Analysis of historical negative control group data from the rat in vivo micronucleus assay.

A database of micronuclei counts for historical negative control data from rat in vivo micronuclei tests performed in 10 different laboratories was established. Data were available from over 4000 negative control rats from 10 laboratories. The mean frequency of micronucleated cells (MN)/1000 cells ranged from 0.44 to 2.22, a 5-fold range. Overall there were no major sex or strain differences in frequency, although there were some small but statistically significant differences within laboratories. There was appreciable variability between experiments compared with variability within experiments in some laboratories. No specific factor was identified which could explain this variability although it was noted that many different vehicles were used in the experiments. It is hoped that these data will help laboratories beginning studies with the rat micronucleus assay and those involved in the assessment of micronucleus assay results.

Comparison of logistic regression and neural networks to predict rehospitalization in patients with stroke.

CONTEXT: Rehospitalization following inpatient medical rehabilitation has important health and economic implications for patients who have experienced a stroke. OBJECTIVE: Compare logistic regression and neural networks in predicting rehospitalization at 3-6-month follow-up for patients with stroke discharged from medical rehabilitation. DESIGN: The study was retrospective using information from a national database representative of medical rehabilitation patients across the US. SETTING: Information submitted to the Uniform Data System for Medical Rehabilitation from 1997 and 1998 by 167 hospital and rehabilitation facilities from 40 states was examined. PARTICIPANTS: 9584 patient records were included in the sample. The mean age was 70.74 years (SD = 12.87). The sample included 51.6% females and was 77.6% non-Hispanic White with an average length of stay of 21.47 days (SD = 15.47). MAIN OUTCOME MEASURES: Hospital readmission from 80 to 180 days following discharge. RESULTS: Statistically significant variables (P <.05) in the logistic model included sphincter control, self-care ability, age, marital status, ethnicity and length of stay. Area under the ROC curves were 0.68 and 0.74 for logistic regression and neural network analysis, respectively. The Hosmer-Lemeshow goodness-of-fit chi-square was 11.32 (df = 8, P = 0.22) for neural network analysis and 16.33 (df = 8, P = 0.11) for logistic regression. Calibration curves indicated a slightly better fit for the neural network model. CONCLUSION: There was no statistically significant or practical advantage in predicting hospital readmission using neural network analysis in comparison to logistic regression for persons who experienced a stroke and received medical rehabilitation during the period of the study.

Adrenocorticotropic hormone testing in idiopathic hirsutism and polycystic ovarian disease: a test of limited usefulness.

The plasma 17 alpha-hydroxyprogesterone (17-OHP) concentration was determined in the basal state and 60 minutes after cosyntropin, 0.25 mg, in 139 patients with idiopathic hirsutism (IH) and polycystic ovarian disease (PCOD). Although there was an increased response of 17-OHP in subjects with PCOD when compared with IH subjects, in no instance was stimulated 17-OHP abnormal in the presence of normal basal 17-OHP. Two subjects with 21-hydroxylase (21-OH) deficiency were discovered; both demonstrated elevated basal levels of 17-OHP. We therefore conclude that routine adrenocorticotropic hormone testing is not a useful tool in detecting 21-OH deficiency in hyperandrogenic women.

An electrophysiological study of the insertion of overt response choice.

Using electrophysiological measures, the authors studied changes in prestimulus state, stimulus identification, and response-related processing when, in a go/no-go task, forced choice between 2 overt go responses was inserted. The authors observed decreased prestimulus motor preparation (electromyogram), no change in stimulus identification time (selection negativity), a minor increase in response selection time (lateralized readiness potential), a large increase in response preparation time (lateralized readiness potential), a minor effect on response execution time (electromyogram), and a decrease in the activation of a response-inhibition process on no-go trials (frontal event-related potential). The existence of the response-inhibition process was verified by the presence of inverted lateralized readiness potentials on no-go trials. Pure insertion of response choice in a task seems impossible because the choice between activation and inhibition (go/no-go) always seems already present.

Development of function-related groups version 2.0: a classification system for medical rehabilitation.

