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Characteristics of anterior cruciate ligament injuries in Australian football.

Anterior cruciate ligament (ACL) injuries are the most costly injuries in football at both professional and amateur levels (Orchard J, Seward H, McGivern J, Hood S. Intrinsic and extrinsic risk factors for anterior cruciate ligament injury in Australian footballers. Am J Sports Med 2001;29:196-200.). In this study video analysis of 34 ACL injuries in Australian football was performed to investigate the causes of these injuries. Factors that may have contributed to the cause of the injury were analysed, rated and reported. The factors analysed were: type of manoeuvre, direction the knee 'gave way', running speed, knee angle, cutting angle and if the player was accelerating or decelerating. The majority of the injuries analysed occurred in non-contact situations (56%). Of these 37% occurred during sidestepping manoeuvres, 32% in landing, 16% land and step, 10% stopping/slowing and 5% crossover cut manoeuvres. Ninety-two percent of the non-contact injuries occurred at extended knee angles of 30 degrees or less, which is also commonly known to place stress on the ACL and reduce the protective role of hamstrings. Over half (54%) of non-contact injuries occurred whilst decelerating. It would be expected that greater speed and angle cut too would increase the frequency of ACL injury. The results could not confirm this with most injuries occurring at running speeds of slow jogging to running and equal number of injuries occurred at cutting to angles of the ranges 15-45 degrees and 45-75 degrees. These results give greater understanding into potential causes or contributors of ACL injury and information to assist in the development of knee injury prevention programs.

Anterior Cruciate Ligament Injuries↗

The shuffling function of resolvases.

Redistribution (shuffling) of genetic material between replicons requires consecutive recombination at four points, two of which (X, X') are involved in the replicon fusion and the other two (Y, Y'), in the cointegrate resolution. The fusion of replicons by bacterial resolvases makes the second recombination round at sites Y and Y' problematic because of the high probability of the reverse reaction. Structural differences of the res sites recognized by resolvase could delay the reverse reaction, thus enhancing the probability of recombination at sites Y, Y', but the direct reaction ensuring it (i.e. the fusion of replicons via different res sites) has not been described yet. Here, a genetic system to test intermolecular recombination at heterogeneous res sites has been developed. The system was based on the res site (RS2) of the novel resolution system, cinH-RS2, encoded by pKLH2, pKLH204 and pKLH205. As its partner, the res site of RP4 located in the par locus, the res site of transposon gammadelta or Tn1721, the incomplete site RS1 consisting only of the (crossover) subsite resI also found in pKLH2/204/205 and others were used. Except for the pairing of RS2 x gammadelta res, recombination was observed in each case even when the homology shared by partners did not exceed 35% (as in RS2 x par). In the latter case, the presence in cis of an additional, enhancer-like-acting element was required. Pairing of crossover subsites during site-specific recombination occurred in either orientation, depending on the structure of res partners and the kind of resolvase acting on the sites. With the complete res sites, the antiparallel alignment resulted in the production of an unusual res having the accessory subsites II and III at both sides of I, and a res lacking II and III. The wide range of frequencies was observed not only in the fusion formation but also in the dissociation of the resulting cointegrates. Hence, the resolvase-mediated interreplicon exchange of the DNA segments by fusion via an inefficient reaction (at sites X, X') and dissociation via an efficient one (at sites Y, Y') become possible.

Artificial Gene Fusion↗

The phosphodiesterase 5 inhibitor sildenafil has no effect on cerebral blood flow or blood velocity, but nevertheless induces headache in healthy subjects.

