Oral itraconazole for epistaxis in hereditary hemorrhagic telangiectasia: a proof of concept study.

The inhibiting effects of itraconazole, an antifungal drug on vascular endothelial growth factor (VEGF) have recently been discovered. By inhibiting VEGF, itraconazole has shown potential in clinical trials as anti-cancer treatment. In hereditary hemorrhagic telangiectasia (HHT) patients, VEGF levels are elevated and inhibition of VEGF can decrease bleeding. Itraconazole could potentially serve as anti-angiogenic therapy for HHT-related bleeding. We report a proof of concept study with HHT patients and severe epistaxis. Patients were treated with daily 200 mg orally administered itraconazole for sixteen weeks. Twenty-one HHT patients, 8 females (38%), 13 males (62%), median age of 59 years (interquartile range (IQR) 55-69) were enrolled. Of these patients, 13 (62%) were diagnosed with HHT type 1, seven (33%) with HHT type 2 and in one patient (5%), no pathognomonic HHT mutation was found. Four patients (19%) prematurely terminated the study (3 due to mild or moderate side-effects) resulting in 17 patients included in the analyses. The median epistaxis severity score significantly decreased during treatment from 6.0 (IQR 5.1-7.2) to 3.8 (IQR 3.1-5.2) (p = 0.006). The monthly epistaxis frequency decreased from 56 to 38 epistaxis episodes (p = 0.004) and the monthly duration from 407 to 278 minutes (p = 0.005). Hemoglobin levels did not significantly change. The quality of life showed a small but significant improvement. In conclusion, oral itraconazole significantly improved epistaxis in HHT patients. The potential benefit of itraconazole in HHT should be further investigated.

Idiopathic and hereditary haemorrhagic telangiectasia associated pulmonary arteriovenous malformations: comparison of clinical and radiographic characteristics.

AIM: To determine whether there are differences between idiopathic and hereditary haemorrhagic telangiectasia (HHT) associated pulmonary arteriovenous malformations (PAVMs) (HHT-PAVM) regarding clinical and radiographic characteristics, and the results of embolotherapy. MATERIALS AND METHODS: A retrospective analysis was undertaken of all adult and adolescent patients who were diagnosed with a PAVM on chest computed tomography (CT) from January 2006 until August 2019. RESULTS: In total, 41 patients with idiopathic PAVMs and 194 patients with genetically confirmed HHT and PAVMs were included. Idiopathic PAVMs were more frequently observed in female patients, were more solitary, and predominantly located in the lower lobes. The diameter of the feeding artery and type of PAVM (simple versus complex) were similar. Embolotherapy results were comparable between both groups with similar re-embolisation rates. CONCLUSIONS: PAVMs of idiopathic origin are predominantly found in women, more frequently located in the lower lobes, and solitary compared to HHT-PAVMs; however, the outcome of treatment is the same, suggesting that treatment and follow-up should be similar in both groups.

Intranasal Efudix reduces epistaxis in hereditary hemorrhagic telangiectasia.

BACKGROUND: Local application of fluorouracil (Efudix, 5-FU) induces sclerosis in patients with sinonasal tumors and superficial basocellular skin carcinoma. As a 'back against the wall' treatment, we investigated the local effect of nasally applied 5-FU and whether this could decrease the burden of severe epistaxis in patients with hereditary hemorrhagic telangiectasia (HHT). METHODS: HHT patients with severe and frequent epistaxis, subsequent anemia and a necessity for blood and/or iron infusions were treated with a nasal tampon with 5-FU. This tampon was placed unilaterally in the nasal cavity on the side of the most severe epistaxis and replaced once weekly during 4 weeks. Outcome measures were safety and side effects, the aspect of the nasal mucosa measured with the mucosal HHT score, the epistaxis severity score (ESS), hemoglobin and ferritin plasma levels, and quality of life assessment pre-treatment, one and three months post-treatment. RESULTS: Six HHT patients participated. During treatment and follow-up, the nasal mucosa turned more pale and sclerotic and the number of telangiectases diminished. The mucosal HHT score improved and the ESS declined (p = 0.01). The decline of ESS persisted up to 3 months post-5-FU treatment. Moreover, mean hemoglobin levels increased from 6.0 pre-5-FU to 6.8 after one month post-5-FU. CONCLUSION: Unilateral application of 5-FU on a nasal tampon diminished the severity and frequency of epistaxis in all HHT patients. This effect sustained up to three months post-treatment, despite the fact that the contralateral side remained untreated. Subsequently, hemoglobin levels increased. Intranasal 5-FU is a promising entity for further research on epistaxis treatment in HHT patients.

