Lymphogranuloma venereum proctitis: An emerging sexually transmitted disease in HIV-positive men in the Netherlands.

A recent outbreak of lymphogranuloma venereum (LVG) proctitis caused by Chlamydia trachomatis serovar L2 has been detected in HIV-positive men in the Netherlands and Belgium. This sexually transmitted disease (STD), which is well known and frequently occurring in tropical countries, was quite unusual in Europe until 2003. STDs with ulcerative lesions, such as LGV, facilitate transmission of other microorganisms, including HIV and hepatitis C. This in combination with risky sexual behavior, such as unprotected anal sexual intercourse or use of sex toys, increases the risk of blood-blood contact and hence the risk of contracting multiple STDs. Two cases of patients who in a short time period contracted multiple STDs, including LGV proctitis, is presented.

[Chronic lead intoxication associated with Ayurvedic medication]. / Chronische loodintoxicatie door ayurvedische kruiden.

A 46-year-old man with multiple sclerosis had severe generalised pain for which treatment with paracetamol, ibuprofen, gabapentin and methyl-prednisolone had been unsuccessful. In addition normocytic anaemia without haemolysis and with a normal iron load was found. Due to bright red rectal blood loss and nausea, vomiting, weight loss, anorexia, abdominal pain and constipation a colonoscopy was planned. However, before this was performed, manual slide differentiation of a blood smear showed basophilic stippling and it turned out that the patient had been taking Ayurvedic medication up to one month before presentation. A moderately severe lead intoxication was diagnosed: 0.77 mg/l. The herbal medication had a very high lead content. The patient was successfully treated with the oral lead chelator 23-dimercaptosuccinic acid. Traditional and folk remedies often are important causes of lead poisoning.

Myocardial air collections as a result of infection with a gas producing strain of Escherichia coli.

Certain strains of Escherichia coli have been shown to cause gas accumulation in--for example, emphysematous pyelonephritis. This paper describes a patient with intramyocardial air collections resulting from an intramyocardial infection with gas forming E coli.

[Two HIV-positive men with anorectal lymphogranuloma venereum and hepatitis C: emerging sexually transmitted diseases]. / Twee HIV-positieve mannen met anorectale lymphogranuloma venereum en hepatitis C: opkomende soa's.

Two men, aged 41 and 28 years, both known to be HIV-positive, contracted multiple sexually-transmitted diseases (STDs) through unprotected anal sexual contact. These included lymphogranuloma venereum (LGV) proctitis and hepatitis C. Recently in The Netherlands and Belgium there has been an outbreak of LGV proctitis in HIV-positive men who have sex with men, caused by Chlamydia trachomatis serovar L2, an STD which up to now has been rare in Europe. Due to information about the epidemic received a few days previously, the LGV proctitis in the second patient could be diagnosed and treated rapidly. The incidence of STDs in men having sex with men is increasing, also in HIV-positive men. STDs with ulcerative lesions, such as LGV, facilitate transmission of other pathogenic micro-organisms, including HIV. This, in combination with high-risk sexual behaviour such as unprotected anal sexual intercourse, will increase the chance of blood-blood contact and hence the chance of contracting multiple STDs concurrently. Hepatitis C is not normally considered as an STD, but ulcerative lesions in one of the partners combined with high-risk sexual behaviour enables the hepatitis C virus to be sexually transmitted.

[Liver transplantation in a HIV-positive patient receiving potent antiretroviral therapy; the first case in The Netherlands]. / Orthotope levertransplantatie bij HIV-positiviteit en krachtige antiretrovirale behandeling; de eerste patient in Nederland.

In a 49-year-old woman infected with HIV who was receiving highly-active antiretroviral treatment (HAART), terminal liver failure developed. She also had an acute exacerbation of hepatitis B. She was treated by means of liver transplantation and was in good condition two years later. At that time she was treated with tacrolimus, lamivudine, tenofovir, nelfinavir and hepatitis-B immunoglobulin. HIV-RNA and the DNA of hepatitis-B virus could not be detected, her CD4-count was not abnormal and the liver transplant functioned well. No opportunistic infections had developed. HIV infection has long been considered an absolute contraindication to solid organ transplantation, due to the increased risk of infection and rapid progression to AIDS. With HAART, restoration of immune function is possible. Currently, international experience with liver transplantation for HIV-positive patients that are not infected with hepatitis C has shown promising results. Specifically, the risks of transplant rejection, opportunistic infections and progression to AIDS are not increased. Therefore, criteria have been defined for solid organ transplantation in HIV-positive recipients.

