Comparison of the precision of two standardized co-ordinate systems for the quantitation of brain anatomy: preliminary results

We assessed reproducible definition of two standardized co-ordinate systems for intersubject analysis of brain images. The baselines in the two co-ordinate systems were a modification of the canthomeatal (inCM) line and the anterior-posterior commissural )AC-PC) line. Axial spin-echo MR images of four subjects at 1.5T were used. Operator error was computed from the replicate analyses of two operators. The mCM line was determined by the lens of the eye and the internal auditory canal, and the AC-PC line was determined by the intersection of the AC and PC with the interhemispheric fissure. Reproducibility of the mCM markers (SD=0.59 mm) did not differ significantly from that of the AC-PC line (SD=0.68 mm). The measurement error of the angle of the baseline (), however, was more than 7 times as large for the AC-PC line as for the mCM line. An additional error affecting the rostrocaudal rotation of the co-ordinate systems, attributable to the distance between the anatomic markers, was 2.1 and 3.6° (3 mm and 5 mm slice thickness) for the mCM co-ordinate system and 8.2 and 11.0° (3 mm and 5 mm slice thickness) for the AC-PC system. The AC-PC line based co-ordinate system is therefore, less reproducible than the mCM line based system. this could be improved if a combination of axial and sagittal images were used for the definition of the AC-PC line.     

Influenza A virus nucleoprotein is a major target antigen for cross-reactive anti-influenza A virus cytotoxic T lymphocytes.

Influenza A virus-specific cytotoxic T lymphocytes (CTL) capable of lysing cells infected with any influenza A virus ("cross-reactive CTL") constitute a major portion of the host CTL response to influenza. The viral nucleoprotein (NP), a major internal virion structural protein, has been implicated as a possible target antigen for cross-reactive CTL. To directly examine CTL recognition of NP, a vaccinia virus recombinant containing a DNA copy of an influenza A virus NP gene was constructed. We found that murine cells infected with this virus were efficiently lysed in a major histocompatibility complex-restricted manner by cross-reactive CTL populations obtained by immunization with a variety of influenza A virus subtypes. In addition, the recombinant vaccinia virus containing the PR8 NP gene was able to both stimulate and prime for a vigorous secondary cross-reactive CTL response. Significantly, splenocytes from mice primed by inoculation with the recombinant vaccinia virus containing the PR8 NP gene could be stimulated by influenza A viruses of all three major human subtypes. Finally, unlabeled target competition experiments suggest that NP is a major, but not the sole, viral target antigen recognized by cross-reactive CTL.     

Primary reversed gastric tube reconstruction in long gap esophageal atresia

Background/purpose

Esophageal reconstruction in long-gap esophageal atresia (EA) poses a technical challenge with several surgical options. The purpose of this study was to review the authors’ experience with the reversed gastric tube (RGT) in esophageal reconstruction.

Methods

This series describes 7 babies with pure EA treated at 2 centers between 1989 and 2001. Data, gathered by retrospective chart review, included clinical details of the esophageal and associated malformations, technique and timing of repair, early and late complications, and long-term follow-up. Institutional review board (IRB) approval of this study has been obtained.

Results

Seven babies were included. Associated malformations were present in 4: trisomy 21 in 2 and imperforate anus in 2. After gastrostomy tube placement, patients were treated with gastrostomy tube feedings and continuous upper pouch suction. Median gap length was 5.5 vertebral segments (range, 3 to 9). RGT with a posterior mediastinal esophagogastric anastomosis was performed at median age of 62 days (range, 38 to 131). There were no anastomotic leaks. Three patients had strictures, one required resection. Exclusive oral nourishment was achieved in 5 patients by 6 months of age. At last follow-up (mean, 4.5 years), 6 patients were receiving oral nutrition exclusively, and all were maintaining growth curves.

Conclusions

In long gap EA, early esophageal reconstruction using an RGT can be performed with minimal morbidity and promising short-term results.     

