In December 2009, Yong et al. [1] isolated a strain of Klebsiella pneumoniae resistant to all β-lactam antibiotics including carbapenem antibiotics from a urine sample of a Swedish patient, and confirmed that its resistance mechanism was to produce a new carbapenemase. Because this patient had been treated in New Delhi for a long time, this new carbapenemase was named New Delhi metallo β-lactamase-1 (NDM-1).
Carbapenem antibiotics are considered to be the most effective antibacterial drugs in the treatment of Gram-negative bacterial infections. With the increasing use of carbapenem antibiotics, the drug resistance of carbapenemes increases continuously, and the main mechanism of their resistance is the production of carbapenemases by bacteria.
The reports of multidrug-resistant gram-negative bacteria-"superbacteria" appearing and leading to death have become the focus of worldwide attention recently. Methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE) and multidrug-resistant gram-negative bacteria pose a threat to public health. The growth rate of drug resistance of gram-negative bacteria is faster than that of gram-positive bacteria. It can mediate the production of various enzymes that hydrolyze antibiotics by plasmids or chromosomes, and can also prevent antibiotics from lysing bacteria by changing cell membrane permeability or antibiotic binding site and active pumping enhancement [1].
TANG Yang-feng, XU Ji-bin, HAN Lin, LU Fang-lin, LANG Xi-long, SONG Zhi-gang, ZOU Liang-jian, XU Zhi-yun
National Medical Journal of ChinaVol.90,No.462010
DOI: 10.3760/cma.j.issn.0376-2491.2010.46.014
Abstract
Objective To improve the understanding of congenital quadricuspid aortic valve ( QAV), explore its echocardiographic diagnostic value and summarize the methods and outcomes of surgical treatments. Methods The clinical data of 11 QAV patients from January 2000 to December 2008 were retrospectively analyzed. There were 9 males and 2 females with a mean operative age of (32 ± 16) years (range: 4-55 ). Results In 766 patients undergoing aortic valve surgery, 11 were of congenital quadricuspid aortic valve ( 1.4% ); cardiac pathology: infective endocarditis ( n = 1 ), left superior vena cava ( n = 1 ), aortic aneurysm ( n = 1 ), mitral prolapse ( n = 1 ) and tricuspid insufficiency ( n = 1 ). The patients of congenital QAV deformity was diagnosed by echocardiography ( n = 7 ), misdiagnosed as single valve ( n = 1 ), misdiagnosed as bicuspid valve (n = 1 ) and misdiagnosed as rheumatic heart disease ( n =2 ). Type B ( n = 7 ), Type A ( n = 2), Type F ( n = 1 ) and Type G ( n = 1 ). Eleven patients underwent the procedure of aortic valve replacement. And the concomitant procedures were aortic root broadening ( n = 1 ),ascending aortoplasty ( n = 1 ), mitral valvuloplasty ( n = 1 ) and tricuspid valvuloplasty ( n = 1 ).Conclusion Quadricuspid aortic valve is rare in clinical practice. And echocardiography plays an important diagnostic role. Surgical replacement of aortic valve is the first-line therapy for these patients.
WANG Tao, LIU Yue-hua, ZHENG He-yi, SUN Qiu-ning, JIN Hong-zhong, LI Feng, FANG Kai, YAN Yan
National Medical Journal of ChinaVol.90,No.462010
DOI: 10.3760/cma.j.issn.0376-2491.2010.46.013
Abstract
Objective To explore the clinical and histopathological manifestations, therapy and prognosis of hypopigmented mycosis fungoides (HMF) in children. Methods Six pediatric cases of HMF from February 2008 to October 2009 were reviewed and analyzed at our hospital. Results There were 5 males and 1 female with a average age of 11 years old (range: 9-14). The lesions appeared poorlydemarcated hypopigmented macula and patches disseminated over the trunk and extremities, scales and infiltrated papules over the hypopigmented lesions or invasive erythemas arose and enlarged gradually.Histologically, there was an epidermal infiltration of atypical lymphocytes. The immunohistochemical staining revealed a pattern of T lymphoma and a predominance of CD8 + T cell. All patients were of T2 N0 M0/Ⅰ B except for one at the stage of T1N0M0/Ⅰ A. Two patients received narrow band ultraviolet B ( NB-UVB),one NB-UVB plus alpha interferon, another NB-UVB plus alpha interferon and topical steroid, one Chinese traditional herbal regimen while the last one none. And NB-UVB alone or plus alpha interferon achieved a clinical complete response (CR). The herbal regimen failed to cure the lesions but achieved no response.The non-treated patient progressed gradually. The average follow-up was 16 months (range: 9-28 ). The progression-free rate was 83.3% and the overall survival rate 100%. Conclusions Visceral and lymph note involvements are rare in HMF of children. The prognosis of early-stage treatment is satisfactory. NB-UVB alone or plus alpha interferon achieves a clinical CR in most early-stage patients.
