Femoral Neck Fracture with Avascular Necrosis.

Hip fractures are common in the aging population, with complications such as avascular necrosis. We describe a case of an 85-y-old woman with early avascular necrosis as a complication from femoral neck fracture discovered on routine bone densitometry screening.

Gene and cell therapy in South Africa: Current status and future prospects.

South Africa has a high disease burden resulting from communicable and non-communicable diseases. Current therapeutic interventions rarely result in a cure and the associated lifelong treatment places a considerable strain on an overburdened health sector. Gene and cell therapies present novel alternatives to disease management, offering the promise of a single treatment and a lifelong cure. Although challenges remain, investment in the field has started to bear fruit, with a number of gene and cell therapeutics reaching the market in the past decade. To take full advantage of these developments, it is important that a proactive approach to nurturing appropriate human and material resources is adopted in the country.

Gene and cell therapy in South Africa: current status and future prospects

South Africa has a high disease burden resulting from communicable and non-communicable diseases. Current therapeutic interventions rarely result in a cure and the associated lifelong treatment places a considerable strain on an overburdened health sector. Gene and cell therapies present novel alternatives to disease management, offering the promise of a single treatment and a lifelong cure. Although challenges remain, investment in the field has started to bear fruit, with a number of gene and cell therapeutics reaching the market in the past decade. To take full advantage of these developments, it is important that a proactive approach to nurturing appropriate human and material resources is adopted in the country

Altered interoceptive activation before, during, and after aversive breathing load in women remitted from anorexia nervosa.

BACKGROUND: The neural mechanisms of anorexia nervosa (AN), a severe and chronic psychiatric illness, are still poorly understood. Altered body state processing, or interoception, has been documented in AN, and disturbances in aversive interoception may contribute to distorted body perception, extreme dietary restriction, and anxiety. As prior data implicate a potential mismatch between interoceptive expectation and experience in AN, we examined whether AN is associated with altered brain activation before, during, and after an unpleasant interoceptive state change. METHODS: Adult women remitted from AN (RAN; n = 17) and healthy control women (CW; n = 25) underwent functional magnetic resonance imaging during an inspiratory breathing load paradigm. RESULTS: During stimulus anticipation, the RAN group, relative to CW, showed reduced activation in right mid-insula. In contrast, during the aversive breathing load, the RAN group showed increased activation compared with CW in striatum and cingulate and prefrontal cortices (PFC). The RAN group also showed increased activation in PFC, bilateral insula, striatum, and amygdala after stimulus offset. Time course analyses indicated that RAN responses in interoceptive processing regions during breathing load increased more steeply than those of CW. Exploratory analyses revealed that hyperactivation after breathing load was associated with markers of past AN severity. CONCLUSIONS: Anticipatory deactivation with a subsequent exaggerated brain response during and after an aversive body state may contribute to difficulty predicting and adapting to internal state fluctuation. Because eating changes our interoceptive state, restriction may be one method of avoiding aversive, unpredictable internal change in AN.

The state of gene therapy research in Africa, its significance and implications for the future.

Gene therapy has made impressive recent progress and has potential for treating a wide range of diseases, many of which are important to Africa. However, as a result of lack of direct public funding and skilled personnel, direct research on gene therapy in Africa is currently limited and resources to support the endeavor are modest. A strength of the technology is that it is based on principles of rational design, and the tools of gene therapy are now highly versatile. For example gene silencing and gene editing may be used to disable viral genes for therapeutic purposes. Gene therapy may thus lead to cure from infections with HIV-1, hepatitis B virus and Ebola virus, which are of significant public health importance in Africa. Although enthusiasm for gene therapy is justified, significant challenges to implementing the technology remain. These include ensuring efficient delivery of therapeutic nucleic acids to target cells, limiting unintended effects, cost and complexity of treatment regimens. In addition, implementation of effective legislation that will govern gene therapy research will be a challenge. Nevertheless, it is an exciting prospect that gene therapy should soon reach the mainstream of medical management. Participation of African researchers in the exciting developments is currently limited, but their involvement is important to address health problems, develop capacity and enhance economic progress of the continent.

18F-FDG PET/CT Imaging of Primary Gastric Lymphoma.

Primary gastric lymphoma (PGL) accounts for less than 4% of gastric neoplasms. 18F-FDG PET with simultaneously acquired CT (18F-FDG PET/CT) allows for staging and differentiation from other gastric cancers. Rapid diagnosis and staging are important because chemotherapeutic response is generally favorable. We describe a case of an 83-y-old woman with stage II1 PGL. 18F-FDG PET/CT can be helpful to differentiate various gastric masses and is an important factor in the staging of PGL.