Cyclic nucleotides are important hemodynamic regulators in many tissues. Glyceryl trinitrate markedly dilates large cerebral arteries and increases cGMP. Here, the authors study the effect of sildenafil, a selective inhibitor of cGMP-hydrolyzing phosphodiesterase 5 on cerebral hemodynamics and headache induction. Ten healthy subjects were included in a double-blind, placebo-controlled crossover study where placebo or sildenafil 100 mg (highest therapeutic dose) were administered on two separate days. Blood velocity in the middle cerebral artery (Vmca) was recorded by transcranial Doppler, and regional cerebral blood flow in the perfusion area of the middle cerebral artery (rCBFmca) was measured using single photon emission computed tomography and xenon inhalation. Radial and temporal artery diameters were studied using high-frequency ultrasound. Blood pressure and heart rate were recorded repeatedly. Headache responses and tenderness of pericranial muscles were scored verbally. Sildenafil caused no significant changes in rCBFmca, Vmca, or in temporal or radial artery diameter, but heart rate increased and diastolic blood pressure decreased significantly compared to placebo. Despite the lack of cerebral arterial dilatation, sildenafil caused significantly more headache than placebo. The present results show that sildenafil 100 mg does not dilate cerebral or extracerebral arteries but nevertheless causes headache, which may be attributed to nonvascular mechanisms.

3',5'-Cyclic-GMP Phosphodiesterases↗

Venlafaxine's effects on healthy volunteers' driving, psychomotor, and vigilance performance during 15-day fixed and incremental dosing regimens.

Effects of venlafaxine, an antidepressant acting by selective serotonin and norepinephrine reuptake inhibition with a potency ratio of 5:1, were assessed in a standardized, actual driving test, a battery of psychomotor tests (Critical Flicker/Fusion Frequency, Critical Tracking, Divided Attention), and a 45-minute vigilance test (Mackworth Clock). Thirty-seven healthy volunteers, 22 of whom completed the study, received venlafaxine in fixed (37.5 mg twice a day) and incremental (37.5-75 mg twice a day) doses as well as mianserin (10-20 mg three times a day) and placebo according to a 4-period (15 days each), double-blind, crossover design. Testing occurred on days 1 and 7 and after dose increments, on days 8 and 15. Plasma concentrations of venlafaxine and its active metabolite were measured on test days for confirming compliance. Venlafaxine had no significant effect on the primary driving parameter (standard deviation of lateral position) and failed to impair psychomotor performance. Mianserin profoundly and consistently impaired driving and psychomotor performance. However, both drugs significantly impaired vigilance performance. Maximal effects occurred on day 1 with mianserin and similarly on day 7 with venlafaxine in both series. The increment in venlafaxine's dose on day 8 did not increase this effect. The drug's selectively impairing effect on vigilance is shared by other "serotonergic" anxiolytics and antidepressants, suggesting that interference with 5-HT transmission reduces arousal in particularly monotonous tasks or environments. This study concludes that venlafaxine does not generally affect driving ability and should be safe for use by patients who drive.

Adult↗

Rare occurrence of the tetratype tetrads in Saccharomycodes ludwigii.

Genetic data suggesting the absence of crossover in Saccharomycodes ludwigii have been described. Tetrad data obtained from 888 asci from 60 pairs of genes with 22 genetic markers showed the absence of tetratype asci, except for 5 asci in which a single pair of alleles showed tetratype segregation to the other genetic markers in each ascus. Spore arrays in the linear asci showed that the + - + - and + - - + (or - + + -) asci occurred at almost equal frequencies. The two coherent spores at each end of an ascus were always marked with different alleles of a gene.

Chromosomes↗

A pilot study of recombinant insulin-like growth factor-1 in seven multiple sderosis patients.