[Manifestations of histoplasmosis]. / Manifestaties van histoplasmose.

Two patients, a 34-year old man-to-woman transsexual and a 32-year-old man, with aids presented with pulmonary symptoms, fever, serious weight loss and an oral ulcer. A third patient, a 16-year-old boy, had signs of transverse myelitis and meningitis without immunodeficiency. All were South American citizens and had disseminated histoplasmosis. After antifungal treatment they recovered, although the third patient remained a wheelchair user. If pulmonary or miliary tuberculosis is suspected in a patient originating from South America, histoplasmosis should be considered. Oral ulcers and skin lesions can be diagnostic clues. Specific stainings of direct preparations and longer-lasting cultures of various materials, especially of biopsy samples, then provide the diagnosis.

Quinine pharmacokinetics: ototoxic and cardiotoxic effects in healthy Caucasian subjects and in patients with falciparum malaria.

OBJECTIVE: To study the pharmacokinetic behaviour of quinine in Caucasians with and without malaria. METHOD: Quinine-dihydrochloride was administered intravenously as a single dose of 300 mg to 12 healthy subjects and as multiple doses of 600 mg in 4 h every 8 h in 10 patients with falciparum malaria. Plasma quinine concentrations were measured by high-performance liquid chromatography RESULTS: Quinine pharmacokinetics are time-dependent: the apparent elimination halftime is shorter in the accumulation phase than in the elimination phase; in malaria patients the maximal quinine concentration was reached in half the time calculated on the basis of the elimination phase after the last quinine infusion. Nevertheless a loading dose seemed advisable to reach adequate therapeutic levels quickly. In malaria patients the highest plasma concentrations during or at the end of the infusions were positively correlated with body weight. There was no correlation between body weight and the volume of distribution of quinine as calculated during the elimination phase. Hearing loss was audiometrically documented in 9 healthy subjects at a mean maximal plasma quinine concentration of only 2 mg/l. All malaria patients suffered serious cochlear hearing impairment. The ototoxic effects in both healthy subjects and patients appeared to be reversible. No electrographic changes were noted in the healthy subjects, whereas a clinically insignificant mean lengthening of the corrected QT interval was seen in the malaria patients. CONCLUSION: Intravenous quinine pharmacokinetics in healthy Caucasians were similar to those reported for Nigerian or Thai subjects. At effective doses quinine causes considerable but reversible cochlear hearing losses in both healthy persons and in patients. Our findings do support the need for a loading dose. The fact that in malaria patients there was no correlation between body weight and quinine VD as calculated during the elimination phase renders questionable the usefulness of dosing quinine according to body weight.

Ototoxic reactions of quinine in healthy persons and patients with Plasmodium falciparum infection.

Audiometric changes following quinine administration were studied in healthy Caucasian subjects and patients suffering from falciparum malaria disease. Quinine-dihydrochloride was administered intravenously as a single dose of 300 mg to 12 healthy subjects and as multiple doses of 600 mg in 4 h every 8 h in 10 Plasmodium falciparum malaria patients. The hearing function was monitored by conventional and high frequency audiometry. In nine healthy subjects hearing loss was documented at 2-4 h after infusion of Quinine-dihydrochloride at a mean maximal plasma quinine concentration of only 2 mg/l. In one healthy subject a persistent loss occurred of 20 dB at 14 kHz in one ear. In all malaria patients severe hearing losses and adverse effects related to ototoxicity were documented, but all the audiograms had returned to normal after 1 week and side effects disappeared. This study has shown that ototoxicity induced by quinine is almost completely reversible in healthy volunteers and in malaria patients.

Cytokine profiles in bronchoalveolar lavage fluid and blood in HIV-seropositive patients with Pneumocystis carinii pneumonia.

