Weil's Disease from a Local New Orleans Bar.

INTRODUCTION: Leptospirosis is a zoonotic infection that typically presents with fever, myalgias, nausea, and vomiting after contact with contaminated waters or infected animals (typically rodents); and their excrements. Conditions favorable to the transmission of leptospirosis are common in LA and, without treatment, leptospirosis can lead to both liver and renal failure, meningitis, pulmonary hemorrhage and ultimately death. CASE: A 56 year old woman with no past medical history presented to the Emergency Department with weakness, myalgias, jaundice and decreased urine output for one week. On arrival, she appeared septic with a heart rate of 130 and fever. Her exam was significant for significant jaundice and diffuse abdominal pain. Laboratory studies were notable for WBC 14, hemoglobin of 12 and platelet count of 63. Creatinine was 8.5mg/dL with a blood-urea nitrogen of 96mg/dl. Total bilirubin was 19.4mg/dL and direct bilirubin was 13.7mg/dL. AST/ALT were 69/38 U/L, respectively and the alkaline phosphate was 160U/L. The patient was admitted to the hospital medicine wards for sepsis and multi-organ failure. She was started on broad spectrum antibiotics but her clinical condition continued to worsen with progressive decline in her hemoglobin and thrombocytopenia and worsening liver failure. She quickly became anuric necessitating dialysis and developed respiratory distress with bilateral pulmonary infiltrates and hemoptysis. Additional history was obtained from her employer that she works at a local New Orleans bar and had been cleaning out rats from the kitchen. Leptospirosis antibody was sent, which returned as positive. Her antibiotics were de-escalated to IV Ceftriaxone. She made a slow recovery over the next two-week period. DISCUSSION: Since 1987, there has been an average of 3 cases of Leptospirosis diagnosed per year, most of which have been from southeast LA. This case illustrates the importance of considering the diagnosis of Leptospirosis and Weil's Disease in patients in the southeast region of LA who present with multi-organ failure. In addition, our patient's occupational exposure was key to her diagnosis which emphasizes the importance of a detailed history in clinical decision making and patient outcomes.

Chemoproteomics-enabled covalent ligand screen reveals a cysteine hotspot in reticulon 4 that impairs ER morphology and cancer pathogenicity.

Chemical genetics has arisen as a powerful approach for identifying novel anti-cancer agents. However, a major bottleneck of this approach is identifying the targets of lead compounds that arise from screens. Here, we coupled the synthesis and screening of fragment-based cysteine-reactive covalent ligands with activity-based protein profiling (ABPP) chemoproteomic approaches to identify compounds that impair colorectal cancer pathogenicity and map the druggable hotspots targeted by these hits. Through this coupled approach, we discovered a cysteine-reactive acrylamide DKM 3-30 that significantly impaired colorectal cancer cell pathogenicity through targeting C1101 on reticulon 4 (RTN4). While little is known about the role of RTN4 in colorectal cancer, this protein has been established as a critical mediator of endoplasmic reticulum tubular network formation. We show here that covalent modification of C1101 on RTN4 by DKM 3-30 or genetic knockdown of RTN4 impairs endoplasmic reticulum and nuclear envelope morphology as well as colorectal cancer pathogenicity. We thus put forth RTN4 as a potential novel colorectal cancer therapeutic target and reveal a unique druggable hotspot within RTN4 that can be targeted by covalent ligands to impair colorectal cancer pathogenicity. Our results underscore the utility of coupling the screening of fragment-based covalent ligands with isoTOP-ABPP platforms for mining the proteome for novel druggable nodes that can be targeted for cancer therapy.

NEVER SEEMS TO GROW PAINS: A CASE OF SUSPECTED PSEUDOSEPTIC ARTHRITIS.

Pseudoseptic arthritis is an acute inflammatory arthritis found in association with a sterile synovial fluid culture despite white blood cell (WBC) counts >100,000 and >75% polymorph neutrophils. This arthritis occurs most frequently in patients with underlying inflammatory or immune disorders. Early distinction from true septic arthritis can decrease the need for unnecessary antibiotics and improve patient outcomes.

Gene expression alterations at baseline and following moderate exercise in patients with Chronic Fatigue Syndrome and Fibromyalgia Syndrome.

