Case Report: Severe Hematological, Muscle and Liver Toxicity Caused by Drugs and Artichoke Infusion Interaction in an Elderly Polymedicated Patient.

BACKGROUND: Case report, in a patient with a history of diabetes and hypertension, treated with metformin, gliclazide, enalapril + hydrochlorothiazide, amlodipine, aspirin and diazepam, recently medicated for a gouty crisis with colchicine and clonixin without improvement. Believing it could help in the treatment of gouty crisis symptoms he took about 1.5 L of artichoke infusion (Cynara cardunculus). He felt better and did agriculture work but developed a distal muscle pain, severe anemia, standard biochemical liver cholestasis, increase of alkaline phosphatase and marked increase of inflammatory parameters (hyperleucocytosis) and enters in the emergency department at the hospital. OBJECTIVE: Evaluation of the cause of complaints and laboratory abnormalities and the involvement of artichoke infusion. RESULTS: The prominence of the inflammatory parameters was ruled out because of exhaustive autoimmune, infectious or para-neoplastic syndrome (blood cultures, serology, diagnostic imaging, bone marrow and bone biopsy, muscle biopsy and nerve, abdominal angiography) were carried out showing normal results. The evaluation pointed out that the concomitant intake of artichoke infusion may have been involved in the framework developed, since the drugs which were being administered to/by the patient have a metabolism mainly mediated by CYP450 3A4 and 2C9 that could be compromised when these isoenzymes are inhibited by phenolic and flavonoid compounds from plants. Colchicine was one of the last drugs took that have as side effects most of the symptoms felt by patient including diarrhea and anemia. CONCLUSION: The spontaneous and complete recovery of the patient and the negativity of research looking for other causes, conduce to a strong possibility of the interaction between artichoke and the drugs in the clinical presentation of this case.

Immunodeficiency and autoimmunity coming together: a nearly missed diagnosis.

The coexistence of human immunodeficiency virus (HIV) and systemic lupus erythematosus (SLE) appears to be unusual and the prevalence of patients who carry the dual diagnosis is currently unknown. We hereby present a case of a C4 deficient HIV-1 positive Caucasian female under highly active antiretroviral therapy for the past eight years, admitted to hospital with an aggressive and potentially fatal clinical presentation of SLE. There was a favorable outcome despite a significant diagnostic delay. Despite its rarity, the case highlights that this association is remarkable and may be overlooked by clinicians familiar with either condition.

Multicentre study highlighting clinical relevance of new high-throughput methodologies in molecular epidemiology of Pneumocystis jirovecii pneumonia.

Pneumocystis jirovecii causes severe interstitial pneumonia (PcP) in immunosuppressed patients. This multicentre study assessed the distribution frequencies of epidemiologically relevant genetic markers of P. jirovecii in different geographic populations from Portugal, the USA, Spain, Cuba and Mozambique, and the relationship between the molecular data and the geographical and clinical information, based on a multifactorial approach. The high-throughput typing strategy for P. jirovecii characterization consisted of DNA pooling using quantitative real-time PCR followed by multiplex-PCR/single base extension. The frequencies of relevant P. jirovecii single nucleotide polymorphisms (mt85, SOD110, SOD215, DHFR312, DHPS165 and DHPS171) encoded at four loci were estimated in ten DNA pooled samples representing a total of 182 individual samples. Putative multilocus genotypes of P. jirovecii were shown to be clustered due to geographic differences but were also dependent on clinical characteristics of the populations studied. The haplotype DHFR312T/SOD110C/SOD215T was associated with severe AIDS-related PcP and high P. jirovecii burdens. The frequencies of this genetic variant of P. jirovecii were significantly higher in patients with AIDS-related PcP from Portugal and the USA than in the colonized patients from Portugal, and Spain, and children infected with P. jirovecii from Cuba or Mozambique, highlighting the importance of this haplotype, apparently associated with the severity of the disease and specific clinical groups. Patients from the USA and Mozambique showed higher rates of DHPS mutants, which may suggest the circulation of P. jirovecii organisms potentially related with trimethoprim-sulfamethoxazole resistance in those geographical regions. This report assessed the worldwide distribution of P. jirovecii haplotypes and their epidemiological impact in distinct geographic and clinical populations.

Liver Retransplantation in Patients With HIV-1 Infection: An International Multicenter Cohort Study.

Liver retransplantation is performed in HIV-infected patients, although its outcome is not well known. In an international cohort study (eight countries), 37 (6%; 32 coinfected with hepatitis C virus [HCV] and five with hepatitis B virus [HBV]) of 600 HIV-infected patients who had undergone liver transplant were retransplanted. The main indications for retransplantation were vascular complications (35%), primary graft nonfunction (22%), rejection (19%), and HCV recurrence (13%). Overall, 19 patients (51%) died after retransplantation. Survival at 1, 3, and 5 years was 56%, 51%, and 51%, respectively. Among patients with HCV coinfection, HCV RNA replication status at retransplantation was the only significant prognostic factor. Patients with undetectable versus detectable HCV RNA had a survival probability of 80% versus 39% at 1 year and 80% versus 30% at 3 and 5 years (p = 0.025). Recurrence of hepatitis C was the main cause of death in the latter. Patients with HBV coinfection had survival of 80% at 1, 3, and 5 years after retransplantation. HIV infection was adequately controlled with antiretroviral therapy. In conclusion, liver retransplantation is an acceptable option for HIV-infected patients with HBV or HCV coinfection but undetectable HCV RNA. Retransplantation in patients with HCV replication should be reassessed prospectively in the era of new direct antiviral agents.

