Post-tonsillectomy Hemorrhage in Patients Receiving Ketorolac Analgesic.

Background Ketorolac, the non-steroidal anti-inflammatory drug, is thought to have less sedation as well as postoperative nausea and vomiting in comparison to opioids, but with higher risk of post-tonsillectomy hemorrhage as reported in some of the literatures. There is no consensus till date in the use of ketorolac in the management of pain following tonsil and adenoid related surgeries. Objective To find out the incidence of hemorrhage following tonsil and adenoid related surgeries in patients receiving ketorolac in postoperative period. Method This is a retrospective chart review of patients undergoing tonsil and adenoid related surgeries who had received ketorolac during April, 2013 to May, 2019 at department of ENT-HNS, Patan Academy of Health Sciences (PAHS), Lalitpur, Nepal. Post-tonsillectomy hemorrhage rate was calculated in pediatric and adult patients. Result During the study period, 103 patients (male - 50 and female - 53) received ketorolac in postoperative period. Tonsillectomy and adenotonsillectomy were performed in 71and 32 patients respectively. Forty-five patients were < 18 years whereas 58 were ≥ 18 years. Most common indication for surgery was recurrent tonsillitis (66/103) followed by adenotonsillar hypertrophy (31/103). Post-tonsillectomy hemorrhage was observed in 15 patients; among them, four out 45 were < 18 years and 11 out of 58 ≥ 18 years. All five patients out of 15, who required surgical intervention for post-tonsillectomy hemorrhage, were ≥ 18 years and were operated for recurrent tonsillitis. Rest of the patients (10/15) were managed conservatively. None of the patients required blood transfusion. Conclusion Ketorolac is not associated with increased risk of post-tonsillectomy hemorrhage in children and can safely be administered. Whereas in adults, recurrent tonsillitis being the most common indication for tonsillectomy, it should be used cautiously.

Indoor Air Pollution (IAP) Traceable to Household Fuel Consumption and its Impact on Health.

Energy is an essential and obligatory prerequisite of life. Indoor air pollution is one of the biggest environmental problems in the world being specifically concentrated in resource limited settings. Inspite of the availability of cleaner fuel technologies, people in resource limited setting still depend on traditional fuel to meet their basic needs resulting even in premature deaths. In Nepal people in rural areas are the pre-dominant users of biomass fuel, there is limited research focusing on rural areas particularly; women as they spend most of their time in kitchen. Reports were extensively searched for literature using preset keywords in English language peer-reviewed journals databases PubMed and Google Scholar published between the years 2005 to 2020. Citation details were examined, titles and abstracts screened for eligibility and if relevant, full text was also reviewed in greater detail. Findings were then presented primarily under two bold themes: Household fuel consumption: existing theories and evidence; and health impact of indoor air pollution. Several health effects were reported of indoor air pollution including respiratory illnesses, cardiovascular diseases, cancer, endocrine system disruption and pregnancy complications. These exposures almost double the health risks predominantly among children and women of rural communities as they are directly involved in household activities causing air pollution. Based on our review of evidence, women and children of rural households were the major victims. Further, determinants of household fuel consumption and health effects should be considered while formulating policies in regard to promoting accessibility of clean fuels and reducing household air pollutants.

The effect of metformin in EML4-ALK+ lung cancer alone and in combination with crizotinib in cell and rodent models.