Bone-site-specific responses to zoledronic acid.

OBJECTIVES: Bisphosphonates are widely used to treat bone diseases such as osteoporosis. However, they may cause osteonecrosis of the jaw. Here, we investigated whether in vivo exposure to bisphosphonates has a different effect on long bone and jaw osteoclasts, and on the turnover of these different bones. MATERIALS AND METHODS: Zoledronic acid (0.5 mg kg-1 weekly) was administered intraperitoneally to 3-month-old female mice for up to 6 months. The effects on the number of osteoclasts, bone mineralization and bone formation were measured in the long bones and in the jaw. RESULTS: Long-term treatment with zoledronic acid reduced the number of jaw bone marrow cells, without affecting the number of long bone marrow cells. Zoledronic acid treatment did not affect the number of osteoclasts in vivo. Yet, the bisphosphonate increased bone volume and mineral density of both long bone and jaw. Interestingly, 6 months of treatment suppressed bone formation in the long bones without affecting the jaw. Unexpectedly, we showed that bisphosphonates can cause molar root resorption, mediated by active osteoclasts. CONCLUSIONS: Our findings provide more insight into bone-site-specific effects of bisphosphonates and into the aetiology of osteonecrosis of the jaw. We demonstrated that bisphosphonates can stimulate osteoclast activity at the molar roots.

Birth prevalence of congenital cytomegalovirus among infants of HIV-infected women on prenatal antiretroviral prophylaxis in South Africa.

BACKGROUND: A high rate of congenital cytomegalovirus (CMV) has been documented in human immunodeficiency virus (HIV)-exposed infants in industrialized settings, both in the pre- and post-highly active antiretroviral therapy (HAART) era. Only limited data on the birth prevalence of congenital CMV among infants of HIV-infected women on prenatal antiretroviral (ARV) prophylaxis are available from sub-Saharan Africa, despite a high prevalence of both infections. We evaluated the prevalence of congenital CMV in HIV-exposed infants in the Western Cape, South Africa. METHODS: HIV-infected mothers were recruited in the immediate postnatal period at a referral maternity hospital between April and October 2012. Maternal and infant clinical data and newborn saliva swabs were collected. Saliva swabs were assayed by real-time polymerase chain reaction for CMV. Data were analyzed using univariate and multivariate logistic regression analyses to determine specific demographic, maternal, and newborn characteristics associated with congenital CMV. RESULTS: CMV was detected in 22 of 748 newborn saliva swabs (2.9%; 95% confidence interval [CI], 1.9%-4.4%). Overall, 96% of mothers used prenatal ARV prophylaxis (prenatal zidovudine, 43.9%; HAART, 52.1%). Maternal age, gestational age, prematurity (<37 weeks' gestation), type of ARV prophylaxis, length of ARV prophylaxis, birth weight, small for gestational age, and infant feeding choice were not significantly different between CMV-infected and -uninfected infants. Maternal CD4 count <200 cells/µL during pregnancy was independently associated with congenital CMV (adjusted odds ratio, 2.9; 95% CI, 1.2-7.3). A negative correlation between CMV load in saliva and maternal CD4 count was observed (r = -0.495, n = 22, P = .019). CONCLUSIONS: The birth prevalence of congenital CMV was high despite prenatal ARV prophylaxis, and was associated with advanced maternal immunosuppression.

