Use of fibrinolytic agents to coat wire implants to decrease infection. An animal model.

RATIONALE AND OBJECTIVES: Infection is a serious complication of metallic prosthesis implantation and may necessitate removal of the prosthesis. This study uses an animal model to evaluate the effects of coating stainless steel wire implants with fibrinolytic agents to prevent infection after bacterial contamination. METHODS: Three types of steel wire implants were used: plain stainless steel, heparin-coated steel, and urokinase-heparin-coated steel. Wire implants were incubated in a known concentration of Staphylococcus epidermidis and placed into the subcutaneous tissues of three groups of anesthetized hamsters. The implants and surrounding tissues were excised after 1 week and submitted for quantitative cultures. RESULTS: Using 100 organisms as the upper allowable limit to categorize abscesses as noninfected, the following rates of noninfectivity were observed: group 1 (control), 0% noninfected; group 2 (heparin-coated wire), 40% noninfected; and group 3 (urokinase-heparin-coated wire), 50% noninfected. The noninfectivity rates of groups 2 and 3 were significantly higher than the rate of group 1 (P < 0.001). There was no significant difference between groups 2 and 3 (P = 0.19). CONCLUSIONS: Both the heparin-coated and urokinase-heparin-coated wire exhibited significantly decreased infection rates compared with uncoated wire; the heparin coating may inhibit bacterial adherence. The urokinase coating of the heparin-coated wire appears to further decrease the infection rate, but not to a statistically significant degree.

Validation of a Telephone Cognitive Assessment Battery.

OBJECTIVE: To present and evaluate an instrument, the Telephone Cognitive Assessment Battery (TCAB), designed to be administered over the telephone to assess the cognitive status of older individuals. The TCAB addresses mental status, reasoning and executive ability, primary and secondary memory, and language. It consists of six neuropsychological tests and takes approximately 15 to 20 minutes to complete. DESIGN: The instrument is evaluated with a comparative cross-sectional design, with data collected both prospectively and retrospectively. SETTING: The University Hospitals of Cleveland/Case Western Reserve University Alzheimer Center Research Registry. PARTICIPANTS: Forty Alzheimer's Disease cases selected from among those most recently recruited into the Registry and 40 cognitively intact Registry controls. Controls were selected randomly so that the two groups had similar distributions of age, sex, and education. MEASUREMENTS: The cognitive status of all participants was assessed utilizing both the TCAB and the usual in-person Registry evaluation, which includes medical history data and in-person assessment of cognitive status. In order to measure the potential learning effect of repeated testing, half of the cases and half of the controls were recruited and assessed over the telephone with the TCAB before their in-person Registry evaluation (with a waiting period of at least 2 weeks between evaluations), whereas the other two halves received the TCAB after they had become part of the Registry. The TCAB was administered to all participants by a single investigator. Two clinical evaluators, blinded to the Registry diagnosis of the subjects, independently classified the subjects as cognitively impaired, normal, or questionable on the basis of the results of the TCAB and a brief listing of medical illness and depressive symptoms. A final classification was achieved through consensus and subsequently compared with the Registry diagnosis, taken here to be the gold standard. RESULTS: Test scores of subjects assessed by TCAB before receiving the in-person assessment were compared with those of subjects receiving the in-person assessment first. There were no significant differences between mean scores of the two groups (those with TCAB first and those with TCAB last) for either cases or normal controls. High values of the kappa statistic were obtained for the two initial evaluators of the TCAB classification, demonstrating excellent interrater reliability. Regarding the reconciled TCAB classification, the ability of the TCAB to correctly classify subjects according to cognitive status, while controlling for potential confounders such as age and educational level, was assessed by means of discriminant analysis techniques. Knowledge of the TCAB classification and age allowed the correct classification of 95% of the participants; this was not significantly improved by knowledge of other potential determinants. Sensitivity and specificity were calculated under two schema for classifying those subjects in the "questionable" category. Positive and negative predictive values of the TCAB were computed assuming a prevalence of cognitive impairment of 10% in the older population. High negative predictive values (over 99%) were obtained under both schema, whereas the positive predictive values were seen to be more dependent on the classification of questionables. CONCLUSION: Research studies involving ascertainment of cognitive status of older people, particularly those that require periodic follow-up, such as those focusing on healthy aging, commonly suffer from lack of representativeness of subjects, often brought about by problems related to mobility of potential participants. It is also crucial that normal individuals who are recruited initially to serve as controls in epidemiologic studies of dementing illnesses be reevaluated periodically, and this may be hindered by the same obstacles. (ABSTRACT TRUNCATED)

Association of Alzheimer's disease and smoking: the case for sibling controls.

