Electrical stimulation for faecal incontinence in adults.

BACKGROUND: Faecal incontinence is a particularly embarrassing and distressing condition with significant medical, social and economic implications. Electrical stimulation has been used with apparent success in the treatment of faecal incontinence. However, standards of treatment are still lacking and the magnitude of alleged benefits has yet to be established. OBJECTIVES: To determine the effects of electrical stimulation for the treatment of faecal incontinence in adults. SEARCH STRATEGY: We searched the Cochrane Incontinence Group Specialised Trials Register (searched 13 March 2007) and reference lists of potentially eligible articles. SELECTION CRITERIA: All randomised or quasi-randomised trials evaluating electrical stimulation in adults with faecal incontinence. DATA COLLECTION AND ANALYSIS: Two reviewers assessed the methodological quality of potentially eligible trials and independently extracted data from the included trials. A wide range of outcome measures were considered. MAIN RESULTS: Four eligible trials with 260 participants were identified. Findings from one trial suggest that electrical stimulation with anal biofeedback and exercises provides more short-term benefits than vaginal biofeedback and exercises for women with obstetric-related faecal incontinence. Another study found contradictory results, with no added benefit from electrical stimulation over biofeedback and exercises alone. Although all trials report that patient's symptoms are generally improved, it is not clear that this is the effect of electrical stimulation. No further conclusions could be drawn from the data available. AUTHORS' CONCLUSIONS: At present, there are insufficient data to allow reliable conclusions to be drawn on the effects of electrical stimulation in the management of faecal incontinence. There is a suggestion that electrical stimulation may have a therapeutic effect, but this is not certain. Larger, more generalisable trials are needed.

Anticholinergic drugs versus placebo for overactive bladder syndrome in adults.

BACKGROUND: Around 16% of adults have symptoms of overactive bladder (urgency with frequency and/or urge incontinence). The prevalence increases with age. Anticholinergic drugs are commonly used to treat this condition. OBJECTIVES: To determine the effects of anticholinergic drugs for the treatment of overactive bladder syndrome. SEARCH STRATEGY: We searched the Cochrane Incontinence Group Specialised Trials Register (searched 14 June 2005) and the reference lists of relevant articles. SELECTION CRITERIA: Randomised or quasi-randomised trials in adults with overactive bladder syndrome that compared an anticholinergic drug with placebo treatment or no treatment. DATA COLLECTION AND ANALYSIS: Two reviewer authors independently assessed eligibility, trial quality and extracted data. Data were processed as described in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2005). MAIN RESULTS: Sixty -one trials, 42 with parallel-group designs and 19 crossover trials were included (11,956 adults). Most trials were described as double-blind but were variable in other aspects of quality. The crossover trials did not present data in a way that allowed inclusion in the meta-analysis. Nine medications were tested: darifenacin; emepronium bromide or carrageenate; oxybutynin; propiverine; propantheline; tolterodine; trospium chloride; and solifenacin. One trial included the newer, slow release formulation of tolterodine. At the end of the treatment period, cure or improvement (relative risk (RR) 1.39, 95% CI 1.28 to 1.51), difference in leakage episodes in 24 hours (weighted mean difference (WMD) -0.54; 95% CI -0.67 to -0.41) and difference in number of voids in 24 hours (WMD -0.69; 95% CI -0.84 to -0.54) were statistically significant favouring medication. Statistically significant but modest sized improvements in quality of life scores were reported in recently completed trials. There was three times the rate of dry mouth in the medication group (RR 3.00 95% CI 2.70 to 3.34) but no statistically significant difference in withdrawal (RR 1.11, 95% CI 0.91 to 1.36). Sensitivity analysis, while limited by small numbers of trials, showed little likelihood that the effects were modified by age, sex, diagnosis, or choice of drug. AUTHORS' CONCLUSIONS: The use of anticholinergic drugs by people with overactive bladder syndrome results in statistically significant improvements in symptoms. Recent trials suggest that this is associated with modest improvement in quality of life. Dry mouth is a common side effect of therapy but did not seem to have an effect on the numbers of withdrawals. It is not clear whether any benefits are sustained during long-term treatment or after treatment stops.

Biofeedback and/or sphincter exercises for the treatment of faecal incontinence in adults.