Ectopic Parathyroid Adenoma in the Carotid Sheath.

Primary hyperparathyroidism is predominantly caused by a single parathyroid adenoma. Knowledge of normal and ectopic locations of parathyroid glands is crucial to help guide surgeons who plan targeted unilateral parathyroidectomy to reduce surgical time and risk. We describe a female patient with clinical primary hyperparathyroidism who underwent a failed initial parathyroidectomy, with subsequent imaging localizing an ectopic parathyroid adenoma in the carotid sheath.

Enhanced Sensitivity of Gas Sensor Based on Poly(3-hexylthiophene) Thin-Film Transistors for Disease Diagnosis and Environment Monitoring.

Electronic devices based on organic thin-film transistors (OTFT) have the potential to supply the demand for portable and low-cost gadgets, mainly as sensors for in situ disease diagnosis and environment monitoring. For that reason, poly(3-hexylthiophene) (P3HT) as the active layer in the widely-used bottom-gate/bottom-contact OTFT structure was deposited over highly-doped silicon substrates covered with thermally-grown oxide to detect vapor-phase compounds. A ten-fold organochloride and ammonia sensitivity compared to bare sensors corroborated the application of this semiconducting polymer in sensors. Furthermore, P3HT TFTs presented approximately three-order higher normalized sensitivity than any chemical sensor addressed herein. The results demonstrate that while TFTs respond linearly at the lowest concentration values herein, chemical sensors present such an operating regime mostly above 2000 ppm. Simultaneous alteration of charge carrier mobility and threshold voltage is responsible for pushing the detection limit down to units of ppm of ammonia, as well as tens of ppm of alcohol or ketones. Nevertheless, P3HT transistors and chemical sensors could compose an electronic nose operated at room temperature for a wide range concentration evaluation (1-10,000 ppm) of gaseous analytes. Targeted analytes include not only biomarkers for diseases, such as uremia, cirrhosis, lung cancer and diabetes, but also gases for environment monitoring in food, cosmetic and microelectronics industries.

Bisphosphonate-associated atypical subtrochanteric femur fracture.

Bisphosphonates help prevent progressive bone mineralization loss and subsequent osteoporotic fractures. However, long-term bisphosphonate therapy paradoxically increases the risk of a unique injury called an atypical subtrochanteric femur fracture. Despite this, the benefits of bisphosphonates outweigh the risks, because far more pathologic fractures are prevented than induced. The early identification of atypical subtrochanteric femur fractures is important as there is high associated morbidity and mortality. We describe a case of a 76-y-old woman with a completed bisphosphonate-associated atypical subtrochanteric femur fracture.

Sustained inhibition of hepatitis B virus replication in vivo using RNAi-activating lentiviruses.

Chronic infection with hepatitis B virus (HBV) puts individuals at high risk for complicating cirrhosis and liver cancer, but available treatment to counter the virus rarely eliminates infection. Although harnessing RNA interference (RNAi) to silence HBV genes has shown the potential, achieving efficient and durable silencing of viral genes remains an important goal. Here we report on the propagation of lentiviral vectors (LVs) that successfully deliver HBV-targeting RNAi activators to liver cells. Mono- and tricistronic artificial primary microRNAs (pri-miRs) derived from pri-miR-31, placed under transcriptional control of the liver-specific modified murine transthyretin (mTTR) promoter, caused efficient inhibition of HBV replication markers. The tricistronic cassette was capable of silencing a mutant viral target and the effects were observed without disrupting the function of an endogenous miR (miR-16). The mTTR promoter stably expressed a reporter transgene in mouse livers over a study period of 1 year. Good silencing of HBV genes, without evidence of toxicity, was demonstrated following intravenous injection of LVs into neonatal HBV transgenic mice. Collectively, these data indicate that LVs may achieve sustained inhibition of HBV replication that is appealing for their therapeutic use.

Current controversies in the initial post-surgical radioactive iodine therapy for thyroid cancer: a narrative review.

Differentiated thyroid cancer (DTC) is the most common endocrine malignancy and the fifth most common cancer in women. DTC therapy requires a multimodal approach, including surgery, which is beyond the scope of this paper. However, for over 50 years, the post-operative management of the DTC post-thyroidectomy patient has included radioactive iodine (RAI) ablation and/or therapy. Before 2000, a typical RAI post-operative dose recommendation was 100 mCi for remnant ablation, 150 mCi for locoregional nodal disease, and 175-200 mCi for distant metastases. Recent recommendations have been made to decrease the dose in order to limit the perceived adverse effects of RAI including salivary gland dysfunction and inducing secondary primary malignancies. A significant controversy has thus arisen regarding the use of RAI, particularly in the management of the low-risk DTC patient. This debate includes the definition of the low-risk patient, RAI dose selection, and whether or not RAI is needed in all patients. To allow the reader to form an opinion regarding post-operative RAI therapy in DTC, a literature review of the risks and benefits is presented.