OBJECTIVES: To study the association between cigarette smoking and Alzheimer's Disease (AD). DESIGN: Intrafamily case-control, with sibling controls and a variable number of controls per case. SETTING: AD cases were identified through the Research Registry of the University Hospitals of the Cleveland/Case Western Reserve University Alzheimer Center. PARTICIPANTS: Study subjects were 86 probable AD cases (index cases) and all of their full siblings, alive or dead, aged > or = 50 years, a total of 238 subjects. MEASUREMENTS: Exposure for each individual was ascertained with a questionnaire answered by several informants. Cognitive status of siblings of the AD cases (impaired or intact) was ascertained by telephone using validated instruments. Diagnosis of dementia in cognitively impaired siblings of index cases was not attempted. RESULTS: Chi-square analysis tested for departure from a random distribution of disease across smokers and nonsmokers within families. No significant departure was found utilizing all families (P > .40) nor utilizing those families where only the index case was affected (P > .90). Conditional logistic regression evaluated the association within families, controlling for age, sex, and education. Analyses both included and excluded secondary cases of cognitive impairment. No association was found between smoking and disease (OR = 1.26; 95% confidence interval, 0.66-2.42, and OR = 1.42; 95% confidence interval, 0.69-2.89, respectively). CONCLUSIONS: No significant association was found between smoking and cognitive status. Further, analyses based on the comparison of persons with AD with their unaffected siblings also suggest that smoking does not decrease the risk of AD.

On the use of surrogate respondents for controls in a case-control study of Alzheimer's disease.

OBJECTIVE: To examine the presence and extent of bias introduced by using surrogate respondents for healthy controls in a case-control study of Alzheimer's disease (AD). DESIGN: Comparative study of matched responses to questionnaire ascertaining lifestyle issues. SETTING: University Hospitals/Case Western Reserve University Alzheimer Center. PARTICIPANTS: Controls (n = 50) were identified through the Research Registry. Surrogates (n = 50) were their healthy relatives or friends. MEASUREMENTS: Answers in the areas of demographic and occupational history, smoking habits, medical history, dietary intake, and leisure and work activities were recorded. The analysis was based on methods for paired data. Continuous variables were analyzed, focusing on paired differences between self and surrogate responses. RESULTS: For occupations and exposures, over 80% of the surrogates agreed with the subjects on over 80% of the questions. On smoking history, over 90% of the surrogates agreed with the subjects on over 70% of the questions. On leisure and work activities, over 70% of the surrogates agreed with the subjects on over 50% of the questions. There was less agreement regarding medical history. For continuous variables, most paired t-tests of zero mean difference between self and surrogate responses resulted in nonrejection of this hypothesis. Computed mean differences were not always positive or always negative. CONCLUSION: We did not find systematic under- or overreporting by the surrogates of the controls. Therefore, if there are biases in the responses of surrogates of the AD cases in our case-control study, they would not be canceled out by using surrogates for the controls.

Retrospective study of fetal effects of prolonged labor before cesarean delivery.

Rising cesarean rates call for review of the indications for this procedure. Suspicion that subtle operatives, not reflected in morbidity and mortality rates, might be present inspired the study presented here. Three hundred fifty-two cesarean operations were done at Huron Road Hospital in the years 1952-1954. Examination of family records identified 97 probands delivered by cesarean after prolonged active labor before or during that period. Research efforts yielded 54 cases that were free of complications and had full historic data for both proband and sibling(s) of the same parentage, totaling 122 children. The intelligence quotient (IQ) scores of these families compared with that of the proband undergoing successive hours of labor suggested a detrimental effect of increasing length of trial labor. Statistical analyses of the 30 families in which the probands' trial labors exceeded 12 hours support that notion, as the probands had significantly lower IQ scores than their siblings born by elective cesarean with no labor (P = .006 to P less than .001). Probands had the lowest IQ scores in their families significantly more often (P less than .025) than could be expected to occur randomly. A similar pattern of school success occurred within the families.

