Varicella zoster virus-associated disease in adult kidney transplant recipients: incidence and risk-factor analysis

Abstract: Varicella zoster virus (VZV)-related disease, particularly herpes zoster, is a complication of organ transplantation due to long-term immunosuppression. We determined the incidence and risk factors for post-transplant VZV infection by retrospectively reviewing the medical records of a cohort of 612 adult renal transplant recipients transplanted at Mayo Clinic Rochester between October 1, 2001 and October 1, 2004. Thirty-seven subjects developed herpes zoster, corresponding to a follow-up time-adjusted incidence of 11.2% at 4 years post transplant. The incidence rate of zoster was relatively constant between 6 months and 4 years, yielding an average incidence of approximately 28 per 1000 person-years. The risk of developing post-transplant zoster increased with increasing age at transplant, with each decade conferring a 1.42-fold ( P =0.009) increase in risk of zoster development. Seronegativity at time of transplant conferred over 3 times the risk of development of post-transplant zoster (hazard ratio 3.4; P =0.04) compared with seropositivity. Adult kidney transplant recipients are at high risk for the development of post-transplant zoster.     

The efficiency of matching in case-control studies of risk-factor interactions

We have examined the relative efficiency of matching vs not matching on a binary exposure variable in a case-control study of its interaction with another binary exposure variable. Interaction is treated as a parameter measuring departure from multiplicativity. Efficiency is considered both in the presence and absence of other matching variables, the former case requiring use of matched-pair estimators. In most circumstances examined, matching on one variable led to a less efficient estimator of the interaction parameter. If both variables were related to disease, the only circumstance in which matching always improved efficiency was when the high-risk level of the matching variable was uncommon and not positively associated with the high-risk level of the other variable. Matching always appeared to harm efficiency when the high risk level of the matching variable was common. Other disadvantages of matching are that it precludes estimation of the main effect of the matching variable and fitting of non-multiplicative models, and increases the difficulty of control selection.     

Influence of frequency of stenting on acute and one-year follow-up results

BACKGROUND: There has been a continuous increase in the frequency of stenting, with recent reports suggesting performing stenting in all coronary angioplasty interventions. The aim of this retrospective investigation was to study the in-hospital and 1-year event rates of the most and the least avid stent user (both highly experienced) at our institution. METHODS: A total of 322 consecutive patients undergoing coronary angioplasty at our institution were retrospectively studied. Post-intervention CK, CK-MB and troponin T values and information of major in-hospital cardiac events were obtained from the charts. Events during a 1-year follow-up were collected. Comparisons were made between patients treated by the most generous (operator 1: 71% stenting) and the most frugal (operator 2: 49% stenting) stent user. RESULTS: The 2 groups were comparable. Post-intervention CK max (418+/- 744 versus 427+/- 1250; p = 0.33), CK-MB (105+/- 159 versus 239+/-263; p = 0.07) and troponin T (149+/-326 versus 282+/- 380; p = 0.3) values were similar in both groups. In-hospital (2% versus 1.8%; p = 1) and 1-year follow-up cardiac events (21% versus 18%; p = 0.58) between both groups were also comparable. CONCLUSIONS: Stenting is a useful tool for selected patients. However, a higher frequency of stenting does not beneficially influence in-hospital or 1-year cardiac events. These findings recommend provisional stenting rather then elective stenting.     

Influence of diabetes on endothelial cell response during sepsis

Aims/hypothesis  

Several endothelial pathways of cell adhesion, coagulation and vascular endothelial growth factor (VEGF) signalling are activated during sepsis. The objective of this analysis was to investigate the influence of diabetes on biomarkers of endothelial cell activation in sepsis.     

