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PubMed1985

Bone remodeling in response to in vivo fatigue microdamage.

It has been suggested that osteonal remodeling is triggered by bone microdamage. The validity of this theory rests on the assumption that loading within the physiological range will produce substantial microdamage with relatively few load cycles. The object of the first experiment was to determine threshold values required to consistently produce fatigue microdamage in vivo. The left forelimb of five groups of dogs, characterized by different strain levels and different numbers of load cycles, were loaded in three point bending. The number of microscopic fields which contained some microdamage was calculated as a percentage of the total number of fields. This experiment indicated that loads producing strains as low as 1500 microstrain on the radius and 1400 microstrain on the ulna for 10,000 cycles will produce significant bone microdamage. A second experiment was performed to verify this threshold and to determine whether microcracks are associated with the initiation of bone remodeling. Procedures in this experiment were the same as those in the first, except that all dogs were loaded in such a way as to produce strains on the radius of 1500 microstrain for 10,000 cycles, and the dogs were sacrificed 1-4 days after loading. The loaded limb demonstrated significantly more microdamage than the control limb (p = 0.03). Moreover, we observed 44 times as many microcracks in association with resorption spaces as expected by chance alone. These data support the hypothesis that fatigue microdamage is a significant factor in the initiation of intracortical bone remodeling.

Animals↗
PubMed2006

Rapid quantification of Vibrio vulnificus in clams (Protochaca staminea) using real-time PCR.

We used a rapid DNA extraction and purification method to obtain the DNA from Vibrio vulnificus seeded into clam tissue homogenates for real-time PCR quantification of the organism. Without enrichment, the limit of detection was 1 x 10(2) cfu/g of tissue with a linear detection range of 1 x 10(2) to 1 x 10(8) cfu/g. With a 5 h non-selective enrichment, the limit of detection was 1 cfu/g of tissue with a linear detection range of 1 to 1 x 10(6) cfu/g of tissue. We found a 10-fold higher detection limit with seeded clam tissue homogenates compared to pure culture in TSB(+). The detection limits with pure broth culture and seeded tissue homogenates were identical, 1 cfu/ml and 1 cfu/ml, respectively, following 5 h non-selective enrichment. However, the Ct value with tissue homogenates was about 3 threshold cycles higher than with pure culture.

Animals↗
PubMed2004

Prognostic use of mean ovarian volume in in vitro fertilization cycles: a prospective assessment.

OBJECTIVE: To determine the predictive value and to define prognostic threshold measurements for mean ovarian volume (MOV) in patients undergoing IVF. DESIGN: Prospective cohort analysis. SETTING: Tertiary care center. PATIENT(S): Two hundred sixty-seven patients. INTERVENTION(S): Transvaginal ultrasound before starting gonadotropins. MAIN OUTCOME MEASURE(S): Number of oocytes retrieved, basal hormone levels, and cycle outcomes. RESULT(S): The MOV for the population was 4.78 +/- 2.6 cm(3) (range 0.9-21.1 cm(3)). The MOV significantly correlated with the majority of prestimulation and poststimulation IVF parameters. Threshold analysis demonstrated a lower pregnancy rate associated with a MOV of <2 cm(3) (31.6% vs. 55.6%). Threshold analysis revealed a trend toward higher cancellation rate associated with a MOV of <2 cm(3) (21.1% vs. 7.3%). CONCLUSION(S): Although MOV correlated with IVF stimulation parameters, its use as an adjunct in counseling patients during IVF appears to be of limited value. A MOV <2 cm(3) was associated clinically with a higher cancellation rate (21.1%) and a lower pregnancy rate (31.6%) in those cycles not cancelled. However, these values do not deviate far from the mean national IVF outcome rates. There was no absolute MOV that was predictive of pregnancy outcome or cycle cancellation.

Cohort Studies↗
PubMedDate not supplied

Pharmacodynamics of 5-fluorouracil combined with carboplatin in patients with head and neck cancer.

