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.     

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.     

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.     

Methicillin-resistant Staphylococcus aureus: investigation of a hospital outbreak using a case-control study

A retrospective case-control study of 50 MRSA-positive patients was carried out during an outbreak of methicillin-resistant Staphylococcus aureus (MRSA) at an acute general hospital in London. Controls were randomly selected from MRSA-negative patients admitted during the outbreak period. Risk factors investigated included length of admission prior to screening, number of ward changes, main diagnosis, extent of staff contact, pressure sores, surgical and other invasive procedures and antibiotic treatment. Outcome variables examined were rates of infection (versus colonization) with MRSA and mortality. Patients with MRSA were in hospital longer before microbiological specimens were taken and moved wards more often than controls. In a logistic regression analysis, length of stay in hospital, pressure sores, physiotherapy and surgical procedures were associated with a significantly increased risk of acquiring MRSA. Odds ratios (and 95% confidence intervals) for having acquired MRSA were: 8·3 (1·02−71·43) if a patient had pressure sores; 3·7 (1·10−12·5) if they received physiotherapy; and 3·2 (1·82−10·0) if they underwent surgical procedures. The rate of clinical infection amongst patients with this strain of MRSA was 26% and included life-threatening infections such as septicaemia, underlining the potential virulence of MRSA. Surgery and physiotherapy may have been markers of debility. Physiotherapy was probably a marker of increased rates of contact with all hospital staff, and high standards of hand hygiene should be promoted amongst all staff as the most important factor in controlling an outbreak of MRSA. Good bed management is essential for hospital infection control.     

S-nitrosoglutathione-containing hydrogel accelerates rat cutaneous wound repair

BACKGROUND: Nitric oxide (NO) plays a key role in wound repair and S-nitrosothiols like S-nitrosoglutathione (GSNO) are well known NO donors. METHODS: Animals were separated in two groups and submitted to excisional wounds on the dorsal surface at the first day. GSNO (100 microm)-containing hydrogels were topically applied on the wound bed in the GSNO group, daily, during the first 4 days. Control group was topically treated with hydrogel without GSNO for the same period. Wound contraction and re-epithelialization were measured. Animals were sacrificed 21 days after wounding. Samples of lesion and normal tissue were formalin-fixed, paraffin embedded for histological analysis. RESULTS: Wound contraction, measured 14 and 21 days after wounding, was greater in the GSNO group than in the control group (P<0.05 for both). The re-epithelialized wound area, measured 14 days after wounding, was higher in the GSNO group than in the control group (P<0.05). A higher amount of inflammatory cells was observed in superficial and deep areas of the granulation tissue of the control group compared to the GSNO group. Twenty-one days after wounding, thin red-yellow collagen fibers arranged perpendicularly to the surface were found in the granulation tissue of the control group, whereas in the GSNO-treated group collagen fibers were thicker and arranged parallel to the surface. Increased number of mast cells was observed in the GSNO group compared with that in the control group. Vascularization and myofibroblast distribution were similar in both groups. CONCLUSION: Topical application of GSNO-containing hydrogel during the early phases of rat cutaneous wound repair accelerates wound closure and re-epithelialization and affects granulation tissue organization.     

Error analysis by simulation studies in renography deconvolution

The renogram, defined as the time-activity curve obtained from measurements with a gamma detector over the kidneys after a prior injection of a radioactive tracer, can be quantified using the deconvolution method. Essentially all the inherent information in the renogram, the estimated relative renal uptake function and transit time spectrum through the kidney, can be derived from the computed renal retention function. This study shows how statistical and physiological noise and different backgrounds affect the accuracy of the derived parameters. Confidence intervals for the estimated relative renal function and mean transit time (MTT) are presented. The principal source of error in relative renal function was due to extrarenal background. It was found that the error in mean transit time due to statistical noise was proportional to MTT, that the presence of extrarenal background strongly affected the accuracy of the MTT, whereas the vascular background in the renogram was of minor importance. Physiological noise, interpreted as periodic changes in transit times does, strictly speaking, invalidate the deconvolution principle, but it was possible to calculate a valid mean value of the different actual transit times. The transit time spectrum, measured by differentiation of the computed retention function, was found to be of no practical value with use of the unconstrained matrix method. The signal to noise ratio and consequently the need for smoothing can be estimated from the sum of the squared second derivatives of the renogram itself. The plateau levels in the renal retention function provide a more reliable estimate for the relative function ratio than the relative amplitude of a renogram in which extrarenal background only has been subtracted.