Evolution of Pulmonary Arteriovenous Malformations: The Role of Contrast Echocardiography.

BACKGROUND: Pulmonary arteriovenous malformations (PAVMs) are direct connections between the pulmonary artery and the pulmonary vein, mostly associated with hereditary hemorrhagic telangiectasia (HHT). PAVMs can lead to severe neurologic complications such as stroke and brain abscess. The risk of complications decreases after embolization. Therefore, screening for PAVMs using transthoracic contrast echocardiography (TTCE) is recommended, including a rescreening interval of 5 years. RESEARCH QUESTION: Is extension of the interval for rescreening patients without a pulmonary right-to-left shunt (RLS) of up to 10 years appropriate? STUDY DESIGN AND METHODS: Adult patients with HHT with 5- or 10-year follow-up TTCE, or both, were included. Patients who underwent PAVM embolization in the past or at baseline were excluded. The RLS grades and presence of a treatable PAVM were compared with baseline. RESULTS: In total, 387 patients (median age, 45 years [interquartile range, 33-54 years]; 56% women) involving 5- and 10-year follow-up data in 363 and 166 patients, respectively, were included. None of the patients (n = 148) without a pulmonary RLS at baseline demonstrated a treatable PAVM after 5 and 10 years. Of the patients with a pulmonary RLS at baseline, 20 patients (9%) and three patients (3%) demonstrated a treatable PAVM at the 5- and 10-year follow-up, respectively. In most patients, the RLS grade remained stable over time. INTERPRETATION: On the basis of the results of this retrospective study, we believe that the rescreening interval for patients with HHT without a pulmonary RLS at initial screening may be extended to 10 years. Those with a pulmonary RLS should be rescreened every 5 years because treatable PAVMs can evolve.

Daylight-mediated photodynamic therapy of moderate to thick actinic keratoses of the face and scalp: a randomized multicentre study.

BACKGROUND: Photodynamic therapy (PDT) is an attractive therapy for nonmelanoma skin cancers and actinic keratoses (AKs). Daylight-mediated PDT is a simple and tolerable treatment procedure for PDT. Methyl aminolaevulinate (MAL)-PDT is approved for the treatment of thin or nonhyperkeratotic AKs on the face and scalp. However, thick AK lesions are often treated as well when present in the field-cancerized treatment area. OBJECTIVES: In a randomized multicentre study to evaluate efficacy of daylight-mediated PDT for different severity grades of AKs. METHODS: One hundred and forty-five patients with a total of 2768 AKs (severity grades I-III) of the face and scalp were randomized to either 1½ or 2½ h exposure groups. After application of a sunscreen (sun protection factor 20) and gentle lesion preparation, MAL was applied to the entire treatment area. Patients left the clinic immediately after application and exposed themselves to daylight according to randomization. Daylight exposure was monitored with a wrist-borne dosimeter. RESULTS: No difference in lesion response was found between the 1½ and 2½ h exposure group. The mean lesion response rate was significantly higher in grade I lesions (75·9%) than in grade II (61·2%) and grade III (49·1%) lesions (P < 0·0001). Most grade II (86%) and III AKs (94%) were in complete response or reduced to a lower lesion grade at follow-up. Large variations in response rate of grade II and III AKs were found between centres. No association was found between response rate and light dose in patients who received an effective light dose of > 3·5 J cm(-2). CONCLUSIONS: Daylight-mediated PDT of moderate to thick AKs was less effective than daylight-mediated PDT of thin AKs especially in some centres. However, nearly all thicker lesions (grades II and III) were reduced to a lower lesion grade at 3 months after a single treatment of daylight-mediated PDT.

Cold air analgesia as pain reduction during photodynamic therapy of actinic keratoses.