Concentrations and ex vivo production of interleukin 1 beta (IL-1), tumour necrosis alpha (TNF), interleukin 6 (IL-6), interleukin-1 receptor antagonist (IL-1RA) and TNF soluble receptors (sTNF-receptors, P55 and P75) were measured in bronchoalveolar lavage (BAL) fluid and blood in 23 HIV-seropositive (HIV+) patients with Pneumocystis carinii pneumonia (PCP) and compared with values found in healthy HIV-seronegative (HIV-) controls and asymptomatic HIV+ subjects. Concentrations of the proinflammatory cytokine IL-1 beta were increased in BAL fluid of HIV+ patients with PCP (184 +/- 47 pg mL-1) compared with undetectable levels in healthy control subjects (P = 0.0001). In plasma of these patients higher concentrations of the anti-inflammatory cytokine IL-1RA were found during acute PCP than after recovery (2.1 +/- 0.7 vs. 0.5 +/- 0.2 ng mL-1, P = 0.01). No correlations could be found between cytokine concentrations and clinical severity of the infection. Corticosteroid treatment did not influence cytokine concentrations in BAL or blood, nor did it suppress the production in alveolar cells. In whole-blood cultures, however, lipopolysaccharide (LPS)-stimulated production was significantly suppressed for IL-1 (1.3 vs. 5.5 ng mL-1, P = 0.009) and for IL-6 (0.6 vs. 2.5 ng mL-1, P = 0.01). The overall data show that in HIV+ patients with PCP (similar to what we had found previously in HIV-patients with PCP) proinflammatory cytokines are more prominently present in BAL, whereas anti-inflammatory reaction is predominant in the circulation.

Pro-inflammatory cytokines in lung and blood during steroid-induced Pneumocystis carinii pneumonia in rats.

To gain more insight into the role of cytokines in Pneumocystis carinii pneumonia (PCP) we followed pro-inflammatory cytokine profiles in rats with steroid-induced PCP at 2-week intervals. The cytokines measured were immunoreactive interleukin-1beta (IL-1beta), bioactive interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-alpha). In vivo cytokine concentrations were determined in three compartments, i.e., bronchoalveolar lavage (BAL) fluid, lung homogenates, and plasma. Lipopolysaccharide (LPS) -stimulated cytokine production by alveolar cells and in whole-blood cultures was measured ex vivo. P carinii load and host inflammatory response, as determined by lung/body weight ratio and 111indium-IgG biodistribution were monitored throughout developing PCP. IL-1beta was elevated in lung homogenates (600, range <20-1260 pg/mL) and IL-6 in BAL fluid (48, range <20-115 pg/mL), whereas the pro-inflammatory cytokine concentrations were not increased in plasma. Thus in rats with PCP elevated pro-inflammatory cytokine concentrations were found to be restricted to the lung compartments. Corticosteroids did not significantly influence cytokine concentrations, but showed profound inhibitory effects on ex vivo cytokine production. The LPS-stimulated cytokine production by alveolar cells gradually decreased during the 6 weeks after the start of the steroid injections, whereas the production in whole blood cultures was immediately and completely suppressed.

Detecting infection and inflammation with technetium-99m-labeled Stealth liposomes.

UNLABELLED: The performance of 99mTc Stealth liposomes was investigated in various rat models. METHODS: Preformed polyethyleneglycol-containing liposomes with encapsulated reduced glutathione, were radiolabeled using the lipophilic 99mTc-HMPAO. The labeled liposomes were intravenously administered to rats with focal S. aureus or E. coli infection, or turpentine-induced inflammation. For comparison, Tc-99m-nanocolloid- and 99mTc-labeled nonspecific IgG were tested. In rats with Pneumocystis carinii pneumonia (PCP), Tc-99m-liposomes were directly compared to In-111 labeled nonspecific IgG. RESULTS: Technetium-99m-liposomes accumulated in the infectious and inflammatory muscle foci over 24 hr (0.59% injected dose per gram tissue (%ID/g) for S. aureus; 1.18 %ID/g for turpentine). Abscess-to-muscle ratios increased to values as high as 24.0, 41.7 and 44.5 for the respective models at 24 hr postinjection. Technetium-99m-liposomes visualized the foci as early as 1 hr postinjection. Technetium-99m-IgG visualized S. aureus infection, but abscess-to-muscle ratios and abscess uptake at the later time points were significantly lower. Technetium-99m-nanocolloid failed to visualize any of the muscle foci. In PCP however, 99mTc-liposomes did not show preferential localization in the infection. The control agent 111In-IgG showed a significant, two-fold increase in lung uptake. CONCLUSION: Technetium-99m-Stealth liposomes preferentially accumulated in abscesses, leading to very high target-to-nontarget ratios. This property appears to be related to a process based on uptake of long-circulating particles. In a specific type of infection, i.c. PCP, 99mTc-liposomes did not accumulate in diseased lung tissue, thus mimicking the in vivo behavior of labeled leukocytes.

Cytokine profiles in bronchoalveolar lavage fluid and blood in HIV-seronegative patients with Pneumocystis carinii pneumonia.

