Bronchiectasis is associated with delayed diagnosis and adverse outcomes in the New Zealand Common Variable Immunodeficiency Disorders cohort study.

Common variable immunodeficiency disorders (CVID) are multi-system disorders where target organ damage is mediated by infective, autoimmune and inflammatory processes. Bronchiectasis is probably the most common disabling complication of CVID. The risk factors for bronchiectasis in CVID patients are incompletely understood. The New Zealand CVID study (NZCS) is a nationwide longitudinal observational study of adults, which commenced in 2006. In this analysis, the prevalence and risk factors for bronchiectasis were examined in the NZCS. After informed consent, clinical and demographic data were obtained with an interviewer-assisted questionnaire. Linked electronic clinical records and laboratory results were also reviewed. Statistical methods were applied to determine if variables such as early-onset disease, delay in diagnosis and increased numbers of infections were associated with greater risk of bronchiectasis. One hundred and seven adult patients with a diagnosis of CVID are currently enrolled in the NZCS, comprising approximately 70% of patients known to have CVID in New Zealand. Fifty patients (46·7%) had radiologically proven bronchiectasis. This study has shown that patients with compared to those without bronchiectasis have an increased mortality at a younger age. CVID patients with bronchiectasis had a greater number of severe infections consequent to early-onset disease and delayed diagnosis. Indigenous Maori have a high prevalence of CVID and a much greater burden of bronchiectasis compared to New Zealand Europeans. Diagnostic latency has not improved during the study period. Exposure to large numbers of infections because of early-onset disease and delayed diagnosis was associated with an increased risk of bronchiectasis. Earlier diagnosis and treatment of CVID may reduce the risk of bronchiectasis and premature death in some patients.

MR Susceptibility Imaging with a Short TE (MR-SISET): A Clinically Feasible Technique to Resolve Thalamic Nuclei.

The thalamus consists of several functionally distinct nuclei, some of which serve as targets for functional neurosurgery. Visualization of such nuclei is a major challenge due to their low signal contrast on conventional imaging. We introduce MR susceptibility imaging with a short TE, leveraging susceptibility differences among thalamic nuclei, to automatically delineate 15 thalamic subregions. The technique has the potential to enable direct targeting of thalamic nuclei for functional neurosurgical guidance.

Pyrocarbon proximal interphalangeal joint arthroplasty: a medium to long term follow-up of a single surgeon series.

We retrospectively reviewed a consecutive single surgeon series of 57 Ascension pyrocarbon proximal interphalangeal joint arthroplasties, with a mean follow-up of 7.1 years (range 2 years to 11 years 6 months). We assessed the ranges of motion, deformity, stability and pain of the operated joints, grip strength of the hand and patient satisfaction. Of the cases, 44 were for osteoarthritis, five for rheumatoid arthritis and eight for post-traumatic arthritis. The median post-operative active arc of motion was from 0° to 60°. The median post-operative visual analogue pain score was 0.3 out of ten. Thirty six of the joints had no complications; 14 had minor complications (squeak, slight swan neck); three required early reoperation (joint release, flexor tenodesis); and five required implant removal. A total of 69% of our patients would have the same operation if they had to make the decision again. The Kaplan-Meier survival method estimates the mean implant survival to be 10.7 years (95% confidence intervals 9.96-11.37 years). All five failures occurred during the first 2 years.Level of evidence 4 (Case-series).

Wrist denervation in isolation: a prospective outcome study with patient selection by wrist blockade.

Surgical wrist denervation involves division of the anterior and posterior interosseous nerves and articular branches of the superficial radial nerve. In this outcome study, 37 patients were individually assessed and deemed suitable for denervation surgery due to appreciable symptom resolution following a local anesthetic wrist block. At a mean of 18 months following denervation surgery, median activity pain scores had decreased by 60% (p < 0.001) from initial assessment levels, and more than three quarters (30/37) of patients reported continued improvement in their activity pain (p < 0.001). More than two thirds of patients had a satisfaction VAS of greater than 50, with less postoperative resting pain and a greater reduction in postoperative activity pain as the important predictors of patient satisfaction. Thirty-one out of the 37 patients had not represented to our department for revision wrist surgery by a mean of 10.3 years follow-up. We have found this procedure useful in ameliorating symptoms for some patients who would conventionally have required partial or total wrist fusions with greater residual functional limitation.

Robust correction of spike noise: application to diffusion tensor imaging.

