Normal Blood Serum Research Articles

An Uncommon Cause of Hiccups: Sarcoidosis Presenting Solely as Hiccups

Common causes of hiccups are over-distension of the stomach, a sudden change in gastrointestinal temperature, excessive alcohol and tobacco ingestion, and sudden excitement or emotional changes. Common presenting symptoms of sarcoidosis include cough, dyspnea, and chest pain. It is very rare for a sarcoidosis patient to present with hiccups. A 48-year-old man presented with hiccups of 2 weeks' duration. He denied having headaches, earache, cough, abdominal pain, fever, or body weight loss history. On physical examination, he had no peripheral lymphadenopathies in the neck, axilla and inguinal regions, no organomegaly in the abdomen and no skin abnormalities. A neurological examination showed normal findings. Laboratory investigations revealed a normal complete blood count, liver function, renal function, serum calcium, and tumor markers. Transabdominal ultrasound was negative, and panendoscopy revealed a small healing duodenal ulcer. Chest radiography showed an enlarged right lung hilum, while computed tomography showed enlargement of multiple mediastinal lymph nodes. Endoscopic ultrasound-guided fine-needle aspiration with a 22-gauge needle and trucut biopsy with a 19-gauge needle (quick-core biopsy needle) were performed, and cytology, cell block and histology revealed non-caseating granuloma, with negative tuberculous and fungus cultures. Mediastinal lymph node due to sarcoidosis can be a rare cause of hiccups.

Laser-induced effects in different biological samples

Experiments were carried out on cancerous HeLa cells and blood serum using a double integrating sphere and a He-Ne laser to investigate the optical properties and cellular effects due to photodynamic therapy (PDT). In the first experiment, HeLa cells were exposed to Photofrin at concentrations of 0, 10, 20, 30, 50 and 112.4 microg/ml at an irradiance of 0.2 W/cm(2) using diode laser light. Using a confocal microscope, cell debris and morphological changes in HeLa cells were recorded at different Photofrin concentrations. The results showed cell debris in HeLa cells at the highest concentration of Photofrin. In a second experiment, photobleaching was observed in HeLa cells in the presence of various concentrations of 5-aminolaevulinic acid ranging from 0-50 microg/ml. There was progressive degradation of the 635 nm peak during continuous laser irradiation at an irradiance of 0.2 W/cm(2). We conclude that cells demonstrating high initial fluorescence undergo bleaching at a faster rate than those with lower fluorescence. Finally in a third experiment, cancerous and noncancerous blood serum was irradiated at an irradiance of 0.1 W/cm(2) using a He-Ne laser in conjunction with a double integrating sphere system. Forward and back scattering of normal and malignant serum showed an exponential decrease in fluorescence amplitude. The results indicate that there is notable amplitude difference between malignant and normal blood serum with malignant blood serum showing decreased scattering. These results have important implications for photodiagnosis and photodynamic therapy.

Study on the shifting of Th1/Th2 balance in patients with interstitial cystitis

Objective To investigate possible disturbance of Th1/Th2 immunoregulation of blood serum and bladder mucosa in patients with interstitial cystitis(IC). Methods Blood serum and bladder mucosal specimens were collected from 16 female patients with IC and 16 female normal controis.The age of IC patients was 51.3±10.2 years.The age of normal controls was 53.1±9.6years.The expressions of Th1(IFN-γ,IL-2)and Th2 cytokines(IL-4,IL-10)were determined by enIFN-γ and IL-2 in IC blood serum were(4.57±2.92),(17.52±7.52)pg/ml and in normal blood serum were(4.11±2.27),(20.99±5.09)pg/ml.Such two factors had no significant differences in these two groups.The expressions of IL-4 and IL-10 in IC blood serum were(0.34±0.22),(4.37±2.34)pg/ml and in normal blood serum were(O.14±O.07),(1.18±0.61)pg/ml.Such two factors had sighad no significant differences with normal bladder tissues(IFN-γ:χ2＝1.900,IL-2:χ2＝0.514).The expressions of IL-4 and IL-10 in IC bladder tissues had significant differences with normal bladder tiswere(0.16±0.11)and(2.42±1.27)pg/ml but in high PUF group were(0.53±0.12)and(6.31±1.21)pg/ml.The expressions of these two factors had significant correlations with the degree of PUF,which intensified in the IC of high PUF. Conclusion The expression of Th2 type eytokines is predominant in IC blood plasm and bladder tissues,the expression of Th2 type cytokines in IC blood plasm and bladder tissues has positive correlation with the degree of PUF. Key words: Cystitis,interstitial; T-lymphocytes; Immunocompetence