Objective To investigate the clinical, pathological and imaging characteristics,misdiagnosis and treatment of pulmonary non-Hodgkin's lymphoma with diffuse ground-glass opacities (GGO). Methods Six cases of pulmonary non-Hodgkin's lymphoma with diffuse GGO on chest CT diagnosed from January 2008 to March 2010 were retrospectively analyzed. Results There were 5 males and 1 female with average age of 52 years old ( range: 30-59). The course had a range of 2-36 months. Most patients presented with dyspnea ( n = 5) and loss of weight (n = 5). Enlargement of superficial lymph nodes ( n = 2) and hepatosplenomegaly (n = 2) were also found. Laboratory tests showed that average hemoglobin decreased to 25 g/L and average serum LDH was 755 U/L. Chest CT showed diffuse GGO (n =2) ,diffuse GGO with consolidations ( n = 3 ), with wide lung septum ( n = 3 ), with multiple nodules ( n = 2 ), with enlargement of mediastinal lymph nodes ( n = 2 ). Diagnosis of the 6 cases were made by lung biopsy.Histological findings including intravascular lymphoma ( n =2), diffuse large B cell lymphoma ( n =2) and T cell lymphoma (n = 2). The average follow-up period was 4 months( range: 2-6). Chemotherapy was administered in 4 patients with B cell lymphoma and all of them improved or remained stable. One patient with T cells lymphoma was lost to follow-up and another patient with T cell lymphoma died due to lung infection. Conclusions Non-Hodgkin's lymphoma with diffuse GGO on chest CT scan is rare. And its misdiagnosis is common due to a lack of specific clinical manifestations. And lung biopsy is necessary for an early diagnosis.
TAI Qiang, HE Xiao-shun, HU An-bin, WU Lin-wei, JU Wei-qiang, ZHU Xiao-feng, MA Yi, WANG Dong-ping, WANG Guo-dong, GUO Zhi-yong, et al.
National Medical Journal of ChinaVol.90,No.462010
DOI: 10.3760/cma.j.issn.0376-2491.2010.46.011
Abstract
Objective To explore the resistance rate, risk factor and mortality of enteroccal bloodstream infections (BSI) after liver transplantation. Methods From January 1993 to May 2010, a retrospective analysis of enteroccus in liver transplants were conducted. Results Fifty-eight BSI occurred in 53 of 695 patients. And a total of 30 enterocci were isolated. Linezolid and glycopeptide antibiotics were the most consistently active against the Enterococcus. The resistance rates to Enterococcus for erythromycin,clindamycin, imipenem, ciprofloxacin, gentamycin and ampicillin-clavulanic acid were all over 70%. The univariate analysis identified the following variables as the risk factors for enterococcal bacteremia:retransplantion ( P = 0. 03 ) and biliary duct complications ( P = 0. 02 ). Enterococcal bloodstream infection increased the mortality at Day 15. No significant difference was found in the mortality rate at Day 30 and 1 year after enterococcal bacteremia. Conclusion Enterococcus after liver transplantion is resistant to multiple agents but active to linezolid and glycopeptide antibiotics. The risk factors commonly associated with enteroccal BSI are retransplantion and biliary duct complications. Enterococcal BSI can increase the mortality at Day 15 after liver transplantation.