Echo-planar imaging (EPI) -based diffusion tensor imaging (DTI) is particularly prone to spike noise. However, existing spike noise correction methods are impractical for corrupted DTI data because the methods correct the complex MRI signal, which is not usually stored on clinical MRI systems. The present work describes a novel Outlier Detection De-spiking technique (ODD) that consists of three steps: detection, localization, and correction. Using automated outlier detection schemes, ODD exploits the data redundancy available in DTI data sets that are acquired with a minimum of six different diffusion-weighted images (DWIs) with similar signal and noise properties. A mathematical formulation, describing the effects of spike noise on magnitude images, yields appropriate measures for an outlier detection scheme used for spike detection while a normalization-dependent outlier detection scheme is used for spike localization. ODD performs accurately on diverse DTI data sets corrupted by spike noise and can be used for automated control of DTI data quality. ODD can also be extended to other MRI applications with data redundancy, such as dynamic imaging and functional MRI.

Whole brain and localized magnetization transfer measurements are associated with cognitive impairment in patients infected with human immunodeficiency virus.

BACKGROUND AND PURPOSE: Patients infected with human immunodeficiency virus (HIV) are susceptible to cognitive deterioration. This study investigated the utility of magnetization transfer (MT) imaging for quantification of brain tissue alterations associated with cognitive deficits in patients with HIV. MATERIALS AND METHODS: MT ratios (MTR) were derived for whole brain and for regions of interest (ROIs) in the basal ganglia and white matter in 11 HIV and 12 control subjects. Relationships with severity of cognitive impairment and specific neuropsychological deficits were also evaluated. RESULTS: MTR values for normalized whole brain histogram peak height, whole brain histogram mean, and all examined ROIs were reduced in the HIV subjects. Normalized histogram peak height and mean for whole brain, as well as means for the corpus callosum, basal ganglia, and frontal white matter (FWM), were significantly correlated with severity of cognitive impairment. MTR values for white matter regions (corpus callosum, FWM, and centrum semiovale) were correlated with specific cognitive deficits. CONCLUSION: Quantitative MTR measurements, determined for the whole brain and for vulnerable ROIs, are sensitive to neuropathologic changes associated with cognitive impairment in HIV-infected patients.

A second RGD motif in the 1D capsid protein of a SAT1 type foot-and-mouth disease virus field isolate is not essential for attachment to target cells.

The amino acid sequence motif Arg-Gly-Asp (RGD), located in the surface-exposed betaG-betaH loop of the 1D protein of different serotypes and subtypes of foot-and-mouth disease virus (FMDV), is highly conserved and participates in binding of FMDV to susceptible cells. Previous sequence analyses of the 1D-encoding region of a FMDV serotype SAT1 field isolate from Namibia (NAM/307/98) indicated the presence of a second RGD motif upstream of the conserved betaG-betaH loop RGD. The role of these RGD sequences in virus infection was investigated by mutating the betaG-betaH loop RGD to a KGE tripeptide, using a genome-length infectious chimeric cDNA clone. Although the infectivity of the derived mutant viruses for baby hamster kidney cells (BHK-21) was lost, subsequent replacement of the KGE sequence with RGD in the mutant cDNA clone led to recovery of infectious viruses. Furthermore, viral RNA replication could be demonstrated with the genetically engineered mutant and non-mutant viruses. The presence of virus particles in the transfected cells could be also demonstrated by electron microscopy. These results demonstrate that, in contrast to the betaG-betaH loop RGD motif, the second RGD sequence in the capsid protein 1D of NAM/307/98 does not function as a ligand for receptor binding in BHK-21 cells.

Monocyte chemoattractant protein-1 correlates with subcortical brain injury in HIV infection.

Various biomarkers have been suggested as associative or predictive of HIV-associated neurocognitive impairment. Plasma levels of monocyte chemoattractant protein 1 (MCP-1), tumor necrosis factor alpha (TNF-alpha), and hematocrit were evaluated for relationships with diffusion tensor imaging measurements of centrum semiovale, caudate, and putamen. MCP-1 levels correlated with tissue status (mean diffusivity) in all examined regions. Plasma markers were also significantly correlated with anisotropy measurements in centrum semiovale (TNF-alpha) and putamen (hematocrit).

Single breath-hold T1 measurement using low flip angle TrueFISP.