BACKGROUND: Faecal incontinence is a particularly embarrassing and distressing condition with significant medical, social and economic implications. Anal sphincter exercises and biofeedback therapy have been used to treat the symptoms of people with faecal incontinence. However, standards of treatment are still lacking and the magnitude of alleged benefits has yet to be established. OBJECTIVES: To determine the effects of biofeedback and/or anal sphincter exercises/pelvic floor muscle training for the treatment of faecal incontinence in adults. SEARCH STRATEGY: We searched the Cochrane Incontinence Group Specialised Trials Register (searched 27 February 2006) and the reference lists of relevant articles. SELECTION CRITERIA: All randomised or quasi-randomised trials evaluating biofeedback and/or anal sphincter exercises in adults with faecal incontinence. DATA COLLECTION AND ANALYSIS: Two reviewers assessed the methodological quality of eligible trials and two reviewers independently extracted data from included trials. A wide range of outcome measures were considered. MAIN RESULTS: Eleven eligible studies were identified with a total of 564 participants. In all but three trials methodological quality was poor or uncertain. No study reported a major difference in outcome between any method of biofeedback or exercises and any other method, or compared to other conservative management. There are suggestions that rectal volume discrimination training improves continence more than sham training and that anal biofeedback combined with exercises and electrical stimulation provides more short-term benefits than vaginal biofeedback and exercises for women with obstetric-related faecal incontinence. Further conclusions are not warranted from the available data. AUTHORS' CONCLUSIONS: The limited number of identified trials together with their methodological weaknesses do not allow a definitive assessment of the possible role of anal sphincter exercises and biofeedback therapy in the management of people with faecal incontinence. We found no evidence of biofeedback or exercises enhancing the outcome of treatment compared to other conservative management methods. While there is a suggestion that some elements of biofeedback therapy and sphincter exercises may have a therapeutic effect, this is not certain. Larger well-designed trials are needed to enable safe conclusions.

Cellulose, modified cellulose and synthetic membranes in the haemodialysis of patients with end-stage renal disease.

BACKGROUND: When the kidney fails the blood-borne metabolites of protein breakdown and water cannot be excreted. The principle of haemodialysis is that such substances can be removed when blood is passed over a semipermeable membrane. Natural membrane materials include cellulose or modified cellulose, more recently various synthetic membranes have been developed. Synthetic membranes are regarded as being more "biocompatible" in that they incite less of an immune response than cellulose-based membranes. OBJECTIVES: To assess the effects of different haemodialysis membrane material in patients with end-stage renal disease (ESRD). SEARCH STRATEGY: We searched MEDLINE, EMBASE, PreMEDLINE, HealthStar CINAHL, the Cochrane Central Register of Controlled Trials (CENTRAL), Biosis, SIGLE, CRIB, UK National Research Register and reference lists of relevant articles. We contacted biomedical companies, known investigators and handsearched selected journals and conference proceedings. Date of most recent search: June 2004. SELECTION CRITERIA: All randomised controlled trials (RCTs) or quasi-RCTs comparing different haemodialysis membrane material in patients with ESRD. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed the methodological quality of studies. Data was abstracted onto a standard form by one reviewer and checked by another. Relative Risk (RR) and weighted mean difference (WMD) with 95% confidence intervals (CI)) MAIN RESULTS: Thirty two studies were identified. Pre-dialysis ss(2) microglobulin concentrations were not significantly lower in patients treated with synthetic membranes (WMD -14.67, 95% CI -33.10 to 4.05). When analysed for change in ss(2) microglobulin, a fall was only noted with high-flux membranes. The incidence of amyloid was less in patients who were dialysed for six years with high-flux synthetic membranes (one study, RR 0.03, 95% CI 0.00 to 0.54). There was a significant difference in favour of the synthetic (high-flux) membrane in comparison to cellulose membranes for triglycerides (WMD -0.66; 95% CI -1.18 to -0.14) but not for modified cellulose membranes. Dialysis adequacy measured by Kt/V was marginally higher when cellulose membranes were used (WMD -0.10; 95% CI -0.16 to 0.04), whereas synthetic membranes achieved significantly higher Kt/V values when compared with modified cellulose membranes (WMD 0.20, 95% 0.11 to 0.29) . There were no data on quality of life measures. AUTHORS' CONCLUSIONS: We found no evidence of benefit when synthetic membranes were compared with cellulose/modified cellulose membranes in terms of reduced mortality no reduction in dialysis-related adverse symptoms. Despite the relatively large number of RCTs undertaken in this area none of the included studies reported any measures of quality of life.

Genetic mapping of a novel X-linked recessive colobomatous microphthalmia.

