[Computed tomography in multiple trauma patients: technical aspects, work flow, and dose reduction]. / Polytrauma-Computertomographie : Technische Grundlagen, Workflow und Dosisreduktion.

CLINICAL/METHODICAL ISSUE: Patients with severe, life-threatening trauma require a fast and accurate clinical and imaging diagnostic workup during the first phase of trauma management. STANDARD RADIOLOGICAL METHODS: Early whole-body computed tomography has clearly been proven to be the current standard of care of these patients. METHODICAL INNOVATIONS: A similar imaging quality can be achieved in the multiple trauma setting compared with routine imaging especially using rapid, latest generation computed tomography (CT) scanners. PERFORMANCE: This article encompasses a detailed view on the use of CT in patients with life-threatening trauma. A special focus is placed on radiological procedures in trauma units and on the methods for CT workup in routine cases and in challenging situations. Another focus discusses the potential of dose reduction of CT scans in multiple trauma as well as the examination of children with severe trauma. ACHIEVEMENTS: Various studies have demonstrated that early whole-body CT positively correlates with low morbidity and mortality and is clearly superior to the use of other imaging modalities. PRACTICAL RECOMMENDATIONS: Optimal trauma unit management means a close cooperation between trauma surgeons, anesthesiologists and radiologists, whereby the radiologist is responsible for a rapid and accurate radiological workup and the rapid communication of imaging findings. However, even in the trauma setting, aspects of patient radiation doses should be kept in mind.

Human monoclonal autoantibodies that react with both pancreatic islets and thyroid.

Transformation of human peripheral blood lymphocytes with Epstein-Barr virus and rapid screening on rat insulinoma cells by an enzyme-linked immunosorbent assay were used to identify monoclonal autoantibodies that reacted with human pancreatic islets. Six such monoclonal autoantibodies were isolated and cloned. All six also were found to react with human thyroid. It is concluded that lymphocytes able to make autoantibodies that react with both the pancreas and thyroid are common in the human B cell repertoire.

The growth of adipose tissue in children and adolescents. Cross-sectional and longitudinal studies of adipose cell number and size.

Adipocyte size and number were determined in 288 subjects ranging in age from 4 mo to 19 yr. The study was performed in 110 obese and 178 non-obese subjects. 4-yr, longitudinal, follow-up studies were also performed in 132 subjects. The results demonstrate that the contribution of cell number and size to the growth of the fat depot in nonobese children varies with age. Deviations from this normal development were observed in obese children shortly after 1 yr of age. By 11 yr of age obese children exceeded the mean cell number found in nonobese adults. Indeed, obese subjects displayed more rapid and earlier elevations in both cell number and size, which were maintained throughout the study. Thus obese children display both quantitative and qualitative differences in fat tissue development when compared to nonobese children. The data indicate that the rate and type of adipose tissue cellular development one encounters in children may play a role in the development of the enlarged fat depots found in obese subjects.

Evaluation of carotid artery stenosis with multisection CT and MR imaging: influence of imaging modality and postprocessing.

BACKGROUND AND PURPOSE: We prospectively evaluated the influence of different imaging techniques (time-of-flight MR angiography [TOF-MRA], contrast-enhanced MR angiography [CE-MRA], multisection CT angiography [CTA]) and postprocessing methods (maximum intensity projection [MIP], multiplanar reformation [MPR]) on carotid artery stenosis grading. MATERIALS AND METHODS: Fifty patients (34 men, 16 women) with symptomatic stenosis of the internal carotid artery were examined with a 16-section spiral CT and a 1.5T MR unit. Two MRA techniques were applied: 3D-TOF and CE-MRA. MPR was used for postprocessing with all modalities; MIP was used only with MRA. Four readers measured and calculated the percentage diameter stenosis independently according to NASCET criteria. The Wilcoxon test was used to measure interobserver variability, and the Friedman test was used to test the null-hypothesis of equality of the modalities. RESULTS: The hypothesis for global equality was rejected (P < .001). TOF-MRA and CTA assessed with MPR showed the highest concordance (difference, 0.6%; confidence interval [CI], -3.0, 4.3%), and CE-MRA with MIP and CTA showed the lowest concordance in stenosis grading (difference, 7.0%; CI, 3.4, 10.6%). MPR resulted in lower degrees of stenosis than MIP for both MRA sequences, although not statistically significant (CE, -3.0%; CI, -6.6, 0.6%; TOF, -2.2%; CI, -5.8, 1.4%). When only studies with good or excellent image quality were considered, the differences decreased, but the trends remained. CONCLUSION: Stenosis grading is dependent on the examination method and postprocessing technique. CTA and TOF-MRA evaluated with MPR revealed highest concordance.