A method for estimating T1 using a single breath-hold, segmented, inversion recovery prepared, true fast imaging with steady-state precession (sIR-TrueFISP) acquisition at low flip angle (FA) was implemented in this study. T1 values measured by sIR-TrueFISP technique in a Gd-DTPA-doped water phantom and the human brain and abdomen of healthy volunteers were compared with the results of the standard IR fast spin echo (FSE) technique. A good correlation between the two methods was observed (R2=0.999 in the phantom, and R2=0.943 in the brain and abdominal tissues). The T1 values of the tissues agreed well with published results. sIR-TrueFISP enables fast measurements of T1 to be obtained within a single breath-hold with good accuracy, which is particularly important for chest and abdominal imaging.

Bone marrow diffusion measures correlate with dementia severity in HIV patients.

BACKGROUND AND PURPOSE: Escalation in monocyte trafficking from the bone marrow into the brain may play a critical role in central nervous system injury and cognitive deterioration in patients with HIV infection. This study tested the hypothesis that the mean diffusivity is sensitive to marrow changes in HIV patients and that these quantitative imaging measurements correlate with the severity of dementia. METHODS: The mean diffusivity (MD), determined for clival and calvarial marrow regions, was compared in 11 HIV-infected patients and 9 control subjects. The imaging measurements were also evaluated for relationships with dementia severity and markers of disease progression (CD4 and viral load in plasma). RESULTS: The MD was significantly reduced in both clival and calvarial marrow in HIV-infected patients (P =.006). Diffusion measurements for clival (P =.02) and for calvarial (P =.03) regions were significantly correlated with the severity of dementia. CONCLUSION: The results of this investigation support the utility of diffusion strategies for monitoring the marrow and provide further evidence of a relationship between marrow status changes and neurologic progression in HIV patients.

Diffusion alterations in corpus callosum of patients with HIV.

BACKGROUND AND PURPOSE: Diffusion alterations have been identified in the corpus callosum and frontal white matter of patients infected with human immunodeficiency virus (HIV), though the relevance of these findings to cognitive deterioration has not yet been determined. This study tested the hypothesis that diffusion tensor imaging can detect tissue status alterations in these regions in cognitively impaired patients infected with HIV and the acquired measurements correlate with the severity of cognitive impairment. METHODS: Fractional anisotropy (FA) and mean diffusivity (MD) were determined for corpus callosum (genu and splenium) and frontal white matter (FWM). The DTI measurements were compared in 11 HIV and 11 control participants. Patterns of relationship were examined with cognitive status measures from concurrent neurologic and neuropsychologic evaluations. RESULTS: FA values for the splenium were significantly reduced in the patients infected with HIV and correlated with dementia severity and deficits in motor speed. MD values for the splenium were significantly increased in the patients infected with HIV and correlated with deficits in motor speed. FA measurements were also significantly correlated with performance on visual memory (genu), visuoconstruction (FWM), and verbal memory (FWM) tasks. CONCLUSION: Diffusion abnormalities were identified in the splenium of the corpus callosum in patients infected with HIV, and these alterations were associated with dementia severity and motor speed losses. In vivo assessment of callosal integrity by using quantitative neuroimaging may have potential utility as a marker of brain injury in patients infected with HIV.

Disease burden in HIV-associated cognitive impairment: a study of whole-brain imaging measures.

OBJECTIVE: To study whole-brain MR measures derived from diffusion tensor imaging and magnetization transfer imaging (MTI) for the in vivo assessment of cumulative neuropathologic changes in HIV and to evaluate the quantitative imaging strategies with respect to cognitive status measures including the severity of dementia and the degree of impairment in specific cognitive domains including attention, memory, constructional abilities, and motor speed. METHODS: Quantitative whole-brain measurements, including fractional anisotropy (FA), apparent diffusion coefficient (ADC), and magnetization transfer ratio (MTR), were derived from histograms and compared in HIV and control participants. Relationships between the MR and cognitive status measures were examined. RESULTS: Whole-brain FA and MTR were reduced in patients with HIV and correlated with dementia severity. Whole-brain MTR and ADC were correlated with psychomotor deficits. Evaluation of relationships between the studied MR measures indicated a correlation between ADC and MTR; FA was not correlated with either ADC or MTR. CONCLUSIONS: Findings from this investigation support the use of quantitative whole-brain MR measures for evaluation of disease burden in HIV. Reductions in whole-brain fractional anisotropy and magnetization transfer ratio (MTR) distinguished HIV and control subjects, and these measures were associated with dementia severity. Relationships were identified between whole-brain MTR and apparent diffusion coefficient and psychomotor deficits. Combining these quantitative strategies in neuroimaging examinations may provide more comprehensive information concerning ongoing changes in the brains of HIV patients.