The purpose of this open-label, crossover study was to determine the safety and efficacy of recombinant insulin-like growth factor-1 (rhIGF-1) using magnetic resonance imaging (MRI) and clinical measures of disease activity in seven multiple sderosis (MS) patients. Monthly clinical and MPI examinations were performed during a 24-week baseline and a 24-week treatment period with rhIGF-1. The primary outcome measure was contrast enhancing lesion (CEL) frequency on treatment compared to baseline. Secondary outcome measures included dinical and MRI measures of disease activity including: white matter lesion load (WMLL), magnetization transfer ratio (MTR), T1-Hypointensity volume, cervical spine cross-sectional area and proton magnetic resonance spectroscopic (MRS) imaging for determining regional metabolite ratios. rhIGF-1 (Cephalon) was administered at a dose of 50 mg subcutaneously twice a day for 6 months. rhIGF-1 was safe and well tolerated with no severe adverse reactions. There was no significant difference between baseline and treatment periods for any MRI or clinical measures of disease activity. Although rhIGF-1 did not alter the course of disease in this small cohort of MS patients, the drug was well tolerated. Further studies using rhIGF-1 alone or in combination with other therapies may be of value because of the proposed mechanism of action of this growth factor on the oligodendrocyte and remyelination.

Aged↗

The efficacy of perturbation training in nonoperative anterior cruciate ligament rehabilitation programs for physical active individuals.

BACKGROUND AND PURPOSE: Treatment techniques involving perturbations of support surfaces may induce compensatory muscle activity that could improve knee stability and increase the likelihood of returning patients to high-level physical activity. The purpose of this study was to determine the efficacy of augmenting standard nonoperative anterior cruciate ligament (ACL) rehabilitation programs with a perturbation training program. SUBJECTS: Twenty-six patients with acute ACL injury or ruptures of ACL grafts participated in the study. Subjects had to have a unilateral ACL injury, be free of concomitant multiple ligament or meniscal damage requiring surgical repair, and pass a screening examination designed to identify patients who had the potential to return to high-level physical activity with nonoperative treatments. Subjects also had to be regular participants in level I activities (eg, soccer, football, basketball) or level II activities (eg, racquet sports, skiing, construction work). METHODS: Subjects were randomly assigned to either a group that received a standard rehabilitation program (standard group) or a group that received the standard program augmented with a perturbation training program (perturbation group). Treatment outcome was determined from scores on the Knee Outcome Survey's Activities of Daily Living Scale (ADLS) and Sports Activity Scale, a global rating of knee function, scores on a series of single-limb hop tests, measurements of maximum isometric quadriceps femoris muscle force output, and the group frequency of unsuccessful rehabilitation. Unsuccessful rehabilitation was defined as the occurrence of an episode of giving way of the knee or failure to maintain the functional status of a rehabilitation candidate on retesting. RESULTS: More subjects had unsuccessful rehabilitation in the standard group compared with the perturbation group. There was a within-group x time interaction for the ADLS, global rating of knee function, and crossover hop test scores. These scores decreased from posttraining to the 6-month follow-up for the standard group. CONCLUSION AND DISCUSSION: Although both the standard program and the perturbation training program may allow subjects to return to high-level physical activity, the perturbation training program appears to reduce the risk of continued episodes of giving way of the knee during athletic participation and allows subjects to maintain their functional status for longer periods.

Activities of Daily Living↗

[The attitudes of primary care professionals on mental patients and psychiatric care].

AIM: To describe the views of different primary care professionals regarding mental illness, psychiatric patients and mental health care. DESIGN: Crossover survey. SITE. Primary care centres in a health zone. PARTICIPANTS: All the primary care centre professionals and social service base teams. Out of 66 possible subjects, 61 answered the questionnaire. MEASUREMENTS AND RESULTS: A questionnaire composed by ourselves about peoples' opinions was given. The chi 2 test was then used to analyse the questionnaire, both item by item and by means of the distribution of frequencies and comparisons. On some items differences between Health Professionals and social service staff occurred. But there were no differences between doctors and nursing staff, nor between men and women (level of importance: 0.50). For 91% of those surveyed, mental health is an illness like any other. 87% believe psychiatry is a science; and 77% that psychiatry is related to the rest of medicine. 48% believe that the majority of mental disturbances are untreatable. 80% affirm that psychiatric admissions should be into special hospitals. CONCLUSION: The authors highlight the need to overcome the discrepancy between positive attitudes on the theoretical side and a reluctance to integrate those attitudes into practice.