Objective To investigate the prognostic and relapsing factors of ulcerative colitis by a 5-year population-based follow-up. Methods A total of 525 patients diagnosed with ulcerative colitis during the period from 1994 to 2005 at our hospital were recruited and followed prospectively for 5 years or until a relapse. The evaluation at 5 years included interview, clinical examination, laboratory tests and colonoscopy. Results Among these patients, 367 patients suffered from a relapse of ulcerative colitis with a median age of 42 years old. And 263 ( 50. 1 % ) patients took part in the follow-up study. The median duration of maintenance treatment was ( 16. 3 ± 3. 9 ) months. The proportion of relapse was significant greater in females ( P < 0. 05 ) and in patients over 60 years old versus those under 60 ( P < 0. 05 ). The value of CRP was unrelated with the relapsing rate( P >0. 05 ). During the follow-up, 36. 5% of the patients relapsed within 12 months, 75.3% within 2 years and 87. 8% within 5 years. And 61.5% of the patients relapsed after drug withdrawal, 11.3% in maintenance treatment and 27.2% with no treatment. Severity,extent of disease and duration of maintenance treatment showed significant differences between the relapsing group and relapsing-free groups ( P < 0. 05 ). Conclusion The relapsing factors of ulcerative colitis are gender, age, severity, extent of disease and duration of maintenance treatment.
L(U) Zhao-hui, ZHU Hai-qing, DOU Jing-tao, YANG Guo-qing, BA Jian-ming, MU Yi-ming, LU Ju-ming
National Medical Journal of ChinaVol.90,No.462010
DOI: 10.3760/cma.j.issn.0376-2491.2010.46.009
Abstract
Objective To retrospectively evaluate the diagnostic accuracy of ultrasonographic (US)features for the pre-operative differentiation of benign and malignant thyroid nodules by using pathological diagnosis as the reference standard. Methods A total of 1501 patients with 2123 thyroid nodules ( 1864 malignant, 259 benign ) diagnosed intra-operatively and undergoing pre-operative ultrasonography at our hospital were recruited. The following characteristics of US images were evaluated: nodule size, shape,margin, echotexture, echogenicity, presence and type of calcification, blood flow inside or around nodules and the presence of ipsilateral cervical lymphadenectasis. Results ( 1 )The risk of malignancy was higher in a solitary nodule than in a non-solitary nodule [16.7% (109/653) vs 10.2% (150/1470), P = 0.000].The mean diameter of benign nodules was larger than that of malignant nodules [( 2.4 ± 1.4 ) vs ( 2.1 ±1.9) cm, P = 0.009]. (2) Microcalcification, irregular shape, ill-defined border, solid and hypoechogenicity were more common in malignant nodules. Irregular shape had the highest sensitivity and positive predictive value while microcalcification had the highest diagnostic accuracy. (3) Nodules with a rich blood flow inside tended to have a higher risk of malignancy. The distribution pattern of blood flow around the nodules was not associated with the differentiation of benign and malignant thyroid nodules.Nodules with the presence of ipsilateral cervical lymphadenectasis had a higher risk of malignancy than those without lymphadenectasis [28.3% ( 80/283 ) vs 9.6% (92/963), P < 0.01]. (4) If microcalcification,irregular shape, ill-defined border, solid, hypoechogenicity and the presence of ipsilateral cervical lymphadenectasis were treated as the characteristics of malignancy, a higher frequency of these characteristics was correlated with a higher risk of malignancy. Conclusion Despite a lack of specific US imaging characteristics in malignant thyroid nodules, microcalcification and irregular shape appear closely correlated with malignancy. A combined use of conventional US characteristics may improve the accuracy of differential diagnosis.
Objective To study the distribution of alphal-adrenoceptor (α1-AR ) subtype in prostate, posterior urethra and bladder detrusor of patients with chronic prostatitis (CP) . Methods The prostate specimens were collected at autopsy from 30 organ donors (aged 20 -35 years old) dying of nonprostatic diseases. The pathological specimens of prostate peripheral zone were examined. The method of real-time reverse transcriptase polymerase chain reaction (real-time RT-PCR ) was employed for quantification of α1a-AR and α1b-AR subtype expression in prostate transition zone and its surrounding zone,posterior urethra and bladder detrusor tissue. Results Among all donors, there were 24 cases with pathological inflammation in prostatic peripheral zone and 6 with pathological non-inflammation. The mRNA expression of α1-AR subtypes in bladder detrusor and posterior urethra was significantly higher in the inflammation group than in the control group (P <0.05). While the mRNA expression of α1-AR subtypes in the bladder detrusor and posterior urethra was significantly lower in the inflammation group than in the control group( P < 0.05 ). Conclusion An abnormal expression of α1 -AR subtypes in bladder detrusor and posterior urethra may explain various urodynamic changes in CP and lead to the occurrence and development of CP in prostate, posterior urethra and bladder detmsor.