Bactericidal activity of human sera against <i> Salmonella Typhi</i>and <i>Salmonella paratyphi</i> A,B,C

Objectives : To determine the sensitivity of Salmonella typhi and paratyphi A,B,C, to normal human blood serum; and assess the role of blood groups (ABO system), Complement and Immunoglobulin in the resistance or susceptibility of Salmonella typhi and Salmonella paratyphi A,B,C infections. Design : Cross sectional study. Subjects : Ninety-six apparently healthy males and females volunteers, aged 18-24 years. Main outcome measure s: Resistance of Salmonella typhi and Salmonella paratyphi A,B,C infections may be blood group and immune status dependent. Results : Blood group B was most resistant to Salmonella typhi and Salmonella paratyphi A,B,C while blood group O showed least resistance (51.9%) and (22.2%) for Salmonella typhi and Salmonella paratyphi A,B,C. There was no difference in resistance pattern when blood was pooled in respect to their group types. Age or sex of the blood donors had no effect on the bactericidal activity of the sera. Conclusion : Blood group is an important factor in the susceptibility or resistance of an individual to Salmonella typhi and paratyphi infections. Individuals of blood group O are likely to be more susceptible to infections caused by Salmonella typhi and paratyphi A,B,C.

In vivo toxicity studies of europium hydroxide nanorods in mice

Lanthanide nanoparticles and nanorods have been widely used for diagnostic and therapeutic applications in biomedical nanotechnology due to their fluorescence and pro-angiogenic properties to endothelial cells, respectively. Recently, we have demonstrated that europium (III) hydroxide [Eu III(OH) 3] nanorods, synthesized by the microwave technique and characterized by several physico-chemical techniques, can be used as pro-angiogenic agents which introduce future therapeutic treatment strategies for severe ischemic heart/limb disease, and peripheral ischemic disease. The toxicity of these inorganic nanorods to endothelial cells was supported by several in vitro assays. To determine the in vivo toxicity, these nanorods were administered to mice through intraperitoneal injection (IP) everyday over a period of seven days in a dose dependent (1.25 to 125 mg kg − 1 day − 1 ) and time dependent manner (8–60 days). Bio-distribution of europium elements in different organs was analyzed by inductively coupled plasma mass spectrometry (ICPMS). Short-term (S-T) and long-term (L-T) toxicity studies (mice euthanized on days 8 and 60 for S-T and L-T, respectively) show normal blood hematology and serum clinical chemistry with the exception of a slight elevation of liver enzymes. Histological examination of nanorod-treated vital organs (liver, kidney, spleen and lungs) showed no or only mild histological changes that indicate mild toxicity at the higher dose of nanorods.

Visual Diagnosis: Four Infants Who Have Red, "Bloody" Stools

1. Jill Lowers, MD* 2. Arthur Jaffe, MD* 3. Joseph A. Zenel, MD† 4. Michael D. Cabana, MD, MPH§ 5. Clement Donahue, MD‡ 6. Alan Uba, MD‡ 1. *(Cases 1, 2, 3) Doernbecher Children's Hospital, Oregon Health & Science University, Portland, Ore 2. †(Cases 1, 2, 3) Associate Editor, Pediatrics in Review 3. §(Case 4) Departments of Pediatrics, Epidemiology and Biostatistics, Division of General Pediatrics, Institute for Health Policy Studies, UCSF Children's Hospital, University of California, San Francisco, Calif 4. ‡(Case 4) Department of Pediatrics, Division of General Pediatrics, Institute for Health Policy Studies, UCSF Children's Hospital, University of California, San Francisco, Calif A 2-year-old, previously healthy boy presents to the clinic with a history of 24 hours of fussiness, decreased appetite, and several short-lived episodes of acute abdominal pain. During the past 8 hours he has had several red, “bloody” stools. There is no vomiting. Physical examination reveals an alert child whose vital signs are normal. His abdomen is soft and nondistended. A palpable “mass” extends through the right upper and lower quadrants. Rectal examination does not reveal any fissures or tears. Auscultation reveals diminished bowel sounds. His remaining physical findings are within normal limits. After examination, the patient passes a red-colored stool (Fig. 1). Laboratory examination shows normal complete blood count and serum electrolyte concentrations. Stool guaiac testing is positive. Additional testing reveals the diagnosis. Figure 1. Red stool, guaiac-positive. A 2-year-old healthy girl presents with the complaint of a single large, red, “bloody” stool. She has had no vomiting, diarrhea, abdominal pain, fussiness, fever, or other systemic complaints. She has no history of constipation. Her mother brings the stool for examination (Fig. 2). Figure 2. Red stool, guaiac-negative. Physical examination reveals an alert, playful child whose vital signs are normal. Findings on abdominal examination are unremarkable, and the rectal examination does not reveal any fissures or tears. The remainder of her physical examination is normal. Stool guaiac testing is negative. Additional history reveals the diagnosis. A 5-month-old boy who has a recent history of acute otitis media presents with three episodes of red, “bloody” stools in the past 48 hours. The child is otherwise well and has no vomiting, diarrhea, fever, or abdominal pain. His appetite is good, and he drinks 8 oz of formula every 3 to 4 hours. He has no prior history of constipation or formula intolerance. Currently, he is taking oral cefdinir for the otitis media. His mother brings …

