Community based multi-disease health screening as an opportunity for early detection of HIV cases and linking them to care.

BACKGROUND: The 95-95-95 UNAIDS global strategy was adapted to end the AIDS epidemic by 2030. The target is based on the premise that early detection of HIV-infected persons and linking them to treatment regardless of their CD4 counts will lead to sustained viral suppression. HIV testing strategies to increase uptake of testing in Western and Central Africa remain inadequate. Hence, a high proportion of people living with HIV in this region do not know their status. This report describes the implementation of a community based multi-disease health screening (also known as "Know Your Status" -KYS), as part of basic science research, in a way that contributed to achieving public health goals. METHODS: A community based multi-disease health screening was conducted in 7 communities within the Eastern region of Ghana between November 2017 and April 2018, to recruit and match HIV seronegative persons to HIV seropositive persons in a case-control HIV gut microbiota study. Health assessments included blood pressure, body mass index, blood sugar, Hepatitis B virus, syphilis, and HIV testing for those who consented. HIV seronegative participants who consented were consecutively enrolled in an ongoing HIV gut microbiota case-control study. Descriptive statistics (percentages) were used to analyze data. RESULTS: Out of 738 people screened during the exercise, 700 consented to HIV testing and 23 (3%) were HIV positive. Hepatitis B virus infection was detected in 4% (33/738) and Syphilis in 2% (17/738). Co-infection of HIV and HBV was detected in 4 persons. The HIV prevalence of 3% found in these communities is higher than both the national prevalence of 1.7% and the Eastern Regional prevalence of 2.7 in 2018. CONCLUSION: Community based multi-disease health screening, such as the one undertaken in our study could be critical for identifying HIV infected persons from the community and linking them to care. In the case of HIV, it will greatly contribute to achieving the first two 95s and working towards ending AIDS by 2030.

Surveillance of Patients with Metal-on-Metal Hip Resurfacing and Total Hip Prostheses: A Prospective Cohort Study to Investigate the Relationship Between Blood Metal Ion Levels and Implant Failure.

BACKGROUND: We designed a prospective, single-center study to assess whether blood metal ion levels could predict implant failure in patients managed with unilateral metal-on-metal hip resurfacing or total hip arthroplasty. METHODS: Five hundred and ninety-seven patients who had received unilateral Articular Surface Replacement prostheses at least twelve months earlier were recruited. Blood metal ion levels were compared between the group of patients with failed implants and the group with non-failed implants. Implant failure was defined as prostheses associated with revision, an intention to revise, or poor patient-reported hip function (Oxford Hip Score, <31 of 48). Specificity, sensitivity, area under the curve, positive and negative predictive values, and odds ratios were calculated. Logistic regression analysis was used to identify other risk factors for implant failure. RESULTS: Patients with failed arthroplasty had significantly higher blood cobalt and chromium ion levels than did patients with non-failed arthroplasty (p < 0.01). Blood cobalt ion levels were disproportionately raised in patients with failed total hip arthroplasty (8.2 µg/L) compared with patients with failed hip resurfacing (2.5 µg/L) (p = 0.018). Blood chromium ion levels were not significantly different in patients with failed total hip arthroplasty and failed hip resurfacing (p = 0.058). The maximum value of either metal ion had good discriminant ability to predict implant failure (area under the curve, 0.76). A 7-µg/L cutoff had a positive predictive value of 0.75 (95% confidence interval, 0.66 to 0.82) and a negative predictive value of 0.82 (95% confidence interval, 0.78 to 0.86). In patients managed with total hip arthroplasty, for each increase of 1 µg/L there was a 23% (p < 0.001) increase in the odds of them being in the failed group. For patients managed with hip resurfacing, the increase in odds was 5% (p < 0.001). CONCLUSIONS: Raised levels of blood metal ions were associated with failed metal-on-metal hip resurfacings and total hip arthroplasties. A threshold level of 7 µg/L had inadequate sensitivity to be used in isolation as a screening test for implant failure, but it provided nearly optimal misclassification rates. No level had a perfect positive predictive value, and so we discourage surgeons from performing revision surgery based on blood metal ion levels alone. Levels of cobalt ions were raised out of proportion to levels of chromium ions in failed total hip arthroplasty and may reflect a different mechanism for metal ion generation. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Sensitivity and specificity of blood cobalt and chromium metal ions for predicting failure of metal-on-metal hip replacement.