OBJECTIVE: To present a new version (2.0) of the Functional Independence Measure-Function Related Group (FIM-FRG) case-mix measure. DATA SOURCE/STUDY SETTING: 85,447 patient discharges from 252 freestanding facilities and hospital units contained in the 1992 Uniform Data System for Medical Rehabilitation. STUDY DESIGN: Patient impairment category, functional status at admission to rehabilitation, and patient age were used to develop groups that were homogeneous with respect to length of stay. Within each impairment category patients were randomly assigned to one data set to create the system (through recursive partitioning) or a second set for validation. Clinical and statistical criteria were used to increase the percentage of patients classified, expand the impairment categories of FIM-FRGs Version 1.1, and evaluate the incremental predictive ability of coexisting medical diagnoses. Predictive stability over time was evaluated using 1990 discharges. PRINCIPAL FINDINGS: In Version 2.0, the percentage of patients classified was increased to 92 percent. Version 2.0 includes two new impairment categories and separate groups for patients admitted to rehabilitation for evaluation only. Coexisting medical diagnoses did not improve LOS prediction. The system explains 31.7 percent of the variance in the logarithm of LOS in the 1992 validation sample, and 31.0 percent in 1990 discharges. CONCLUSIONS: FIM-FRGs Version 2.0 includes more specific impairment categories, classifies a higher percentage of patient discharges, and appears sufficiently stable over time to form the basis of a payment system for inpatient medical rehabilitation.

A new concept for the management of rectal prolapse.

The various modified fixation procedures used for rectal prolapse take into account the pathophysiologic concept of complete prolapse of the rectum as a sliding hernia of the pouch of Douglas. The possibility of intussusception by reinforcement of the wall of the extensively mobilized rectum was successfully prevented by a new technique. The use of this simple technique in another form of prolapse, namely, prolapse of the terminal colostomy, convinced us to its usefulness.

Simultaneous evaluation of clastogenicity, aneugenicity and toxicity in the mouse micronucleus assay using immunofluorescence.

An improved antikinetochore antibody technique was established in the mouse micronucleus assay to simultaneously evaluate toxicity, clastogenicity and aneugenicity induced by various test agents. The procedure involved the use of cellulose column fractionated cytospun slides for analysis. The staining method consisted of sequential treatment of slides with crest serum, fluorosceinated goat-antihuman and swine-antigoat antibodies, and propidium iodide. In this method, polychromatic erythrocytes (PCEs, dark red), normochromatic erythrocytes (NCEs, green), chromosome(s)/fragments/micronuclei (orange), and kinetochores (yellow), are identified using the same filter setting under blue excitation (440-490 nm) with a barrier filter at 520 nm. Using this method, three agents, cyclophosphamide, X-rays and vincristine were tested for micronucleus/aneuploidy induction and bone marrow toxicity. The aneugen, vincristine, and clastogens, X-rays and cyclophosphamide, induced predominantly kinetochore positive (K+) and negative (K-) micronucleated PCEs, respectively. At the doses tested, cyclophosphamide caused a slight but statistically significant decrease in PCEs in females, and other agents did not produce any severe bone-marrow toxicity in either male or female mice. These results are comparable with the results reported in the literature on these compounds with various methods and thus demonstrate the usefulness of this assay in distinguishing clastogenicity from aneugenicity and in evaluating toxicity.

Simultaneous analysis of chromosome damage and aneuploidy in cytokinesis-blocked V79 Chinese hamster lung cells using an antikinetochore antibody.

A modified antikinetochore antibody technique was established in the V79 Chinese hamster lung cells to simultaneously analyze chromosome damage and aneuploidy induced by various agents. The method involved sequential treatment of slides with crest serum, fluoresceinated goat-antihuman and swine-antigoat antibodies, and propidium iodide. In this method, cytoplasm (green), nuclei or micronuclei (red), and kinetochores (yellow), are identified using the same filter setting under blue excitation (440-490 nm) with a barrier filter at 520 nm. Using this method, three agents, vinblastine (VB), X-rays, and methyl methanesulfonate (MMS) were tested for micronucleus/aneuploidy induction. An aneugen, VB and a clastogen, X-rays, induced predominantly kinetochore positive (K+) and negative (K-) micronucleated binucleate (MNBN) cells, respectively, in a dose-dependent fashion. An alkylating agent, MMS, produced both K+ and K- MNBN cells. These results are comparable with the results reported in the literature on these compounds using various methods and thus demonstrate the usefulness of this assay in distinguishing clastogenicity from aneugenicity.

In vitro induction of micronuclei and chromosome aberrations by quinolones: possible mechanisms.