Appendicitis in adults with incidental midgut malrotation: CT findings.

AIM: To report the computed tomography (CT) findings of acute and complicated appendicitis in adults with incidental midgut malrotation. MATERIALS AND METHODS: The medical records and CT studies of eight patients with appendicitis and incidental midgut malrotation who presented to two medical centres between 1998 and 2009 were reviewed. RESULTS: All patients presented with 1-5 days of acute abdominal pain, which was diffuse in two, left-sided in two, lower abdominal in two, and in the right lower quadrant in two patients. The inflamed appendix was right-sided in three, left-sided in three, and in the midline in two patients. Three cases were complicated by a peri-appendicular abscess, and one patient also had a small bowel obstruction. All patients had a complete non-rotation with right-sided duodenum and jejunum, and left-sided colon. All eight patients had an abnormal superior mesenteric artery-superior mesenteric vein (SMA/SMV) relationship and a dysplastic uncinate process of the pancreas. Urgent surgery was performed in six patients and the remaining two were treated conservatively. CONCLUSION: Altered anatomy in malrotation affects the typical clinical and CT findings of acute appendicitis, therefore delaying diagnosis. When CT shows focal inflammation anywhere within the abdomen, along with an abnormal SMA/SMV relationship, the position of the caecum should be ascertained and acute appendicitis ruled out.

Nephrographic and pyelographic analysis of CT urography: differential diagnosis.

OBJECTIVE: The differential diagnosis of renal disease is extensive. The purpose of this article is to enable the reader to recognize and understand the abnormal nephrographic patterns encountered in practice. CONCLUSION: Recognizing the different nephrographic patterns on CT urography can be invaluable in understanding the morphologic and physiologic condition of the kidney and ultimately diagnosing the disease process.

Nephrographic and pyelographic analysis of CT urography: principles, patterns, and pathophysiology.

OBJECTIVE: Careful analysis of the nephrogram is an integral component of the evaluation of the kidneys during CT urography. This is a review of the anatomy and physiology required to produce a normal nephrogram, as well as the basic principles affecting the interpretation of the nephrogram. CONCLUSION: The eight abnormal nephrographic patterns will be illustrated and discussed. This review will enable the reader to recognize and understand the abnormal nephrographic patterns encountered in practice.

Orbital involvement in extranodal natural killer T cell lymphoma: an atypical case presentation and review of the literature.

PURPOSE: To report a rare case of extranodal NK/T cell lymphoma (NKTL) and to compare its features with those cases previously reported. DESIGN: Case report, observational and literature review. METHODS: Complete ophthalmologic examinations followed by excisional biopsy, histopathologic examination and therapy with radiation and chemotherapy. MAIN OUTCOME MEASURES: Evaluation of clinical presenting features and histopathologic diagnosis along with patient outcome. RESULTS: A 22 year old female presented as a referral with right orbital swelling, decreased vision and eye pain for 5 weeks. Subsequent orbital CT and multiple biopsies resulted in a diagnosis of extranodal natural killer (NK)/T cell lymphoma (NKTL). Despite continued chemotherapy and orbital radiation the patient expired within 3 months of diagnosis. To our knowledge, only 8 cases of orbital involvement without nasal mucosal involvement are reported in the literature, the majority in patients of male gender around the fifth decade. CONCLUSIONS: Here we present an atypical and aggressive case of extranodal NK/T cell lymphoma presenting in a 22 year old Caucasian female as orbital swelling without evidence of nasal mucosal involvement. It is important to distinguish NKTL from the more common benign lymphoproliferative lesions of the orbital adnexa as prognosis of these two clinical entities varies and timely diagnosis is key. The present case demonstrates that extranodal NKTL can occur in the orbit without evidence of the more common nasal mucosal presentations and should be included in the differential diagnosis of ocular adnexal lesions suspicious for a lymphoproliferative disorder and/or an inflammatory process.

Enlargement of the spleen as an incidental finding on CT in post-partum females with fever.