Influence of extracorporeal photopheresis on clinical and laboratory parameters in chronic graft-versus-host disease and analysis of predictors of response

We report 28 patients with advanced chronic graft-versus-host disease (cGVHD) treated with extracorporeal photopheresis (ECP). All had failed conventional immunosuppressive therapy. Of the patients, 27 had extensive cGVHD and 20 had more than 50% cutaneous surface area involvement. ECP was initiated approximately 2 years after onset of cGVHD and 3 years following allogeneic stem cell transplantation and administered fortnightly for 4 months and then monthly. Response was assessed using quantifiable disease measures, including skin score, liver function tests (LFTs), blood counts, and lung function tests. Regression analysis allowed assessment of any pretreatment clinical or laboratory parameters that predicted response. There were 25 patients who completed 3 months and 21 who completed 6 months of treatment. Systemic immunosuppression was stable or reduced in 86% of patients. There were 3 patients who died from cGVHD. After 6 months, median skin scores were 53% lower (P =.003) in sclerodermoid and lichenoid disease. Of 6 patients with mucosal ulceration, 3 improved. A nonsignificant improvement of LFTs occurred. We infer that ECP is effective even in patients with extensive cutaneous cGVHD of 2 years duration that is resistant to conventional therapy. Furthermore, both sclerodermoid and lichenoid subtypes responded. However, no baseline parameters predicted a favorable response to ECP, so patient selection must continue to be made on clinical grounds.     

Influence of cold stimulation on the normal pharyngeal swallow response

We examined the potential influence of cold stimulation of the anterior tonsillar pillars, before and after topical anesthesia, on the temporal linkage between the oral and pharyngeal components of the swallow. We hypothesized that if elicitation of the pharyngeal swallow were dependent upon stimulation of faucial mucosal receptors this response would be facilitated by cold tactile stimulation and inhibited by topical anesthesia. In 14 healthy volunteers undergoing simultaneous videoradiography and manometry we measured and compared regional transit and clearance times, and the timing of hyoid motion, upper esophageal sphincter relaxation, and opening within the swallow sequence. There was a significant, volume-dependent forward shift in timings of hyoid motion, upper esophageal sphincter (UES) relaxation profile, and opening which were influenced neither by cold stimulation nor topical anesthesia. Regional transit and clearance times and UES coordination were not influenced by cold stimulation. Pharyngeal clearance time was prolonged by tonsillar pillar anesthesia due to earlier arrival of the bolus head at this region (p=0.002). We conclude that the normal pharyngeal swallow response is neither facilitated nor inhibited by prior cold tactile stimulation or topical anesthesia to the tonsillar pillars, respectively. These observations do not support the hypothesis that elicitation of the pharyngeal swallow response is dependent upon stimulation of mucosal receptors in the tonsillar arches.     

Influence of prostaglandins on papillary blood flow and pressure-natriuretic response

The present study examined whether renal prostaglandins influence the pressure-natriuretic response by altering medullary hemodynamics or renal interstitial pressure. The diuretic and natriuretic responses to changes in renal perfusion pressure were compared in control rats (n = 15) and in rats receiving either meclofenamate (2 mg/kg, n = 9) or indomethacin (2 mg/kg, n = 4). In control rats, urine flow and sodium excretion increased from 10 +/- 2 to 118 +/- 10 microliters/min/g kidney wt and from 1.8 +/- 0.3 to 21.0 +/- 1.5 mueq/min/g kidney wt, respectively, when renal perfusion pressure was increased from 109 to 167 mm Hg. Urinary excretion of prostaglandin E2 and thromboxane B2 increased significantly by 152% and 190%, respectively. Meclofenamate lowered thromboxane B2 and prostaglandin E2 excretion and prevented the increase in eicosanoid excretion produced by elevations in perfusion pressure. The pressure-diuretic and pressure-natriuretic responses of rats given meclofenamate or indomethacin were approximately half of those observed in the control rats. Papillary blood flow increased 21% and renal interstitial pressure rose from 5.0 +/- 0.7 to 8.2 +/- 0.7 mm Hg in control rats when pressure was elevated from 100 to 150 mm Hg. Meclofenamate and indomethacin lowered papillary blood flow and renal interstitial pressure and blunted the increases in these values produced by elevations in perfusion pressure. These results support the view that renal prostaglandins modulate the pressure-natriuresis relation by altering renal medullary hemodynamics and suggest that an intact renal prostaglandin system is necessary for the full expression of the medullary hemodynamic and natriuretic responses to increases in renal perfusion pressure.     