Comparison of patient and doctor responses to a total hip arthroplasty clinical evaluation questionnaire

BACKGROUND: Surgeons traditionally undertake a prospective evaluation of patients undergoing total hip arthroplasty in order to determine outcomes. The validity of doctor-derived data is questionable because of the potential for interobserver error, reporting bias, and differences between the perceptions of doctors and patients. Also, the use of doctor-derived data necessitates the use of costly outpatient services. Consequently, there are likely to be benefits associated with the use of patient-derived clinical evaluation data. However, few studies have focused on whether data obtained from the patient and doctor differ. METHODS: The agreement between patient and doctor responses on a sixteen-item total hip arthroplasty clinical evaluation questionnaire completed at more than 2900 clinical assessments was determined. Data from repeated assessments performed preoperatively and postoperatively enabled stratified analyses that were used to examine reasons for disagreement and factors influencing agreement. Agreement was measured with use of the kappa coefficient. RESULTS: For twelve of the sixteen items, the patient responses had acceptable agreement with the doctor responses. Some important differences between patient-derived and doctor-derived data were found. If the patient had other joint or health problems, had a revision total hip arthroplasty, or reported mild or moderate pain, there was a greater chance of reduced agreement on the pain items. Younger patients demonstrated better agreement with doctors than older patients did. CONCLUSIONS: Patients' perceptions of symptoms and outcomes after total hip arthroplasty are relatively similar to those of their doctor. There is minimum risk of misinterpreting outcomes data by replacing doctor-completed questionnaires with patient-completed questionnaires in uncomplicated total hip arthroplasty cases. For patients with comorbid joint problems or other health problems, and for those reporting substantial pain, direct physician involvement in the evaluation of pain is recommended. The selective use of patient-completed questionnaires has the potential to substantially reduce the costs of outcomes evaluation programs by minimizing doctor input. Pending revision of some of the items, the use of this patient-completed questionnaire is advocated.     

Sweet and simple as syrup: A review and guidance for use of novel antihyperglycemic agents for post-transplant diabetes mellitus and type 2 diabetes mellitus after kidney transplantation

Uncontrolled type 2 diabetes mellitus (T2DM) and post-transplant diabetes mellitus (PTDM) increase morbidity and mortality after kidney transplantation. Conventional strategies for diabetes management in this population include metformin, sulfonylureas, meglitinides and insulin. Limitations with these agents, as well as promising new antihyperglycemic agents, create a need and opportunity to explore additional options for transplant diabetes pharmacotherapy. Novel agents including sodium glucose co-transporter 2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP1RA), and dipeptidyl peptidase IV inhibitors (DPP4i) demonstrate great promise for T2DM management in the non-transplant population. Moreover, many of these agents possess renoprotective, cardiovascular, and/or weight loss benefits in addition to improved glucose control while having reduced risk of hypoglycemia compared with certain other conventional agents. This comprehensive review examines available literature evaluating the use of novel antihyperglycemic agents in kidney transplant recipients (KTR) with T2DM or PTDM. Formal grading of recommendations assessment, development, and evaluation (GRADE) system recommendations are provided to guide incorporation of these agents into post-transplant care. Available literature was evaluated to address the clinical questions of which agents provide greatest short- and long-term benefits, timing of novel antihyperglycemic therapy initiation after transplant, monitoring parameters for these antihyperglycemic agents, and concomitant antihyperglycemic agent and immunosuppression regimen management. Current experience with novel antihyperglycemic agents is primarily limited to single-center retrospective studies and case series. With ongoing use and increasing comfort, further and more robust research promises greater understanding of the role of these agents and place in therapy for kidney transplant recipients.     

Lower leg arterial calcification assessed by high-resolution peripheral quantitative computed tomography is associated with bone microstructure abnormalities in women

Summary

In older women, the presence of lower leg arterial calcification assessed by high-resolution peripheral quantitative computed tomography is associated with relevant bone microstructure abnormalities at the distal tibia and distal radius.

Introduction

Here, we report the relationships of bone geometry, volumetric bone mineral density (BMD) and bone microarchitecture with lower leg arterial calcification (LLAC) as assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT).

Methods

We utilized the Hertfordshire Cohort Study (HCS), where we were able to study associations between measures obtained from HR-pQCT of the distal radius and distal tibia in 341 participants with or without LLAC. Statistical analyses were performed separately for women and men. We used linear regression models to investigate the cross-sectional relationships between LLAC and bone parameters.