The objective of our work was to investigate the pharmacodynamics of 5-fluorouracil (5-FU) in 23 patients with head and neck cancer treated with carboplatin (360 mg/m2) followed by 5 day continuous infusion of 5-FU (lg/m2/day). The pharmacokinetic profile of 5-FU was characterized for 36 cycles and was compared with the patient's tolerance. Toxic cycles (> or = grade 1, WHO grading) were associated with higher values of area under the serum concentration-time curve (AUC) than those of non toxic cycles. In addition, AUC values of 37000 ng.h.ml-1 and 21000 ng.h.ml-1 for the entire cycle and the half-cycle respectively were found to be predictive of toxicity. These threshold values are identical to those determined in our previous study with the cisplatin-5-FU regimen. Hence, patients treated with carboplatin and infusional 5-FU might benefit from 5-FU blood level, monitoring using the same dose adjustment diagram.

Adult↗
PubMed1995

Accuracy of breath-by-breath analysis of flow-volume loop in identifying sleep-induced flow-limited breathing cycles in sleep apnoea-hypopnoea syndrome.

1. Inspiratory flow limitation is involved in the pathophysiology of sleep-related breathing disorders. Since the definition of flow-limited cycle is based on a dissociation between flow and respiratory efforts, identification of inspiratory flow limitation requires upper airway or intrathoracic pressure measurements. We examined the accuracy of the analysis of the flow-volume loop of a tidal breath in identifying inspiratory flow limitation during sleep in ten patients with a sleep apnoea-hypopnoea syndrome. 2. Measurements were taken during continuous positive airway pressure trials. After data acquisition, the presence of inspiratory flow limitation was identified by the presence of an inspiratory plateau or decrease in inspiratory flow independently of the increase in inspiratory efforts. The flow-volume loop was reconstructed for each breathing cycle by plotting the instantaneous flow and the tidal volume. The instantaneous inspiratory and expiratory flows were measured at 50% of the respective portion of the tidal volume, and a breath-by-breath analysis of the mid-tidal volume-flow ratio (inspiratory/expiratory ratio) was obtained. The analysis of the flow-volume loop was compared with standard inspiratory flow limitation criteria using different values of the inspiratory/expiratory ratio threshold, below which breathing cycles were classified as flow-limited. With a lower limit of the normal inspiratory/expiratory ratio threshold of 0.97, the sensitivity and specificity of the method were both 76%. In each subject, the proportion of breathing cycles identified as flow-progressively decreased with an increasing positive pressure level.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1981

Induction of chromosome shattering by ultraviolet irradiation and caffeine: comparison of whole-cell and partial-cell irradiation.

Synchronized and asynchronously growing cells of a V79 sub-line of the Chinese hamster were either whole-cell irradiated ( gamma, 254 nm) or laser-UV-microirradiated ( gamma, 257 nm). Post-incubation with caffeine (1-2 mM) often resulted in chromosome shattering, which was a rare event in the absence of this compound. In experiments with caffeine, the following results were obtained. Shattering of all the chromosomes of a cell (generalized chromosome shattering, GCS) was induced by whole-cell irradiation at the first post-irradiation mitosis when the UV fluence exceeded a "threshold" value in the sensitive phases of the cell cycle (G1 and S). GCS was also induced by laser-UV-microirradiation of a small part of the nucleus in G1 or S whereas microirradiation of cytoplasm beside the nucleus was not effective. An upper limit of the UV fluence in the non-irradiated nuclear part due to scattering of the microbeam was experimentally obtained. This UV fluence was significantly below the threshold fluence necessary to induce GCS in whole-cell irradiation experiments. In other cells, partial nuclear irradiation resulted in shattering of a few chromosomes only, while the majority remained intact (partial chromosome shattering, PCS). G1/early S was the most sensitive phase for induction of GCS by whole-cell and partial nuclear irradiation. The frequency of PCS was observed to increase when partial nuclear irradiation was performed either at lower incident doses or at later stages of S. We suggest that PCS and GCS indicate 2 levels of chromosome damage which can be produced by the synergistic action of UV irradiation and caffeine. PCS may be restricted to microirradiated chromatin whereas GCS involves both irradiated and unirradiated chromosomes in the microirradiated nucleus.

Animals↗
PubMed2005

Repeated testing of basal FSH levels has no predictive value for IVF outcome in women with elevated basal FSH.