Cell based studies have suggested that the diabetes drug metformin may combine with the anaplastic lymphoma kinase receptor (ALK) inhibitor crizotinib to increase ALK positive lung cancer cell killing and overcome crizotinib resistance. We therefore tested metformin alone and in combination with crizotinib in vivo, by employing a xenograft mouse model of ALK positive lung cancer. We found that 14 days of daily oral metformin (100 mg/kg) alone had a moderate but statistically significant effect on tumour growth suppression, but in combination with crizotinib, produced no greater tumour suppression than crizotinib (25 mg/kg) alone. We also reassessed the effect of metformin on EML4-ALK positive lung cancer (H3122) cell viability. Although metformin alone did have a moderate effect on cell viability (30% suppression) this was only at a clinically irrelevant concentration (5 mM) and there was no additive effect with cytotoxic concentrations of crizotinib. Moreover, metformin did not overcome crizotinib resistance in our resistant cells. Nevertheless, we were able to show that metformin induces a G1-cell cycle arrest and apoptosis alone and in combination with crizotinib. Also, consistent with earlier work, the addition of insulin-like growth factor-1 (IGF-1) to EML4-ALK positive cancer cells reduced cell killing by crizotinib. We therefore hypothesised that the effect of metformin in vivo was not due to direct cytotoxicity on cancer cells, but by modulation of IGF-1 expression. We therefore measured levels of IGF-1 in plasma taken from mice treated with metformin, but found no difference between the drug treatment and control groups. We further hypothesised that the effect of metformin could be due to modulation of thrombospondin 1 (TSP-1), which metformin has been proposed to regulatein vivo, but again we found no difference between the experimental groups. Finally, we investigated the potential for liver and kidney toxicity, as well as CYP3A based interactions, from the combination of metformin with crizotinib.

Inhibition of Mitogen-Activated Protein Kinase Kinase Alone and in Combination with Anaplastic Lymphoma Kinase (ALK) Inhibition Suppresses Tumor Growth in a Mouse Model of ALK-Positive Lung Cancer.

Anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer most commonly arises through EML4 (Echinoderm Microtuble Like 4)-ALK chromosomal fusion. We have previously demonstrated that combination of the ALK inhibitor crizotinib with the MEK inhibitor selumetinib was highly effective at reducing cell viability of ALK-positive non-small-cell lung cancer (H3122) cells. In this study, we further investigated the efficacy of crizotinib and selumetinib combination therapy in an in vivo xenograft model of ALK-positive lung cancer. Crizotinib decreased tumor volume by 52% compared with control, and the drug combination reduced tumor growth compared with crizotinib. In addition, MEK inhibition alone reduced tumor growth by 59% compared with control. Crizotinib and selumetinib alone and in combination were nontoxic at the dose of 25 mg/kg, with values for ALT (<80 U/l) and creatinine (<2 mg/dl) within the normal range. Our results support the combined use of crizotinib with selumetinib in ALK-positive lung cancer but raise the possibility that a sufficient dose of an MEK inhibitor alone may be as effective as adding an MEK inhibitor to an ALK inhibitor. SIGNIFICANCE STATEMENT: This study contains in vivo evidence supporting the use of combination MEK inhibitors in ALK+ lung cancer research, both singularly and in combination with ALK inhibitors. Contrary to previously published reports, our results suggest that it is possible to gain much of the benefit from combination treatment with an MEK inhibitor alone, at a tolerable dose.

Mechanisms of suppression of cell growth by dual inhibition of ALK and MEK in ALK-positive non-small cell lung cancer.

Anaplastic lymphoma kinase (ALK) rearrangement, a key oncogenic driver in a small subset of non-small cell lung cancers, confers sensitivity to ALK tyrosine kinase inhibitors (TKIs). Crizotinib, a first generation ALK-TKI, has superiority to standard chemotherapy with longer progression-free survival and higher objective response rate. However, clinical benefit is limited by development of resistance, typically within a year of therapy. In this study the combined effect of crizotinib and the MEK inhibitor selumetinib was investigated in both crizotinib naïve (H3122) and crizotinib resistant (CR-H3122) ALK-positive lung cancer cells. Results showed that combination treatment potently inhibited the growth of both H3122 and CR-H3122 cells, resulting from increased apoptosis and decreased cell proliferation as a consequence of suppressed downstream RAS/MAPK signalling. The drug combination also elicited a greater than 3-fold increase in Bim, a mediator of apoptosis, and p27, a cyclin dependent kinase inhibitor compared to crizotinib alone. The results support the hypothesis that combining MEK inhibitors with ALK inhibitor can overcome ALK inhibitor resistance, and identifies Bim, PARP and CDK1 as druggable targets for possible triple drug therapy.

