Does determining serum alcohol concentrations in emergency department patients influence physicians' civil suit liability?

Emergency physicians may incur liability when impaired patients who have been treated and released are subsequently involved in traffic crashes. We surveyed attorneys to assess their perception of how serum alcohol determinations might influence their liability in civil suits. Overall, 63.9% of the attorneys surveyed would advise patients that they received potentially negligent care if they were impaired following treatment in the emergency department and were involved in a traffic crashes. Perceived liability was altered by physician behavior as follows: 43.1% of attorneys would advise clients that they received potentially negligent care when impairment was documented by a test for serum alcohol concentration and no advice was given regarding drunk driving, and 17.3% of attorneys would give similar advice when impairment was not documented by a test for serum alcohol concentration and no advice was given regarding drunk driving. In contrast, only 3.5% of attorneys would suggest possible negligence when impairment was documented by a test for serum alcohol concentration and with advice subsequently given not to drive. The coupling of diagnosing impairment by the serum alcohol concentration and driving advice is medically sensible and might result in minimal civil liability.

Erythrocyte anisocytosis. Visual inspection of blood films vs automated analysis of red blood cell distribution width.

An improved anemia classification may be available by combining measures of red blood cell size variability with mean corpuscular volume. Visual inspection of the peripheral blood film allows semiquantitative description of anisocytosis while quantitative measures are determined from electronic cell counter analyzers' red blood cell distribution width. We evaluated correlations between semiquantitative and quantitative measures of anisocytosis for different groups of observers. Hematologists', medical students', and medical residents' semiquantitative assessment of anisocytosis correlated with the quantitative red blood cell distribution width. The interobserver variability demonstrated that all observers correlated with each other, while the intraobserver variability of semiquantitative anisocytosis demonstrated that observers were more precise than could be predicted by chance. However, the extreme precision of the red blood cell distribution width strongly suggests that it should be the "gold standard" for measuring red blood cell size variability.

Primary care clinicians' performance for detecting actinic keratoses and skin cancer.

BACKGROUND: If skin cancer screening is to become widely adopted, its effectiveness depends on the ability of primary care clinicians to detect cutaneous malignancies. OBJECTIVE: To assess primary care clinicians' proficiency for detecting skin cancers and actinic keratoses in a clinic population. METHODS: A convenience sample of 190 white male patients aged 40 years or older presenting to a university-affiliated Veterans Affairs general internal medicine or dermatology clinic were included in the study. Each patient was independently examined by a primary care clinician and a dermatologist to measure interobserver agreement. We compared the ability of primary care clinicians to diagnose actinic keratoses and skin cancers using dermatologists' examinations as a pragmatic reference standard. RESULTS: Agreement was moderate as to whether a patient had single actinic keratosis (kappa, 0.36; 95% confidence interval [CI], 0.22-0.50), multiple actinic keratoses (kappa, 0.48; 95% CI, 0.34-0.61), or skin cancer (kappa, 0.48; 95% CI, 0.34-0.62). Agreement decreased when individual lesions were the unit of analysis. When the patient was the unit of analysis, primary care clinicians identified the presence of skin cancer with a sensitivity of 57% (95% CI, 44%-68%), specificity of 88% (95% CI, 81%-93%), positive likelihood ratio of 4.9 (95% CI, 3.0-8.3), and negative likelihood ratio of 0.48 (95% CI, 0.35-0.63). When the lesion was the unit of analysis the sensitivity was 38% (95% CI, 29%-47%), the specificity was 95% (95% CI, 93%-96%), the positive likelihood ratio was 7.1 (95% CI, 4.8-10.3), and the negative likelihood ratio was 0.66 (95% CI, 0.56-0.75). CONCLUSIONS: Examinations performed by primary care clinicians for diagnosing skin cancer lacked sensitivity. Without improved diagnostic skills, primary care clinicians' examinations may be ineffective as a screening test.