BACKGROUND: Photodynamic therapy (PDT) is an effective treatment for actinic keratoses and non-melanoma skin cancer. The main side effect of PDT is pain during the illumination. OBJECTIVES: To assess the effect of cold air as pain relief during MAL-PDT for field cancerization on different body areas. METHODS: A prospective, open, intra-individual right-left comparison study was performed in 43 patients with MAL-PDT as field cancerization. One area received cold air analgesia while the other did not. Pain was evaluated by numeric rating scale (NRS) during the illumination. The patients' received a questionnaire and recorded pain and postinflammatory symptoms on a visual analogue scale (VAS). RESULTS: We found a statistical significant difference in overall pain score at 3 and 9 minutes. The area receiving cold air during illumination had a mean NRS of 5.1 while the opposite side, not receiving cold air, had NRS of 6.1. At 9 minutes the side receiving cold air had mean NRS of 5.0, and the side without had 5.7. The pain difference on the chest was the most pronounced with a NRS of 5.2 without air and 3.5 with cold air. There was a significant difference in erythema immediately after, 1 h and 24 h after illumination. LIMITATIONS: Small, open, not blinded study. The difference in pain was small. CONCLUSION: Cold air is an effective method for moderate pain relief. It is an easy, noninvasive method that can be used on all body parts.

A randomized, multicentre study of directed daylight exposure times of 1½ vs. 2½ h in daylight-mediated photodynamic therapy with methyl aminolaevulinate in patients with multiple thin actinic keratoses of the face and scalp.

BACKGROUND: Actinic keratoses (AKs) are common dysplastic skin lesions that may differentiate into invasive squamous cell carcinomas. Although a superior cosmetic outcome of photodynamic therapy (PDT) is advantageous compared with equally effective treatments such as cryotherapy and curettage, the inconvenience of clinic attendance and discomfort during therapy are significant drawbacks. Daylight-mediated PDT could potentially reduce these and may serve as an alternative to conventional PDT. OBJECTIVES: To compare the efficacy of methyl aminolaevulinate (MAL)-PDT with 1½ vs. 2½ h of daylight exposure in a randomized multicentre study. METHODS: One hundred and twenty patients with a total of 1572 thin AKs of the face and scalp were randomized to either 1½- or 2½-h exposure groups. After gentle lesion preparation and application of a sunscreen of sun protection factor 20, MAL was applied to the entire treatment area. Immediately after, patients left the clinic and exposed themselves to daylight according to the randomization. Daylight exposure was monitored with a wristwatch dosimeter and patients scored their pain sensation during treatment. RESULTS: The mean lesion response rate at 3 months was 77% in the 1½-h group and 75% in the 2½-h group (P = 0·57). The mean duration of daylight exposure was 131 and 187 min in the two groups. The mean overall effective light dose was 9·4 J cm(-2) (range 0·2-28·3). Response rate was not associated with effective daylight dose, exposure duration, treatment centre, time of day or time of year during which the treatment was performed. Treatment was well tolerated, with a mean ± SD maximal pain score of 1·3 ± 1·5. CONCLUSIONS: Daylight-mediated MAL-PDT is an effective, convenient and nearly pain-free treatment for patients with multiple thin AKs. Daylight-mediated PDT procedures were easily performed and 2 h of daylight exposure resulted in uniformly high response rates when conducted in the period from June to October in Nordic countries.

Guidelines for practical use of MAL-PDT in non-melanoma skin cancer.

Methyl aminolaevulinate photodynamic therapy is increasingly practiced in the treatment of actinic keratoses, Bowen's disease and basal cell carcinomas. This method is particularly suitable for treating multiple lesions, field cancerization and lesions in areas where a good cosmetic outcome is of importance. Good treatment routines will contribute to a favourable result. The Norwegian photodynamic therapy (PDT) group consists of medical specialists with long and extensive PDT experience. With support in the literature, this group presents guidelines for the practical use of topical PDT in non-melanoma skin cancer.

Effect of isoprinosine on HIV antigenaemia.