ZHANG Jian, WEI Bing-qi, XU Hui-cong, HUANG Chu-lin, ZHANG Yu-hui, WANG Dong, YANG Yue-jin, GAO Run-lin
National Medical Journal of ChinaVol.90,No.462010
DOI: 10.3760/cma.j.issn.0376-2491.2010.46.007
Abstract
Objective To detect the occurring and developing patterns of multiple organ damage in patients dying from acute decompensated heart failure (ADHF). Methods The clinical data of 30 hospitalized patients of ADHF were analyzed. The dying causes included renal, hepatic, respiratory dysfunctions, infection and anemia. All patients received continuous cardiac rhythm monitoring. Their renal,hepatic and respiratory function, infection and anemia were evaluated at admission and during the last 24 hours pre-death respectively. And the results were compared. Results There were 19 males and 11 females. The average age was (55 ± 22) years old. Among them, 7 cases were of NYHA class Ⅲ and 23 cases NYHA class Ⅳ at admission. The causes of heart failure included valvular heart disease ( n = 17 ),dilated cardiomyopathy ( n = 6 ), ischemic cardiomyopathy ( n = 4 ), valvular heart disease and previouscardiac infarction ( n = 2) and restrictive cardiomyopathy ( n = 1 ). From admission to death, the average hospitalization duration was( 8.8 ± 7.4) days. Eleven cases suffered from sudden cardiac death due to lethal arrhythmias including ventricular tachycardia, ventricular fibrillation and sinus arrest. Another 19 cases had no lethal arrhythmias, but they suffered cardiac shock eventually. Among all 30 cases, there were 15 cases with pulmonary infection, 13 caseswith hepatic dysfunction, 6 cases with renal dysfunction, 7 caseswith respiratory failure, 7 cases with anemia and 15 cases with multiple organ damage at admission. However, the pre-death values increased to 26 (87%, P<0.01), 19 (63%, P <0.05), 24 (80%, P <0.01 ), 20(67%, P<0.01), 9 (30%, P>0.05) and29 (97%, P<0.01) respectively. Conclusion Multiple organ damage evolves and worsens to result in death in ADHF patients.
LIU Fen, MA Yi-tong, YANG Yi-ning, XIE Xiang, LI Xiao-mei, HUANG Ying, MA Xiang, CHEN Bang-dang, GAO Xia, DU Lei
National Medical Journal of ChinaVol.90,No.462010
DOI: 10.3760/cma.j.issn.0376-2491.2010.46.006
Abstract
Objective To investigate the prevalence and distribution pattern of hypertension in Xinjiang adult population. Methods A total of 15 061 adults at 35 years old or over were surveyed. Fourstage selected random sampling was employed to analyze the prevalence and distribution pattern of selfreported congestive hypertension in different groups of nationality, age and gender. The sampled adult population was collected from 7 localities ( Urumqi, Ke lamayi, Fukang, Turfan Basin, Hetian, Altay, Yili Hazakh autonomous prefecture) in 23 municipalities and 5 autonomous counties in Xinjiang. The proportion of male to female was 50% each. Results The prevalence of hypertension was 36.21% (male: 38.70% vs female: 34.22% ). The Prevalence of hypertension was 33.42% , 28.50% and 48.69% in Han, Uygur and Hazakh populations respectively. The prevalence of hypertension was higher in Hazakh than Han people ( χ2 = 29.36,P < 0.01 ). The males had a higher frequency of hypertension than the females ( χ2 = 20.01, P<0.01). The risk of hypertension increased substantially with age. The analysis of multiple logistic regression revealed that age ( OR = 1.06 ), alcohol consumption, obesity ( OR = 3.12 ) and levels of triglyceride( OR = 1.30) and cholesterol( OR = 1.32) and serum glucose ( OR = 1.41 ) were risk factors of hypertension. The corresponding relative hazards were age, alcohol consumption, obesity and levels of triglyceride and cholesterol and serum glucose for Han; the risk factors were similar in Uygur except serum glucose. Age, obesity and levels of triglyceride were only for Hazakh. Conclusion There is still a higher prevalence of hypertension in Xinjiang. The prevalence of hypertension increases substantially with age and there is difference between different nationalities.