Smoking behavior on the first day of a quit attempt predicts long-term abstinence.

BACKGROUND: The nicotine patch has been widely used for smoking cessation, but not all smokers quit using the patch. Knowing which smokers are likely to succeed with the nicotine patch may improve the efficiency of nicotine patch use. OBJECTIVE: To identify predictors of smoking abstinence using baseline characteristics, smoking behavior, and withdrawal symptoms. METHODS: Using 2 randomized clinical trials of pharmacologic treatment, brief counseling, and quit date formats in the outpatient research clinic setting, predictors of smoking cessation were derived in 1 sample (n = 159), then prospectively validated in an independent sample (n = 48). Subjects smoked 1 pack of cigarettes per day or more and were motivated to quit smoking. Self-report of abstinence at 6 months verified by exhaled carbon monoxide of 8 ppm or less was used. RESULTS: Abstinence at 6 months was 24% in the derivation set and 25% in the validation set. Using logistic regression, a model containing quit date abstinence (odds ratio, 10.6; 95% confidence interval [CI], 2.9-38.7) and baseline nicotine dependence (odds ratio, 0.75; 95% CI, 0.6-1.0 per unit increase in Fagerstrom score) provided the optimal predictive ability and was validated in the independent set. Quit date abstinence improved the likelihood of 6-month abstinence by 4.1 over baseline (95% CI, 2.6-6.4) for low-nicotine-dependent smokers and 1.2 (95% CI, 0.6-2.2) for high-nicotine-dependent smokers. Quit date smoking altered the likelihood of 6-month abstinence by 0.2 (95% CI, 0.0-0.8) for low-dependent smokers and 0.1 for high-dependent smokers (95% CI, 0.0-0.6). CONCLUSIONS: Abstinence on the quit date and low-nicotine dependence improve the likelihood of smoking abstinence at 6 months. Smoking on the quit date may be an indication for postponing the cessation attempt or adjusting the therapy for smoking cessation.

Cranial computed tomography before lumbar puncture: a prospective clinical evaluation.

OBJECTIVE: To prospectively identify which patients can safely undergo lumbar puncture (LP) without screening cranial computed tomography (CT). METHODS: Emergency department physicians examined patients before CT. Examiners recorded the presence or absence of 10 clinical findings and answered 8 additional questions. The criterion standard was noncontrast cranial CT interpreted by staff radiologists. Clinical findings were prospectively compared with those of CT. RESULTS: One hundred thirteen consecutive adults with the urgent need for LP (median age, 42 years) were studied. Fifteen percent of patients meeting entrance criteria had new CT-documented lesions, with 2.7% having lesions that contraindicated LP. Sensitivity, specificity, and likelihood ratios (LRs) were measured for the clinical findings. Three statistically significant predictors of new intracranial lesions were identified: altered mentation (positive LR, 2.2; 95% confidence interval [CI], 1.5-3.2), focal neurologic examination (positive LR, 4.3; 95% CI, 1.9-10), and papilledema (positive LR, 11.1; 95% CI, 1.1-115). No single item adequately predicted the absence of CT abnormalities, but the clinical screening items in aggregate significantly predicted the results (negative LR, 0; upper 95% confidence limit, 0.6). The overall clinical impression had the highest predictive value in identifying patients with CT-defined contraindications to LP (positive LR, 18.8; 95% CI, 4.8-43). CONCLUSIONS: Because of the low prevalence of lesions that contraindicate LP, screening cranial CT solely to establish the safety of performing an LP typically provides limited additional information. Physicians can use their overall clinical impression and 3 clinical predictors to identify patients with the greatest risk of having intracranial lesions that may contraindicate LP.

Is streptokinase safe during menses?

We used intravenous streptokinase to treat a young woman with deep venous thrombosis manifested during her menses. There was no increase in menstrual bleeding, and she was symptom free six months later. Because menstrual endothelium after the first day of menses relies on arteriolar constriction for hemostasis rather than the formation of fibrin, we think that streptokinase may not be contraindicated in thrombotic disorders that occur during menses after the first day.