Next generation sequencing reveals packaging of host RNAs by brome mosaic virus.

Although RNA viruses evolved the mechanisms of specific encapsidation, miss-packaging of cellular RNAs has been reported in such RNA virus systems as flock house virus or cucumber necrosis virus. To find out if brome mosaic virus (BMV), a tripartite RNA virus, can package cellular RNAs, BMV was propagated in barley and in Nicotiana benthamiana hosts, purified by cesium chloride (CsCl) gradient ultracentrifugation followed by nuclease treatment to remove any contaminating cellular (host) RNAs. The extracted virion RNA was then sequenced by using next-generation sequencing (NGS RNA-Seq) with the Illumina protocol. Bioinformatic analysis revealed the content of host RNAs ranging from 0.07% for BMV extracted from barley to 0.10% for the virus extracted from N. benthamiana. The viruses from two sources appeared to co-encapsidate different patterns of host-RNAs, including ribosomal RNAs (rRNAs), messenger RNAs (mRNAs) but also mitochondrial and plastid RNAs and, interestingly, transposable elements, both transposons and retrotransposons. Our data reveal that BMV virions can carry host RNAs, having a potential to mediate horizontal gene transfer (HGT) in plants.

Propionibacterium acnes endocarditis: a case series.

OBJECTIVES: Propionibacterium acnes remains a rare cause of infective endocarditis (IE). It is challenging to diagnose due to the organism's fastidious nature and the indolent presentation of the disease. The purpose of this study was to describe the clinical presentation and management of P. acnes IE with an emphasis on the methods of diagnosis. METHODS: We identified patients from the Cleveland Clinic Infective Endocarditis Registry who were admitted from 2007 to 2015 with definite IE by Duke Criteria. Propionibacterium acnes was defined as the causative pathogen if it was identified in at least two culture specimens, or identified with at least two different modalities: blood culture, valve culture, valve sequencing or histopathological demonstration of microorganisms. RESULTS: We identified 24 cases of P. acnes IE, 23 (96%) of which were either prosthetic valve endocarditis or IE on an annuloplasty ring. Invasive disease (71%) and embolic complications (29%) were common. All but one patient underwent surgery. Propionibacterium acnes was identified in 12.5% of routine blood cultures, 75% of blood cultures with extended incubation, 55% of valve cultures, and 95% of valve sequencing specimens. In 11 of 24 patients (46%), no causative pathogen would have been identified without valve sequencing. CONCLUSIONS: Propionibacterium acnes almost exclusively causes prosthetic valve endocarditis and patients often present with advanced disease. The organism may not be readily cultured, and extended cultures appear to be necessary. In patients who have undergone surgery, valve sequencing is most reliable in establishing the diagnosis.

Microbiological and Clinical Profile of Uropathogenic Escherichia coli Isolates in Kathmandu University Hospital.

BACKGROUND: Treatment of patients infected by multidrug resistant bacteria is a major challenge. Immunocompromised status, prolonged hospital stay, malignancy, diabetes are some of the risk factors for emergence of multidrug resistance. Our study focused on microbiological and clinical profile of multidrug resistant uropathogenic Escherichia coli. METHODS: This was a cross-sectional study conducted between June 2014-May 2015 in Kathmandu University Hospital. Urine sample from outpatients and inpatients from which Escherichia coli isolated was included. Specimen collection, culture, identification tests were done following guidelines given by American Society for Microbiology. RESULTS: Total number of urine samples received during the study were 3,554. Escherichia coli isolates were 645(18.14%) and 245(37.98%) were Extended Spectrum Beta-Lactamase producer. Extended Spectrum Beta-Lactamase producers were found more among inpatients 148(60.41%) [p<0.001], patients with underlying urological abnormalities 38 (15.51%) [p=0.0039], pregnant ladies 46(18.77%) [p=0.0028], diabetic patients 27 (11.02%) [p=0.0084], patients who received prior antibiotic therapy 155 (63.26%) [p=0.0043] than Extended Spectrum Beta-Lactamase non-producer. Malignancy was seen more among Extended Spectrum Beta-Lactamase producer having patients 5 (2.04%) [p=0.031] and all these isolates were more resistant to fluoroquinolones 168(68.57%), Trimethoprim-sulfamethoxazole 239 (97.55%) [p=0.0633], aminoglycosides [p=0.0001] but only 2(0.80%) were resistant to carbapenems. CONCLUSIONS: Diabetes, pregnancy, malignancy, prior antibiotic therapy, underlying urological abnormalities were found associated with emergence of Extended Spectrum Beta-Lactamase producer in urine samples. Proper antibiotic usage may help to overcome the problem of emergence of antibiotic resistance.