Delayed Diagnosis of Splenic Hematoma after Routine Colonoscopy

Purpose: Sixty-seven cases of splenic hematoma after colonoscopy have been reported in the literature. This complication is rare, however it is associated with significantly increased morbidity and mortality. We report a case of a large splenic hematoma following colonoscopy, highlighting a delay in the diagnosis of this complication. Methods: A 46-yr-old woman with a family history of colon cancer underwent an elective outpatient screening colonoscopy. She did not use anti-platelet or anti-coagulant agents prior to the procedure. The procedure was uneventful with intubation of the cecum. The patient tolerated the procedure well. Numerous colonic diverticula and a single 5 mm polyp in the rectosigmoid region were noted. Polypectomy was performed using cold biopsy forceps. Results: She presented to her family practitioner 8 days following the procedure with a sharp left upper quadrant pain radiating to the sternum and left shoulder tip. The pain was worse with deep inspiration and unchanged with movement of the left shoulder joint. The physical examination was unremarkable except for mild diffuse abdominal tenderness. A 12 lead electrocardiogram was normal. She was treated with omeprazole 20 mg po daily for presumed gastroesophageal reflux disease. Musculoskeletal pain due to faulty sleep position was thought to be the cause of her shoulder pain and she was therefore instructed not to lie on the affected shoulder. Six weeks later, she presented to the Emergency Department with similar complaints, which had been continuous with no improvement after the empirical therapy. A chest x-ray showed blunting of the left costophrenic angle. The blood tests revealed normal complete blood count, metabolic profile, liver enzymes, serum amylase and serum lipase levels. She was treated with levofloxacin for presumed pneumonia. A subsequent contrast enhanced chest and abdominal CT found a large (9 × 6.3 × 11 cm) subcapsular splenic fluid collection, which was confirmed by an ultrasound exam. A total of 360 ml of old blood and fluid were drained percutaneously with ultrasound guidance. The patient made an uneventful recovery with resolution of her symptoms. A 4-week follow-up ultrasound showed complete resolution of the splenic hematoma. Conclusion: To our knowledge, the delay to diagnosis from the colonoscopy is the longest reported in a patient with continuous symptoms. This case highlights the need for a high index of suspicion for splenic injury after colonoscopy in order to avoid a delayed or missed diagnosis. With the higher number of colonoscopies performed each year in the United States, it is likely that this complication is significantly under recognized and reported.

Prognostic values of serum cystatin C and β2 microglobulin, urinary β2 microglobulin and N-acetyl-β-D-glucosaminidase in early acute renal failure after liver transplantation