A meta-analysis of randomized controlled trials of laparoscopic versus conventional appendectomy.

BACKGROUND: Despite many randomized controlled trials, the merits of laparoscopic appendectomy remain unclear. A meta-analysis may provide insights not evident from any individual studies. DATA SOURCES: Systematic literature search yielded 17 trials (1,962 subjects) of true randomized design with usable statistical data comparing laparoscopic and conventional appendectomy in adults. The effect sizes for operating time, hospitalization, postoperative pain, return to normal activity, wound infection, and intra-abdominal abscess were calculated, using the random effects model to allow for heterogeneity. An estimate of the robustness of all positive findings was also calculated. RESULTS: Modest but statistically significant effect sizes were found for four of the six outcome measures. Laparoscopic appendectomy takes 31% longer to perform, but results in less postoperative pain, faster recovery (by 35%), and lower wound infection rates (by 60%). CONCLUSION: Laparoscopic appendectomy offers significant improvement in postoperative outcomes at the cost of a longer operation.

Long-term developmental outcomes of method of delivery.

OBJECTIVE: In the general framework of relating birthing events to later mental development, this study addresses the hypothesis that uneventful non-vertex delivery is associated with higher intelligence than uneventful vertex delivery. STUDY DESIGN: In the course of a developmental obstetrical survey, data was gathered prospectively on families having a non-vertex birth at Huron Road Hospital during the 1950s and early 1960s. The intelligence quotient (IQ) scores and school success ratings for the cohort of 658 children who had been delivered uneventfully by specific non-vertex methods of birth (viz. elective section, breech and internal podalic version) are compared with those of 1151 of their own siblings and peers delivered by cephalic presentation without complication. Intrafamily comparisons allow the control of genetic and socioeconomic factors. RESULTS: The one-sided 95% confidence intervals (using the t-statistic) for mean values do not overlap. They are: IQ > 112.1 (non-vertex) vs. < 110.1 (vertex) and school success scores > 2.64 (non-vertex) vs. < 2.54 (vertex). These findings are confirmed for IQ when the analysis is restricted to only those 434 children in the families allowing intrafamily comparisons (i.e. comparable siblings born by both non-vertex and vertex deliveries). The one-sided 95% confidence intervals for mean values do not overlap. They are: IQ > 112.89 (non-vertex) vs. < 112.86 (vertex). CONCLUSIONS: Speculation is given as to the reasons for this phenomenon. It is unclear whether these differences are due to physical phenomena related to delivery or to effects due to differing levels of anesthesia-analgesia or whether these differences in intellectual potential are associated with the cause of obstetrical difficulties.

Statistical certification of eradication of poliomyelitis in the Americas.

The last confirmed case of paralytic poliomyelitis due to indigenous wild poliovirus in the Americas occurred in Peru in 1991. In 1994 the International Commission on Polio Eradication of the Pan American Health Organization (PAHO) deemed eradication of polio from the area to have occurred, based on its strategic efforts and the observed results. A mathematical model is presented here which relates the time elapsed since that last detected case of paralytic poliomyelitis caused by wild poliovirus to the probability that the transmission of indigenous wild poliovirus has been stopped. The appropriateness of applying the model to various geographical areas of the Americas is investigated using data about the occurrence of confirmed cases of polio since 1984, the time of the eradication initiative adopted by PAHO. The model suggests that if four year have elapsed since the last reported confirmed case of polio caused by wild poliovirus, and no other confirmed cases have been identified, the probability of undetected indigenous wild poliovirus transmission is less than 5%. An important assumption is that the eradication strategy implemented by PAHO has yielded steady improvements. A consequence of this approach is that the annual probabilities of persistence given by the model are conservative, in the sense of being higher than the true, but unknown a priori probabilities, and more so with each passing year. It is thus seen that the model results are compatible with the conclusion reached by PAHO in 1994. The model takes into account the intensity of surveillance of each country in the region, measured by the corresponding rates of acute flaccid paralysis (AFP). Because importations of wild poliovirus may occur from other regions of the world, surveillance efforts are being maintained in the Americas until global eradication has been achieved.

