Hemorrhagic Herpes Simplex Virus Type 1 Nephritis: An Unusual Cause of Acute Allograft Dysfunction.

Interstitial nephritis due to viruses is well-described after solid organ transplantation. Viruses implicated include cytomegalovirus; BK polyomavirus; Epstein-Barr virus; and, less commonly, adenovirus. We describe a rare case of hemorrhagic allograft nephritis due to herpes simplex virus type 1 at 10 days after living donor kidney transplantation. The patient had a favorable outcome with intravenous acyclovir and reduction of immunosuppression.

Significance of predicted future liver remnant volume on liver failure risk after major hepatectomy: a case matched comparative study.

Introduction: Future liver remnant volume (FLRV), a risk factor for liver failure (PHLF) after major hepatectomy (MH), is not routinely measured. This study aimed to evaluate the association between FLRV and PHLF. Patients and methods: All patients undergoing MH (4 + segments) between 2011 and 2018 were identified from a prospectively maintained single-centre database. Perioperative data were collected for patients with PHLF, who were matched (1:2) with non-PHLF controls. FLRV and FLRV% (i.e., % of total liver volume) were calculated retrospectively from preoperative CT scans using Synapse-3D software, and compared between the PHLF and matched control groups. Results: Of 711 patients undergoing MH, PHLF occurred in 27 (3.8%), of whom 24 had preoperative CT scans available. These patients were matched to 48 non-PHLF controls, 98% of whom were classified as being at high risk of PHLF on preoperative risk scoring. FLRV% was significantly lower in the PHLF group, compared to matched controls (median: 28.7 vs. 35.2%, p = 0.010), with FLRV% < 30% in 58% and 29% of patients, respectively. Assessment of the ability of FLRV% to differentiate between PHLF and matched controls returned an area under the ROC curve of 0.69, and an optimal cut-off value of FLRV% < 31.5%, which yielded 79% sensitivity and 67% specificity. Conclusions: FLRV% is significantly predictive of PHLF after MH, with over half of patients with PHLF having FLRV% < 30%. In light of this, we propose that all patients should undergo risk stratification prior to MH, with the high risk patients additionally being assessed with CT volumetry.

Cellular Concentrations and Uniformity of Cell-Type Accumulation of Two Lea Proteins in Cotton Embryos.

The levels and cell-type distribution of late embryogenesis abundant (Lea) proteins D-7 and D-113 have been determined in mature cotton embryos by immunochemical methods. The two proteins were expressed in and purified from Escherichia coli and utilized for antibody production in rabbits. The antiserum to each protein was found to interact with all members of each protein family in cotton extracts by protein gel blotting. Using these antibodies in quantitative "rocket" immunoelectrophoreses, D-7 proteins were found to accumulate to ~8 x 1015 molecules per embryo, which is equivalent to ~109 molecules per "average cell." D-113 proteins accumulate to ~1016 molecules per embryo, which equates to ~1.3 x 109 molecules per average cell. These values calculate to concentrations of about 226 and 283 [mu]M, respectively, in the cell aqueous phase immediately prior to seed desiccation. In immunocytochemical studies using the fluorophor rhodamine linked to the secondary antibody, both proteins appeared to be evenly present in the cytosol of all cell types present in the embryo, including both cotyledon and axis epidermal cells. Thus, their function does not appear related to unique functions of specific cell or tissue types. The very high molar concentrations of the two proteins, coupled with their unusual predicted structure and their cytosol location, would seem to reduce the number of their conceivable functions.

Interventions to improve psychosocial well-being for children affected by HIV and AIDS: a systematic review.

