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High prevalence of the 999del5 mutation in icelandic breast and ovarian cancer patients.

Studies on Icelandic breast cancer families have shown that most of them segregate a 999del5 BRCA2 mutation. Here, we report the frequency of the 999del5 BRCA2 mutation in an Icelandic control population and four different groups of cancer patients diagnosed with (a) breast cancer; (b) ovarian cancer; (c) prostate cancer (patients younger than 65 years); and (d) other cancer types. The proportions of individuals carrying the mutation were 0.4% in the control population and in the patient groups 8.5%, 7.9%, 2.7%, and 1.0%, respectively. Our results indicate that BRCA2 confers a very high risk of breast cancer and is responsible for a substantial fraction of breast and ovarian cancer in Iceland, but only a small proportion of other cancers.

Adult↗

Outcomes in breast reduction surgery.

Previous studies have established that patients with macromastia rate their physical and emotional health as substantially poorer than a control population. The aim of the current study was to confirm this discrepancy, and to evaluate the hypothesis that patients with macromastia who undergo bilateral reduction mammaplasty experience a marked improvement of their general health, both physical and emotional, when compared with their preoperative state and age-matched control population. Sixty-nine consecutive patients were enrolled and evaluated preoperatively and 9 months postoperatively. The methods used for patient evaluation were the Short Form SF-36, a health-related quality-of-life questionnaire, and the Brief Symptom Inventory (BSI), a self-reporting instrument used to assess psychological symptoms. Preoperatively, all patients reported physical health poorer than the age-matched control group. At 9 months postoperatively, patients reported substantial improvement in all areas measured by SF-36 and in the variables this study measured with BSI. Postoperative groups reported their health to be similar to the nonpatient control groups. These findings confirm the therapeutic role of bilateral reduction mammaplasty in alleviation of symptoms associated with macromastia and in restoration of normal physical and emotional functioning.

Adult↗

SV40 T-antigen expression in skin fibroblasts from clinically normal individuals and from ten cases of Fanconi anemia.

Previous studies of the expression of SV40 genetic information by skin fibroblasts included limited numbers of cell donors and failed to adequately consider possible effects of age, sex, and ethnic origin on assay results. A population of 76 healthy subjects were selected for study following determination of personal and family disease history and karyological analysis. Skin fibroblasts from these individuals were tested for expression of SV40 T-antigen by indirect immunofluorescent assay. The data were normally distributed and showed no significant differences between the age, sex, or ethnic groups tested. The occurrence of rare karyological anomalies in this control population had no effect on T-antigen expression. Fibroblasts from 10 Fanconi anemia patients demonstrated significantly elevated expression of T antigen compared to the well-defined control population, based on simple statistical criteria. T-antigen expression was elevated in two young patients prior to the onset of anemia and did not appear to correlate with the incidence or severity of other specific symptoms. Thus, elevated T-antigen expression in Fanconi anemia fibroblasts reflects an actual defect at the cellular level, rather than clinical, age, sex or ethnic factors not previously considered.

Anemia, Aplastic↗

Perceived body image and eating behavior in young adults with cystic fibrosis and their healthy peers.

Treatment aimed at achieving an ideal nutritional status is an integral part of the management of patients with cystic fibrosis (CF). Emphasis is continually placed upon dietary intake and weight. The effects of this on eating behavior and self-perceptions are unclear. This work compared male and female CF adults with a healthy male and female control population with regard to (a) clinical variables, (b) actual, perceived, and desired body shape/body mass index (BMI), and (c) body satisfaction, eating behaviors and attitudes, and self-esteem. Clinical data were recorded for 221 adults with CF and 148 healthy controls. All subjects completed BMI Charts (perception of body weight/BMI), the Eating Attitudes Test, and scales of body satisfaction and self-esteem. CF patients had poorer lung function and nutritional status than controls. Control males accurately perceived their body shape/BMI and were content with it, whereas CF males viewed their BMI as greater than it actually was and desired to be much heavier. Control females viewed their body shape/BMI as less than it actually was and desired to be even slimmer, in comparison with CF females, who perceived their BMI as less than it actually was but were happy with their perceived shape/weight. Control subjects, especially females, dieted to a greater extent and were more preoccupied with food (with binge eating and intended vomiting) than CF patients. Conversely, those with CF reported greater pressure from others to eat than did controls. More problems with food/eating behavior were associated with less body satisfaction and reduced self-esteem. In comparison with a healthy control population, the perceptions and behaviors of CF adults relating to eating, weight, and body image are not abnormal. Indeed, females with CF have fewer problems than their healthy peers.