OBJECTIVE: The objective of this study was to evaluate the effect of isoprinosine on HIV-antigen expression in HIV-positive patients without AIDS. DESIGN: Serum samples from anti-HIV-positive patients without AIDS participating in a double-blind, placebo-controlled trial of isoprinosine in the treatment of HIV infection were analysed for the presence of HIV antigen. SETTING: Data and samples were collected from the 21 medical centres who participated in the Scandinavian multicentre placebo-controlled isoprinosine study. PATIENTS, PARTICIPANTS: Samples were available from 19 of 21 participating centres. Of 866 patients who enrolled, baseline serum samples were available for 642 (74%; 308 isoprinosine- and 334 placebo-treated patients). INTERVENTIONS: Treatment was 1 g isoprinosine administered orally three times a day or matching placebo for 24 weeks. MAIN OUTCOME MEASURES: Comparison of HIV-antigen levels before and during treatment in both the isoprinosine-treated group and the placebo-treated group of patients. RESULTS: During the study, AIDS developed in 19 patients; 17 of whom were receiving placebo treatment and two isoprinosine. The proportion of HIV-antigen-positive patients developing AIDS during treatment was significantly different from the proportion of HIV-antigen-negative patients in whom AIDS developed (6 versus 2%; P = 0.02). No significant changes in HIV-antigen levels were observed between the isoprinosine- and the placebo-treated group of HIV-antigen-positive patients. Median HIV-antigen levels did not change significantly in either the isoprinosine- or the placebo-treated group. CONCLUSION: Our results suggest that isoprinosine does not have antiviral activity against HIV in vivo.

Acetylcholinesterase and its association with heparan sulphate proteoglycans in cortical amyloid deposits of Alzheimer's disease.

Previous studies have used a sensitive histochemical technique to demonstrate acetylcholinesterase and butyrylcholinesterase within the pathological lesions of Alzheimer's disease. In this study, we used this technique to show that acetylcholinesterase localized in either frozen or fixed neocortical tissue sections is removed after treatment with various glycosaminoglycans, heparinases or proteases. Heparan sulphate, heparinase lyase type I and to a lesser degree, heparin and chondroitin sulphate were effective in solubilizing a large part of the cholinesterase activity. At physiological concentrations, the protease papain or trypsin readily removed activity but collagenase or pronase were relatively less effective. Peptide protease inhibitors and divalent metals did not exhibit any clear effect. The specificity of these observations was shown by inhibition of activity with various anticholinesterases including diisofluorophosphate. Our results suggest that acetylcholinesterase is anchored to and may be released from the heparan sulphate glycosaminoglycans shown to be contained in the lesions. We further suggest that the localization of cholinesterases is closely associated with the accumulation of the glycosaminoglycans in amyloid plaques and neurofibrillary tangles.

Identification and expression of the Na+/H+ exchanger in mammalian cerebrovascular and choroidal tissues: characterization by amiloride-sensitive [3H]MIA binding and RT-PCR analysis.

We report the initial characterization of [3H]5-(N-methyl-N-isobutyl)amiloride (MIA) binding to the Na+/H+ exchanger (NHE) and expression of its gene in mammalian cerebrovascular, choroidal and neocortical tissues. [3H]MIA bound reversibly to particulate fractions of rat, pig and human cerebral microvessels, choroid plexus and cerebral cortex. Scatchard analyses revealed binding to a single amiloride-sensitive site with dissociation constants (Kd) ranging from 20 to 90 nM for the various tissue preparations. The maximal binding capacities (Bmax) were between 2 to 17 pmol/mg protein and were several-fold greater in cerebral microvessels compared to the cerebral cortex. Amiloride, MIA, 5-(N, N-hexamethylene)amiloride (HMA), 5-(N, N-dimethyl)amiloride (DMA) and 5-(N-methyl-N-isopropyl)amiloride (IPA) variably displaced [3H]MIA binding to the microvessels in the following rank order: MIA>HMA>/=IPA>DMA>amiloride. Benzamil, a potent ligand of the Na+/Ca+ transporter was the least sensitive. These binding results were most compatible with the existence of the amiloride-sensitive NHE type 1 in the brain vascular and choroidal tissues. To substantiate this, we utilized reverse transcription polymerase chain reaction (RT-PCR) techniques to search for NHE-1 mRNA. Using primers corresponding to conserved sequences of the human growth factor-activatable NHE gene, RT-PCR revealed strong expression of NHE-1 mRNA in cerebral microvessels, choroid plexus, pial vessels and vascular smooth muscle cells relative to neocortical tissues from several species including rat, pig, cow, monkey and human subjects. Further confirmation of NHE-1 isoform mRNA expression in the cerebrovascular tissues was obtained by HpaII restriction digestion analysis and by subcloning and sequencing of the PCR amplified products. Our study suggests that mammalian cerebrovascular and choroidal tissues contain high amounts of the ubiquitous amiloride-sensitive [3H]MIA binding proteins consistent with the expression of NHE type 1 mRNA.

