Acute effect of running exercise on physiological Achilles tendon blood flow.

Sonographically detectable intratendinous blood flow (IBF) is found in 50%-88% of Achilles tendinopathy patients as well as in up to 35% of asymptomatic Achilles tendons (AT). Although IBF is frequently associated with tendon pathology, it may also represent a physiological regulation, for example, due to increased blood flow in response to exercise. Therefore, this study aimed to investigate the acute effects of a standardized running exercise protocol on IBF assessed with Doppler ultrasound (DU) "Advanced dynamic flow" in healthy ATs. 10 recreationally active adults (5 f, 5 m; 29±3 years, 1.72±0.12 m, 68±16 kg, physical activity 206±145 minute/wk) with no history of AT pain and inconspicious tendon structure performed 3 treadmill running tasks on separate days (M1-3) with DU examinations directly before and 5, 30, 60, and 120 minutes after exercise. At M1, an incremental exercise test was used to determine the individual anaerobic threshold (IAT). At M2 and M3, participants performed 30- minute submaximal constant load tests (CL1 /CL2 ) with an intensity 5% below IAT. IBF in each tendon was quantified by counting the number of vessels. IBF increased in five ATs from no vessels at baseline to one to four vessels solely detectable 5 minutes after CL1 or CL2 . One AT had persisting IBF (three vessels) throughout all examinations. Fourteen ATs revealed no IBF at all. Prolonged running led to a physiological, temporary appearance of IBF in 25% of asymptomatic ATs. To avoid exercise-induced IBF in clinical practice, DU examinations should be performed after 30 minutes of rest.

Is Sonographic Assessment of Intratendinous Blood Flow in Achilles Tendinopathy Patients Reliable?: Consistency of Doppler Ultrasound Modes and Intra- and Inter-observer Reliability.

PURPOSE: The purpose of this study was to investigate the consistency between different Doppler ultrasound (DU) modes as well as the intra- and inter-observer reliability of investigators with different experience level in assessing intratendinous blood flow (IBF) in Achilles tendinopathy patients. MATERIAL AND METHODS: 18 participants (36 Achilles tendons, AT) with Achilles tendinopathy (24 AT) were examined with power Doppler ultrasound (PDU), colour Doppler ultrasound (CDU) and "Advanced Dynamic Flow" (ADF) (Toshiba Xario SSA-660 A; 14MHz transducer) by 2 investigators (experienced, EI; inexperienced, II) in a test-retest design (M1/M2). A modified Öhberg score was used to quantify IBF. Data was analysed descriptively (absolute and relative). Consistency of the 3 modes was presented by Kendall's Coefficient of Concordance (Kendall's W). Intra- and inter-observer reliability were calculated by use of Kendall's tau b correlation coefficient. RESULTS: IBF was detected in 79-92% of symptomatic AT and in 33-50% of contralateral asymptomatic AT. Comparing the 3 modes, Kendall's W ranged from 0.97-0.98. Analysis of intra-observer reliability resulted in Kendall's tau 0.90-0.92 for EI and 0.84-0.87 for II. Inter-observer reliability resulted in Kendall's tau 0.64-0.69 in M1 and 0.68-0.70 in M2. CONCLUSION: The very good consistency between PDU, CDU and ADF indicates a comparable applicability for assessing IBF in ATs. Intra-observer reliability was high for both investigators, independent of experience. The moderate inter-observer reliability reflects the challenge in sonographic detection of intratendinous blood flow (IBF) amount.

Influence of Age and Pathology on Achilles Tendon Properties During a Single-leg Jump.

Prevalence of Achilles tendinopathy increases with age leading to a weaker tendon with predisposition to rupture. Conclusive evidence of the influence of age and pathology on Achilles tendon (AT) properties remains limited, as previous studies are based on standardized isometric conditions. The study investigates the influence of age and pathology on AT properties during single-leg vertical jump (SLVJ). 10 children (C), 10 asymptomatic adults (A), and 10 tendinopathic patients (T) were included. AT elongation [mm] from rest to maximal displacement during a SLVJ on a force-plate was sonographically assessed. AT compliance [mm/N]) and strain [%] was calculated by dividing elongation by peak ground reaction force [N] and length, respectively. One-way ANOVA followed by Bonferroni post-hoc correction (α=0.05) were used to compare C with A and A with T. AT elongation (p=0.004), compliance (p=0.001), and strain were found to be statistically significant higher in C (27±3 mm, 0.026±0.006 [mm/N], 13±2%) compared to A (21±4 mm, 0.017±0.005 [mm/N], 10±2%). No statistically significant differences (p≥0.05) was found between A and T (25±5 mm, 0.019±0.004 [mm/N], 12±3%). During SLVJ, tendon responded differently in regards to age and pathology with children having the most compliant AT. Higher compliance found in healthy tendons might be considered as a protective factor against load-related injuries.