BACKGROUND: It is a common practice to repeatedly test the level of basal FSH early in the cycle and to start IVF treatment only when the FSH level is below a certain threshold value. This is based on the idea that these women will respond better to ovarian stimulation when the basal FSH level is lower at the start of the cycle. The aim of this study is to assess the value of this practice. METHODS: Between January 1995 and January 2003, 39 women were identified. These women underwent two IVF treatment cycles within a 12 month period. The basal FSH level prior to each of these cycles was known to have changed. The treatment cycles were divided into cycles with a high basal FSH (> or =10 IU/l) and cycles with a low basal FSH (<10 IU/l). RESULTS: The 39 women underwent a total of 78 treatment cycles (in the first cycle 20 had elevated level of FSH and 19 had low FSH and vice versa in the second cycle). Therefore, there were 39 cycles with high FSH and 39 cycles with low FSH. There was obviously no live birth in the first treatment cycle, hence the reason for the patient undergoing another treatment cycle within 12 months of the first one. In the high FSH group, six became pregnant [pregnancy rate (PR) = 15.4%] and five delivered [live birth rate (LBR) = 12.8%]. In the low FSH group, three became pregnant (PR = 7.7%) and two delivered (LBR = 5.1%). The difference in PR and LBR, however, was not significant. Neither were there significant differences between the two groups with regard to the number of oocytes collected, oocytes fertilized, embryos transferred or miscarriage rate. CONCLUSION: The results of this study reveal that women who are poor responders or with reduced ovarian reserve have a poor outcome and repeatedly testing them will add no value. Cycling women with a history of elevated FSH should be offered treatment without further delay. Delaying treatment for these women could be counterproductive, as they may have to wait for many months, during which time they are getting older and closer to their menopause.

Adult↗
PubMed1996

Serum testosterone, 5-alpha-dihydrotestosterone and different sex characteristics in male fallow deer (Cervus dama): a long-term experiment with accelerated photoperiods.

To investigate the photoperiodic influence on androgen, testis volume, neck girth, and antler-cycles, five fallow bucks were exposed consecutively to different accelerated photoperiodic cycles (three 6-month, three 4-month, and one 3-month cycle). All parameters immediately followed artificial light cycles. Unlike in natural conditions, antler casting, regrowth, and velvet shedding occurred at decreasing day-lengths. The experiment provided further evidence that in fallow bucks the reproductive system is under strictly photoperiodic control and directly and/or indirectly dictates the course of the antler cycle via gonadal hormones. Depending on the test-system, the experiment revealed similar threshold values for the effect of testosterone (T) and/or 5-alpha-dihydrotestosterone (DHT) concentrations on the antler cycle as previously detected in fallow bucks living under natural conditions. Antlers were cast when T levels dropped below 3 ng/ml, and velvet shedding occurred after T and/or DHT values reached at least 5 to 7 ng/ml. In all cases, amplitudes of androgens remained lower than observed under natural conditions. Frequently during early antler growth, DHT values appeared higher than T levels. With increasing acceleration of the photoperiod, the antler cycle achieved limits of adaptation. The faster the photoperiods were accelerated, the smaller the antlers were developed. In addition, the antler tips were porous, blunt, and not completely mineralized. In all animals, accelerations of the photoperiods evoked phase displacements between measured parameters, pointing to an increasing internal desynchronisation. The present results indicate that the whole reproductive system of fallow deer is directly controlled by the photoperiod and that related morphological and physiological processes are indirectly determined by photoperiodic changes.

Animals↗
PubMed2005

Quantitative polymerase chain reaction used for the rapid detection of Carnobacterium species from French soft cheeses.

An identification method by PCR, specific to the Carnobacterium genus, was optimised by testing it on 28 bacterial strains. Primers from the literature were tested to differentiate Carnobacterium strains present among various bacterial species. The DNA of Carnobacterium species (C. alterfunditum, C. divergens, C. funditum, C. gallinarum, C. inhibens, C. maltaromaticum, C. mobile, C. viridans), specifically amplified by the Cb1-Cb2R primer couple at a hybridization temperature of 69 degrees C, gave only one band of 340 bp. The validation of this technique was carried out on a French soft cheese made with pasteurised milk inoculated with C. maltaromaticum LMA 28. Using classical PCR, detection was not possible for decimal dilutions of the cheese above 1 g L(-1). With Sybr Green I real time PCR, the specificity of the reaction was confirmed by the T(m) value. The standard curve constructed using the main threshold cycle and various concentrations of C. maltaromaticum LMA 28 (ranging from 10(0) to 10(8) cfu mL(-1)) showed good linearity and a sensitivity limit of > or = 10(4) cfu g(-1) of cheese. This technique was applied on commercially available cheeses made from raw cow's milk. The Sybr Green I real time PCR method constitutes an effective and easy-to-perform method to quantify Carnobacterium sp. in cheese.