OBJECTIVES: To determine mRNA expression differences in genes involved in signalling and modulating sensory fatigue, and muscle pain in patients with chronic fatigue syndrome (CFS) and fibromyalgia syndrome (FM) at baseline, and following moderate exercise. DESIGN: Forty-eight patients with CFS only, or CFS with comorbid FM, 18 patients with FM that did not meet criteria for CFS, and 49 healthy controls underwent moderate exercise (25 min at 70% maximum age-predicted heart rate). Visual-analogue measures of fatigue and pain were taken before, during and after exercise. Blood samples were taken before and 0.5, 8, 24 and 48 h after exercise. Leucocytes were immediately isolated from blood, number coded for blind processing and analyses and flash frozen. Using real-time, quantitative PCR, the amount of mRNA for 13 genes (relative to control genes) involved in sensory, adrenergic and immune functions was compared between groups at baseline and following exercise. Changes in amounts of mRNA were correlated with behavioural measures and functional clinical assessments. RESULTS: No gene expression changes occurred following exercise in controls. In 71% of patients with CFS, moderate exercise increased most sensory and adrenergic receptor's and one cytokine gene's transcription for 48 h. These postexercise increases correlated with behavioural measures of fatigue and pain. In contrast, for the other 29% of patients with CFS, adrenergic α-2A receptor's transcription was decreased at all time-points after exercise; other genes were not altered. History of orthostatic intolerance was significantly more common in the α-2A decrease subgroup. FM-only patients showed no postexercise alterations in gene expression, but their pre-exercise baseline mRNA for two sensory ion channels and one cytokine were significantly higher than controls. CONCLUSIONS: At least two subgroups of patients with CFS can be identified by gene expression changes following exercise. The larger subgroup showed increases in mRNA for sensory and adrenergic receptors and a cytokine. The smaller subgroup contained most of the patients with CFS with orthostatic intolerance, showed no postexercise increases in any gene and was defined by decreases in mRNA for α-2A. FM-only patients can be identified by baseline increases in three genes. Postexercise increases for four genes meet published criteria as an objective biomarker for CFS and could be useful in guiding treatment selection for different subgroups.

Myalgic encephalomyelitis: International Consensus Criteria.

The label 'chronic fatigue syndrome' (CFS) has persisted for many years because of the lack of knowledge of the aetiological agents and the disease process. In view of more recent research and clinical experience that strongly point to widespread inflammation and multisystemic neuropathology, it is more appropriate and correct to use the term 'myalgic encephalomyelitis' (ME) because it indicates an underlying pathophysiology. It is also consistent with the neurological classification of ME in the World Health Organization's International Classification of Diseases (ICD G93.3). Consequently, an International Consensus Panel consisting of clinicians, researchers, teaching faculty and an independent patient advocate was formed with the purpose of developing criteria based on current knowledge. Thirteen countries and a wide range of specialties were represented. Collectively, members have approximately 400 years of both clinical and teaching experience, authored hundreds of peer-reviewed publications, diagnosed or treated approximately 50 000 patients with ME, and several members coauthored previous criteria. The expertise and experience of the panel members as well as PubMed and other medical sources were utilized in a progression of suggestions/drafts/reviews/revisions. The authors, free of any sponsoring organization, achieved 100% consensus through a Delphi-type process. The scope of this paper is limited to criteria of ME and their application. Accordingly, the criteria reflect the complex symptomatology. Operational notes enhance clarity and specificity by providing guidance in the expression and interpretation of symptoms. Clinical and research application guidelines promote optimal recognition of ME by primary physicians and other healthcare providers, improve the consistency of diagnoses in adult and paediatric patients internationally and facilitate clearer identification of patients for research studies.

Applied technologies in humanitarian assistance: report of the 2009 Applied Technology Working Group.

Information and communication technologies, especially in the forms of mobile telecommunications, satellite imaging, and geographical information systems, promise to significantly improve the practice of humanitarian relief. A working group convened at the Humanitarian Action Summit 2009, has begun investigating the challenges to implementing these technologies in field operations, keeping in mind the ethical considerations of linking people to place, and pledging to build a community of practice among academics, practitioners, and developers.