Auditing HIV Testing Rates across Europe: Results from the HIDES 2 Study.

European guidelines recommend the routine offer of an HIV test in patients with a number of AIDS-defining and non-AIDS conditions believed to share an association with HIV; so called indicator conditions (IC). Adherence with this guidance across Europe is not known. We audited HIV testing behaviour in patients accessing care for a number of ICs. Participating centres reviewed the case notes of either 100 patients or of all consecutive patients in one year, presenting for each of the following ICs: tuberculosis, non-Hodgkins lymphoma, anal and cervical cancer, hepatitis B and C and oesophageal candidiasis. Observed HIV-positive rates were applied by region and IC to estimate the number of HIV diagnoses potentially missed. Outcomes examined were: HIV test rate (% of total patients with IC), HIV test accepted (% of tests performed/% of tests offered) and new HIV diagnosis rate (%). There were 49 audits from 23 centres, representing 7037 patients. The median test rate across audits was 72% (IQR 32-97), lowest in Northern Europe (median 44%, IQR 22-68%) and highest in Eastern Europe (median 99%, IQR 86-100). Uptake of testing was close to 100% in all regions. The median HIV+ rate was 0.9% (IQR 0.0-4.9), with 29 audits (60.4%) having an HIV+ rate >0.1%. After adjustment, there were no differences between regions of Europe in the proportion with >0.1% testing positive (global p = 0.14). A total of 113 patients tested HIV+. Applying the observed rates of testing HIV+ within individual ICs and regions to all persons presenting with an IC suggested that 105 diagnoses were potentially missed. Testing rates in well-established HIV ICs remained low across Europe, despite high prevalence rates, reflecting missed opportunities for earlier HIV diagnosis and care. Significant numbers may have had an opportunity for HIV diagnosis if all persons included in IC audits had been tested.

Diagnosis of Pneumocystis pneumonia: evaluation of four serologic biomarkers.

The diagnosis of Pneumocystis pneumonia (PCP) relies on microscopic visualization of Pneumocystis jirovecii organisms or DNA detection in pulmonary specimens. This study aimed to assess the usefulness of (1-3)-ß-d-glucan (BG), Krebs von den Lungen-6 antigen (KL-6), lactate dehydrogenase (LDH) and S-adenosyl methionine (SAM) as serologic biomarkers in the diagnosis of PCP. Serum levels of BG, KL-6, LDH and SAM were investigated in 145 Portuguese patients, 50 patients from the Netherlands, 25 Spanish patients and 40 Portuguese blood donors. Data on clinical presentation, chest imaging and gasometry tests were available. PCP cases were confirmed by microscopy and PCR techniques. A cost-effectiveness analysis was performed. BG was found to be the most reliable serologic biomarker for PCP diagnosis, followed by KL-6, LDH and SAM. The BG/KL-6 combination test was the most accurate serologic approach for PCP diagnosis, with 94.3% sensitivity and 89.6% specificity. Although less sensitive/specific than the reference standard classic methods based on bronchoalveolar lavage followed by microscopic or molecular detection of P. jirovecii organisms, the BG/KL-6 test may provide a less onerous procedure for PCP diagnosis, as it uses a minimally invasive and inexpensive specimen (blood), which may be also a major benefit for the patient's care. The BG/KL-6 combination test should be interpreted within the clinical context, and it may be used as a preliminary screening test in patients with primary suspicion of PCP, or as an alternative diagnostic procedure in patients with respiratory failure or in children, avoiding the associated risk of complications by the use of bronchoscopy.

Coreceptor usage by HIV-1 and HIV-2 primary isolates: the relevance of CCR8 chemokine receptor as an alternative coreceptor.

The human immunodeficiency virus replication cycle begins by sequential interactions between viral envelope glycoproteins with CD4 molecule and a member of the seven-transmembrane, G-protein-coupled, receptors' family (coreceptor). In this report we focused on the contribution of CCR8 as alternative coreceptor for HIV-1 and HIV-2 isolates. We found that this coreceptor was efficiently used not only by HIV-2 but particularly by HIV-1 isolates. We demonstrate that CXCR4 usage, either alone or together with CCR5 and/or CCR8, was more frequently observed in HIV-1 than in HIV-2 isolates. Directly related to this is the finding that the non-usage of CXCR4 is significantly more common in HIV-2 isolates; both features could be associated with the slower disease progression generally observed in HIV-2 infected patients. The ability of some viral isolates to use alternative coreceptors besides CCR5 and CXCR4 could further impact on the efficacy of entry inhibitor therapy and possibly also in HIV pathogenesis.