Acute renal failure (ARF) after liver transplantation is associated with high mortality and morbidity. Early therapeutic or preventive intervention is hampered by the lack of early effective prognostic factors. Recent studies indicated that serum levels of cystatin C and beta2-microglobulin (beta2 MG) as well as urinary beta2 MG and N-acetyl-beta-D-glucosaminidase (NAG) would increase in patients with early and mild renal impairment. In this study, these factors were detected during the different stages in patients who accepted orthotopic liver transplantation (OLT), and their feasibilities to predict early ARF after OLT were also analyzed. Sixty patients with normal blood urea nitrogen (BUN) and serum creatinine (SCr) who received modified piggyback liver transplantation without veno-venous bypass were prospectively studied. Blood samples were drawn from patients for the determination of serum beta2 MG (n = 60), SCr (n = 60) and serum Cystatin C (n = 39) at following 5 intervals: before operation (T0), 20 minutes before anhepatic phase (T1), 25 minutes in anhepatic (T2), 60 minutes after reperfusion (T3) and at the end of operation (T4). Urinary beta2 MG (n = 60) and NAG (n = 60) were also examined at following 3 intervals: before operation (T0), 60 minutes after reperfusion (T3) and at the end of operation (T4). According to the Rimola A criteria of ARF in 24 hours after operation, all the patients were divided into two groups: ARF group and non-ARF group. The data were statistically analyzed to evaluate the feasibiliy of regarding these factors as prognostic factors for early ARF after liver transplantation in patients with normal SCr and BUN before operation. Ten of sixty cases showed ARF (16.7%). The Logistic regression analysis showed that the levels of serum and urinary beta2 MG as well as serum cystatin C before operation were correlated with early ARF after liver transplantation (P < 0.05), while only serum levels of cystatin C and Cr at the end of operation correlated with early ARF (P < 0.05, P < 0.01) after liver transplantation. The serum beta2 MG, Cystatin C, SCr and urinary beta2 MG levels in ARF group were much more higher than that in non-ARF group (P < 0.05, P < 0.01). There were significant differences between the correct and false predictive positive ratios of serum cystatin C, serum and urinary beta2 MG levels before operation (P < 0.05, P < 0.01), while only SCr showed significant difference between these groups at the end of operation (P < 0.01). The results revealed that there was potential renal damage among those patients who demonstrated normal SCr and BUN before operation, and that liver transplantation could aggravate this damage and causing ARF. Here we provided the prognostic values of serum Cystatin C, beta2 MG, urinary beta2 MG and NAG in patients with early acute renal failure after liver transplantation.

Cardiomyopathy Associated With Ephedra‐Containing Nutritional Supplements

with both S3 and S4 gallops. The lungs were clear, and extremities were without edema. The remainder of the results of the physical examination were normal. Laboratory findings included normal complete blood cell count, serum chemistry, and liver function test results. Serum ferritin and thyroid function test findings were normal. Immunologic testing for Toxoplasma species, Lyme disease, and Ehrlichia species were negative. Chest radiography showed cardiomegaly, and electrocardiography revealed sinus tachycardia. Two-dimensional echocardiography demonstrated left ventricular dysfunction with severe global hypokinesia and an estimated left ventricular ejection fraction (LVEF) of 10% to 15%. Right heart catheterization revealed a pulmonary capillary wedge pressure of 24 mm Hg and mild pulmonary hypertension. Left heart catheterization revealed an LVEF of 10% with severe global hypokinesia, a left ventricular end-diastolic pressure of 7 mm Hg, and a left dominant coronary system with normal coronary arteries. Right ventricular biopsy revealed minimal changes and probable idiopathic cardiomyopathy. The patient was advised to stop taking the ephedra-containing dietary supplement, and medical treatment was started with aspirin, a b-blocker, and an angiotensin-converting enzyme inhibitor, with subsequent symptom improvement. The patient could not tolerate spironolactone therapy because of hyperkalemia. Repeat echocardiography performed 3 years later showed marked improvement in left ventricular systolic function, with an estimated LVEF of 45% to 50%.

Spontaneous Resolution of Idiopathic Aldosteronism After Long-Term Treatment With Potassium Canrenoate

To the Editor: Primary aldosteronism (PA) is the most common form of secondary hypertension. The prevalence of PA is raised from 1% to 3% to 10% to 15% because of the introduction of the upright plasma aldosterone/plasma renin activity ratio (APR) as screening procedure.1 The pathogenesis of idiopathic PA (IPA), which accounts for 50% of the cases of PA, is still not clear, and several factors have been involved, such as hypersensitivity to angiotensin II or to other stimulating factors or aberrant receptors in the glomerulosa. IPA is usually treated with aldosterone receptor blockers, such as spironolactone, potassium canrenoate (KC), canrenone, or eplerenone, which have, respectively, a high (spironolactone), low (KC and canrenone), or quite absent (eplerenone) antiandrogen activity. The dose of these drugs can be progressively reduced to the lowest amount able to keep normal both blood pressure (BP) and serum potassium. In a previous study,2 we reevaluated 15 patients with IPA 1 month after withdrawal of therapy with KC after 3 to 24 years of treatment. One month after withdrawal, APR was increased only …

Application of Umbilical Cord Serum Eyedrops for the Treatment of Neurotrophic Keratitis