A telephone-delivered intervention for patients with NIDDM. Effect on coronary risk factors.

OBJECTIVE: To examine whether a telephone-delivered intervention (TDI), designed to improve glycemic control in patients with non-insulin-dependent diabetes mellitus (NIDDM), improved coronary risk factors in high-risk patients. RESEARCH DESIGN AND METHODS: This randomized controlled trial involved 275 veterans with NIDDM followed in a general medical clinic. Intervention (TDI) patients were telephoned at least monthly by a nurse. Calls emphasized compliance with the medical regimen (diet, medications, and exercise), encouraged behavioral changes, and facilitated referrals to a dietitian or smoking cessation clinic. Control patients received no such calls. Baseline and 12-month follow-up measurements included fasting lipid profiles, weight, smoking status (self-reported; cessation verified by measurement of exhaled CO), adherence to diet and exercise (self-reported), appointments, and medications (hospital computerized data base). RESULTS: After 12 months, equal numbers of obese patients in the two groups reported adhering to a diabetic diet and exercising, although more obese TDI patients had seen a dietitian (30 vs. 7%, P = 0.003). Weight loss was not seen in either group (-0.9 +/- 5.3 vs. -0.1 +/- 3.6 kg, P = 0.202). Hyperlipidemic TDI patients were more likely to see a dietitian (31 vs. 6%, P = 0.003) and receive lipid-lowering medications (22 vs. 9%, P = 0.096), but serum cholesterol reduction was similar between groups (-11.7 +/- 33.4 vs. -4.3 +/- 32.7 mg/dl, P = 0.270); comparable results were seen for high-density lipoprotein, low-density lipoprotein, and triglyceride levels. More TDI group smokers reported quitting (26 vs. 0%, P = 0.033), but the difference was not significant for CO-verified abstention (10 vs. 0%, P = 0.231). CONCLUSIONS: The TDI improved self-reported adherence to regimens that might reduce coronary risk, but had little effect on objective measures of risk.

Correction of hypoprothrombinemia by immunosuppressive treatment of the lupus anticoagulant-hypoprothrombinemia syndrome.

A 66-year-old man with the lupus anticoagulant-hypoprothrombinemia syndrome was treated with cyclophosphamide and prednisone to correct a factor II deficiency prior to elective major surgery. Whereas the lupus anticoagulant activity persisted, functional factor II levels normalized and he underwent surgery without a bleeding diathesis. Immunosuppressive therapy may temporarily normalize factor II levels in patients with the lupus anticoagulant-hypoprothrombinemia syndrome and reduce the risk of excessive hemorrhage. The disparate response of the lupus anticoagulant and hypoprothrombinemia to immunosuppression suggests that the lupus anticoagulant did not directly cause the hypoprothrombinemia.

Does lacrimal duct occlusion decrease intraocular pressure in patients refractory to medical treatment for glaucoma? A randomized, sham-controlled, crossover trial.

We temporarily occluded lacrimal ducts with dissolvable collagen inserts in a randomized, double masked, sham-controlled crossover trial to test whether longer ocular contact of eye drops lowers intraocular pressure in patients with refractory glaucoma. Patients were randomized to the sequence temporary lacrimal duct occlusion----21 day washout----sham occlusion (6 patients), or the reverse order (5 patients); all maintained their usual medication. Compliance was greater than 90% for every patient as assessed by medication diaries kept by each patient's medication partner. There was no treatment effect (bivariate Wilcoxon chi 2 = 0.10, p = 0.95) or treatment-period interaction (chi 2 = 2.87, p = 0.24). However, whichever treatment was received first significantly lowered intraocular pressure (left eye first period X:[ipr50] = 3.0: [-6.0, -1.0] mmHg, right eye = -3.0:[-6.0, -1.0] mmHg, bivariate response chi 2 = 5.92, p = 0.05). Although lacrimal duct occlusion appears to have no clinical benefit, more careful supervision of eye drop administration may be efficacious for treating some patients with medically refractory glaucoma.