The bacterial gyrase inhibitors, ciprofloxacin and PD 124816, were tested for clastogenic and aneugenic activity in V79 Chinese hamster lung cells in vitro. Cells were exposed for 3 h, washed free of drug, and subcultured for assessment of various endpoints. For structural chromosomal aberration (SCA) analysis, cells were incubated for 18 h, and treated with Colcemid for 2 h before harvest. For micronucleus (MN) analysis, treated cells were incubated with cytochalasin B (CYB) for 16 h. Aneugenicity was assessed by utilizing antikinetochore antibody to detect kinetochore-containing (K +) MN. Both quinolones induced significant increases in SCAs and MN, indicating clastogenic activity. With both compounds, however, the MN response was apparent at lower doses, and remained much higher throughout the dose range than the SCA response. The induced MN were predominantly K --, indicating that aneugenicity was not playing a major role in their induction. A possible explanation for the chromosome effects is that cross-reactivity of the gyrase inhibitors with mammalian topoisomerase II interferes with the separation of chromatids at anaphase leading to chromosome breaks and MN. Quinolones are known to inhibit resolution of the normally transient topoisomerase II-DNA cleavable complex, which may result in chromosome stickness. Thus, SCAs detected in metaphase cells may be attributed to quinolone-induced inhibition of topoisomerase II prior to mitosis while MN arise in binucleated cells as a result of this effect which interferes with chromatid separation during anaphase.

Minimal chronic inactive gastritis: indicator of pre-existing helicobacter pylori gastritis?

Minimal chronic inactive gastritis is regularly observed in routine histopathology. Presently, it is not clear whether this type of gastritis should be regarded as a histopathological entity or a normal variant. The similarity to lesions observed after H.pylori eradication prompted us to look for an association between minimal chronic inactive gastritis and status post H.pylori eradication. In a prospective study of 110 consecutive patients undergoing upper gastrointestinal endoscopy, at least two mucosal biopsies were taken from the gastric antrum and body. Gastritis was classified according to the Sydney System. Antibodies to H.pylori were determined serologically by immunofluorescence test, ELISA, and complement binding reaction. A status post eradication of H.pylori was revealed by medical history and/or positive serology; H.pylori gastritis was found in 39.1%, reactive gastritis in 12.7%, and minimal chronic inactive gastritis in 29.1%. In 19.1% a combination of reactive/ minimal chronic gastritis was diagnosed according to morphology. Status post eradication was observed significantly more often in cases with minimal chronic inactive gastritis (43.8%) than in cases with reactive gastritis (7.1%, p < 0.004). Furthermore, positive ELISA and/or status after eradication was found in 50% of the cases with minimal chronic inactive gastritis (p < 0.005 vs reactive gastritis), in 42.9% of the cases with mixed reactive/chronic inactive gastritis (p < 0.03 vs reactive gastritis), and in 7.1% of the cases with reactive gastritis. Lymphoid aggregates, considered another sign of former H.pylori presence, were found significantly more often in minimal chronic inactive gastritis than in reactive gastritis (50% versus 7.1%, p < 0.005). Minimal chronic inactive gastritis is significantly associated with both positive H.pylori serology and status post eradication and is, therefore, an indicator of pre-existing H.pylori gastritis.

Case report. Mini-epidemic of thyrotoxicosis occurring in physicians.

This report describes the appearance of thyrotoxicosis over the past eight years in three male physicians working in the Division of Endocrinology at The Mount Sinai Hospital. Since no other instances of hyperthyroidism developed among the hospital medical or dental attending staff, to the authors' knowledge, during the years of 1953-1973, this incidence appears to indicate an unusual occurrence. (Information regarding other possible instances of thyrotoxicosis was obtained by questioning all of the physicians in the Division of Endocrinology at The Mount Sinai Hospital, members of the Division of Endocrinology at the other major institutions in the city and, finally, inquiry of the physicians in the Department of Medicine at The Mount Sinai Hospital.)

[First clinical experience with a full-size, flat-panel detector for imaging the peripheral skeleton - Part II: Post-processing with a newly developed adaptive autowindow algorithm]. / Erste klinische Erfahrungen mit einem grossformatigen Flächendetektorsystem bei Aufnahmen des peripheren Skelettsystems - Teil 2 : Nachverarbeitung mit einem neu entwickelten adaptiven Autofensteralgorithmus -

PURPOSE: of the second part of the investigation was the evaluation of a newly developed adaptive autowindow algorithm in comparison to the system processing radiographs of the wrist and ankle to further optimize the image quality with softcopy reading. MATERIAL AND METHODS: All 120 radiographs of the wrist and all 100 radiographs of the ankle used in the 1st part of this paper were processed with the adaptive autowindow algorithm. The evaluation was again performed by 5 radiologists with softcopy reading. For the data analysis a variation of the Visual Grading Analysis (VGA) was used. RESULTS: Up to 19 % of the wrist radiographs and 2 % of the ankle radiographs processed with the system software had to be processed manually afterwards to get acceptable results. By the application of the adaptive autowindow algorithm a manual post-processing was no longer necessary. Highly significant (p less-than-or-equal 0.001) differences for all criteria to be evaluated were found for the wrist radiographs and in the case of the ankle radiographs for the bone contrast, the contrast in soft-tissue regions, the fine details in the bone and the artifacts, the adaptive autowindow algorithm performed always better than the system software. CONCLUSION: Using half of the exposition dose on a flat-panel detector, an optimized post-processing leads to comparable or better results compared to the conventional film-screen-system concerning the image quality.

