CGH-detected DNA sequence copy number amplifications can be confirmed by interphase-FISH: new possiblities for prognostic approaches in oral squamous cell carcinomas

OBJECTIVE: Following the observation of two patients affected by true precocious puberty who went on to develop polycystic ovary syndrome (PCOS) and who were found to be heterozygotes (carriers) for 21-hydroxylase deficiency (21-OHD), we decided to evaluate the frequency of heterozygosity for adrenal 21-OHD in patients with true precocious puberty. STUDY DESIGN: We investigated 32 girls affected by true precocious puberty, by the single-dose ACTH stimulation test, HLA typing and the molecular analysis of the CYP21B gene encoding for the 21-OH enzyme, in order to detect gene deletions or point mutations. Twenty-eight cases were on LHRH analogue treatment and the remaining four, untreated owing to parental refusal, were investigated 0.5-1.5 years after spontaneous menarche. RESULTS: After ACTH testing, 13 out of the 32 (41%) cases displayed higher 17-hydroxyprogesterone (17-OHP) levels than normal but less than those found in patients affected by nonclassical adrenal hyperplasia (CAH); these levels were similar to those observed in obligate heterozygotes for CAH due to 21-hydroxylase deficiency (21-OHD). HLA typing showed a significantly increased frequency of the HLA alleles A28 and B14 which are peculiar to the HLA haplotypes of nonclassical CAH due to 21-OHD. Molecular analysis of the CYP21B gene showed that in four out of the 10 tested patients with an exaggerated 17-OHP response there were heterozygous point mutations of the CYP21B gene. In contrast, no CYP21B gene abnormalities were detected in the eight tested patients with normal 17-OHP. No differences were found between carriers and non-carriers of the 21-OHD with regard to age at onset of precocious puberty, clinical features, bone age acceleration and gonadal suppression induced by LH-RH analogue treatment. Two out of the four untreated patients who were investigated after menarche were found to be carriers of the 21-OHD; these girls showed signs of androgen excess, irregular menses and polycystic ovaries. CONCLUSIONS: A high frequency of heterozygosity for adrenal steroid 21-OHD was found in our patients with true precocious puberty. This adrenal defect does not seem to influence the pattern of central precocious puberty, but these patients require long-term follow-up as they might go on to develop polycystic ovary syndrome (PCOS). Whether or not heterozygosity of the 21-OHD may be related to the premature activation of the hypothalamo-pituitary-gonodal axis remains to be defined.     

The frequency of late-onset 21-hydroxylase and 11 beta-hydroxylase deficiency in women with polycystic ovary syndrome

OBJECTIVE: To determine the frequency of late-onset adrenal hyperplasia (LOCAH) due to 21-hydroxylase (21-OH) and 11 beta-hydroxylase (11 beta-OH) deficiency in women with clinical and biochemical features of polycystic ovary syndrome (PCOS). DESIGN: Eighty-three consecutively selected women with PCOS and eighteen normal women were included in the study. METHODS: Ultrasound, clinical and hormonal parameters were used to define PCOS. Basal FSH, LH, testosterone, free testosterone, androstenedione, dehydroepiandrosterone sulfate (DHEA-S), sex hormone-binding globulin (SHBG) and cortisol levels were measured. Serum 17-hydroxyprogesterone (17-OHP) and 11-deoxycortisol (11-DOC) levels were also measured before, 30 and 60 min after a single bolus injection of 0.25 mg ACTH (1-24) at 0900 h during the mid-follicular phase of the cycle. ACTH-stimulated 17-OHP levels > 30 nmol/l were considered as the criteria of 21-OH deficiency. The diagnosis 11 beta-OH deficiency was made if the adrenal 11-DOC response to ACTH stimulation exceeded threefold the 95th percentile of controls. RESULTS: Basal serum testosterone, free testosterone, androstenedione, DHEA-S, cortisol and 11-DOC levels were significantly higher in PCOS than in control subjects. ACTH-stimulated 17-OHP (P < 0.05) and 11-DOC (P < 0.0005) levels were found to be significantly higher in patients with PCOS than in controls. Seven (8.4%) patients had an 11-DOC response to ACTH higher than threefold the 95th percentile of controls, while no patients showed evidence of 21-OH deficiency. CONCLUSIONS: We have found that 8.4% of the women with clinical and biochemical features of PCOS could be presumed to have 11 beta-OH deficiency. No patients among the women with PCOS showed evidence of 21-OH deficiency. 11 beta-OH deficiency is unexpectedly more common than 21-OH deficiency in women with PCOS.     