A randomized controlled trial comparing quantitative informed consent formats.

Informed consent has been indirectly studied only in settings that do not replicate the actual consent process. We designed a sham study and randomly allocated adult ambulatory patients to receive one of two consent forms: Consent A (n = 52) described a randomized trial of usual treatment vs a new medication that "may work twice as fast as the usual treatment"; or Consent B (n = 48) that described a randomized trial of a new medication that "may work half as fast as the usual treatment". Patients randomized to Consent A were more likely to consent than those randomized to Consent B (consent rate A = 67%, consent rate B = 42%, p less than 0.01). Among patients who cited quantitative information, the difference in consent rate was even more marked (95% vs 36%, p less than 0.001); patients who did not cite quantitative information had equivalent consent rates. Patients who perceived minimal or severe symptoms had lower consent rates than those with mid-range symptom scores (chi 2(2) = 8.35, p = 0.015). Patients who recognize quantitative information will use it to make informed consent decisions.

Likelihood ratios with confidence: sample size estimation for diagnostic test studies.

Confidence intervals are important summary measures that provide useful information from clinical investigations, especially when comparing data from different populations or sites. Studies of a diagnostic test should include both point estimates and confidence intervals for the tests' sensitivity and specificity. Equally important measures of a test's efficiency are likelihood ratios at each test outcome level. We present a method for calculating likelihood ratio confidence intervals for tests that have positive or negative results, tests with non-positive/non-negative results, and tests reported on an ordinal outcome scale. In addition, we demonstrate a sample size estimation procedure for diagnostic test studies based on the desired likelihood ratio confidence interval. The renewed interest in confidence intervals in the medical literature is important, and should be extended to studies analyzing diagnostic tests.

Likelihood ratios for continuous test results--making the clinicians' job easier or harder?

Clinicians' paradigms for considering diagnostic test results require decisions based on the actual test value. However, when the test result is reported on a continuous scale each possible outcome may not result in unique actions. To simplify decision making, clinicians often break down the continuous scale into dichotomous or ordered outcomes. Likelihood ratios, reported with the test outcome, help summarize the impact of diagnostic tests. Although commonly applied to dichotomous outcomes, likelihood ratios can also be applied to ordinal or continuous results. This application allows investigators to consider the effect of clinically simplifying continuous data into dichotomous or ordinal categories. The parameters of a simple logistic regression equation summarize continuous likelihood ratios, evaluate covariates, generate likelihood ratio lines, and help assess the statistical significance of more complex models. Having visually inspected likelihood ratio lines and considered statistical differences, the investigator should choose the test report format that best accounts the realities driving clinical decisions.

Who should have intravenous pyelograms before hysterectomy for benign disease?

A review of 493 cases was undertaken to identify which patients undergoing hysterectomy for benign disease had received a preoperative intravenous pyelogram (IVP), an abnormality identified by IVP, and intraoperative ureteral injuries. Intravenous pyelograms were performed on 299 patients (60.6%). Factors significantly associated with obtaining a preoperative IVP included an abdominal approach, uterine size of 12 weeks or greater, and uterine prolapse. Seventy-seven patients (27%) had an abnormal IVP; factors likely to be associated with abnormality included uterine size of 12 weeks or larger or an adnexal mass of 4 cm or larger. Endometriosis, pelvic inflammatory disease, pelvic relaxation, and previous intra-abdominal surgery were not associated with an increased prevalence of abnormal IVP findings. Two ureteral injuries were documented, one in the IVP group (0.3%) and one in the non-IVP group (0.5%). Clinical findings may be used to select for a preoperative IVP those patients who are likely to have abnormalities of importance to the pelvic surgeon.