Fluctuating hearing loss with otorrhoea in Hughes syndrome.

We present an unusual case of bilateral aural symptoms in a 34-weeks pregnant woman with Hughes syndrome. This report underscores the unpredictable nature of this syndrome and its ENT complications. No previous case of fluctuating hearing loss and otorrhoea in Hughes syndrome has been described.

Sensorineural hearing loss with brainstem auditory evoked responses changes in homozygote and heterozygote sickle cell patients in Guadeloupe (France).

This prospective study involved 79 homozygote and heterozygote sickle cell anaemia patients (16 to 50 years old) and a control group of 40 people.All patients underwent ENT, audiological and brainstem auditory evoked responses (BSER) examinations in order to evaluate the incidence of sensorineural hearing loss (SNHL), to identify the changes at the level of the cochlear nerve and the central pathways, and to determine the most vulnerable group, in order to intervene with early prevention and rehabilitation for this condition.A hearing loss of greater than 20 dB at two or more frequencies was found in 36 (45.57 per cent) sickle cell patients (19 (47.22 per cent) HbSC patients and 17 (43.59 per cent) HbSS patients) and three (7.5 per cent) members of the control group. Homozygote and heterozygote patients, as well as both sexes, were equally affected. Bilateral hearing loss occurred in 19 (52.78 per cent) patients, unilateral right-sided hearing loss in five (13.89 per cent) patients and unilateral left-sided hearing loss in 12 (33.33 per cent) patients. Brainstem auditory evoked potential demonstrated a prolonged I-V (III-V) interpeak latency in 13 (25.35 per cent) sickle cell patients (11 men (eight with HbSS) and two women). The hearing loss in HbSS patients was neural in nature and of earlier onset; the hearing loss in HbSC patients was usually cochlear in nature and of later onset. Despite high medical standards and 100 per cent social security cover, the high incidence of SNHL in our sickle cell affected patients (the majority with the Benin haplotype) was probably due to their specific haematological profile and to the original geographical distribution of the disease in the tropics. Our results highlight the necessity for early and regular hearing assessment of sickle cell patients, including BSER examination, especially in male patients with SNHL.

Nutrition support improves patient outcomes, treatment tolerance and admission characteristics in oesophageal cancer.

AIMS: Patients with oesophageal cancer undergoing chemoradiation with curative intent are at high risk of malnutrition and its complications, including increased side effects of treatment. We have developed a nutrition pathway (NP), involving the early then periodic nutrition assessment of all patients presenting to the multidisciplinary oesophageal clinic who were planned to receive definitive chemoradiation. MATERIALS AND METHODS: Patients were assessed as at 'low', 'moderate' or 'severe' nutrition risk, and were provided with appropriate nutrition intervention ranging from preventative advice (low risk), oral nutrition support (moderate risk) to enteral feeding (severe risk). Outcomes for 24 patients treated before implementation of the NP were compared with those of 24 patients treated using the NP. RESULTS: Patients managed using the NP experienced less weight loss (mean weight change -4.2 kg +/-6.4 cf. -8.9 kg +/- 5.9, P = 0.03), greater radiotherapy completion rates (92% cf. 50%, P = 0.001), fewer patients had an unplanned hospital admission (46% cf. 75%, P = 0.04), and those that did had a shorter length of stay (3.2 days +/- 5.4 cf. 13.5 days +/- 14.1, P = 0.002). CONCLUSION: Early and regular nutrition assessment/intervention and a multidisciplinary approach to nutrition care results in improved treatment tolerance for patients with oesophageal cancer receiving chemoradiation.

Potentially misleading extratemporal lobe lesions in patients with temporal lobe epilepsy.

From a series of 217 consecutive temporal resections for intractable epilepsy between 1993 and 2000, we identified all patients with large non-neoplastic extratemporal lesions. Only patients with known postsurgical outcomes with follow up for more than two years were included. Fifteen patients were identified. All patients had a history of medically refractory epilepsy with clinical and ictal evidence of mesial temporal seizure onset. Eleven patients had extratemporal lesions ipsilateral to the seizure focus, whereas four patients had the lesions contralateral to the seizure focus. Nine of the 15 patients had evidence of hippocampal atrophy on magnetic resonance imaging (MRI). Following temporal resection, nine of these patients (60%) became seizure free (Engel class 1A), two patients were free of disabling seizures only (Engel class 1B), and two patients had a few early seizures but then became seizure free for at least two years (Engel class 1C). Two patients had significant improvement (Engel class 2). Thus, the finding of large extratemporal lesions on MRI was potentially misleading. When clinical semiology and ictal EEG recordings provide evidence of temporal onset seizures, anterior temporal resection should be considered in patients with extratemporal lesions.