Home monitoring of 17 alpha-hydroxyprogesterone levels by filter paper blood spots in patients with 21-hydroxylase deficiency

BACKGROUND: 21-Hydroxylase (21-OH) deficiency is characterized by an excess of androgen in both sexes and premature skeletal maturation resulting in short adult stature and male infertility. To achieve optimal height in children and fertility in adults, the replacement treatment of 21-OH deficiency with glucocorticoids should be regulated in order to adequately reduce the excess of androgens while minimizing the dose of glucocorticoids required. Neonatal screening for 21-OH deficiency is based on the measurement of the 17 alpha-hydroxyprogesterone (17-OHP) level from blood spotted on filter paper. The aim of this study was to examine whether repeated daily blood sampling on filter paper can assist in improving the monitoring of, and compliance to, 21-OH deficiency treatment. METHODS: During a 5-year period (1989-1994) we instructed 8 patients with 21-OH deficiency (2 males with salt losing, 2 males and 1 female simple virilizing, and 1 male and 2 females with nonclassical 21-OH deficiency) aged 1.3-36 years to sample blood on filter papers 1-4 times a day and send the papers to our neonatal screening laboratory by mail. On 62 occasions we measured both serum and filter paper 17-OHP levels in order to assess the degree of correlation between the two methods. RESULTS: Comparison between the filter paper and serum 17-OHP levels showed a correlation coefficient of r = 0.87. The filter paper levels were almost always higher than the serum levels. The serum 17-OHP levels were < 1 ng/ml whenever the filter paper levels were < 3 ng/ml. On long-term follow-up of 17-OHP filter paper levels we observed major diurnal and day-to-day fluctuations which might not have been noticed on routine follow-up clinic visits. CONCLUSIONS: Filter paper follow-up of 17-OHP levels can assist in optimizing the replacement treatment in patients with 21-OH deficiency while reinforcing compliance and decreasing the need for frequent clinic visits and hospitalizations. By adjusting the glucocorticoid type, dose, and time of administration to each patient we should be able to achieve optimal growth without bone age acceleration in children, to avoid overtreatment, and to improve fertility in adults.     

Soft-tissue sarcomas in the adult: news and trends]

The mechanism of growth retardation in Turner's syndrome has not been resolved. It is often referred to as a bone dysplasia, although endocrine derangement has not been ruled out. The present study was undertaken to evaluate the maturation of individual bones of the hand and wrist in girls with Turner's syndrome and thereby obtain information which may aid in elaborating the possible mechanism of the growth retardation in girls with Turner's syndrome. Hand and wrist films of 24 girls with Turner's syndrome, 11 normal girls with short stature and 23 normal controls were evaluated, using the references of Greulich and Pyle. Each bone or epiphysis was given an individual 'age'. During childhood the Turner patients showed the greatest delay in bone age of the phalangeal bones while the least delayed were the radius and ulna (long bones) and metacarpals. The carpal bones showed intermediate retardation. This pattern and extent of maturational retardation was clearly different from that of the short stature normal group, who showed uniform retardation of all bones. During adolescence, the phalangeal bones were further retarded and the carpal bones showed a moderate retardation. The unique profile of bone maturation in Turner's syndrome suggests an insult to chondroplasia, which may be related to estrogen deficiency or to an as yet undetermined endocrine or paracrine derangement.     