Colobomatous microphthalmia is a common ocular malformation with a heterogeneous phenotype. The majority of cases without associated systemic abnormalities have an autosomal dominant inheritance pattern [McKusick, 1990: Mendelian inheritance in man]. A few isolated cases with autosomal recessive transmission have been described [Zlotogora et al., 1994: Am J Med Genet 49:261--262]. To our knowledge, no cases of X-linked colobomatous microphthalmia that are not a part of a syndrome or a multisystem disorder have been reported. In this study, we describe a genetic and clinical evaluation of a large pedigree in which colobomatous microphthalmia is segregating in an X-linked recessive fashion. Based on recombination breakpoint analysis, we have determined that the critical interval exists between markers DXS989 and DXS441, placing the disease locus on the proximal short arm or the proximal long arm of the X chromosome. Using linkage analysis, we obtained two-point lod scores of 2.71 at zero recombination with markers DXS1058, DXS6810, DXS1199, and DXS7132. Overlapping multipoint analysis established a broad maximum from marker DXS1068 to marker DXS7132, a region spanning approximately 28 cM. This study provides evidence for the presence of a new locus for colobomatous microphthalmia.

Dental caries history in nine children with chromosome 18p deletion syndrome.

Chromosome 18p deletion syndrome is caused by the deletion of a portion of genetic material on the short (p) arm of chromosome 18. Many of 100 prior case reports in the medical literature describing the dental health of subjects with this syndrome reported multiple caries associated with the syndrome. At the third annual international conference of The Chromosome 18 Registry & Research Society, dental examinations were carried out on nine children with chromosome 18p deletion syndrome and five of their unaffected siblings. The dental examination included an intra-oral evaluation of coronal decay and filled permanent teeth surfaces (DFS) and decayed and filled primary tooth surfaces (dfs) using a mouth mirror, explorer, and a high-intensity fiber optic light. An evaluation of the data revealed that five of nine children with 18p deletion syndrome (56%) were free of tooth decay or a history of tooth decay. Four of the nine (44%) had tooth decay or a history of tooth decay. The prevalence of decay was quite similar in the genetically unaffected siblings. Three of the five (60%) unaffected siblings of the children with 18p were free of tooth decay, whereas two of the five (40%) had tooth decay. One of the affected children had a missing mandibular left central incisor. None of the children had abnormally shaped teeth. The caries pattern seems to be similar to that reported in the NHANES III data collected in the United States from 1988-1991. Analysis of these preliminary data suggests that the risk for caries in chromosome 18p deletion syndrome may be lower than previously reported.

The spectrum of growth abnormalities in children with 18q deletions.

The objective of this study was to assess the spectrum of growth abnormalities in children with 18q deletions. The growth axis of 50 individuals with a cytogenetically and molecularly confirmed 18q deletion was investigated by determining height, growth velocity, insulin-like growth factor I (IGF-I), IGF-binding protein-3, bone maturation, and response to pituitary stimulants of GH. Children with 18q deletions are short; 64% have a height more than -2 SD below the mean. Affected children also grow slowly; 68% have a growth velocity more than -1 SD below the mean. Half of the individuals have delayed bone maturation. Growth factors are skewed downward; 72% of the IGF-I values and 83% of the IGF-binding protein-3 values are below the mean for chronological age. Similarly, 72% of the children had a reduced or absent response to either of the GH stimulants, arginine and clonidine. In the total group of 50 children only 2 were normal for all parameters evaluated. Short stature and poor growth are common features of individuals with 18q deletions. GH deficiency is common in this cohort of patients and probably plays a role in the short stature seen in many of the affected individuals.

Haplosufficiency of the melancortin-4 receptor gene in individuals with deletions of 18q.

The melanocortin-4 receptor (MC4R) is a seven, transmembrane G-protein-coupled receptor whose ligand, alpha-melanocyte-stimulating hormone (alpha-MSH), is a post-translational derivative of pro-opiomelanocortin (POMC). The regulatory pathway, of which MC4R is a part, has become an area of intense interest because of its potential role in obesity. Three studies have identified individuals with dominantly inherited obesity segregating with mutations in the MC4R gene. It has been hypothesized that the mutation found in these subjects resulted in a loss of gene function resulting in obesity due to haploinsufficiency of the MC4R gene. We have been studying the molecular basis of the phenotype of individuals with large deletions of chromosome 18q. Due to its location at 18q21.3, the MC4R gene is hemizygous in approximately one-third of the individuals in our study. If hemizygosity of the MC4R gene results in haploinsufficiency-induced obesity, then individuals with deletions of 18q whose deletions include the MC4R gene should be obese in comparison with those individuals whose deletion does not include the gene. Our data indicate no difference in obesity among those deleted and not deleted for the gene. This supports the hypothesis that the MC4R gene product is haplosufficient and the involvement of MC4R in obesity may reflect a dominant negative effect.