Concentrations and ex vivo production of interleukin-1beta (IL-1beta), tumour necrosis factor-alpha (TNF), interleukin-6 (IL-6), interleukin-1 receptor antagonist (IL-1RA) and TNF soluble receptors were followed in bronchoalveolar lavage (BAL) fluid and blood from 10 HIV-seronegative patients with Pneumocystis carinii pneumonia (PCP) and compared with values found in healthy volunteers. During the acute phase of PCP, TNF but not IL-6 or IL-1beta was detectable in BAL fluid. At that time, plasma concentrations of the proinflammatory cytokines were low, whereas plasma concentrations of the anti-inflammatory cytokines were high. The ex vivo production capacity of proinflammatory cytokines was suppressed in the acute phase, in the blood as well as at the site of infection. During convalescence the production capacity of the blood cells normalized. The IL-1RA production capacity of the alveolar cells was also suppressed in the acute phase, but preserved in blood cells.

Serial indium-111-labelled IgG biodistribution in rat Pneumocystis carinii pneumonia: a tool to monitor the course and severity of the infection.

To study the effect of new therapeutic strategies, we developed an animal model to monitor the course and severity of experimental Pneumocystis carinii pneumonia (PCP) in rats. P. carinii density scores in Giemsa-stained impression smears were used to follow P. carinii load. Indium-111 labelled IgG scintigraphy and biodistribution, histology of paraffin-embedded tissue sections, lung/body weight (L/B wt) ratio and cell count and differentiation of broncho-alveolar lavage (BAL) fluid were used as parameters of host inflammatory response. Statistically significant differences in L/B wt ratio, number of neutrophils in BAL fluid, P. carinii density score, histological extent of inflammation and 111In-IgG accumulation in the lung were seen between the rats sacrificed at various time points. 111In-IgG accumulation in the lung correlated well with L/B wt ratio and P. carinii density score and correlated moderately with number of neutrophils in BAL fluid and with the histological extent of inflammation.

Clinical features of HIV seropositive and HIV seronegative patients with tuberculous lymphadenitis in Dar es Salaam.

SETTING: The medical wards of a referral hospital in Dar es Salaam, Tanzania. OBJECTIVE: To investigate the impact of HIV infection on clinical features in tuberculous lymphadenitis. DESIGN: A prospective clinical study of HIV seropositive and HIV seronegative patients with lymphadenopathy. RESULTS: Of 128 patients with peripheral lymphadenopathy, 24 had no tuberculosis (TB) and in 10 patients TB was found only in other organs. The remaining 94 patients, of whom 76% were HIV seropositive, formed our study population. TB lymphadenitis was considered proven in 89 and probable in 5 patients. Disseminated TB (both TB adenitis and TB in other organs) was diagnosed more often in HIV seropositive than in HIV seronegative patients (52% versus 26%, P < 0.03). 59% of the 71 HIV-infected patients compared to only 4% of the 23 patients without HIV infection were over 30 years of age (P < 0.02). The following clinical features were significantly associated with HIV infection: dyspnoea, respiratory rate > 20/min, low motility score (bedridden), neurological abnormalities, hepatomegaly, splenomegaly, lymph node size < 2.5 cm, negative PPD skin test, lymphopenia (< 1000/cm3) and presence of pleural fluid. CONCLUSION: Co-infection with HIV influences several clinical and laboratory features in patients with tuberculous lymphadenitis.

Diagnosis of tuberculous lymphadenitis in an area of HIV infection and limited diagnostic facilities.

In order to evaluate procedures leading to the diagnosis of tuberculous lymphadenitis, a prospective clinical study was carried out of patients with lymphadenopathy admitted to the medical wards of a referral hospital in Tanzania. The yield of diagnostic procedures (direct auramine/Ziehl-Neelsen (ZN) stained smears, Löwenstein-Jensen (LJ) cultures, cytology and histological examinations of fine needle aspirations (FNA) and biopsy material of lymph nodes, respectively, was compared. We also tried to identify clinical diagnostic markers. One hundred and twenty-eight (99 HIV-seropositive) patients were included. In 89 (67 HIV-positive) patients TB lymphadenitis could be proven. Histology and LJ culture of a lymph node biopsy had the highest diagnostic yield, 85% and 88% respectively, followed by detection of acid-fast bacilli (AFB) in biopsy smear (53%) and in fine-needle aspirations (35%). The diagnostic yield of the several procedures was not affected by associated HIV infection. Macroscopic caseation was 100% predictive for TB with a sensitivity of 69%. Firm and matted lymph nodes, ESR > 100 mm/hr, a positive PPD skin test and pleural opacity on a chest x-ray proved to be independent predictors for TB. Retrospective testing of a stepwise diagnostic approach based on direct smears of FNA, macroscopic visible caseation and direct smear of biopsy tissue, suggests that in 93% of the patients a definite diagnosis of TB lymphadenitis could have been made. Our data suggest that in HIV/TB epidemic areas most of the cases of TB lymphadenitis can be diagnosed correctly by simple and cheap methods which are generally available at district hospitals. Our findings need further prospective validation, however.

