Gene/Protein Disease Symptom Drug Enzyme Compound
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Valganciclovir is a prodrug of ganciclovir which has been developed for the treatment of cytomegalovirus (CMV) retinitis in patients with AIDS. Oral valganciclovir is rapidly absorbed and hydrolysed to ganciclovir. The oral bioavailability of ganciclovir after oral valganciclovir administration is high. Oral valganciclovir 900 mg provides a daily exposure of ganciclovir comparable to that of intravenous ganciclovir 5 mg/kg. A single, randomised, nonblind study indicated that oral valganciclovir (900mg twice daily for 3 weeks then 900 mg once daily) and intravenous ganciclovir (5 mg/kg twice daily for 3 weeks then 5 mg/kg once daily) were equally effective in the treatment of newly diagnosed CMV retinitis in 160 patients with AIDS. Valganciclovir appears to have a similar tolerability profile to intravenous ganciclovir during induction therapy in patients with AIDS and newly diagnosed CMV retinitis. During maintenance therapy with valganciclovir, the most commonly reported adverse events included neutropenia, anaemia, thrombocytopenia, gastrointestinal (including diarrhoea, nausea, vomiting and abdominal pain), fever, headache, insomnia, peripheral neuropathy, paraesthesia and retinal detachment.
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PMID:Valganciclovir. 1146 75

Most patients with advanced cancer develop diverse symptoms that can limit the efficacy of pain treatment and undermine their quality of life. The present study surveys symptom prevalence, etiology and severity in 593 cancer patients treated by a pain service. Non-opioid analgesics, opioids and adjuvants were administered following the WHO-guidelines for cancer pain relief. Other symptoms were systematically treated by appropriate adjuvant drugs. Pain and symptom severity was measured daily by patient self-assessment; the physicians of the pain service assessed symptom etiology and the severity of confusion, coma and gastrointestinal obstruction at each visit. The patients were treated for an average period of 51 days. Efficacy of pain treatment was good in 70%, satisfactory in 16% and inadequate in 14% of patients. The initial treatment caused a significant reduction in the average number of symptoms from four to three. Prevalence and severity of anorexia, impaired activity, confusion, mood changes, insomnia, constipation, dyspepsia, dyspnoea, coughing, dysphagia and urinary symptoms were significantly reduced, those of sedation, other neuropsychiatric symptoms and dry mouth were significantly increased and those of coma, vertigo, diarrhea, nausea, vomiting, intestinal obstruction, erythema, pruritus and sweating remained unchanged. The most frequent symptoms were impaired activity (74% of days), mood changes (22%), constipation (23%), nausea (23%) and dry mouth (20%). The highest severity scores were associated with impaired activity, sedation, coma, intestinal obstruction, dysphagia and urinary symptoms. Of all 23 symptoms, only constipation, erythema and dry mouth were assessed as being most frequently caused by the analgesic regimen. In conclusion, the high prevalence and severity of many symptoms in far advanced cancer can be reduced, if pain treatment is combined with systematic symptom control. Nevertheless, general, neuropsychiatric and gastrointestinal symptoms are experienced during a major part of treatment time and pain relief was inadequate in 14% of patients. Cancer pain management has to be embedded in a frame of palliative care, taking all the possibilities of symptom management into consideration.
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PMID:Symptoms during cancer pain treatment following WHO-guidelines: a longitudinal follow-up study of symptom prevalence, severity and etiology. 1151 84

The side-effect profile of levofloxacin was compared with that of other fluoroquinolones based on European and international data from approximately 130 million prescriptions. Levofloxacin was found to be very safe with a low rate of hepatic abnormalities (1/650,000). In contrast, 140 trovafloxacin-treated patients developed hepatic problems, 14 of which were severe, and 8 required transplantation. The main CNS problems associated with fluoroquinolones include dizziness, convulsions, psychosis, and insomnia. Levofloxacin, ofloxacin, and moxifloxacin reportedly have the lowest potential of inducing central nervous system (CNS) adverse events among the fluoroquinolones currently available. Cardiovascular problems were seen in 1/15 million levofloxacin prescriptions compared to 1-3% of sparfloxacin patients having QTc prolongation of greater than 500 msec. Moxifloxacin was also associated with QTc prolongation when compared to non-fluoroquinolone comparators. Nausea, vomiting, and diarrhoea remain the main adverse drug reactions (ADRs) associated with levofloxacin. However, the ADR rate for levofloxacin is still one of the lowest of any fluoroquinolone at 2% (compared to 2-10% for other fluoroquinolones). Ofloxacin and levofloxacin have a very low phototoxic potential, whereas this is a problem for sparfloxacin, enoxacin, and pefloxacin. The tolerance profile of levofloxacin can be considered to be very good, and better than most, if not all of the fluoroquinolones available.
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PMID:Comparison of side effects of levofloxacin versus other fluoroquinolones. 1154 84