Tendon Adaptation to Sport-specific Loading in Adolescent Athletes.

Tendon adaptation due to mechanical loading is controversially discussed. However, data concerning the development of tendon thickness in adolescent athletes is sparse. The purpose of this study was to examine possible differences in Achilles (AT) and patellar tendon (PT) thickness in adolescent athletes while considering age, gender and sport-specific loading. In 500 adolescent competitive athletes of 16 different sports and 40 recreational controls both ATs and PTs were sonographically measured. Subjects were divided into 2 age groups (< 13; ≥ 13 years) and 6 sport type categories (ball, combat, and water sports, combined disciplines, cycling, controls). In addition, 3 risk groups (low, moderate, high) were created according to the athlete's risk of developing tendinopathy. AT and PT thickness did not significantly differ between age groups (AT/PT:<13: 5.4±0.7 mm/3.6±0.5 mm;≥13: 5.3±0.7 mm/3.6±0.5 mm). In both age groups males presented higher tendon thickness than females (p<0.001). AT thickness was highest in ball sports/cyclists and lowest in controls (p≤0.002). PT thickness was greatest in water sports and lowest in controls (p=0.02). High risk athletes presented slightly higher AT thickness compared to the low risk group (p=0.03). Increased AT and PT thickness in certain sport types compared to controls supports the hypothesis of structural tendon adaptation due to sport-specific loading.

Ultrasound Applied to Subcutaneous Fat Tissue Measurements in International Elite Canoeists.

Subcutaneous adipose tissue (SAT) measurements with ultrasound have recently been introduced to assess body fat in elite athletes. However, appropriate protocols and data on various groups of athletes are missing. We investigated intra-rater reliability of SAT measurements using ultrasound in elite canoe athletes. 25 international level canoeists (18 male, 7 female; 23±4 years; 81±11 kg; 1.83±0.09 m; 20±3 training h/wk) were measured on 2 consecutive days. SAT was assessed with B-mode ultrasound at 8 sites (ISAK): triceps, subscapular, biceps, iliac crest, supraspinal, abdominal, front thigh, medial calf, and quantified using image analysis software. Data was analyzed descriptively (mean±SD, [range]). Coefficient of variation (CV%), intraclass correlation coefficient (ICC, 2.1) and absolute (LoA) and ratio limits of agreement (RLoA) were calculated for day-to-day reliability. Mean sum of SAT thickness was 30.0±19.4 mm [8.0, 80.1 mm], with 3.9±1.8 mm [1.2 mm subscapular, 8.0 mm abdominal] for individual sites. CV for the sum of sites was 4.7%, ICC 0.99, LoA 1.7±3.6 mm, RLoA 0.940 ( * /÷1.155). Measuring SAT with ultrasound has proved to have excellent day-to-day reliability in elite canoe athletes. Recommendations for standardization of the method will further increase accuracy and reproducibility.

[Tendinopathies of the Lower Extremities in Sport--Diagnostics and Therapy]. / Tendinopathien der unteren Extremität im Sport--Diagnostik und Therapie.

Tendinopathies are frequently the cause of chronic, load-dependent complaints of the lower extremity. Commonly, the large tendons of the ankle and knee joints are affected, especially the Achilles and patellar tendons. Repeated overuse in sports and/or daily activities is assumed as the aetiology. Besides the clinical examination including a comprehensive anamnesis of pain and training/loading, sonographic imaging has a high training/loading relevance for the diagnosis of tendon pathologies of the lower extremity. Training concepts are considered in first line as the treatment of choice. A combination with physical therapy interventions can be useful. In cases of a more severe pathology and long-standing complaints multimodal therapeutic options should be employed. The use of surgical treatment procedures should only be taken into account in case of failed response to conservative treatment.

Prevalence of Achilles and patellar tendinopathy and their association to intratendinous changes in adolescent athletes.