Congenital heart disease in patients with Turner's syndrome. Italian Study Group for Turner Syndrome (ISGTS)

OBJECTIVE: There is a high prevalence of congenital heart defects in patients with Turner's syndrome. Few studies have reported echocardiographic data in unselected patients according to the different chromosomal patterns. The aim of our study was to evaluate a large series of patients with Turner's syndrome, comparing these data with those of the general population. METHODS: Five hundred ninety-four patients with Turner's syndrome, aged 1 month to 24 years, in the Italian Study Group for Turner Syndrome underwent full cardiologic evaluation. Karyotype distribution was: 45,X (54%), X-mosaicism (13%), and X-structural abnormalities (33%). RESULTS: The prevalence of cardiac malformations was 23%. Bicuspid aortic valve (12.5%), aortic coarctation (6.9%), and aortic valve disease (3.2%) were the most prevalent malformations. In comparison with the general population, partial anomalous pulmonary venous drainage had the highest relative risk. A correlation was found between type of congenital heart defect and karyotype. The patients with 45,X karyotype had the greatest prevalence of partial anomalous pulmonary venous drainage and aortic coarctation, whereas bicuspid aortic valve and aortic valve disease were more common in the patients with X-structural abnormalities. The patients with severe dysmorphic signs showed a significantly higher relative risk of cardiac malformations. CONCLUSION: X-linked factors may be involved in determining cardiac defects in Turner's syndrome.     

Association of Sj?gren's syndrome with HLA-B8

HLA antigens were examined by microdroplet lymphocyte cytotoxicity in 31 patients with Sj?grens syndrome. Fifty percent of 22 Causcasian patients (7 of 17 females and 4 of 5 males) had HLA-B8, as compared to 21% of 1205 controls (P=0.002). The presence of HLA-B8 was not correlated with parotid salivary flow, keratoconjunctivitis sicca, or focus score. Because of its association with a number of autoimmune diseases, including Sj?gren's syndrome, it is suggested that HLA-B8 is genetically liked to an immune response gene(s) that predisposes the individual to autoimmune phenomena. The expression of autoimmunity may be determined by infectious or environmental factors.     

Patients with Turner's syndrome may have an inherent endometrial abnormality affecting receptivity in oocyte donation

OBJECTIVE: To evaluate whether endometrial receptivity is compromised in patients with premature ovarian failure (POF) due to Turner's syndrome who undergo oocyte donation. DESIGN: Retrospective analysis. SETTING: In vitro fertilization-ET units, anonymous oocyte donation program. PATIENTS: The study included 53 patients with POF who underwent oocyte donation. These included 7 patients with Turner's syndrome (45,X) who underwent 22 ET cycles, 15 women with Turner variants (mosaics, deletions, or isochromosomes) who underwent 36 ET cycles, and 31 other patients with POF and a normal karyotype who underwent 69 oocyte donation cycles. INTERVENTION: All patients on standby for donation were treated with E2 valerate 6 mg/d until oocytes became available; then P 100 mg/d was added. Oocyte donors were healthy women < 34 years who underwent IVF themselves. MAIN OUTCOME MEASURES: Clinical pregnancy rates (PRs), biochemical pregnancies, early abortions, and delivery rates were evaluated. RESULTS: Turner's syndrome patients had a significantly higher rate of biochemical pregnancies (22.7% versus 4.3%), a lower clinical PR (22.7% versus 33.3%), a significantly higher rate of early abortions (60% versus 8.7%), and a significantly lower rate of deliveries per pregnancy (20.0% versus 73.1%) compared with non-Turner patients. CONCLUSIONS: Patients with a complete or partial deficiency of an X chromosome have reduced PRs and an increase in early implantation failure after oocyte donation. This may indicate an inherent endometrial abnormality, possibly associated with a deficiency of X-linked genes regulating endometrial receptivity.     