Investigation and control of a large outbreak of multi-drug resistant tuberculosis at a central Lisbon hospital.

An increase in the number of new cases of tuberculosis (TB) combined with poor clinical outcome was identified among HIV-infected injecting drug users attending a large HIV unit in central Lisbon. A retrospective epidemiological and laboratory study was conducted to review all newly diagnosed cases of TB from 1995 to 1996 in the HIV unit. Results showed that from 1995 to 1996, 63% (109/173) of the Mycobacterium tuberculosis isolates from HIV-infected patients were resistant to one or more anti-tuberculosis drugs; 89% (95) of these were multidrug-resistant, i.e., resistant to at least isoniazid and rifampicin. Eighty percent of the multidrug-resistant strains (MDR) available for restriction fragment length polymorphism (RFLP) DNA fingerprinting clustered into one of two large clusters. Epidemiological data support the conclusion that the transmission of MDR-TB occurred among HIV-infected injecting drug users exposed to infectious TB cases on open wards in the HIV unit. Improved infection control measures on the HIV unit and the use of empirical therapy with six drugs once patients were suspected to have TB, reduced the incidence of MDR-TB from 42% of TB cases in 1996 to 11% in 1999.

[Infective endocarditis]. / Endocardite infecciosa.

Two different series of patients with Infectious Endocarditis (IE), hospitalized in the same ward of Curry Cabral Hospital in Lisbon, are presented and compared. The two series were separated by a ten-year period--the first included patients observed from 1970 to 1976 and the second from 1988 to 1998. In the first series (20 patients), IE occurred mainly in patients with previous cardiac valvular lesion, the course was subacute and Streptococcus viridans was the predominant agent. In the last series (65 patients), most of the patients were young and had no previous valvular lesions. Right side endocarditis predominated and the course was acute. Most of patients were drug addicts and had HIV infection. Staphylococcus aureus was the predominant agent. The ages of the two series were significantly different (p < 0.005). The diagnostic value of transthoracic and transesophageal echocardiography is stressed. The details of the evolution of patients with HIV infection are presented according to the values of CD4+ lymphocyte counts. The relatively good prognosis of IE in drug addicts with antibiotic treatment, even with HIV infection, is emphasized.

[Will acanthosis nigricans be a new cutaneous manifestation of human immunodeficiency virus infection?]. / Será a acanthosis nigricans uma nova manifestação cutânea de infecção pelo vírus da imunodeficiência humana?

The authors describe a clinical case of AIDS presented by three opportunistic infections (esophageal candidiasis, tuberculosis and atypical mycobacteriosis) and a dermatological manifestation--acanthosis nigricans--not described in medical literature as accompanying those entities. The exclusion of most common etiologies of acanthosis nigricans and its regression following treatment for those infections suggests that with AIDS it behaves like a paraneoplastic syndrome. Screening for HIV antibodies should be the rule whenever this dermatological manifestation is present.

[Mucocutaneous pathology in HIV infection]. / Patologia cutâneo-mucosa na infecção pelo VIH.

Several infectious, neoplastic or inflammatory skin diseases, may be early manifestations of HIV infection. We reviewed the clinical data of 226 HIV seropositive male patients with cutaneous disease, from a total of 337 inpatients at the Infectious Diseases Unit--Department of Medicine 1--Curry Cabral Hospital, from 1985 to 1991. Some considerations are made about the most common dermatological disorders: oral candidiasis, seborrheic dermatitis, Kaposi's sarcoma, herpes simplex infection, drug-related skin disorders, herpes zoster and dermatophytosis. The high prevalence of cutaneous manifestations in HIV infection, the uncommon clinical findings and their occasional therapeutic problems, makes an early diagnosis essential.

[Yersinia enterocolitica. A seroprevalence study and report of 3 clinical cases]. / Yersínia enterocolítica. Estudo da seroprevalência e apresentação de 3 casos clínicos.

Yersinia enterocolitica is a gram negative bacillus that emerged in the past two decades as an important enteric pathogen associated with a wide spectrum of clinical manifestations. The authors present a seroepidemiological survey, in 200 hospitalized patients, and describe three curious case reports of this infection, including a serious case of endocarditis.

[Significance of the captopril test in the diagnosis of primary hyperaldosteronism --apropos of 4 clinical cases]. / O valor do teste do captopril no diagnóstico do hiperaldosteronismo primário--a propósito de 4 casos clínicos.

We describe four cases of primary hyperaldosteronism whose initial presentation was a moderate to severe hypertension. In three patients an adrenal adenoma was found; in another patient was due to unilateral adrenal hyperplasia. A good therapeutic response was achieved in all cases by unilateral adrenalectomy. The captopril test (Lyons version) proved useful to exclude essential hypertension and, may be, in distinguishing the new sub-types of primary hyperaldosteronism recently described. Indeed, only in the case of unilateral adrenal hyperplasia a fall in plasma aldosterone levels was observed. However, we feel that further investigation is needed to clarify this point.