Achilles (AT) and patellar tendons (PT) are commonly affected by tendinopathy in adult athletes but prevalence of symptoms and morphological changes in adolescents is unclear. The study aimed to determine prevalence of tendinopathy and intratendinous changes in ATs and PTs of adolescent athletes. A total of 760 adolescent athletes (13.0 ± 1.9 years; 160 ± 13 cm; 50 ± 14 kg) were examined. History, local clinical examination, and longitudinal Doppler ultrasound analysis for both ATs and PTs were performed including identification of intratendinous echoic changes and vascularization. Diagnosis of tendinopathy was complied clinically in case of positive history of tendon pain and tendon pain on palpation. Achilles tendinopathy was diagnosed in 1.8% and patellar tendinopathy in 5.8%. Vascularizations were visible in 3.0% of ATs and 11.4% of PTs, hypoechogenicities in 0.7% and 3.2% as well as hyperechogenicities in 0% and 0.3%, respectively. Vascularizations and hypoechogenicities were statistically significantly more often in males than in females (P ≤ 0.02). Subjects with patellar tendinopathy had higher prevalence of structural intratendinous changes than those without PT symptoms (P ≤ 0.001). In adolescent athletes, patellar tendinopathy is three times more frequent compared with Achilles tendinopathy. Longitudinal studies are necessary to investigate physiological or pathological origin of vascularizations and its predictive value in development of tendinopathy.

Blood lactate concentrations are mildly affected by mobile gas exchange measurements.

We sought to investigate the effects of wearing a mobile respiratory gas analysis system during a treadmill test on blood lactate (bLa) concentrations and commonly applied bLa thresholds. A total of 16 recreational athletes (31±3 years, VO2max: 58±6 ml · min(-1) · kg(-1)) performed one multistage treadmill test with and one without gas exchange measurements (GEM and noGEM). The whole bLa curve, the lactate threshold (LT), the individual anaerobic thresholds according to Stegmann (IATSt) and Dickhuth (IATDi), and a fixed bLa concentration of 4 mmol ∙ l(-1) (OBLA) were evaluated. The bLa curve was shifted slightly leftward in GEM compared to noGEM (P<0.05), whereas the heart rate response was not different between conditions (P=0.89). There was no difference between GEM and noGEM for LT (2.61±0.34 vs. 2.64±0.39 m · s(-1), P=0.49) and IATSt (3.47±0.42 vs. 3.55±0.47 m · s(-1), P=0.12). However, IATDi (3.57±0.39 vs. 3.66±0.44 m · s(-1), P<0.01) and OBLA (3.85±0.46 vs. 3.96±0.47 m · s(-1), P<0.01) occurred at slower running velocities in GEM. The bLa response to treadmill tests is mildly affected by wearing a mobile gas analysis system. This also applies to bLa thresholds located at higher exercise intensities. While the magnitude of the effects is of little importance for recreational athletes, it might be relevant for elite athletes and scientific studies.

[Intra- and interrater variability of sonographic investigations of patella and achilles tendons]. / Intra- und interobserver Variabilität sonografischer Untersuchungen an Patella- und Achillessehnen.

BACKGROUND: Clinical examinations of tendon disorders routinely include ultrasound examinations, despite the fact that availability of data concerning validity criteria of these measurements are limited. The present study therefore aims to evaluate the reliability of measurements of Achilles- and Patella tendon diameter and in the detection of structural adaptations. MATERIALS AND METHODS: In 14 healthy, recreationally active subjects both asymptomatic Achilles (AT) and patella tendons (PT) were measured twice by two examiners in a test-retest design. Besides the detection of anteroposterior (a.p.-) and mediolateral (m.l.-) diameters, areas of hypoechogenicity and neovascularisation were registered. Data were analysed descriptively with calculation of test-retest variability (TRV), intraclass-correlation coefficient (ICC) and Bland and Altman's plots with bias and 95 % limits of agreement (LOA). RESULTS: Intra- and interrater differences of AT- and PT-a.p.-diameter varied from 0.2 - 1.2 mm, those of AT- and PT-m.l-diameter from 0.7 - 5.1 mm. Areas of hypoechogenicity were visible in 24 % of the tendons, while 15 % showed neovascularisations. Intrarater AT-a.p. -diameters showed sparse deviations (TRV 4.5 - 7.4 %; ICC 0.60 - 0.84; bias -0.05 - 0.07 mm; LOA -0.6 - 0.5 to -1.1 - 1.0 mm), while interrater AT- and PT-m.l.-diameters were highly variable (TRV 13.7 - 19.7 %; ICC 0.11 - 0.20; bias -1.4 - 4.3 mm; LOA -5.5 - 2.7 to -10.5 - 1.9 mm). CONCLUSION: Our results suggest that the measurement of AT- and PT-a.p. -diameters is a reliable parameter. In contrast, reproducibility of AT- and PT-m.l.-diameters is questionable. The study corroborates the presence of hypoechogenicity and neovascularisation in asymptomatic tendons.