Adult↗

Comparison of diltiazem, nitrendipine, and their combination for systemic hypertension and stable angina pectoris.

The relative efficacies of 240 mg/day diltiazem and 20 mg/day nitrendipine were compared in a placebo-controlled, randomized, crossover study of 48 patients who had both moderate systemic hypertension and stable angina pectoris. Hemodynamic indices were measured by impedance cardiography and echocardiography and bicycle ergometry was performed. Compared with placebo, both diltiazem and nitrendipine decreased systolic (p less than 0.05 for both) and diastolic (p less than 0.05 for both) blood pressure, the total peripheral vascular resistance (p less than 0.01 for both), the frequency of anginal attacks (p less than 0.001 for both) and nitroglycerin usage (p less than 0.01 for both), and increased exercise duration (p less than 0.01 and p less than 0.05), exercise time to angina (p less than 0.01 and p less than 0.05) and time to the onset of ST-segment deviation (p less than 0.01 and p less than 0.05). There were no significant differences in the antihypertensive and antianginal effects of the two drugs. Resting heart rate was increased from placebo baseline with nitrendipine (p less than 0.01) during the first week of the treatment, and the reduction of the rate-pressure product and the decrease of the left ventricular mass were greater using diltiazem (p less than 0.05). Sixteen patients had insufficient responses to monotherapy and continued in the study for additional treatment with the combination 120 mg/day diltiazem and 20 mg/day nitrendipine. The normalization of diastolic blood pressure was achieved and more pronounced rate-pressure product reduction was found. No additional side effects were mentioned.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Beta 1 versus nonselective blockade in therapy of essential tremor.

The beta 1-selective blocker metoprolol was compared to propranolol and a placebo in a double-blind crossover trial in 24 patients with essential tremor. Both beta blockers suppressed the essential tremor, but metoprolol, which caused a mean reduction of 32.0% in tremor intensity from the base-line value, was less effective than propranolol, which reduced mean tremor intensity by 41.3%. Subjective benefit for their tremor was found by 15 of the patients taking propranolol and by one taking metoprolol. The tremor frequency was not affected. No serious side effects were observed. Metoprolol may offer an alternative for those essential tremor patients who cannot tolerate propranolol.

Adult↗

Human VNTR mutation and sex.

Seven hypervariable VNTR loci have been studied in about 1200 parent/child pairs about equally divided between the sexes. Mutations were observed with all seven probes, the total number being 71. Fourty-four of these involved increased fragment length. Gains in fragment length were on average larger than losses. These findings indicate that mutation might be a basis for evolutionary expansion of VNTR fragment length. For five probes YNH24 (D2S44), MS31 (D7S21), g3 (D7S22), MS43A (D12S11), and CMM101 (D14S13), mutation rates were relatively low (less than 1%) with no obvious sex difference. MS1 (D1S7) mutation frequencies were substantially higher, with a tendency towards a higher paternal than maternal mutation rate (5.4% and 2.0%, respectively). The probe B6.7 (provisionally assigned to chromosome 20) exhibits about five times higher paternal than maternal mutation rates. The mutation rate of 7.6% in paternal chromosomes is among the highest reported in any VNTR locus. These findings could indicate that while low-mutant VNTRs might reflect meiotic crossover, mutation events in high-mutant loci could more often be caused by other mechanisms during cell division.

Biological Evolution↗

Influence of edeine on intergenic and interallelic recombination in Neurospora crassa.