Influence of prednisolone on gastric alkaline response in rat stomach

Exposure of the rat stomach for 10 min to 1 M NaCl produced an increase of luminal pH (alkaline response) with a concomitant reduction of the transmucosal potential difference (PD) and an increased generation of mucosal prostaglandins of E2 and 6-keto F1 alpha. Prednisolone (3-50 mg/kg), given subcutaneously 4 hr before exposure to 1 M NaCl, dose-dependently inhibited alkaline response without affecting the PD reduction, and at 50 mg/kg completely prevented the increased production of mucosal prostaglandins after exposure to 1 M NaCl. The inhibitory effect of prednisolone on alkaline response was significantly antagonized by pretreatment with 16,16-dimethyl prostaglandin E2 (16,16-dmPGE2) (3 micrograms/kg) or cycloheximide (1.5 mg/kg). A repeated administration of prednisolone (3-50 mg/kg), once daily for 4 days, produced gastric lesions dose-dependently. At 50 mg/kg, gastric lesions appeared after administration of this drug for more than 2 days, and the inhibition of alkaline response caused by 1 M NaCl became more potent as the days of treatment increased. Either 16,16-dmPGE2 (10-100 micrograms/kg) or cycloheximide (1 or 3 mg/kg), given daily in two divided doses for 4 days, dose-dependently inhibited formation of gastric lesions in response to prednisolone (50 mg/kg). These results indicate that prednisolone inhibits gastric alkaline response caused by 1 M NaCl by reducing generation of endogenous prostaglandins. The weakened self-defense mechanisms caused by prednisolone may be involved in the pathogenesis of steroid-induced gastric lesions.     

Influence of differential vascular remodeling on the coronary vasomotor response

OBJECTIVES: Arterial remodeling may increase or decrease the luminal encroachment of atherosclerotic plaques in the coronary circulation. However, the factors determining the nature and consequences of the remodeling process remain poorly characterized. The study aims were to assess whether the pattern of vascular remodeling influences the physical and vasomotor responses of the coronary arteries in vivo in man. METHODS: Coronary vessel area, distensibility and stiffness were determined in positively, negatively and non-remodeled arterial segments using intravascular ultrasound and Doppler flow measurement. Epicardial vasomotor responses were determined following intracoronary boluses of acetylcholine (10(-6) and 10(-4) M), adenosine (24-30 microg) and nitroglycerin (200 microg). RESULTS: Fifty-six coronary arterial segments were studied in 25 patients. In comparison to non- and positively remodeled segments, negatively remodeled segments had a higher stiffness index (67+/-16 vs. 33+/-5 and 38+/-8, respectively; P<0.02) and appeared to have lower compliance and distensibility (0.66+/-0.17 vs. 1.65+/-0.54 and 0.94+/-0.18/mmHg; P=NS). Non-remodeled segments had a greater change in vessel area with 10(-6) M acetylcholine (4.9+/-0.8%), compared to positively and negatively remodeled segments (0.6+/-1.8% and -4.9+/-1.8%, respectively, P<0.05). A significant degree of preservation of vasodilatation to 10(-6) M acetylcholine was evident in positively remodeled compared with negatively remodeled segments (P<0.05). Nitroglycerin caused greater vasodilatation in non-remodeled segments (7.2+/-3.8%) than either positively or negatively remodeled segments (4.7+/-0.9 and 3.7+/-0.6%, respectively, P<0.05). CONCLUSIONS: Vascular remodeling is an important and major determinant of local epicardial vasomotor responses. Both structural and functional abnormalities are associated with negative remodeling that may contribute to the adverse effects of such lesions.     

Association of coronary atherosclerosis detected by multislice computed tomography and traditional risk-factor assessment

Framingham risk score is an office-based tool used for long-term coronary heart disease risk stratification. Most acute coronary events occur in association with proximal nonobstructive atherosclerotic plaque. Multislice computed tomography detects both obstructive coronary artery disease (CAD) and proximal atherosclerotic plaque with high accuracy. The association of Framingham risk score with obstructive CAD and proximal atherosclerotic plaque was tested. Coronary multislice computed tomography was performed in 295 patients (61% men, mean age 54 +/- 13 years) without documented CAD referred for evaluation of cardiac symptoms. Framingham risk score was computed and patients were stratified according to 10-year risk (n = 213 [72%] low, n = 74 [25%] intermediate, and n = 8 [3%] high). Obstructive CAD was defined as > or =50% stenosis in > or =1 epicardial coronary artery. Proximal atherosclerotic plaque was defined as calcified or noncalcified plaque in the left main or proximal left anterior descending artery. In the low- and intermediate-Framingham risk score groups, there was a high frequency of proximal atherosclerotic plaque (44% and 75%) and obstructive CAD (16% and 34%), although both findings were more prevalent in the high-Framingham risk score group (63% for atherosclerotic plaque, 88% for obstructive CAD), respectively. Proximal atherosclerotic plaque was noncalcified in approximately 13 of patients. In women (n = 114) and younger (<55 years) patients (n = 148), most (93% and 91%, respectively) had a low Framingham risk score. There were 48 women and 51 younger patients with proximal atherosclerotic plaque, of whom only 40% (in each group) were on statin therapy. In conclusion, of patients with a low and intermediate Framingham risk score, a significant proportion had proximal atherosclerotic plaque or obstructive CAD.     

