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Biomedical subjects

D Marriott

Publications and source records attributed to D Marriott.

At least 19 recordsLinked to original sources

Irritable bowel syndrome: a review on the role of intestinal protozoa and the importance of their detection and diagnosis.

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder in which abdominal pain is associated with a defect or a change in bowel habits. Gut inflammation is one of the proposed mechanisms of pathogenesis. Recent studies have described a possible role for protozoan parasites, such as Blastocystis hominis and Dientamoeba fragilis, in the etiology of IBS. Dientamoeba fragilis is known to cause IBS-like symptoms and has a propensity to cause chronic infections but its diagnosis relies on microscopy of stained smears, which many laboratories do not perform, thereby leading to the misdiagnosis of dientamoebiasis as IBS. The role of B. hominis as an etiological agent of IBS is inconclusive, due to contradictory reports and the controversial nature of B. hominis as a human pathogen. Although Entamoeba histolytica infections occur predominately in developing regions of the world, clinical diagnosis of amebiasis is often difficult because symptoms of patients with IBS may closely mimic those patients with non-dysenteric amoebic colitis. Clinical manifestations of Giardia intestinalis infection also vary from asymptomatic carriage to acute and chronic diarrhoea with abdominal pain. These IBS-like symptoms can be continuous, intermittent, sporadic or recurrent, sometimes lasting years without correct diagnosis. It is essential that all patients with IBS undergo routine parasitological investigations in order to rule out the presence of protozoan parasites as the causative agents of the clinical signs.

Animals↗

Secondary syphilis presenting as tonsillitis in three patients.

We describe three homosexual men presenting to the ear, nose and throat clinic with severe tonsillitis. All were subsequently diagnosed with secondary syphilis of the tonsil. Syphilis should be considered as a diagnosis in high risk patients presenting with tonsillar lesions, even in the absence of other classical features of the disease.

Adult↗

Minor changes in calculated creatinine clearance and anion-gap are associated with tenofovir disoproxil fumarate-containing highly active antiretroviral therapy.

BACKGROUND: Tenofovir disoproxil fumarate (Tenofovir DF, TDF), the first nucleotide reverse transcriptase inhibitor approved for the treatment of HIV disease, has been associated with renal dysfunction in isolated cases. The aim of this study was to assess changes in renal parameters in individuals receiving TDF- and non-TDF-containing highly active antiretroviral therapy (HAART). METHODS: All individuals on HAART attending our clinic were included in the analysis. Time-weighted changes in serum creatinine, calculated creatinine clearance (CCrCl) and anion-gap were assessed for individuals on TDF- and non-TDF HAART. RESULTS: Of 948 individuals on HAART, 290 (31%) and 618 (65%) were on TDF- and non-TDF HAART, with 40 (4%) having ceased TDF HAART. Baseline values for serum creatinine, CCrCl and anion-gap were similar for those on TDF- and non-TDF HAART. In a multivariate analysis, statistically significant differences were observed in time-weighted change from baseline in anion-gap and CCrCl between individuals on TDF- and non-TDF HAART [mean difference in change between groups: anion-gap 0.78 mmol/L (standard error, 0.19) and CCrCl-6.80 (standard error 2.2); P = 0.005 and P = 0.032, respectively] after adjusting for baseline anion-gap and CCrCl, respectively. Two cases of TDF-associated renal failure were observed. CONCLUSION: Overt renal failure with TDF HAART is rare. However, subtle but statistically significant changes in anion-gap and CCrCl were observed which were associated with TDF HAART. These parameters may be of use in monitoring individuals on HAART.

Acid-Base Equilibrium↗

Evaluation of three diagnostic methods, including real-time PCR, for detection of Dientamoeba fragilis in stool specimens.