To investigate the efficacy of umbilical cord serum eyedrops for the treatment of neurotrophic keratitis. Prospective noncomparative case series. Twenty-eight eyes of 28 patients with neurotrophic keratitis who were refractory to conventional treatment. The patients with neurotrophic keraitis were treated with 20% umbilical cord serum eyedrops 6 to 10 times a day. Ophthalmic examinations including best-corrected visual acuity (VA) measurement, corneal sensitivity test, corneal fluorescein staining, and anterior segment photography were performed before and after the treatment. Concentrations of substance P, insulinlike growth factor 1 (IGF-1), and nerve growth factor (NGF) in umbilical cord serum, normal peripheral blood serum, and tears were measured. Epithelial healing time; changes of VA and corneal sensitivity after treatment; and levels of substance P, IGF-1, and NGF in umbilical cord serum, normal peripheral blood serum, and tears. The epithelial defect healed completely in all eyes, with a mean healing time of 4.4+/-4.0 weeks. The epithelial defect healed within 2 weeks in 8 eyes (28.6%), between 2 and 4 weeks in 14 eyes (50.0%), and after 4 weeks in 6 eyes (21.4%). After treatment, VA improved by >2 lines in 17 eyes (60.7%). Mean pretreatment corneal sensitivity was 21.1+/-10.5 mm, and mean posttreatment corneal sensitivity was 24.3+/-11.7 mm (P<0.01). Mean concentrations of substance P, IGF-1, and NGF were 245.3+/-53.9 pg/ml, 239.0+/-77.1 ng/ml, and 729.7+/-72.0 pg/ml in umbilical cord serum; 169.5+/-81.0 pg/ml, 375.5+/-51.3 ng/ml, and 401.7+/-98.1 pg/ml in peripheral blood serum; and 69.8+/-24.9 pg/ml, 75.7+/-50.5 ng/ml, and 107.5+/-70.9 pg/ml in tears, respectively. Umbilical cord serum contains many neurotrophic factors, and umbilical cord serum eyedrops appeared to be effective for the treatment of neurotrophic keratitis.

Plasmablastic lymphoma of visceral cranium, cervix and thorax in an HIV-negative woman

Dear Editor, We would like to report a case of aggressive plasmablastic lymphoma (PBL) in an HIV-negative individual, characterised by a unique combination of unusual clinical and immunophenotypic features. A 67-year-old woman presented with a 20-day history of a painless mass lesion in the left supraclavicular fossa. She was also complaining of blurred vision and a continuous mild retrosternal pain. She denied fever, night sweats or weight loss. Her past medical history was negative for diseases or treatments associated with immunodeficiency. On physical examination, she had diplopia on upward gaze. A painless firm mass 3×4 cm in size was palpated in the left supraclavicular fossa. There was no peripheral lymphadenopathy, organomegaly or other remarkable findings. Laboratory investigations showed a normal full blood count and serum biochemical profile, including normal lactate dehydrogenase levels. No paraprotein was present on serum and urine electrophoresis. Enzyme-linked immunosorbent assay testing for HIV antibodies was negative. Computerised tomography (CT) imaging studies revealed a mass with soft tissue density occupying the left sphenoid sinus and infiltrating the ethmoid sinus and ipsilateral concha with associated areas of bone destruction. The mass was extending to the left orbit with thickening of the left inferior rectus muscle. There was also an evidence of tumour invasion of the left maxillary antrum and mandibular ramus. Furthermore, soft tissue masses compatible with multiple lymph node enlargement and block formation were present in the inferior frontolateral cervical region with extension to the anterior upper mediastinum. CT imaging of abdomen was negative for lymphadenopathy or organomegaly. A bone marrow biopsy was negative for neoplastic invasion. Biopsy of the cervical mass revealed a neoplasm causing complete effacement of nodal architecture and extending to the adjacent adipose tissue. The neoplastic tissue consisted of diffusely growing largeand medium-sized cells with polymorphic nuclei, frequent mitoses and moderate-to-large amount of eosinophilic or amphiphilic cytoplasm (Fig. 2a). Immunohistochemical investigation using markers of epithelial (Ker HMW, Ker LMW, Ker7, Ker20, EMA, Cam 5-2), lymphoid (CD3, CD20, CD45RO, CD45, CD30, CD21, CD79a, CD8, CD56, CD138, kappa and lambda chains, immunoglobulins), mesenchymal (S-100, vimentin, actin, desmin, CD31, CD34, GFAP (glial fibrillary acidic protein)), histiocytic (CD68), melanocytic (HMB-45) differentiation and various others (Bcl-2, CD99, neuron-specific enolase [NSE]) revealed only a strong expression of vimentin and a small percentage of cells with moderate positivity for NSE. Blind biopsies from the nasopharynx indicated only nonspecific immunologic stimulation of the lymphoid tissue. Ann Hematol (2007) 86:615–618 DOI 10.1007/s00277-007-0280-z

