The clinical features and laboratory findings in acute Plasmodium falciparum malaria in Harare, Zimbabwe

The immune status of patients in Harare modifies their response to acute P.falciparum infection. Malnourished children were the group at greatest risk and fits were a feature of malaria in this age group. Fever and headache were the commonest symptoms overall, but 12,5% of patients were never pyrexial. Splenomegaly was common in young children but uncommon in adults. A leukocytosis, thrombocytopenia and normochromic normocytic anemia were common features of acute P. falciparum malaria as were hyponatremia and hypokalemia. The leukocytosis and hypokalemia are not well documented features of acute malaria and genetic differences may account for varying responses. The diagnosis was proven in only 26% of cases thought clinically to have malaria. In several cases malaria was not considered in the differential diagnosis. More than 1/2 the patients with positive blood slides received antibiotics as well as chloroquine. Bacteria were isolated from blood cultures in 8 patients. Septicemia may be an uncommonly recognized complication of acute P. falciparum malaria.     

Acute hepatitis C: clinical aspects, diagnosis, and outcome of acute HCV infection

Acute hepatitis C virus (HCV) infection is often a clinically silent infection, and is therefore rarely detected. A high index of clinical suspicion in addition to careful serological and virological assessment is required to identify the disease, and to determine the eventual clinical outcome after primary infection; the minority of acutely infected individuals spontaneously control viremia in long term whilst the majority become persistently infected. Here, we describe the clinical presentation of acute HCV infection and the patterns of viremia and liver alanine transaminase levels (ALT) observed. We discuss the serological and virological assessment and potential pitfalls in accurately diagnosing acute HCV. Good prospective studies that identify host and virological factors that determine clinical symptoms and disease outcome are difficult to perform due to the asymptomatic nature of infection, but some progress has been made in this field. Host factors including gender, age at time of infection, prior resolution of infection, symptomatic infection and host immune responses, and viral factors such as the nature of the infecting quasispecies and more speculatively viral genotype, are some features that have been correlated with disease outcome. In spite of this, on an individual patient level, it is currently not possible to predict those that will resolve infection. Identifying, in detail therefore, those factors that are responsible for viral control remains an important research goal not only to aid clinical management but also to develop effective treatment and vaccination strategies.     

Pediatric asthma: natural history, assessment, and treatment

Wheezing and childhood asthma are not synonymous but rather comprise a heterogeneous group of conditions that have different outcomes over the course of childhood. Most infants who wheeze have a transient condition associated with diminished airway function at birth and have no increased risk of asthma later in life. However, children with persistent wheezing throughout childhood and frequent exacerbations represent the main challenge today. Studying the natural history of asthma is important for the understanding and accurate prediction of the clinical course of different phenotypes. To date, a great improvement has been achieved in reducing the frequency of asthma symptoms. However, neither decreased environmental exposure nor controller treatment, as recommended by the recent National Asthma Education And Prevention Program, can halt the progression of asthma in childhood or the development of persistent wheezing phenotype. This review focuses on the recent studies that led to the current understanding of asthma phenotypes in childhood and the recommended treatments.     

Clinical presentation of acute viral hepatitis

Acute viral hepatitis may be asymptomatic, symptomatic but anicteric, or a classical icteric hepatitis; rarely it is very severe and may be fatal. Different types of illness may be caused by the various hepatitis viruses. This does not help precise diagnosis, which is based on serological tests. This paper describes hepatitis seen with the A, B, C, D and E viruses, and also some of the unusual complications which have been recognized. Serological tests allow precise diagnosis of acute hepatitis A and B, and should be used more widely, because viral hepatitis is often diagnosed when jaundice is caused by other conditions. They also allow diagnosis when viral hepatitis has an atypical presentation, and is thus not considered as the cause of the liver disease. Negative tests suggest the need for further investigation.     

