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.

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.

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.

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.

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.

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).

Symptom control in advanced cancer.

Most important is the physician's attitude, energy, and skill focused toward helping the patient through the difficulties in the last weeks of life. Many causes of nausea, dyspnea, and other troublesome symptoms can be effectively treated, and pharmacologic palliation is nearly always possible. A multidisciplinary team (ie, hospice) can help the physician see the whole picture and needs the physician's input to effectively manage physical, psychosocial, and spiritual components of the situation. The physician who attends to his own physical, psychosocial, and spiritual needs will have the stamina and depth of insight to help his patients through these difficult days. They can then complete their lives in the place of their choosing with the comfort and support needed to finish business, address strained relationships, and open to the mysteries of life and death.

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.

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.

Loss of sigma binding sites in the CA1 area of the anterior hippocampus in Alzheimer's disease correlates with CA1 pyramidal cell loss.

The densities of [3H]1,3-di-o-tolylguanidine ([3H]DTG) binding to sigma binding sites in the CA1 stratum pyramidale region in 7 hippocampi affected by Alzheimer's disease, were compared with densities in 7 normal hippocampi. There was an average reduction of 26% in [3H]DTG binding in this area, which was correlated with an average 29% pyramidal cell loss in the same region. These results are consistent with experiments in animals indicating that sigma binding sites are preferentially associated with the somata of large cells.

Clinical epidemiology and classification of human oesophagostomiasis.

The intestinal helminth Oesophagostomum bifurcum is highly and focally endemic in northern Ghana and Togo, and its juveniles produce a nodular inflammatory response as they develop in the intestinal wall. This pathology can produce clinical symptoms. We report on 156 cases of oesophagostomiasis presenting in 1996-98 to Nalerigu hospital in northern Ghana. The disease accounted for 0.2% of the out-patient department new presentations (about 1 patient per week), and 1% (16) of the major acute surgical cases. Children aged 5-9 years were most commonly affected. Multinodular disease (13% of the cases) results from hundreds of pea-sized nodules within the colon wall and other intra-abdominal structures, and presents with general abdominal pain, persistent diarrhoea and weight loss. Dapaong tumour (87%) presents as an abdominal inflammatory mass often associated with fever. The 3-6-cm tumour is painful, well-delineated, smooth, spherical, 'wooden', periumbilical, and adhered to the abdominal wall. Cases most commonly presented during the late rains and early dry season. Diagnosis by ultrasound has reduced the need for exploratory surgery, and the ability to sonographically evaluate conservative treatment with albendazole has curtailed management by colectomy or incision and drainage.

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.

The role of pigs as transport hosts of the human helminths Oesophagostomum bifurcum and Necator americanus.

We conducted a study in an endemic area of both Oesophagostomum bifurcum and Necator americanus in northern Ghana to examine the possibility of pigs acting as transport hosts for these two human helminth species, due to the commonly observed coprophagic habits of pigs. Under controlled conditions four parasite-free pigs consumed fresh faeces from people heavily infected with both helminths, and faeces were subsequently collected from the rectum of the pigs from 5 to 50 h post-feeding. Four to five per cent of the O. bifurcum and N. americanus eggs fed to the pigs were viable and retrieved as third-stage larvae after coproculture of the pigs' faeces. We discuss the possible impact of the coprophagic habits of pigs as potential parasite transport hosts during different seasons in this area of West Africa.

Subcutaneous methadone in terminally ill patients: manageable local toxicity.

Methadone has been found to be useful in pain uncontrolled by large doses of conventional opioids such as hydromorphone and morphine. While the subcutaneous route is effective and may afford cost-savings over the intravenous route in patients unable to take oral medication, its utility for the administration of methadone may be hampered by local toxicity, specifically erythema and induration. To examine the issue of limiting toxicity, we analyzed our inpatient hospice experience in six consecutive patients who received subcutaneous methadone for severe cancer pain. We confirm the high incidence of local toxicity, but note that the severity is subject to considerable individual variation. Furthermore, toxicity is uniformly manageable by site rotation and the use of dexamethasone infused concurrently with the methadone. We recommend that the infusion of subcutaneous methadone should be considered in the appropriate patients who can be closely monitored.

Subcutaneous infusions for control of cancer symptoms.

Continuous subcutaneous infusions offer a safe, simple, effective alternative to intravenous or intramuscular injections when oral medications cannot be used. They are extremely useful for cancer patients suffering from pain, vomiting, seizures, and other symptoms. Hydromorphone or morphine may be combined with metoclopramide, methotrimeprazine, or haloperidol (in D5W only), in the same pump to control both pain and nausea. Seizures can be controlled by subcutaneous infusion of phenobarbital or midazolam. If proper doses are prescribed and skin irritation is watched for, they can be used safely in the patient's home.

Ability analysis of gender relevance and sex differences in cardiovascular response to behavioral challenge.

Cardiovascular effects of gender-specific ability perceptions (ability perceptions linked to one's identity as being female or male) were examined under different task conditions. In Study I, participants were led to believe that either men (masculine task) or women (feminine task) tend to do well on a memory task and then were provided the chance to avoid noise by attaining a low or high performance standard. As expected, sex differences in systolic blood pressure response during performance depended not only on task type but also on the degree of challenge. In Study 2, high standard effects were strengthened and extended through the use of an appetitive procedure and the inclusion of conditions in which the performance standard was extreme. Findings are discussed in terms of an interactional analysis of ability percepts, task demand, and cardiovascular responsivity.

Ultrasound diagnosis of oesophagostomiasis.

Human infection with Oesophagostomum bifurcum, a parasitic intestinal helminth, is endemic in parts of West Africa. Oesophagostomum bifurcum juveniles develop in the colonic wall, causing pus-filled granulomas. The pathology has two distinct forms. Multinodular oesophagostomiasis comprises hundreds of small nodules within a thickened, oedematous wall of the large intestine. Uninodular oesophagostomiasis, called the Dapaong tumour, presents as a painful 30-60 mm granulomatous mass in the abdominal wall or within the abdominal cavity. Diagnosis of oesophagostomiasis on clinical grounds alone is difficult. We describe cases illustrating the ultrasound appearance of these two presentations. Multinodular disease shows nodular "target" and "pseudokidney" colonic lesions. The Dapaong tumour is an echo-free ovoid lumen enveloped within a well defined poorly reflective wall.

Environmental enrichment for rhesus macaques: a cost-effective exercise cage.

Providing suitable and varied environmental enrichment opportunities for nonhuman primates is both challenging and expensive, requiring institutions to be innovative when planning an enrichment program. Equipment must be durable, nontoxic, easily sanitized and disinfected, and readily assembled or prepared by animal care personnel. We developed a portable exercise cage for singly housed macaques from pre-existing but outdated caging; our cage met the described requirements and was used in animal-holding rooms. Modifying existing caging for this purpose led to substantial cost savings. These cages have proved to be popular with animals and their affiliated research teams.

Health care in South Africa: the rights and responsibilities of the community.

Both community mobilisation and expert intervention are required for proper health care. All members of the South African Community have a right to justice, equity and participation in their health care system. Justice demands equal facilities for all, and in South Africa cannot be achieved without fundamental political change. Equity demands freedom from financial anxiety. Arguments for the further privatisation of health care in South Africa are immoral and unconvincing. Participation demands that a patient be actively involved in deciding the nature of health care rather than merely a 'consumer'. This requires both demythologising the medical profession and vesting power in the community. Practical steps towards these ends are suggested.