Animals↗
PubMed2005

Influence of the estrous cycle on urodynamic and morphometric measurements of the lower portion of the urogenital tract in dogs.

OBJECTIVES: To compare the values of the urodynamic parameters of the lower portion of the urinary tract and vaginourethral measurements obtained during the phases of the estrous cycle in dogs and determine possible functional or anatomic modifications of the lower portion of the urinary tract associated with those phases. ANIMALS: 7 adult female Beagles. PROCEDURE: Urethral pressure profilometry, diuresis cystometry, and vaginourethrography were performed in each dog during proestrus; estrus; early, mid, and late diestrus; and early and late anestrus. The maximum urethral pressure (MUP), maximum urethral closure pressure (MUCP), urethral functional and anatomic profile lengths (UFPL and UAPL, respectively), integrated pressure, threshold pressure, threshold volume, compliance, urethral length, and vaginal length and width were measured. RESULTS: For all measurements, significant interindividual variation was detected. Integrated and threshold pressures, APL, and each morphometric value significantly increased from late anestrus to proestrus. Compared with other phases, MUP, MUCP, and integrated pressure values were significantly lower in estrus and early diestrus; UAPL and UFPL values were significantly lower in late diestrus. At each cycle phase in old dogs, MUP, MUCP, threshold pressure, and vaginal length and width were significantly lower (except in proestrus for vaginal measurements) and threshold volume and compliance values were significantly higher, compared with middle-aged dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Urodynamic and morphometric measurements of the lower portion of the urogenital tract are affected by the changes in hormonal balance that occur during the estrous cycle. In sexually intact female dogs, estrous phase determination is important for the interpretation of urodynamic data.

Analysis of Variance↗
PubMed1995

A prospective evaluation of ifosfamide-related nephrotoxicity in children and young adults.

BACKGROUND: Ifosfamide has been associated with proximal renal tubular dysfunction resembling Fanconi-like syndrome and leading to rickets in young children. The characteristic manifestations of this nephrotoxicity include phosphaturia and hypophosphatemia, glycosuria, aminoaciduria, renal tubular acidosis, and urinary loss of low molecular weight serum proteins. However, the relationship between acute ifosfamide nephrotoxicity, which is frequently subclinical, and long term renal damage is unclear. In this prospective study, the laboratory features of ifosfamide-induced acute nephrotoxicity were characterized further and correlated with the development of chronic nephropathy. METHODS: The renal function of newly diagnosed children and young adults with high risk sarcomas was followed during therapy with a high dose ifosfamide-containing regimen. Serum and urine were collected regularly immediately before and after 5-day cycles of ifosfamide throughout treatment for determination of the fractional excretion of electrolytes (sodium, potassium, phosphate, magnesium, calcium) and glucose and urinary excretion of amino acids and beta 2-microglobulin. RESULTS: Significant changes in the renal threshold of phosphate excretion, the fractional excretion of calcium and glucose, and the urinary excretion of beta 2-microglobulin were observed when comparing pretreatment values with those at the end of a 5-day treatment cycle. The median renal threshold of phosphate excretion decreased from 1.22 to 0.82 mmol/L (P < 0.0001). The median fractional excretions of calcium and glucose increased from 1.05% to 1.68% (P < 0.0001) and 0.05% to 0.08% (P = 0.0006), respectively. Beta 2-microglobulin excretion increased by 70-fold from 0.02 to 1.42 mg/mmol (P < 0.0001). Except for glucose and beta 2-microglobulin excretion, renal parameters returned to baseline before the next ifosfamide treatment cycle. Acute aminoaciduria was observed in 21 of 23 patients. Chronic nephrotoxicity, as defined by the development of a Fanconi-like syndrome or chronic tubular electrolyte loss requiring oral supplementation, developed in the three patients with the highest urinary excretion of beta 2-microglobulin after ifosfamide therapy. CONCLUSIONS: Prospectively, high dose ifosfamide was associated with a 4% incidence of Fanconi-like syndrome; however, evidence of acute reversible subclinical nephrotoxicity was observed for all patients. Severe beta 2-microglobulinuria appeared to be a prognostic laboratory indicator for the development of chronic nephrotoxicity.

