Nitric oxide (NO) is a free radical of physiological significance. The changes in the production of NO during the fracture healing process are not well known. This clinical prospective study was planned to determine these changes in patients with fractured long bone(s), who underwent surgery in the 3rd week after fracture. The patients were divided into two groups: 20 patients with an isolated femoral fracture and 20 patients with multiple fractures, including a femoral fracture. Venous blood was drawn from the healthy volunteers (n = 20) once, and from the patients seven times during 21 days after fracture. NO level was measured as nitrite in each serum sample. The serum NO levels at all measurements of the patients were significantly higher than those of the control subjects. The time-dependent changes in the NO levels were similar in both patient groups. The serum NO levels were highest in the first 6 hrs, and then decreased to the lowest level on the 3rd day. Subsequently, there was an increasing trend on the 5th, 7th and 14th days. At all times of the measurements, the NO levels were higher in patients with multiple fractures than in those with the femoral fracture, with the significant difference observed at the 6 hrs and on the 7th day. The NO levels were decreased on the 21st day after surgery. The present study suggests that NO production may be increased in considerable amounts during the first 2 weeks of fracture healing, particularly in the first 6 hrs.
The cloaca is a single canal from which the urinary, genital, and intestinal tracts arise around gestational weeks 5-6. Persistent cloaca can result from cystic mass formation within the pelvis, which is commonly association with multiple developmental defects. VATER association, which is a spectrum of anomalies, manifested by vertebral defects, anal atresia, tracheo-esophageal fistula with esophageal atresia, and renal dysplasia, arises from abnormalities in mesodermal differentiation. Recently, both conditions have been proposed to represent a continuous spectrum of anomalies, but the pathophysiology concerning the continuity of the development and the clinical condition are still unclear. Since renal failure becomes a serious problem after birth, timely infant delivery is essential to avoid loss of renal function. We report a patient, in whom the overlap between these two conditions was identified, and renal function was lost from one kidney. A polycystic mass was found in the fetal abdomen at 26 weeks of gestation. By ultrasonography, we detected a polycystic left kidney, a single umbilical artery, a ventricular septal defect, an esophageal atresia, ascites, an anal atresia, and a cystic mass with debris behind the bladder. The left kidney was non-functioning and the right kidney showed signs of hydronephrosis at 30 weeks of gestation. We measured the size and the blood flow of renal artery sequentially, and could deliver the fetus before the function was lost from the right kidney. Our observations will help inform future patients where prompt intervention can help improve renal function and infant health.
Rheumatoid arthritis (RA) is associated with progressive joint destruction and disability. Early diagnosis of RA is important, since early and aggressive treatments lead to a better outcome. Circulating autoantibodies are a serological hallmark of systemic rheumatic diseases. More recently, antibodies directed to a cyclic citrullinated peptide, anti-CCP antibodies, have been established as specific diagnostic and prognostic tools for RA. The aims of this study were to assess the diagnostic and radiological prognostic value of the anti-CCP antibody in Turkish patients with RA (n = 97) and those with Behçet's disease (BD) (n = 46). The study also included 35 healthy controls. Anti-CCP antibodies were measured by ELISA, and radiological damage was evaluated by using modified Larsen scoring. In the RA group, sensitivity and specificity were 80.4% and 93.5% for rheumatoid factor (RF), and 74.2% and 97.8% for anti-CCP antibody, respectively. RF was positive in 3 BD patients (6.5%) and in one of the controls (2.9%). In contrast, anti-CCP antibodies were detected in one BD patient (2.2%), but not in the control subjects. Deformed joint counts and radiographic scores were higher in anti-CCP antibody-positive RA patients (n = 72) than those in anti-CCP antibody-negative patients (n = 25) (p < 0.05). Moreover, anti-CCP antibody titer correlated with deformed joint count (r = 0.224, p < 0.05) and radiographic score (r = 0.308, p < 0.05). This study indicates the diagnostic and prognostic utility of anti-CCP antibodies in Turkish patients with RA. Importantly, anti-CCP antibodies are not associated with BD.
The diagnosis of diabetic foot infection (DFI) is usually a challenge to the clinician. Procalcitonin (PCT), a 116-amino acid propeptide of calcitonin, is a new marker of bacterial infections and sepsis. We evaluated the serum value of PCT as a marker of bacterial infection in diabetic patients with foot ulcers. Forty-nine diabetic patients with foot ulcers were consecutively enrolled into the study. DFI was diagnosed clinically by the presence of purulent secretions or at least two of the symptoms of inflammation including redness, warmth, swelling, and pain. According to these criteria, DFI was determined in 27 patients (DFI group) and not detected in 22 patients (NDFI group). The blood samples were taken for biochemical analysis on admission. PCT, white blood cell count (WBC) and erythrocyte sedimentation rate (ESR), but not C-reactive protein (CRP), was found significantly higher in DFI group compared with NDFI group. The best cut-off value, sensitivity and specificity were 0.08 ng/ml, 77% and 100% for PCT, 32.1 mg/dl, 29% and 100% for CRP, 8.6 109/L, 70% and 72% for WBC and 40.5 mm/h, 77% and 77% for ESR, respectively. The area under the receiver operating characteristic curve for infection identification was greatest for PCT (0.859; p < 0.001), followed by WBC (0.785; p = 0.001), ESR (0.752; p = 0.003), and finally CRP (0.625; p = 0.137). These results suggest that PCT may be a useful diagnostic marker for DFI. Additional research is needed to better define the role of PCT in DFI.