Dientamoeba fragilis is a protozoan parasite of humans that infects the mucosa of the large intestine and is associated with gastrointestinal disease. We developed a 5' nuclease (TaqMan)-based real-time PCR assay, targeting the small subunit rRNA gene, for the detection of D. fragilis in human stool specimens and compared its sensitivity and specificity to conventional PCR and microscopic examination by a traditional modified iron-hematoxylin staining procedure. Real-time PCR exhibited 100% sensitivity and specificity.

Animals↗

Post-kala-azar dermal leishmaniasis due to Leishmania infantum in a human immunodeficiency virus type 1-infected patient.

We report the first case of post-kala-azar dermal leishmaniasis due to Leishmania infantum in a human immunodeficiency virus type 1-infected patient in Australia. Molecular characterization of the isolate was performed using PCR restriction fragment length polymorphism targeting both repetitive sequences from Leishmania nuclear DNA and repetitive kinetoplast DNA minicircles for species differentiation.

AIDS-Related Opportunistic Infections↗

Detection of Dientamoeba fragilis in fresh stool specimens using PCR.

Dientamoeba fragilis is a trichomonad parasite that causes human gastrointestinal disease. Currently microscopy is considered to be the gold standard for diagnosis of D. fragilis infection. However, this method is time-consuming and relatively insensitive. A PCR assay based on the small-subunit ribosomal RNA gene of D. fragilis for the specific detection of D. fragilis DNA in fresh unpreserved stool samples was developed. The D. fragilis PCR was positive in 29/31 samples with positive microscopy and did not cross-react with other protozoan parasites. The PCR protocol showed a specificity of 100% and a sensitivity of 93.5% and the entire procedure can be performed in one day.

Animals↗

Prospective study of the prevalence, genotyping, and clinical relevance of Dientamoeba fragilis infections in an Australian population.

A prospective study was conducted over a 30-month period, in which fecal specimens from 6,750 patients were submitted to the Department of Microbiology at St. Vincent's Hospital, Sydney, Australia. Trophozoites of Dientamoeba fragilis were detected in 60 (0.9%) patients by permanent staining, and confirmation was performed by PCR. Gastrointestinal symptoms were present in all patients, with diarrhea and abdominal pain the most common symptoms. Thirty-two percent of patients presented with chronic symptoms. The average age of infected patients was 39.8 years. No correlation was found between D. fragilis and Enterobius vermicularis, a proposed vector of transmission for D. fragilis. The genetic diversity of 50 D. fragilis isolates was examined by PCR, and the PCR products were analyzed for the presence of restriction fragment length polymorphisms. These results showed no variation in the small-subunit rRNA gene and demonstrated a single genotype for all Australian isolates. This study shows the potential pathogenic properties of D. fragilis and the need for all laboratories to routinely test for this organism.

Abdominal Pain↗

Early syphilis presenting as a painful polyradiculopathy in an HIV positive individual.

Neurosyphilis and neurological complications from syphilis may be commoner in HIV disease. With outbreaks of early syphilis in HIV positive individuals being observed over recent years, rare neurological manifestations of secondary syphilis will be observed more commonly. We describe a case of an HIV positive individual whose first presenting feature of early syphilis was a polyradiculopathy.

HIV Infections↗

Epidemiology and host- and variety-dependent characteristics of infection due to Cryptococcus neoformans in Australia and New Zealand. Australasian Cryptococcal Study Group.

A prospective population-based study was conducted in Australia and New Zealand during 1994-1997 to elucidate the epidemiology of cryptococcosis due to Cryptococcus neoformans var. neoformans (CNVN) and C. neoformans var. gattii (CNVG) and to relate clinical manifestations to host immune status and cryptococcal variety. The mean annual incidence per 10(6) population was 6.6 in Australia and 2.2 in New Zealand. Of 312 episodes, CNVN caused 265 (85%; 98% of the episodes in immunocompromised hosts) and CNVG caused 47 (15%; 44% of the episodes in immunocompetent hosts). The incidence of AIDS-associated cases in Australia declined annually (P<.001). Aborigines in rural or semirural locations (P<.001) and immunocompetent males (P<.001) were at increased risk of CNVG infection. Cryptococcomas in lung or brain were more common in immunocompetent hosts (P< or =.03) in whom there was an association only between lung cryptococcomas and CNVG. An AIDS-associated genetic profile of CNVN serotype A was confirmed by random amplification of polymorphic DNA analysis. Resistance to antifungal drugs was uncommon. The epidemiology of CNVN infection has changed substantially. Clinical manifestations of disease are influenced more strongly by host immune status than by cryptococcal variety.

