Four to 6 months of conventional interferon alpha (IFN-alpha) (5MU daily or 10MU three times weekly) resulted in HBeAg loss in approximately 33% of HBeAg positive patients (controls: 12%). Longer treatment duration improved HBeAg seroconversion. Children with chronic HBV infection and high ALT respond to IFN-a at similar rates. Good end-of-treatment (ET) biochemical and virological response were also achieved with IFN-alpha in HBeAg negative, HBV-DNA positive hepatitis patients. Sustained response (SR) however, was disappointing, but improved with longer duration of treatment: (10-15% SR with 4/6 months treatment: 30% SR with 24 months treatment). Weekly pegylated IFN-alpha2a (PegIFN-alpha2a) for 24 weeks gave a significantly higher HBeAg conversion rate (33%) than conventional IFN-alpha2a (25%). Fifty-two weeks of PegIFN-alpha2b gave a sustained HBeAg loss in 35% patients and HBeAg seroconversion in 29% patients. Similar results were obtained with 48 weeks of weekly PegIFN-alpha2a. PegIFN-alpha2a monotherapy was found to be superior to lamivudine monotherapy in affecting a 6-month SR (normal ALTs and HBV DNA < 20,000 copies/mL) in HBeAg negative/anti-HBe positive chronic hepatitis B patients. There is a tendency for IFN-a and lamivudine combination to result in better sustained response than lamivudine monotherapy. This tendency is also observed with PegIFN-a and lamivudine combination although the combination did not appear to be better than PegIFN-alpha monotherapy. IFN induced HBeAg seroconversion is durable, could increase over time and resulted in better overall survival and survival free of hepatic decompensation or hepatocellular cancer. The main advantage of IFN-a therapy is that a course of finite duration may achieve sustained off-therapy response in a proportion of both HBeAg positive and HBeAg negative chronic hepatitis B patients. However, IFN treatment is usually associated with side-effects, especially flu-like symptoms, fatigue, neutropenia, thrombocytopenia and depression. These are usually tolerable but may require dose modification and premature cessation of treatment (5%). Interferon therapy induced hepatitis flares may lead to decompensation in patients with cirrhosis and can be dangerous in patients with decompensated liver function despite dose reduction.
Although Pakistan has a high burden of multidrug-resistant tuberculosis (MDR-TB), little is known about prevalence, management, and risk factors for adverse drug reactions (ADRs) in MDR-TB patients in Pakistan. To evaluate occurrence, management, and risk factors for ADRs in MDR-TB patients, and its impact on treatment outcomes, this observational cohort study was conducted at programmatic management unit for drug resistant TB of Lady Reading Hospital Peshawar, Pakistan. A total of 181 MDR-TB patients enrolled at the study site from January 1, 2012 to February 28, 2013 were included. Patients with drug resistant TB other than MDR-TB, transferred out patients and those who were still on treatment at the end of study duration (January 31, 2015) were excluded. Patients were followed until treatment outcomes were reported. ADRs were determined by laboratory data and/or clinical criteria. SPSS 16 was used for data analysis. A total of 131 patients (72.4%) experienced at least 1 ADR. Gastrointestinal disturbance was the most commonly observed adverse event (42%), followed by psychiatric disturbance (29.3%), arthralgia (24.3%), and ototoxicity (21%). Potentially life-threatening ADRs, such as nephrotoxicity (2.7%) and hypokalemia (2.8%) were relatively less prevalent. Owing to ADRs, treatment regimen was modified in 20 (11%) patients. On multivariate analysis, the only risk factor for ADRs was baseline body weight ≥ 40 kg (OR = 2.321, P-value = 0.013). ADRs neither led to permanent discontinuation of treatment nor adversely affected treatment outcomes. Adverse effects were prevalent in current cohort, but caused minimal modification of treatment regimen, and did not negatively impact treatment outcomes. Patient with baseline body weight ≥ 40 kg should be closely monitored.
The current study has been designed to examine the effect of multifunctional drug therapy on carbofuran induced acute (2.187 mg/kg, s.c.) and sub-acute (0.2187 mg/kg, s.c.) neurotoxicity in male wistar rats. Drug treatment which includes nimodipine (Ca(2+) channel blocker), diazepam, ropinirole (dopamine agonist) and GSPE (antioxidant) was started 2h after carbofuran administration. Morris water maze was employed for aiming spatial memory. Narrow beam walk and rotarod were employed for testing motor functions. Brain acetylcholinesterase activity, thiobarbituric acid reactive species, nitrite, reduced glutathione, catalase levels, and mitochondrial complexes were also estimated. Carbofuran treatment resulted in significant development of cognitive and motor functions manifested as impairment in learning and memory along with increased thiobarbituric acid reactive species, nitrite levels and decreased acetylcholinesterase activity, reduced glutathione, catalase levels, and mitochondrial complexes. The standard antidote therapy (atropine) was not able to provide neuroprotection but was able to provide symptomatic relief. The multifunctional drug therapy attenuated carbofuran induced cognitive and motor dysfunction, acetylcholinesterase activity and other biochemical parameters. The triple combination in sub-acute study may be avoided in future as two drug combinations provide adequate neuroprotection. Thus it can be concluded that standard antidotal therapy may not provide neuroprotection while the multifunctional drug therapy offers neuroprotection against carbofuran and may dramatically increase survival and life quality.