New reliable biochemical marker for screening 21 alpha-hydroxylase deficiency without index person among hirsute women in agreement with HLA-haplotyping

Late onset congenital adrenal hyperplasia due to 21 alpha-hydroxylase deficiency (LO21OH def), as many other diseases, is the cause of hirsutism, menstrual disorders, infertility (PCO-like symptoms). We evaluated the reliability of a new biochemical marker for screening LO-21OH def in 47 women with PCO-like symptoms and 11 men, members of their families, comparing the results of separation using this new marker with those of HLA-haplotyping in 21 members of the patient population. All subjects were stimulated with 0.25 mg synthetic ACTH iv. Serum progesterone (P), 17-hydroxyprogesterone (17-OHP) and cortisol (F) at 0, 15, 30, 45 and 60 min following ACTH administration were determined and the new marker, namely the difference between 60min and 0min of the ratio F/17-OHP [delta F/17-OHP (60 min -0 min)] was calculated. According to the established biochemical criteria for the detection of LO-21OH def cases, (Gutai 30 min > or = 12 ng/dl/min and 17-OHP 60 min > or = 12 ng/ml for severe 21-OH def and Gutai 30 min < 6.5 ng/dl/min and 17-OHP 60 min < 5 ng/ml for "healthy" individuals regarding 21-OH def) two groups, A and B respectively, were separated from the patient population. In group A (n = 8), with LO-21OH def, the new marker showed negative values in all cases, while in group B (n = 9), without LO-21OH def, this marker was positive. The remaining subjects, depending on the results of the new marker were separated in 2 subgroups, Cneg (n = 28), with negative values, composed, consequently, of members with 21-OH def and Cpos (n = 13), with positive values, composed, consequently, of subjects with absence of LO-21OH def. HLA-typing was in agreement with the results of screening by the new marker, in 20 out of 21 cases, while there was only one false negative result. In conclusion, the proposed biochemical marker delta F/17-OHP (60 min-0 min) seems to be a reliable parameter for the LO-21OH def detection among young women with PCO-like symptoms as well as males suspected for congenital adrenal hyperplasia.     

Vasitis nodosa

PURPOSE: To report the association of keratoconus and Turner's syndrome in three patients and to review the ophthalmic manifestations of Turner's syndrome. METHODS: Three patients with keratoconus and Turner's syndrome were identified and reported in a retrospective review. RESULTS: These three cases represent the first series of patients with keratoconus and Turner's syndrome. All three patients underwent penetrating keratoplasty with good visual rehabilitation. None of the patients had other ocular features associated with Turner's syndrome. CONCLUSION: Turner's syndrome is commonly associated with ocular problems. In this series we identify an association of keratoconus with Turner's syndrome. Clearly, a careful ocular examination in this condition with attention to ocular features of Turner's syndrome is important.     

Biological monitoring of environmental exposure to PAHs in the vicinity of a S?derberg aluminium reduction plant

OBJECTIVES: To assess environmental exposure to polycyclic aromatic hydrocarbons (PAHs) in the vicinity of a S?derberg aluminium reduction plant in Shawinigan, Canada with urinary 1-hydroxypyrene (1-OHP) as a biomarker. METHODS: Urine samples were collected from 20 non-occupationally exposed subjects living less than 500 m from the plant and from 20 controls living in Trois-Rivières, another industrial town 40 km from Shawinigan. Concentrations of 1-OHP were measured by high performance liquid chromatography (HPLC). RESULTS: Among controls, geometric mean (range) 1-OHP concentrations were 0.046 (0.012-0.116) mumol/mol creatinine in non-smokers and 0.125 (0.051-0.282) mumol/mol creatinine in smokers. Among exposed subjects, values were 0.103 (0.056-0.196) mumol/mol creatinine in non-smokers and 0.250 (0.112-0.448) mumol/mol creatinine in smokers. Excretion of 1-OHP was significantly higher in exposed subjects than in controls among non-smokers and smokers (P < 0.05). CONCLUSION: Based on urinary 1-OHP as a biomarker, it seems that living near an industrial point source of PAHs is associated with higher exposure. The health significance of this finding will require further investigation.     