Adolescent↗

HLA-DRw antigens in Mexican-American and Black-American diabetic patients.

HLA-A, - B, and -C antigens were studied in 67 Mexican-American and 38 black-American diabetic patients who had the onset of their disease before age 31 yr. Control populations consisted of 322 Mexican-American and 367 black-American subjects for HLA-A, -B, and -C antigens. In addition, HLA-DRw antigens were studied in 60 Mexican-American and 34 black-American diabetic patients. Control populations for HLA-DRw antigens consisted of 189 Mexican-American and 145 black-American subjects. We found that juvenile-onset--diabetic patients of Mexican-American origin who had the onset of their disease before age 19 demonstrated a significant increase in HLA-DRw4. HLA-DRw4 was also significantly increased in black-American patients with juvenile-onset diabetes mellitus. HLA-DRw2 was not detected in any patient with juvenile-onset diabetes in either ethnic group. A significant association was found between HLA-B18 and HLA-DRw3 in Mexican-American juvenile-diabetic patients. These findings, which are comparable to those in similar Caucasian patients, provide additional information to support the hypothesis that HLA-DRw antigens play a major role in determining the susceptibility to juvenile-onset diabetes mellitus.

Adult↗

Does cervical spinal cord injury induce a higher incidence of complications after prophylactic Greenfield inferior vena cava filter usage?

PURPOSE: To determine whether acute cervical spine injury represents a risk factor for complications from prophylactic placement of current generation Greenfield inferior vena cava (IVC) filters. MATERIALS AND METHODS: A retrospective chart review performed during a 7-year period identified 11 patients with acute cervical spinal cord injuries who underwent prophylactic Greenfield IVC filter insertion. Specific complications evaluated included symptomatic pulmonary embolism (PE), migration, filter base diameter changes, caval perforation, and thrombosis. The amount of migration and changes in filter base dimension were compared statistically with a control population of IVC filter patients (n = 16) without cervical spine injuries. RESULTS: Filter migration (> 10 mm) was the most common complication (46%). Migration usually is caudally directed (64%), may occur early (36% moved > 10 mm within a 30-day period), and is often asymptomatic. The prevalence of filter migration greater than 30 mm was 27%. The average amount of migration for the subpopulation under study was greater than that seen with the control population (P < .05). No statistically significant change in filter base size occurred. The study population also had rates of PE (9%-18%), caval perforation (9%), and IVC thrombus formation (18%) that were higher than the rates in historical controls. The majority of patients with these complications received vigorous pulmonary toilet (46%), including "quad coughs" or cardiopulmonary resuscitation (18%). CONCLUSIONS: Acute cervical spinal cord injury and the associated supportive care may be associated with an increased risk for caudal IVC filter migration, IVC perforation, caval thrombosis, and PE.

Adult↗

Children may not benefit from neuroblastoma screening at 1 year of age. Updated results of the population based controlled trial in Germany.

Neuroblastoma is the second most frequent malignancy in childhood. We investigated whether screening for neuroblastoma at 1 year of age reduces the incidence of metastatic disease or mortality. Screening was offered in 6 of the 16 German states from 1995 to 2000 with the remaining states serving as controls. We studied 2,581,188 children in the screening area born between 1994 and 1999 and 2,117,600 in the control area. We compared mortality from neuroblastoma and the incidence of disseminated disease in the two groups. The screened group and the control group had similar rates of stage 4 neuroblastoma and mortality due to neuroblastoma. Comparison of the screened group and the control area revealed substantial over diagnosis in the screened participants. The present findings provide no support for mass screening for neuroblastoma at 1 year of age.

Child, Preschool↗

KLF6 IVS1 -27G>A variant and the risk of prostate cancer in Finland.