In addition to its contribution to child mortality, HIV/AIDS has a substantial impact on the psychosocial well-being of children across the globe and particularly in sub-Saharan Africa. We conducted a systematic review of the literature in order to identify studies that assess the effectiveness of interventions developed to improve the psychosocial well-being of children affected by HIV/AIDS, published between January 2008 and February 2016. Studies that were eligible for the review included male and/or female children under the age of 18 years of age, who had lost a parent to HIV/AIDS, were living with a parent with HIV/AIDS, or were vulnerable because of other social and economic factors and living in communities of high HIV and AIDS prevalence, including child and caregiver reports. Studies were included if they documented any intervention to improve the psychosocial well-being of children including psychological therapy, psychosocial support and/or care, medical interventions and social interventions, with psychological and/or social factors as outcomes. We identified 17 interventions to improve the psychosocial well-being of children affected by HIV/AIDS. Of these, 16 studies took place in eight different low and middle-income countries (LMIC), of which 6 were in southern and eastern Africa. One study took place in a high-income setting. Of the total, fifteen showed some significant benefits of the intervention, while two showed no difference to psychosocial outcomes as a result of the intervention. The content of interventions, dosage and length of follow up varied substantially between studies. There were few studies on children under seven years and several focused mostly on girls. Efforts to improve evaluation of interventions to improve the psychosocial well-being of children affected by HIV/AIDS have resulted in a number of new studies which met the inclusion criteria for the review. Most studies are specially designed research projects and not evaluations of existing services. We call for increased partnerships between policy-makers, practitioners and researchers in order to design evaluation studies and can feed into the growing evidence base.

Ten Year Experience of Radioiodine Dosimetry: is it Useful in the Management of Metastatic Differentiated Thyroid Cancer?

AIMS: When a fixed activity of radioiodine is given for differentiated thyroid cancer (DTC), absorbed doses of radioiodine can vary widely and are not usually measured. Leeds Cancer Centre has routinely used a form of lesion-specific dosimetry for radioiodine patients. This study investigated if the results of dosimetry influenced treatment decisions for patients with advanced DTC. MATERIALS AND METHODS: Since 2005, patients with regionally advanced/metastatic DTC, who underwent radioiodine treatment together with dosimetry, were included in this study. Patients were excluded if their radioiodine post-treatment scan showed no abnormal uptake. Dosimetry was calculated using images taken 2, 3 and 7 days post-radioiodine. Regions of interest were drawn around lesions that required dosimetry and a time-dose activity curve was created. The total cumulative activity was equal to the area under the curve. Each patient's results were prospectively assessed by their oncologist regarding the usefulness of dosimetry in making management decisions. RESULTS: Thirty patients were studied and underwent 102 admissions of radioiodine between them. Dosimetry was carried out during 83 of 102 admissions. An absorbed dose of >20 Gy was taken as significant from dosimetry calculations, following which further radioiodine was considered. In 80% of patients, dosimetry was found to be useful when making treatment decisions. Only on 1/19 admissions did dosimetry calculate a minimum dose above 20 Gy in patients who had a total of four or more admissions for radioiodine. Ten per cent (3/30) had a complete response to radioiodine, both biochemically and radiologically, with a median follow-up of 6.7 months. Thirty-three per cent had a partial response/stable disease to radioiodine. The remainder had progressive disease. The decision to discontinue radioiodine therapy was often based on dosimetry and thyroglobulin results. Dosimetry was very useful for patients with thyroglobulin antibodies. CONCLUSION: Only 10% had a complete response. Therefore, a significant number of patients became refractory to radioiodine during a course of repeat admissions for treatment. Dosimetry (often together with thyroglobulin and anatomical scans) helped to identify these patients to avoid further futile radioiodine therapy.

NMR adventures in the metabolic labyrinth within plants.

The era of metabolic engineering has begun, but there is only limited knowledge about metabolic fluxes and how they are regulated in plants. Particular challenges are the non-linearities between enzyme abundances, metabolite concentrations and metabolic fluxes, and the existence of metabolic networks that provide multiple routes between many important metabolites. NMR offers the means to distinguish and quantitate the fluxes along different routes to key metabolites. NMR can therefore help us understand and resolve the apparent paradox of, on the one hand, great metabolic flexibility evident in the natural responses of plants and, on the other hand, the unpredictable changes in metabolism reported in genetically engineered plants.

Observation of uridine triphosphate:glucose-1-phosphate uridylyltransferase activity in maize root tips by saturation transfer 31P-NMR. Estimation of cytoplasmic PP.

Saturation transfer 31P nuclear magnetic resonance was used to estimate the unidirectional rate of phosphorus exchange between Glc-1-P and UDPGlc in maize root tips. The rate was determined to be approx. 4 mumol.min-1 per g fresh weight. This estimated rate is much higher than net rates of other reactions in glucose metabolism (e.g., more than 10-times faster than the maximal glycolytic flux in this tissue). Furthermore, exchange between Glc-1-P and UDPGlc was not significantly inhibited by the metabolic poison KCN. We conclude that the unidirectional rate of conversion of Glc-1P to UDPGlc is much faster than the net rate of UDPGlc synthesis--the UTP:Glc-1-P uridylyltransferase reaction is near-equilibrium in vivo. From the equilibrium constant for this transferase reaction and the concentrations of Glc-1-P, UTP and UDPGlc, the level of cytoplasmic PPi was estimated to be approx. 10 nmol.g-1.