Prenatal and postnatal prevalence of Turner syndrome. A registry-based study

The prevalence of Turner's syndrome in Denmark 1970-1993 was studied and the validity of prenatal diagnosis was assessed. The study was conducted on prenatal and postnatal Turner's syndrome in the Danish Cytogenetic Central Register. All registered Turner's syndrome karyotypes (100 prenatal cases and 215 postnatal cases) at the Danish Cytogenetic Central Register were included. The main outcome measures were prevalence of Turner's syndrome karyotypes among prenatally tested fetuses and Turner's syndrome among liveborn infants. The results showed that among infant girls, prevalence of Turner's syndrome was 32/100,000. Among female fetuses tested by amniocentesis, prevalence of Turner's syndrome karyotypes was 176/100,000 (relative risk of syndrome, 6.74 compared with prevalence among untested pregnancies). Among female fetuses tested by chorion villus sampling, prevalence of syndrome karyotypes was 392/100,000 (relative risk, 16.8). We excluded prenatal tests referred because of results of ultrasound scanning: among fetuses tested by amniocentesis revised relative risk was 5.68, while revised relative risk among fetuses tested by chorion villus sampling was 13.3. For 29 fetuses with prenatal diagnosis of possible Turner's syndrome, pregnancy was allowed to continue and 24 of the children were live born. Thirteen of the liveborn children were karyotyped postnatally, and the diagnosis of Turner's syndrome had to be revised for eight, seven being normal girls and one boy. This gives a tentative predictive value of amniocentesis in the diagnosis of Turner's syndrome between 21% and 67%. There was no significant relation between mother's age and risk of Turner's syndrome. In conclusion, a discrepancy between prenatal and postnatal prevalence of Turner's syndrome challenges the specificity of prenatal examination in diagnosing Turner's syndrome.     

The defective nature of hepatitis delta virus

Forty-nine out of 66 patients with Turner's syndrome and different karyotypes underwent full cardiological evaluations (physical examination, electrocardiography, chest X-ray and echocardiography). Congenital cardiovascular anomalies were found in 11 patients (22.4%). Among the cardiac anomalies in patients with Turner's syndrome, aortic malformations (aortic coarctation [27%], aortic stenosis [18%] and bicuspid aortic valve [18%]) were the most frequent. We observed that the most severe malformations were found in those with karyotype 45,X or 45,X/46,XX. No anomalies were detected in patients with the X isochromosome or those mosaic with the Y component.     

Prevalence and genotype of hepatitis C virus infection in pregnant women and blood donors in Ghana

BACKGROUND: Short stature is one of the features of Turner syndrome and a form of presentation of monosymptomatic celiac disease. METHODS: The recognition of celiac disease in two antiendomysium antibody-positive Turner syndrome girls who did not respond to growth hormone treatment led us to perform as a screening for celiac disease IgA and IgG antigliadin antibodies and antiendomysium antibodies determination in other 35 Turner syndrome patients. Intestinal biopsy was proposed to the antiendomysium antibodies-positive girls; in the former, subtotal villous atrophy was found; in the latter, one parent's consent for intestinal biopsy was not obtained. RESULTS: The prevalence of celiac disease in Turner syndrome patients observed in the present study (8.1 if we consider 3 villous atrophy, 10.8 if we consider 4 antiendomysium antibody-positive) is quite high and seems to indicate that the association of these two disorders could not be coincidental. As to the clinical picture, celiac disease appeared atypical in one case, typical in another one and as a silent form in the third case. Of the 3 cases with villous atrophy on gluten-free diet growth hormone therapy was not effective in two girls, who were older than 16 years, while in the younger patient, detected by the screening, a significant increment of height velocity and height Standard Deviation Score for Chronological Age according to Turner references was observed. CONCLUSIONS: This study suggests that celiac disease can be associated with Turner syndrome and even responsible for a failure of growth hormone therapy. Therefore we propose to perform in Turner syndrome patients antiendomysium antibody determination as a screening followed by intestinal biopsy in positive cases. This would be advisable at least before starting growth hormone treatment.     