Excess of DR3/4 in type I diabetes. What does it portend?

The HLA-DR genotypes of 158 new type I diabetic probands from simplex families are compared with those of 43 multiply affected sibships. There were no significant differences in the gene frequencies of the insulin-dependent diabetes mellitus (IDDM)-associated alleles, DR3 and DR4, and whereas the DR3/4 heterozygotes were as frequent among simplex probands as among the first affected of multiplex sibships, subsequently affected sibs displayed lower frequencies of this genotype in this as well as in previously reported samples, indicating that the excessive risk associated with DR3/4 heterozygosity depends on the order of affection and thus on environmental factors. It is proposed that the penetrance of the susceptibility gene is enhanced by epistatic effects of this genotype and that this enhancement is strongest under conditions of low environmental liability. Thus, the excessive risk for DR3/4 individuals appears to depend on secondary interactions between DR and the environmental factors that trigger the onset of this disease and does not in itself indicate the existence of distinct susceptibility alleles in coupling with these genes, i.e., of genetic heterogeneity or overdominance.

Factitial panniculitis and necrotizing fasciitis in juvenile diabetes.

A fifteen-year-old diabetic girl developed multiple inflammatory areas on the extremities and abdominal wall at the site of insulin injection. The bizarre clinical manifestations led to great difficulties in determining both its etiology and its treatment. However, three months after her initial hospitalization, we found that the lesions were probably secondary to self-injection with a chemical agent rather than a result of insulin allergy. If idiopathic recurrent dermal infection is observed, then factitial origin should be suspected.

Cytotoxic islet cell surface antibodies (ICSA) in patients with type I diabetes and their first-degree relatives.

We describe a nonradioactive microcytotoxicity assay for ICSA using a cloned rat insulinoma cell line. This assay system had good reproducibility (r = 0.93) and was suitable for the study of large numbers of samples. The following results were obtained by testing the sera of 111 patients with IDDM (type I diabetes) and all of their first-degree relatives. (1) Thirty-five percent of IDDM patients had ICSA, as compared with only 2% of healthy controls. (2) ICSA was found more frequently in patients within 2 yr of onset (45%) than in those with disease for longer than 2 yr (27%) (P less than 0.05). (3) The prevalence of ICSA was associated with the presence of cytoplasmic islet cell antibodies (ICA) (P less than 0.05). (4) No association was found between the prevalence of ICSA and specific HLA-DR alleles. Association with the HLA haplotypes in families with ICSA-positive probands, on the other hand, is suggested although not proven by these data. (5) Among the nondiabetic relatives of IDDM patients, 5% of the parents and 14% of the sibs had ICSA. Increased prevalence of ICSA occurred in the unaffected sibs of ICSA-positive probands (31%) but not in those of ICSA-negative probands (4%) (P less than 0.001); in fact, the relatives of ICSA-negative probands had ICSA with a frequency not higher than in unrelated controls. (6) Female relatives of ICSA-positive probands were more often ICSA-positive than males, but no such difference was found among probands. (7) In multiplex sibships, ICSA were not associated with disease in the sibs.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-insulin antibodies in children with type I diabetes mellitus. Genetic regulation of production and presence at diagnosis before insulin replacement.

We evaluated the production of antibodies against insulin in a genetically well-defined population. In the first study, 124 young patients with type I diabetes for longer than 6 mo were included. Anti-insulin antibodies were detected by polyethyleneglycol (PEG) precipitation after incubation of acidified, charcoal-stripped sera with 125I-labeled pork insulin and were expressed as microunits insulin bound per milliliter whole serum. For comparison, the patients were divided into six groups based on HLA DR antigens: 3/3, 3/-, 4/4, 4/-, 3/4, and -/-(-is non-DR3 or -DR4). The mean age of the patients was 14.7 +/- 0.5 yr; the duration of diabetes was 5.8 +/- 0.4 yr; and the glucose control, as measured by hemoglobin A1c was average (7.6 +/- 0.2%). There were no significant differences in any of these parameters among the patients in any of the HLA DR groups. Patients expressing DR3/3 had significantly lower insulin binding than the rest of the groups (2.5 +/- 0.4 vs. 13.6 +/- 1.4 microU/ml, P less than 0.0001). Patients with DR3/ - did not differ in insulin-binding capacity from the other groups. The type of insulin used for replacement was not correlated with the serum insulin-binding capacity. In a second study, sera from 48 children, newly diagnosed with type I diabetes, were examined for the presence of insulin binding before treatment with exogenous insulin and compared with sera from 80 children without diabetes or a family history of diabetes and from 103 unaffected HLA-identical or haploidentical siblings of a child with type I diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)

Strong association between diabetes and displacement of mouse anti-rat insulinoma cell monoclonal antibody by human serum in vitro.