GUO Hai-peng, TANG Qi-zhu, DENG Wei, ZHOU Heng, QIU Tian-yi, YAN Ling, SHEN Di-fei
National Medical Journal of ChinaVol.90,No.462010
DOI: 10.3760/cma.j.issn.0376-2491.2010.46.005
Abstract
Objective To explore the relationship among heart rate turbulence (HRT), QT dispersion (QTd) and heart function in patients with dilated cardiomyopathy (DCM) and assess its clinical value. Methods A total of 81 DCM patients with ventricular premature contraction (VPC) were divided into two groups according to heart function: Group A (NYHA class Ⅰ -Ⅱ , n = 34) and Group B (NYHA class Ⅲ-V, n =47). Thirty out-patient control cases were chosen from those undergoing regular physical examination. 24hour holter was performed to monitor turbulence onset ( TO ) and turbulence slope (TS).Electrocardiogram (ECG) was used to assess QTd. Meanwhile left ventricular ejection fraction ( LVEF),left ventricular end-diastolic dimension ( LVEDD), E and A-wave peak velocities, E/A were measured by echocardiogram. After a comparison of all indicators in each group, an investigation was conducted to discern the relationship among HRT, QTd and heart function. Results Compared with normal group, TO significantly increased in DCM A and B group: [0. 38 ( - 0.99 ~ 1.85 ) % vs 1.82 ( 0. 02 ~ 3.92 ) % vs ( -4. 03 ± 3.48 )%, P < 0. 01]. TS significantly decreased while QTd increased. The trend of QTd addition was apparent along with heart failure. TO was negatively correlated with LVEF ( r = -0. 701, P <0. 05 ) but positively correlated with LVEDD ( r =0. 621, P <0. 05 ). There was no correlation with E and A-wave peak velocities. TS and QTd also had an obvious correlation with LVEF and LVEDD ( all P < 0. 05 ) .Conclusions HRT is dramatically blunted in DCM patients and has a certain correlation with cardiac dysfunction. A combined test of HRT and QTd is a sensitive and indirect index in assessing autonomic nerve functions. It has a high clinical value of predicting the prognosis.
L(U) Jin-xing, YAN Chun-yin, PU Jin-xian, HOU Jian-quan, YUAN He-xing, PING Ji-gen
National Medical Journal of ChinaVol.90,No.462010
DOI: 10.3760/cma.j.issn.0376-2491.2010.46.016
Abstract
Objective To study the protection of gene transfer-induced human heme oxygenase-1over-expression against renal ischemia reperfusion injury in rats. Methods The model of kidney ischemiareperfusion injury was established with Sprague-Dawley rats. In the therapy group (n = 18) ,the left kidney was perfused and preserved with Ad-hHO-1 at 2. 5 × 109 pfu/1. 0 ml after flushed with 0 ~4 ℃ HC-A organ storage solution via donor renal aorta. The rats in control groups were perfused with 0. 9% saline solution ( n = 12) or the vector carrying no interest gene Ad-EGFP 2. 5 × 109 pfu/1. 0 ml ( n = 18 ) instead of AdhHO-1. BUN and Cr in serum were measured by slide chemical methods. The kidney samples of rats were harvested for assay of histology, immunohistochemistry and quantification of HO enzymatic activity.Apoptosis cells in the kidney were measured by TUNEL. Results Ad-hHO-1 via donor renal aorta could transfect renal cells of rats effectively, enzymatic activity of HO in treated group [(1.62 ± 0. 07 )nmol · mg- 1 · min- 1] is higher than in control groups treated with saline solution team [( 1.27 ± 0. 07 )nmol·mg-1 · min-1] and vector EGFP team[(1.22 ±0.06) nmol · mg-1 · min-1] (P<0. 01).Immunohistochemically , we found that the rats treated with Ad-hHO-1 expressed hHO-1 in kidneys at a high level. Corresponding to this, the level of BUN and Cr, as well as the number of apoptosis cells, were decreased, and the damage in histology by HE staining was ameliorated. Conclusion Over-expression of human HO-1 can protect the kidney from ischemia/reperfusion injury in rats.