The effect of edeine and the mutation edr-2 to edeine resistance on genetic recombination in Neurospora crassa was investigated. For this purpose crosses between pairs of edeine sensitive and edeine resistant strains respectively were set up without or in the presence of the drug (0-750 microg/ml). The genetic markers ylo-1, ad-1, pan-2 (B3 and B5) and tryp-2, all on linkage group VI, were used for scoring recombinants. These were ad+, tryp+ (intergenic recombination) and pan+ (interallelic recombination). Frequencies of about 6-7% for intergenic and of about 0.4% for interallelic recombination were found in crosses between eds strains and ed(r) strains respectively, if edeine was absent. However, crosses in the presence of edeine gave higher frequencies of both intergenic and interallelic recombination (about 12% intergenic and 1% interallelic with 180 to 200 microg ed/ml). The pan+ prototrophs (interallelic recombinants) obtained in the different crosses were tested for distribution of outside markers. The data thus obtained revealed that under the effect of both the mutation to edeine resistance and edeine itself the relative number of noncrossover (gene conversion) recombinants decreases in favour of crossover recombinants, and the relative number of double crossover recombinants (events outside the pan locus) decreases in favour of single crossover recombinants. It is concluded that a) edeine and the mutation ed(r)-2 to edeine resistance affect recombination via related pathways, and b) noncrossover and crossover recombinants are caused by different molecular mechanisms, in agreement with the work of other authors.

Anti-Bacterial Agents↗

Enhancement of heart rate variability by cholinergic stimulation with pyridostigmine in healthy subjects.

The purpose of this study was to determine the effect of the oral administration of pyridostigmine bromide on indices of heart rate variability (HRV) in healthy young volunteers. Seventeen healthy participants (11 men, 6 women; aged 27 +/- 8 y) submitted to a randomized, crossover, double-blind protocol, in which they received 30 mg pyridostigmine bromide (PYR) or placebo orally at 8-hour intervals for 24 hours, on two separate days. Venous blood samples were collected 2 and 24 hours after the first dose for determination of serum cholinesterase activity. Holter tapes were recorded during the 24-hour period and analyzed using a semiautomatic technique to evaluate time- and frequency-domain indices of HRV and to build three-dimensional return maps for later quantification. Symptoms were mild and occurred similarly during administration of PYR and placebo (p = 0.140). Serum cholinesterase activity was reduced by 15% at 2 hours (p = 0.013) and by 14% at 24 hours (p = 0.010) after the first dose of PYR, but not after administration of placebo. Pyridostigmine administration caused a significant increase in the mean 24-hour R-R interval (placebo: 814 +/- 20 msec; PYR: 844 +/- 18 msec; p = 0.003) and in time-domain indices of HRV, such as the standard deviation of all R-R intervals (SDNN; placebo: 151 +/- 9 msec; PYR: 164 +/- 9 msec; p = 0.017), and the percentage of pairs of adjacent R-R intervals differing by more than 50 msec (pNN50; placebo: 12.8 +/- 1.8%; PYR: 13.9 +/- 1.5%; p = 0.029). Pyridostigmine had no significant effect on frequency-domain indices of HRV, but resulted in significant increase in P2, a parasympathetic index derived from the three-dimensional return map (placebo: 93 +/- 13 msec; PYR: 98 +/- 13 ms; p = 0.029). In conclusion, low-dose pyridostigmine reduced mean heart rate and increased HRV during a 24-hour period in healthy young subjects.

Administration, Oral↗

Double-blind randomised crossover trial comparing isosorbide dinitrate cream and oral sustained-release tablets in patients with angina pectoris.

Percutaneous isosorbide dinitrate cream and sustained-release tablets were compared in a double-blind randomised crossover trial in 28 patients with coronary artery disease and chronic stable angina pectoris. Twenty-two patients completed the trial. Both preparations significantly increased the mean exercise time to the onset of angina (P less than 0.001) and to termination of exercise (P less than 0.001) compared to the pre-treatment period. There were no significant differences between the cream and tablets with respect to frequency of anginal attacks, glyceryl trinitrate consumption, heart rate and ST segment depression at the onset of angina, ST segment depression at maximal exercise and the double product of heart rate and systolic blood pressure at maximal exercise. Equal numbers of patients expressed preference for cream and tablets. We conclude that in this group of patients isosorbide dinitrate sustained-release tablets have no clinical advantage over isosorbide dinitrate cream which, may, therefore, be of particular value for those patients with angina pectoris who dislike taking tablets or who prefer this form of nitrate preparation.