OBJECTIVES: A recent report demonstrated that KLF6 IVS1 -27G>A substitution increases the transcription of alternatively spliced isoforms; this action was suggested to be associated with prostate cancer (pCA). To evaluate these findings among the Finnish population, a total of 3348 samples were analysed. METHODS: The variant was genotyped in 164 patients with familial pCA, 852 patients with unselected pCA, 459 patients with benign prostate hyperplasia (BPH), 923 male population controls, and 950 men from a Finnish prostate-specific antigen (PSA) screening trial with PSA levels less than 1.0ng/ml. Odds ratios (ORs) and corresponding 95% confidence intervals (95%CIs) were calculated by using logistic regression to estimate pCA risk. RESULTS: Association testing revealed no significant differences between familial prostate cancer patients and population controls (OR: 0.84; 95%CI, 0.56-1.28; p=0.42), unselected cases and controls (OR: 0.95; 95%CI, 0.76-1.19; p=0.63), or BPH cases and controls (OR: 1.12; 95%CI, 0.86-1.46; p=0.39). pCA and BPH cases were also compared with PSA-screened controls. None of these analyses revealed any significant associations. CONCLUSIONS: Our results do not support the suggested association of KLF6 IVS1 -27G>A germline polymorphism with pCA risk and also suggest that the variant is not a risk allele for BPH in the Finnish population.

Adenine↗

Thyroid function in mothers of hypothyroid newborns.

OBJECTIVE: To assess etiologic significance of maternal autoimmune thyroid disease on incidence of transient congenital hypothyroidism in newborns. METHODS: Thyroid function was assessed in 259 mothers of hypothyroid newborns from the Quebec newborn screening program between 1984 and 1996. Maternal blood samples were taken routinely at the time of follow-up serum sampling of the infants, for measurements of free thyroxine, TSH, and antimicrosomal autoantibodies. Thyroid scans were conducted to characterize the type of thyroid dysfunction in affected infants. Results were compared with similar data from a control population of 1773 pregnant women recruited from Quebec City between 1991 and 1992. These samples were collected at routine second-trimester prenatal screenings. RESULTS: The mothers of congenitally hypothyroid infants had higher prevalence of suppressed serum TSH concentrations compared with the control population (6.1% versus 2.9%, P = .01), higher prevalence of increased serum TSH levels (7.0% versus 0.9%, P < .001), and similar prevalence of positive antimicrosomal antibodies (11.6% versus 12.1%, P = .90). The prevalence of transient congenital hypothyroidism in the study population of hypothyroid infants was 27%, which is significantly greater than the 15% observed in our overall population of 523 congenitally hypothyroid infants studied between 1974 and 1996 (P = .04). Antimicrosomal antibodies were demonstrable in ten (77%) of 13 mothers of infants with transient congenital hypothyroidism, and antimicrosomal antibodies or abnormal serum TSH levels in 13 of 13 (100%). CONCLUSION: These results indicate that most, if not all, cases of transient congenital hypothyroidism were attributable to maternal autoimmune thyroid disease, and presumably to maternal TSH receptor-blocking antibody. They suggest that maternal autoimmune thyroid disease is associated with much higher prevalence of transient congenital hypothyroidism than suspected. Because of the 20% prevalence of autoimmune thyroid disease and thyroid dysfunction in the mothers of congenitally hypothyroid infants, we recommend thyroid assessment of such women, if this information is not available.

Autoantibodies↗

Phase II trial of single agent carboplatin followed by dose-intense paclitaxel, followed by maintenance paclitaxel therapy in stage IV ovarian, fallopian tube, and peritoneal cancers: a Southwest Oncology Group trial.