Routine molecular genotyping of HLA-B27 in spondyloarthropathies overcomes the obstacles of serological typing and reveals an increased B *2702 frequency in ankylosing spondylitis

OBJECTIVE: To evaluate the reproducibility and reliability of polymerase chain reaction (PCR) in HLA-B27 typing compared to the conventionally used microlymphocytotoxicity test (MLCT). To determine the HLA-B27 subtype frequencies (B*2701-B*2709) in patients with HLA-B27 associated disease and healthy persons using sequence specific oligonucleotides (SSO). METHODS: 398 consecutive patients were HLA-B27 typed by MLCT and PCR. Subtyping by SSO was performed in 142 patients with HLA-B27 associated disease [ankylosing spondylitis (AS) n = 38, reactive arthritis 44, undifferentiated spondyloarthropathy (uSpA) 45, psoriatic arthritis 15] and 125 healthy HLA-B27 controls. RESULTS: MLCT identified 61 HLA-B27 positive patients (15.3%); PCR identified 78 positive patients (19.6%). MLCT gave false negative results for 8 patients (2.0%) and false positives for a further 7 (1.8%). Only subtypes B*2702 and B*2705 were present in patients and controls. Overall frequencies of B*2702 in patients and controls were 14.1 and 9.6%, respectively. The B*2702 frequency was significantly (pcorr. < 0.04) higher in AS (23.7%) and lower in uSpA (6.7%) patients. CONCLUSION: HLA-B27 typing by PCR is reliable and reproducible and therefore recommended for routine typing. It overcomes the obstacles of serological typing, i.e., equivocal results and cross-reactivity. In addition, subtype frequencies (B*2702 and B*2705) are equally distributed among patients and controls, although subtype B*2702 seems to be more frequent in AS and less so in uSpA.     

The majority of myeloid-antigen-positive (My+) childhood B-cell precursor acute lymphoblastic leukaemias express TEL-AML1 fusion transcripts

BACKGROUND & AIMS: Crohn's disease and ulcerative colitis show a familial aggregation. In both diseases, anti-goblet cell autoantibodies (GABs) have been described. The aim of this study was to define the role of GABs in the pathogenesis of inflammatory bowel disease. METHODS: The study population comprised 61 patients with ulcerative colitis, 76 patients with Crohn's disease, 101 first-degree relatives of patients with ulcerative colitis, and 105 first-degree relatives of patients with Crohn's disease. Thirty-five patients with infectious enterocolitis and 56 healthy unrelated subjects served as controls. Autoantibodies were detected by indirect immunofluorescence. RESULTS: Thirty-nine percent of patients with ulcerative colitis (24 of 61) and 30% of patients with Crohn's disease (23 of 76) were positive for GABs. GABs were detected in 21% (21 of 101) of first-degree relatives of patients with ulcerative colitis and in 19% (20 of 105) of first-degree relatives of patients with Crohn's disease. In patients with infectious enterocolitis and in healthy controls, GABs were seen in 3% (1 of 35) and 2% (1 of 56), respectively. The differences between control groups and both groups of patients or their first-degree relatives were significant. CONCLUSIONS: The high prevalence in first-degree relatives suggests that GABs may represent a marker characterizing susceptibility to inflammatory bowel disease.     

Induction of beta-cell rest in type 1 diabetes. Studies on the effects of octreotide and diazoxide

We report on two siblings with classic simple virilizing 21-hydroxylase deficiency whose neonatal screening for serum 17alpha-hydroxyprogesterone (17-OHP) gave normal results. The proband, a girl with clitoromegaly whose screening 17-OHP value had been 9.2 ng/ml, was diagnosed at the age of 6 months, and her elder brother with the initial screening level of 15.7 ng/ml was diagnosed at the age of 6 years due to precocious puberty. Although the occurrence of false-negative cases is extremely rare, it can happen in a simple virilizing form of 21-hydroxylase deficiency. This experience informs that normal results for neonatal screening cannot be an excuse for not evaluating siblings of the proband with congenital adrenal hyperplasia.     

Sj?gren's syndrome association with HLA-Dw3

Sj?gren's syndrome is associated with a serologically defined histocompatibility antigen of the HLA-B locus, HLA-B8. Another closely linked locus, HLA-D, determines lymphocyte-defined cell-surface antigens. In laboratory animals such antigens are closely linked to immune response genes. To determine whether Sj?gren's syndrome is primarily associated with an HLA-D antigent or with HLA-A and HLA-B antigens as well as HLA-Dw3, which is known to be in linkage disequilibrium with HLA-B8. We found the primary association of association of Sj?gren's syndrome to be with HLA-Dw3, which we observed in 84 percent of patients with Sj?gren's syndrome in the absence of rheumatoid arthritis as compared to 24 percent in controls (P less than 0.00001). The frequency of HLA-B8 and HLA-Dw3 in patients with both Sj?gren's syndrome and rheumatoid arthritis did not differ from that in controls. Patients with Sj?gren's syndrome and rheumatoid arthritis comprise genetically distinct groups.     