This paper reviews the safety data for levofloxacin utilizing reports from clinical and post-marketing surveillance trials. The side effect incidence rates are 1.3% for nausea, 0.1% for anxiety, 0.3% for insomnia, and 0.1% for headache. No levofloxacin-related adverse events were reported at a rate higher than 1.3%, and most were lower. Four clinical trials were reported. Levofloxacin achieved superior clinical and microbiological results compared to ceftriaxone/macrolide combination, and was better tolerated. Results comparing IV azithromycin plus ceftriaxone versus 500 mg levofloxacin in hospitalised CAP demonstrated that levofloxacin performed better, with more adverse events associated with the comparators (levofloxacin 5.3%, comparators 9.3%). High-dose levofloxacin (750 mg) was also evaluated and found to be well tolerated. Surveillance data reported low ADR rates for levofloxacin: nausea 0.8%, rash 0.5%, abdominal pain 0.4%, and diarrhoea, dizziness, and vomiting 0.3%. Worldwide and US surveillance data confirmed that tendon rupture occurred in less than 4 per million prescriptions, taste perversion in less than 3 per million, convulsions in 2 per million, and photosensitivity, hepatitis, hepatic failure, QT prolongation, torsade de pointes or empyema all in less than 1 per million.
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PMID:Latest industry information on the safety profile of levofloxacin in the US. 1154 87

The aim of the present study is to determine the effect of blood lead on the health of industrial workers in United Arab Emirates (UAE). This is a cross-sectional pilot survey of blood lead levels (BLL) of 100 industrial workers (exposed) and 100 non-industrial workers (nonexposed), matched for age, sex and nationality selected from Al-Ain, Abu-Dhabi Emirate. Industrial workers had significantly higher mean of BLL (77.5+/-42.8 microg/dl and median 80.9 microg/dl) than non-industrial workers (19.8+/-12.3 microg/dl and median 11.0 microg/dl). In the present study, reported symptoms among industrial workers were strongly associated with BLL nausea/vomiting, muscular symptoms, dizziness, fatigue, irritability, memory disturbances, insomnia and allergic conjuctivitis, rhinitis and dermatitis. Furthermore, the present study revealed that industrial workers had higher prevalence of respiratory symptoms for phlegm, shortness of breath and diagnosed asthma. In conclusion, this study determined that occurrence of certain symptoms might be associated with lead exposure among industrial workers.
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PMID:A pilot survey of blood lead levels in various types of workers in the United Arab Emirates. 1168 41

To determine the prevalence, severity, and correlates of fatigue among patients with cancers of the prostate or breast receiving high dose radiotherapy with curative intent, a prospective, questionnaire-based study evaluated a convenience sample of 62 patients who were about to start a course of radiotherapy. Patients were assessed immediately prior to treatment, and again within a week of finishing. Fatigue was assessed using the Fatigue Severity Scale (FSS) and the Bidimensional Fatigue Scale (BFS). Quality of life was assessed using the European Organisation for Research and Treatment of Cancer 30-item Quality of Life Questionnaire (EORTC QLQc30). Psychological distress was assessed using the Hospital Anxiety and Depression Scale (HADS). Personality Traits were assessed using the Eysenck Personality Inventory (EPI). Fatigue severity increased significantly on 3 out of the 5 assessment instruments used. Radiotherapy was associated with a decline in global quality of life, role, cognitive and social functioning, and an increase in nausea/vomiting, pain, insomnia, diarrhea, and financial difficulty. At baseline, 39% of the variation in fatigue scores among the patients could be explained by a combination of measures of their global quality of life and physical functioning. A combination of fatigue and anxiety scores at baseline was able to predict 54% of the variation in fatigue scores at the completion of radiotherapy. These data indicate that fatigue is a significant problem for patients receiving radical radiotherapy, although its severity is relatively modest.
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PMID:Fatigue in patients with cancers of the breast or prostate undergoing radical radiotherapy. 1173 63

This study examined the prevalence of somatic symptoms and psychiatric characteristics of major depression in a Japanese psychosomatic outpatient clinic. A total of 2,215 outpatients referred for mind/body complaints were assessed by DSM-III-R or DSM-IV. Somatic symptoms were rated using the Cornell Medical Index Questionnaire. Ninety-one outpatients (4.1%) were diagnosed with major depression. Prevalence of fatigue (86%), insomnia (79%), nausea/vomiting (50%), and back pain (36%) as well as degrees of psychosocial stress (DSM-III-R axis IV) were higher (all p < 0.05) and scores of global assessment of psychosocial functioning (DSM-III-R/DSM-IV axis V) were lower (p < 0.001) in the major depressive patients compared to the remaining outpatients. Among the major depressive patients, the total number of somatic symptoms was larger (p < 0.05) in patients with 'severe' major depressive episodes than in those with 'mild' depressive episodes. These findings suggest that the level of depression is closely linked to the reporting of somatic symptoms in a psychosomatic medicine population.
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PMID:Major depression and somatic symptoms in a mind/body medicine clinic. 1179 17