Adolescent↗
PubMed2003

A rapid and direct real time PCR-based method for identification of Salmonella spp.

The aim of this work was the validation of a rapid, real-time PCR assay based on TaqMan technology for the unequivocal identification of Salmonella spp. to be used directly on an agar-grown colony. A real-time PCR system targeting at the Salmonella spp. invA gene was optimized and validated through a four times repeated blind experiment performed in two different laboratories including 50 Salmonella spp. with representative strains from each of the 5 different Salmonella subgenera and 30 non-Salmonella strains. Both parameters DeltaR(n) (fluorescence intensity of template through a normalized reporter value) and C(T) (cycle at which the fluorescence intensity achieved a pre-established threshold) were analyzed. Overall mean DeltaR(n) and C(T) values for Salmonella strains (2.14+/-0.87 and 15.30+/-0.90, respectively) were statistically different from values for non-Salmonella strains, allowing the establishment of cut-off DeltaR(n) and C(T) values based on 95% confidence intervals that allowed the correct identification of all strains tested in each independent experiment. The accuracy of this assay in terms of inclusivity and exclusivity was 100%. Moreover, the PCR system proved to be especially convenient because the pre-mix containing all PCR reagents except for the bacterial cells could be kept at -20 degrees C for at least 1 month before its use. The optimized TaqMan real-time PCR assay is a useful, simple and rapid method for routine identification of Salmonella spp., irrespective of the particular subgenus.

Bacterial Proteins↗
PubMed2004

Association of nucleophosmin/B23 mRNA expression with clinical outcome in patients with bladder carcinoma.

OBJECTIVES: To determine whether nucleophosmin/B23 mRNA expression in bladder carcinoma predicts recurrence, progression, and survival. METHODS: Real-time reverse transcriptase-polymerase chain reaction was performed on 50 fresh cancer specimens. The change in the cycle of threshold (Ct)was the difference in the Ct values derived from the nucleophosmin/B23 gene assayed and the 18S ribosomal RNA control [Ct (18S)-Ct (nucleophosmin/B23)]. RESULTS: Fifty patients diagnosed with bladder cancer were followed up postoperatively for a median of 24 months. Overexpression of nucleophosmin/B23 mRNA was observed in 37.1% of patients with Stage pT1 and 73.3% of those with pT2-T4 disease. Nucleophosmin/B23 overexpression was not associated with tumor grade (P = 0.163) but was associated with bladder cancer recurrence (68.2%) and progression (88.9%) when adjusted for the effects of clinical stage. Multivariate analysis revealed that the overall tumor stage and nucleophosmin/B23 mRNA overexpression were important prognostic indicators for bladder carcinoma (P <0.05). Patients with nucleophosmin/B23 mRNA overexpression were at a significantly greater risk of disease recurrence and progression than those with low expression of nucleophosmin/B23 mRNA. CONCLUSIONS: Overexpression of nucleophosmin/B23 mRNA was independently associated with bladder cancer recurrence and progression. In patients with muscular invasion disease, overexpression of nucleophosmin/B23 mRNA was associated with the greatest risk of recurrence and progression, suggesting a potential rationale for early definitive therapy in these patients.

Adult↗
PubMed1996

Intermittent androgen suppression with leuprolide and flutamide for prostate cancer: a pilot study.

OBJECTIVES: To affirm the feasibility of using intermittent androgen suppression in patients with hormone-naive prostate cancer. METHODS: Leuprolide and flutamide were administered for 9 to 12 months and then discontinued until prostate-specific antigen (PSA) levels reached a threshold value determined by the baseline PSA value. This constituted one cycle of treatment. Androgen suppression was then administered intermittently as described until there was evidence of androgen independence. RESULTS: Twenty-two patients with PSA failure after primary therapy with surgery and/or radiation and untreated early or Stage D2 disease were treated. Twenty-one patients completed androgen suppression during cycle 1, with a median time to PSA nadir of 3.5 months (range, 2 to 12). Fifteen patients completed cycle 1 with a median time off treatment of 6 months (range, 2 to 19) or 38% (range, 17% to 64%) of a treatment cycle. Six patients continued off treatment during cycle 1 for 1+ to 31+ months. During cycle 2, 12 patients achieved a PSA nadir in a median time of 3.5 months. Two patients completed cycle 2 with a median time off treatment of 10 months (51%). Median follow-up for all patients is 26 months (range, 10 to 51). While off treatment, all patients reported a reduction of symptoms associated with androgen suppression. CONCLUSIONS: Intermittent androgen suppression is a feasible alternative to continuous androgen suppression for treatment of prostate cancer, and quality of life is improved while off treatment.