Administration, Oral↗

Spontaneous mutation rates to new length alleles at tandem-repetitive hypervariable loci in human DNA.

Tandem-repetitive minisatellite regions in vertebrate DNA frequently show substantial allelic variation in the number of repeat units. This variation is thought to arise through processes such as unequal crossover or replication slippage. We show here that the spontaneous mutation rate to new length alleles at extremely variable human minisatellites is sufficiently high to be directly measurable in human pedigrees. The mutation rate at different loci increases with variability in accord with the neutral mutation/random drift hypothesis, and rises to 5% per gamete for the most unstable human minisatellite isolated. Mutations are sporadic, occur with similar frequencies in sperm and oocytes, and can involve the gain or loss of substantial numbers of repeat units, consistent with length changes arising primarily by unequal exchange at meiosis. Germline instability must therefore be taken into account when using hypervariable loci as genetic markers, particularly in pedigree analysis and parenthood testing.

Alleles↗

Arrhythmogenic potential of diuretic induced hypokalaemia in patients with mild hypertension and ischaemic heart disease.

In view of evidence suggesting an association of mild hypokalaemia with cardiac arrhythmia, the arrhythmogenic potentials of potassium losing and potassium sparing diuretic treatments were compared in a controlled prospective crossover study of 10 patients with mild hypertension and ischaemic heart disease. Mean (SEM) plasma potassium was 4.3(0.06) mmol/l and 3.3(0.07) mmol/l after potassium sparing and potassium losing treatments respectively. Blood pressure and volume depletion as assessed by weight change, plasma renin activity, and noradrenaline concentrations did not differ significantly in the two treatment periods. The potassium losing treatment phase was associated with an increased frequency of ventricular extrasystoles, a higher Lown grading during ambulatory electrocardiographic monitoring, prolonged duration and decreased phase 0 velocity of the monophasic action potential, a prolonged ventricular effective refractory period, and increased myocardial electrical instability as assessed by programmed ventricular stimulation. It is concluded that minor changes in plasma potassium concentration are associated with increased ventricular electrical instability in patients with ischaemic heart disease. Mild hypokalaemia in such patients may predispose to life threatening arrhythmias and should be avoided.

Amiloride↗

The profile and severity of lithium-induced side effects in mentally healthy subjects.

In a double-blind, placebo-controlled, crossover design various side effects (= unwanted effects) during 6 months of therapeutic serum lithium levels (0.7-1.1 mmol/1) to nonpsychiatric patients were studied. The side effects were measured by self-rating scales and independent observer rating scales administered every 2-4 weeks throughout the study. After months of treatment, lithium induced hand tremor and thirst/polyuria; however, without any relationship to the serum levels of lithium. The frequency of tremor was highest in patients above the age of 60 years. No initial sedative-like lithium effect was found.

Adult↗

Minor aphthous oral ulceration: a double-blind cross-over study of beclomethasone dipropionate aerosol spray.

A double-blind crossover study is described of the effect of beclomethasone dipropionate aerosol spray in patients with recurrent (minor) aphthous oral ulceration. Patients included in the study had normal haematological parameters of haemoglobin, ferritin, vitamin B12 and corrected whole blood folate. The design of the study incorporated a washout period and duration of effect was evaluated up to six months. Beclomethasone dipropionate significantly reduced ulcer pain severity and ulcer frequency, but had no significant effect on recurrence of oral ulceration. The preparation was associated with a high patient compliance and has benefit in relieving symptoms in patients with recurrent minor aphthous ulceration.

Adult↗