OBJECTIVE: To improve the survival of women with stage IV epithelial ovarian cancer the Southwest Oncology Group conducted a phase II trial examining two novel treatment strategies: (a) modification of the chemotherapy regimen (carboplatin/paclitaxel) based on evidence of response during treatment and (b) "maintenance therapy," with the monthly administration of single agent paclitaxel (maximum 2 years). METHODS: Individuals with histologically documented stage IV ovarian, fallopian tube, or peritoneal cancers initially received a maximum of 3 courses of single agent carboplatin (AUC 6), with the decision to administer a subsequent course based on specific response criteria (i.e., declines in serum CA-125 or shrinkage of measurable mass lesions). This was followed by single agent paclitaxel (150 mg/m(2)), delivered every 2 weeks for a maximum of 6 courses, again based on evidence of continued response to the treatment program. Finally, in the absence of disease progression or unacceptable toxicity, patients received single agent paclitaxel (175 mg/m2) for a maximum of 24 monthly courses. The primary study end point was 2-year overall survival, which was to be compared to the survival of a previously published historical control population [stage IV ovarian cancer patients treated with a "standard" cisplatin/paclitaxel regimen (GOG 111; McGuire WP, N Eng E J Med 1996; 334:1)]. This analysis was employed to determine if this novel strategy was worthy of further clinical investigation in a controlled clinical trial. RESULTS: There were 53 patients entered this multicenter study, of whom 50 were evaluable for toxicity and 51 for survival. There were 2 treatment-related deaths. Grades 2 and 3 neutrotoxicity were observed in 18 and 4% of patients, respectively. There were no major treatment-related protocol violations. The overall 2-year survival was 48% (95% CI, 34-62%), compared to 60% for the historical control group. CONCLUSIONS: While this trial demonstrated the feasibility of delivering a treatment regimen requiring frequent alternations in therapy based on predetermined changes in objective parameters of response, further exploration of this specific management approach does not appear warranted in stage IV ovarian cancer, based on the survival outcome compared to a reasonably similar historical control population. As this trial demonstrates, the prospective determination of clinical end points in a phase II study (e.g., 2-year survival) that will lead to continued evaluation of a particular investigative strategy in a large-scale randomized trial can be an effective method to reduce the bias and uncertainty often associated with this complex decision process.

Adult↗

Studies of Campylobacter jejuni in patients with inflammatory bowel disease.

Cultures, serology, and immunohistochemical tests for Campylobacter jejuni were performed on 74 patients with inflammatory bowel disease of various disease activity and in healthy and diseased control populations. Fecal cultures were negative in all groups tested. Antibodies to C. jejuni were assessed both by a complement fixation assay and an enzyme-linked immunosorbent assay to multiple serotypes of the organism. Antibody titers in inflammatory bowel disease patients and control populations were similar, and titers in these groups were significantly lower than in patients with acute Campylobacter enteritis. Intestinal tissues examined for Campylobacter antigens by an indirect fluorescent antibody assay were negative. These data do not etiologically implicate C. jejuni in Crohn's disease or chronic ulcerative colitis.

Antibodies, Bacterial↗

Paraoxonase-1 (PON1) activity, but not PON1(Q192R) phenotype, is a predictor of coronary artery disease in a middle-aged Serbian population.

BACKGROUND: Paraoxonase-1 (PON1) is a high-density lipoprotein (HDL)-associated serum enzyme that protects lipoproteins from oxidative modifications. Polymorphisms in the gene, including PON1Q192R, have been studied. However, inconsistencies regarding the above-mentioned polymorphism obscure its association with vascular disease. METHODS: Using a two-substrate (paraoxon/diazoxon) activity method, we investigated the frequencies of PON1Q192R phenotypes in 261 middle-aged subjects: 156 patients with angiographically assessed coronary heart disease (CHD) and 105 CHD-free subjects as the control group. The PON1(192) phenotype was predicted from examination of the two-dimensional plot of hydrolysis rates of diazoxon vs. paraoxon and by using the antimode of the histogram of the ratio of diazoxonase/paraoxonase activity. RESULTS: The PON1Q192R phenotype frequencies in 113 patients with occlusion >50% (coronary artery disease-positive, CAD+ group) vs. control population were as follows: QQ (0.552 vs. 0.510), QR (0.382 vs. 0.408) and RR (0.066 vs. 0.082); chi2=0.414, p=0.813. We found lower paraoxonase (POase) and diazoxonase (DZOase) activities in the CAD+ patients when compared to the control population. According to logistic regression analysis, POase activity was a better predictor of coronary disease onset compared with DZOase activity measurements and PON1Q192R phenotyping. CONCLUSIONS: We conclude that enzyme activity (within a particular phenotypic group) is more important than phenotype alone in predicting susceptibility to coronary artery disease.

Aryldialkylphosphatase↗

Increased risk of Graves' disease after pregnancy.