Correlations of dual-energy X-ray absorptiometry, quantitative computed tomography, and single photon absorptiometry with spinal and non-spinal fractures.

Controversy continues as to which method of measuring bone mineral density (BMD) best detects osteoporosis and best correlates with fractures of the spine, hip and elsewhere. To answer these questions the prevalence of fractures was carefully determined among 90 subjects (70 with osteoporosis, 6 with mild primary hyperparathyroidism, 1 with osteomalacia and 13 normals) and simultaneous measurements were made using spinal computed tomography (QCT), spinal anteroposterior (AP) and supine lateral dual X-ray absorptiometry (DXA), femoral neck and total hip DXA, and distal third radial DXA and single photon absorptiometry (SPA). The DXA measurements which had the greatest sensitivity in detecting osteoporosis (defined as a BMD lower than -2.5 SD of peak bone mass at age 30 years) were the supine lateral spine DXA (84%) and femoral neck DXA (75%); less sensitive were the DXA measurements of the distal third of the radius (61%) and AP spine (51%). DXA measurements of the femoral neck and distal third of the radius were more useful than spinal measurements in detecting the osteopenia of mild primary hyperparathyroidism. Vertebral compression fractures (VCF) correlated well with spinal QCT (r = 0.38) and lateral spine DXA (r = -0.41), but poorly with AP spine DXA (r = -0.17) and distal third radial DXA (r = -0.02). Non-spinal fractures correlated best with the distal third radial DXA (r = -0.42). In conclusion, spinal QCT, supine lateral spine DXA and femoral neck DXA are the best BMD methods to screen for osteoporosis, whereas AP spine DXA is a poor screening method in women over 60 years of age. Spinal QCT and lateral spine DXA correlate well with VCFs, whereas correlations of VCFs with AP spine DXA, femoral neck DXA and distal third radial DXA are poor.

Meta-analyses of randomized controlled trials of laparoscopic vs conventional inguinal hernia repairs.

BACKGROUND: Despite randomized controlled trials, the merits of laparoscopic hernia repair remain poorly defined. A meta-analysis may provide a timely overview. METHODS: An electronic MEDLINE search, supplemented by a manual search, yielded 14 randomized controlled trials with usable statistical data, involving 2,471 patients. The trials were grouped for separate meta-analyses according to the control operation, either a tension-free or sutured repair, used for comparison. The effect sizes for operating time, postoperative pain, return to normal activity, and early recurrence were calculated, using a random-effects model when the effect sizes were heterogeneous and without subcategories. RESULTS: In all meta-analyses, the laparoscopic operation was significantly longer. When compared with tension-free repairs, the laparoscopic operation showed no advantage in terms of postoperative pain, but resulted in a shorter recovery (marginal significance). As compared with sutured repair, both postoperative pain and recovery were in favor of the laparoscopic operation. When all 14 trials were analyzed together, laparoscopic repairs still had moderately reduced postoperative pain and recovery time. CONCLUSIONS: Laparoscopic hernia repair has a modest advantage over conventional repairs. This advantage is more apparent when laparoscopic repairs are compared with sutured repairs rather than tension-free repairs.

Bleeding due to needle biopsy: effect of venopirin in an animal model and implications for humans.

PURPOSE: This study was undertaken to address the effect of platelet dysfunction on bleeding associated with percutaneous needle biopsy. MATERIALS AND METHODS: With use of an established animal model, 199 biopsies were performed on the livers of 13 anesthetized pigs (95 on control animals, 104 on venopirin-treated animals). The needles used were 16-22-gauge Chiba type, 18-gauge Tru-Cut, and 18-gauge Menghini. The biopsies were performed under direct vision at laparotomy with consistent technique. Blood loss was measured, and the results were compared. Statistical analysis was performed with the Student t test and the Turkey test, after logarithmic transformation of the data. RESULTS: A substantial increase in blood loss resulting from the biopsy procedures was demonstrated in the animals with platelet dysfunction. This was much greater than the effect of either needle size or prothrombin time prolongation previously reported by the authors. CONCLUSION: Platelet function may be an important factor in determining the risk of bleeding due to percutaneous needle biopsy.