A comparison of hepatitis C treatment and outcomes at academic, private and Veterans' Affairs treatment centres

BACKGROUND: Currently, there is a lack of published data examining hepatitis C treatment practices in different care settings. AIM: To provide data describing treatment practices for patients with hepatitis C virus infection in actual clinical practice, and to examine clinical outcomes in patients treated with interferon alpha-2b/ribavirin combination therapy in academically affiliated centres, private treatment centres and Veterans' Affairs treatment centres. METHODS: This multi-centre, retrospective, cohort study of 231 patients examined hepatitis C virus treatment practices in patients receiving interferon alpha-2b from January 1997 to May 2001 and explored outcomes in academically affiliated, private and Veterans' Affairs centres. RESULTS: Differences in treatment practice and use of diagnostic procedures were found. Genotype testing was under-utilized in non-academic sites (academic centres, 79.2%; private centres, 33.7%; Veterans' Affairs centres, 35.9%; P<0.001). Liver biopsies were performed less often in private sites (academic centres, 95.8%; private centres, 80.0%; Veterans' Affairs centres, 92.2%; P<0.01). End-of-treatment viral response (academic centres, 40.0%; private centres, 31.3%; Veterans' Affairs centres, 17.2%; P<0.05) was lower than that found in published trial data. Multivariate analysis revealed genotype 1 as the single significant predictor of treatment failure (P<0.01). CONCLUSIONS: Outside of the academic setting, there is significantly less diagnostic work-up performed prior to the initiation of hepatitis C virus therapy. This suggests a need for a standardization of care across treatment settings.     

The clinical application of laboratory animal experimental findings: treatment of hypersexualized behavior in a male.

Exposure of animals to drugs which induce hepatic enzymes results in an acceleration of hydroxylation of endogenous as well as exogenous steroid hormones (Conney, A.H., Pharma. 19 [1967] 317). Fahim et al. in a two part study, noticed when phenobarbital was administered to sexually mature male rats, it accelerated the metabolism of androgen as reflected by significant reductions in weight and RNA content of male accessory organs [3]; it was also observed that vitamin B 12 is an enzyme inducer [2]. Currently we observed a significant synergism between vitamin B 12 and phenobarbital in acceleration of drug metabolizing enzymes in rats. This demonstration of drug-steroid interaction reinforces the possibility of utilizing such phenomena as therapeutic modalities for human reproductive syndromes associated with overprodduction of sex hormones. This was applied in a young 16 year old mildly retarded male who was having much difficulty coping with sexual urges. His serum testosterone level was 960 ng%, which is abnormally high for his age. The patient was treated with 30 mg phenobarbital, morning and evening, and 50 mcg vitamin B 12 daily. After three months of treatment, his testosterone level decreased significantly to 620 ng%, and his hypersexualized behavior with girls had completely dropped out. There were no side effects in his physical appearance or general health. This therapy encourages its utilisation in humans with androgen overproduction instead of utilizing estrogen or other drugs which may have side effects.     

乙肝康治疗慢性乙型肝炎近期疗效分析

目的 :评价中药复合制剂乙肝康对慢性乙型肝炎治疗作用。方法 :选择HBeAg、HBV DNA阳性 ,肝功能异常的 31例慢性乙型肝炎作治疗对象 ,给予乙肝康 10mL加入 5 %葡萄糖 2 5 0mL内每日滴注 1次 ,疗程 3个月 ,并与 2 5例静滴甘利欣 ,泰特病人作对照。结果 :完全应答 11例 ,部分应答 13例 ,无应答 7例。HBV DNA14例阴转 ( 45 .1% ) ,HBeAg11例阴转 ( 35 .5 % ) ,其中 9例HBeAg/抗HBe血清转换 ( 2 9% )。 结论 :乙肝康具有治疗慢性乙型肝炎肝功能的作用 ,同时具有清除体内病毒的作用 ,值得进一步研究。     

Pathophysiology, clinical presentation and treatment of gout

Gout is a common form of inflammatory arthritis that has been managed primarily in general medical practices for centuries. It appears that there has been an increasing prevalence of gout over the past decades, implying a growing public health burden. Accurate diagnosis and recognition of the various stages and manifestations of gout enable realistic goal setting for management. Recent evidence suggests new risk factors and potentially refutes others. Management of gout requires characterising and modifying risk factors and associated disorders, and commonly initiating drug therapy. Pharmacotherapy of gout includes the management of acute flares with anti-inflammatory agents such as NSAIDs and glucocorticoids and long-term treatment with urate-lowering drugs. Although pharmacotherapy is generally safe and effective, there are caveats and limitations to all gout therapies. Patient non-adherence and errors with the use of drugs for gout treatment are important factors leading to medical failures. With early intervention, careful monitoring and patient education, gout is a condition that can be managed very effectively. The advent of new drugs (such as febuxostat and urate oxidase [uricase]) and enhanced understanding of the pathogenesis of gout continue to improve our therapeutic options, particularly in a subset of patients with refractory disease and those who are intolerant to currently available medications.     

