Considerations in dosage selection for third generation cephalosporins.

Pharmacokinetic parameters of third generation cephalosporins vary widely, requiring different dosage regimens and adjustment methods for each agent. Although their antibacterial spectrum favours their usage in infections caused by aerobic Gram-negative organisms, due to their limited post-antibiotic effect against these organisms, dosage regimens should ensure that free drug concentrations at the site of infection remain above the minimum inhibitory concentration for as much of the dosage interval as possible in patients with normal host defence mechanisms and for the entire dosage interval in immunocompromised patients. Altered protein binding encountered in various disease states can affect both microbiological and pharmacokinetic properties especially for drugs with high protein binding. Since the concentrations at the site of action are often different from those in serum, a higher or lower range of dosages needs to be selected depending on the target site. Decreased renal function affects the elimination of most third generation cephalosporins, whereas the presence of hepatic disease does not generally necessitate dosage adjustment. Because of the complex age-related physiological changes in paediatric and elderly patients, dosage should be adjusted on the basis of the reported pharmacokinetic data in these populations. The usual recommended dose may or may not be optimal in a given condition depending on the complex interactions between pharmacokinetic, microbiological and other host factors.     

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.     

Acute diverticulitis: safety and value of contrast studies in predicting need for operation

Results of treatment of 70 patients hospitalized with acute diverticulitis were analysed to determine the value of early contrast enema in management. A water-soluble enema done during the first week of hospitalization in 48 patients showed diverticulosis with spasm (30), a leak or peridiverticulitis (16) and a normal study (two). No complications were caused by the study. Forty patients improved on medical therapy, but four relapsed after discharge. Thirty-four (49%) patients had urgent operation during hospitalization for the acute episode of diverticulitis. Findings on contrast enema correlated with the need for surgery during the acute phase: 13 of 16 with peridiverticulitis or a leak compared with three of 30 with diverticulosis/spasm (P less than 0.001). Operations performed were: sigmoid resection and primary anastomosis (17) with covering colostomy (five). Hartmann's operation (eight), colostomy and/or drainage (seven), right hemicolectomy (two). Findings at surgery were: abscess (15), phlegmon (12), peritonitis (five) and colovesical fistula (two). It is concluded that early contrast enemas of the distal colon done with appropriate precautions are useful in confirming the diagnosis of diverticular disease: only two of 48 studies were falsely negative. A pericolic extravasation (as opposed to a small sinus tract) or abscess usually indicates need for operation, whereas the finding of diverticulosis/spasm suggests a favourable outcome of conservative management.     

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.