T1 efficacy of EVP-ABD: a potential manganese-based MR contrast agent for hepatic vascular and tissue phase imaging.

PURPOSE: To evaluate the T1 efficacy of EVP-ABD, a new manganese (Mn)-based contrast agent, for vascular and liver tissue enhancement in comparison with currently approved agents. MATERIALS AND METHODS: Ten Yorkshire pigs (body weight, 26 -46 kg) were used for the efficacy evaluation, nine for kinetic T1 evaluation (three each agent) and one for post EVP-ABD imaging. With a fast imaging scheme to monitor T1 values of blood and liver, 10 micromol/kg EVP-ABD was injected intravenously and compared with gadopentetate dimeglumine (Magnevist, GdDTPA) and mangafodipir trisodium (Teslascan, mangafodipir trisodium) at routine clinical dosages. All were imaged with 3D T1 Gradient Recalled Echo (GRE) sequence (TR/TE/alpha = 3.8/1.6/25 degrees ) prior to and 10 minutes post injection using a 1.5-T whole-body scanner. Additional high-resolution 2D liver images (TR/TE/alpha = 50/4.6/40 degrees ) and arterial phase images of the upper aorta were acquired from the pig for post EVP-ABD imaging. RESULTS: At 10 micromol/kg, EVP-ABD provided a dramatic decline in blood T1, comparable to 0.1 mmol/kg GdDTPA, followed by a rapid return to blood baseline T1 values. In addition to the blood enhancement phase, EVP-ABD achieved a 70% reduction in liver T1 within 2 minutes postadministration, with an imaging window of at least 2 hours. A substantially improved signal-to-noise ratio (SNR) was observed in both the 2D and 3D liver images postcontrast. CONCLUSION: EVP-ABD demonstrated peak vascular enhancement similar to GdDTPA and prolonged specific liver enhancement exceeding mangafodipir trisodium. EVP-ABD has favorable T1 enhancing characteristics with the potential to allow for a comprehensive liver evaluation.

Intraobserver and interobserver variation of ultrasound diagnosis of Oesophagostomum bifurcum colon lesions.

Infection by the nematode Oesophagostomum bifurcum is focally distributed in Africa and causes a syndrome of abdominal pain, obstruction, or abdominal mass because of its predilection for invasion of colonic mucosa. To determine the reliability of ultrasound for the detection of colon pathology induced by this parasite, three studies to assess the intraobserver and interobserver variation of the technique were performed. In an area of northern Ghana endemic for O. bifurcum, 181 people from a low-prevalence village and 62 people from a high-prevalence village were examined twice by the same observer, and 111 people were independently examined by two observers in a moderately endemic village. The kappa statistics for the prevalence observations in the three studies were 0.82, 0.87, and 0.81, respectively, and kappa values for the intensity observations were 0.66, 0.63, and 0.71, respectively. The upper 95% confidence intervals of the average absolute difference in nodule size measurements in Study 1 and Study 3 were 3.6 and 4.5 mm, respectively. Therefore, ultrasound is useful in the diagnosis and management of O. bifurcum colon infection.

MR ventilation-perfusion imaging of human lung using oxygen-enhanced and arterial spin labeling techniques.

Magnetic resonance ventilation-perfusion (V/Q) imaging has been demonstrated using oxygen and arterial spin labeling techniques. Inhaled oxygen is used as a paramagnetic contrast agent in ventilation imaging using a multiple inversion recovery (MIR) approach. Pulmonary perfusion imaging is conducted using a flow-sensitive alternating inversion recovery with an extra radiofrequency pulse (FAIRER) technique. A half Fourier single-short turbo spin echo (HASTE) sequence is used for data acquisition in both techniques. V/Q imaging was performed in ten of the twenty volunteers, while either ventilation or perfusion was imaged in the other ten. This V/Q imaging scheme is completely noninvasive, does not involve ionized radiation, and shows promising potential for clinical use in the diagnosis of lung diseases such as pulmonary embolism.

Human oesophagostomiasis: a histomorphometric study of 13 new cases in northern Ghana.

