Surface-enhanced Raman scattering measurement from a lipid bilayer encapsulating a single decahedral nanoparticle mediated by an optical trap.

We present a new technique for the study of model membranes on the length-scale of a single nano-sized liposome. Silver decahedral nanoparticles have been encapsulated by a model unilamellar lipid bilayer creating nano-sized lipid vesicles. The metal core has two roles (i) increasing the polarizability of vesicles, enabling a single vesicle to be isolated and confined in an optical trap, and (ii) enhancing Raman scattering from the bilayer, via the high surface-plasmon field at the sharp vertices of the decahedral particles. Combined this has allowed us to measure a Raman fingerprint from a single vesicle of 50 nm-diameter, containing just ∼104 lipid molecules in a bilayer membrane over a surface area of <0.01 µm2, equivalent to a volume of approximately 1 zepto-litre. Raman scattering is a weak and inefficient process and previous studies have required either a substantially larger bilayer area in order to obtain a detectable signal, or the tagging of lipid molecules with a chromophore to provide an indirect probe of the bilayer. Our approach is fully label-free and bio-compatible and, in the future, it will enable much more localized studies of the heterogeneous structure of lipid bilayers and of membrane-bound components than is currently possible.

Label-free critical micelle concentration determination of bacterial quorum sensing molecules.

A practical label-free method for the rapid determination of small-molecule critical micelle concentration (CMC) using a fixed-angle light-scattering technique is described. Change in 90° light scattering at a fixed wavelength of incident radiation with increasing bacterial quorum molecule concentration and the observation of a break point is used to determine CMC. In our study, this technique is utilized to investigate the aqueous CMC of previously uncharacterized Pseudomonas aeruginosa quorum sensing signaling molecules (QSSM) belonging to the n-acylhomoserine lactone and 2-alkyl-4-quinolone classes. Several were found to form micelles within a physiologically relevant concentration range and potential roles of these micelles as QSSM transporters are discussed. The influence of temperature and the presence of biological membranes or serum proteins on QSSM CMC are also investigated and evidence is obtained to suggest the QSSMs studied are capable of both membrane and serum protein interaction. This demonstrates that the fixed-angle light-scattering technique outlined can be used simply and rapidly to determine small-molecule CMC under a variety of conditions.

Lymphogranuloma venereum presenting as genital ulceration and inguinal syndrome in men who have sex with men in London, UK.

OBJECTIVES: To describe a series of lymphogranuloma venereum (LGV) cases presenting as inguinal syndrome and/or genital ulceration seen among men who have sex with men (MSM) in London, UK. METHODS: Collaborative retrospective case note review. Clinicians from three London genitourinary medicine (GUM) clinics accessed by large populations of MSM within the current LGV outbreak collected clinical data from confirmed cases of LGV inguinal syndrome or genital ulcer. LGV was confirmed by the detection of LGV-specific DNA from specimens such as bubo aspirates, ulcer swabs, urethral swabs, first void urine and rectal biopsy material. RESULTS: There were 13 cases detected overall: 5 cases of urethral LGV infection with inguinal adenopathy, 3 cases of genital ulcer with LGV inguinal adenopathy, 3 cases of isolated LGV-associated inguinal buboes, 1 case of a solitary LGV penile ulcer and 1 case with a penile ulcer and bubonulus. Only 6 of the 13 were HIV positive and all tested negative for hepatitis C. The majority of cases reported few sexual contacts in the 3 months preceding their diagnosis. CONCLUSIONS: Clinical manifestations of LGV in MSM have not been confined to proctitis in the current outbreak in the UK and a small but significant number of inguinogenital cases of LGV have been observed. Epidemiologically, many of the cases described seem to have occurred at the periphery of the current MSM LGV epidemic. Clinicians need to be vigilant for these less common presentations of LGV among MSM and specific diagnostic tests should be done from the relevant lesions.

HIV and travel.

There is a high demand for travel among HIV-positive individual. This demand arises partly from those who have benefited from advances in antiretroviral therapy as well as those with disease progression. The key to a successful and uneventful holiday lies in careful pre-trip planning, yet many patients fail to obtain advice before travelling. Travel advice for HIV patients is becoming increasingly specialized. In addition to advice on common travel-related infectious diseases, HIV-positive travellers are strongly advised to carry information with them and they need specific advice regarding country entry restrictions, HIV inclusive travel insurance, safety of travel vaccinations and highly active antiretroviral therapy-related issues. A wide range of relevant issues for the HIV-positive traveller are discussed in this review and useful websites can be found at the end.

Knowledge, attitudes and health outcomes in HIV-infected travellers to the USA.