The improvement in autoimmune thyroid disease during pregnancy and the subsequent exacerbation postpartum is secondary to immune system changes necessary to a normal pregnancy. Prior studies have shown that a clinically significant number of women develop Graves' disease (GD) in the postpartum period. The aim of this study was to examine the risk of post pregnancy GD and define patient characteristics that may impact the diagnosis and treatment strategies for this group. We performed a retrospective review of 152 consecutive women, aged 18-39 years when diagnosed with GD, to examine the relation between disease diagnosis and prior pregnancy. Differences in patient characteristics and treatment outcomes of women were analyzed. New York City population data were used to estimate a relative risk for the development of postpartum GD. We found that in parous women, 45% were diagnosed with GD in the postpartum period and 55% had an onset in subsequent years. No significant differences were noted in patient characteristics or treatment outcomes. We found that the risk of women developing post pregnancy GD was greatest in the older patients (35-39 years), with 56% developing GD compared to 42% of nulliparous women. These data, therefore, suggest an increased risk for older women. We were able to calculate the increase in estimated relative risk for postpartum disease by using control population data. The risk maximized at 5.6 for the age group 35-39 years when compared to the control population. These data support earlier studies that showed that a clinically significant number of women develop GD after childbirth compared to nulliparous women and extends this risk for many years. The mechanism of this long-standing increased susceptibility requires further delineation.

Adolescent↗

Investigation of the thoracic aorta in cholesterol embolism by transoesophageal echocardiography.

OBJECTIVES: To examine the thoracic aorta of patients with severe cholesterol embolism (CE) by transoesophageal echocardiography (TOE). METHODS: The thoracic aorta of 20 consecutive patients with CE was compared with that in a control population matched for age and risk factors by TOE. Patients were prescribed steroids after CE was diagnosed. Follow up is reported and compared with results in the literature. RESULTS: Aortic plaques and debris were more common in patients with CE than in the control population (p < 0.001 and p < 0.0001, respectively). The mean (SD) number of aortic plaques in the CE patients was 2.6 (0.7). This aortic atheroma was found predominantly in the descending aorta. One patient died during a mean (SD) follow up of 24 (10) months. CONCLUSIONS: Aortic atheroma, as detected by TOE, should be considered as the main source of CE. In addition, the prognosis in our series, in which steroids were systemically prescribed, is much better than in others reported in the literature.

Aged↗

Hemiparkinsonism with hemiatrophy.

We studied fifteen patients with hemiparkinsonism and ipsilateral hemiatrophy (HP/HA) to better characterize the clinical features of this syndrome and its rate of progression. Patients were distinguished by highly asymmetric parkinsonism with predominant signs on the side of HA, early age of onset (43.7 years versus 60.2 years in our control population of idiopathic Parkinson's disease [IPD], abnormal birth history (7/15), and dystonia occurring prior to levodopa therapy (10/15). In six patients, the mean duration of disease until the initiation of levodopa therapy was 14.2 years, as compared with 4.1 years in our control population of IPD. The slow progression of disease underscores the relatively favorable prognostic significance of HP/HA and its distinction from IPD.

Adult↗

Effect of age, gender, and parity on anal canal pressures. Contribution of impaired anal sphincter function to fecal incontinence.

The contribution of the resting anal canal pressure (RAP) and the maximal squeeze pressure (MSP) to the problem of fecal incontinence was assessed by comparing 143 incontinent patients to a control population of 157 healthy subjects. These parameters were determined using a multilumen continuously perfused catheter and a mechanized rapid pull-through technique. In 10 male volunteers both RAP and MSP were determined using catheters that varied from 3 mm to 18 mm in diameter. In the control population, the RAP was significantly lower in females 40 years of age and over as compared to males. MSP values were significantly lower in females at virtually all ages. In women, parity did not correlate with RAP (coefficient = -0.099, P greater than 0.05) and MSP (coefficient = -0.123, P greater than 0.05) and any decrease in pressures was related to aging. Aging in women was associated with a consistent reduction in RAP (coefficient = -0.614, P less than 0.00005) and MSP (coefficient = -0.372, P = 0.0006). In males, there was a similar but less impressive age-related reduction for the RAP (coefficient = -0.333, P = 0.006) but not for the MSP (coefficient = -0.196, P greater than 0.05). Nine percent of the volunteer population were essentially unable to increase the RAP with maximal squeeze efforts. A linear increase in anal pressures was recorded as catheter diameter increased from 3 to 12 mm. Normative data for the RAP and MSP (mean +/- 2 SD) were constructed for each sex on a decade basis and showed a wide range of pressures for each age grouping. In the group with fecal incontinence (FI) 39% of females and 44% of males fell within the "normal" range for both the RAP and MSP. For all patients with FI, 41% and 17% had impairment of one or both parameters, respectively. It is concluded that: aging affects the RAP in both sexes but to a greater degree in women. The MSP is related to aging in women only; child bearing has no effect upon these parameters; clinical problems of bowel control can occur when sphincter pressure measurements are within the low "normal" range; and recording instrument diameter consistently affects RAP and MSP.