Storing sparse and repeated data in multivariate Markovian models of tuberculosis spread.

Through the use of appropriate sparse storage techniques, we were able to reduce memory usage in a multivariate Markovian model for the spread of tuberculosis in the United States through the year 2010. A straightforward software implementation of the model would have required approximately 2.5 x 10(9) bytes of storage for the population of each year being modeled and approximately 1.3 x 10(14) bytes of storage for each year-to-year set of transition probabilities. We were able to reduce memory usage in the model by 96% for cross-sectional population data and over 99.9% for transition probability data. Data structure initialization time for population data was increased by a factor of 16.48 and lookup time for population data was increased by a factor of 11.3 over times required for an array implementation. For transition data the initialization and lookup times were increased by negligible factors. This work was done under contract from the Centers for Disease Control and the Association of Teachers of Preventive Medicine.

Effect of needle gauge, level of anticoagulation, and target organ on bleeding associated with aspiration biopsy. Work in progress.

Percutaneous fine-needle aspiration biopsy has gained wide acceptance due to its accuracy, ease of performance, and safety. This study was performed to evaluate the effect of needle size, coagulation impairment, or biopsy of different organs on risk of bleeding during the procedure. Multiple biopsy procedures were performed on the livers and kidneys of anesthetized pigs with 14-22-gauge Chiba-type needles. The procedures were performed under direct vision at laparotomy, and blood loss was measured. While larger needles generally produced more bleeding, the differences were statistically significant only when comparing 14- with 16-gauge needles and 16-gauge needles with the group of 18-, 20-, and 22-gauge needles in the liver. In the kidney, no significant difference was noted between 18-, 20-, and 22-gauge needles. Anticoagulation did not produce significantly greater blood loss but did allow separation of the group of 18- and 20-gauge needles from 22-gauge needles in the kidney. Renal biopsy resulted in greater overall blood loss than did liver biopsy.

Morphological evaluation of human embryos and derivation of an embryo quality scoring system specific for day 3 embryos: a preliminary study.

A scoring system specific for day 3 embryos has not been extensively explored. Most IVF laboratories continue to grade embryos solely on the basis of cell number and percentage fragmentation as was traditionally done for day 2 embryos. Additional morphological features, some unique to day 3 embryos, may be useful in selecting embryos most likely to blastulate and implant. The objective of this study was to derive an embryo scoring system for day 3 transfers which is predictive of positive pregnancy outcomes. A total of 316 transferred embryos from 93 patients was recorded on videotape and evaluated. The following parameters were used to grade the embryos: cell number, fragmentation pattern (FP), cytoplasmic pitting, compaction, equal sized blastomeres, blastomere expansion and absence of vacuoles. The clinical pregnancy rate was 41.9%, with an implantation rate of 18% per embryo transferred. The mean number of embryos transferred per patient was 3.4. Three formulae were derived to score embryo quality in each transfer based on the average score of individual embryos transferred. In the first scoring system, cell number alone was used to predict pregnancy outcome. The second scoring system was based on blastomere number and the observed FP. The third scoring system utilized both blastomere number and FP but also combined this with five morphological criteria to yield a final day 3 embryo quality (D3EQ) score. We found the D3EQ score to be prognostic of pregnancy outcome. This study suggests that although cell number and FP are certainly predictors of positive pregnancy outcomes, additional parameters specific to day 3 embryos should be used to stratify a cohort of embryos further.

Multivariate Markovian modeling of tuberculosis: forecast for the United States.

We have developed a computer-implemented, multivariate Markov chain model to project tuberculosis (TB) incidence in the United States from 1980 to 2010 in disaggregated demographic groups. Uncertainty in model parameters and in the projections is represented by fuzzy numbers. Projections are made under the assumption that current TB control measures will remain unchanged for the projection period. The projections of the model demonstrate an intermediate increase in national TB incidence (similar to that which actually occurred) followed by continuing decline. The rate of decline depends strongly on geographic, racial, and ethnic characteristics. The model predicts that the rate of decline in the number of cases among Hispanics will be slower than among white non-Hispanics and black non-Hispanics a prediction supported by the most recent data.