Variable disease severity associated with a Paget's disease predisposition gene.

We have recently identified a region on the long arm of chromosome 18 that carries a predisposition gene for Paget's disease using linkage analysis. This region was explored because of earlier studies demonstrating the presence of a gene for another bone disorder, familial expansile osteolysis (FEO) within this region. FEO has many similarities to Paget's disease including osteoclast abnormalities and viral-like nuclear inclusions. Therefore, it was proposed that FEO and Paget's disease are disorders resulting from mutations at the same locus. For our linkage study, we utilized a large kindred with a high incidence of Paget's disease. The propositus in this family had polyostotic disease symptoms beginning at age 31. During the process of characterizing this family, four other family members were diagnosed with Paget's disease. One of the proband's siblings was asymptomatic but had high normal serum alkaline phosphatase levels; Paget's disease was identified only after bone scanning (at age 50). This implies that the predisposition gene does not consistently cause severe disease and raises a question concerning the mechanism of predisposition: Does the predisposition gene affect the age of onset and/or the severity of disease? To further explore this question, two individuals from this kindred, under age 30 and carrying the affected haplotype, were evaluated for early onset Paget's disease. No evidence of disease was observed after thorough evaluation. This implies that the age of onset is highly variable for this locus, indicating variable expression of disease in individuals carrying the same mutation.

Gene expression patterns in cell lines from patients with 18q- syndrome.

Some studies have suggested that for trisomies, some genes are expressed far in excess of the expected 150% level and that this "dysregulation" is one of the mechanisms for the pathogenesis of trisomies. In an attempt to generalize this result to a monosomy, we examined mRNA isolated from lymphoblastoid cell lines derived from patients with 18q- syndrome, a deletion syndrome involving loss of the distal long arm of chromosome 18. Expression levels of ten chromosome 18 genes were compared between cell lines from eight patients with 18q- syndrome and four diploid controls. Gene expression was investigated by a quantitative reverse-transcription polymerase chain reaction (RT-PCR) method. With the exception of the transcription factor NFATC1, which shows a tendency towards gene dosage compensation (the expression pattern correlates with IgA deficiency), all of the other genes were expressed at a level proportional to their gene copy number. This was true regardless of mRNA abundance or different patterns of gene expression (ubiquitous versus tissue-specific gene expression). These results indicate that, unlike dysregulated gene expression apparent in some trisomies, this monosomic syndrome is largely due to consequences of reduced gene expression.

Congenital anomalies and anthropometry of 42 individuals with deletions of chromosome 18q.

Deletions of chromosome 18q are among the most common segmental aneusomies compatible with life. The estimated frequency is approximately 1/40,000 live births [Cody JD, Pierce JF, Brkanac Z, Plaetke R, Ghidoni PD, Kaye CI, Leach RJ. 1997. Am. J. Med. Genet. 69:280-286]. Most deletions are terminal encompassing as much as 36 Mb, but interstitial deletions have also been reported. We have evaluated 42 subjects with deletions of 18q at our institution. This is the largest number of individuals with this chromosome abnormality studied by one group of investigators. Here we report the physical findings in these individuals. We have compared our findings with those of previously reported cases and have found a significantly different incidence of several minor anomalies in our subjects. We also describe here several anomalies not previously reported in individuals with deletions of 18q, including short frenulum, short palpebral fissures, disproportionate short stature, overlap of second and third toes, and a prominent abdominal venous pattern. Characteristics found in subjects were analyzed for correlation with cytogenetic breakpoints. Several traits were found to correlate with the extent of the deletion. Large deletions were associated with significantly decreased head circumference and ear length as well as the presence of proximally placed and/or anomalous thumbs. Individuals with the smallest deletions were more likely to have metatarsus adductus. Although relatively few genotype/phenotype correlations were apparent, these data demonstrate that correlations with breakpoint are possible. This implies that more correlations will become evident when the more precise molecularly based genotyping is completed. These correlations will identify critical regions on the chromosome in which genes responsible for specific abnormal phenotypes are located.