BACKGROUND: The USA bans entry to non-citizens unless they obtain a waiver visa. AIM: To establish how many people with HIV infection travelled to the USA, whether they were aware of the travel restriction, whether they travelled with a waiver visa and HIV inclusive medical insurance and how they managed with their antiretroviral medication (ARV). DESIGN: Collation of data from cross-sectional studies conducted independently at three different medical centres, Manchester, Brighton and London, using a structured self-completion questionnaire. RESULTS: The overall response rate was 66.6% (1113 respondents). 349 (31%) had travelled to the USA since testing HIV positive, of whom only 14.3% travelled with a waiver visa. 64% and 62% of the respondents at Manchester and Brighton were aware of the need of a waiver visa. 68.5% (212) were on ARV medication at the time of travel and, of these, 11.3% stopped their medication. Of those taking ARV medication, only 25% took a doctors' letter, 11.7% posted their medication in advance. Of those discontinuing treatment (n=27), 55.5% sought medical advice before stopping, 11 were on NNRTI-based regimen and one developed NNRTI-based mutation. Only 27% took up HIV inclusive medical insurance. Many patients reported negative practical and emotional experiences resulting from travel restrictions. CONCLUSION: The majority of HIV patients travel to the USA without the waiver visa, with nearly half doing so with insufficient planning and advice. A significant minority (11.3%) stop their medication in an unplanned manner, risking the development of drug resistance.

Genital manifestations of tropical diseases.

Genital symptoms in tropical countries and among returned travellers can arise from a variety of bacterial, protozoal, and helminthic infections which are not usually sexually transmitted. The symptoms may mimic classic sexually transmitted infections (STIs) by producing ulceration (for example, amoebiasis, leishmaniasis), wart-like lesions (schistosomiasis), or lesions of the upper genital tract (epididymo-orchitis caused by tuberculosis, leprosy, and brucellosis; salpingitis as a result of tuberculosis, amoebiasis, and schistosomiasis). A variety of other genital symptoms less suggestive of STI are also seen in tropical countries. These include hydrocele (seen with filariasis), which can be no less stigmatising than STI, haemospermia (seen with schistosomiasis), and hypogonadism (which may occur in lepromatous leprosy). This article deals in turn with genital manifestations of filariasis, schistosomiasis, amoebiasis, leishmaniasis, tuberculosis and leprosy and gives clinical presentation, diagnosis, and treatment.

Condoms and seat belts: the parallels and the lessons.

PIP: This paper investigates the relation between behavior adaptation and safety benefits of seat belts and whether condom promotion can be undermined by unintended changes in sexual risk perception and behavior. The comparison between 13 countries that passed seat belt laws and 4 countries without such laws shows a significant number of deaths among countries with seat belt laws. It has been suggested that drivers who wear seat belts feel safer and drive faster and more carelessly compared to those without seat belts. A model of individual risk management, postulating that every individual is comfortable with a certain level of risk and aims to balance the rewards of risk-taking against perceived hazards was developed to describe the behavior. This increase in seat belt use was then paralleled with condom use since the rise of HIV, with 3 ways in which a large increase in condom use could fail to affect transmission: 1) it appeals to risk-averse individuals who contribute little to epidemic transmission; 2) increased use of condom increases the number of transmission caused by condom failure; and 3) the increased use of condoms reflect the change in the decision of individuals from one partner to maintaining higher rates of partners and reliance on condoms. This paper, in conclusion, emphasizes the need for program development and implementation in response to this sexual behavior, particularly among developing countries.^ieng

Cardiac failure in children with pneumonia in Papua New Guinea.

BACKGROUND: Cardiac failure is suspected of contributing to mortality from pneumonia in children in developing countries, but its role has not been clearly defined. METHODS: A convenience sample of 47 children admitted to Goroka Hospital in Papua New Guinea was studied prospectively with ultrasound, chest radiographs and assays of creatine kinase and lactate dehydrogenase. Results. Seven (15%) of the 47 children died. Of the 43 children who had a chest radiograph, 31 (72%) had severe or very severe pneumonia. No child had poor contractility of the heart on ultrasound examination or unequivocally raised cardiac isoenzymes; therefore no evidence of myocardial injury from sepsis was found. However, ultrasound examination showed dilatation of the right ventricle or hepatic veins in 12 (26%) of the children (both were dilated in 7 children) and 4 (33%) of these children died; this suggests that right ventricular cardiac failure secondary to pulmonary hypertension was present in 26% (95% confidence interval, 14 to 40%) of these children with severe pneumonia. Tachycardia was not associated with right ventricular dilatation on ultrasound, but 3 of the 4 children with more than 3 cm of liver palpable in the abdomen had right ventricular dilatation. Only 4 of the 12 children with right heart failure had hepatomegaly, tachycardia, raised jugular venous pressure or peripheral edema. CONCLUSIONS: Right ventricular failure is common in children with severe pneumonia, and it is probably caused by pulmonary hypertension rather than septic toxemia. The clinical signs of heart failure are unreliable. There is no evidence that digoxin is effective treatment for right ventricular failure secondary to pulmonary hypertension.