Cytoplasmic malate levels in maize root tips during K+ ion uptake determined by 13C-NMR spectroscopy.

13C-NMR spectroscopy was used to determine the level of cytoplasmic malate in maize root tips that exhibited different rates of malate synthesis. Intracellular malate was 13C-labeled at carbons 1 and 4 by perfusing root tips with 5 nM H13CO3-. This labeling reflects the activities of phosphoenolpyruvate carboxylase and malate dehydrogenase (production of [4-13C]malate), and fumarase (scrambling of 13C-label between C1 and C4 of malate). In vivo 13C-NMR spectra contained a clearly resolved resonance from cytoplasmic [4-13C]malate, while the resonance from cytoplasmic [1-13C]malate overlapped with others. After 90 min of H13CO3- treatment, 13C-labeling of organic acid pools had reached steady-state. Thereafter, the ratios [13C]malate/[12C + 13C]malate and [1-13C]malate/[4-13C]malate in tissue extracts remained constant; evidence is presented that these ratios were the same for both cytoplasmic and total cellular malate. Hence, the intensity of the cytoplasmic [4-13C]malate signal was proportional to the amount of cytoplasmic malate in root tips. Potassium sulfate stimulate malate synthesis in maize root tips, relative to root tips perfused with HCO3- alone; total cellular malate doubled after approx. 1 h of 5 mM K2SO4-treatment. Cytoplasmic malate increased from approx. 3.5 mM to approx. 7.5 mM within 45 min of the onset of K2SO4-treatment, declining slightly thereafter. The possible effects of these changing cytoplasmic malate concentration on the enzymes involved in malate metabolism are discussed.

Use of Modeling and Simulation in the Design and Conduct of Pediatric Clinical Trials and the Optimization of Individualized Dosing Regimens.

Mathematical models of drug action and disease progression can inform pediatric pharmacotherapy. In this tutorial, we explore the key issues that differentiate pediatric from adult pharmacokinetic (PK) / pharmacodynamic (PD) studies, describe methods to calculate the number of participants to be enrolled and the optimal times at which blood samples should be collected, and therapeutic drug monitoring methods for individualizing pharmacotherapy. The development of pediatric-specific drug dosing dashboards is also highlighted, with an emphasis on clinical-relevance and ease of use.

Outcome following Resection of Biliary Cystadenoma: A Single Centre Experience and Literature Review.

Background. Biliary cystadenomas (BCAs) are rare, benign, potentially malignant cystic lesions of the liver, accounting for less than 5% of cystic liver tumours. We report the outcome following resection of biliary cystadenoma from a single tertiary centre. Methods. Data of patients who had resection of BCA between January 1993 and July 2014 were obtained from liver surgical database. Patient demographics, clinicopathological characteristics, operative data, and postoperative outcome were analysed. Results. 29 patients had surgery for BCA. Male : female ratio was 1 : 28. Clinical presentation was abdominal pain (74%), jaundice (20%), abdominal mass (14%), and deranged liver function tests (3%). Cyst characteristics included septations (48%), wall thickening (31%), wall irregularity (38%), papillary projections (10%), and mural nodule (3%). Surgical procedures included atypical liver resection (52%), left hemihepatectomy (34%), right hemihepatectomy (10%), and left lateral segmentectomy (3%). Median length of stay was 7 (IQ 6.5-8.5) days. Two patients developed postoperative bile leak. No patients had malignancy on final histology. Median follow-up was 13 (IQ 6.5-15.7) years. One patient developed delayed biliary stricture and one died of cholangiocarcinoma 11 years later. Conclusion. Biliary cystadenomas can be resected safely with significantly low morbidity. Malignant transformation and recurrence are rare. Complete surgical resection provides a cure.

Testing the validity of the lacunar hypothesis: the Northern Manhattan Stroke Study experience.