Identification of cryptic rearrangements in patients with 18q- deletion syndrome.

The majority of patients with 18q- syndrome appear cytogenetically to have a terminal deletion of the long arm of chromosome 18. These 18q- patients are diagnosed by use of standard cytogenetic banding techniques, which have resolution insufficient for precise genotyping. In our effort to obtain a thorough genotype, we have analyzed the DNA from 35 patients who originally were diagnosed as having de novo terminal deletions of chromosome 18. Molecular analysis was performed with polymorphic markers throughout the 18q- region. Cytogenetic FISH was performed with two human 18q telomeric probes, a chromosome 18-specific alpha-satellite probe, and whole chromosome 18-specific paint. Of 35 patients previously reported to have terminal deletions of 18q, we found that 5 (14%) have more-complex cryptic rearrangements and that 3 (9%) retain the most distal portion of 18q, consistent with an interstitial rather than a terminal deletion. These findings indicate that a standard karyotype can lead to insufficient characterization in 18q- syndrome. This has important ramifications for phenotype mapping of this syndrome, as well as for proper prognosis.

Chromosome 18q paracentric inversion in a family with mental retardation and hearing loss.

We report on a mother and child with a paracentric inversion of the long arm of chromosome 18: 46,XX,inv(18)(q21.1q23). The child had findings in common with those seen in 18q- syndrome including: microcephaly, epicanthal folds, midface hypoplasia, and abnormally modeled ears, dermatoglyphic whorls on fingertips, clubfeet, hearing loss, and developmental delay. The mother and several maternal relatives had mild mental retardation and hearing loss. Magnetic resonance imaging of the child's brain showed abnormal myelination. Molecular studies including PCR-based markers for the MBP locus and fluorescent in situ hybridization with a P1 genomic clone on mother and child demonstrated only one copy of the MBP locus (18q23) with the deletion extending beyond the MBP locus. Therefore, the deletion in the MBP region may account for the abnormal myelination seen in the patient. The other clinical findings, including mental retardation and hearing loss in this family, may reflect disruption of distal or proximal genes within the deleted MBP region or at the more proximal breakpoint 18q21.1, and may represent a contiguous gene syndrome. Further study of this family may help define those genes functioning in the MBP region that contribute to the phenotype of 18q- syndrome.

Genetic linkage of Paget disease of the bone to chromosome 18q.

Paget disease is a common bone disease characterized by abnormal osteoclasts that are large, multinucleated, and overactive and that contain paramyxovirus-like nuclear inclusions. There is evidence for a major genetic component to Paget disease, with up to 40% of patients having affected first-degree relatives; however, the locus (loci) and gene(s) involved are unknown. Another bone disorder, familial expansile osteolysis (FEO), although extremely rare, also is characterized by similar osteoclast abnormalities but has an earlier age at onset and a more aggressive clinical progression. The causative gene for FEO has been localized to a region of human chromosome 18q. On the basis of the presence of similar clinical findings and of viral-like nuclear inclusions in osteoclasts, we hypothesized that FEO and Paget disease are allelic versions of the same locus. Therefore, a large kindred with a high incidence of Paget disease was examined to determine if Paget disease was linked to genetic markers in the same region of chromosome 18 as that for FEO. Our analysis yielded a two-point LOD score of 3.40, with the genetic marker D18S42, a marker tightly linked to the FEO locus. This demonstrates that the gene(s) responsible for FEO and that for Paget disease are either closely linked or the same locus.

Growth hormone insufficiency associated with haploinsufficiency at 18q23.

Growth hormone insufficiency is a common cause of growth failure in children with the 18q- syndrome. Individuals with this syndrome have a deletion as large as 36 Mb from the long arm of chromosome 18. We have evaluated 33 children with this syndrome for growth hormone production and have identified a region of approximately 2 Mb, which is deleted in every growth hormone insufficient patient. Two genes contained in this region, myelin basic protein, and the galanin receptor, are candidate genes for the growth hormone insufficiency phenotype.

Magnetic resonance imaging demonstrates incomplete myelination in 18q- syndrome: evidence for myelin basic protein haploinsufficiency.