Oesophagostomiasis is an infrequently described and recognised parasitic infection in humans, caused by Oesophagostomum bifurcum. Although the disease is most often found in the northern part of Togo and the neighbouring part of Ghana, sporadic cases have been described in other parts of Africa and in Asia and South America: Uganda, Ivory Coast, Sudan, Kenya, Ethiopia, Indonesia, Malaysia and Brazil. Infection probably occurs by way of the ingestion of L3 larvae. These larvae penetrate the intestinal wall, especially that of the colon. Some of these larvae develop into young adult worms and return to the bowel lumen. Other larvae, however, develop into immature worms, which fail to settle in the lumen, forming abscesses in the bowel wall and causing pathology. In the literature 105 human cases have been described, many originating in the northern regions of Ghana and Togo. The present study was performed to evaluate 13 new cases originating in the northern part of Ghana (7 female and 6 male patients, aged between 2 and 60 years). Histopathologically, the patients could be divided into two groups: the first group showed multinodular disease, while patients in the second group presented with a single, nodular mass. In the first group, abscesses were seen throughout the colonic wall. The mean size of the cavities was 4.3+/-0.7 mm. There was no relation between the size and the localisation in the colonic wall. Abscesses were significantly larger in male patients than in female patients. There was no correlation with age. In the second group, histopathological examination showed a cyst of variable wall thickness with very limited inflammation. These cysts represented older lesions, often encapsulated in the mesentery. In conclusion, in this study we present 13 new cases of human oesophagostomiasis. The abscess formation was found to be organ specific, independent of age, and gender-related, producing a more intense tissue reaction in male patients.

Natural progression of Oesophagostomum bifurcum pathology and infection in a rural community of northern Ghana.

An estimated 250,000 people in northern Ghana and Togo are infected with the intestinal helminth parasite Oesophagostomum bifurcum, as detected by stool cultures. Clinical disease caused by O. bifurcum is responsible for about 50 cases per year at the region's central hospital, and presents as painful abdominal masses: inflammatory colonic nodules containing live juvenile stages of the helminth. In individuals living in villages highly endemic with O. bifurcum infection, colonic pathology visible by ultrasound is also highly prevalent. These nodules also contain O. bifurcum juvenile worms but are apparently asymptomatic. Thus, O. bifurcum infection and asymptomatic colonic pathology are highly prevalent within this area, but clinical disease is relatively uncommon. The natural evolution and regression of the colonic pathology in an endemic community in northern Ghana and its distribution within the population is described. Of the 299 individuals in the study group, 28% had colonic pathology at recruitment in the late-rainy season, which decreased with a half-life of 3-4 months during the dry season. Of those negative at recruitment, 28% developed nodules during the year, the majority appearing at the end of the subsequent rainy season. Children tended to have a higher prevalence and intensity of ultrasound-visible pathology compared to adults. Almost half (49%) of the study group had colonic nodules at least once during the year, and 2% of these individuals presented with clinical disease to the local hospital during the mid-rainy season.

Spiritual care at the end of life.

An essential part of end-of-life medical care, spiritual care allows physicians to recognize problems like meaninglessness, anguish, and hopelessness, for which effective interventions are available. This form of care can be a deeply rewarding area of medical practice.

Ultrasonographic detection and assessment of preclinical oesophagostomum bifurcum-induced colonic pathology.

In northern Ghana and Togo, Oesophagostomum bifurcum infects an estimated 250,000 people, as determined by cultures of stool samples. The juvenile stages of the helminth develop within colonic wall nodules, causing Dapaong tumor or multinodular disease, at the rate of 1 case per week at Nalerigu Hospital in Ghana. Our aim was to discover whether suspected colonic-wall pathology is ultrasonographically visible in asymptomatic individuals living in the area where O. bifurcum is endemic. A total of 464 persons from 3 villages, ranging from highly infected to noninfected, were examined with ultrasonography. Anechogenic colonic lesions with posterior wall enhancement were observed in 71 (54.2%) of 131 and 57 (24.5%) of 233 persons from the villages of endemicity, and no lesions were seen in persons from the village outside the area of endemicity. We describe the lesions noted in this study as nodules caused by O. bifurcum, on the basis of their association at a population level with prevalence of larvae in stools, their expected ultrasonographic appearance and distribution (on the basis of our surgical experience with oesophagostomiasis), and the lack of a convincing differential diagnosis.