Blood metal ions have been widely used to investigate metal-on-metal hip replacements, but their ability to discriminate between well-functioning and failed hips is not known. The Medicines and Healthcare products Regulatory Agency (MHRA) has suggested a cut-off level of 7 parts per billion (ppb). We performed a pair-matched, case-control study to investigate the sensitivity and specificity of blood metal ion levels for diagnosing failure in 176 patients with a unilateral metal-on-metal hip replacement. We recruited 88 cases with a pre-revision, unexplained failed hip and an equal number of matching controls with a well-functioning hip. We investigated the 7 ppb cut-off level for the maximum of cobalt or chromium and determined optimal mathematical cut-off levels from receiver-operating characteristic curves. The 7 ppb cut-off level for the maximum of cobalt or chromium had a specificity of 89% and sensitivity 52% for detecting a pre-operative unexplained failed metal on metal hip replacement. The optimal cut-off level for the maximum of cobalt or chromium was 4.97 ppb and had sensitivity 63% and specificity 86%. Blood metal ions had good discriminant ability to separate failed from well-functioning hip replacements. The MHRA cut-off level of 7 ppb provides a specific test but has poor sensitivity.

An analysis of metal ion levels in the joint fluid of symptomatic patients with metal-on-metal hip replacements.

We retrospectively analysed concentrations of chromium and cobalt ions in samples of synovial fluid and whole blood taken from a group of 92 patients with failed current-generation metal-on-metal hip replacements. We applied acid oxidative digestion to our trace metal analysis protocol, which found significantly higher levels of metal ion concentrations in blood and synovial fluid than a non-digestive method. Patients were subcategorised by mode of failure as either 'unexplained pain' or 'defined causes'. Using this classification, chromium and cobalt ion levels were present over a wider range in synovial fluid and not as strongly correlated with blood ion levels as previously reported. There was no significant difference between metal ion concentrations and manufacturer of the implant, nor femoral head size below or above 50 mm. There was a moderately positive correlation between metal ion levels and acetabular component inclination angle as measured on three-dimensional CT imaging. Our results suggest that acid digestion of samples of synovial fluid samples is necessary to determine metal ion concentrations accurately so that meaningful comparisons can be made between studies.

The painful metal-on-metal hip resurfacing.

We carried out metal artefact-reduction MRI, three-dimensional CT measurement of the position of the component and inductively-coupled plasma mass spectrometry analysis of cobalt and chromium levels in whole blood on 26 patients with unexplained pain following metal-on-metal resurfacing arthroplasty. MRI showed periprosthetic lesions around 16 hips, with 14 collections of fluid and two soft-tissue masses. The lesions were seen in both men and women and in symptomatic and asymptomatic hips. Using three-dimensional CT, the median inclination of the acetabular component was found to be 55 degrees and its positioning was outside the Lewinnek safe zone in 13 of 16 cases. Using inductively-coupled plasma mass spectrometry, the levels of blood metal ions tended to be higher in painful compared with well-functioning metal-on-metal hips. These three clinically useful investigations can help to determine the cause of failure of the implant, predict the need for future revision and aid the choice of revision prostheses.

A novel mouse model of experimental asthma.

BACKGROUND: Animal models that mimic the pulmonary features observed in human asthma are important tools to study the mechanism(s) of allergen-induced asthma. Cockroach and dust mite allergens are two common allergens found in the 'inner city' environment. In this study, we examined the interaction between recombinant cockroach (r Bla g 2) and dust mite (r Der f 1) allergens in inbred mouse strain (A/J). The tested hypothesis was that there are enhanced effects of exposure to r Bla g 2 and r Der f 1 allergens in the airway inflammatory response in A/J mice. METHODS: Five groups of mice (male, 6-8 weeks) were examined: vehicle (saline) controls; adjuvant (alum) controls; r Bla g 2 immunized (0.01-10 microg/mouse), r Der f 1 immunized (0.01-10 microg/mouse), and combined immunization with r Der f 1 (0.05 microg/mouse) and r Bla g 2 (0.0 5 microg/mouse). Mice were immunized at days 0 and 7, challenged by oro-tracheal inhalation with r Der f 1 and/or r Bla g 2 allergen at day 14, and were studied and sacrificed on day 17. Airway hyperreactivity was measured by peak airway pressure and airway pressure time index (APTI). Differential cell analysis and total proteins in bronchoalveolar lavage returns were used to assess airway inflammation and epithelial injury. RESULTS: Dose-related statistically significant increases in peak pressure, APTI, total cells, eosinophils, epithelial cells, but not total proteins, were induced by r Bla g 2 challenge in r Bla g 2-immunized mice. Similar allergen-induced dose-related increases in airway total cells, eosinophils, epithelial cells and total proteins were observed in r Der f 1 immunized mice. Compared to either allergen alone, enhanced airway inflammation and epithelial damage, but not airway reactivity, were detected in the combined group. CONCLUSION: This novel mouse model will allow investigation of the immunopathogenesis of human asthma and should provide insight into the common form of 'inner city asthma'.