Visual evoked potentials (VEP) can be used as an objective non-invasive method to study the electrical activity of the visual system. Latency and amplitude measurements of VEP demonstrated that diabetes mellitus has been associated with increases in the latencies whereas the amplitude measurements revealed contradictory results. Although physical exercise has been reported to reduce the complications of diabetes mellitus, the effect of exercise on the visual system remains unknown. We investigated the effects of long-term moderate physical exercise on VEP in streptozotocin (STZ)-diabetic rats. We also measured brain thiobarbituric acid-reactive substances (TBARS) to explore the possible contribution of lipid peroxidation on the visual system. Animals were divided into four groups: control (C), control exercise (CE), diabetic (D) and diabetic exercise (DE) groups. Diabetes was induced by a single intraperitoneal injection of STZ (60 mg/kg). Three days after the confirmation of diabetes, DE and CE groups were trained by running on a motor-driven treadmill with a progressive eight-week programme. The animals began running at 10 m/min, 0° slope, 10 min/day and reached a level of 28 m/min, 6° slope, 60 min/day by week 8. TBARS were elevated and VEP latencies were delayed in diabetic rats, indicating diabetes-induced defects in the optic pathway. These prolonged latencies were restored by exercise training. VEP amplitudes of the DE group were found unaltered with the exception of a decrement in P2N2 which represents an early component of VEP, suggesting that exercise improves visual system defects in diabetic animals at different levels of the optic pathway.
Soft tissue gas gangrene with myonecrosis is a severe complication of traumatic and non-traumatic conditions with a potentially lethal outcome. Emphysematous cholecystitis is a complication of acute cholecystitis, which is characterized by air accumulation in the gallbladder wall and is reported in the literature as a rare causative factor of soft tissue gas gangrene. Here we report 4 patients who developed soft tissue gas gangrene as a complication of emphysematous cholecystitis. Two patients were female octogenarians (one with a history of diabetes mellitus), and underwent percutaneous trans-gallbladder drainage and fascia incisions of the affected soft tissue with prompt administration of antibiotics. Finally, both of them died. The other two patients were male (32 years old diabetic and 47 years old with a history of chronic alcoholism). They underwent open cholecystectomy. Fascia incisions of the gangrenous areas and antibiotic therapy administration were also performed. Both of them were discharged from the hospital and are currently in excellent clinical status. We also present the ultrasonographic and/or radiologic images of these four patients. Soft tissue gas gangrene may complicate emphysematous cholecystitis, and clinicians should be aware of the coexistence of these two clinical conditions, since immediate management is needed in order to prevent fatal outcome.
Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS). The etiology of MS remains unclear, but T cells specific for myelin components, such as myelin oligodendrocyte glycoprotein (MOG), are thought to play a critical role in the onset of MS. Experimental autoimmune encephalomyelitis (EAE) has been used as an animal model of MS, and T helper type 1 (Th1) cells play an essential role for the pathogenesis of EAE through the production of Th1 cytokines, interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α). We examined CD4+ and CD8+ T cell responses in the spleen and CNS of EAE mice, generated by immunization with a peptide (35-55 amino acid residues) of MOG. The number of both CD4+ and CD8+ T cells and their MOG-reactivity in the CNS were associated with increasing disease severity but not those in the spleen, suggesting that the MOG-specific CD4+ and CD8+ T cells in the CNS are involved in the development of EAE. Polymerase chain reaction analysis suggested that both CD4+ and CD8+ T cells produced IFN-γ and TNF-α, while CD4+ T cells also produced interleukin-17 (IL-17), an important factor in the development of EAE. Thus, CD4+ T cells may contribute to the induction of EAE by producing IL-17. Furthermore, CD8+ T cells express higher levels of a suppressive cytokine, IL-10. Taking together, our data suggest that CD4+ T cells are involved in the early phase of EAE, whereas CD8+ T cells have a regulatory role in the later stage of EAE.
