Colorimetric and thin-layer chromatographic methods for field assay of chloroquine and its metabolites in urine

Three field-adapted methods for the quantification of the antimalarial drug chloroquine are described. Two of the methods are modifications of the Haskins test and are based on ion-pair formation between chloroquine and methyl orange in either dichloromethane or chloroform. Absorbance values measured at 420 nm with a hand-held, battery-operated filter photometer were linearly related to chloroquine concentrations in urine up to 100 μmol/l (32 μg/ml) for both methods. The contribution of the desethylchloroquine metabolite to the measured absorbance for both methods is less than that of chloroquine; the relative sensitivity for this metabolite is about 50% of that of chloroquine for both methods. The detection limit for modification I is 1 μmol/l (0.3 μg/ml), while that for modification II is 3 μmol/l (1 μg/ml). A single dose of chloroquine diphosphate (300 mg as base) administered to each of three volunteers yielded detectable levels by modification I of chloroquine in the urine for 28 days after dosing. Results for the colorimetric methods correlated well with the liquid chromatographic reference method used. The related thin-layer chromatographic method confirmed the presence of chloroquine and desethylchloroquine in the urine and permitted independent estimation of the concentration of these two compounds if desired. The two colorimetric methods may be used in remote locations where no electricity is available.     

Management of postoperative mediastinitis in infants and children by muscle flap rotation

Between July 1, 1976, and June 30, 1986, at the Henrietta Egleston Hospital for Children, 2,242 infants and children underwent palliation or repair of a congenital heart defect. Twenty-one (0.94%) of these patients developed mediastinitis following a median sternotomy. Nineteen of these twenty-one patients had required cardiopulmonary bypass. All patients had positive mediastinal cultures. The first 8 patients were managed traditionally by debridement and irrigation. Three of these patients suffered serious metabolic complications related to the povidone-iodine irrigant, which resulted in 1 death. Another patient died from persistent sepsis following debridement. Subsequently, 13 patients were managed by early debridement and rotation of the pectoralis major or rectus abdominis muscle flaps, or both. Following muscle flap rotation and early wound closure, 2 patients had subsequent incisional complications. One patient had incisional dehiscence and 1 had a superficial skin separation. Two deaths in this group, 28 and 51 days, respectively, following muscle flap rotation, resulted from nonincisional problems in patients with healed median sternotomies. The group having muscle flap rotation required a significantly shorter duration of postoperative ventilatory support (3.2 versus 24 days, p less than 0.05) and a significantly shorter confinement in the intensive care unit (6.2 versus 33 days, p less than 0.01). Also, the physiological and physical trauma of continued wound care in the awake child was minimized in the group with muscle flap rotation.     

Vaterian cancer in siblings

The simultaneous occurrence of Vaterian carcinoma in two siblings suggests a genetic influence in their pathogenesis. Their classic clinical presentation of obstructive jaundice and weight loss required pancreaticoduodenectomy for this neoplasm. Pedigree analysis revealed a third sibling who died from an unresectable periampullary malignancy. Neither of the probands exhibited, as late as the seventh decade, evidence compatible with a diagnosis of familial polyposis coli or Gardner's syndrome. Flow cytometry studies revealed an aneuploid distribution in one tumor and tetraploid in the other. The rarity of this neoplasm, in the absence of contributing epidemiologic factors, suggests that this is a pleotrophic manifestation of a cancer-prone genotype.     

Does supervised exercise offer adjuvant benefit over exercise advice alone for the treatment of intermittent claudication? A randomised trial.

OBJECTIVE: Exercise advice is the main treatment for symptom relief in the UK for patients with mild to moderate Intermittent Claudication (IC). Would a weekly exercise and motivation class for 6 months offer adjuvant benefit over written and verbal exercise advice alone? PATIENTS AND METHODS: Fifty-nine patients attending a regional vascular centre for whom IC was the main factor affecting mobility were randomised to either exercise advice alone (n=30) or exercise advice with a once a week 45 min supervised exercise/motivation class (n=29). The mean age was 68 years. Baseline and 6-month assessment included a Quality of Life Questionnaire--the Short-Form-36, the Charing Cross Symptom Specific Claudication Questionnaire (CCCQ) and treadmill walking distance (3.5 km/h 12%). RESULTS: At 6-month follow-up the supervised exercise group had improved their treadmill walking by 129% compared to 69% in the advice alone group (p=0.001). This significant improvement was maintained at the subsequent 9 and 12-month follow-up assessments. By the 9-month stage the advice only group CCCQ score had improved 16% from baseline, while the supervised exercise group had a significantly better 43% improvement in base line score (p<0.05). Self reported frequency of walks was higher in the exercise class group being significant for improvement in CCCQ score. CONCLUSION: A weekly, supervised exercise and motivation class for a 6-month period provides a significant improvement in patients' symptoms, quality of life, and distance walked compared with advice alone and this improvement continues after attendance at class has ceased.     