Molindone hydrochloride: a review of laboratory and clinical findings

Molindone hydrochloride, a dihydroindolone neuroleptic, is structurally distinct from other classes of neuroleptics. Molindone exhibits many similarities to other neuroleptics, including dopamine receptor blockade, antipsychotic efficacy, and extrapyramidal side effects. Despite these similarities, molindone also has atypical properties and inhibits the enzyme monoamine oxidase in vitro and in vivo. Several studies have shown that molindone causes less dopamine receptor supersensitivity than other neuroleptics and thus may be less likely to cause tardive dyskinesia. It also appears to have a greater effect on mesolimbic and mesocortical dopamine neurons than on those in the nigrostriatal dopamine system. Clinically, molindone has a tendency to cause weight loss and may have less effect on seizure threshold than conventional antipsychotic agents. The authors review the laboratory and clinical data on molindone and discuss the relevance of atypical research findings to the clinical characteristics of this antipsychotic agent.     

药源性血小板减少症的发病机制和临床表现及防治

药源性血小板减少症是指药物使血小板计数低于正常范围(<100×109/L)引致出血等症状的疾病。药源性血小板减少症按发病机制至少有以下3种:骨髓抑制性、免疫性及非免疫性的血小板减少症。引致血小板减少症的常见药物有:肿瘤化疗药物、肝素、奎尼丁、奎宁、金盐、丙戊酸及抗菌药等。肿瘤化疗药物所致血小板减少症的发生率大体高于其他药物。药源性血小板减少症的体征和症状为皮肤瘀点、瘀斑、鼻出血和牙龈出血,严重者有消化道出血、血尿、阴道出血和颅内出血。药源性血小板减少症可选用以下方法治疗:停用可疑致病药物,给予泼尼松、免疫球蛋白及输注血小板,金盐或砷化物引起的血小板减少症可肌内注射二巯基丙醇以排出重金属离子。     

Etiology, natural history and treatment of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is linked to environmental, dietary and lifestyle factors. Patients with cirrhosis and chronic carriage of hepatitis B virus (HBV) are at risk for HCC at annual rates of 3%. HCC risk is particularly high in patients with evidence of cirrhosis and histological markers of increased liver cell proliferation. In addition, thrombocytopenia, prolonged prothrombin time and over 55 years of age also predict the development of HCC. Treatment options are defined according to the presence or absence of cirrhosis, number and size of tumors, and degree of hepatic decompensation. Hepatic resection is the primary intervention for these few patients with tumor but surrounding normal liver tissue and well preserved hepatic function. Under such circumstances, the cumulative 5-year survival is approximately 45%. Liver transplantation (OLT) provides long term survivals (90% at 5 years) in patients with a HCC discovered by chance as a minute nodule and of 75% in patients with viral cirrhosis and a single <5 cm tumor or fewer than three <3 cm nodes. Since liver transplantation cannot be offered to most patients with HCC, hepatic resection remains the primary therapeutic option; 5-year survival of 50% is anticipated in patients with compensated cirrhosis and <5 cm of tumor and 75% for those with moderate portal hypertension and normal serum bilirubin values. Ultrasound-guided tumor injection with absolute ethanol or tumor thermoablation with radiofrequency provide similar survival rates but with fewer complications. Whether arterial chemoembolization benefits patients with HCC remains controversial.     

免疫治疗相关垂体炎的临床表现、治疗和生物学展望

免疫治疗的进展已经改变了转移性黑素瘤的治疗方式,并在其他恶性肿瘤的治疗方面产生了令人鼓舞的结果.免疫不良事件(immunerelated adverse events,IRAEs)是免疫制剂的副作用,其形式多种多样的,包括多发性的内分泌疾病.伊匹单抗(Ipilimumab,Ipi)诱导的垂体炎(limumab-induced hypophysitis,IH)是最近被认识的内分泌性免疫不良事件.根据目前已公布的数据我们进行了总结,通过关注应用Ipi治疗的患者,积累了免疫治疗相关垂体炎在发病率、临床表现和治疗方法方面的数据,并对其发病机制提出了假设.     