Experimental observations in the rat on the influence of cadmium on skin wound repair.

Wound healing in the skin depends upon the availability of appropriate trace metals as enzyme cofactors and structural components in tissue repair. The present study forms part of a series of experimental investigations to examine the influence of xenobiotic elements with no known nutritional function and which are known to compete with essential trace metals. It was designed to investigate further the importance of trace metals in wound healing as an aid to wound management and to identify mechanisms of nonhealing which constitute a major problem in human medicine. Surgically induced skin wounds in young adult male Wistar rats were exposed topically to 0.2 ml of 0.01, 0.10 or 1.0% cadmium chloride (aq.) daily for up to 10 days. Control wounds received de-ionized water only. Wounds exposed to cadmium chloride at 0.01 or 0.10% healed in a similar fashion to controls and exhibited a comparable histological profile with metallothionein distribution. Wounds receiving 1.0% cadmium chloride failed to heal or fully re-epithelialize within 7 days and animals were humanely killed. They showed a persistent mass of inflammatory cell infiltration, oedema, wound debris and aberrant epidermal cell growth. Metallothionein concentrations in the epidermis and fibroblasts of the papillary dermis increased greatly by 5 days postwounding and remained high through the observation period. Cadmium was identified in the liver, kidney and wound sites. In the wound, 1.0% cadmium chloride induced statistically significant (P > 0.001) changes in local concentrations of zinc and calcium at key stages in the healing process, and as a consequence disturbed the trace metal balance necessary for normal wound repair. Zinc levels were increased twofold after 7 days, but calcium was markedly reduced. Local changes in the distribution of metallothionein indicate interaction of cadmium and trace metal carrier proteins as a probable mechanism for impaired wound healing. The cytotoxicity of cadmium is considered to be largely responsible.

Self-surgery: removal of ankle surgical implants--A case report.

Self-surgery is rare, but numerous cases of self-mutilation are reported in the literature (eg, castration, enucleation of an eye, and amputation of a limb).[1] We have found no previous reports in the literature of a patient who has performed self-surgery to remove fracture fixation implants.

Impact of enhanced ultraviolet-B radiation on flower, pollen, and nectar production.

Intensified ultraviolet-B radiation or UV-B (wavelengths between 280 and 320 nm) can delay flowering and diminish lifetime flower production in a few plants. Here we studied the effects of enhanced UV-B on floral traits crucial to pollination and pollinator reproduction. We observed simultaneous flowering responses of a new crop plant, Limnanthes alba (Limnathaceae), and a wildflower, Phacelia campanularia (Hydrophyllaceae), to five lifetime UV-B dosages ranging between 2.74 and 15.93 kJ·m·d. Floral traits known to link plant pollination with bee host preference, host fidelity and larval development were measured. Intensified UV-B had no overall effect on nectar and pollen production of L. alba and P. campanularia flowers. A quadratic relationship between UV-B and nectar sugar production occurred in P. campanularia and showed that even subambient UV-B dosages can be deleterious for a floral trait. Other floral responses to UV-B were more dramatic and idiosyncratic. As UV-B dosage increased, L. alba plants were less likely to flower, but suffered no delays in flowering or reductions to lifetime flower production for those that did flower. Conversely, an equal proportion of P. campanularia plants flowered under all UV-B treatments, but these same plants experienced delayed onset to bloom and produced fewer flowers at greater UV-B intensities. Therefore, intensified UV-B elicits idiosyncratic responses in flowering phenology and flower production from these two annual plants. Diurnal patterns in nectar and pollen production strongly coincided with fluctuating humidity and only weakly with UV-B dosage. Overall, our results indicated that intensified UV-B can alter some flowering traits that impinge upon plant competition for pollinator services, as well as plant and pollinator reproductive success.

Human prostaglandin transporter gene (hPGT) is regulated by fluid mechanical stimuli in cultured endothelial cells and expressed in vascular endothelium in vivo.

