Coinfections by HIV, hepatitis B and hepatitis C in imprisoned injecting drug users

In order to know the prevalence and risk factors for coinfections by human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV) among injecting drug users (IDUs), a cross-sectional study was carried out in two prisons of the province of Cantabria, northern Spain. Three hundred and sixty-two IDU inmates were recruited. All inmates were interviewed and their blood tested for HIV, HBV and HCV. Crude and multiple risk factor adjusted for (by polychotomous logistic regression) odds ratios were calculated. Prevalence of HBV-HCV coinfection (42.5%) was higher than HIV-HBV-HCV coinfection (37.3%), whereas monoinfections were very uncommon (overall: 13%). Long-term injectors and reincarceration were the foremost risk factors for both coinfections, showing a trend between the degree of association and the number of viruses infecting a patient. No significant relationship between coinfection status and sexual practices was observed. The results related to coinfections are consistent with previous studies of prevalence and risk factors for HIV, HBV and HCV, in indicating that the high rates of coinfections among IDU inmates emphasise the need to harm-reduction policy across prisons in Spain.     

伏马菌素B1免疫检测方法的研究

本研究建立了用于检测粮食、饲料中伏马菌素Ｂ１（ＦＢ１）的快速、灵敏、简便的免疫检测方法—建立在单克隆抗体基础上的直接竞争性酶联免疫吸附测定方法（ＤＣ—ＥＬＩＳＡ法）;其最低检出浓度为１０ｎｇ／ｍｌ,线性范围在１０ｎｇ～５μｇ／ｍｌ。对新疆、安徽、黑龙江、哈尔滨四省市玉米样品中的ＦＢ１含量进行了测定,结果表明１５６份样品中有３４份检出ＦＢ１,阳性率为２１．７９％,含量在０．１８～３１．３２μｇ／ｇ范围内,平均含量为１２．０４μｇ／ｇ。     

1993～1996年新生入学体检乙型肝炎病毒标志物及肝功能检测结果分析

目的：调查新生五项乙型肝炎病毒标志物（ＨＢＶＭ）及肝功能的结果,达到控制乙肝传染的目的。方法：选用四届入学新生１４６２份血清,采用酶联免疫吸咐法（ＥＬＩＳＡ）检测五项ＨＢＶＭ,应用改良赖氏法,检测了肝功能。结果：ＨＢＶＭ阳性组合例数７０９例,占４８．５０％,乙肝病毒抗原（ＨＢｓＡｇ）阳性者１４９例,占１０．８８％。乙肝病毒抗体（ＨＢｓＡｂ）阳性占３０２例,占２０．６６％。丙氨酸转氨酶（ＧＰＴ）异常者５３例,占３．６３％。结论：新生乙型肝炎病毒（ＨＢＶ）感染人数及ＨｓＡｇ携带者较多,对结果异常者应采取积极治疗和适当管理。ＨＢｓＡｂ阳性率逐年增高,结果提示,注射乙肝疫苗是防止乙肝传染的重要措施。     

Relationship between corneal thickness and measured intraocular pressure in a general ophthalmology clinic