BACKGROUND/OBJECTIVE: Few studies have attempted to validate the "lacunar hypothesis." The accuracy of identifying lacunar and other nonlacunar mechanisms of infarction will be increasingly important in evaluating potential stroke treatments. The aim of this study was to determine the value of lacunar syndromes in predicting radiologic lacunes and the value of clinicoradiologic lacunes in predicting "lacunar infarction" as final stroke mechanism. METHODS: From 1990 to 1994, 591 patients with cerebral infarction, who were from northern Manhattan and over the age of 39, were prospectively examined. Data were collected on the admitting clinical syndrome (lacunar or nonlacunar) and brain imaging findings. Lacunar syndromes were categorized as pure motor hemiparesis (PMH), pure sensory syndrome (PSS), sensorimotor syndrome (SMS), ataxic-hemiparesis (A-H), and other lacunar syndromes. Brain imaging findings were classified as radiologic lacune or nonlacune. Positive predictive values, sensitivities, and specificities of lacunar syndromes for identifying radiologic lacunes were calculated. The final mechanism of infarction was determined after review of all the diagnostic tests and compared among the lacunar groups. RESULTS: Lacunar syndromes occurred in 225 cases. PMH was the most common lacunar syndrome, accounting for 45%, SMS 20%, A-H 18%, and PSS 7%. Lacunar syndromes had an overall positive predictive value (PPV) of 87% for detecting radiologic lacune: PSS 100%, A-H 95%, SMS 87%, and PMH 79%. Among the 195 patients who presented with a lacunar syndrome and had this condition confirmed radiologically, 147 were classified as having a final diagnosis of lacunar mechanism of infarction (PPV = 75%). Atherosclerosis accounted for 17 (9%), cardioembolism 10 (5%), cryptogenic 17 (9%), and other unusual causes 4 (2%). CONCLUSION: While lacunar syndromes, especially PSS and A-H, are highly predictive of lacune, in about one in four patients presenting with lacunar syndromes confirmed radiologically the condition is associated with nonlacunar mechanisms of infarction. Noninvasive neurovascular and cardiac evaluations are still warranted even among patients with lacunes.

Low thromboembolic risk without anticoagulation using advanced-design left ventricular assist devices.

BACKGROUND: A major limitation of cardiac assist devices has been the high incidence of thromboembolic events and their requirement for systemic anticoagulation. The Thermo Cardiosystems HeartMate 1000 IP left ventricular assist device (LVAD) employs a design that may reduce thromboembolic risk and obviate the need for systemic anticoagulation. METHODS: Two hundred twenty-three patients with nonreversible heart failure were supported with the HeartMate LVAD as a bridge to heart transplantation. All patients were monitored prospectively for thromboembolic events. Anticoagulation regimens and occurrence of subclinical thromboembolic events, including those seen by transcranial Doppler examinations in selected patients, were also recorded. RESULTS: Total time of LVAD support use was 531.2 patient-months. Twenty-three patients (10%) received warfarin postoperatively for 42.4 patient-months (8.2% of total support time). Six patients (2.7%) had thromboembolic events, representing 0.011 events per patient-month of device use. CONCLUSIONS: The thromboembolic complication rate associated with this LVAD is acceptably low despite the minimal anticoagulation employed in this series, allowing consideration of long-term device use for the treatment of heart failure.

Neuropsychiatric complications of mental retardation.

Certain aspects of mental retardation and organic brain disease are discussed: notably, psychopathology, the delayed effects of congenital infections, epilepsy, and the association between Down's syndrome and dementia.

A vented laryngeal stent with phonatory and pressure relief capability.

This prototype vented laryngeal stent incorporates a dome-shaped, one-way valve that allows articulation of transmitted vibrations to produce speech, while preventing aspiration and not interfering with deglutition. The stent is placed endoscopically and is used in conjunction with a T-tube or a tracheostomy tube. The stent has been placed in seven patients for chronic aspiration, after partial laryngectomy, and with laryngotracheal reconstruction for stenosis. Aspiration pneumonia has not been seen in any patient after placement of the appropriate stent, with follow-up of 2 to 6 months. One patient's swallowing improved and none deteriorated. All patients were able to phonate with the stent in place. No significant long-term sequelae are apparent in three patients whose stents were removed after resolution of their primary diseases.

Squamous cell carcinoma of the head and neck in patients 40 years of age and younger.