In an attempt to identify novel pancreatic beta-cell surface antigens, mouse monoclonal antibodies (MoAbs) were raised against rat insulinoma (RIN5F) cells with standard techniques. Several clones were identified whose antibodies bound specifically to RIN5F cells but not to other rat, mouse, and human target cells. Each of these MoAbs was radiolabeled, and the specificity of binding of each MoAb was determined by the ability of excess cold homologous MoAb to displace the labeled MoAb. Six RIN5F cell-specific MoAbs of different epitopic specificities were identified. The relevance of these beta-cell epitopes to human insulin-dependent diabetes (IDDM) was demonstrated by the differential ability of human serums from control and diabetic children to displace the radiolabeled MoAbs from the RIN5F cells. Serums from 333 children without diabetes or a family history of diabetes and from 156 newly diagnosed IDDM patients were tested. Only one IgM MoAb was specifically displaced by the IDDM serums, i.e., 146 of 156, compared to serums from control children, i.e., 10 of 333. With immunofluorescence, the serum component responsible for the displacement of the mouse MoAb was identified as IgG. Most of the positive control serums were from children with active autoimmune thyroiditis. Serums from children with other forms of glucose intolerance did not displace MoAb 1A2. There was no correlation between age and the degree of displacement of 1A2. Thus, the displacement of 1A2 is a specific and sensitive marker of diabetes susceptibility easily applicable to mass screening.(ABSTRACT TRUNCATED AT 250 WORDS)

HLA antigens, cytoplasmic islet cell antibodies, and carbohydrate tolerance in families of children with insulin-dependent diabetes mellitus.

Cytoplasmic pancreatic islet cell antibodies were found in 21% of 244 unaffected first degree relatives of type I diabetic patients. Twenty-five percent of HLA-identical, 35% of HLA-haploidentical, 16% of HLA-nonidentical siblings, and 14% of parents were ICA-positive. In the HLA-identical sibs, irrespective of ICA, and in the 18 ICA-positive parents but not the other groups, increased plasma glucose levels were observed after the administration of glucose. In most children, these were associated with reduced insulin levels, while in the adults elevated insulin responses were noted. In 48% of the ICA-positive children and 84% of the ICA-positive parents, other evidence of "autoimmunity" was obtained either by history or by testing for specific autoantibodies. Two of the originally unaffected HLA-identical and ICA-positive siblings developed diabetes during the course of the study. These findings, plus previously reported data in families with two diabetic sibs demonstrating that the empiric risk for developing IDDM is of the order of 30% for HLA-identical sibs but less than 5% for those that are HLA-haploidentical, suggest that HLA-identity may be a useful predictor of potential type I diabetes. The presence of ICA may, at times, portend the need for future antidiabetic therapy but prospective studies must be continued to fully elucidate this relationship.

The HLA system in congenital rubella patients with and without diabetes.

The HLA antigens of 173 patients with the congenital rubella syndrome (CR) are reported. Twenty-one of these patients are also clinically diabetic, and among them the frequencies of the HLA antigens DR2 and DR3 are significantly lower and higher, respectively, than in CR patients without diabetes or in controls. These data suggest that the genes that control susceptibility to type I or insulin-dependent diabetes mellitus are necessary for the development of glucose intolerance in CR patients.

No excess of DR*3/4 in Ashkenazi Jewish or Hispanic IDDM patients.

The gene frequencies, haplotype relative risks, and zygotic assortments of HLA-DR in three ethnically defined samples of insulin-dependent diabetes mellitus (IDDM) patients were determined in a prospective family study. Although DR3 and DR4 were positively associated with IDDM in the probands of 123 northern European, 94 Ashkenazi Jewish, and 49 New York Hispanic families, significant excess of DR*3/4 heterozygotes was observed only among the probands from families of northern European ancestry. There was also a significant decrease in the frequency of Bw62,DR4 haplotypes derived by northern European patients from their mothers compared with their fathers. This difference, together with data reported in the literature, suggests that the expressivity of the susceptible genotype(s) in IDDM patients may be modified by protective maternal effects associated with Bw62,DR4 and probably other DR4 haplotypes. Samples of IDDM patients from populations with high frequencies of these modifiers should have different DR-gene frequencies contributed by fathers and mothers, capable of accounting for the observed Hardy-Weinberg disequilibrium. We postulate that, because the mechanism of action of these modifiers is distinct from that of the susceptibility gene, the difference must be considered in devising strategies for elucidation of the mode of inheritance of the disease and for understanding the molecular nature of the susceptibility.