Aged↗
PubMed2004

Detection and quantification of airborne conidia of Fusarium circinatum, the causal agent of pine pitch canker, from two California sites by using a real-time PCR approach combined with a simple spore trapping method.

Pinus radiata (Monterey pine), a tree native to coastal California and Mexico, is widely planted worldwide for timber production. A major threat to Monterey pine plantations is the fungal disease pine pitch canker, caused by Fusarium circinatum (Hypocreales). We present a novel trapping approach using filter paper in combination with a rapid molecular method to detect the presence of inoculum in the air. The assay is also useful for diagnosing the presence of the pathogen on plants. The test is based on the F. circinatum specific primer pair CIRC1A-CIRC4A, which amplifies a 360-bp DNA fragment in the intergenic spacer region of the nuclear ribosomal operon. Real-time PCR was used to calculate the number of fungal spores present in each reaction mixture by comparing the threshold cycle (Ct) of unknown spore samples to the Ct values of standards with known amounts of F. circinatum spores. The filter paper method allows prolonged and more sensitive spore sampling in the field compared to traditional traps using petri dishes filled with selective medium. A field test at two sites in coastal California infested with pine pitch canker was carried out during the summer and fall of 2002. Spore counts were in the range of ca. 1 x 10(3) to ca. 7 x 10(5)/m(2), with the highest spore counts in the fall, suggesting a seasonal fluctuation.

Air Microbiology↗
PubMed1993

The prognostic value of serum concentrations of progesterone, estradiol, and luteinizing hormone during superovulation with and without adjunctive leuprolide therapy.

OBJECTIVE: To determine the predictive value of preovulatory serum concentrations of P, E2, and LH for pregnancy achieved with IUI after superovulation with and without adjunctive leuprolide acetate (LA) therapy. DESIGN: Randomized, crossover study of superovulation with and without LA therapy. SETTING: Infertility clinic. PATIENTS: Subfertile patients referred for superovulation and IUI. MAIN OUTCOME MEASURES: Preovulatory serum concentrations of P, E2, and LH on the day of hCG administration; pregnancy. RESULTS: Preovulatory serum concentrations of P, E2, and LH had equivalent predictive value for pregnancy during cycles stimulated without LA therapy. No single parameter was particularly useful in clinical decision making. Threshold P concentrations proposed in other studies as useful in predicting pregnancy did not correlate with cycle fecundity. The predictive value of preovulatory concentrations of P during superovulation with adjunctive LA therapy was significantly worse than P concentrations during superovulation without LA therapy. CONCLUSIONS: Preovulatory serum P, E2, and LH concentrations in superovulation and IUI are not helpful in determining prognosis for pregnancy. The relative utility of predictive parameters may vary for different treatment regimens.

Chorionic Gonadotropin↗
PubMed1996

The six-minute walking test in children with cystic fibrosis: reliability and validity.