Is EMG of the lower leg dependent on weekly running mileage?

Neuromuscular activity of the lower leg is dependent on the task performed, speed of movement and gender. Whether training volume influences neuromuscular activity is not known. The EMG of physically active persons differing in running mileage was analysed to investigate this. 55 volunteers were allocated to a low (LM: < 30 km), intermediate (IM: > 30 km & < 45 km) or high mileage (HM: > 45 km) group according to their weekly running volume. Neuromuscular activity of the lower leg was measured during running (3.33 m·s - 1). Mean amplitude values for preactivation, weight acceptance and push-off were calculated and normalised to the mean activity of the entire gait cycle.Higher activity in the gastrocnemius group was observed in weight acceptance in LM compared to IM (+30%) and HM (+25%) but lower activity was present in the push-off for LM compared to IM and HM. For the peroneal muscle, differences were present in the push-off where HM showed increased activity compared to IM (+24%) and LM (+60%). The tibial muscle revealed slightly lower activity during preactivation for the high mileage runners. Neuromuscular activity differs during stance between the high and intermediate group compared to low mileage runners. Slight adaptations in neuromuscular activation indicate a more target-oriented activation strategy possibly due to repetitive training in runners with higher weekly mileage.

Fluorescence in situ hybridization of metaphase chromosomes in suspension.

PURPOSE: To describe a new method for FISH analysis of metaphase chromosomes in suspension. MATERIALS AND METHODS: Metaphase chromosomes in suspension were isolated from a Chinese hamster human hybrid cell line, 314-2 (1) Y, and a human cell line, GM 130B. During suspension hybridization, specific chromosomes were labeled from these two cell lines using either biotin-labeled human genomic DNA, a directly labeled human pancentromere DNA probe or a chromosome #1 locus-specific probe. RESULTS: The method allows, for the first time, recovery of large numbers of isolated individual hybridized chromosomes with good morphology for both human x hamster hybrid and human cell lines. The results showed that 46-73% of the starting number of total chromosomes can be recovered after a FISH in suspension procedure. The well-preserved morphology of hybridized metaphase chromosomes allowed (1) rapid detection of individual human and hamster chromosome aberrations, (2) rapid counting of the painted human chromosomes and (3) fast, clear detection of chromosome region-specific probes. This method offers a new tool to assay chromosomes and DNA: it offers the possibility to develop new techniques for sorting chromosomes based on FISH signals, for early detection and screening of genetic diseases and for bulk measurement of both balanced or unbalanced chromosomal exchanges and rearrangements. CONCLUSION: The potential of the method described should facilitate fast, sensitive population monitoring, and increase sensitivity of the measurements in chromosome-based biodosimetry.

Bacteremic pneumococcal pneumonia in HIV-seropositive and HIV-seronegative adults.