[Subcutaneous emphysema and pneumomediastinum after dental drilling]. / Emphysème sous-cutané et pneumo-médiastin suite au fraisage dentaire.

Subcutaneous emphysema and pneumomediastinum is a rare complication of dental treatment. Our case report describes a case secondary to dental drilling with a high-speed air drill, and diffusion of the compressed air. Our case had the classical clinical features of sudden subcutaneous emphysema starting in the face, and subsequently extending into the neck and thorax, accompanied by severe pain and dyspnoea. Rapid medical treatment for this emergency avoided the surgical decompression.

A distal histidine mutant (H52Q) of yeast cytochrome c peroxidase catalyzes the oxidation of H(2)O(2) instead of its reduction.

A H52Q variant of yeast cytochrome c peroxidase (CcP), in which the distal histidine is replaced by glutamine, catalyzes oxidation of H(2)O(2) instead of reduction. This redirection of catalytic action is detected by protein film voltammetry. In the presence of H(2)O(2), wild-type CcP, adsorbed on a graphite electrode, shows a strong catalytic reduction wave commencing at about 0.8V (pH 5.4); by contrast, H52Q does not exhibit this activity but instead shows a catalytic oxidation current at potentials in the region of 0.9 V. The oxidation current is partly suppressed in the presence of tetranitromethane (a superoxide scavenger) and is not observed for other mutants studied, including H52A. The only significant structural change in the H52Q variant is that the Q-52 side chain occupies the space vacated by the H-52 imidazole; specifically, the N-epsilon atom that is believed to transfer a proton and induce O--O cleavage is replaced, to within 0.75 A, by the carbamide-O. Thus, while the weakly basic amide functionality is unable to serve in the reorganization of bound H(2)O(2), it is able to facilitate its oxidation, most obviously by serving as a H-bond acceptor to assist formation of a labile superoxide intermediate.

Consistency of condom use among users of injectable contraceptives.

Use of condoms for protection against sexually transmitted diseases (STDs) was examined over a nine-month period among 536 women from 17 clinics in southeastern Texas who had selected the injectable depot-medroxyprogesterone acetate (DMPA) as a contraceptive. Among women who were using condoms prior to receiving DMPA, nearly half said they never or rarely did so after initiating DMPA use; only 18% of all women in the study used condoms consistently while relying on DMPA. Factors associated with consistent condom use were being black (odds ratio of 2.0), being unmarried (odds ratio of 2.2), having a history of STD infection (odds ratio of 1.8), having previously used condoms (odds ratio of 2.7) and having no interest in future childbearing (odds ratio of 1.8). Our data suggest that the majority of users of injectables may not be protected from exposure to the human immunodeficiency virus and other STDs.

Experiences of injectable contraceptive users in an urban setting.

OBJECTIVE: To examine method-related experiences and acceptability of depot medroxyprogesterone acetate (DMPA) among women using this contraceptive for the first time. METHODS: Five hundred thirty-six women who received an injection of DMPA from any of seventeen clinical settings in southeast Texas, United States, were followed for 1 year. At each follow-up visit, patients were asked about their experiences with DMPA during the past 3 months and their plans to use this method in the future. RESULTS: Amenorrhea, irregular bleeding, and weight gain were the conditions reported most frequently. Reports of amenorrhea, weight gain, and acne or skin problems increased over time, but complaints of longer periods decreased (P < .001). Two pregnancies occurred during the study period. However, of these, one existed before the first injection. Depot medroxyprogesterone acetate's continuation rate at 1 year was 28.6%. Heavier and more frequent bleeding, increased cramping, amenorrhea, weight gain, headaches, depression, and nervousness were more frequent complaints of women who discontinued DMPA (P < .05), whereas lighter and less frequent bleeding were reported more often by those who continued to use this method (P <.05). Women who discontinued use of DMPA were more likely to be married and have a concern about injectable contraceptives than those who continued to use this method. CONCLUSION: Intolerable side effects and changes in menstrual pattern are the most frequently indicated reasons for discontinuing DMPA use. Our results suggest that DMPA's 1-year continuation rate may be lower than previously reported.