There is a need to judge general exercise tolerance in children with cystic fibrosis (CF) under normal daily activity conditions and -when more extensive testing is required-in an exercise laboratory in a specialized center. We investigated the reproducibility, validity, and criterion for a 6-minute walking test, which simulates normal childhood activities. In Part A, we evaluated the reproducibility of a 6-minute walking test in 23 children (12 girls and 11 boys; ages 11.1 +/- 2.2 years; range, 8.2 15.6 years) with mild symptoms of CF [forced expiratory volume in 1 second (FEV1) 94.4 +/- 16.5% of predicted values (range, 60.6-129.7); body weight Z-score -0.71 +/- 0.81 (range, -1.73-0.93)]. The subjects performed two standardized 6-minute walking tests with 1 week between tests. There was no significant difference between the two walking distances reached (737 +/- 85 versus 742 +/- 90 meters; P = 0.56), and there was a strong correlation between the two walking distances reached by the individuals (r = 0.90, P < 0.0001). In Part B, the validity of the walking test was evaluated in 15 children (6 girls and 9 boys; ages 14.5 +/- 2.0 years; range, 10.2-16.9 years) with moderate symptoms of CF [FEV1 = 58 +/- 16.0% of predicted values, (range, 41.1-89.4); RV/TLC ratio = 46.3 +/- 6.5% (range, 31.6-57.2); body weight Z-score: -1.29 +/- 0.60 (range, -2.20-0.14)]. They underwent standardized maximum incremental exercise testing on a cycle ergometer and a 6-minute walking test. Postexertional lactate values exceeded threshold values (as described in the literature) in all patients but one. Correlation analysis (Pearson) showed a significant correlation between the walking distance reached (WD = 697 +/- 104 meters), and the maximum workload (Wmax = 118 +/- 44 watt; r = 0.76, P < 0.001) or the maximum oxygen uptake (1,688 +/- 495 ml; r = 0.76, P < 0.001), the latter two being determined on a cycle ergometer, RV/TLC% showed a significant negative correlation (r = -0.72, P < 0.01) with WD. Stepwise multiple regression analysis showed a multiple regression coefficient of R = 0.84 (P < 0.001) for Wmax and RV/TLC % as the independent variables vs. WD as the dependent variable. We conclude that the 6-minute walking test is a valid and useful test in children with mild to moderate symptoms of CF to assess their exercise tolerance and endurance. Exercise test results correlated negatively with pulmonary hyperinflation expressed by the RV/TLC ratio.

Adolescent↗
PubMed1997

Pinacidil's Effects on Defibrillation Outcomes: Role of Increased Potassium Conductance Via the K(ATP) Channel.

BACKGROUND: It has been shown that the inhibition of potassium ion conductance decreases defibrillation threshold. We postulated that if potassium conductance is a primary mechanism affecting defibrillation threshold values, then increasing potassium ion conductance will increase defibrillation values. The primary objective of this study was to determine if the ATP-dependent potassium (K(ATP)) channel opener pinacidil would increase defibrillation threshold values. The second objective was to prove that the observed changes were due to potassium conductance by using the K(ATP) inhibitor, glyburide, to reverse the electrophysiologic actions of pinacidil. The third objective was to determine if the electrophysiology action sof pinacidil correlate with changes in defibrillation threshold value. METHODS AND RESULTS: Domestic farm swine (n = 14) were anesthetized and intubated. Subsequently, they were instrumented with monophasic action potential catheters and epicardial defibrillation patches. Defibrillation threshold values, action potential duration, effective refractory period, and ventricular fibrillation cycle length were determined at baseline and during treatment phase 1 and treatment phase 2. Pigs were randomized into 2 groups: group 1 (n = 6) received D(5)W in treatment phase one followed by D(5)W in treatment phase 2 and group 2 (n = 8) received pinacidil in treatment phase one followed by the addition of glyburide in treatment phase two. DFT(ED50) did not change at baseline, treatment phase one or treatment phase two for group 1 (10.5 +/- 2, 11.1 +/- 1.7, 10.5 +/- 1.0 J) or for group 2 (10.1 +/- 2.2, 11.4 +/- 4.2, 11.4 +/- 3.0 J). Electrophysiologic parameters )QRS, effective refractory period, action potential duration(90), and ventricular fibrillation cycle length) were not significantly changed from baseline in group 1. In contrast, effective refractory period, action potential duration(90), and ventricular fibrillation cycle length significantly decreased at all recorded sites after the administration of pinacidil in group 2 (range of 7-13%, 6-9%, and 12-17%, respectively). However, pinacidil did not change the basal level of dispersion in effective refractory period, action potential duration, and ventricular fibrillation cycle length during paced rhythm or ventricular fibrillation. Glyburide reversed pinacidil's electrophysiologic actions. CONCLUSIONS: Pinacidil does not alter defibrillation threshold, but it reduces effective refractory period, action potential duration, and ventricular fibrillation cycle length and does not increase electrical heterogeneity. Therefore, changes in potassium channel conductance as well as shortening repolarization are unlikely primary mechanisms for elevating defibrillation threshold.

Journal Article↗