Bone marrow-derived cells (BMDC) play crucial roles in tissue regeneration. Granulocyte-colony stimulating factor (G-CSF) mobilizes BMDC and may facilitate the repair of kidney tissues after ischemia/reperfusion (I/R) injury. The tissue protective action of resveratrol, an antioxidant, might modify the regenerating potential of BMDC in I/R renal injury. This study examined whether G-CSF and/or resveratrol affect the recruitment of BMDC into vascular endothelial cells and renal tubular cells and the kidney function after I/R injury. I/R renal injury was induced in female mice that had been lethally irradiated and transplanted with male bone marrow cells. The mice were given saline, resveratrol or G-CSF, daily for 7 days. Non-irradiated and non-bone-marrow-transplanted female mice, which underwent the same kidney injury, were included as control. White blood cell (WBC) count and serum creatinine were monitored. Immunohistologic evaluation for renal tubular cells (cytokeratin) and endothelial cells (factor VIII-related antigen), and fluorescence in situ hybridization for mouse Y chromosome were performed. Although WBC was significantly higher in the G-CSF group, there was no significant difference in creatinine levels among all groups. Factor VIII-related antigen-positive cells with a Y-chromosome signal were identified in the capillary wall between renal tubuli and most frequently seen in the G-CSF group (p < 0.0001). Resveratrol did not affect kidney recovery in this model. No cytokeratin-positive renal tubular cells having a Y-chromosome signal were identified. In conclusion, BMDC are recruited into endothelial cell in I/R renal injury without apparent renal tubular cell regeneration, and G-CSF facilitates the endothelial cell regeneration.
Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is rare among Asian individuals, and the clinical course and biochemical findings remain unclear. We report herein a 3-year-old Japanese girl with MCADD. The diagnosis was suggested by acylcarnitine profiles and confirmed by enzyme activity and genetic analysis after clinical presentation. Our described method with high-performance liquid chromatography/tandem mass spectrometry allows quantification of levels of n-octanoylcarnitine (C8-N) and other isomers (e.g. valproylcarnitine). We examined the patient's acylcarnitine profiles in serum and urine samples during carnitine loading and 14-hr fasting tests with/without carnitine supplementation. Under hypocarnitinemia, serum level of C8-N was 0.16 μmol/l and C8-N/decanoylcarnitine (C10) ratio was 1.8, which did not correspond to the diagnostic criteria for MCADD. However, intravenous carnitine loading test (100 mg/kg/day for 3 days and 50 mg/kg/day for 1 day) led to increased serum C8-N levels and urinary excretion was obvious, strongly suggesting MCADD. In the fasting test with carnitine supplementation, marked production of acylcarnitines (C8-N > C2 >> C6 > C10) was found, compared to the fasting test without carnitine supplementation. These results indicate that carnitine supplementation may be useful for detoxification of accumulated acylcarnitines even in an asymptomatic state. Moreover, the one-point examination for serum C8-N level and/or C8-N/C10 ratio may make the diagnosis of MCADD difficult, particularly in the presence of significant hypocarnitinemia. To avoid this pitfall, attention should be given to serum levels of free carnitine, and carnitine loading may be demanded in hypocarnitinemia.
Renal impairment is often observed in acute heart failure (HF), which is an independent prognostic factor. It is important to identify high-risk patients, who need close follow-up and intensive care for renal protection. This study was conducted to identify the factors associated with the subsequent occurrence of HF-related renal dysfunction in patients, who were admitted to the hospitals due to acute HF symptoms. We evaluated 254 consecutive patients with acute HF. HF-related renal dysfunction was defined when highest serum creatinine level was greater than 1.2 mg/dl and the serum creatinine level increased by more than 50% compared with the baseline value during the admission. Forty patients with acute HF (16%) had subsequent renal dysfunction after admission. Elevated serum C-reactive protein (CRP) levels (≥ 5 mg/dl, odds ratio 2.51, p = 0.008 by univariate analysis, odds ratio 2.43, p = 0.019 by multivariate analysis) during the first week after admission and over-reduction of body weight (≥ 4.5 kg, odds ratio 2.68, p = 0.005 by univariate analysis, odds ratio 2.53, p = 0.010 by multivariate analysis) by acute HF treatment were significantly associated with this phenomenon. Patients with high CRP levels (≥ 5 mg/dl) during the first week after admission showed a significantly greater elevation of serum creatinine levels as compared to the levels before admission than those with low CRP levels (< 5 mg/dl). In conclsion, higher serum levels of CRP could predict the subsequent renal impairment in patients admitted with the worsening of HF symptoms.
Internal stress can modify values in blood examinations such as glucose. Mood change releases us from the stress state, and the mood change tendency (MCT) may show individual differences. However, little is known about whether individual mood change tendencies in daily life affect fasting plasma glucose (FPG) levels. We investigated the effects of clinical characteristics including age, body mass index (BMI), smoking, alcohol habits and self-reported MCT (an answer to the inquiry on their daily MCT: good, average, or poor) on FPG values among 272 Japanese females (mean age 48.4 ± 9.3 years). Subjects with normal to impaired fasting glucose levels (less than 7.0 mmol/L) were included in this study. The mean FPG levels in subjects with good, average and poor MCT were 5.32 ± 0.48, 5.36 ± 0.50 and 5.58 ± 0.69 mmol/L, respectively. A significant difference was noted between subjects with good and poor MCT (p = 0.02). There was no significant difference in BMI levels among MCT-based groups. Pearson's rank correlation and multiple regression analysis, using FPG levels and other variables, demonstrated a significant relationship between FPG levels and MCT (p le; 0.01), along with age and BMI. These results suggest slight but significant effects of individual MCT on FPG, and that a consideration of MCT may occasionally be needed in the interpretation and management of FPG levels in the Japanese female population.