OBJECTIVE: To assess whether central corneal thickness (CCT) is a confounding factor in the classification of patients attending for glaucoma assessment in a district general hospital. DESIGN: Cross-sectional study by a single observer. PARTICIPANTS: Patients attending a general ophthalmic clinic: 235 clinically normal eyes, 52 eyes with normal-tension glaucoma (NTG), 335 eyes with primary open-angle glaucoma (POAG), 12 eyes with pseudoexfoliative glaucoma (PXE), 42 eyes with chronic angle closure glaucoma (CACG), and 232 glaucoma suspect (GS) eyes. INTERVENTION: Central corneal thickness was measured using ultrasonic pachymetry. MAIN OUTCOME MEASURE: Correlation of CCT and diagnosis. RESULTS: Mean CCT was 553.9 microm (95% confidence intervals [CI] for the mean, 549.0-558.8 microm) in the clinically normal eyes, 550.1 microm (95% CI, 546.6-553.7 microm) in the POAG eyes, 514.0 microm (95% CI, 504.8-523.3 microm) in the NTG eyes, 530.7 microm (95% CI, 511.2-550.1 microm) in the PXE eyes, 559.9 microm (95% CI, 546.8-573.0 microm) in the CACG eyes, and 579.5 microm (95% CI, 574.8-584.1 microm) in the GS eyes. The differences of mean CCT between the groups were highly significant (P< 0.001 analysis of variance). Eighty-five percent of eyes with NTG and only 36% of eyes with POAG had a mean CCT of 540 microm or less. Thirteen percent of eyes with POAG and 42% of GS eyes had a mean CCT greater than 585 microm. CONCLUSIONS: The CCT measurement is desirable in patients attending for glaucoma assessment in a district general hospital to avoid misclassification resulting from the relationship between CCT and tonometric pressure. Central corneal thickness alone is not an accurate predictor for the clinical diagnosis in this group of eyes. However, many eyes diagnosed as having NTG have thin corneas, which would tend to lower the tonometrically recorded intraocular pressure (IOP), so the finding of a less-than-normal thickness cornea introduces some doubt as to the diagnosis of NTG. For the GS eyes, most eyes had thick corneas, which would tend to increase the tonometrically recorded IOP. Thus, GS eyes with modest elevation of IOP and a thick cornea may be at low risk of progressing to POAG. Thus, many patients with "high IOPs" and a thick CCT do not necessarily have high IOPs and may not need to be followed as GS eyes.     

异体LAK细胞联合IL-2治疗慢性乙型肝炎的近期疗效观察

对７３例慢性乙型肝炎患者随机分为两组,即异体ＬＡＫ细胞联合ＩＬ－２治疗组４８例和一般护肝药物对照组２５例。在治疗前及治疗后一个月检测直炎病毒ＤＮＡ〉两对半血清ＨＢＶ标志物、肝功能等项目。结果显示治疗组ＨＢｅＡｇ为６０．４％,ＨＢｃＡｇ、抗ＨＢｃＩｇＭ及ＨＢＶＤＮＡ的阴转率分别为３７．５％、２９．２％和４１．７％。ＨＢｓＡｇ阴转率为６．３％与对照组无显著性差异。治疗组肝功能恢复较对照组佳 。     

Identification of an amino acid residue important for binding of methiothepin and sumatriptan to the human 5-HT(1B) receptor.

Site-directed mutagenesis of the human 5-HT_1B receptor was performed to investigate the role of the amino acid residues cysteine 326 and tryptophan 327 in transmembrane region VI and aspartic acid 352 in transmembrane region VII in ligand binding. Binding studies were performed with the antagonist radioligand [³H]GR125743 on mutant and wild-type receptors stably expressed in Chinese hamster ovary cells (CHO)-K1 cells. Substitution of tryptophan 327 by alanine resulted in decreased affinities of all ligands tested. The most prominent changes in affinity were observed for the antagonist methiothepin and the antimigraine drug sumatriptan, which were reduced approximately 300- and 60-fold, respectively. Nevertheless, the affinity of 5-HT remained the same. Replacement of the aspartic acid 352 by alanine reduced high-affinity binding of 5-HT. Substitution of cysteine 326 by alanine had minor effects on ligand binding. Some of these results agree with the results from mutagenesis studies of the corresponding amino acids in other receptors. However, some notable differences also emerge showing that functional roles of individual amino acid residues must be tested experimentally in each receptor subtype.     

Activation of 5-HT1B receptors in the nucleus accumbens reduces amphetamine-induced enhancement of responding for conditioned reward

