Quinine pharmacokinetics: ototoxic and cardiotoxic effects in healthy Caucasian subjects and in patients with falciparum malaria

OBJECTIVE: To study the pharmacokinetic behaviour of quinine in Caucasians with and without malaria. METHOD: Quinine-dihydrochloride was administered intravenously as a single dose of 300 mg to 12 healthy subjects and as multiple doses of 600 mg in 4 h every 8 h in 10 patients with falciparum malaria. Plasma quinine concentrations were measured by high-performance liquid chromatography RESULTS: Quinine pharmacokinetics are time-dependent: the apparent elimination halftime is shorter in the accumulation phase than in the elimination phase; in malaria patients the maximal quinine concentration was reached in half the time calculated on the basis of the elimination phase after the last quinine infusion. Nevertheless a loading dose seemed advisable to reach adequate therapeutic levels quickly. In malaria patients the highest plasma concentrations during or at the end of the infusions were positively correlated with body weight. There was no correlation between body weight and the volume of distribution of quinine as calculated during the elimination phase. Hearing loss was audiometrically documented in 9 healthy subjects at a mean maximal plasma quinine concentration of only 2 mg/l. All malaria patients suffered serious cochlear hearing impairment. The ototoxic effects in both healthy subjects and patients appeared to be reversible. No electrographic changes were noted in the healthy subjects, whereas a clinically insignificant mean lengthening of the corrected QT interval was seen in the malaria patients. CONCLUSION: Intravenous quinine pharmacokinetics in healthy Caucasians were similar to those reported for Nigerian or Thai subjects. At effective doses quinine causes considerable but reversible cochlear hearing losses in both healthy persons and in patients. Our findings do support the need for a loading dose. The fact that in malaria patients there was no correlation between body weight and quinine VD as calculated during the elimination phase renders questionable the usefulness of dosing quinine according to body weight.     

Cloning and characterization of Schistosoma mansoni fructose-1,6-bisphosphate aldolase isoenzyme

A Schistosoma mansoni cercarial cDNA expression library, constructed in lambda gt11, was screened using the IgG fraction of sera taken from rabbits vaccinated with irradiated cercariae. A positive cDNA clone (1,431 base pairs) was selected and characterized. The amino acid sequence predicted from the cDNA sequence identified a polypeptide of 363 amino acids that showed significant homology to different family members of the enzyme fructose-1,6-bisphosphate aldolase (EC 1.4.2.13). The identity was 66% and 65% with human C and A isoenzymes, respectively. Active sites and substrate-binding determinant analysis suggest that the isolated enzyme in terms of function resembles type A aldolase. The recombinant protein expressed in the vector pGEX-2T was found to be active enzymatically. Antibodies raised against the purified recombinant protein recognized a 40-kDa band in extracts from cercariae, schistosomula (5 and 25 days), adult worms, and eggs. Using immunocytochemistry, aldolase localized to the tegumental region of the adult worms.     

Characterization of two monoclonal antibodies against the RON tyrosine kinase receptor

An anthropometric assessment was conducted at 238 !Kung San hunter-gatherers aged between 18 and 65 years (mean = 30.8 years), 156 Kavango horticultural pastoralists aged between 18 and 61 years (mean = 29.2 years) and for 87 urbanized Kavango people aged between 18 and 61 years (mean = 29.3 years) living as wage earning employees in northern Namibia. Weight status was estimated by using body mass index categories according to the recommendations of the WHO. As is typical for human populations, men were taller and heavier than women within the same ethnic groups. An interethnic comparison showed that both !Kung San women and men were lighter than Kavango women and men. The mean BMI of !Kung San women was 19.1 and of !Kung San men 19.4 kg/m2. Kavango people exhibited higher average BMI values, 19.4 for women, 20.3 kg/m2 for men. With the exception of the male urban Kavango people a high percentage (more than 30%) of the subjects were thin and underweight, as shown by a BMI of < 18.5 kg/m2. This was especially true of the !Kung San of both sexes and the rural Kavango men. Nearly 25% of !Kung San women met the criterion of weight depletion (BMI < 17.0). The cultural transition from nomadic hunter gatherer subsistence to a more sedentary life style over the last 20 years can be interpreted as an environmental stress which affected male as well as female nutritional status. The hard economic situation of the rural Kavango people may also be a stress factor which negatively influenced their nutritional status, especially of the men. The significantly better nutritional status of the urban Kavango men may be the result of the opportunities for work as wage earners or as soldiers.     