Long-term follow-up analysis after rituximab therapy in children with refractory symptomatic ITP: identification of factors predictive of a sustained response

We report the long-term follow-up (median 39·5 months) of 49 paediatric patients (33 females and 16 males) with refractory symptomatic immune thrombocytopenic purpura (ITP) treated with rituximab. The overall response rate was 69% (34/49 patients). Twenty-one responders had a platelet count >50 × 10⁹/l at a median 20·2 months from treatment. Kaplan–Meier analysis showed a probability of relapse-free survival (RFS) of 60% at 36 months from the first rituximab infusion. The number of infusions and a previous splenectomy did not influence overall response rate. Patients who achieved complete response were significantly older at diagnosis and first rituximab infusion than partial responders ( P  = 0·027). Older children displayed a significantly greater probability of sustained response (RFS) at 36 months than younger children (88·9% vs. 56·7%, P  = 0·037). Earlier responses (within 20 d from treatment) were significantly associated with both complete ( P  = 0·004) and sustained response ( P  = 0·002). Only mild and transient side-effects were observed in 9/49 children; no major infections nor delayed toxicities were recorded during the follow-up.     

Influence of follow-up on health-related quality of life after radical surgery for colorectal cancer.

BACKGROUND: The possible benefit for patients of follow-up examinations after curative surgery for colorectal cancer is at present not proven. The purpose of this study was to evaluate the influence of follow-up examinations on health-related quality of life and to assess the attitude of the patients to check-ups. METHODS: A total of 350 patients who had had curative surgery for colorectal cancer and who had been subsequently randomized to either frequent follow-up or virtually no follow-up completed the Nottingham Health Profile and a second questionnaire assessing their attitude to the follow-up visits. RESULTS: The patients who were receiving more frequent follow-up had greater confidence in the check-ups, but the improvement in the health-related quality of life was only marginally better than that of those receiving few follow-up visits. CONCLUSION: The relatively small benefit for health-related quality of life does not justify expensive frequent routine examinations after surgery for colorectal cancer. The Nottingham Health Profile proved to be a reliable instrument within this patient group.     

Influence of cardiac-resynchronization therapy on heart rate and blood pressure variability: 1-year follow-up

BACKGROUND: Several studies have shown that cardiac-resynchronization therapy (CRT) improves haemodynamic function, cardiac symptoms, and heart rate variability (HRV) and reduces the risk of mortality and sudden death in subjects with chronic heart failure (CHF). In subjects with CHF, power spectral values for the low-frequency (LF) component of RR variability < or =13 ms2, are associated with an increased risk of sudden death. AIMS AND METHODS: To assess whether spectral indexes obtained by power spectral analysis of HRV and systolic blood pressure (SBP) variability could predict malignant ventricular arrhythmias in patients with severe CHF treated with an implantable cardioverter-defibrillator (ICD) alone or with ICD+CRT. In addition, changes in non-invasive spectral indices using short-term power spectral analysis of HRV and SBP variability during controlled breathing in 15 patients with CHF treated with an ICD alone and 16 patients receiving ICD+CRT, were assessed pre-treatment and at 1 year. RESULTS: Arrhythmias necessitating an appropriate ICD shock were more frequent in subjects who had low LF power. CRT improved all spectral components, including LF power. CONCLUSIONS: Low LF power values predict an increased risk of malignant ventricular arrhythmias; after 1 year of CRT most non-spectral and spectral data, including LF power, improved. Whether these improvements lead to better long-term survival in patients with CHF remains unclear.