The amiloride-sensitive Na+/H+ exchange antiporter and control of intracellular pH in hippocampal brain slices.

The intracellular pH, 7.54 +/- 0.03 (mean +/- S.D., n = 15), determined with the Neutral red method, of the hippocampal brain slice preparation under baseline incubation conditions is considerably more alkaline than the bath buffer pH. Neutralization by amiloride suggests that the alkalinity was due to Na+/H+ exchange antiporter activation. To characterize the brain Na+/H+ exchange antiporter we compared the inhibitory effects of MIA, amiloride and other 5-N substituted analogues on proton extrusion after acid loading by transient exposure to ammonium chloride in the isolated hippocampal brain slice preparation. The potencies of amiloride compounds on the initial recovery rate of intracellular pH after acid-loading were DMA > MIA > HMA = MHA > or = IPA-HCI > IPA > MNPA = Amil > Benzamil. The greater potency of the 5-N substituted analogs of amiloride over amiloride and benzamil strongly suggest that Na+/H+ exchange antiporter is the mechanism responsible for alkalinization in the isolated hippocampal brain slice in vitro.

Heterosexually acquired human immunodeficiency virus infection in women in Copenhagen: sexual behavior and other risk factors.

In order to describe the risk pattern including sexual behaviour among HIV-infected women in Copenhagen we studied the charts of all women tested seropositive between January 1985 and August 1988 in the three main hospitals handling HIV/AIDS. One hundred and fifteen women were positive for HIV antibodies: 35 (31%) were infected by heterosexual contact and 63 (55%) were intravenous drug users. Among the heterosexually transmitted cases 25 (71%) had intercourse with a man from a high risk group and nine women had intercourse with a known HIV antibody positive man without known risk factors. Use of condoms was claimed by 31% of the heterosexually-transmitted women before the HIV test, and by 74% (P = 0.002) after the test. In 1988 73% of the women tested HIV positive were infected by heterosexual contact, in 1985 only 14%. We conclude that among HIV infected women in Copenhagen heterosexual transmission is a problem. These women seem to change sexual behaviour when informed about HIV positivity.

[Sexual behavior in HIV antibody positive homosexual and bisexual men]. / Seksualadfaerd hos HIV-antistofpositive homo- og biseksuelle maend.

With the object of describing how their own health is experienced, the social circumstances and sexual behaviour in anti-HIV-positive homosexual and bisexual men, an anonymous questionnaire to be completed by the recipient was distributed in 1987 in connection with a placebo controlled investigation to assess the value of isoprinosin (Imunovir) in preventing the development of AIDS. 87% participated. Among the total of 85 participants, 78% considered that their health was good, 29% met family members and 75% friends at least once weekly. Fifty patients (65%) felt stressed in their daily lives which was definitely higher than in the normal population. All of the participants had altered their sexual behaviour in a manner which reduced the risk of HIV-transmission but 18 (21%) had had sexual behaviour known to transmit HIV within the past year. This behaviour occurred more frequently in young persons (p = 0.09) and in smokers (p = 0.03). In addition, no connection could be demonstrated between a series of possible determinants for this, which may, however, be due to the limited extent of the material. It is demonstrated that awareness that one is infected with HIV does not eliminate dangerous sexual behaviour in all cases.