Concurrent group treatment for hepatitis C: Implementation and outcomes in a methadone maintenance treatment program

Chronic hepatitis C virus (HCV) infection is highly prevalent among current and former drug users. However, the minority of patients enrolled in drug treatment programs have initiated HCV treatment. New models are needed to overcome barriers to care. In this retrospective study, we describe the implementation and outcomes of 42 patients treated in a concurrent group treatment (CGT) program. Patients participated in weekly provider-led group treatment sessions which included review of side effects; discussion of adherence and side effect management; administration of interferon injections; brief physical examination; and ended with brief meditation. Of the first 27 patients who initiated CGT, 42% achieved a sustained viral response. In addition, 87% (13/15) of genotype-1 infected patients treated with direct acting antiviral agent achieved an undetectable viral load at 24 weeks. The CGT model may be effective in overcoming barriers to treatment and improving adherence and outcomes among patients enrolled in drug treatment programs.     

Hepatitis C virus infection in the elderly: epidemiology, natural history and management

Hepatitis C virus (HCV) infection frequently occurs in elderly individuals, with a prevalence in individuals aged >60 years of up to approximately 40%. Although progression to cirrhosis is accelerated and occurs more frequently in patients who acquire the infection in old age, this outcome is often not seen because most elderly infected patients acquired HCV when they were young. Data on progression of HCV infection to cirrhosis and eventually to hepatocellular carcinoma are often derived from studies of HCV-infected individuals who present or are referred to hospitals, and which are therefore likely to overestimate the seriousness of the disease; indeed, population-based studies indicate that in many elderly individuals the disease is asymptomatic and runs a fairly benign course. Treatment is based on use of pegylated interferon-alpha and ribavirin, and is overall less effective and more toxic in the elderly. Therefore, treatment should be carefully considered on an individual basis and proposed only in patients up to the age of 75 years with a significant risk of progression of liver disease, no serious co-morbidities and good life expectancy. All treated patients should be followed long term in order to assess the influence of therapy on the evolution of liver disease (decompensated cirrhosis, hepatocellular carcinoma) and survival. It is hoped that liver biopsy, which is still required in order to assess prognosis appropriately, will be replaced in the future by less invasive methods based on combinations of biochemical markers of fibrosis and/or transient elastography, and that newer and less toxic orally administered drugs for HCV infection will become available.     

Extinguishing conditioned responses during opiate dependence treatment turning laboratory findings into clinical procedures

Former opiate addicts (even those who have remained drug-free for several months) often report symptoms of opiate withdrawal (eg. nausea, gooseflesh, etc.) and/or intense drug craving when exposed to stimuli previously associated with the act of drug injection. This phenomenon of learned or "conditioned" withdrawal/craving is widely reported and is potentially important in explaining relapse to drug use. However, no effective, clinically applicable intervention had been available to "extinguish" these conditioned phenomena. An ongoing project to develop such an intervention has revealed: Conditioned withdrawal and craving are pervasive among both methadone maintained patients (even though actual physical withdrawal is blocked) and drug-free patients even after 30 days of inpatient Therapeutic Community rehabilitation. Conditioned withdrawal and craving can be effectively extinguished in an intensive, three-week, inpatient procedure. Emotional states such as anger, depression and anxiety can elicit and exacerbate conditioned withdrawal and craving. They may also act as an integral part of a conditioned stimulus complex. The authors discuss the problems associated with turning a laboratory-based procedure into a clinical intervention. Encouraging preliminary results from an integrated treatment "package" are presented.     

Treatment of acute hepatitis C

Progression from acute to chronic HCV infection occurs in 50% to 84% of cases. In light of the risk of developing chronic disease and the response rate to treatment once the disease is established, it is important to consider early treatment of acute HCV infection before it progresses to the chronic state. Several studies evaluated the efficacy of either alpha or beta IFN monotherapy in patients with acute hepatitis C, but nearly all trials are small and present great variability regarding timing, schedule, response definition and patient characteristics. To overcome these limits, IFN efficacy has been assessed by meta-analyses demonstrating that antiviral therapy during the acute phase of HCV significantly reduces evolution to chronic hepatitis. Accordingly, treatment of persons with acute hepatitis C is warranted. However, several issues remain to be addressed, such as the optimal regimen and timing. Recent data would indicate that induction with daily IFN is needed to optimize response and pegylated IFN monotherapy could be the best option. Combination therapy with ribavirin does not seem to increase the response rate but could be proposed as a second choice to patients non responding to IFN monotherapy. Delaying treatment by 2-3 months might allow the identification of cases who would spontaneously resolve without compromising efficacy. However, additional data are required to improve the selection of those patients at great risk of progressing to chronic disease, and also to establish the optimal treatment in terms of risk/benefit and cost-effectiveness ratio.