Multiple Ipsilateral Lower Extremity Masses in a 46-year-old Man

Multiple Ipsilateral Lower Extremity Masses in a 46-year-old Man

Prevalence and Implications of Isolated Microscopic Hematuria in Asymptomatic Chinese Pregnant Women

Background: IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. However, the actual prevalence of microscopic hematuria and IgAN is unknown in the Chinese population. Methods: We screened 7,828 consecutive pregnant women for microscopic hematuria in the antenatal clinic of a tertiary referral center. Persistent microscopic hematuria was defined as urine Hemastix® (Bayer Diagnostics, Hong Kong) of 1+ for red cells in two clinic visits. Subjects were referred to the renal clinic for specialist evaluation, including measurement of blood pressure, serum creatinine, urine bacterial culture, and quantification of proteinuria. Result: There were 207 women (2.64%) with microscopic hematuria. Mean age was 31.8 ± 5.0 years. In 101 patients (48.8%), there was proteinuria >0.1 g/day by quanti- tative assay. Hematuria was found to resolve before or shortly after delivery in 126 (60.9%) and 68 women (32.9%), respectively. Five patients (2.4%) had urinary tract infection proved by repeated urine culture, 1 had papillary necrosis, and 1 had duplex collecting system. Three patients were confirmed to have IgAN by renal biopsy; all had normal blood pressure and serum creatinine, but dysmorphic red cells in urine microscopy, and proteinuria of over 0.5 g/day that persisted after delivery. Renal biopsy on another woman showed no specific pathology. Two women were lost to follow-up, both with normal renal function and no detectable proteinuria. The overall prevalence of IgAN was 38 cases per 100,000 population (95% confidence interval: 8–112 cases). Conclusion: Microscopic hematuria is not uncommon in pregnant women, and IgAN is present in a small proportion of these patients. Further study is needed to determine whether screening for microscopic hematuria would allow early diagnosis and improve the prognosis of these patients.

Periorbital Ecchymoses Are Not Pathognomonic of the Light-chain Type of Amyloidosis

CASE REPORT A 52-year-old man presented with a progressive 16month course of severe sensorimotor polyneuropathy. He had no personal or familial medical past history. Clinical manifestations appeared in July 2003 and were characterized by decreased sensation and painful paraesthesia of the upper extremities, followed 4 months later by distal weakness. Then, decreased sensation, painful paraesthesia and distal weakness of the lower limbs progressively appeared. Alternating diarrhoea and constipation, Raynaud’s syndrome and erectile dysfunction were noted at the same time. The patient also complained of effort dyspnoea and orthopnoea. Electromyography demonstrated a severe axonal sensorimotor polyneuropathy involving all 4 limbs. Investigations revealed a normal blood count and serum glucose, creatinine, and urea, electrolytes and liver function test. There were no inflammatory biological markers. Classical causes of axonal polyneuropathy, such as alcoholism, vitamin deficiency, diabetes melli tus, dysthyroidea and auto-immune diseases, were ruled out. The suspected dysautonomia was confirmed by an abnormal heart-rate variability on electrophysiological tests. Echocardiography showed thickened ventricular walls with a granular sparkling appearance and impaired diastolic dysfunction. The patient developed periorbital and scleral ecchymoses after vomiting (Fig. 1). Since periorbital ecchymoses are classically considered as pathognomonic of AL amyloidosis, we performed a salivary gland biopsy and a sural nerve biopsy. Amyloid deposits were observed in both figures, but immunofluorescence with anti-light-chain (lambda or kappa) antibodies did not reveal any immunoreactivity. There was no evidence of monoclonal gammopathy in spite of an exhaustive work-up comprising blood and urinary immunoelectrophoresis, nephelometric assay of light chain in serum and an osteomedullar biopsy. Since the AL type of amyloidosis was not confirmed, a molecular analysis of the TTR gene was performed and revealed a heterozygous Ser77Tyr mutation, resulting in a diagnosis of familial TTR type amyloid polyneuropathy. Immunohistochemistry confirmed the transthyretin nature of the amyloid deposits (Fig. 2).

