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PubMed1977

Double-blind placebo-controlled study of loperamide (Imodium) in chronic diarrhoea caused by ileocolic disease or resection.

Loperamide (R 18 553) was compared with placebo in a double-blind crossover study of 21 patients with chronic diarrhoea caused by ileocolic disease or resection. Eighteen patients completed the trial. At a median daily dose of 6 mg the new antidiarrhoeal preparation was found to be superior to placebo in controlling chronic diarrhoea. The frequency and weight of stools significantly decreased, the stools became more solid, and carmine transit time was prolonged during loperamide therapy. Loperamide was consistently preferred to placebo by the patients. Gastrointestinal side-effects were few and comparable during both treatment periods.

Adult↗
PubMed2001

Randomized controlled trial of sheaths in diagnostic neuroangiography.

PURPOSE: To determine the value of arterial sheaths in diagnostic neuroangiography in a randomized controlled trial. MATERIALS AND METHODS: A total of 842 patients (411 men, 431 women; mean age, 59.4 years; age range, 29.5-94.3 years) undergoing diagnostic neuroangiography were randomly assigned to groups in which a sheath was introduced immediately after puncture of the femoral artery (sheath group) or in which a diagnostic catheter was introduced without a sheath (control group). Two hundred twenty-four (26.7%) of 839 patients were receiving anticoagulants immediately prior to the procedure. RESULTS: Complications (mostly small hematomas of the groin) occurred in 106 (12.6%) of 842 patients, with no difference between groups (53 [12.6%] of 421 patients in both; P >.99). Ease of catheter manipulation was greater in the sheath group than in the control group. Incidence of bleeding at the femoral puncture site during the procedure was less in the sheath group (seven [1.7%] of 421 patients) versus the control group (150 [35.6%] of 421 patients), with a P value less than.001. Because of bleeding, sheath insertion was necessary in 165 (39.2%) of 421 patients in the control group. This crossover group also had a higher rate of local complications (28 [17.0%] of 165 patients) than the sheath and control groups. Serious complications, such as stroke (one [0.12%] of 842 patients) and transient ischemic attacks (five [0.60%] of 842 patients), occurred with equal frequency in both the sheath and control groups. CONCLUSION: Use of arterial sheaths lessens the incidence of intraprocedural bleeding at the femoral puncture site and increases ease of catheter manipulation without increasing the number of groin complications.

Adult↗
PubMed1987

Black-white differences in cholesterol levels of serum high-density lipoprotein subclasses among children: the Bogalusa Heart Study.

Cholesterol levels of serum high-density lipoprotein (HDL) subclasses, HDL2 and HDL3, were examined in a random subsample (n = 561) of children (7 to 17 years of age) from a total biracial community. Overall, black children in younger (7 to 10 years) and older (11 to 17 years) age groups alike had significantly higher HDL2 cholesterol (HDL2-C) and HDL3-C than their white counterparts. In addition, black children had a relatively higher frequency of joint occurrence of high levels of both HDL2-C and HDL3-C. A significant sex-related difference, with girls showing higher values than boys, was noted among younger age groups for HDL2-C. A male-female crossover trend in HDL2-C levels was apparent only among white children, with girls showing higher values after age 11. Both age and sexual maturation were inversely associated with HDL3-C levels in white children, irrespective of sex (p less than .001). Serum triglycerides were inversely related to both HDL2-C and HDL3-C only in white children (p less than .001). A black-white difference in HDL2-C persisted only among boys and girls in the older age group after adjusting for the covariates (sexual maturation, age, adiposity, oral contraceptive use, cigarette smoking, alcohol use, and serum triglycerides). With respect to HDL3-C, the covariate-adjusted difference remained significant only among boys in the older age group. Metabolic variations between the races in response to both physiologic and environmental factors likely account for the divergence in antiatherogenic HDL pattern.

Adolescent↗
PubMed1990

Esophageal acid contact time and heartburn in acute treatment with ranitidine and metoclopramide.

