Increased production of peroxidation products associated with cardiac operations. Evidence for free radical generation

We investigated the degree and time course of neutrophil sequestration into human lungs during cardiac operations. At the same time, measurement of the concentration of peroxidation products in the plasma was used as an index of oxidant free radical activity. The study was performed in two groups of patients. Group A (n = 11) had studies extending over the entire operative period and showed a highly significant sequestration of neutrophils into the lung, together with a highly significant (p less than 0.001) rise in peroxidation products from 2.8 +/- 0.12 nmol/ml(mean +/- standard error of the mean)before bypass to a peak of 5.05 +/- 0.13 nmol/ml at the end of bypass. As these changes occurred only during the time after release of the aortic cross-clamp, we investigated this period in more detail in a second group of patients (Group B, n = 7). Results from this group showed that significant release of peroxidation products occurred at the same time as pulmonary neutrophil sequestration. This study has produced evidence of increased oxidant activity in the lung associated with cardiac operations. Nevertheless, it is not known whether the neutrophils sequestered into the lung alone induced the increased activity. Similarly, whether neutrophil-derived oxidant species are the sole cause of lung tissue injury remains unproved.     

Service profiles of general practitioners in Europe. European GP Task Profile Study.

BACKGROUND: General practice is the focal point of primary care. There are national differences in the structure and organization of practice, the relationship with secondary care is being redefined, and in some countries major changes are taking place. AIM: To describe and examine differences in the service profiles of general practitioners (GPs) in European countries. METHOD: Standardized questionnaires in the national languages were sent to samples of GPs in 1993. Four areas of service provision were measured: the GP's position in the first contact with selected health problems, the involvement in minor surgery and the application of medical procedures, disease management and preventive care. The importance of the gatekeeping role, remuneration system, and geographical region in Europe was examined by comparing scores in appropriate national groupings. RESULTS: Data were received from 7233 GPs in 30 countries. Most national samples were random and the average response rate was 47%. In countries where GPs have a gatekeeping role, they had a relatively stronger position as doctors of first contact. In those countries where GPs were usually self-employed, they had a stronger role in disease management and screening for blood cholesterol. In the examination of the three structural elements of health care, the most striking differences were evident in the comparison between eastern and western Europe. GPs throughout Europe had a comparatively small role in organized health education. CONCLUSION: The position of GPs is weak in eastern Europe and some Mediterranean countries, where service profiles have a limited range. General practice was more comprehensive where the doctors had a gatekeeping role.     

Changes to the ocular biota with time in extended- and daily-wear disposable contact lens use.

Gram-negative bacteria may play a role in the etiology of certain soft contact lens (SCL)-related diseases. Contact lens (CL) wear may modify the normal ocular biota, providing a more favorable environment for potential pathogens. This study reports temporal changes in ocular biota in daily-wear (DW) and extended-wear (EW) disposable SCL use in experienced and neophyte wearers. Lid margin and bulbar conjunctival biota were sampled prior to CL fitting in 26 previous DW SCL users, 18 previous EW SCL users, and 26 neophytes. Wearers were fitted with an etafilcon A CL in one eye and a polymacon CL in the fellow eye. Lenses were worn on a daily basis by the 26 previous DW SCL wearers and on an EW basis by the remaining 44 subjects. The ocular biota was further sampled after 1, 3, 6, 9, and 12 months of wear. The ocular biota consisted of coagulase-negative staphylococci, Corynebacterium spp., Micrococcus spp., and Propionibacterium spp. Potential pathogens were rarely isolated at baseline. No significant trend of increasing ocular colonization was shown for extended CL wear. Lid and conjunctival colonization increased with DW SCL use (P < 0.001), although this increase occurred for nonpathogenic species only. Fewer potential pathogens were isolated from DW SCL than from EW SCL users (P < 0.05). The lid margin consistently showed greater colonization than the conjunctiva and may be a source of potential pathogens during CL wear. Hydrogel CL wear appears to modify the ocular biota. An increased number of commensal organisms were present in DW SCL use. EW SCL use altered the spectrum of organisms isolated. These alterations may suppress the normal ocular defense mechanisms and may be relevant in the pathogenesis of CL-related disease.     