Characteristics and experiences of American women electing for early removal of contraceptive implants.

The study describes the experiences of 430 women who had Norplant(R) contraceptive implants removed prior to the five years of method effectiveness. Each subject was surveyed when the implants were inserted and again at the time of removal. Descriptive data are presented concerning perceptions of the method before insertion and after removal, reactions to the contraceptive and experiences associated with the removal procedure. Subjects' use of Norplant implants ranged from 14 days to 40 months, with a mean of 13.3 and median of 13 months. Over 95% reported changes in menstrual bleeding patterns and 95% experienced other non-bleeding related side effects. Non-bleeding side effects were the most frequently indicated reasons for removal, followed by bleeding changes. The mean removal time was 34 minutes with a median of 25 minutes. Over 48% reported experiencing significant pain during the removal procedure, and 27% stated that the pain was greater than expected. Despite electing for early removal of implants,the majority of women surveyed indicated satisfaction with all aspects of the method save its effect on their overall health. Although method-related side effects were intolerable for most subjects, their overall perception of the method was generally satisfactory.

PIP: 430 women enrolled at the time of acceptance in a longitudinal study of Norplant acceptability elected to have their implants removed between May 13, 1991 and September 8, 1994 (within 40 months of insertion). 225 of these women were surveyed immediately after removal, and 205 were identified during the follow-up study. The study provided information sociodemographic characteristics of the women and on 1) contraceptive method used before and after Norplant; 2) concerns about Norplant which were expressed prior to insertion; 3) reasons indicated for having implants removed; 4) changes in bleeding patterns; 5) side effects unrelated to menstrual bleeding; 6) significant pain reported during each of six stages of the removal process; and 7) user satisfaction in terms of comfort, convenience, cost, health effect, insertion, removal, and medical care. Most of the women chose early removal because they were unable to tolerate the side effects, but 13% chose removal because of discomfort at the implantation site and 10% because they no longer desired contraception. Removal was related to a pregnancy in three women (not method failure), and five others were acting on their physicians' advice. 48% of the women reported significant pain during removal, which was a larger number than expected. Since the cost-effectiveness of Norplant depends upon longterm use, it will be helpful to identify women who might be better served by a shorter term contraceptive. Despite the desire for removal, more than 25% of the women stated that they would consider Norplant use again in the future. Because side effects caused most women to discontinue, it is important that patients be properly counseled on the disadvantages of a longterm method.

Characteristics of injectable contraceptive users in a low-income population in Texas.

Among 600 women at 17 family planning clinics in Texas who expressed interest in using the hormonal injectable depot medroxyprogesterone acetate (DMPA), 536 (89%) actually received the injectable. Thirty percent of the DMPA recipients were younger than 21 and 77% were not married. The average numbers of pregnancies and births were 1.9 and 1.2 per woman; one-third of the women had had at least one abortion. The majority of women receiving DMPA (66%) were using it to space births. Their main sources of information about the method were friends (42%) and health care providers (37%), and the most commonly reported reason for its use was dissatisfaction with previous contraceptive methods.