Ranitidine and metoclopramide were compared for their ability to reduce esophageal acid contact time and heartburn. Twelve patients with histories of heartburn received ranitidine 150 mg bid, metoclopramide 10 mg qid, and placebo (ranitidine-matched) bid in a randomized, open-label, crossover fashion. Esophageal pH was monitored with an antimony electrode and portable recording unit for 24 h under strictly controlled laboratory conditions. Ranitidine significantly (p less than or equal to 0.05) reduced 24-h acid contact time from 11.6% to 6.4%. Reflux episode frequency was also significantly (p less than or equal to 0.05) reduced from 82 to 45 episodes per day and from 12 to 2 episodes at night. In contrast, metoclopramide did not reduce 24-h acid contact time or daytime reflux episode frequency, although nighttime episode frequency was significantly (p less than or equal to 0.05) decreased. Only ranitidine significantly reduced heartburn frequency and severity. We conclude that acute treatment with ranitidine, but not metoclopramide, significantly reduces esophageal acid contact time, reflux episode frequency, and heartburn frequency and severity in patients with gastroesophageal reflux.

Adult↗
PubMed1996

[Drug consumption by people over 60 years of age in a rural area].

OBJECTIVES: To describe the frequency and distribution of the consumption of medicines in a census-based sample of people of 60 or over. To determine the association between the consumption of medicines and other socio-demographic and clinical (presence of disease) variables. DESIGN: An epidemiological crossover study based in the community. SETTING: Rural population: the Health District of Arévalo in Castilla y León. PARTICIPANTS: 825 subjects (446 women and 379 men) over 60, with an average age of 71,84. MEASUREMENTS: A standard questionnaire was used, containing medicine consumption, prescription, and clinical and demographic features. RESULTS: The consumption of medicines per person per day was 1,92. Therapeutic groups most consumed were, in this order, hypotension drugs, cardiotonics, antirheumatics, peripheral vasodilators, digestive system drugs, neurotropics and analgesics. The number of illnesses suffered by this age-group was 2,19. There is a strong connection between consumption of medicines and age, especially in the over 80's. CONCLUSIONS: 75% of the target population took some medicine each day. Consumption is higher among women than men. Cardiovascular drugs are the most frequently used therapeutic group. Consumption of medicines is directly related to age and the number of illnesses.

Age Factors↗
PubMedDate not supplied

A pilot pharmacokinetic-pharmacodynamic study of benzodiazepine antagonism by flumazenil and aminophylline.

STUDY OBJECTIVES: To develop a pharmacokinetic-pharmacodynamic model using quantitative electroencephalographic (EEG) analysis to compare two separate benzodiazepine antagonists and generate data concerning response variability. DESIGN: A pilot study using a randomized, blinded, crossover design. SETTING: The Neurology Laboratory at the Akron City Hospital campus of SUMMA Health System. PATIENTS: Four healthy volunteers completed the protocol. INTERVENTIONS: Subjects received midazolam 0.1-0.2 mg/kg by intravenous bolus on 3 study days, separated by a minimum washout period of 1 week. Subjects participated in an initial open-label response phase followed by a randomized, crossover trial of each benzodiazepine antagonist. MEASUREMENTS AND MAIN RESULTS: Venous blood samples were obtained to characterize the pharmacokinetics of all study compounds. The EEG parameter of total number of waves/second (recorded from FP1-F3 and FP2-F4 electrodes) in the frequency of 12-30 Hz was used to quantify effect. Flumazenil appeared to prolong the elimination half-life of midazolam significantly (p < 0.05). Theophylline (aminophylline) also appeared to prolong the half-life of flumazenil (p < 0.05). Despite considerable variability, flumazenil resulted in reversal of sedation at concentrations achieved by routine dosing. Resedation was apparent for all subjects following flumazenil reversal. Only partial reversal of sedation by theophylline was achieved by an aminophylline dose of 1-2 mg/kg. CONCLUSIONS: Flumazenil was consistently effective in reversing sedation by midazolam at routinely recommended dosing. Further investigation of aminophylline as a reversal agent should use an estimated dose of 6-8 mg/kg aminophylline. To achieve adequate reversal, some patients may require aminophylline dosages that exceed safe clinical administration.

Adult↗
PubMed1985

Comparison of propafenone and disopyramide for treatment of chronic ventricular arrhythmias: placebo-controlled, double-blind, randomized crossover study.