Epidemiology and risk factors for infections in myelodysplastic syndromes.

We conducted a case-control study to describe the epidemiology and risk factors for infections requiring hospitalization in patients with myelodysplastic syndromes (MDS). Of 497 patients identified, 103 patients developed 201 episodes of infection. The probability of acquiring an infection 1 year from date of MDS diagnosis was 15% (95% confidence interval [CI] 12-18%). Patients developing infections had decreased survival compared to those who did not (P = 0.007). Significant risk factors for infection were higher risk MDS (hazard ratio [HR] = 2.7, 95% CI = 1.7-4.1, P < 0.0001), nadir absolute neutrophil count <500/mL (HR = 1.8, 95% CI = 1.2-2.7, P < 0.007), chronic obstructive pulmonary disease (HR = 2.6, 95% CI = 1.4-4.9, P < 0.003), history of other malignancy (HR 2.0, 95% CI = 1.3-3.1, P < 0.003), and autoimmune disease (HR 2.9, 95% CI = 1.4-6.0, P < 0.005). Age, nadir platelet count <20,000/mL, diabetes mellitus, and MDS treatment were not significant risk factors. Pneumonia was the most common infection, and bacteria the predominant pathogens.

Experiences of gynecological laparoscopic surgeries in a teaching hospital.

BACKGROUND: Laparoscopic surgery has revolutionised the field of gynaecological surgery. Presently, almost all gynaecological procedures can find an alternative laparoscopic or hysterescopic approach. The aim of the study was to share the early experience of gynecological laparoscopic surgeries performed at Kathmandu Medical College Teaching Hospital. METHODS: A study was carried out at Kathmandu Medical College Teaching Hospital from 1st January 2009 to 16th August 2012. All the patients undergoing gynecological laparoscopic surgeries were analyzed for the indication, type of procedure and its complications. RESULTS: Overall 300 patients successfully underwent laparoscopy during the study period of which diagnostic laparoscopy was in 115. Operative laparoscopy was in 185. Sixty five cases underwent laparoscopic cystectomy. Sixty cases underwent laparoscopic assisted vaginal hysterectomy (LAVH). Salpingectomy for ectopic pregnancy was done in sixteen cases. Twelve cases contemplated for laparoscopic cystectomy underwent laparotomy. LAVH was converted to abdominal hysterectomy in four cases and laparotomy was done in two cases because of bladder injury and primary hemorrhage (from vault). Of minor complications the most common was port site infection and post-operative nausea and vomiting. CONCLUSIONS: Laparoscopic gynecological surgery has tremendous potential in Nepal. Most of the surgeries can be carried out safely and favorable outcome has been noted in all the cases undertaken.

Changes in expression of c-Fos protein following cocaine-cue extinction learning.