Laparoscopic appendicectomy — A successful operation in adults and children

Laparoscopic appendicectomy has been the subject of several encouraging reports, but has not as yet gained widespread acceptance. We present a series of 159 consecutive laparoscopic appendicectomies performed, over a 4 yr period, in both adults and children. We find the procedure as safe as its open counterpart, with patients fit to leave hospital within the same time period. Perforated appendices were amenable to this procedure, and the location of the appendix did not alter the outcome. Children responded as well as adults post-operatively. Obesity may be an indication for this form of treatment. Removal of displaced faecoliths associated with perforated appendicitis is a difficult technical problem in less than 5 per cent of patients.     

Compatibility of cisplatin and fluorouracil in 0.9% sodium chloride injection

The effect of drug concentration and light on the compatibility and stability of cisplatin and fluorouracil in i.v. admixtures was studied. Two sets of admixtures were prepared in 0.9% sodium chloride injection in polyvinyl chloride bags--(1) cisplatin 200 micrograms/mL and fluorouracil 1,000 micrograms/mL and (2) cisplatin 500 micrograms/mL and fluorouracil 10,000 micrograms/mL. Half of the admixtures were protected from light. All admixtures were stored at room temperature (24-26 degrees C), and those admixtures not protected from light were stored under room fluorescent light. After visual inspection, the pH of each admixture was determined, and an aliquot was assayed for drug concentration using a stability-indicating high-performance liquid chromatographic assay. Over a four-hour period, no visual changes were observed and the pH changes observed were negligible. In admixtures containing the lower concentrations of cisplatin and fluorouracil, it took approximately 1.5 hours for the concentration of cisplatin to reach 90% of the initial concentration. By four hours (lower concentration range) and three hours (higher concentration range) after the admixtures were prepared, less than 75% of the initial cisplatin concentration remained. There was less than a 5% decrease measured in the fluorouracil concentrations over the observation time. Admixtures of cisplatin and fluorouracil in 0.9% sodium chloride injection at the concentrations evaluated in this study must be used within one hour of preparation, whether or not they are protected from light. Intravenous administration of fluorouracil and cisplatin by continuous infusion will require alternative approaches to mixing the two drugs in the same container.     

The influence of levodopa on gastric emptying in man.

1. Simultaneous radioisotopic (99Tc-DTPA) gastric emptying measurements and paracetamol pharmacokinetic studies were performed in eight healthy male volunteers with and without levodopa (125 mg orally). 2. In the absence of levodopa gamma camera imaging showed rapid mono or biexponential emptying in all subjects and the plasma concentration-time curves for paracetamol displayed a single major peak. 3. In the presence of levodopa the time to 90% emptying was prolonged from 32 +/- 24 min to 81 +/- 20 min (P less than 0.01). Gastric emptying was interrupted by a plateau phase in six subjects and this pattern of emptying was associated with double peaks in the plasma concentration-time curves of both levodopa and paracetamol. The time to the end of the plateau phase of emptying correlated with the time to the trough plasma concentrations of paracetamol and levodopa. 4. There was excellent agreement between the plasma concentration-time curves of levodopa and paracetamol, i.e. time to initial peak, r = 0.946, P less than 0.001; time to trough concentration r = 0.943, P less than 0.01; time to second peak r = 0.974, P less than 0.001. 5. The results indicate that levodopa inhibits gastric emptying and thus influences its own absorption. Temporary inhibition of gastric emptying by levodopa (or a metabolite) is the cause of the multiple plasma peaks commonly observed following oral levodopa.     

Assessment of deposition of inhaled aerosol in the respiratory tract of man using three-dimensional multimodality imaging and mathematical modeling.

Multimodality medical imaging enables measurement of the three-dimensional spatial distribution of a radiolabeled aerosol within the lung. Using a conceptual spatial morphological model these data may be transformed to provide information on deposition per airway generation. This methodology has been used to study the intrapulmonary deposition patterns of two formulations of a metered dose inhaler and two nebulizers in control subjects. The nebulizer study has also been stimulated using a computer model of deposition. The comparison between derived experimental results and those from computer modeling shows areas of agreement, although there are also areas of discrepancy. The new methodology has considerable potential value in the fields of inhalation therapy and deposition modeling, although more detailed validation is still required.