Safety, tolerance, and efficacy of atevirdine in asymptomatic human immunodeficiency virus-infected individuals.

Atevirdine is a nonnucleoside reverse transcriptase inhibitor of human immunodeficiency virus type 1 (HIV-1). In this study we investigated the effect of atevirdine in asymptomatic antiretroviral naive HIV-infected patients with CD4+ cell counts of between 200 and 750 cells per mm3. Patients were randomized to receive 600 mg of atevirdine (n = 15) or a placebo (n = 15) three times a day for 12 weeks. There was no statistically significant effect of atevirdine on viral loads (HIV p24 antigen and HIV-1 RNA levels by PCR) or CD4+ cell counts. The data do not support the use of atevirdine as a monotherapy in the treatment of HIV-infected patients.

Typhoid in the highlands of Papua New Guinea 1984-1990: a hospital-based perspective.

A first-hand account is given of the epidemic of typhoid in the Goroka area as it evolved from 1984 to 1990. The monthly admissions for typhoid to Goroka Base Hospital showed a peak in 1988. The sex and age distribution showed a predominance of young adults. The overall case fatality rate of hospitalized patients was of the order of 10-15%; in a carefully documented group of 374 patients 27% were assessed as having severe typhoid and this subgroup had a case fatality rate of 44%. The clinical features were studied in 516 patients. The high mortality appeared to result from septic shock; ileal perforation was found in only 1.3% of patients. A skin lesion equivalent to but significantly different from the classic rose spot was found in 30% of patients. The typhoid facies was commonly encountered in patients with well-established typhoid. Cerebellar tremor and hearing loss were frequent diagnostic findings. Blood and bone marrow cultures were used to confirm the diagnosis; bone marrow culture proved practicable but gave little increased yield over blood culture. A clinical algorithm to help distinguish typhoid and malaria was developed, principally for use in health centres in the highlands. The mainstay of treatment was chloramphenicol and very few problems were encountered with its use in inpatients. Bacteriological resistance to chloramphenicol did not develop over the study period. Other drugs, such as fluorinated quinolones, may be more effective when all aspects are considered, despite higher cost, but this remains to be investigated. Hydrocortisone in patients with severe disease was evaluated and shown to be ineffective but whether high-dose dexamethasone would reduce the mortality from typhoid in patients in Papua New Guinea still remains an unanswered question.

The spondyloarthropathies.

The spondyloarthropathies occur with variable frequency in the tropics. Ankylosing spondylitis, in particular, is thought to be rare in tropical Africa, reflecting a low frequency of the HLA B27 gene. However, in the Melanesian populations of Papua New Guinea where there is a relatively high frequency of HLA B27, ankylosing spondylosis is infrequent. These diverse observations may be related to variations in B27 sub-types. Reactive arthritis is a common and important form of acute arthritis in the tropics and in Papua New Guinea at least has a strong association with HLA B27. In Africa an increasing prevalence of reactive arthritis may be related to the spread of HIV infection. Extra-articular features such as balanitis and enthositis are helpful pointers to the diagnosis. Disseminated gonococcal infection and tuberculosis must always be considered and treatment offered if doubt exists. The mainstay of treatment of reactive arthritis is, as always, an anti-inflammatory drug, supplemented by hydrocortisone injections; docycline is available for chlamydia-triggered arthritis and chloroquine or dapsone for more chronic, unresponsive cases.

Sexually transmitted diseases in children in developing countries.