BACKGROUND: biomechanical forces generated by blood flow within the cardiovascular system have been proposed as important modulators of regional endothelial phenotype and function. This process is thought to involve the regulation of vascular gene expression by physiological fluid mechanical stimuli such as fluid shear stresses. METHODS AND RESULTS: We demonstrate sustained upregulation of a recently identified gene encoding a human prostaglandin transporter (hPGT) in cultured human vascular endothelium exposed to a physiological fluid mechanical stimulus in vitro. This biomechanical induction is selective in that steady laminar shear stress is sufficient to upregulate the hPGT gene at the level of transcriptional activation, whereas a comparable level of turbulent shear stress (a nonphysiological stimulus) is not. Various biochemical stimuli, such as bacterial endotoxin and the inflammatory cytokines recombinant human interleukin 1beta cytokines (rhIL-1beta) and tumor necrosis factor-alpha (TNF-alpha), did not significantly induce hPGT. Using a specific antiserum to hPGT, we demonstrate endothelial expression within the arterial vasculature and the microcirculation of highly vascularized tissues such as the heart. CONCLUSIONS: Our results identify hPGT as an inducible gene in vascular endothelium and suggest that biomechanical stimuli generated by blood flow in vivo may be important determinants of hPGT expression. Furthermore, this demonstration of regulated endothelial expression of hPGT implicates this molecule in the regional metabolism of prostanoids within the cardiovascular system.

Metastasizing mixed tumor of the parotid gland: a rare tumor with unusually rapid progression in a cardiac transplant recipient.

We report the case of a 69-year-old man who had a mixed tumor (pleomorphic adenoma) removed from his parotid gland 3 years after orthotopic heart transplantation. Two years later, he presented with widely metastatic mixed tumor, which resulted in his death within 6 months. Metastatic mixed tumor is histologically identical to a benign mixed tumor, but it inexplicably metastasizes. Such tumors are rare and have not been reported to date in a transplant recipient. This case illustrates the rapid and aggressive course that malignancies can follow in an immunosuppressed population. Mixed tumors are common salivary neoplasms, so transplant recipients should be carefully followed after resection for evidence of metastatic spread.

Health needs of coronary artery bypass graft surgery patients at discharge.

Shortened hospital stays could potentially lead to unmet patient needs. This descriptive study utilizes critical pathway data and the Omaha System to identify the health needs of coronary artery bypass surgery patients at time of discharge. The most common health needs were education, sleep/rest and rehabilitation. Nursing implications relating to these health needs are also identified.

Broncholithiasis and thoracoabdominal actinomycosis from dropped gallstones.

We report a case of successfully managed invasive, thoracoabdominal actinomycosis caused by the intraperitoneal spillage of gallstones during laparoscopic cholecystectomy. The infected gallstones traversed the diaphragm, migrated into the lung parenchyma, and obstructed a segmental bronchus, causing pneumonia. Treatment involved retrieval of the obstructing stone, debridement and drainage of the pleuroperitoneal phlegmon/abscess, and intravenous antibiotics. The case illustrates the need to remove gallstones at the time of cholecystectomy.

A case of hyperzincemia with functional zinc depletion: a new disorder?

We report the case of an 1l-y-old boy with a plasma Zn concentration greater than 200 micromol/L, but with symptoms consistent with Zn deficiency. He has had hepatosplenomegaly, rashes, stunted growth (<3rd centile), anemia, and impaired immune function since infancy. He also has vasculitis and osteoporosis. A plasma Zn-binding protein has been separated and characterized by a combination of size exclusion and ion exchange chromatography and electrophoretic studies and by immunologic methods. Antibodies to the partially purified protein have been raised in rabbits. Size exclusion chromatography shows that Zn is bound to a protein with a mass 110000-300000 kD. Electrophoretic and mass spectrometry studies suggest that the protein may be composed of several subunits. One component of the isolated protein reacts with antiserum to alpha2-macroglobulin; immunoprecipitation studies confirm that the protein is not alpha2-macroglobulin or a histidine-rich glycoprotein. Kinetic studies of zinc metabolism in the patient and his mother with stable Zn isotopes show the presence of increased exchangeable Zn, with a rapid flux from plasma to a stable pool. Liver and muscle Zn and Cu concentrations are raised, but with no abnormal liver histology. Immunoreactive metallothionein in the liver is increased. We suggest that this boy may suffer from a previously unrecognized inborn error of Zn metabolism causing symptomatic zinc deficiency.