AIDS-Related Opportunistic Infections↗

Epidemiology: surveillance of fungal infections.

Surveillance for fungal diseases is essential to improve our understanding of their epidemiology and to enable research and prevention efforts to be prioritized. In order to conduct better surveillance for fungal diseases, it is important to develop more accurate and timely diagnostic tests, to follow rigorous epidemiological methods and to have adequate support from public health agencies and the pharmaceutical industry. Investigations of nosocomial and community outbreaks of fungal infection have also resulted in a better understanding of the sources and routes of transmission of these diseases, and of the risk factors for infection. This has led to more effective prevention and control strategies. In addition, outbreak investigations have offered excellent opportunities to develop new molecular sub-typing methods, and to evaluate and validate older ones. For example, results obtained from a global epidemiological study of the genomic structure of Cryptococcus neoformans have led to a better understanding of the epidemiology of cryptococcosis. Similarly, a study of variations in the genotype of Trichophyton rubrum has found that patients may become infected with multiple strains, which has important implications for study design when looking at the epidemiology of dermatophyte infections.

Arthrodermataceae↗

Treatment of HIV-1-associated microsporidiosis and cryptosporidiosis with combination antiretroviral therapy.

BACKGROUND: Enterocytozoon bieneusi and Cryptosporidium parvum cause chronic antimicrobial-resistant gastrointestinal infections in HIV-1-infected individuals. HIV-1 reverse transcriptase inhibitors delay the onset of opportunistic infections, but are not known to reverse established infections. HIV-1 protease inhibitors are more effective across a broader range of HIV-1-infected immune cells. Combination antiretroviral therapy that includes a protease inhibitor could improve immunity to E bieneusi and C parvum. METHODS: HIV-1 infected patients with chronic microsporidiosis (five), cryptosporidiosis (three), or dual infection (one), were treated with combination therapy that included at least one HIV-1 protease inhibitor. Outcome measures were symptoms, weight, use of antidiarrhoeal and antimicrobial drugs, T-lymphocyte subsets, HIV-1 viraemia, stool microscopy, and biopsy by endoscopy. FINDINGS: All patients had complete clinical responses, gained a median 15 kg in weight, and ceased all antidiarrhoeal and antimicrobial therapies. Biliary cryptosporidiosis responded in both affected patients. Neither pathogen was detected in follow-up stool microscopy (eight of eight patients) or in biopsy samples by endoscopy (five of five). Intestinal architecture returned to normal in three patients. There was a dense CD8 lymphocyte and macrophage infiltrate and staining of intraepithelial E bieneusi with interferon-gamma before and after treatment, but little staining for CD4 or B lymphocytes, interleukin 10, or HIV-1 gp41. Five patients remained symptom-free after a median 13 months follow-up. Four patients had recurrent diarrhoea at 7-13 months (one with positive stool microscopy), associated with declining CD4 counts. INTERPRETATION: Combination antiretroviral therapy that includes a protease inhibitor can restore immunity to E bieneusi or C parvum in HIV-1 infected individuals, and result in complete clinical, microbiological, and histological responses. The persistent CD8 cell and macrophage infiltrate, and the rapid time to relapse in patients with declining CD4 lymphocyte counts, suggest that neither infection was eradicated.

AIDS-Related Opportunistic Infections↗

Intrachain disulfide bond in the core hinge region of human IgG4.