In a double blind, placebo-controlled study, the efficacy of propafenone, a new antiarrhythmic drug was compared to that of disopyramide. Sixteen patients with frequent and complex premature ventricular contractions (PVCs) were studied by serial 24-hour ambulatory monitoring, while they were receiving propafenone, 300 mg, and disopyramide, 200 mg, both every 8 hours. A reduction in the mean frequency of PVCs per hour, in comparison to the placebo period, from 574 +/- 535 to 100 +/- 130, was observed after propafenone (p less than 0.005) and from 629 +/- 455 to 231 +/- 280 after disopyramide (p less than 0.008). A greater than 70% reduction in PVCs in comparison to placebo was observed in 11 of 14 after propafenone and 9 of 15 after disopyramide (NS). A greater than or equal to 90% reduction in PVCs was observed in 9 of 16 with propafenone and in 4 of 15 with disopyramide (p less than 0.05). The suppression of complex PVCs (repetitive, polymorphic, or more than 5/min with bigeminism) was observed in 11 of 14 after propafenone and in 9 of 14 after disopyramide. The abolition of nonsustained ventricular tachycardia was observed in 6 of 6 and 3 of 5, respectively, after propafenone and disopyramide (p less than 0.05). A lower incidence of side effects, 4 of 16 vs 8 of 16, was observed during propafenone than during disopyramide treatment. We conclude that propafenone, in a dose of 900 mg daily, is more effective than disopyramide, in a dose of 600 mg daily, in the treatment of frequent and complex PVCs and nonsustained ventricular tachycardias. Propafenone also showed a lower incidence of side effects.

Adult↗
PubMed2003

Low-frequency behavior of beads constrained on a lattice.

We study sound propagation in a triangular lattice of spherical beads under isotropic stress. Polydispersity of real beads breaks some contacts, creating a disordered lattice of contacting beads. At large stress, the sound velocity behaves according to Hertz contact law and departs from it at lower stress. This evolution is reversible, with the same crossover when increasing or decreasing the stress, for a given piling. Correlations are much more sensitive to disorder. When calculated with signals propagated in the same lattice, they evolve reversibly with the stress, being much higher at large stress when the contact lattice is more regular. This leads to an interpretation of the non-Hertzian behavior in terms of progressive activation of contacts, in discrepancy with previous models involving buckling of force chains.

Journal Article↗
PubMed2001

A crossover randomized trial of transcutaneous electrical nerve stimulation and oxybutynin in patients with detrusor instability.

PURPOSE: Management of idiopathic detrusor instability is difficult in most patients mainly due to the lack of a complete understanding of the pathophysiology. Oxybutynin and transcutaneous electrical nerve stimulation have been used but to our knowledge no direct comparisons have been made. MATERIALS AND METHODS: Patients with frequency, urgency, urge incontinence and proved detrusor instability were studied with urodynamics, quality of life instruments, and frequency and volume charts. Patients were randomized to transcutaneous electrical nerve stimulation or oxybutynin. After 6 weeks of treatment, they were reassessed and after a washout of 2 weeks, they were started on the second arm of treatment and reassessed 6 weeks later. RESULTS: A total of 13 male and 30 female patients were studied. Functional capacity had increased and number of voids daily had decreased significantly compared with before treatment in both arms (p <0.005). There were significant improvements in symptom specific quality of life measures but no changes were found on the global Short Form 36 (SF-36) quality of life questionnaire. The volume to first desire to void and first unstable contraction had increased significantly with oxybutynin but not with transcutaneous electrical nerve stimulation. Of 23 patients 7 were stabilized with treatment, including 2 with oxybutynin only, 2 with either nerve stimulation or oxybutynin and the remaining 3 with only nerve stimulation. Total bladder capacity did not change significantly with either treatment but patients noticed side effects more commonly with oxybutynin. CONCLUSIONS: Both treatments clearly improved subjective parameters. However, only oxybutynin showed significant improvements in objective urodynamic parameters. Transcutaneous electrical nerve stimulation can be used in patients who cannot take oxybutynin. Further studies are needed to show the long-term efficacy and cost analyses of nerve stimulation.

Adult↗
PubMed2002

Remacemide for drug-resistant localization related epilepsy.