Hormone replacement therapy and the risk of colorectal cancer: a meta-analysis.

OBJECTIVE: To review systematically the association between hormone replacement therapy (HRT) and the risk of developing or dying from colorectal cancer. DATA SOURCES: We searched the English-language literature using MEDLINE, Current Contents, CancerLit, and bibliographies of selected studies. METHODS OF STUDY SELECTION: We included studies that specifically addressed the association of HRT with colorectal cancer, had adequate controls, and had retrievable risk estimates. We excluded letters, reviews, and multiple publications of the same data. TABULATION, INTEGRATION, AND RESULTS: Studies were evaluated independently by two of the authors. The exposures of interest were ever, recent, or former use of HRT, and the main outcome measures were colon and rectal cancer incidence and mortality. To reduce the risk of a "healthy estrogen user" bias, we defined recent HRT use as either at time of assessment or within the previous year. The most adjusted risk estimates were extracted. We used a random-effects model to calculate summary relative risks (RRs) and confidence intervals (CIs). Recent use of HRT was associated with a 33% reduction in the risk of colon cancer (RR = 0.67; 95% CI 0.59, 0.77). Protection was limited to recent users; the risk of colon cancer with ever use of HRT was 0.92 (95% CI 0.79, 1.08). Duration of use was not significant. Three studies addressed the risk of fatal colon cancer; the summary RR for death from colon cancer in HRT users was 0.72 (95% CI 0.64, 0.81) compared with nonusers. Rectal cancer incidence was not associated with HRT. CONCLUSION: The risk of colon cancer may be decreased among recent postmenopausal HRT users. Although data are limited, the risk of fatal colon cancer also may be lower in HRT users.

A Bayesian method for evaluating medical test operating characteristics when some patients' conditions fail to be diagnosed by the reference standard.

The evaluation of a diagnostic test when the reference standard fails to establish a diagnosis in some patients is a common and difficult analytical problem. Conventional operating characteristics, derived from a 2 x 2 matrix, require that tests have only positive or negative results, and that disease status be designated definitively as present or absent. Results can be displayed in a 2 x 3 matrix, with an additional column for undiagnosed patients, when it is not possible always to ascertain the disease status definitively. The authors approach this problem using a Bayesian method for evaluating the 2 x 3 matrix in which test operating characteristics are described by a joint probability density function. They show that one can derive this joint probability density function of sensitivity and specificity empirically by applying a sampling algorithm. The three-dimensional histogram resulting from this sampling procedure approximates the true joint probability density function for sensitivity and specificity. Using a clinical example, the authors illustrate the method and demonstrate that the joint probability density function for sensitivity and specificity can be influenced by assumptions used to interpret test results in undiagnosed patients. This Bayesian method represents a flexible and practical solution to the problem of evaluating test sensitivity and specificity when the study group includes patients whose disease could not be diagnosed by the reference standard.

Intermediate, indeterminate, and uninterpretable diagnostic test results.

Diagnostic tests do not always yield positive or negative results; sometimes the results are intermediate, indeterminate, or uninterpretable. No consensus exists for the incorporation of such results into data assessment. Conventional Bayesian analysis leads investigators to either exclude patients with non-positive, non-negative results from their studies or categorize such results into inappropriate cells of the standard four-cell decision matrix. The authors propose a standardized method for reporting results in studies dealing with diagnostic test use and discuss how researchers should expand the four-cell matrix to six cells when non-positive, non-negative results occur. They suggest that the six-cell matrix with new operational definitions of sensitivity, specificity, likelihood ratios, and test yield should be adopted routinely. In addition, they define the different types of non-positive, non-negative results and demonstrate how clinicians can use tree-structured decision analysis from the six-cell matrix. While their method does not solve all problems posed by non-positive, non-negative results, it does suggest a standard method for reporting these results and utilizing all the data in decision making.

Antibiotics for acute maxillary sinusitis.