Extinguishing abnormally strengthened learned responses to cues associated with drugs of abuse remains a key tactic for alleviating addiction. To assist in developing pharmacotherapies to augment exposure therapy for relapse prevention, investigation into neurobiological underpinnings of drug-cue extinction learning is needed. We used regional analyses of c-Fos and GluR2 protein expression to delineate neural activity and plasticity that may be associated with cocaine-cue extinction learning. Rats were trained to self-administer cocaine paired with a light cue, and later underwent a single 2h extinction session for which cocaine was withheld but response-contingent cues were presented (cocaine-cue extinction). Control groups consisted of rats yoked to animals self-administering cocaine and receiving saline non-contingently followed by an extinction session, or rats trained to self-administer cocaine followed by a no-extinction session for which levers were retracted, and cocaine and cues were withheld. Among 11 brain sites examined, extinction training increased c-Fos expression in basolateral amygdala and prelimbic prefrontal cortex of cocaine-cue extinguished rats relative to both control conditions. In dorsal subiculum and infralimbic prefrontal cortex, extinction training increased c-Fos expression in both cocaine-cue and saline-cue extinguished rats relative to the no-extinction control condition. GluR2 protein expression was not altered in any site examined after extinction or control training. Findings suggest that basolateral amygdala and prelimbic prefrontal cortex neurons are activated during acquisition of cocaine-cue extinction learning, a process that is independent of changes in GluR2 abundance. Other sites are implicated in processing the significance of cues that are present early in extinction training.

Anaesthetic management of patients with Xeroderma pigmentosum. A series of three cases.

Xeroderma pigmentosum is a rare autosomal recessive disorder with clinical and cellular hypersensitivity to ultraviolet radiation and defective DNA repair. Skin cancer, mainly on the face, head or neck is very common. Inhalational anaesthetic agents and muscle relaxants are best avoided due to the possibility of inducing DNA damage and prolonged effects of muscle relaxants. These patients may have a difficult airway. These patients may have immature brain development which may render them sensitive to synergistic effect of benzodiazepines and opioids as seen in the first case. Total intravenous anaesthesia is preferred. Nonsteroidal anti inflammatory agents and opioids for multimodal analgesia may be beneficial.

Changing routes of hysterectomy: a cross sectional and comparative study.

Hysterectomy is one of the most frequently performed major surgical procedure in women. Traditionally, the uterus has been removed either by abdominal or vaginal route. In spite of the recommendations in favor of vaginal hysterectomy majority of the hysterectomies are still done by the means of abdominal route and vaginal route is utilized mostly for prolapsed uterus. This study was done to see the current trend of routes of hysterectomy for benign condition at Kathmandu Medical College Teaching Hospital and its indication. This was a cross-sectional and comparative study done for 24 months (Jan 2008- Dec 2009). Data for the year 2009 was collected prospectively and for the year 2008 case notes of all the cases of hysterectomy was reviewed. Total 317 cases of hysterectomy were done for benign condition in KMCTH during the 2 year study period. Of the 317 cases 124 was done during the year 2008 and 193 during 2009. Three major route namely vaginal hysterectomy (VH), Abdominal Hysterectomy (AH), and Laparoscopic hysterectomy (LH) was utilized for performing hysterectomy. Major indication for hysterectomy was pelvic organ prolapse (POP) followed by abnormal uterine bleeding (AUB), and fibroid uterus during both the years. Route of hysterectomy in the cases with non prolapsed pelvic organ were AH (94.0%) and LH (6.0%) during the year 2008 and VH (6.0%), AH (76%) and LH (18.0%) during the year 2009. Major indications for hysterectomy are POP, AUB, and fibroid uterus. VH is mainly done for the cases of POP. AH is still the major route for indications other than POP. Minimally invasive approach like VH for non descent uterus and LH although is rising needs to be practiced more.

Effect of haemodynamic and metabolic predictors on echocardiographic left ventricular mass in non-diabetic hypertensive patients.