BACKGROUND: Epilepsy is a common neurological condition, affecting 0.5 to 1% of the population. Nearly 30 per cent of people with epilepsy have seizures that are refractory to currently available drugs. In response to this problem, potential new drugs are being developed. Remacemide is one of these. OBJECTIVES: To evaluate the effects of add-on treatment with remacemide upon seizures, adverse effects, cognition and quality of life for people with drug-resistant localization related epilepsy. SEARCH STRATEGY: We searched the Cochrane Epilepsy Group trials register (4 July 2002), the Cochrane Controlled Trials Register (The Cochrane Library Issue 2, 2002) and MEDLINE (28 May 2002). In addition, we contacted AstraZeneca (makers of remacemide) and colleagues in the field to see if they were aware of any trials that we had missed. SELECTION CRITERIA: Randomized placebo controlled add-on trials of people of any age with localization related seizures, in which an adequate method of concealment of randomization was used. The studies could be blinded or unblinded and be of parallel or crossover design. They had to have a minimum treatment period of eight weeks. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials for inclusion and extracted data. Any disagreements were resolved by discussion. Outcomes investigated included 50 per cent or greater reduction in seizure frequency, treatment withdrawal, adverse effects, effects on cognition and quality of life. The primary analyses were by intention-to-treat. Dose response was evaluated in regression models. MAIN RESULTS: Two parallel group trials were included representing 514 individuals. Daily doses of 300, 600, 800 and 1200mg of remacemide were tested. The overall relative risk (RR) for remacemide versus placebo with 95% confidence intervals(CI) for a 50 per cent or greater reduction in seizure frequency was 1.59(95% CI 0.91 to 2.79). Due to differences in response rates among trials, regression models were unable to provide reliable estimates of responses to individual doses. Regression models did however suggest a significant effect for 800-1200mg remacemide per day. Remacemide was more likely to be withdrawn than placebo, the RR for treatment withdrawal was 1.90(95% CI 1.00 to 3.60). The RR for dizziness indicates that it is significantly associated with remacemide 3.08(99% CI 1.37 to 6.95). Effects on cognition and quality of life were not reported. REVIEWER'S CONCLUSIONS: Given the modest effect on seizure frequency and significant withdrawal rate it is unlikely that remacemide will be further developed as an antiepileptic drug.

Acetamides↗
PubMed1979

Antihypertensive effects of clonidine.

The antihypertensive effect of clonidine given either two or three times a day with a diuretic was compared in a double-blind crossover study in 18 hypertensive patients. In 11 patients given clonidine three times a day there was better control of blood pressure, although the differences in most instances were of the order of only a few millimeters Hg. There were no differences in the frequency or severity of side effects. Clonidine twice daily with a diuretic appears to be adequate for most patients.

Adult↗
PubMed1992

Lactitol or lactulose in the treatment of chronic hepatic encephalopathy: results of a meta-analysis.

Lactitol (beta-galactosido-sorbitol) has been recently compared with lactulose for the treatment of chronic hepatic encephalopathy in a few studies, each comprising a small number of patients. The results are controversial. We studied the efficiency and tolerance of both compounds by using a meta-analysis on the basis of published controlled trials. Our study only included controlled or randomized trials comprising cirrhotic patients with chronic hepatic encephalopathy. Analyzed parameters were the portosystemic encephalopathy index of Conn after treatment, the percentage of improved patients and the percentage of patients who had ill effects related to the treatment (flatulence, diarrhea). Bibliographical screening revealed five studies comparing the effects of lactitol and lactulose in chronic hepatic encephalopathy. Four crossover studies were done that included 48 patients and one parallel study that included 29 patients. The duration of the treatment ranged from 3 to 6 mo. All studies found a similar efficiency with both drugs. However, they exhibited some discrepancies in the relative frequency of adverse reactions (flatulence). Meta-analysis showed no statistical differences in the portosystemic encephalopathy index after lactitol or lactulose treatment. The percentage of improved patients after lactitol or lactulose was similar. In contrast, the analysis revealed a higher frequency (p less than 0.01) of flatulence in patients treated with lactulose compared with those treated with lactitol. In conclusion, this meta-analysis shows no statistical difference between therapeutic effects of lactitol and lactulose, but it does show a higher frequency of flatulence with lactulose. This suggests that lactitol should be preferred to lactulose for the treatment of chronic hepatic encephalopathy.

Chronic Disease↗
PubMed2002

Tryptophan depletion effects on EEG and MEG responses suggest serotonergic modulation of auditory involuntary attention in humans.