PIP: The purpose of this prospective study was to add to the little data that exists concerning the characteristics and attitudes of depot medroxyprogesterone acetate (DMPA) users. Among 600 women at 17 family planning clinics in Texas who expressed interest in using the hormonal injectable DMPA, 536 (89%) actually received the injectable. DMPA users were significantly more likely than other women to be 20-24 years old, whereas a smaller percentage were 30 or older (p 0.001). 30% of the DMPA recipients were younger than 21; 50% were Black; and the rest were either White (25%) or Hispanic (24%). 77% of women adopting DMPA were not married. In contrast, most of the other patients who received contraceptive care at these clinics were married (64%; p 0.001). The average education of the DMPA acceptors was 11.9 years: Hispanic women had significantly less education (10.6 years) than did either Blacks or Whites (p or= 0.001). The average numbers of pregnancies and births were 1.9 and 1.2 per woman; 1/3 of the women had had at least 1 abortion. 34% of the women indicated they had no desire for more children. The majority of women receiving DMPA (66%) were using it to space births. Their main sources of information about the method were friends (42%) and health care providers (37%). 58% of the women reported dissatisfaction with previous contraceptive methods as the reason for its use, while 42% chose it because they were curious about it. 17% of the women were concerned about the method's effect on future pregnancies and 10% about the women's ability to conceive. In addition, a possible hormonal effect and the newness of the method were each cited by about 15% of DMPA users. The most frequently cited reasons for not receiving the injection involved the fear of bleeding (21%), acne or skin problems (21%), abdominal pain (19%), and weight gain (14%). One potential limitation of these findings is that the attitudes of women of lower socioeconomic status about DMPA may differ from their more affluent counterparts.

A cross-sectional survey of condom use in conjunction with other contraceptive methods.

A cross-sectional survey of 3,136 women attending family planning clinics in Texas was conducted to examine past use of and future plans for use of condoms by partners during sexual intercourse for disease prevention in conjunction with other contraceptive methods. Following the receipt of clinical services, including counseling about family planning and disease prevention, both contraceptive and planned condom use reporting increased for the majority of subjects. However 22% of the sample indicated that they intended to reduce condom use in the future and instead use a contraceptive which protects from pregnancy but not from disease. Condom use was indicated more frequently for those who reported at least one risk factor for HIV, but 17% of those at risk indicated lower future condom use than past use. This suggests that without changes in risk behavior, these women will be at increased risk of HIV or another sexually transmitted disease.

PIP: During May 10-July 20, 1993, clinic staff interviewed 3136 women aged 12-45 attending 13 family planning clinics in southeastern Texas so researchers could determine the frequency of condom use for prevention of sexually transmitted diseases (STDs) in women using other forms of contraception for pregnancy prevention. 30% had had unprotected intercourse at least once in the last month. Clients who planned to always use a contraceptive method in the future increased from 58% to 83% after counseling. After counseling, 31% planned to always use a condom in the future. Before the visit, 10% had always used a condom. After counseling, condom use with oral contraceptives, IUD, diaphragm, cervical cap, implants, Depo Provera, or sexual sterilization increased from 28% to 42%. 35% of clients used condoms when they thought that protection was needed. 72% were currently in a monogamous relationship. 10% considered themselves not at risk of HIV. Women with one sexual partner tended to think that they were not at risk of HIV or not concerned about HIV. They were much less likely to intend to use condoms in the future with another method than their counterparts. Three women had HIV infection. 4% had genital herpes. 13% had had another STD. 260 women (8%) had had intercourse with partners engaging in risky behavior. 47% of clients had at least one risk factor for HIV (e.g., recent STD). After counseling, condom use increased among clients with risk factors for HIV. These same clients were also more likely to use condoms than those with no risk factors. 17% of these clients planned to reduce condom use in the future, however. 22% of clients planned to decrease condom use in the future and use a contraceptive method to protect against pregnancy rather than STDs. These findings show that many women at risk for STDs who request contraception do not protect themselves from STDs, indicating an additional unmet need. The researchers suggest that there should be research and development for intervention methods for women at risk for STDs who stop using condoms when they receive another contraceptive method.

Comparison of three types of ultrasound transducers in evaluating the amniotic fluid index.

The purpose of this study was to determine whether there was good correlation between amniotic fluid index measurements obtained with different types of ultrasound transducer. Women undergoing obstetric ultrasonography for multiple indications between 26 and 40 weeks' gestation had the four-quadrant amniotic fluid index measured with three ultrasound transducers: 3.5-MHz linear, 3.5-MHz sector and 3.5-MHz convex. Pearson product-moment correlation and linear regression analysis were utilized to compare the amniotic fluid index values. Sixty-five women participated in the study. A statistically significant correlation was noted between the three ultrasound transducers evaluated (P < .001). Placental location did not appear to affect the results. Amniotic fluid index values obtained with the sector or convex transducers were as reliable as those obtained with the "gold standard" linear transducer and may be interpreted in the same manner.