BACKGROUND: Left ventricular hypertrophy is a forerunner of coronary heart disease, congestive cardiac failure, stroke and may also lead to sudden death. Estimation of left ventricular mass by echocardiography offers prognostic information better than the evaluation of traditional cardiovascular risk factors. OBJECTIVE: The aim of this study was to determine the relative contributions of haemodynamic and metabolic factors affecting left ventricular mass in non-diabetic patients with essential hypertension. MATERIAL AND METHODS: 100 non-diabetic hypertensive patients were taken. The association between age, gender, smoking, alcohol, height, weight, heart rate, clinic blood pressure, fasting blood glucose, lipid profile, haemoglobin, body mass index and stroke volume with LV mass was studied. Left ventricular mass was measured by using standard M-mode echocardiography measurement obtained by way of standard recommended by the American Society of Echocardiography. RESULTS: Left ventricular mass was analyzed as a continuous variable. In males body mass index (r = .35, p < .004) and stroke volume(r = -.26, p<.039) were significantly correlated with LV mass. In females body weight was significantly related to left ventricular mass(r = .36, p < .02). The independent association between significant factors and left ventricular mass was assessed by stepwise multivariate logistic regression. Body mass index and systolic blood pressure came as independent determinants of left ventricular mass in all patients. A maximum of 13% of left ventricular mass variability could be explained by these two factors. CONCLUSION: In untreated patients with hypertension patient's body mass index and systolic blood pressure are independent predictors of left ventricular mass after adjustment for other haemodynamic and metabolic factors. They explain a maximum of 13% of left ventricular mass variability. More knowledge is needed about factors that may alter cardiac morphology in the evolution of hypertensive patients.

A study on complication and monitoring of warfarin in post-valve surgery.

INTRODUCTION: This study was carried out to determine the incidence of complication related to warfarin in patients with valve surgery and identify potential risk factors for complication and study its monitoring aspects. METHODS: A combined retrospective and prospective observational study including a total of 185 patients who underwent mechanical valve replacement in Shahid Gangalal National Heart Centre. The study was conducted from 4 November 2006 till 1 February 2007. RESULTS: There were a total of 141 episodes of bleeding. Among them significant bleeding occurred in 15.7% patients, major bleeding was 3.2 per 100 patient-years (3.8%) and minor bleeding was 11.8 per 100 patient-years (11.9%). Epistaxis (16.8%) was the most common bleeding complication. Menorrhagia was the most common bleeding complication in females with 20.5 per 100 patient-years (27.4%). Thromboembolic complications occurred at the rate of 2.3 per 100 patient-years. Patients on warfarin were outside the INR target range 67.8% of the time, with 21% INR values above range and 46.8% INR values below range. However, dose adjustment was done only 31.8% of times when INR was outside range. CONCLUSIONS: There is high incidence of bleeding complication in patients on warfarin and hypertension is significantly associated with bleeding. Difficulty in tightly controlling INR probably is related to high incidence of bleeding. Better patient education, stricter adjustment of INR, frequent monitoring of INR at peripheral hospitals and standardization of the test at different hospitals are suggested to reduce the warfarin related complications.

Patients choice for method of early abortion among comprehensive abortion care (CAC) clients at Kathmandu Medical College Teaching Hospital (KMCTH).

OBJECTIVE: The over all objective of the study was to determine different methods of abortion opted by CAC clients at KMCTH. The specific objective of the study was to know the reasons for pregnancy termination and to know the reasons opted for either medical or surgical method of abortion. METHODOLOGY: A hospital based prospective study was carried out for a period of six months at KMCTH from 1st January 2006 to 31st June 2006. All the patient undergoing CAC services were included for the study. Clients were provided with written and verbal information regarding the methods of terminating early abortion and its associated complications. After that they were asked to give their informed choice and decision. All the pertinent information was entered on pre-structured questionnaire. RESULTS: During the study period a total of 100 patients underwent CAC services. The commonest reason for termination pregnancy was no desire for additional children (60%) followed by youngest child too small or short spacing (21%). 74% of the patients opted for surgical abortion, 23% patient opted for medical abortion and 3% of the patient remain undecided. Reasons for favouring surgical method of abortion was that surgical abortion is complete (35), repeated visits are avoided (18), quick (10) would be with service provider and feel safe (5), lack of expectancy (2) side effect of medical treatment (1), twin pregnancy (1), easy (1), fear of pain (1). Medical method of abortion was favoured due to fear of surgery (9), easy and less painful (8) and maintains privacy (6). CONCLUSION: Factors affecting the choice of abortion method appear to be numerous and complex. Providers need to be sensitive to differences in women's values and life circumstances when counselling them about an abortion method. In particular, providers should incorporate into their counselling sessions what women need to know about the characteristics of abortion methods and help women to identify what is the best option for them. Key words: Early abortion medical methods, surgical methods, choice.