Involuntary attention shifting, i.e., detecting and orienting to unexpected stimulus changes, may be altered at low brain serotonin (5-hydroxytryptamine; 5-HT) levels. This was studied in 13 healthy subjects (21-30 years old; 6 females) by using a dietary challenge, acute tryptophan depletion (ATD), which decreases 5-HT synthesis in the brain. Five hours after ingestion of either ATD or control mixture (randomized, double-blinded, crossover design), brain responses indexing involuntary attention were measured with simultaneous 64-channel electroencephalography (EEG) and 122-channel magnetoencephalography (MEG). During the measurement, the subjects were instructed to discriminate equiprobable 200- and 400-ms tones by pressing one of two buttons rapidly. Occasionally, the frequency of the tones changed (10% increase/decrease), causing involuntary attention shifting. ATD significantly lowered plasma tryptophan concentrations (total tryptophan decreased by 75%, free tryptophan decreased by 35%). As compared to the control condition, ATD reduced the amplitude of the deviant-tone N2 wave, including the overlapping mismatch negativity (MMN) and N2b subcomponents, which are suggested to reflect change detection in the brain. The EEG results were accompanied by a significant increase in the peak latency of the magnetic counterpart of MMN. However, no ATD effects were observed in P3 to task-irrelevant frequency change. Reaction time (RT) to deviants per se was not significantly affected, but RT in trials succeeding the deviant-frequency tones was increased by ATD, which suggested impaired reorienting to the task-relevant activity. In conclusion, the results suggest that decreased level of central 5-HT function after ATD may decrease involuntary attention shifting to task-irrelevant sound changes and thus modulate resource allocation to the task-relevant activity.

Acoustic Stimulation↗
PubMed1997

Two amino acid changes at the N-terminus of transmissible gastroenteritis coronavirus spike protein result in the loss of enteric tropism.

To study the molecular basis of TGEV tropism, a collection of recombinants between the PUR46-MAD strain of transmissible gastroenteritis coronavirus (TGEV) infecting the enteric and respiratory tracts and the PTV strain, which only infects the respiratory tract, was generated. The recombinant isolation frequency was about 10(-9) recombinants per nucleotide and was 3.7-fold higher at the 5'-end of the S gene than in other areas of the genome. Thirty recombinants were plaque purified and characterized phenotypically and genetically. All recombinant viruses had a single crossover and had inherited the 5'- and 3'-halves of their genome from the enteric and respiratory parents, respectively. Recombinant viruses were classified into three groups, named 1 to 3, according to the location of the crossover. Group 1 recombinants had the crossover in the S gene, while in Groups 2 and 3 the crossovers were located in ORF1b and ORF1a, respectively. The tropism of the recombinants was studied. Recombinants of Group 1 had enteric and respiratory tropism, while Group 2 recombinants infected the respiratory, but not the enteric, tract. Viruses of both groups differed by two nucleotide changes at positions 214 and 655. Both changes may be in principle responsible for the loss of enteric tropism but only the change in nucleotide 655 was specifically found in the respiratory isolates and most likely this single nucleotide change, which leads to a substitution in amino acid 219 of the S protein, was responsible for the loss of enteric tropism in the closely related PUR46 isolates. The available data indicate that in order to infect enteric tract cells with TGEV, two different domains of the S protein, mapping between amino acids 522 and 744 and around amino acid 219, respectively, are involved. The first domain binds to porcine aminopeptidase N, the cellular receptor for TGEV. In the other domain maps a second factor of undefined nature but which may be the binding site for a coreceptor essential for the enteric tropism of TGEV.

Animals↗
PubMed2005

Effectiveness of frequency-modulated electromagnetic neural stimulation in the treatment of painful diabetic neuropathy.

AIMS/HYPOTHESIS: The largely unsatisfactory results reported for the pharmacological treatment of diabetic neuropathy has spurred the search for alternative therapies. The aim of this study was to evaluate the efficacy of frequency-modulated electromagnetic neural stimulation (FREMS) as a novel treatment for painful diabetic neuropathy. METHODS: Patients (n=31) with painful neuropathy associated with decreased nerve conduction velocity (<40 m/s) and increased vibration perception threshold (>25 V) were enrolled in a randomised, double-blind, crossover study designed to compare the effects of FREMS with those of placebo. Each patient received two series of ten treatments of either FREMS or placebo in random sequence, with each series lasting no more than 3 weeks. The primary efficacy end point was the change in pain measured by a visual analogue scale (VAS). RESULTS: FREMS induced a significant reduction in daytime and night-time VAS pain score (all p<0.02). Furthermore, FREMS induced a significant increase in sensory tactile perception, as assessed by monofilament; a decrease in foot vibration perception threshold, as measured by a biothesiometer; and an increase in motor nerve conduction velocity (all p<0.01). No significant changes were observed after placebo. Comparison of measurements at the 4-month follow-up with those at baseline revealed that a significant benefit persisted for all measures that showed an improvement at the end of treatment, with an additional improvement in quality of life evaluated by the Short Form-36 questionnaire (all p<0.05). No significant side effects were recorded during the study. CONCLUSIONS/INTERPRETATION: FREMS is a safe and effective therapy for neuropathic pain in patients with diabetes and is able to modify some parameters of peripheral nerve function.

