorded in the eight patients that were re-evaluated after 12 mo of hemodialysis. Serum leptin concentrations are approximately three times higher in patients with CRF compared with healthy control subjects with a similar body mass index. In this study, it is also demonstrated that serum leptin is a good marker for the body fat content in CRF patients and correlates strongly to changes in body fat during 12 mo of peritoneal dialysis. These findings suggest that serum leptin could serve as a valuable clinical marker for the body fat content in patients with CRF. Further studies are needed to verify the hypothesis that increased serum leptin concentrations may contribute to uremic anorexia.     

Suppression of thyrotropin (TSH) and prolactin (PRL) release by pyridoxine in chronic primary hypothyroidism

A single iv dose of pyridoxine (V) (300 mg) caused a significant decrease in the concentration of serum thyrotropin (TSH) in 6 patients with primary hypothyroidism. There was no consistent change in serum thyroxine and triiodothyronine concentrations suring the experiment. The serum prolactin (PRL) levels were also suppressed by pyridoxine administration. These findings suggest that pyridoxine inhibits TSH secretion as well PRL by a direct action on the hypothalamus or pituitary gland.     

Renal failure after open heart surgery

One hundred fifty of 490 patients undergoing open heart surgery had renal failure attributable to cardiopulmonary bypass. In 69, serum creatinine concentrations did not exceed 2 mg/dl and returned to normal by the fourth postoperative day. In 60 patients, serum creatinine attained levels between 2 and 5 mg/dl, oliguria did not develop, and recovery of renal function occurred within 4 to 37 days. Serum creatinine increased to levels exceeding 5 mg/dl in 21 patients, 11 of whom were oliguric. Despite dialysis, 14 of these patients died from cardiac causes or sepsis. Prolonged cardiopulmonary bypass time, hypotension, oliguria, low output syndrome, and hemoglobinemia during open heart surgery correlated with the development of renal failure postoperatively. Although severe renal failure was an uncommon complication after open heart surgery, its occurrence carried a grave prognosis.     

Acetohexamide hypoglycemia: treatment by peritoneal dialysis

Acetohexamide hypoglycemia in a patient with renal failure has been successfully treated by peritoneal dialysis. Peritoneal dialysis was done in such a patient, and specimens of serum were collected to measure levels of acetohexamide and its main active metabolite, hydroxyhexamide. During dialysis, hypoglycemia was corrected. After 17 1/2 hours of dialysis, serum acetohexamide level was essentially unchanged. Serum hydroxyhexamide level had decreased at a slower rate than the rate of decrease previously measured in a uremic patient not on dialysis. Although peritoneal dialysis may correct the hypoglycemia, the data suggest that acetohexamide and hydroxyhexamide are not dialyzable. Due to these problems this drug should not be used in patients with chronic renal failure. The drug of choice to control hyperglycemia in patients with renal insufficiency is insulin. If for any reason insulin cannot be used, tolbutamide is the oral hypoglycemic agent of choice.     

Serum ionic fluoride levels in haemodialysis and continuous ambulatory peritoneal dialysis patients

High serum fluoride (F-) in patients with chronic renal failure (CRF) and end-stage renal disease (ESRD) is associated with risk of renal osteodystrophy and other bone changes. This study was done to determine F- in normal healthy controls and patients with ESRD on haemodialysis (HD) or peritoneal dialysis (PD). Seventeen healthy controls (12 males, 5 females) and 39 ESRD patients on dialysis (17 males, 22 females) were recruited in the study in a community with 47.4 +/- 3.28 microM/l (range 44-51 microM/l) of F- content in drinking water. Control subjects showed a mean serum F- concentration of 1.08 +/- 0.350 microM/l. Males in control group showed slightly higher F- levels (1.15 +/- 0.334, range 0.55-1.9 microM/l) than females (0.92 +/- 0.370, range 0.6-1.5 microM/l). Mean serum F- concentration did not correlate significantly with age and sex among control subjects, whereas such correlation was observed in patients with ESRD on dialysis. Mean serum F- concentration was significantly higher in patients on dialysis (2.67 +/- 1.09, range 0.8-5.2 microM/l) than normal controls. When grouped according to sex, the mean serum F- concentration in males (3.05 +/- 1.04, range 1.8-5.2 microM/l) was significantly higher than females (2.38 +/- 1.08, range 0.8-5.2 microM/l). When patients were grouped according to age, it was observed that F- concentration was significantly higher in patients with age groups 21-70 (2.86 +/- 1.05) than those with age group 13-20 years (1.42 +/- 0.531). Thus F- concentration correlated with age and sex, being higher in males and above 20 years. Despite appreciable clearance of F- (39-90%) across the peritoneum, patients on CAPD showed higher serum F- concentration than those on HD (3.1 +/- 1.97 vs 2.5 +/- 1.137 microM/l). Of the total 39 patients on dialysis 39% had their serum F- concentration above 3.0 microM/l, posing the risk of renal osteodystrophy.     

