Monoclonal Antibody Specific for TIRC7 Induces Donor-specific Anergy and Prevents Rejection of Cardiac Allografts in Mice

T cell immune response c-DNA (TIRC7) is up-regulated during the early stages of T-cell activation in response to alloantigens. In this study, we analyzed the effects of newly developed monoclonal antibodies (mAb) against TIRC7 in acute cardiac allograft rejection. Fully vascularized heterotopic allogeneic heart transplantation was performed in mice across a full-mismatch barrier (C57Bl/10 into CBA). Recipients received seven injections (day 0-7) of a novel anti-TIRC7 mAb or remained untreated. Graft survival, histology and ex vivo lymphocyte functions were tested. Targeting of TIRC7 with an anti-TIRC7 mAb diminishes lymphocyte infiltration into grafts resulting in delay of morphological graft damage and prolongation of allograft survival. The lymphocytes from anti-TIRC7 mAb-treated animals exhibit hypo-responsiveness without evidence of lymphocyte depletion against the donor allo-antigens. Proliferation and expression of interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) were down-regulated while interleukin-4 (IL-4) and IL-10 expression were spared. Moreover, anti-TIRC7 mAb enhanced up-regulation of CTLA-4 expression but suppressed up-regulation of CD25 on stimulated lymphocytes in vitro and in vivo. Ligation of TIRC7 has important effects on the regulation of co-stimulatory signaling pathways associated with suppressing of T-cell activation. Targeting of TIRC7 may therefore provide a novel therapeutic approach for modulating T cell immune responses during organ transplantation.     

Cerebellar abscess and syringomyelia due to isoniazid-resistant Mycobacterium tuberculosis.

A 19-year-old immunocompetent man was admitted to hospital with diplopia, nausea, vomiting and change in mental status. The patient had a history of tuberculous meningitis that was diagnosed at another hospital 6 months before the present admission, and at that time anti-tuberculosis treatment was initiated using a first-line drug combination. A computed tomography (CT) scan of the brain revealed non-communicating hydrocephalus. A ventriculo-peritoneal shunt was inserted surgically. Two months later, the patient was hospitalized again for fever, dysphagia and left hemiparesis. At that time, his cranial CT findings were within normal limits; however, magnetic resonance imaging (MRI) revealed an irregular multilocular peripheral contrast-enhancing lesion in the posterior fossa. The abscess was surgically drained. The presence of acid-fast bacilli in the abscess material was demonstrated by Ziehl-Neelsen staining. Mycobacterium tuberculosis grew on Lowenstein-Jensen culture medium, and the strain was found to be resistant to isoniazid. One month after the operation, the patient became quadriparetic. Cervical MRI revealed a cervico-thoracic syringomyelitic cavity, after which a syringoperitoneal shunt was placed. Treatment with four drugs was continued for 10 months, and then treatment with three drugs for a total period of 18 months. The patient recovered, with residual quadriparesis. Even though very rare, isoniazid-resistant M. tuberculosis may be the causative agent of progressive tuberculosis.     

The ultrasonographic diagnosis of bleeding into a pancreatic pseudocyst

Bleeding into a pancreatic pseudocyst is a rare but life-threatening entity. Early diagnosis is crucial in its management. There are reports suggesting that computed tomography (CT), scintigraphy, endoscopic retrograde cholangiopancreatography (ERCP), and angiography could be the diagnostic maneuvers. In this report, we present a case of arterial bleeding into a pancreatic pseudocyst, which was diagnosed by the turbulent echo-currents seen in real-time ultrasonography.     

Capsular ataxic tetraparesis

A 42-year-old man with ataxic tetraparesis is reported. Computerized tomography showed bilateral and symmetrical lacunar infarcts at the junctions of the posterior limb of the internal capsule and the corona radiata. Previously this clinical syndrome had been reported only with a lesion in the pons.     

Serum fructosamine correlates with gingival index in children with insulin-dependent diabetes mellitus (IDDM)

Abstract Fructosamine assay, which is used in diagnosing and monitoring diabetic patients, is compared with the hemoglobin and plasma glucose assays in children and adolescent insulin-dependent diabetes mellitus patients. We demonstrated that the gingival index scores were correlated with fructosamine values in insulin-dependent diabetes mellitus patients but not in non-diabetic controls. We also found that there was no correlation between gingivitis scores and fasting plasma glucose and HbAlc values. Periodontitis was found to be rare in diabetic children and adolescents.     

The effect of renal artery-only or renal artery–vein clamping during partial nephrectomy on short and long-term functional results: Is clamping technique important?

Purpose

To evaluate the effect of artery-only (AO) and artery–vein (AV) clamping during partial nephrectomy (PN) on short- and long-term renal function outcome.

Methods

Medical records of 154 patients in the AO group and 192 patients in the AV group who underwent open and minimally invasive (laparoscopic/robotic) PN between January 2011 and January 2018 were retrospectively assessed. Preoperative patient and tumor-specific characteristics in addition to perioperative factors and renal function outcomes were compared. The change in the estimated glomerular filtration rate (eGFR) from postoperative 1–3 days, 12 and 24 months after surgery was calculated. Acute kidney injury (AKI) was defined a as a?>?25% reduction in eGFR.

Results

There were no statistically significant differences between the clamping techniques in terms of postoperative 1–3 days, 12 and 24 months eGFR change percentage and risk of progression to chronic kidney disease (CKD). No significant difference in short- and long-term renal functions was found between the minimally invasive or open AO and AV clamping subgroups at any time point. In multivariate analysis, the R.E.N.A.L score (AO group p?=?0.026, AV group p?<?0.001) and preoperative eGFR (AO group p?<?0.001, AV group p?=?0.010) were strong predictors of the acute kidney injury in both groups. Older age (AO group p?=?0.045, AV group p?=?0.010) and preoperative eGFR (AO group p?=?0.008, AV group p?=?0.002) were significantly associated with CKD progression at 2-year follow-up in both groups.