PIP: In order to evaluate procedures leading to the diagnosis of tuberculous lymphadenitis, a prospective clinical study was carried out on patients with lymphadenopathy admitted to four medical wards of the Muhibili Medical Center, Dar es Salaam, Tanzania, from January to August 1991. The yield of diagnostic procedures (direct auramine/Ziehl-Neelsen stained smears, Lowenstein-Jensen [LJ] cultures, cytology and histological examinations of fine needle aspirations [FNA], and biopsy material of lymph nodes) was compared. Clinical diagnostic markers were also identified. 128 (99 HIV-seropositive) patients with a mean age of 30 years were included. 41% were male. In 89 (67 HIV-positive) patients, TB lymphadenitis could be demonstrated. 46 (30 HIV-positive) had TB lymphadenitis only and 43 (37 HIV-positive) had disseminated TB. In 10 patients TB was found in specimens other than the lymph node, making the total of TB patients 99. Histology and LJ culture of lymph node biopsy had the highest diagnostic yield, 85% and 88%, respectively, followed by detection of acid-fast bacilli in biopsy smears (53%) and in FNAs (35%). The diagnostic yield of the procedures was not affected by associated HIV infection. Macroscopic caseation was 100% predictive of TB with a sensitivity of 69%. Multivariate logistic regression analysis demonstrated four independent predictors of TB: 1) firm and matted lymph nodes (odds ratio [OR] 11.8); 2) erythrocyte sedimentation rate (ESR) 100 mm/hr (OR 4.6); 3) a positive purified protein derivative (PPD) skin test (OR 10.2); and 4) pleural opacity on a chest X-ray (OR 9.5). Retrospective testing of a stepwise diagnostic approach based on direct smears of FNA, macroscopic visible caseation, and direct smears of biopsy tissue suggests that in 93% of the patients a definite diagnosis of TB lymphadenitis could have been made. These data suggest that in HIV/TB epidemic areas most of the cases of TB lymphadenitis can be diagnosed correctly by simple and cheap methods which are generally available at district hospitals.

[The course of illness in ulcerative colitis]. / Het ziektebeloop bij colitis ulcerosa.

The data of 301 ulcerative proctitis/colitis patients, with a mean follow-up of 10 (1/2-26) years were analysed retrospectively. In 84 patients (28%) the diagnosis was made in this hospital (non-selected group), the other 217 patients were referred from other hospitals with an established diagnosis of ulcerative colitis. At any time after the fifth year of illness approximately 55% of the non-selected patients were free of symptoms, for the referred patients this proportion was 30%. In one half of the cases the inflammation started as a proctitis, almost 60% of these progressed to colitis later. Fourteen patients (5%) had a toxic megacolon, and a colon carcinoma developed in 9 patients (3%) on average 13 years after the first symptoms of colitis. We recorded 9 colitis-related deaths. Fifty patients (17%) underwent a colectomy, mostly because of failure of conservative therapy.

Quinine-induced hearing loss.

Sensorineural hearing loss due to quinine therapy for malaria has frequently been mentioned in the literature but has not been a subject of research during the last decades. The global spreading of chloroquine-resistant falciparum malaria brings about an increasing use of quinine. The ototoxicity of quinine can accurately be studied with ultrahigh frequency audiometry (up to 20 kHz). The case of a 29-year-old man suffering from falciparum malaria disease who got a reversible hearing loss from quinine therapy is presented.

[Mondor's disease]. / De ziekte van Mondor.

Mondor's disease, a harmless superficial thrombophlebitis of mainly thoracic veins, was diagnosed in four patients. Two of them were initially suspected of carcinoma of the breast, while the two others were thought to have a helminthic infection. Symptoms, signs, pathology and aetiology of this disease are discussed.