Focus group interviews: defining clinical supervision

In the companion article to a literature review published recently in Nursing Standard (Sloan 1998), the author demonstrates the use of focus groups as a data collection method. He details how the group discussion was analysed, and reproduces the findings relevant to the 'good characteristics' of a clinical supervisor from the supervisee's perspective.     

Digital wavelet-encoded MRI: a new wavelet-encoding methodology

A new digital wavelet-encoding method for MRI is described. The method differs from previously described wavelet-encoding approaches, because the point-spread function is made independent of the wavelet basis used. This has a significant practical advantage, because wavelet bases can now be considered that would otherwise be excluded due to the difficulty of precisely exciting wavelet-shaped RF profiles. The method has been implemented on a clinical MRI system, and human images are presented.     

UV-spectrophotometric determination of ampicillin sodium and sulbactam sodium in two-component mixtures

A simple spectrophotometric method is used for the resolution of the binary mixtures of ampicillin sodium and sulbactam sodium. In aqueous solution, zero-order spectra are subject to interference, so first-derivative spectrophotometry was used to enhance the spectral details allowing the determination of ampicillin sodium from the signal at the zero-crossing point for sulbactam sodium at 268 nm. In 0.1 N sodium hydroxide, sulbactam sodium was determined from the absorbance at 260 nm with negligible contribution from ampicillin sodium. Also, sulbactam sodium was determined without interference using first- and second-derivative spectra in 0.1 N sodium hydroxide at 276 nm (peak-height) and 262-284 nm (peak-to-peak), respectively. The method is rapid, simple, does not require a separation step and allows the determination of each drug without interference from the other. The proposed method has been applied successfully to the assay of these drugs in mixtures and in commercial injections.     

The diagnostic and treatment characteristics of focal liver lesions using computed tomography

Under analysis is an experience with examining and treatment of 167 patients with focal lesions of the liver using computed tomography. Percutaneous transhepatic puncture and draining the hepatic abscesses and cysts under control of computed tomography is an independent method of treatment used in 53 patients. The technique of performing the puncture and drainage is described. Specific features of surgical treatment of focal lesions of the liver are described. Decompression of bile ducts in the postoperative period is shown to be necessary. A conclusion is made about high efficiency of computed tomography in diagnosis and treatment of focal lesions of the liver.     

Ki-1 large cell anaplastic lymphoma--a clinicopathological study

Ki-1 large cell anaplastic lymphoma is a recently described variant of malignant lymphoma. A retrospective study of 10 cases of Ki-1 lymphoma was carried out at the Armed Forces Institute of Pathology (AFIP) Rawalpindi to document its clinical and morphological features. The morphological features were evaluated by a study of paraffin embedded sections stained with haematoxylin and eosin stains. Immunohistochemical stains for BER-H2 and leucocyte common antigen (LCA) were performed in all cases. The age of the patients ranged from 2 to 60 years and male to female ratio was 2.3:1. Cervical lymphadenopathy was the most common presentation. Histologically, there was a complete effacement of the lymph node architecture in 8 cases. The Reed-Sternberg like cells were seen in 2 and histiocyte like cells in 7 cases. Immunohistochemically all cases were positive for BER-H2. It is suggested that the possibility of Ki-1 lymphoma should be considered in all cases of lymphoma with pleomorphic morphology.     

Historical evolution of the treatment of esophageal cancer at the Hospital A. C. Camargo, S?o Paulo, Brazil

OBJECTIVES: From 1947-1986 we reviewed a historical series of 1,900 cases of esophageal cancers registered at the A.C. Camargo Hospital, S?o Paulo, Brazil. Two hundred and thirty four cases were submitted to surgical resection. During these 4 decades the treatment philosophy of these tumors has changed. METHOD: Five different historical groups were identified and the results are presented. RESULTS: The first group (1947-60) consisted of 47 cases only submitted to surgical resection. The second group (1961-70) of 56 cases had pre and pos surgery radiotherapy in low doses and the reconstruction was made using subcutaneous colon. From 1971-75 the same approach was used except with high dose preoperative radiotherapy (31 cases). In the 4th group (1976-82) of 68 cases preoperative radiotherapy (high dose) and chemotherapy were used. In the last group (1983-86) composed of 32 cases the treatment was preoperative chemotherapy, surgical resection with gastric reconstruction followed with high doses radiotherapy in the surgical bed and chemotherapy. The only significant prognostic factors in the statistical analysis were tumor size and involvement peri-esophageal lymph nodes. CONCLUSION: A five year survival from 3.7% to 9.0% was obtained through the use of the fifth group treatment planning.