BACKGROUND: For adults seeking care in ambulatory medical practices, sinusitis is the most common diagnosis treated with antibiotics. OBJECTIVES: We examined whether antibiotics are indicated for acute sinusitis, and if so, which antibiotic classes are most effective. SEARCH STRATEGY: Relevant studies were identified from searches of MEDLINE and EMBASE in December 2001, contacts with pharmaceutical companies and bibliographies of included studies. SELECTION CRITERIA: Randomized trials were eligible that compared antibiotic to control or antibiotics from different classes, for acute maxillary sinusitis. Additional criteria for inclusion were diagnostic confirmation by radiograph or sinus aspiration, outcomes that included clinical cure or improvement, and a sample size of 30 or more adults. Of 2058 potentially relevant studies, two or more reviewers identified 49 studies meeting selection criteria. DATA COLLECTION AND ANALYSIS: Data were extracted independently by two persons and synthesized descriptively. Some data were analyzed quantitatively using a random effects model. Primary outcomes were: a) clinical cure, and b) clinical cure or improvement. Secondary outcomes were radiographic improvement, relapse rates, and dropouts due to adverse effects. MAIN RESULTS: Forty-nine trials, involving 13,660 participants, evaluated antibiotic treatment for acute maxillary sinusitis. Major comparisons were antibiotic versus control (n of 5); newer, non-penicillin antibiotic versus penicillin class (n of 10); and amoxicillin-clavulanate versus other extended spectrum antibiotics (n of 17), where n is the number of trials. Most trials were conducted in otolaryngology settings. Only 8 trials described adequate allocation and concealment procedures; 20 were double-blind. Compared to control, penicillin improved clinical cures [relative risk (RR) 1.72; 95% CI 1.00 to 2.96]. Treatment with amoxicillin did not significantly improve cure rates (RR 2.06; 95% CI 0.65 to 6.53) but there was significant variability between studies. Radiographic outcomes were improved by antibiotic treatment. Comparisons between classes of antibiotics showed no significant differences: newer non-penicillins versus penicillins (RR for cure 1.07; 95% CI 0.99 to 1.17); newer non-penicillins versus amoxicillin-clavulanate (RR for cure 1.03; 95% CI 0.96 to 1.11). Compared to amoxicillin-clavulanate, dropouts due to adverse effects were significantly lower for cephalosporin antibiotics (RR 0.47; 95% CI 0.30 to 0.73). Relapse rates within one month of successful therapy were 7.7%. REVIEWER'S CONCLUSIONS: For acute maxillary sinusitis confirmed radiographically or by aspiration, current evidence is limited but supports the use of penicillin or amoxicillin for 7 to 14 days. Clinicians should weigh the moderate benefits of antibiotic treatment against the potential for adverse effects.

Antibiotics for acute maxillary sinusitis.