Liver biopsy: effects of biopsy needle caliber on bleeding and tissue recovery.

PURPOSE: To evaluate different-caliber biopsy cutting needles in terms of the benefits and potential risk of bleeding in a swine model. MATERIALS AND METHODS: A total of 190 sequential liver biopsy specimens were obtained in 11 Yorkshire pigs (weight, 50-70 lb [22.5-31.5 kg]) by using 14-, 18-, and 20-gauge cutting needles. For each biopsy procedure, blood loss was determined by weighing sponges used to absorb bleeding, and sample-tissue DNA content was measured with spectrofluorometry. Analysis of variance was used to compare results. RESULTS: The larger the caliber of needle, the greater the absolute blood loss (for 14-gauge, 1.69 g; for 18-gauge, 0.74 g; for 20-gauge, 0.32 g) and DNA content per sample (for 14 gauge, 40.38 microg; for 18-gauge, 12.18 microg; for 20-gauge, 5.86 microg). The ratio of blood loss to amount of DNA recovered did not differ among the different-caliber needles. To obtain the same amount of diagnostic tissue, more passes were needed with the smaller-caliber needles. CONCLUSION: Use of larger-caliber needles is more efficient despite the greater amount of blood loss, because more tissue can be recovered and because fewer passes are necessary, which reduces the chances of complications.

Prognostic factors in vitrectomy for epiretinal membranes of the macula.

A retrospective multivariate analysis of 264 consecutive cases of vitrectomy for removal of epiretinal membranes of the macula was performed. Two main preoperative prognostic factors were identified that were associated with the visual outcome of surgery: (1) the preoperative visual acuity, and (2) the duration of blurred vision before surgery. Discriminant functions constructed using these two factors allowed correct classification of eyes into an outcome group with good visual acuity with a 69% accuracy, and an 80% accuracy in classifying eyes into a group showing significant improvement in the level of visual acuity. Eyes that began with vision better than 20/100 tended to have slightly better postoperative visions than eyes with poorer preoperative visual acuity. However, eyes with worse preoperative vision tended to improve the greatest amount after surgery. Eyes with a longer history of blurred vision had poorer visual acuity after surgery and also less improvement in vision. Other statistically significant prognostic factors were identified; however, they did not appreciably improve the accuracy of the discriminant function in predicting visual outcome.

Young Investigator Award. In vivo treatment of infected prosthetic graft material with urokinase: an animal model.

PURPOSE: Pyogenic infection of vascular grafts represents a serious complication that may necessitate graft removal. If better treatment methods could be developed, perhaps some infected grafts could be salvaged and not removed. This study reports an animal model that evaluates the sterilization of contaminated vascular graft material implants with urokinase and antibiotics. MATERIALS AND METHODS: Polytetrafluoroethylene (PTFE) implants were incubated overnight in a known concentration of bacteria (Staphylococcus epidermidis) and were then implanted subcutaneously into four groups of anesthetized hamsters. The first group (control) received no treatment. The second group received urokinase injections twice daily into each abscess. The third group received intraabscess urokinase and systemic gentamicin twice daily. The fourth group received only systemic gentamicin. The hamsters were killed after 1 week. The graft implants and surrounding tissues were excised and submitted for quantitative cultures. RESULTS: With use of a cutoff value of 100 organisms per milliliter, below which the abscesses were considered noninfected, the following rates of noninfectivity were observed: group 1 (control), 5% noninfected; group 2 (urokinase only), 19.4%; group 3 (urokinase and gentamicin), 63.2%; and group 4 (gentamicin only), 32.5%. The noninfectivity rate of group 3 was significantly higher than that of all other groups combined (P < .001) and was significantly better than that of group 4 alone (P = .013). CONCLUSION: The combination of intraabscess urokinase and systemic gentamicin is very synergistic in graft sterilization. Urokinase may assist in the degradation of both fibrin and the biofilm produced by S epidermidis, thus improving penetration of antibiotics and local host defense mechanisms.