Wide-area network connecting a hospital drug informatics center with a university

Bone age maturation in 116 untreated patients with Turner's syndrome was evaluated in a cross-sectional and longitudinal analysis. A total of 265 radiographs were rated using the TW2-RUS method on the computer-assisted skeletal age score (CASAS) system. Bone age was found to be retarded from the chronological age of 3 to 6y. Between the ages of 7 and 12 y bone age almost equalled chronological age and progressed normally at a rate of 1 y y(-1). Bone maturation slowed down thereafter and epiphyseal closure was not reached before the age of 17 y. Reference data are presented on bone age and a bone age maturation curve for untreated patients with Turner's syndrome to be used in clinical practice. In the assessment of bone age and bone age velocity in Turner's syndrome the CASAS system produced reliable and valid results. The absolute difference between repeated bone age ratings was 0.26 "y" (median) with a range of 0.00-0.56 "y". Future studies evaluating the effect of growth-promoting treatment in Turner's syndrome should use a computerized method for the determination of bone age.     

Dental evidence for the peopling of the New World: some methodological considerations

Turner (1985b) and Greenberg et al. (1986) proposed that New World populations originated in northern Asia and entered the Americas in three migratory waves: Macro-Indian, Aleut-Eskimo, and Na-Dene. Biological support for this model comes from Turner's unweighted pair group (UPGMA) cluster analysis of discrete dental traits in world populations. Unfortunately, UPGMA analysis often creates suspect clusters and may not be valid as a method for displaying evolutionary relationships because it assumes that rates of evolution are equal among all populations. To test whether Turner's results are an artifact of his analytical method, I analyzed his published data (Turner 1985b) using two alternative techniques that do not assume homogeneous rates of change: a Wagner distance algorithm employing the Fitch-Margoliash criterion for goodness of fit and a maximum parsimony analysis using segment-coded dental trait frequencies. Both alternative methods produce trees that are similar to the UPGMA analysis results, supporting Turner's original results and basic conclusions. Comparisons of tree topology demonstrate that there is strong congruence between trees produced by all three methods, although the placement of certain populations, such as Na-Dene, depends on the method of analysis employed.     

Determination of copper and arsenic in refined beet sugar by stripping voltammetry without sample pretreatment

OBJECTIVE: To determine whether the association between increased humoral reactivity against Klebsiella and HLA-B27 associated diseases could be confirmed in Dutch patients with ankylosing spondylitis (AS) and acute anterior uveitis (AAU). METHODS: Under coded conditions sera from Dutch patients with AS, AAU, and rheumatoid arthritis (RA) and from HLA-B27 positive and negative healthy controls were studied for IgA anti-Klebsiella (K54) and IgG anti-Proteus antibodies with the indirect immunofluorescence assay on whole bacteria fixed in suspension with paraformaldehyde. Each group consisted of at least 17 sera. RESULTS: IgA anti-Klebsiella antibody titers were elevated in AS and HLA-B27 negative AAU compared to the HLA-B27 positive and negative controls or patients with active RA (p < 0.001). Furthermore, patients with active RA had elevated levels of IgG antibodies against P. mirabilis compared to every other test or control group (p < 0.001). There was no significant difference between the AS and RA patients in terms of serum C-reactive protein levels, although these were significantly elevated in both compared to healthy controls (p < 0.001), suggesting that the antibody elevations were not due to a nonspecific inflammatory effect. The same sera were blindly tested with negative results by 2 other centers. The discrepancies are probably the result of differences in the methods used. CONCLUSION: Our data support the hypothesis that Klebsiella are involved in the pathogenesis of AS and AAU and that the same might be true for Proteus in RA.