PIP: The populations of developing countries have younger age structures than the populations of more developed, Western countries. That is, children, adolescents, and youth constitute a far greater proportion of the populations of developing countries than in developed countries. These young people experiment with sex and sexual intercourse or have coitus on a regular basis depending upon their individual personalities and circumstances. The prevalence of sexually transmitted diseases (STD) among younger age groups in developing countries is not well documented. It may, however, be inferred on the basis of reported experience of STD in surveys of adolescents and young adults that many children are infected with STDs. Some young people have sex consensually, some are coaxed into it, and others are coerced. On the one hand, young children have been thought to contract STD by sitting on the laps of infected, scantily-clad adults where such limited attire is the norm. Close contact between youngsters such as communal sleeping, for example, could then facilitate the spread of the STD among children. Sex, consensual or otherwise, is not involved in such infection and transmission beyond the index adult. On the other hand, however, many children and adolescents are forced to have sexual relations and/or intercourse either directly against their will or as a result of the primal need to ensure their individual survival. For example, there are an estimated 100-200 million street children worldwide; many have little alternative but to sell sex to survive. When having sex, they may not use condoms because they are unaware of the STD risk they face, they have no access to free condoms, clients/employers/peers prevent them from using condoms, or due to a myriad of other reasons. Struggling to survive, many such kids place condom use very low on their list of priorities. Children and adolescents can also become infected and transmit STDs to others by engaging in sexual intercourse under more narrowly-defined cultural norms. For example, the belief exists that a male with urethritis can be cured by sexual intercourse with a virgin or prepubertal girl. Elsewhere, it is normal practice for an adult male, typically a boy's uncle, to have anal insertive sexual intercourse with the boy on a regular basis over the period of a couple years to facilitate his transition into manhood. People in young age groups around the world have sex for a range of reasons under a variety of conditions. Measures are needed to ensure that they have the means to prevent infection with STDs and control that infection, if possible, once acquired. Sections discuss vulvovaginitis, donovanosis, chancroid, and venereal and nonvenereal treponematosis, as well as prevention and future research.^ieng

Arthritis in the highlands of Papua New Guinea.

Acute polyarthritis is an important cause of morbidity in many tropical countries. Classification has often been difficult, with the term tropical polyarthritis used for those in whom a diagnosis could not be made. The implication that this is a distinct entity is probably incorrect, with likely causes being septic arthritis or post-infective reactive arthritis. This study aimed to determine the types of arthritis found in 43 patients (30 men) presenting consecutively to the Goroka Base Hospital in the Eastern Highlands of Papua New Guinea. Gonococcal arthritis was diagnosed in eight patients (six men) on the basis of isolation of Neisseria gonorrhoeae from the joint aspirate. In all cases the N gonorrhoeae was identified by the closed culture system on chocolate agar, but not always by routine plating. There were no specific clinical features that identified patients with a gonococcal septic arthritis. The remaining 34 patients had an undifferentiated oligoarthritis. The pattern of arthritis in men and women was of a lower limb pauciarticular arthritis with a predilection for the knee and ankle joints. A total of 30% of male patients had a history of urethral discharge and 44% of all patients had preceding diarrhoea. Arthritis was the only feature in 59% of patients and in 32% there was an associated enthesitis. In this study most patients had an oligoarthritis consistent with a reactive arthritis or a septic arthritis due to N gonorrhoeae. Broth inoculation of synovial fluid was the best method to isolate N gonorrhoeae, with standard methods for gonococcal isolation failing in some patients. It is recommended that the term 'tropical polyarthritis' is no longer used as it does not refer to a specific entity but consists of several known arthritides.

An algorithm for the clinical differentiation of malaria and typhoid: a preliminary communication.

The objective of this study was to determine which clinical features of typhoid and malaria are most helpful in distinguishing the two diseases among Papua New Guinean highlanders. In a study of 35 patients with culture-positive typhoid and 49 with blood-slide-positive malaria (Group 1), the odds of typhoid were increased most in patients with altered bowel habit, an illness of more than 2 week's duration, tremor or the presence of typhoid facies. The odds of typhoid were lowest in patients with pallor or jaundice. These findings were used to derive a clinical diagnostic algorithm, which was then evaluated in a further group of 34 typhoid patients and 41 malaria patients (Group 2). The sensitivity of the algorithm in diagnosing malaria was 91% in Group 1 and 71% in Group 2, with specificities of 85% and 79% respectively. For typhoid, the sensitivity of the algorithm was 85% and 79% for Groups 1 and 2, respectively, and the specificities were 91% and 71%. We conclude that the algorithm merits further evaluation in a primary health care setting and may prove useful in making an earlier diagnosis of typhoid.

Travel to the coast by highlanders and its implications for malaria control.

Three groups of highland subjects were questioned about malaria and their visits to coastal areas: patients admitted to Goroka Base Hospital with malaria, patients admitted with diagnoses other than malaria who had visited the coast within the previous six months, and health staff working in Goroka. Nearly a third in all groups reported having had two or three attacks of malaria. 82% of malaria patients had visited the coast in the previous 4 weeks compared to 26% of patients without malaria. Most malaria seen in Goroka is imported from the coast. Most patients in the survey came from rural areas and were uneducated. However, health workers also failed in most cases to take adequate precautions when they visited the coast. It is suggested that a malaria prophylaxis station should be set up at the gateway to the highlands on the Highlands Highway, where malaria education and the means for chemoprophylaxis and protection from mosquitoes could be made available for all travellers.