Previously, we have demonstrated that 5-hydroxytryptamine (5-HT) injected into the nucleus accumbens attenuates the potentiating effects of d-amphetamine on responding for conditioned reward (CR). The present studies examined the 5-HT receptor involved in this effect by investigating the effects of 5-HT agonists with differing affinities for 5-HT₁ and 5-HT₂ receptors on d-amphetamine-induced potentiation of responding for CR. Rats were trained to associate a light/tone stimulus (subsequently the CR) with water delivery. In a test phase, they were allowed access to a lever delivering the CR, and an inactive (NCR) lever. Responding on the CR lever was greater than responding on the NCR lever, indicating that the light/tone stimulus functioned as a CR. Responding for the CR was selectively potentiated by injections of d-amphetamine (10 μg) into the nucleus accumbens. This effect was reduced by injections into the nucleus accumbens of 5-CT (0.5 and 1 μg), RU24969 (10 μg), CP93,129 (1.25 and 2.5 μg) but not by DOI (10 μg) or 8-OH-DPAT (5 μg). The lower doses of 5-CT and CP93,129 did not reduce baseline responding for CR, or responding for water in a separate group of animals, indicating that the effects of these drugs were behaviourally selective. The higher doses abolished the CR effect, and in the case of 5-CT and RU24969 also reduced responding for water. All of the effective drugs share in common the ability to stimulate 5-HT_1B receptors, albeit with differing selectivities. The effect of CP93,129, the most selective of the 5-HT_1B agonists, to inhibit the response-potentiating effect of d-amphetamine was reversed by the5-HT_1B/1D antagonist GR127935 (3 mg/kg). The results indicate that activation of 5-HT_1B receptors within the nucleus accumbens attenuates the effects of a dopamine-dependent behaviour, and that activation of these receptors can oppose the behavioural effects of elevated mesolimbic dopamine transmission. Received: 22 April 1998/Final version: 28 July 1998     

A phase II study of Didemnin B (NSC 325319) in advanced malignant melanoma: an Eastern Cooperative Oncology Group study (PB687)

Purpose: Didemnin B is a novel marine natural product cyclic depsipeptide containing unusual amino acid moieties. This agent demonstrates promising preclinical antitumor activity, including activity against B16 melanoma and against melanoma isolates in the human tumor stem cell assay.Methods: We conducted a phase II study of Didemnin B, given in Cremophor, at a starting dose of 4.2 mg/m2/IV q 28 days. Patients with measurable metastatic or advanced malignant melanoma were eligible. All patients were previously untreated with chemotherapy and had performance status 0 or 1. Doses were escalated to 4.9 and 5.6 mg/m2 in cycles 2 and 3, respectively.Results: Nineteen patients were entered and treated with a median of one cycle per patient. Eight of these patients went off study for toxicity including 7 with anaphylactoid reactions in the first or second cycle. One patient went off study after 3 cycles with severe myopathy, a newly described toxicity. Two were not evaluable for response and five were considered stable, including one patient with a transient PR of soft tissue disease in the first cycle. Another patient had stable disease for twelve cycles before progressing and one went off study electively after 3 cycles, for a total of 7 patients with stable disease. One patient with a measurable partial remission (PR) and went off study after three cycles due to severe myopathy, a then newly-described toxicity. No hematologic toxicity was seen. Nausea and vomiting were controlled with anti-emetics.Conclusions: This study was indeterminate with respect to the activity of Didemnin B in melanoma. Signs of activity were seen, particularly in soft tissue masses, though a large number of patients could not be evaluated fully for activity due to the occurrence of anaphylactoid reactions. This study does not preclude a clinically important level of activity for Didemnin B.     

Phase I clinical study of didemnin B

Didemnin B (NSC-325319), a new depsipeptide isolated from a Caribbean tunicate, has been evaluated in a clinical phase I study. The drug was administered in a schedule of a 4 weekly intravenous injection in a six-weeks cycle. Fifty-three patients received 71 evaluable cycles in an escalated dose ranging from 0.4 mg/m²/week to 2.5 mg/m²/week. No hematological toxicity was demonstrated at any dose level. Without prophylactic antiemetics nausea and vomiting was dose limiting at 1.2 mg/m²/week. Due to the use of Cremophor EL as a solvent, hypersensitivity reactions occurred in 9 patients. These reactions occurred following prior exposure to the drug and were commonly seen at the 3rd dose. They were not dose related but became more frequent at 1.5 mg/m²/week necessitating prophylactic treatment with H₁ and H₂ receptor blocking agents. Non-hematological toxicities included mild diarrhea, mucositis, anorexia, headaches, and local phlebitis. The dose- limiting toxicity was generalized weakness which became severe and disabling in 3 of 6 patients treated at 2.5 mg/m²/week. No objective responses were documented in 39 patients with evaluable disease. The recommended dose for phase II studies was 2.3 mg/m²/week × 4 4 in a 6-weeks cycle given with prophylactic antiemetics and H₁ and H₂ receptor blocking agents.