Visual Diagnosis: A Child Who Has Acute Onset of Unusual Skin Lesions and Edema

1. Ceyda Acun, MD* 2. Gonca Ustundag, MD* 3. Ayhan Sogut, MD* 4. Rafet Koca, MD† 5. Gamze Numanoglu, MD‡ 1. *Department of Pediatrics 2. †Department of Dermatology 3. ‡Department of Pathology, Karaelmas University, School of Medicine, Zonguldak, Turkey A 13-month-old boy presents to the emergency department with a 1-day history of rash on his face, medial thighs, and upper trunk and swelling of his face, ears, hands, and feet. He has a 3-day history of an upper respiratory tract infection. There is no recent history of immunization or drug intake. The physical examination reveals an alert child who has a widespread rash over his peroral area, chin, cheeks, and ears, with sparing of the mucous membranes (Figs. 1, 2). His vital signs are appropriate for his age. The rash appears in a rosette pattern of 1 to 2-cm diameter, purplish-red, slightly raised macules. A milder rash appears on his medial thighs and upper trunk. Both his face and ears are significantly swollen, and the flexor surfaces of the hands and feet are mildly swollen. The patient is admitted for observation and evaluation. Figure 1. Purplish-red, slightly raised macules on the face and trunk. Figure 2. Purplish-red, slightly raised macules on the face and ear. Over the next 3 days, the rash spreads to his arms and legs (Figs. 3, 4). However, apart from a transient mild fever, the child appears well, having no obvious systemic symptoms. Figure 3. Rash over extremities. Figure 4. Rash over legs and buttocks. The laboratory examination reveals a normal complete blood count, serum immunoglobulins, C3 and C4 levels, circulating immune complexes, antistreptolysin titers, coagulation studies, urinalysis, renal …

Increased protein glycation in fructosamine 3-kinase-deficient mice

Amines, including those present on proteins, spontaneously react with glucose to form fructosamines in a reaction known as glycation. In the present paper, we have explored, through a targeted gene inactivation approach, the role of FN3K (fructosamine 3-kinase), an intracellular enzyme that phosphorylates free and protein-bound fructose-epsilon-lysines and which is potentially involved in protein repair. Fn3k-/- mice looked healthy and had normal blood glucose and serum fructosamine levels. However, their level of haemoglobin-bound fructosamines was approx. 2.5-fold higher than that of control (Fn3k+/+) or Fn3k+/- mice. Other intracellular proteins were also significantly more glycated in Fn3k-/- mice in erythrocytes (1.8-2.2-fold) and in brain, kidney, liver and skeletal muscle (1.2-1.8-fold), indicating that FN3K removes fructosamines from intracellular proteins in vivo. The urinary excretion of free fructose-epsilon-lysine was 10-20-fold higher in fed mice compared with mice starved for 36 h, and did not differ between fed Fn3k+/+ and Fn3k-/- mice, indicating that food is the main source of urinary fructose-epsilon-lysine in these mice and that FN3K does not participate in the metabolism of food-derived fructose-epsilon-lysine. However, in starved animals, the urinary excretion of fructose-epsilon-lysine was 2.5-fold higher in Fn3k-/- mice compared with Fn3k+/+ or Fn3k+/- mice. Furthermore, a marked increase (5-13-fold) was observed in the concentration of free fructose-epsilon-lysine in tissues of fed Fn3k-/- mice compared with control mice, indicating that FN3K participates in the metabolism of endogenously produced fructose-epsilon-lysine. Taken together, these data indicate that FN3K serves as a protein repair enzyme and also in the metabolism of endogenously produced free fructose-epsilon-lysine.

Application of Umbilical Cord Serum Eyedrops for the Treatment of Dry Eye Syndrome