[First clinical experience with a full-size, flat-panel detector for imaging the peripheral skeletal system]. / Erste klinische Erfahrungen mit einem grossformatigen Flächendetektorsystem bei Aufnahmen des peripheren Skelettsystems - Teil 1: halbierte Patientendosis -

PURPOSE: This investigation was intended to show that exposures of the peripheral skeleton system can be done with half of the dose used for conventional screen-film systems with a full-size CsI/a-Si flat panel detector. MATERIAL AN METHODS: 120 exposures of the wrist and 100 exposures of the ankle have been made on a full-size flat panel detector system (43 x 43 cm). The patient dose has been reduced by a factor of two compared to conventional images. Five radiologists evaluated every image as a softcopy and a hardcopy image. For the evaluation, a variation of the Visual Grading Analysis (VGA) without reference images was used. For the determination of the patient entrance dose, measurement of a phantom were performed. RESULTS: A dose reduction of about 50 % is possible with the same or even better image quality in routine diagnostics. Only 3 % of the ankle and approx. 21 % of the wrist exposures required a postprocessing. Exposures with implants did not show any artifacts and some of the those achieved better evaluation results compared with exposures without implants. CONCLUSION: A halving of the patient dose is possible with acceptable results for the image quality. The effect of an improved image processing remains to be evaluated. The patient entrance dose is suitable for an evaluation of a radiographic detector and especially for a dose-referred comparison of digital X-ray units.

Noninvasive assessment of internal thoracic artery for reoperative coronary artery surgery.

To determine whether previous sternotomy alters internal thoracic artery (ITA) anatomy and flow characteristics, a duplex scanner was used for noninvasive evaluation of the ITA in 59 patients who were scheduled for reoperative coronary artery bypass surgery. The left ITA was insonated through the third intercostal space by use of a duplex scanner (5.0 MHz probe). Measurements of the ITA diameter (mm) and peak systolic velocity (cm/sec) were obtained; ITA flow was calculated from velocity and cross-sectional area. These findings were compared with the values obtained from 105 patients who were scheduled to undergo first-time (primary) coronary artery surgery during the same time period. In the reoperative group, preoperative mean ITA diameter was 2.26 +/- 0.06 mm; this was not significantly different from the primary group's mean ITA diameter of 2.15 +/- 0.04 mm (p = 0.09). Mean peak systolic velocity was 79.9 +/- 2.4 cm/sec and calculated systolic blood flow was 204.6 +/- 13.1 ml/min in the reoperative patients, as compared with 83.3 +/- 2.1 cm/sec and 189.5 +/- 8.6 ml/min in the primary group, respectively. Values were similar in both groups for the peak systolic velocity (p = 0.31) and calculated systolic blood flow (p = 0.32). These results suggest that previous heart surgery or sternotomy does not adversely affect ITA anatomy and flow characteristics. We conclude that ultrasonic imaging is an easily applicable technique for preoperative assessment of ITA in patients who have undergone previous sternotomy.

Research skills for medical students: a summer assistantship in family medicine.

This report presents a description of a summer research assistantship program for first- and second-year medical students. The program's goals are to develop and enhance students' research capabilities and to familiarize students with clinical research in family practice. The program provides sponsorship of a student by a faculty member, with a $1,120 stipend for students, as well as seminars on research skills. A pre- and post-program questionnaire and test documented significant improvements in students' perceived knowledge of research methodology. This structured summer research program is an effective way to introduce and emphasize essential research skills.

Is interleukin-6 concentration in the dialysate of continuous ambulatory peritoneal dialysis patients a prognostic parameter in peritonitis?