K1 strain of Plasmdoium falciparum is resistant in vitro to chloroquine, pyrimethamine and sulfadoxine. Response of this strain to combinations of antimalarial drugs in the in vitro hypoxanthine incorporation test was coupled with that of a line of strain NF54 relatively sensitive to chloroquine and fully sensitive to other antimalarials. Pyrimethamine and sulfadoxine showed potentiative synergism against NF54 and less marked against K1. Erythromycin and chloroquine showed potentiation, but less marked against NF54. Quinine and clindamycin had an additive effect against NF54 but potentiated against K1. Combinations of chloroquine with quinine or amodiaquine or of amodiaquine with clindamycin or erythromycin showed mild antagonistic or additive effects. In vivo studies in mice, using the 4-day suppressive test, the AS(3CQ) clone of Plasmodium chabaudi was resistant to pyrimethamine and chloroquine but sensitive to sulfadoxine. Similar combinations as above were carried out and their responses were compared between the resistant and sensitive strains. For both strains, the combinations of chloroquine-erythromycin, pyrimethamine-sulfadoxine, quinine-clindamycin showed potentiation; antagonistic effects were observed in chloroquine-amodiaquine combinations whereas when amodiaquine combined with erythromycin the effect was additive. Amodiaquine-clindamycin and chloroquine-quinine combinations have an antagonistic effect against the sensitive strain but additive against the resistant strain.
An observational study of all children with intractable epilepsy at the Paediatric Institute prescribed Lamotrigine as an add-on therapy between January 1994 and November 1998 was conducted. A total of 30 children were recruited. Three had adverse effects to the drug and it was withdrawn. Of the remaining 27, there were 20 boys and 7 girls, ranging from 2 to 17 years. Fifteen children had generalised epilepsy, 6 had partial epilepsy, 2 had West syndrome and 4 had Lennox Gastaut syndrome. Six children (20%) became seizure free, and 14 (54%) had a greater than 50% reduction in seizure frequency. However 7 children (23%) did not respond and 3 experienced a deterioration in seizure severity. Nine children were noted to have an improvement in alertness and behaviour. Our small series suggests that Lamotrigine is useful as add-on therapy in childhood intractable epilepsy.
A patient who was referred to the eye department for routine ocular assessment prior to commencement of antituberculous therapy was found to have periphlebitis in both eyes despite being visually asymptomatic. Fluorescein angiography confirms the presence of vasculitis without any retinal oedema or areas of non-perfusion, which may sometimes accompany the condition. Within 2 months of systemic treatment, the ocular signs regressed without any permanent effect on vision. This case highlights a rare ocular complication associated with systemic tuberculosis which fortunately did not result in loss of vision due to prompt treatment.
This report deals with a young man having prolonged fever presenting with hypercalcaemic crisis. Subsequent investigations confirmed tuberculosis (TB) peritonitis in the absence of pulmonary involvement as the cause of his symptoms. His hypercalcaemia and fever resolved with anti-TB therapy. Abdominal TB needs to be included in the differential diagnosis of otherwise unexplained hypercalcaemia especially in our region where TB is an endemic problem and is treatable.
A young man presented with primary multi-drug resistant tuberculosis. The institution of second-line regimes with insufficient efficacy due to clinical inexperience, unreliable sensitivity reports and the inavailability of second-line drugs led to the development of an organism that was resistant to ten anti-tuberculous drugs. Accurate sensitivity testing done in an overseas laboratory enabled the institution of a six-drug regimen that has resulted in clinical cure.
We describe a case of adult chickenpox which was complicated by severe varicella pneumonia, mild hepatitis and thrombocytopenia. The hepatitis and the thrombocytopenia were asymptomatic clinically and were diagnosed on biochemistry and blood count results. These eventually improved without specific interventions. The pneumonia, however, deteriorated rapidly despite the early commencement of oxygen supplementation, acyclovir and antibiotic. Subsequently, systemic corticosteroid therapy was initiated and the patient was ventilated in the intensive care unit. The patient eventually recovered.