The Parkinson-Control study: a 1-year randomized, double-blind trial comparing piribedil (150 mg/day) with bromocriptine (25 mg/day) in early combination with levodopa in Parkinson's disease.

Dopamine agonists have been recommended as early treatment for Parkinson's disease (PD), alone or combined with levodopa. Piribedil is a non-ergot selective D(2)/D(3) agonist with alpha(2) antagonist properties shown to be effective in the treatment of PD. This 12-month international, randomized, double-blind trial aimed to assess the efficacy of piribedil 150 mg versus bromocriptine 25 mg, in early combination with levodopa in Stage I to III PD patients. Motor efficacy was assessed using the Unified Parkinson's Disease Rating Scale (UPDRS III, Items 18-31) as improvement from baseline. Response rate was defined as a 30% improvement. Among the 425 randomly assigned patients, 178 were also included in a substudy on cognitive follow-up evaluated by a dysexecutive syndrome oriented battery. A relevant improvement in UPDRS III over the 12-month study duration was observed both in the piribedil and bromocriptine groups (-7.9 +/- 9.7 points from baseline versus -8.0 +/- 9.5; not significant [n.s.]) with a response rate of 58.4% and 55.3% (n.s.), respectively. Piribedil and bromocriptine resulted in similar improvement on all UPDRS III subscores. Piribedil patients required less levodopa dose increase than those on bromocriptine. Cognitive performance remained generally unchanged in both groups, with a significant effect of piribedil limited to the Wisconsin Card Sorting Test. An overall good tolerability of piribedil was observed. Early combination of piribedil 150 mg with levodopa resulted in significant long-term improvement of all motor symptoms in PD patients insufficiently controlled by levodopa alone. Taking into account both efficacy and acceptability in the long-term, piribedil proved in this bromocriptine controlled study to be an effective and safe treatment for PD.     

Physiological response to cycling with both circular and noncircular chainrings.

The purpose of this study was to compare physiological variables of endurance-trained cyclists riding with four different chainring designs: round, Shimano Biopace, and two engineered ellipse designs. The ellipse designated Eng10 had the crank arm oriented 10 degrees forward of the major (i.e. longer) axis. Eighty degrees further forward, along the minor axis, was the crank arm orientation for the second ellipse, Eng90. With the major to minor axis ratio of 22.9 cm/16.8 cm (1.36), both ellipses imposed a crank angular velocity variation of 27% relative to the highest velocity assuming constant chain velocity. Best described as a skewed ellipse (i.e., major and minor axes not perpendicular), the Biopace had a major to minor axis ratio of 1.09 thus giving a crank angular velocity variation of 8%. Eleven male cyclists rode at a high (80% of maximum VO2) and a low (60% of maximum VO2) workrate using each chainring. The study was conducted over four consecutive days with the presentation order of the chainrings randomized. Open circuit spirometry was used to collect continuous respiratory data. Heart rate, blood lactate, and cadence values also were measured. None of the physiological variables including rates of oxygen consumption showed significant differences among the chainrings. Thus, the gross efficiency of cycling was not improved by any of the noncircular chainrings. For cycling events where efficiency is a determinant of performance, the noncircular chainrings do not offer any advantage over round chainrings.     

Transplantation of the cornea.

Corneal transplantation is the most widely practised form of allografting in clinical practice. The operation is used to correct developmental abnormalities of corneal shape such as keratoconus, to overcome opacities of the cornea, to relieve pain and to mend perforations. Corneal transplantation is generally successful but contrary to popular belief, corneal grafts can be rejected. This is a particular problem for patients treated for the sequelae of inflammatory disease. The relative importance of measures such as systemic immunosuppression and tissue typing is less in corneal transplantation than in other forms of clinical allografting. Overcoming rejection, achieving the best optical configuration in a graft, and increasing the number of donor corneas available for transplantation represent the main avenues for achieving improvements in corneal transplantation.