In continuous ambulatory peritoneal dialysis (CAPD) patients, peritonitis is a dangerous complication. Chemical examinations in the dialysate can be successfully used to assess permeability disturbances, hemostatic balance, and (for early detection and follow-up) cellular inflammatory reaction. In 7 CAPD patients (age: 50 +/- 15 years; dialysis duration: 40 +/- 24 months) with peritonitis episodes, and in 17 age-matched CAPD patients (age: 50 +/- 13 years; dialysis duration: 29 +/- 18 months) without peritonitis, we examined daily dialysate cell count (CC) and concentrations of albumin (ALB), immunoglobulin G (IgG), thrombin-antithrombin III complex (TAT), D-dimer (DD), and interleukin-6 (IL-6) after the long dwell (8-10 hours) over an interval of at least 14 days. In CAPD patients with peritonitis episodes, all parameters (CC, ALB, IgG, TAT, DD, IL-6) were significantly increased in the first days [IL-6 mean: 25,190 pg/mL (range: 2560-52,708 pg/mL) vs 66 pg/mL (range: 21-163 pg/mL)]; then, up to day 14 after successful therapy with antibiotics, the levels showed no differences as compared with CAPD patients without peritonitis. In the case of relapse of peritonitis (4 cases), concentration of IL-6 rose again on day 14, 1 day earlier than did the other parameters. Determination of IL-6 in the dialysate is a reliable prognostic parameter for the course of peritonitis (start, end, relapse) in CAPD patients.

Rational use of polymerase chain reaction--based detection of viral genomes in patients with serologic markers of hepatitis B or C virus infection.

We studied the value of additional diagnostic information obtained by detection of hepatitis B virus (HBV) DNA or hepatitis C virus (HCV) RNA using the qualitative polymerase chain reaction (PCR) in patients with serologic markers of hepatitis B or hepatitis C virus infection. In HBV infection, all HBsAg+HBeAg+ patients and all HBsAg+HBeAg- patients with alanine aminotransferase (ALT) levels > 100 U/L were positive for HBV-DNA by PCR, whereas in HBsAg+HBeAg- patients with ALT < 100 U/L 58% and in HBsAg+HBeAg- patients with normal aminotransferase 45% were found to be positive. In HBsAg+ patients no further clinically useful information can be obtained by PCR as the presence of HBsAg proves infection. However in three of 42 (7%) patients with markers of past HBV infection (antiHBs and/or antiHBc+) HBV-DNA was detected in the serum. Similarly, in some patients with acute hepatitis B HBV-DNA was demonstrable up to four months after the disappearance of HBsAg from serum, pointing to persistence of viremia despite the loss of serological markers of ongoing HBV infection. Demonstrating ongoing HBV infection in patients with serological markers of past infection is valuable additional information in only selected patients. In HCV infection, 10% of anti-HCV+ patients with increased ALT levels had a negative serum HCV-RNA. However, in 20% of those patients HCV-RNA was demonstrated in a serum sample collected later during follow-up, indicating that a single negative HCV-RNA determination cannot be taken as evidence for the resolution of infection.

Preparing nursing students for contemporary practice: restructuring the psychomotor skills laboratory.

The restructured laboratory experience offered a safe environment that supported student experimentation with psychomotor skills and self-initiated approaches to problem solving. Restructuring psychomotor laboratory experiences with emphasis on communication and conceptualization of principles supported students to begin addressing clinical problems with flexibility, creativity, and the premise for lifelong skill acquisition. Students who have skills that extend beyond technique will inevitably be better prepared to meet the demands of health care systems and patients now and in the future.

[Mutilating complex trauma of the pelvis]. / Ein mutilierendes Komplextrauma des Beckens.

Traumatic hemipelvectomy is a rare, but devastating pelvic injury with few survivors reported in the literature. We report on a 19-year-old motorcyclist with a near-total hemipelvectomy. After a complicated course, the patient survived with good potential for a functional level of activity. We review the experience of other authors and give details on the management of one of the most challenging injuries confronting surgeons. Successful treatment requires extraordinary efforts and multidisciplinary team cooperation.

The Interest Checklist: a factor analysis.

OBJECTIVE: The purpose of this study was to determine whether the 80 items on the Interest Checklist empirically cluster into the five categories of interests described by Matsutsuyu, the developer of the tool. METHOD: The Interest Checklist was administered to 367 subjects classified in three subgroups: students, working adults, and retired elderly persons. An 80-item correlation matrix was formed from the responses to the Interest Checklist for each subgroup and then used in a factor analysis model to identify the underlying structure or domains of interest. RESULTS: Results indicated that the Social Recreation theoretical category was empirically independent for all three subgroups; the Physical Sports and Cultural/Educational theoretical categories were empirically independent for only the college students and working adults; and the Manual Skills theoretical category was empirically independent for only the working adults. CONCLUSION: Although therapists should continue to be cautious in their interpretation of patients' Interest Checklist scores, the tool is useful for identifying patients' interests in order to choose meaningful activities for therapy.