Squamous cell carcinoma of the head and neck is largely a disease of the middle-aged and elderly. When it occurs in younger patients, the prognosis for long-term survival appears to be worse than in the older age group. The records of 41 patients aged 40 years and younger who presented with squamous cell carcinoma of the head and neck were reviewed. Twenty-eight of these patients (68%) developed recurrence; of these, 21 (51%) died with disease, and two are alive with disease. These results indicate a trend toward poorer survival than previous rates reported nationally for all patients with carcinoma of the head and neck over a similar time period. Lesions of the oral tongue, nasopharynx, and paranasal sinuses seem to have a particularly poor prognosis.

Evaluation of syncope from head and neck cancer.

Five patients suffering from recurrent syncope in association with metastatic squamous cell carcinoma of the head and neck were examined. Two patients had exhaustive diagnostic work-up for syncope, which eventually disclosed previously undiagnosed, recurrent squamous cell carcinoma. Case reports describe glossopharyngeal neuralgia, a well recognized cause of syncope in the head and neck cancer patient, characterized by acute unilateral head or neck pain preceding each syncopal episode. The literature on the diagnosis of syncope is reviewed, and the syncopal mechanisms unique to the head and neck cancer patient are analyzed and discussed. A diagnostic approach to syncope in head and neck cancer is proposed.

Squamous cell carcinoma of the paranasal sinuses: the Cleveland Clinic experience 1977-1986.

Fifty-four of 103 malignancies of the paranasal sinuses treated at the Cleveland Clinic Foundation between 1977 and 1986 were squamous cell carcinomas. Six arose from the ethmoid sinus and 48 from the maxillary sinus. Of the maxillary sinus patients, 11 presented with T1 or T2 lesions, 20 with T3, 16 with T4, and 7 of these had nodal disease. Treatment was surgery and/or radiation therapy. There was local recurrence in 25 of 48 maxillary sinus patients and in 1 of 6 ethmoid patients. Overall 5-year survival was 38.2% in the maxillary sinus group: T1, 100.0%; T2, 85.7%; T3, 31.8%; and T4, 6.7%. Three of six patients with ethmoid tumors were cured. There was a statistical trend for better prognosis in those patients presenting with ethmoid primaries, with early lesions, treated with both radiation and surgery, and with history of inverting papilloma. There were complications of treatment in 10 patients, four of which resulted in death. Local control was the major problem for these patients; therefore, early detection and aggressive local treatment are desirable.

Laryngotracheal reconstruction. Sternohyoid myocutaneous rotary door flap.

The vascularized sternohyoid myocutaneous rotary door flap has been used for laryngotracheal reconstruction in ten patients in the past two years. Nine were reconstructed for laryngotracheal stenosis and one for immediate reconstruction after conservation laryngeal surgery for carcinoma. Before reconstruction, the nine patients with stenosis had each undergone a mean of eight surgical attempts at correction. Eight patients were tracheostomy dependent, and only two patients had effective voices. To date, seven patients have been decannulated and all ten have effective voices. No significant complications have been noted. This flap can provide a readily applicable, dependable technique that is useful in management of difficult laryngotracheal stenosis and for reconstruction after conservation laryngeal surgery.

Near-total laryngectomy with epiglottic reconstruction. Long-term results.

A previous report reviewed the technique and indications for near-total laryngectomy with epiglottic reconstruction in the management of squamous cell carcinoma of the glottis. This approach permits removal of most of both vocal folds, with immediate reconstruction using the epiglottis without the need for stenting or multistage procedures. Forty-eight patients underwent the procedure and were followed up for at least 2 years or until death. Seventeen underwent the surgery for recurrence after failure of radiation therapy for cure. Complications included one wound infection and one laryngocutaneous fistula. All patients underwent decannulation, with little or no compromise of swallowing. All but 1 now have functional voices. Of 8 patients with recurrence, 6 have been salvaged. Two patients died of disease. The value of near-total laryngectomy with epiglottic reconstruction for management of glottic cancer is reviewed.

Cancer of the periauricular region.

Cutaneous carcinoma of the auricular and periauricular region can be diagnosed early and often can be cured; however, many of these tumors become difficult to treat because of local spread and regional metastasis. Those tumors that are not treated early often require more aggressive treatment with ear canal resection, partial temporal bone resection, or even parotidectomy and radiation therapy. Mohs histographic surgery combined with conventional excision affords the best marginal control for local eradication of these tumors.