Dermal toxicity and percutaneous absorption of cadmium in rats and mice.

Cadmium is a common contaminant in sawdust and other materials used in laboratory animal bedding. This study was conducted to assess the irritancy of a soluble cadmium compound to the skin and percutaneous absorption of the cadmium ion. Cadmium chloride solution was administered to the shaved skin of the dorsum of rats and mice daily for 10 days at concentrations of 1.0, 0.1, and 0.01% (wt/vol). Cadmium accumulated in the skin in association with approximately 6,000 ng/g in animals exposed to the high dose. Skin damage of hyperkeratosis and acanthosis with some ulcerative change was dose-related. The mitotic index in mouse skin was increased up to twofold. In rat blood, concentrations of cadmium, after 10 days of administration of a 1% concentration, were 11.65 micrograms/L, indicating percutaneous absorption. Clear evidence was seen of an accumulation of cadmium in the liver (526 ng/g) and kidney (216 ng/g), but histopathologic evidence of damage was absent, after this period at least. Concentrations of zinc were increased in the skin, probably as a consequence of local increases in metallothionein, a zinc-binding protein.

Development of an enzyme-linked immunosorbent assay for human metallothionein-1 in plasma and urine.

The development of a sensitive enzyme-linked immunosorbent assay (ELISA) for human metallothionein-1 is reported. Metallothionein was purified from postmortem human liver and used to raise high-titer antibodies in rabbits. The assay was specific for human metallothionein-1 (MT-1), and there was no significant cross-reaction with human metallothionein-2. The detection limit (sensitivity) of the assay was 5 ng/ml, and the added MT-1 could be fully recovered from plasma and urine. The normal reference range for MT-1 was 32 +/- 16 ng/ml in plasma and 10 +/- 6 ng MT-1 per micromole of creatinine in random samples of urine. No significant differences were found between the values for males and females. The concentration of MT-1 was greatly increased between 24 and 48 hours after surgery, indicating that the protein behaves like an acute phase reactant in human subjects.

Early plasma protein and mineral changes after surgery: a two stage process.

Sequential changes in albumin, transferrin, alpha 1-acid glycoprotein, C reactive protein, fibrinogen, copper, iron, and zinc in plasma up to 24 h after hysterectomy were measured. No increases in the concentrations of the acute phase proteins alpha 1-acid glycoprotein, C reactive protein, and fibrinogen were observed until 6 h after the skin incision. These increases were preceded by significant falls at 2-4 h, and this was shown also by albumin, transferrin, iron, zinc, and copper. The ratios of iron and zinc to their binding proteins, transferrin and albumin, did not decrease until 4-6 h and their concentrations remained low for at least 24 h. These patterns suggest that at least two mechanisms operate after trauma. The early fall in the concentrations of the proteins in plasma is consistent with a prompt increase in microvascular permeability. The later decrease in binding of the metals iron and zinc to their transport proteins and the increase in concentrations of the acute phase proteins could be initiated by a common mediator.

Urinary iron loss in the nephrotic syndrome--an unusual cause of iron deficiency with a note on urinary copper losses.

Two patients with long-standing nephrotic syndrome are described in whom urinary iron losses may have contributed towards an iron deficiency state. Seven other nephrotic patients were also studied. Increased urinary iron excretion was found in six out of nine patients and increased urinary copper excretion in all eight patients in whom it was measured. Trace metal losses in the urine in nephrotics may be important clinically.

Acquired von Willebrand's disease: demonstration of a circulating inhibitor to the factor VIII complex in four cases.

We have studied four patients suffering from acquired von Willebrand's disease. All patients had a severe bleeding diathesis with recurrent life-threatening haemorrhages. Three of the patients had a monoclonal gammopathy and one of these developed multiple myeloma. In three patients tested, a plasma inhibitor to ristocetin cofactor activity was detected. In each case this was localized to the IgG fraction of plasma. In addition, VIII:C activity was found to be associated with the IgG fraction of patients' plasma and altered mobility of VIII:C was detected on Laurell immunoelectrophoresis. Furthermore, plasma from all four patients and the IgG fraction therefrom resulted in a dissociation of normal VIII:C into two components separable by gel-filtration on Sepharose 6B. Finally the circulating half-life of the three factor VIII activities was found to be markedly reduced in the patients with acquired von Willebrand's disease. We conclude that in the patients studied the coagulation defect was related to the presence of a circulating inhibitor to the factor VIII complex and that this inhibitor was associated with the IgG fraction of plasma.