IgG is a tetrameric protein composed of two copies each of the light and heavy chains. The four-chain structure is maintained by strong noncovalent interactions between the amino-terminal half of pairs of heavy-light chains and between the carboxyl-terminal regions of the two heavy chains. In addition, interchain disulfide bonds link each heavy-light chain and also link the paired heavy chains. An engineered human IgG4 specific for human tumor necrosis factor-alpha (CDP571) is similar to human myeloma IgG4 in that it is secreted as both disulfide bonded tetramers (approximately 75% of the total amount of IgG) and as tetramers composed of nondisulfide bonded half-IgG4 (heavy chain disulfide bonded to light chain) molecules. However, when CDP571 was genetically engineered with a proline at residue 229 of the core hinge region rather than serine, CDP571 (S229P), or with an IgG1 rather than IgG4 hinge region, CDP571(gamma 1), only trace amounts of nondisulfide bonded half-IgG tetramers were observed. Trypsin digest reversephase HPLC peptide mapping studies of CDP571 and CDP571(gamma 1) with on-line electrospray ionization mass spectroscopy supplemented with Edman sequencing identified the chemical factor preventing inter-heavy chain disulfide bond formation between half-IgG molecules: the two cysteines in the IgG4 and IgG1 core hinge region (CPSCP and CPPCP, respectively) are capable of forming an intrachain disulfide bond. Conformational modeling studies on cyclic disulfide bonded CPSCP and CPPCP peptides yielded energy ranges for the low-energy conformations of 31-33 kcal/mol and 40-42 kcal/mol, respectively. In addition, higher torsion and angle bending energies were observed for the CPPCP peptide due to backbone constraints caused by the extra proline. These modeling results suggest a reason why a larger fraction of intrachain bonds are observed in IgG4 rather than IgG1 molecules: the serine in the core hinge region of IgG4 allows more hinge region flexibility than the proline of IgG1 and thus may permit formation of a stable intrachain disulfide bond more readily.

Alkylation↗

Managing HIV. Part 5: Treating secondary outcomes. 5.2 HIV and oral disease.

Oral manifestations of HIV infection often represent the first clinical signs of this disease. Early management of oral lesions reduces the prospect of what would normally be routine procedures in the mouth becoming compromised and complicated when the immune system is further suppressed.

AIDS-Related Opportunistic Infections↗

Managing HIV. Part 2: Phases of disease. 2.4 HIV and advanced immune deficiency.

Advanced immune deficiency is defined as a CD4 cell count below 200/microL. This phase is marked by considerable medical intervention requiring close coordination between general practitioner and specialist, with the goal of minimising the patient's time in hospital. The patient must be assisted with the psychological adjustments that lead to death with dignity. Managing HIV in all its manifestations will make a great difference to the quality of both life and death.

Acquired Immunodeficiency Syndrome↗

Association between HIV distal symmetric polyneuropathy and Mycobacterium avium complex infection.

OBJECTIVES: Pronounced infiltration of activated macrophages occurs in the peripheral nerves of patients with HIV distal symmetric polyneuropathy (DSPN). Mycobacterium avium complex (MAC) is a common facultative intracellular parasite of the macrophage in advanced HIV disease and may induce macrophage activation. Whether MAC disease is associated with DSPN was examined prospectively. METHODS: One hundred and fifty consecutive patients with HIV infection were assessed for the probability of DSPN. Blood cultures for MAC were performed, independently of neurological assessment, as part of the investigation of unexplained fever, anaemia, weight loss, or, less commonly, diarrhoea. RESULTS: There were 20 patients with possible, 14 with probable, and 22 with definite HIV DSPN. Blood cultures for MAC were performed on 80 patients, of whom 39 were positive and 41 negative. The test for trend, when corrected for CD4 count, disclosed a significant association (P = 0.01). There was no statistically significant association between DSPN and cytomegalovirus (CMV) disease. CONCLUSION: Coinfection of the macrophage by MAC may further activate the HIV infected macrophage thereby accelerating the elaboration of neural toxins or MAC infection of the macrophage itself may lead to the production of neural toxins.

Adult↗