High risk nonmetastatic persistent gestational trophoblastic tumour following an abortion.

Locally invasive non-metastatic persistent gestational trophoblastic tumours (PGTT) following a non-molar pregnancy occur very rarely. Non-metastatic tumours usually falls in low risk group in WHO scoring system based on prognostic factors. We report a case of high risk non-metastatic PGTT which followed a spontaneous first trimester abortion. Complete remission of the tumour was achieved by chemotherapy EMA-CO regimen.

Impaired phagocyte respiratory burst responses to opportunistic fungal pathogens in transplant recipients: in vitro effect of r-metHuG-CSF (Filgrastim).

Phagocyte respiratory burst capacity in response to pathogenic fungi and the in vitro effects of granulocyte colony-stimulating factor (G-CSF) were examined in 15 normal volunteers and 39 transplant recipients (4 autologous and 4 allogeneic bone marrow, 3 heart, 10 liver, 8 lung, and 10 kidney). Chemiluminescence was measured for reaction mixtures of diluted whole blood, opsonized fungi, and luminol, with and without in vitro incubation with r-metHuG-CSF (Filgrastim). Transplant patients exhibited significantly impaired respiratory burst responses to conidia and yeast compared with controls, but this was reversed with Filgrastim. Responses to hyphae were low for both groups, and G-CSF had little or no effect. There was excellent correlation between responses to fungi and responses to opsonized zymosan. In vitro respiratory burst capacity is impaired in transplant recipients. This may predict susceptibility to invasive fungal infections. G-CSF can reverse impaired phagocyte function and is of potential benefit in the prevention and/or treatment of fungal infection in transplant patients.

High levels of inflammatory cytokines are associated with poor clinical response to steroid treatment and recurrent episodes of type 1 reactions in leprosy.

Levels of leprosy antigen-induced interferon-gamma (IFN-gamma), tumour necrosis factor alpha (TNF-alpha) and interleukin-10 (IL-10) were measured in 96 leprosy patients with type 1 reactions (T1R) before, during and after a standard 12-week course of steroids. Peripheral blood mononuclear cells (PBMC) from leprosy patients with untreated T1R produced significantly more TNF-alpha than leprosy patients without T1R. Median levels of IFN-gamma and TNF-alpha in T1R patients fell during treatment with steroids; however, TNF-alpha levels increased as the steroid dose was reduced. Median IL-10 levels increased throughout the steroid treatment period and were associated strongly with TNF-alpha levels. Patients with high cytokine levels had a poorer recovery of sensory or voluntary muscle nerve function, a higher risk of reactivation of symptoms during steroid treatment, and a higher risk of another episode of T1R within 2 months of completing the steroid regimen. Rapid and effective reversal of the inflammatory process in T1R is critical to prevent permanent nerve damage from T1R and monitoring cytokine levels during treatment may be useful.

Two-dimensional echocardiographic diagnosis of left-atrial thrombus in rheumatic heart disease. A clinicopathologic study.

Two-dimensional echocardiographic studies were performed in 293 patients with rheumatic heart disease who underwent open-heart mitral valve surgery during an 18-month period. Diagnostic confirmation of a left atrial thrombus was based on direct inspection of the left atrium during surgery and histopathologic examination. Two-dimensional echocardiographic recordings were reviewed. Of the 293 patients, 33 had left atrial thrombi by two-dimensional echocardiographic criteria. This diagnosis was confirmed at surgery and histopathologic study in 30 (specificity 98.8%). A thrombus was not found in three patients. In 21 other patients, left atrial thrombi were present but were not detected by two-dimensional echocardiography (sensitivity 58.8%). Ten of these 21 had thrombi in the left atrial cavity. In 11 patients, thrombi were located in the left atrial appendage, all of which were missed by two-dimensional echocardiography. Excluding these 11 left atrial appendage thrombi, the sensitivity of two-dimensional echocardiography for detecting left atrial cavity thrombi was 75.0%.