Functional properties of a naturally occurring Trp1200----Ser1200 mutation of the insulin receptor.

Based on the sequence of cDNA encoding the intracellular domain of the insulin receptor beta-subunit, we recently defined a heterozygous point mutation causing a Ser for Trp substitution at position 1200 in the tyrosine kinase domain of a patient (BI-2) with the type A syndrome of insulin resistance. We have now sequenced the remainder of BI-2's insulin receptor cDNA-coding region and find no additional alterations in the encoded proreceptor protein. The nucleotide sequence of cDNA encoding the portion of the beta-subunit which includes Trp1200 was normal in BI-2's unaffected mother. Hybridization of a mutant allele-specific oligonucleotide to polymerase chain reaction-amplified cDNA confirmed the presence of the mutant allele in the proband and excluded it in her unaffected sister and mother, 18 normal control subjects, and six other subjects with insulin resistance. To determine whether this mutation had functional consequences for receptor signalling, we reconstructed it into a full-length insulin receptor cDNA expression vector. Chinese hamster ovary cells were transfected with mutant cDNA, and the expressed insulin receptors were compared to receptors expressed by cells transfected with wild-type receptor cDNA. Both mutant and wild-type receptors were properly processed into receptor alpha- and beta-subunits, were expressed on the cell surface, and displayed similar insulin-binding affinity. In contrast, insulin-stimulated autophosphorylation of the mutant receptors was severely impaired, whether assessed in intact cells or with a partially purified receptor preparation.(ABSTRACT TRUNCATED AT 250 WORDS)

Randomized, controlled trial of diabetic patient education: improved knowledge without improved metabolic status.

We randomized 749 insulin-treated patients on the rolls of the Mount Sinai Medical Center Diabetes Clinic in a controlled trial of diabetic patient education; 345 agreed to participate, of whom 165 were assigned to the education group and 180 to the control group. Cognitive scores increased from 5.3 +/- 1.6 to 5.8 +/- 1.6 in the education group, but there was no change in the control group, whose score was 5.3 +/- 1.7 before and after the intervention (P = .0073). HbA1c fell from 6.8 +/- 2.1 to 6.1 +/- 2.0% in the education group and from 6.6 +/- 2.0 to 6.3 +/- 2.0% in the control group, an insignificant difference (P = .1995). The fasting blood glucose decreased from 223 +/- 94 to 179 +/- 73 mg/dl in the education group and from 199 +/- 81 to 185 +/- 76 mg/dl in the controls (P = .1983). Triglycerides, high- and low-density lipoprotein cholesterol, and insulin dosage also failed to show significant variation among groups. The foot-lesion score showed similar progression in the education and control groups. Neither diastolic nor systolic blood pressure showed significantly greater change in the education or the control group, with falls noted, particularly in diastolic pressures, in both patient groups. Differences between the groups were not significant for sick days, hospitalizations, emergency room visits, or outpatient visits. The sample sizes of the study and control populations were sufficiently large to detect a difference in means between the education and control groups in the HbA1c, the primary outcome variable, of greater than 1.0%, with alpha = .05 and a power of .95. Thus, our study suggests that patient education may not be an efficacious therapeutic intervention in most adults with insulin-treated diabetes mellitus.

Measurement of thyroid-stimulating hormone in human amniotic fluid.

TSH was measured in human amniotic fluid after 3- to 8-fold concentration of the fluids. Amniotic fluid TSH was identical to standard pituitary TSH by immunological and gel chromatographic criteria. In 201 samples of normal second trimester amniotic fluid (16-19 weeks of pregnancy), amniotic fluid TSH concentrations had a mean value of 0.4 microunits/ml (range, less than 0.15 to 1.7 microunits/ml). In 21 samples of third trimester amniotic fluid (obtained to check fetal lung maturity), amniotic fluid TSH concentrations had a mean value of 0.25 microunits/ml (range, less than 0.15 to 0.55 microunits/ml). The capability of measuring TSH in amniotic fluid and the relative constancy of these values between the second and third trimesters of pregnancy suggest that the determination of TSH levels in amniotic fluid may be useful in the diagnosis of fetal hypothyroidism in utero.