STUDY OBJECTIVES: To compare the demographic, clinical, laboratory, and microbiological data, and the hospital course and outcome of HIV-seropositive and HIV-seronegative adults with bacteremic pneumococcal pneumonia. DESIGN: Retrospective observation study conducted over a 2-year period. SETTING: Academic teaching hospital attached to the University of the Witwatersrand, Johannesburg, South Africa. PATIENTS: Consecutive patients with bacteremic pneumococcal pneumonia were identified on the basis of positive blood culture results. INTERVENTIONS: All available demographic, clinical, routine laboratory, radiographic, and microbiological data were recorded retrospectively for each of the patients, and the combined data for the HIV-seropositive patients were compared with those of the HIV-seronegative patients. MEASUREMENT AND RESULTS: A total of 112 patients (31 HIV-seropositive and 81 HIV-seronegative patients) were entered into the study. The HIV-seropositive patients were significantly younger than the HIV-seronegative patients (32.8 vs 39.6 years old) and had lower admission hemoglobin (11.8 vs 13.4 g/dL), WBC count (10.3 vs 14.3 x 10(9)/L), serum albumin (31 vs 36 g/L), sodium (129 vs 132 mmol/L), and potassium (3.0 vs 3.5 mmol/L), respectively. Although the HIV-seropositive patients appeared to have more multilobar pulmonary consolidation on the chest radiograph than the HIV-seronegative patients (60% vs 34%), this did not quite reach statistical significance. In addition, the HIV-seropositive patients had significantly more infections (48.4% vs 20.8%) with pneumococcal serogroups/serotypes (serogroups 6, 19, 23, and serotype 14) that are found more commonly in children, and they also had more penicillin-resistant isolates (13% vs 2.5%) than the HIV-seronegative patients, respectively. Similarly, it was noted that when these data were analyzed according to gender (irrespective of HIV status), women had significantly more infections than men (47% vs 21%) with serogroups/serotypes that are usually found in children, more penicillin-resistant isolates (15% vs 1%), and more co-trimoxazole-resistant isolates (21% vs 5%), respectively. There were no differences noted in any of the other parameters, including initial APACHE (acute physiology and chronic health evaluation) II score, PaO2/fraction of inspired oxygen ratio, duration of temperature, duration of IV therapy, duration of hospitalization, complications, and outcome, when comparing HIV-seropositive and HIV-seronegative patients. Two patients in each group died. CONCLUSIONS: The clinical features of bacteremic pneumococcal pneumonia are similar in HIV-seropositive and HIV-seronegative patients. Although differences are noted in various laboratory and microbiological parameters, they do not appear to have an impact on outcome.

Preimplantation genetic analysis of translocations: case-specific probes for interphase cell analysis.

Carriers of balanced translocations show an increased risk of infertility and spontaneous abortions, because of errors in gametogenesis, and constitute a significant fraction of patients seeking assisted reproduction. The objective of this study was to design approaches for preimplantation diagnosis of chromosome translocations and to apply such techniques to the selection of chromosomally normal or balanced embryos prior to their transfer to the mother's womb. Three slightly different approaches were assessed by means of chromosome-specific, non-isotopically labeled DNA probes and an assay based on fluorescence in situ hybridization- to score and characterize chromosomes in single blastomeres biopsied from embryos on their third day of development. The three approaches were used for preimplantation genetic diagnosis involving four couples who had enrolled in our IVF program and in which one of the partners was a carrier of one of the following translocations: 46,XX,t(12;20)(p 13.1 ;q 13.3), 46,XY,t(3;4) (p24;p15), 45,XY,der(14;15)(10q;10q), and 46,XY,t(6;11) (p22.1;p15.3). A total of 33 embryos were analyzed, of which 25 (75.8%) were found to be either unbalanced or otherwise chromosomally abnormal. Only a single embryo could be transferred to patients A and D, whereas three embryos were transferred to patient B in a total of two IVF cycles. Transfer of two embryos to patient C resulted in an ongoing pregnancy. Re-analysis of non-transferred embryos with additional probes confirmed the initial results in 95% (20/21) of the cases. In conclusion, case-specific translocation tests can be applied to any translocation carrier for the selection of normal or chromosomally balanced embryos prior to embryo transfer. This is expected significantly to increase the success rates in IVF cycles of translocation carriers, while preventing the spontaneous abortion or birth of abnormal offspring.

Epididymal sperm aneuploidies in three strains of rats detected by multicolor fluorescence in situ hybridization.

A multicolor fluorescence in situ hybridization (FISH) method was developed to detect aneuploidy and diploidy in epididymal sperm of rats using DNA probes specific for chromosomes 4 and Y. Fourteen healthy young-adult rats from three strains were evaluated: inbred Fisher 344/N/ehs, outbred Sprague-Dawley, and outbred WU Wistar/CPB. The hybridization efficiency of the FISH procedure was > 99.9%, the sex-ratio in sperm was approximately 1 as expected, and there was no significant variation among two independent scorers. No significant variations were detected within or among strains in the frequencies of sperm disomy for chromosome 4 (1-6.5 per 10,000 cell per animal) or the Y chromosome (0-2.5 per 10,000 cells per animal). There was a trend toward increased variation among Wistar rats. The frequencies of sperm-carrying hyper- and hypohaploidy for chromosome 4 were similar, suggesting a symmetrical mechanism of chromosome gain and loss during meiosis. The frequencies of Y-Y-4-4 sperm, which represent genomic meiosis II errors, did not differ significantly across strains (0.1-0.7 per 10,000 cells per strain). This FISH method for detecting aneuploidy in rat epididymal sperm provides a promising interspecies biomarker of male germ cell aneuploidy and introduces the rat as an animal model for investigating the heritable risk to offspring associated with paternal genotype, physiology, and exposure to environmental mutagens. There appear to be no significant differences among young healthy rats, mice, and men in the baseline frequencies of sperm with Y chromosomal disomy, the only chromosome for which data currently exists for all three species.