OBJECTIVE: The aim was to evaluate whether enlargement of the spleen on CT in a post-partum female with fever is a common phenomenon. METHODS: In this retrospective institutional review board-approved study, the spleen was measured by CT in 77 females (average age 30.7 years) examined for post-partum fever and a control group of 58 febrile females imaged for suspected appendicitis (average age 29.7 years). The splenic length, width and thickness were measured and used to calculate the splenic index. The measurements of both groups of patients were compared. The size of the spleen was assessed again in 12 of the 77 post-partum female who had a follow-up CT for unrelated reasons. Continuous variables were compared, by groups, using analysis of variance (ANOVA). ANOVA with repeated measures was used to evaluate changes over time. A p-value <0.05 was considered significant. RESULTS: The length, thickness and width of the spleen were significantly larger in the patients imaged after delivery compared with those in the control group (p<0.001 for all three comparisons). The mean splenic index was 686.6 cm(3) in the post-partum group and 408.1 cm(3) in the control group (p<0.001). The splenic dimensions and index were significantly smaller in the 12 post-partum females who had a follow-up study. CONCLUSION: An enlarged spleen in febrile females undergoing CT in the puerperium may reflect physiological changes occurring during pregnancy.

Mortality and utilisation of critical care resources amongst high-risk surgical patients in a large NHS trust.

Previous reports describe a population of non-cardiac surgical patients at high risk of complications and death. Outcomes are sub-optimal for such patients, perhaps in part related to inadequate provision or ineffective utilisation of critical care resources. In this study, data describing 26,051 in-patient non-cardiac surgical procedures performed in a large NHS Trust between April 2002 and March 2005 were extracted from local databases. Of these procedures, 2 414 (9.3%) were high risk with an overall mortality rate of 12.2% and a prolonged hospital stay (high-risk population median (IQR) 16 (9-30) days vs standard risk 3 (2-6) days). Mortality rates for specific procedures were consistent with UK averages. However, only 852 (35.3%) high-risk patients were admitted to a critical care unit at any stage after surgery. Of 294 high-risk patients who died, only 144 (49.0%) were admitted to a critical care unit at any time and only 75 (25.6%) of these deaths occurred within a critical care area. Mortality rates were high amongst patients discharged and readmitted to critical care (37.7%) and amongst those admitted to critical care following initial postoperative care on a standard ward (29.9%). These data suggest that the outcome of high-risk general surgical patients could be improved by adequate provision and more effective utilisation of critical care resources.

Bloodstream infection due to Acinetobacter spp: epidemiology, risk factors and impact of multi-drug resistance.

Acinetobacter spp. are increasingly reported as important causes of human infection. Many isolates exhibit multi-drug resistance, raising concerns over our ability to treat serious infections with these organisms. The impact of infection on clinical outcome as well as the importance of multi-drug resistance is poorly defined. A descriptive retrospective observational study was undertaken of all episodes of Acinetobacter bacteremia occurring in a UK tertiary care centre from 1998-2006. Demographics of infected patients, characteristics and antimicrobial susceptibility of infecting strains were recorded and the impact of antimicrobial therapy on all causes of 30-day mortality assessed. Three hundred ninety-nine episodes of Acinetobacter bacteremia were identified, with A. baumannii being the most frequently isolated species. Most episodes occurred in critical care and were associated with multidrug resistance, with carbapenem resistance rising from 0% in 1998 to 55% in 2006. Although bacteremia due to carbapenem-resistant Acinetobacter and a requirement for critical care were associated with a higher mortality, mortality was not reduced by the administration of appropriate empirical antimicrobial therapy. A prospective study is required to identify both the most effective intervention and those most likely to benefit from treatment.

The wandering spleen: CT findings and possible pitfalls in diagnosis.

AIM: To report the CT features of wandering spleen, a rare condition which can be incidentally detected as an abdominal or pelvic mass or can present with torsion, causing an acute abdomen. MATERIALS AND METHODS: The CT studies of seven patients, two children and five adults, with wandering spleen were reviewed. CT was performed urgently in three patients for acute abdomen, and electively in four. RESULTS: CT findings of wandering spleen included absence of the spleen in its normal position and a mass located elsewhere in the abdomen or pelvis, i.e. an ectopic spleen, enhancing homogeneously in four cases and failing partially or completely to enhance in the other three, indicating infarction. A "whirl" appearance representing the twisted splenic pedicle was seen in the three cases with torsion. Urgent splenectomy confirmed infarction secondary to torsion. CONCLUSION: The possible diagnosis of wandering spleen should be kept in mind when CT shows the spleen to be absent from its usual position and a mass is found elsewhere in the abdomen or pelvis. When, in addition, a "whirl" or partial or no enhancement of this mass are seen in a case presenting with acute abdomen, torsion of a wandering spleen is a likely diagnosis.