Antepartum diagnosis of goitrous hypothyroidism by fetal ultrasonography and amniotic fluid thyrotropin concentration.

Ultrasonography of a 26-week-old fetus suggested the presence of a goiter. Amniocentesis was performed at 26 and 38 weeks gestation to evaluate thyroid function. An elevated amniotic fluid TSH level was found on both occasions, though amniotic fluid T4, T3, and rT3 levels were similar to those of euthyroid fetuses. The diagnosis of goitrous hypothyroidism was confirmed at birth. Therapy with thyroid hormone was instituted on the first day of life. Growth and development of the infant have been normal during the first year of his life. We suggest that the measurement of amniotic fluid TSH can be useful in the diagnosis of intrauterine primary hypothyroidism.

Overweight and obesity in preschool children in New York City.

In an effort to ascertain the prevalence of obesity in young children, 48 nursery schools in Manhattan and Queens, New York City were surveyed. The weights and heights of 2606 children, ages 3 to 6 yr, were obtained. Three-hundred seventeen children (12.2%) were above 120% of ideal body weight and 122 (4.7%) were above 130% of ideal weight. Twenty percent of the children from schools attended by youngsters from low income families, 12% from schools attended by pupils from middle income families, and 5% from schools with pupils from families with a high income were classified as obese. Of the obese children's actual body weights 90% were at or greater than the 75th percentile for age while mean higher percentiles of the obese and nonobese children were not significantly different. Sex specific prevalence rates were similar for boys and girls. These data indicate that obesity is already prevalent in the nursery school population and that such obese children can be easily identified from weight and height measurements at a time when programs for successful permanent weight reduction and maintenance may be feasible.

Ischemia and sensory nerve conduction in diabetes mellitus.

Sensory conduction along the median nerve was evaluated during 30 minutes of ischemia in patients with diabetes mellitus. There was abnormal persistence of the sensory evoked potential in 19 of 22 diabetic patients, but not in normal controls, patients with nonmetabolic neuropathies, or 5 of 6 patients with motor neuron diseases. There was an excellent correlation between ischemic resistance and effective control of glucose metabolism, as manifested by Hb A1C levels. These data suggest that abnormal ischemic resistance in diabetes may be the most sensitive indicator of peripheral neural dysfunction even when there are no other electrophysiologic or clinical abnormalities.

Elevated hemoglobin A1c and low-density lipoprotein cholesterol levels in thiazide-treated diabetic patients.

Despite the well-known hyperglycemic effect of thiazide diuretics, these agents are often administered to diabetic patients. This study compared 89 insulin-treated diabetic patients receiving hydrochlorothiazide, 57 receiving furosemide, and 255 receiving no diuretic. Hemoglobin A1c level was 7.2 +/- 1.8 percent (mean +/- SD) with hydrochlorothiazide, significantly higher than the levels of 5.9 +/- 2.3 percent with furosemide and 6.4 +/- 2.0 percent with no diuretic. Low-density lipoprotein cholesterol level was 154 +/- 43 mg/dl with hydrochlorothiazide, but 134 +/- 42 mg/dl with furosemide and 130 +/- 42 mg/dl with no diuretic. Multivariate analysis showed that the associations remained significant after adjustment for age, sex, race, type and duration of diabetes, body mass index, blood pressure, serum potassium level, insulin dose, and treatment with other medications. These findings suggest that treatment with thiazide diuretics in the diabetic population may increase low-density lipoprotein cholesterol and hemoglobin A1c levels.

Cerebral edema and ophthalmoplegia reversed by mannitol in a new case of insulin-dependent diabetes mellitus.

Cerebral edema is a sometimes fatal complication of diabetic ketoacidosis which occurs unpredictably and when biochemical parameters show improvement. A case of a young, newly diagnosed insulin-dependent diabetic boy who developed this complication while receiving a low-dose continuous insulin infusion is reported. Two hours after treatment signs of headache, ophthalmoplegia, and blurred disc margins suggested early cerebral edema. Despite fluid restriction, avoidance of alkali, and phosphate supplementation, cerebral edema ensued three hours later. This complication was then reversed by administration of mannitol. Our patient's ophthalmoplegia, unlike typical diabetic ophthalmoplegia, improved immediately and completely resolved within two weeks after this episode. It is concluded that the use of mannitol in the cerebral edema of diabetic ketoacidosis is beneficial if it is instituted promptly.