To investigate the efficacy of umbilical cord serum eyedrops for the treatment of severe dry eye syndrome. Fifty-five eyes of 31 patients with severe dry eye syndrome were treated with umbilical cord serum eyedrops. Symptom scoring, tear film break-up time (BUT), Schirmer test, corneal sensitivity test, and corneal fluorescein staining were performed before and 1 and 2 months after treatment, and conjunctival impression cytology was performed before and 2 months after treatment. The concentrations of epidermal growth factor (EGF), vitamin A, and transforming growth factor-beta (TGF-beta) in umbilical cord serum and normal peripheral blood serum were measured. Two months after treatment, significant improvement was observed in symptom score (from 3.07 +/- 0.54 to 0.96 +/- 0. 58), BUT (from 3.96 +/- 1.56 to 5.45 +/- 2.54 seconds), and keratoepitheliopathy score (from 4.87 +/- 3.22 to 1.71 +/- 1.84) (P < 0.01). There was no statistically significant change in Schirmer and corneal sensitivity tests. In impression cytology, the grade of squamous metaplasia (from 2.35 +/- 0.72 to 1.44 +/- 0.69) and goblet cell density (from 80.91 +/- 31.53 to 154.68 +/- 43.06 cell/mm) improved significantly (P < 0.01). The mean concentrations of EGF, TGF-beta, and vitamin A were 0.48 +/- 0.09, 57.14 +/- 18.98, and 230.85 +/- 13.39 ng/mL in umbilical cord serum and 0.14 +/- 0.03, 31.30 +/- 12.86, and 372.34 +/- 22.32 ng/mL in peripheral blood serum, respectively. Umbilical cord serum contains essential tear components, and umbilical cord serum eyedrops are effective and safe for the treatment of severe dry eye syndrome.

Urinary Podocyte mRNA Excretion in Children with D+HUS: A Potential Marker of Long-Term Outcome

Background. Diarrhea-associated hemolytic uremic syndrome (D+HUS) causes acute renal failure and may lead to podocyte loss. Objective. To determine if the urinary mRNA excretion of podocyte proteins is detectable in children with D+HUS and if it is a biomarker of a poor long-term outcome. Methods. Patients were randomly selected from participants in the SYNSORB Pk® trial. Urine samples were collected daily during the first week of hospitalization. Specimens were also obtained in healthy volunteers. Synaptopodin and nephrin mRNA levels were measured using real-time PCR. Results. Fifteen children, aged 4.9±2.8 years, were studied. Patients were categorized based on urinary mRNA levels into normal (marker:GAPDH≤mean + SD) or high (marker:GAPDH>mean + SD) in controls. Twelve patients (80%) had increased urinary podocyte mRNA excretion; 11 (73%) had high synaptopodin and 5 (33%) had high nephrin mRNA levels. Follow-up data were available in 13/15 patients, all of whom had normal blood pressure, urinalysis, and serum creatinine concentration. Conclusion. The isolation of podocyte mRNA from routine urine samples is feasible in children with D+HUS. Most patients have podocyturia based on synaptopodin and nephrin mRNA excretion. Larger studies with extended follow-up are required to determine the relationship of these biomarkers to long-term renal prognosis in D+HUS.

LONG TERM LAMIVUDINE TREATMENT FOR CHRONIC HEPATITIS B INFECTION IN CHILDREN UNRESPONSIVE TO INTERFERON

Background: Three years ago we reported the results of an open prospective study that investigated the efficacy and safety of one year lamivudine treatment in children (n = 22) with chronic hepatitis B (CHB) who failed interferon treatment. We showed that one year lamivudine treatment resulted in decreased HBV replication and improved ALT values, but an exceptionally high rate (65%) of lamivudine-resistant mutants. Aims: The present study examined the efficacy and safety of prolonged lamivudine therapy in this group of children (aged 8.5-19 years of age). Methods: This cohort of 22 children (17 boys, 5 girls) was prospectively followed for a median of 3.6 years (range 3 to 4 years). Children were treated with lamivudine 3 mg/kg/day up to 100 mg/day, and were instructed to come back to follow up every 4 months. At each visit children underwent physical examination, compliance to treatment and side effects were recorded and blood tests were performed, including blood count, liver enzymes and bilirubin, HBeAg/antiHBe, HBV DNA and HBV mutants. Results: Of the 22 children that started the study, only five were taking lamivudine after 4 years. The reasons for drop out from the study were lack of adherence to treatment (10/17), HBeAg/antiHBe seroconversion (5/17) and lack of response to treatment (2/17). Children who maintained lamivudine treatment at the end of 4 years had persistent ALT normalization and low HBV DNA levels and YMDD mutant was present only in one child. No clinical adverse effects were recorded during lamivudine treatment or after treatment termination. Transient ALT flare up (×12 ULN) was present in one patient. Two patients showed persistent elevated CPK values (1753 IU/L to 478 IU/L) with normal blood gases and serum lactate. Conclusions: In this cohort, children with CHB who failed to respond to previous IFN therapy and were treated with lamivudine for up to 4 years, had high rates of drop out, mainly because of lack of compliance to treatment and poor HBeAg seroconversion rate, suggesting that prolonged lamivudine treatment in children is hard to achieve and probably not efficient.