Zolpidem is a nonbenzodiazepine hypnotic of the imidazopyridine class that is used to treat insomnia in humans. Zolpidem binds selectively to the benzodiazepine omega-1 receptor and increases the frequency of chloride channel opening, which results in inhibition of neuronal excitation. A retrospective study was conducted of zolpidem ingestion in dogs that were reported to the ASPCA Animal Poison Control Center (APCC) between January 1998 and July 2000. Data analysis included amount ingested, clinical effects, and time of onset of signs. Thirty-three reports of zolpidem ingestion in dogs (ranging in age from 5 months to 16 years) were evaluated. Approximate ingested dosages ranged from 0.24 to 21 mg/kg. Clinical signs reported included ataxia (18 dogs; 54.5%), hyperactivity (10 dogs; 30.3%), vomiting (7 dogs; 21.2%), and lethargy (5 dogs; 15.2%), as well as panting, disorientation, nonspecific behavior disorder, and hypersalivation (4 dogs each sign; 12.1%). Other signs reported include tachycardia, tremors, apprehension, vocalization, hypersalivation, weakness, and hyperesthesia. In 85% percent of reports, clinical signs developed within 1 hour and usually resolved within 12 hours. Although central nervous system (CNS) depression is reported as a primary effect of zolpidem in humans and would also be expected in dogs, information obtained from this study indicates that some dogs may exhibit a paradoxical excitation reaction. This effect appears to vary among individual dogs.
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PMID:Clinical syndrome associated with zolpidem ingestion in dogs: 33 cases (January 1998-July 2000). 1189 40

The effectiveness of pulsed high-dose oral dexamethasone therapy in children with refractory chronic idiopathic thrombocytopenic purpura (ITP) is evaluated. Thirteen children with severe chronic ITP were enrolled in the study from an outpatient pediatric hematology clinic (ages 2-14 years), 5 boys and 7 girls. They did not maintain a response to other forms of therapy (IVIg, Anti-D, conventional steroids, danazol) and one girl relapsed after splenectomy. Dexamethasone was administered orally at a dosage of 40 mg/M2/day (maximum 40 mg/day) for 4 consecutive days. The cycle was repeated once a month for 6 months. The immediate response to therapy was excellent as the mean platelet count at day 1 was 15 x 10(9)/L, while mean platelet count at day 4 was 158 x 10(9)/L. At the end of 6 cycles 3 patients maintained a platelet count of >150 x 10(9)/L and 4 patients showed partial response. At the end of the first year and second year (12 and 24 months after onset of treatment) 3 patients still had complete response, 3 patients had partial response, and 7 patients were failures. Six of the failures underwent splenectomy and one was shifted to dapsone, had no response, and refused splenectomy. Side effects were tolerable. They included bloating, nausea, vomiting, insomnia, anxiety, and depression, and transient glucosuria; however, they were not severe enough to discontinue the cycles. Mean duration of illness prior to start of dexamethasone was not significantly different in between responders and nonresponders. Dexamethasone given orally in high doses is an effective drug in achieving short-term platelet responses. Long-term remission is obtained in nearly half the patients with well-established chronic ITP. Its effectiveness in almost half the patients, minimal side effects, and low cost indicate that this treatment should be considered in patients with chronic ITP who do not tolerate the disease well before considering splenectomy.
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PMID:Pulsed high-dose dexamethasone therapy in children with chronic idiopathic thrombocytopenic purpura. 1207 64

This work uses clinical examples to explore sources of conflict and denial of patients and physicians during contraception consultations. The discovery of oral contraceptives (OCs) and improvements in mechanical contraception raised hopes that couples could achieve total control of their fertility. But continued high abortion rates and the persistence of sexual problems and maladjustments have demonstrated that contraception alone is not a panacea. Conflicts about contraception may be conscious and quickly expressed during a consultation, even if a medical pretext is given. The resentment when 1 partner desires a child and the other does not for example can translate into a conflict about contraception. Some women are fully aware of their own ambivalence about pregnancy and contraception and able to express it openly, but very often the woman's concerns are expressed by questions, fears, and verbal slips. The fear that pills are unnatural or will cause congenital defects can be interpreted as an expression of guilt over the pleasure that pills permit. Sterility is the ultimate fear caused by this unlimited possibility for pleasure. In the majority of cases, physical complaints are the means by which contraception clients address their physicians. In some cases, intolerance to OCs may actually be a hysterical manifestation that is not understood. Such symptoms as nausea, breast swelling, dizziness, vomiting, nervousness, and insomnia may be signs of early pregnancy as well as of intolerance for pills. Intolerance to pills may be caused by intolerance of a sexuality in which all things seem possible but in which the individual feels unrecognized by the partner. The resulting aggression may be turned inward in the form of a morbid symptom or of forgetting or stopping pill use, recourse to abortion, and demand for recognition. Acting out, especially by adolescents, is common in the area of contraception. In some cases the psychological or emotional needs of the patient might be better met by contraception that leaves some risk of failure, such as low-dose progestins or local methods. Their relative efficacy may allow the ambivalent desire for a child not to be completely stifled. Cases also arise in which patients use contraceptives to mask problems and to give the illusion of a normally functioning body. The possibility of having a child is very seldom raised during contraceptive consultations, perhaps because for the physician contraception subconsciously evokes the forces of death. The doctor can take refuge in the technical aspects of contraception, ignoring the emotional needs of the client.
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PMID:[The difficulties of contraception: conflicts and paradoxes]. 1231 42


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