OBJECTIVES: For adults seeking care in ambulatory practices, sinusitis is the most common diagnosis treated with antibiotics. We examined whether antibiotics are indicated for acute sinusitis, and if so, which antibiotic classes are most effective. SEARCH STRATEGY: Relevant studies were identified from searches of MEDLINE and EMBASE in October 1998, contacts with pharmaceutical companies and bibliographies of included studies. SELECTION CRITERIA: Randomized trials were eligible that compared antibiotic to control or antibiotics from different classes for acute maxillary sinusitis. Additional criteria were diagnostic confirmation by radiograph or sinus aspiration, outcomes that included clinical cure or improvement and a sample size of 30 or more adults. Of 1784 potentially relevant studies, two or more reviewers identified 32 studies meeting selection criteria. DATA COLLECTION AND ANALYSIS: Data were abstracted independently by 2 persons and synthesized descriptively. Some data were analyzed quantitatively using a random effects model. Primary outcomes were a) clinical cure and b) clinical cure or improvement. Secondary outcomes were radiographic improvement, relapse rates, and dropouts due to adverse effects. MAIN RESULTS: Thirty-two trials, involving 7,330 subjects evaluated antibiotic treatment for acute maxillary sinusitis. Major comparisons were antibiotic vs. control (n=5); newer, non-penicillin antibiotic vs. penicillin class (n=10); and amoxicillin-clavulanate vs. other extended spectrum antibiotics (n=10). Most trials were conducted in otolaryngology settings. Only 5 trials described adequate allocation and concealment procedures; 10 were double-blind. Compared to control, penicillin improved clinical cures [relative risk (RR) 1.72, 95% CI 1.00 to 2.96]. Treatment with amoxicillin did not significantly improve cure rates (RR 2.06; 95% CI 0.65 to 6.53), but there was significant variability between studies. Radiographic outcomes were improved by antibiotic treatment. Comparisons between classes of antibiotics showed no significant differences: newer non-penicillins vs. penicillins (RR for cure 1.07; 95% CI 0.99 to 1.17); newer non-penicillins vs. amoxicillin-clavulanate (RR for cure 1.01, 95% CI 0.97 to 1.04). Compared to amoxicillin-clavulanate, dropouts due to adverse effects were significantly lower for cephalosporin antibiotics. Relapse rates within one month of successful therapy were 5%. REVIEWER'S CONCLUSIONS: For acute maxillary sinusitis confirmed radiographically or by aspiration, current evidence is limited but supports penicillin or amoxicillin for 7 to 14 days. Clinicians should weigh the moderate benefits of antibiotic treatment against the potential for adverse effects.

Granulocyte deformability and F-actin content: relationship to diabetes mellitus and retinopathy.

Capillary closure in diabetic retinopathy may be initiated by lumenal occlusion by granulocytes. To determine whether subjects with diabetes mellitus have less deformable granulocytes than healthy subjects, granulocyte deformability was measured by mean entry time into a model capillary system in 16 diabetic-nondiabetic pairs. Granulocyte F-(filamentous) actin content between groups was compared, under basal conditions and after cellular stimulation. The relationship of granulocyte deformability to several diabetes-related variables was examined. Diabetic granulocytes were only 9% +/- 22% less deformable than normal granulocytes (p = 0.16). Deformability was increased in subjects with retinopathy and those with the worst glycemic control (r = 0.61, p = 0.026); both findings were in the opposite direction from that predicted. Basal and stimulated granulocyte F-actin content did not differ between the two groups (p > 0.2 for all assays). Although granulocytes may be important in the pathogenesis of diabetic retinopathy, granulocyte deformability (measured by mean entry time) and F-actin content are not significantly different between healthy patients and those with diabetes.

Anti-inflammatory effects of pentoxifylline in claudication.

We measured neutrophil elastase/alpha 1 proteinase inhibitor complex (E/alpha) levels by ELISA in plasma samples drawn from 19 patients with claudication, before and at 1 and 2 months after initiation of pentoxifylline (PTF), 400 mg. p.o. tid. Plasma E/alpha levels declined in all eight patients whose initial values were more than 300 ng elastase per ml. Whole blood viscosity (wbv) was reduced by two months' treatment in 12 of 14 patients tested. The relative change in wbv was significantly related to the relative change in E/alpha (R2 = 0.8), for patients with elevated initial E/alpha levels, suggesting a common or related mechanism for the two effects. Plasma crosslinked fibrin D-dimer fragments (XDP) measured by ELISA as indicators of coagulation activity were lower compared to pretreatment levels in 9 of 10 samples drawn when symptoms were improved on PTF, whereas they were increased in 6 of 9 samples drawn when symptoms were worse or unchanged. Plasma viscosity, C-reactive protein and alpha 1-acid-glycoprotein did not change significantly with PTF treatment. Together these findings are consistent with the possibility that reduced microvascular neutrophil activation and coagulation play a role in the clinical efficacy of PTF in intermittent claudication.