Results

The mean (SD) age of participants was 76.4 (2.6) and 76.1 (2.5)?years in women and men, respectively. One hundred and eleven of 341 participants (32.6 %) had LLAC that were visible and quantifiable by HR-pQCT. The prevalence of LLAC was higher in men than in women (46.4 % (n?=?83) vs. 17.3 % (n?=?28), p?<?0.001). After adjustment for confounding factors, we found that women with LLAC had substantially lower Ct.area (β?=??0.33, p?=?0.016), lower Tb.N (β?=??0.54, p?=?0.013) and higher Tb.Sp (β?=?0.54, p?=?0.012) at the distal tibia and lower Tb.Th (β?=??0.49, p?=?0.027) at the distal radius compared with participants without LLAC. Distal radial or tibial bone parameter analyses in men according to their LLAC status revealed no significant differences with the exception of Tb.N (β?=?0.27, p?=?0.035) at the distal tibia.

Conclusion

In the HCS, the presence of LLAC assessed by HR-pQCT was associated with relevant bone microstructure abnormalities in women. These findings need to be replicated and further research should study possible pathophysiological links between vascular calcification and osteoporosis.

     

A randomised, double-blind, parallel group study to compare subcutaneous interferon alpha-2a plus podophyllin with placebo plus podophyllin in the treatment of primary condylomata acuminata.

OBJECTIVES--The primary objective was to determine if six weeks treatment with subcutaneous interferon alpha-2a (IFN) and podophyllin 25% W/V administered twice per week, preceded by IFN alpha-2a three times weekly for one week showed a greater complete response rate in patients with primary condylomata acuminata when assessed at week 10 than treatment with podophyllin and placebo injections in the same schedule. The secondary objective was to compare recurrence rates in complete responders at six months in the two treatment groups. DESIGN--Randomised, double-blind parallel group study. SETTING--Multicentre study in six genitourinary clinics within the U.K. PATIENTS--One hundred and twenty-four patients with primary anogenital warts. MAIN OUTCOME MEASURES--Complete response rate at week 10, and recurrence rate at week 26 in complete responders. RESULTS--At week 10 analysis of the efficacy population showed complete response in 36% (15/42 patients) of IFN-treated group and 26% (11/43 patients) in the placebo group (no significant difference). Analysis of the safety population at week 26 showed persistence of the complete response in 57% (8/14 patients) of the IFN-treated group and 80% (12/15 patients) of the placebo group (no significant difference). Adverse effects were more common in IFN-treated patients, involved particularly application site reaction and malaise but were generally mild. CONCLUSIONS--At the dose and with the regime described treatment with IFN alpha-2a in combination with podophyllin is no more effective in the treatment of primary anogenital warts than podophyllin alone and is associated with more adverse events.     

Serum glucose and triglyceride determine high-risk subgroups in non-diabetic postinfarction patients

A strategy was developed to identify subgroups at high risk for recurrent coronary events in non-diabetic postinfarction patients as a function of metabolic, inflammatory, and thrombogenic blood markers. A graphical screening technique for presumptively identifying high-risk subgroups from outcome prevalence maps was devised that was equally sensitive for all values of risk factors in contrast to traditional approaches where risk is presumed for the highest or the lowest values. Traditional statistical analysis confirms high risk in identified subgroups. Serum glucose and triglyceride served as bivariate search domain. Results demonstrated three high-risk subgroups. One was characterized as pre-diabetic; another as metabolic syndrome-enriched; and the third, with unexpectedly high risk, as normoglycemic and modestly hypertriglyceridemic. Within-subgroup risk as determined by Cox proportional hazards model gave for odds ratios and 95 percentile confidence intervals: glucose, 2.49 (1.17-5.33) in pre-diabetic; PAI-1, 3.95 (1.81-8.61) in metabolic syndrome-enriched; and BMI, 2.79 (1.17-6.63) and fibrinogen, 2.79 (1.29-6.04) in normoglycemic, modestly hypertriglyceridemic patients. We conclude that the graphical approach holds promise in screening for high-risk patient subgroups. Finding different within-subgroup predictors of risk underscores the notion of context-dependent risk, an observation that may be relevant for determining optimal use of emerging risk factors.