[Effect of a safe-sex campaign on women attending a clinic of venereology. Sex behavior and prevalence of sexually transmitted diseases in women examined at the Venereaklinik in Copenhagen in 1984 and 1988]. / "Sikker sex"-kampagnens virkning blandt kvinder på en venereaklinik. Seksuel adfoerd og proevalens af seksuelt overførte sygdomme hos kvinder undersøgt på Københavns Venereaklinik i 1984 og 1988.

Consecutive female patients attending the Copenhagen Venereal Disease Clinic were interviewed about sexual behaviour in 1984 (981 women) and in 1988 (684 women). Details of symptoms, age at coitarche, number of sexual partners, contraceptive methods, and obstetric history were recorded together with the results of the venereological examination. A substantially higher proportion of women used condoms in 1988 (51%) than in 1984 (11%), but otherwise the safe sex campaigns had had a limited effect on the sexual behaviour in this group of women until 1988. The prevalence of gonorrhea decreased significantly (from 22% to 6%, p < 0.01), whereas an increase in the prevalence of genital warts was observed (from 4% to 10%, p < 0.01).

[HIV infected women in Copenhagen. Risk factors and sex behavior]. / HIV-smittede kvinder i København. Risikofaktorer og seksualadfaerd.

A total of 115 women were found to be HIV-antibody positive during the period January 1985 to September 1988 in the three large hospitals in Copenhagen. Thirty-five women (31%) had been infected heterosexually, 63 (55%) were intravenous drug addicts, 12 (10%) had been infected by transfusion and in five (4%) the mode of transmission was unknown. In 1988, 73% of the women who were found to be HIV-positive were infected heterosexually while only 14% were infected in this manner in 1985. Out of the heterosexually HIV-infected women, 25 (71%) had probably been infected by a man from a risk group while nine further women were infected by a known HIV-positive man with-out connection to any risk group. Eleven women (31%) stated that they practised "safe sex" prior to the HIV test while 22 (74%) did so after the positive HIV-test, which represents a considerable improvement. Out of the drug addicted women, six (10%) stated that they had always practiced "safe sex" prior to the test while 13 (28%) did so after the HIV-test. Approximately 1/3 of these women periodically shared syringes and needles with others. It is concluded that heterosexual contact among HIV-infected women in Copenhagen is a route of transmission of significance. Women infected heterosexually appear to alter their sexual behavior when they are made aware of the positive HIV-test.

[Survival time after the diagnosis of AIDS in the county of Funen]. / Livslaengde efter diagnosen AIDS på Fyn.

Since the diagnosis of AIDS was first made, a lot of efforts have been made to improve survival. Different studies have found varied results, both geographically as well as over periods of time. During the period 1.1.1985 to 31.12.1993 142 patients that were HIV-positive were seen in the geographically well defined area of Funen. During the period 1.1.1985 to 31.12.1990 the median time elapsed between the patient being found to be HIV-positive and the patient presenting with an AIDS-defining disease was found to be 8.8 years. In the period 1.1.1991 to 31.12.1993 it was 2.6 years (95% CL 1,3-?). The AIDS defining diseases were Pneumocystis carinii pneumonia in 43% of the cases, and oesophageal candidiasis in 24%. The median survival time after being diagnosed with AIDS was 2.0 years (95% CL 1,7-2,4). Heterosexual infection seems more pronounced in our material than for the country as a whole.

Nevirapine concentrations in preterm and low birth weight HIV-exposed infants: implications for dosing recommendations.

World Health Organisation guidelines recommend nevirapine 2 mg/kg/d for HIV-exposed infants <2 kg, but 4-6 mg/kg/d for infants >2 kg. In 116 low birth weight infants, nevirapine 2 mg/kg/d until 14 days, and 4 mg/kg/d thereafter, was safe (1 mild possibly related rash) and achieved target plasma concentrations. Concentrations decreased with treatment duration. Routine dose increase at 14 days should be considered.