Cross-Over Studies↗
PubMed1995

Effect of amlodipine, atenolol and their combination on myocardial ischemia during treadmill exercise and ambulatory monitoring. Canadian Amlodipine/Atenolol in Silent Ischemia Study (CASIS) Investigators.

OBJECTIVES: This study compared the effects of amlodipine, atenolol and their combination on ischemia during treadmill testing and 48-h ambulatory monitoring. BACKGROUND: It is not known whether anti-ischemic drugs exert similar effects on ischemia during ambulatory monitoring and exercise treadmill testing. METHODS: Patients with stable coronary artery disease and ischemia during treadmill testing and ambulatory monitoring were randomized to receive amlodipine (n = 51) or atenolol (n = 49). Each group underwent a counterbalanced, crossover evaluation of single drug and placebo, followed by evaluation of the combination. RESULTS: Amlodipine and the combination prolonged exercise time to 0.1-mV ST segment depression by 29% and 34%, respectively (p < 0.001) versus 3% for atenolol (p = NS). During ambulatory monitoring, the frequency of ischemic episodes decreased by 28% with amlodipine (p = 0.083 [NS]), by 57% with atenolol (p < 0.001) and by 72% with the combination (p < 0.05 vs. both single drugs; p < 0.001 vs. placebo). Suppression of ischemia during exercise testing and ambulatory monitoring was similar in patients with and without exercise-induced angina. Exercise time to angina improved by 29% with amlodipine (p < 0.01), by 16% with atenolol (p < 0.05) and by 39% with the combination (p < 0.005 vs. placebo, atenolol and amlodipine). In patients with angina, total exercise time improved by 16% with amlodipine (p < 0.001), by 4% with atenolol (p = NS) and by 19% with the combination (p < 0.05 vs. placebo and either single drug). In those patients without angina, no therapy significantly improved total exercise time. CONCLUSIONS: Ischemia during treadmill testing was more effectively suppressed by amlodipine, whereas ischemia during ambulatory monitoring was more effectively suppressed by atenolol. The combination was more effective than either single drug in both settings.

Amlodipine↗
PubMedDate not supplied

Gelation of xyloglucan by addition of epigallocatechin gallate as studied by rheology and differential scanning calorimetry.

Interaction of tamarind seed xyloglucan (TSX) and epigallocatechin gallate (EGCG) was investigated. TSX alone showed the rheological behaviors of dilute and semidilute solution types in the temperature range from 10 to 50 degrees C and the concentration range from 1 to 10%. Addition of a small amount of EGCG changed the rheological properties of TSX solutions to induce a thermoreversible gelation. The sol-gel transition was detected as a crossover of the storage and loss shear moduli at a certain temperature in thermal scanning rheological measurements and an endo- and exo- thermic peaks in curves obtained by differential scanning calorimetry on heating and cooling. High storage modulus of the gels at all experimental frequencies also indicated the formation of a network structure. Increase in the gel strength and the enthalpy of the transition with increasing EGCG concentration at fixed TSX concentration suggested that EGCG was directly involved in the network formation through association with TSX. The TSX gel was obtained by addition of appropriate amount of EGCG. Addition of an excessive amount of EGCG induced precipitation.

Calorimetry, Differential Scanning↗
PubMed1995

Multilocus analysis for gene-centromere mapping using first polar bodies and secondary oocytes.

Polar body and oocyte typing is a new technique for gene-centromere mapping and for generating female linkage maps. A maximum likelihood approach is presented for ordering multiple markers relative to the centromere and for estimating recombination frequencies between markers and between the centromere and marker loci. Three marker-centromere orders are possible for each pair of markers: two orders when the centromere flanks the two markers and one order when the centromere is flanked by the two markers. For each possible order, the likelihood was expressed as a function of recombination frequencies for two adjacent intervals. LOD score for recombination frequency between markers or between the centromere and a marker locus was derived based on the likelihood for each gene-centromere order. The methods developed herein provide a general solution to the problem of multilocus gene-centromere mapping that involves all theoretical crossover possibilities, including four-strand double crossovers.

Animals↗