Adult↗

Occupational life course and lung cancer risk in men. Findings from a socio-epidemiological analysis of job-changing histories in a case-control study.

Psychosocial factors in general, and the social and psychological conditions of work and occupation in particular, have attracted little attention to the epidemiological investigation into the occupational-related causes of lung cancer. There is some evidence available concerning the impact of loss events--including job losses--on cancer development. During our research presented in this article, we examined job changes and job transitions in the occupational biography of men with regard to their circumstances in terms of (in-)voluntariness both as individual events and the job-changing histories of individuals. We expected the job-changing histories of lung cancer cases to be more involuntary than those of population controls, and vice versa. Our sample contains 391 male case-control pairs. Cases are defined as newly-diagnosed men of German nationality with a histologically- or cytologically-confirmed diagnosis of primary lung cancer. Population controls were drawn randomly from the municipality records of residents and individuals matched to cases 1:1 by age and region. Occupational histories were reconstructed, and information about other classical and suspected risk factors was collected during standardized interviews by trained interviewers. We categorized the reported reasons for job changes, and classified them with respect to voluntariness on a seven-stepped rating scale from -3 'very involuntary' to +3 'very voluntary', defining relations within the empirically established categories. The job-changing histories of individuals are described by using the average score of voluntariness. We measured the degree of voluntariness for the occupational history: (1) by the rounded average score; and (2) by the quintiles of the average score. On the basis of individuals matched odds ratios (OR) estimates are derived for the score of voluntariness unadjusted and adjusted for smoking, asbestos exposure and socio-economic group by conditional logistic regression. The investigation into job-changing histories using the average score of voluntariness lead to similar results for both measuring methods for the total study group. When the rounded score was used, job-changing histories which were assessed as 'very involuntary' and 'involuntary' (score -3 and -2) showed an elevated odds ratio of adjusted 1.41 (95%-CI: 0.57; 3.48), and when they were assessed as 'moderately involuntary' (score -1) the adjusted odds ratio was 1.59 (95%-CI: 1.02; 2.48), as compared with job-changing histories assessed as neutral (score 0). When the degree of voluntariness was measured by quintiles, the first quintile (score -3- < -0.6) showed an elevated risk of adjusted OR 1.36 (95%-CI: 0.79; 2.36) as compared to the third quintile (score -0.2- < -0.1).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Evaluation of the pituitary-thyroidal axis in newborns undergoing exchange transfusion.

To evaluate whether the hypothyroxinaemia, previously noted in hyperbilirubinaemic newborns immediately after exchange transfusion for Rh or AB0 incompatibility, was due to impairment in the secretion of thyroid stimulating hormone (TSH) by the pituitary, we studied the thyroid hormone response to thyrotropin releasing hormone (TRH) and compared this response to that seen in a control population of healthy neonates. All infants studied responded with a brisk TSH increase; 30 min after TRH injection the mean TSH concentration of the hyperbilirubinaemic patients was 37 microU/ml, ten times their basal level, which was not different from the value noted in the control population. No significant change in total thyroxine (T4), 3,5,3' triiodothyronine (T3), free thyroxine (FT4) or 3,3',5' triiodothyronine (rT3), (FT4) or (rT3) was noted after TRH administration in either group of neonates. In addition the effect of exchange transfusion on the thyroid axis of hyperbilirubinaemic newborns was evaluated. Before the exchange transfusion TSH, T4, rT3, T3 and FT4 levels were higher in the hyperbilirubinaemic newborns than in donor blood; immediately post-exchange transfusion TSH and T4 concentrations of the hyperbilirubinaemic neonates decreased significantly and remained significantly below pre-exchange values 30 h later. Newborns undergoing an exchange transfusion respond appropriately to TRH stimulation and seem to have an intact pituitary-thyroidal axis.

Exchange Transfusion, Whole Blood↗