Carrier-specific breakpoint-spanning DNA probes: an approach to preimplantation genetic diagnosis in interphase cells.

Carriers of chromosomal inversions or other balanced rearrangements represent a significant fraction of patients in in-vitro fertilization (IVF) programmes due to recurrent reproductive problems. In most cases, chromosomal imbalance in fertilized oocytes is incompatible with embryo survival leading to increased rates of spontaneous abortions. Assuming that a fraction of the germ cells is karyotypically normal, these patients would greatly benefit from efficient procedures for generation and use of breakpoint-specific DNA hybridization probes in preconception and preimplantation genetic diagnosis (PGD). We describe the generation of such patient-specific probes to discriminate between normal and aberrant chromosomes in interphase cells. First, a large insert DNA library was screened for probes that bind adjacent to the chromosomal breakpoints or span them. Then, probe and hybridization parameters were optimized using white blood cells from the carrier to increase in hybridization signal intensity and contrast. Finally, the probes were tested on target cells (typically polar bodies or blastomeres) and a decision about the colour labelling scheme was made, before the probes can be used for preconception or preimplantation genetic analysis. Thus, it was demonstrated that cells with known structural abnormalities could be detected, based on hybridization of breakpoint spanning yeast artificial chromosome (YAC) DNA probes in interphase cells.

Chemotherapy induces transient sex chromosomal and autosomal aneuploidy in human sperm.

Each year more than 20,000 children and young persons of reproductive age are exposed to known mutagens in the form of chemo- and/or radiotherapy for cancer in the States. As more of these treatments are effective there is growing concern that genetic defects are introduced in the germ cells of these young patients. It is well documented for male rodents that treatment with chemo- and radio-therapeutic agents before mating can cause genetic damage in the germ line, and the magnitude of heritable effects depends on the spermatogenic cell stage treated. Similar germinal effects are suspected to occur in humans but remain unproven. Hodgkin's disease (HD) is an example of a malignancy which is typically diagnosed during a patient's reproductive years. In our study we observed eight male HD patients who were treated with NOVP (Novanthrone, Oncovin, Vinblastine, Prednisone) chemotherapy. We evaluated sperm aneuploidy using multi-colour fluorescence in situ hybridization (FISH), and found approximately 5-fold increases in sperm with disomies, diploidies and complex genotypes involving chromosome X, Y and 8. Increases in sex chromosome aneuploidies arose from segregation errors at meiosis I as well as meiosis II. The aneuploidy effects were transient, however, declining to pretreatment levels within approximately 100 days after the end of the therapy. When compared with normal men, some HD patients showed higher proportions of certain sperm aneuploidy types even before their first therapy.

The therapeutic value of nimodipine in experimental focal cerebral ischemia. Neurological outcome and histopathological findings.

Recent studies suggest that nimodipine, a potent calcium-channel antagonist that causes significant cerebrovascular dilatation, may improve neurological outcome after acute experimental permanent focal cerebral ischemia when given before or immediately after occlusion of the middle cerebral artery (MCA) in various animals. The authors describe the effect of nimodipine on cerebral ischemia in a rat model. At 1, 4, or 6 hours after occlusion of the MCA, rats were treated in a double-blind technique with either nimodipine, placebo, or saline. Neurological and neuropathological evaluation was performed at 24 hours. Neurological outcome was better in rats treated with nimodipine 1, 4, or 6 hours after occlusion (p less than 0.001, p less than 0.01, p less than 0.05 respectively), and the size of areas of infarction was statistically smaller in nimodipine-treated groups (p less than 0.01, p less than 0.01, p less than 0.05, respectively) when compared with control rats treated with saline or placebo. The best neurological outcome and the smallest area of infarction were found in nimodipine-treated rats 1 hour after occlusion. Compared with controls, the size of the periphery of the infarcted area was smaller in nimodipine-treated rats. The results show that nimodipine improves neurological outcome and decreases the size of infarction when administered up to 6 hours after ischemic insult. These results suggest a possible mechanism of action of nimodipine on the "penumbra" of the ischemic area.