Magnetic resonance imaging (MRI) and MRI relaxometry were used to investigate disturbed brain myelination in 18q- syndrome, a disorder characterized by mental retardation, dysmorphic features, and growth failure. T1-weighted and dual spin-echo T2-weighted MR images were obtained, and T1 and T2 parametric image maps were created for 20 patients and 12 controls. MRI demonstrated abnormal brain white matter in all patients. White matter T1 and T2 relaxation times were significantly prolonged in patients compared to controls at all ages studied, suggesting incomplete myelination. Chromosome analysis using fluorescence in situ hybridization techniques showed that all patients with abnormal MRI scans and prolonged white matter T1 and T2 relaxation times were missing one copy of the myelin basic protein (MBP) gene. The one patient with normal-appearing white matter and normal white matter T1 and T2 relaxation times possessed two copies of the MBP gene. MRI and molecular genetic data suggest that incomplete cerebral myelination in 18q- is associated with haploinsufficiency of the gene for MBP.

Growth hormone deficiency associated in the 18q deletion syndrome.

The 18q- syndrome is one of the commonest deletion syndromes. Clinical characteristics are variable but may include: hypotonia, tapered digits, "carp-like" mouth, mental retardation, and hearing impairment. Growth failure (GF; both weight and height < 3%) was reported in 80% of affected individuals. We evaluated growth hormone (GH) sufficiency in 5 18q- syndrome patients, 3 of whom had growth failure (< 3% weight and height); the remaining 2 had normal growth parameters. Laboratory evaluation of growth included measurement of IGF-1, IGFBP-3, bone ages and GH response to pituitary provocative agents. Three patients failed to produced adequate GH following stimulation testing. Of 3 patients with inadequate GH production, 1 had normal growth (above 3%). Only 1 of 5 patients had normal GH production and normal growth parameters. Our findings to date suggest that GH deficiency is common in individuals with the 18q- syndrome. The pathogenesis of this finding is unknown. We postulate that a gene(s) on 18q is involved in GH production.

Preferential loss of the paternal alleles in the 18q- syndrome.

Individuals with the 18q- syndrome have variable deletions from the long arm of chromosome 18. They also exhibit a highly variable phenotype. To correlate genotype with phenotype accurately, extensive molecular and phenotypic analyses are needed on each affected individual. As a part of this analysis, we have determined the parental origin of the deleted chromosome in 34 individuals with the 18q- syndrome. We have found that 85% of the de novo deletions are paternal in origin. The percentage of fathers of individuals with paternally derived deletions who were > 30 years old was (not significantly) greater than that of the general population. The mothers of individuals with maternally derived deletions were near an average age for childbearing compared to the general population. Individuals with maternally derived terminal deletions had breakpoints as varied as those with paternally derived deletions. These results are consistent with the hypothesis that the reduced incidence of maternally derived deletions is not due to reduced viability, since individuals with large maternally derived deletions of chromosome 18q were found. We hypothesize that the prevalence of paternally derived deletions is due to an increased frequency of chromosome breakage in male germ cells. These results are consistent with results observed in other segmental aneusomies in which there is a high incidence of paternally derived deletions.

Issues Pertaining to Monitoring the Abuse of Amphetamines in Workplace Drug Testing.

Literature pertaining to three potential problematic areas in forensic drug urinalysis of amphetamines is reviewed. The first topic involves analytical artifacts causing false positive results for methamphetamine, as well as approaches to instrumental and chemical resolutions. The second topic addresses enantiomeric compositions, including sources, analytical approaches, metabolic mechanisms, and interpretation criteria. The third topic is concerned with legal and illicit drugs that may produce amphetamine or methamphetamine as metabolites, and relevant information regarding interpretation of these results.

Metabolic Precursors to Amphetamine and Methamphetamine.

Analysis and interpretation of amphetamine results is a challenging process made difficult by a number of factors. One of the complications comes from determination of the origin of amphetamine or methamphetamine in a sample. Given the relatively rare occasions that either of these two drugs are prescribed, legal prescription of one of these drugs is seldom a reason for positive findings. A number of other precursor compounds are metabolized by the body to amphetamine or methamphetamine, many of which could be used for legitimate reasons. Fourteen different metabolic precursors of amphetamine or methamphetamine are included in this review. They are amphetaminil, benzphetamine, clobenzorex, deprenyl, dimethylamphetamine, ethylamphetamine, famprofazone, fencamine, fenethylline, fenproporex, furfenorex, mefenorex, mesocarb, and prenylamine. Medical use, metabolism, analysis, and interpretation are described to afford sufficient information to evaluate the possible involvement of these drugs in positive amphetamine or methamphetamine results.