ZHENG Jin-xu, XU Qing, TANG Yan, LIU Ji-zhu, L(U) Xiao-ting
National Medical Journal of ChinaVol.90,No.462010
DOI: 10.3760/cma.j.issn.0376-2491.2010.46.015
Abstract
Objective To study the in vitro effect and mechanism of Napsin A gene transfection into type Ⅱ alveolar epithelial cells on pulmonary fibrosis. Methods A recombinant lentiviral plasmid PLJM1Napsin A was constructed and transfected into human type Ⅱ alveolar epithelial cell line A549. The model of pulmonary fibrosis was established by the in vitro stimulation of A549 cells by transforming growth factor beta-1 (TGF-β1). The morphological changes were observed continuously under inverted microscopy. The proliferation of transgenic and non-transgenic cells was detected by MTT. To observe the degree of epithelialmesenchymal transition ( EMT ) by TGF-β1 intervening A549 cells, the expressions of E-cadherin and fibronectin were determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot.Lastly the protein expression of focal adhesion kinase (FAK) was detected by Western blot to investigate the mechanism. Results The result of sequencing the recombinant lentiviral plasmid PLJM1-Napsin A was the same as the design sequence. Napsin A mRNA and protein were expressed in transgenic A549 cells( P <0. 01 ). The model of pulmonary fibrosis was established successfully based on the morphology of transformed interstitial cell. As compared with the control group, the proliferation rate of transgenic cells decreased significantly (P <0. 05 ). The mRNA and protein expression of E-cadherin significantly decreased in the model of pulmonary fibrosis ( P < 0. 01 ), while the expression of fibronectin markedly increased ( P < 0. 01 ).But the change rate of transgenic cells decreased ( P < 0. 01, P < 0. 05 ). The expression of FAK was significantly elevated after the stimulation of TGF-β1 ( P < 0. 01 ). But the upward trend of the transgenic cells was smaller as compared with the control group (P < 0. 01 ). Conclusion Pulmonary fibrosis may be suppressed by the transfection of Napsin A gene into type Ⅱ alveolar epithelial cells. And the mechanism may be through the inhibition of integrin signal transduction.
A 39-year-old female was found to have neck thickening accompanied by neck pain and fever without obvious trigger in July 2004. The body temperature was 37.0~37.9℃. The thyroid function was examined in a local hospital. Free triiodothyronine (FT3) was 14.05 pmol/L [immunochemiluminescence method (ICMA) 2.3~6.3 pmol/L; reference values are the same below], free thyroxine (FT4) was 57.5 pmol/L (ICMA, 10.3~24.4 pmol/L), thyroid stimulating hormone (TSH) was 0.05 mU/L (ICMA, 0.4~4.0 mU/L), thyroid peroxidase antibody (TPOAb) was 9.4% (Elisa,<20%), thyroglobulin antibody (TgAb) was 11.3% (Elisa,<20%), white blood cells were 2.8×109/L, erythrocyte sedimentation rate (ESR) was 61 mm/1 h, multiple density heterogeneity was shown on thyroid ultrasound, hypotechnetium function was shown on thyroid imaging, and thyroid iodine uptake rate was low, 0.1% at 2 h and 0.3% at 4 h.
A 67-year-old female was admitted to the hospital due to "retrosternal discomfort for 2 years, physical examination showed that the esophagus occupied space for 1 1/2 months". Two years ago, she developed retrosternal pain and discomfort without obvious inducement, retention when eating, no swallowing difficulty, no chest and back pain, and went to the local hospital for gastroscopy without any abnormalities.
A 67-year-old female was admitted to the hospital on July 2, 2003 due to petechia and ecchymosis on her skin for 2 months. The platelet (PLT) was 4×109/L in the emergency department of admission, and it was diagnosed as immune thrombocytopenic purpura (ITP) by bone marrow puncture. After treatment with bonisone, the PLT was (18~29) ×109/L.
The patient was a 20-year-old female who was seen in the Department of Endocrinology of the First Affiliated Hospital of China Medical University on April 17, 2009 due to amenorrhea for 3 years. The patient was 17 years old with menarche, her parents had no history of close marriage, and there were no hereditary diseases in her family. Physical examination: height 150 cm, slightly wider distance between eyes, no abnormal skin color, slightly higher palatal arch, no neck web, second degree thyroid enlargement, small breast, elbow valgus, no beard, axillary hair and pubic hair missing.