Abnormal thyroid and adrenocortical function test results in intensive care patients

A prospective, cohort study of 75 consecutive patients requiring management in the medical intensive care unit (MICU) of the Singapore General Hospital was carried out over a five-month period to determine thyroid and adrenocortical profiles and evaluate their use in predicting patient outcome. Up to 88% of patients had at least one abnormal thyroid function and 77% had abnormal adrenocortical function test results. There were significantly lower triiodothyronine, thyroxine and free thyroxine, but not thyrotropin levels, and higher cortisol levels in non-survivors compared to survivors (all P < 0.01). Of the endocrine parameters, triiodothyronine and cortisol concentrations were independent predictors of outcome. The overall predictive accuracy of combining these two variables on admission into the MICU was 74%. The APACHE II (acute physiology and chronic health evaluation II) score alone predicted outcome with 71% accuracy, and in combination with triiodothyronine and cortisol levels improved accuracy to 84%. The use of dopamine alone predicted outcome with 74% accuracy, and in combination with triiodothyronine and cortisol levels, improved accuracy to 84%. Measurements of total triiodothyronine and cortisol concentrations on admission to the MICU, and consideration of the use of dopamine improve on the APACHE II score in outcome prediction.     

A novel 22q11.2 microdeletion in DiGeorge syndrome

BACKGROUND: Decreased red blood cell survival contributes to the anemia of chronic renal failure patients. Because patients on chronic dialysis therapy are frequently exposed to excessive complement activation, we investigated the susceptibility of this patient population to erythrocyte C5b-9 deposition, complement-mediated lysis, and ghost formation. METHODS: We developed a flow cytometric assay using antibodies to both glycophorin and the C5b-9 complex to detect C5b-9 deposition on intact erythrocytes and erythrocyte ghosts. Serum C5b-9 levels and C5b-9 deposition on erythrocyte ghosts were measured by enzyme-linked immunosorbent assay. RESULTS: A significant increase in C5b-9 deposition on intact erythrocytes was demonstrated in patients with advanced chronic renal failure (2.2 +/- 0.5%) and in patients on chronic maintenance hemodialysis (2.3 +/- 0.4%) compared with normal volunteers (0.9 +/- 0.1%, P = 0.005 vs. chronic renal failure, P < 0.001 vs. chronic hemodialysis patients). There was also a significantly higher percentage of C5b-9-positive erythrocyte ghosts in patients with advanced chronic renal failure (20.6 +/- 5%) and in chronic hemodialysis patients (15.5 +/- 3.1%) compared with normal controls (2.6 +/- 0.9%, P < or = 0.001 vs. advanced chronic renal failure and chronic hemodialysis patients). Treatment of erythrocyte preparations with cobra venom factor, which activates the complement cascade, resulted in dramatic increases in the percentages of C5b-9-positive erythrocyte ghosts in patients with chronic renal failure (49.9 +/- 6.9%) and in chronic hemodialysis patients (45.0 +/- 4.2%) compared with normal volunteers (22.3 +/- 2.7%, P < 0.001 vs. chronic renal failure and chronic hemodialysis patients). Erythrocyte membrane expression of the complement regulatory proteins CD59 and CD55 did not significantly differ between normal controls and hemodialysis patients. Plasma C5b-9 levels after cobra venom factor stimulation were higher in chronic renal failure patients (538 micrograms/ml) compared with normal controls (345 micrograms/ml, P < 0.001). CONCLUSIONS: Patients with chronic renal failure and on hemodialysis therapy are susceptible to erythrocyte C5b-9 deposition with subsequent lysis and ghost formation. Susceptibility to complement-mediated erythrocyte injury may contribute to the anemia of chronic renal disease.