Conclusion

AV clamping does not adversely affect postoperative renal function compared to AO clamping. Preoperative patient- and tumor-related factors are more important for renal function regardless of the clamping technique.

     

Assessment of changes in penile sensation by electrophysiological study after radical prostatectomy: A pilot study

Background:To evaluate the changes in penile sensation by electrophysiological tests in patients who underwent radical prostatectomy (RP) and to demonstrate the role of dorsal penile nerve injury in postoperative erectile dysfunction.Materials and methods:Twenty-six volunteer patients who were eligible for RP were included in the study. Preoperative penile sensory electromyography and the International Index of Erectile Function-5 (IIEF-5) questionnaire were done for each patient. Erectile function assessment and electrophysiological evaluation of penile sensation were repeated at postoperative 3rd and 6th months.Results:Postoperative IIEF-5 scores and electromyography values were significantly lower than preoperative findings (p < 0.05). The IIEF-5 scores in the nerve sparing-RP (NS-RP) group were significantly higher than the non-nerve sparing-RP (NNS-RP) group in the postoperative period. Nerve conduction velocity values in the NS-RP group were also higher than the NNS-RP group at the postoperative 3rd and 6th months. However, these changes were not statistically significant (p > 0.05).Conclusions:Patients who underwent RP have decreased penile sensation due to cavernous nerve damage and a possible dorsal penile nerve injury. The decrease of penile sensation may be associated with postoperative erectile dysfunction.     

Relationship of ambulatory blood pressure monitoring data to echocardiographic findings in haemodialysis patients

BACKGROUND: The present study was performed to assess the value of ambulatoryblood pressure monitoring (ABPM) in determining the adequacyof blood pressure (BP) control, and its relationship to echocardiographicfindings in haemodialysis (HD) patients. METHODS: We studied 40 non-diabetic adult patients who had been on regularHD treatment for a median duration of 43 months. Twenty-four-hourABPM was performed using a non-invasive ABP monitor (Pressurescan,ERKA). Casual BP (cBP) was defined as the average of two measurementsobtained at two HD sessions, one preceding and one followingthe ABP recordings, and was calculated for both the predialysisand postdialysis phases. Two-dimensional and M-mode echocardiographywere performed in each patient to determine interventricularseptal thickness (IVS), left ventricular posterior wall thickness(LVPW), left ventricular fractional shortening (FS), and leftventricular mass index (LVMI) RESULTS: According to average 24-h BP levels, 50% of the patients hadsystolic hypertension (HT) (>139 mmHg), and 72.5% had diastolicHT (>87 mmHg), while only 25% had been diagnosed as HT bycBP measurements (P>0.01 and P>0.0001 respectively). Diurnalvariation in BP was not present in about 80% of the patients.Echocardiography was normal in only four patients (10%). LVMIand LV wall thickness were correlated to ABPM data better thanto cBP measurements. Using stepwise linear regression analysis,LVMI and FVS were positively correlated with systolic BP load(P> 0.0001 and P=0.0001 respectively), and LVPW was positivelycorrelated with night-time systolic BP level (P>0.001). CONCLUSIONS: ABPM is necessary to assess the adequacy of BP control, andis well correlated to end-organ damage of HT in HD patients.     

Effect of aluminum adjuvants on safety and immunogenicity of Haemophilus influenzae type b-CRM197 conjugate vaccine

OBJECTIVE: The present study was carried out to evaluate the safety and immunogenicity of the Haemophilus influenzae type b-CRM197 (Hib-CRM197) conjugate vaccine in relation to the change of adjuvant from aluminum hydroxide to aluminum phosphate (AlPO4). METHODS: The present study was a clinical phase II, observer-blind, randomized, multicenter, controlled study. Subjects were healthy infants aged 6-12 weeks, eligible for expanded program of immunization (EPI) routine vaccination and admitted to Hacettepe University Department of Social Pediatrics and Gülveren Health Center, Ankara. A total of 520 healthy infants were randomized in a 2:2:1 ratio to receive at either Chiron Hib/AlPO4 vaccine or VaxemHib (aluminum hydroxide adjuvant) vaccine or HibTiter (no adjuvant). Vaccines were administered simultaneously with routine diphtheria, tetanus and pertussis (DTaP) and oral polio vaccine (OPV) vaccines at 2, 4 and 6 months of age. Blood samples for anti-plain polysaccharide (PRP) antibody measurement were collected before the first vaccination and 1 month after the last vaccination. After each vaccination parents filled out a diary for 7 days. RESULTS: Out of 520 subjects enrolled, 514 received three doses and were included for safety analysis. Local and systemic reactions occurred with low and similar frequencies in all groups. Only erythema was more common in Chiron Hib/AlPO4 vaccine (19, 10, 11% in Chiron Hib/AlPO4, VaxemHib and HibTiter, respectively, P < 0.05). Nine serious adverse events were reported in seven cases of which none were related to vaccines. A total of 504 subjects were included in the immunogenicity analysis. The three vaccines were highly immunogenic and equivalent in terms of percentage of acquisition of long-term protective levels. The anti-PRP geometric mean titers were 9.9, 8.3 and 5.14 micro g/mL, respectively (P < 0.05). CONCLUSIONS: The use of aluminum compounds adjuvants in Hib-CRM197 conjugate vaccines does not impact the safety profile, while it does increase the magnitude of anti-PRP antibody titers.