We have studied the antiemetic efficacy of droperidol alone, and in combination with metoclopramide in first trimester termination of pregnancy in day surgery. The aim was to determine whether the addition of metoclopramide could further reduce the incidence of postoperative nausea and vomiting (PONV) but avoid excessive sedation. Group I (control, n = 40) received i.v. droperidol 0.625 mg at induction. Group II (study, n = 40) received i.v. droperidol 0.625 mg and i.v. metoclopramide 10 mg at induction. The incidence of nausea at 1 and 2 hours postoperatively was 23% and 10% in group I, and 5% and nil in group II respectively. The difference in the incidence of nausea was significant at p < 0.05 at one hour but not at two hours postoperatively. No patients vomited. There was no difference in the sedation and pain score between them. We did not observe any significant side effects attributable to either drug. All patients were discharged home within 3 hours. We conclude that in the prevention of PONV, the combination of metoclopramide and droperidol is superior to the use of droperidol alone at one hour but not at two hours postoperatively.
The effectiveness of sodium citrate and sodium citrate/ranitidine were compared in two randomised groups of elective caesarean patients during the various phases of anaesthesia. The mean pH values (3.5, 3.3, 3.6) were lower in the citrate group compared to the citrate/ranitidine group (6.1, 6.3, 5.9). The percentage of patients with pH values less than 2.5 was 40% in the citrate group compared to 7% in the citrate/ranitidine group. Sodium citrate alone is less effective than sodium citrate/ranitidine for acid aspiration prophylaxis.
BACKGROUND: The benefit of adding theophylline to beta 2 agonists in acute asthmatic attacks has been debated frequently.
METHODS: In an open randomised study 25 patients with severe acute asthma who presented to the emergency department were treated with either a combined nebulised salbutamol (5 mg/dose) and aminophylline infusion (0.6-0.9 mg/kg/hour), or nebulised salbutamol alone.
RESULTS: The responses to treatment as measured by peak expiratory flow (PEF) and the time taken to achieve maximum PEF were similar in both groups. Side effects were observed more commonly in patients receiving the combined treatment.
CONCLUSIONS: Nebulised salbutamol is equally efficacious in acute asthma when given alone or in combination with aminophylline.
Study site: Emergency department, Hospital Kuala Lumpur, Malaysia
We review our experience with 27 cases of pulmonary and meningeal cryptococcosis at the University Hospital, (Kuala Lumpar, Malaysia) where this is the most common cause of adult meningitis in patients without debilitating illnesses. Of the 27 cases analysed, six presented primarily with pulmonary symptomatology which usually were mainly cough, chest pain and low grade fever. The rest presented with primarily central nervous system (CNS) symptomatology of which headaches and fever were the most consistent symptoms although a third of these patients also had pulmonary lesions noted on chest radiographs. Treatment in all cases was with amphotericin B and 5-fluorocytosine and usually till a total cumulative dose of 1.5 g of amphotericin had been reached (an average of 10 weeks). Primary pulmonary presentations, if symptomatic, were treated as per CNS cryptococcosis due to the high likelihood of CNS dissemination. Incidental pulmonary cryptococcoma found on routine chest radiographs were confirmed by biopsy under ultrasound or fluoroscopy guidance and booked for surgical resection. Death usually occurred early in patients who presented late. Once patients responded to therapy, mortality was usually avoided. The only cause of morbidity in survivors was visual impairment or blindness, and this was attributed mainly to intracranial hypertension with residual deficits determined by the measures taken to lower intracranial pressures. Our experience suggests that: (i) symptomatic patients should have combination therapy with 5-fluorocytosine and amphotericin B till at least a cumulative dose of 1.5 g amphotericin B is reached irrespective of whether they have primary CNS or pulmonary symptomatology; (ii) non-symptomatic pulmonary cryptococcoma could be treated primarily by surgical resection; (iii) visual failure or papilloedema should be treated aggressively; and (iv) prognosis is good with adequate therapy and early presentation.
We reviewed 31 cases (19 males and 12 females) of spinal tuberculosis seen at the National Tuberculosis Centre from 1985 to 1989. The mean age was 35.4 years. The predominant clinical feature was backache (90.3%), while neurological features were found in 30.9%. An elevated erythrocyte sedimentation rate (in 80.0%) and a positive Mantoux test (in 70.9%) served as useful investigations. Spinal x-ray was abnormal in all cases, the lumbar spine being most commonly involved. Bacteriological or histopathological confirmation was obtained in only 29.0% of cases. The mainstay of treatment was anti-tuberculous chemotherapy with surgery being performed in 41.9% of patients.
The prevalence of clinically observed oral lichenoid reaction in 186 Malay army personnel using Fansidar for 9 weeks was found to be 4.8%. The prevalence was found to be 0.5% in 186 army personnel who had stopped using Fansidar for 2 months and 0% in 143 army personnel (control group) who had not used Fansidar for at least 4 months. The lesion showed a higher prevalence for the gingiva. There was no correlation between cigarette smoking and the occurrence of these lesions in each group.
The neuroleptic malignant syndrome is a rare but potentially fatal complication of neuroleptic administration. Many clinicians may not be familiar with this complication. This case report highlights the clinical features of neuroleptic malignant syndrome and its management.