The "Trigger" Thumb Locked in Extension - An Unusual Presentation of a Common Paediatric Condition.

BACKGROUND: We report a variant of paediatric trigger thumb which is locked in extension rather than flexion. METHODS: Eleven children with 14 trigger thumbs (three bilateral) locked in extension were reviewed retrospectively over a 12-year period. The number of flexed trigger thumbs encountered over this period was established from the operating room database. RESULTS: All children were treated with release of the A1 pulley. Nine children achieved a full range of motion at the interphalangeal joint. One child with bilateral extended trigger thumbs required bilateral dorsal capsulotomy and another child developed temporary mild triggering in flexion. CONCLUSIONS: Approximately 1% of trigger thumbs treated operatively at this institution presented as the extended variant. Trigger thumb locked in extension should be considered in a child presenting with inability to flex the thumb.

Absence of previously reported variants in the SCNA (G88C and G209A), NR4A2 (T291D and T245G) and the DJ-1 (T497C) genes in familial Parkinson's disease from the GenePD study.

Parkinson's disease (PD) is a neurodegenerative disorder in which relatives of the probands are affected approximately 4 times as frequently as relatives of control subjects. Several genes have been implicated as genetic risk factors for PD. We investigated the presence of six reported genetic variations in the SCNA, NR4A2, and DJ-1 genes in 292 cases of familial Parkinson's disease from the GenePD study. None of the variants were found in the GenePD families. Our results suggest that other variants or genes account for the familial risk of PD within the GenePD study.

Are men at greater risk for Parkinson's disease than women?

Parkinson's disease seems to occur more commonly in men than women based primarily on studies of death rates and prevalence. In recent years, several population based incidence studies of Parkinson's disease that included sex data have been conducted in a variety of populations around the world. To investigate whether these incidence studies suggest an increased risk of Parkinson's disease in men, a meta-analysis was performed of the differences in incidence of Parkinson's disease between men and women reported in seven studies that met the inclusion criteria. A significantly higher incidence rate of Parkinson's disease was found among men with the relative risk being 1.5 times greater in men than women. Possible reasons for this increased risk of Parkinson's disease in men are toxicant exposure, head trauma, neuroprotection by oestrogen, mitochondrial dysfunction, or X linkage of genetic risk factors.

A haplotype at the PARK3 locus influences onset age for Parkinson's disease: the GenePD study.

OBJECTIVE: To identify a haplotype influencing onset age for Parkinson's disease (PD) in the PARK3 region on chromosome 2p13. METHODS: Single nucleotide polymorphisms (SNP) spanning 2.2 Mb and located in or near potential candidate genes were used to fine map the PARK3 region in 527 patients with familial PD, from 264 families. RESULTS: TT homozygotes for rs1876487 (G/T) had a 7.4-year younger mean age at onset (p = 0.005) compared to patients with GT and GG genotypes. Furthermore, SNP flanking the sepiapterin reductase (7,8-dihydrobiopterin: NADP+ oxidoreductase) (SPR) gene, rs1876487 (p = 0.02) and rs1150500 (p = 0.04), were associated with younger onset age among persons who did not carry the 174 allele of D2S1394. The SPR gene is implicated in dopamine synthesis. Haplotype analysis of three SNP-rs2421095, rs1876487, rs1561244-revealed an association with onset age (p = 0.023) and a haplotype of A-T-G alleles was associated with younger onset for PD (p = 0.005). CONCLUSIONS: A haplotype at the PARK3 locus, harboring the SPR gene, is associated with onset age of PD. This may suggest a role for the SPR gene in modifying the age at onset of PD.

Segregation analysis of Parkinson disease revealing evidence for a major causative gene.

The role of genetics in Parkinson disease (PD) continues to be an area of considerable interest and controversy. We collected information involving the nuclear families of 948 consecutively ascertained PD index cases from the University of Virginia (UVA) Health System, the University of Medicine and Dentistry of New Jersey-Robert Wood Johnson (RWJ) School of Medicine, and Boston University (BU) School of Medicine. We performed a segregation analysis to assess evidence for the presence of a Mendelian pattern of familial transmission. The proportion of male (60.4%) and female (39.6%) cases, the mean age of onset (57.7 years), and the proportion of affected fathers (4.7%), mothers (6.6%), brothers (2.9%), and sisters (3.2%) were similar across the three sites. While most of the index cases were male, modestly more of the reported affected relatives were female. These analyses support the presence of a rare major Mendelian gene for PD in both the age-of-onset and susceptibility model. The age-of-onset model provides evidence for a gene that influences age-dependent penetrance of PD, influencing age of onset rather than susceptibility. We also found evidence for a Mendelian gene influencing susceptibility to the disease. It is not evident whether these two analyses are modeling the same gene or different genes with different effects on PD. The finding of significant genes influencing penetrance for PD raises the question of whether these may interact with environmental factors or other genes to increase the risk for PD. Such gene environment interactions, involving reduced penetrance in PD, may explain the low concordance rates among monozygotic twins for this disease.

Epidemiologic study of 203 sibling pairs with Parkinson's disease: the GenePD study.

OBJECTIVE: To examine patterns of familial aggregation and factors influencing onset age in a sample of siblings with PD. METHODS: Sibling pairs (n = 203) with PD were collected as part of the GenePD study. Standardized family history, medical history, and risk factor data were collected and analyzed. RESULTS: The mean age at onset was 61.4 years and did not differ according to sex, exposure to coffee, alcohol, or pesticides. Head trauma was associated with younger onset (p = 0.03) and multivitamin use with later onset (p = 0.007). Age at onset correlation between sibling pairs was significant (r = 0.56, p = 0.001) and was larger than the correlation in year of onset (r = 0.29). The mean difference in onset age between siblings was 8.7 years (range, 0 to 30 years). Female sex was associated with increased frequency of relatives with PD. The frequency of affected parents (7.0%) and siblings (5.1%) was increased when compared with frequency in spouses (2.0%). CONCLUSIONS: The greater similarity for age at onset than for year of onset in sibling pairs with PD, together with increased risk for biological relatives over spouses of cases, supports a genetic component for PD. Risk to siblings in this series is increased over that seen in random series of PD cases; however, patients in this sample have similar ages at onset and sex distribution as seen for PD generally. These analyses suggest that factors influencing penetrance are critical to the understanding of this disease.

The use of fibrin glue in skin grafts and tissue-engineered skin replacements: a review.

Fibrin glue has been widely used as an adhesive in plastic and reconstructive surgery. This article reviews the advantages and disadvantages of its use with skin grafts and tissue-engineered skin substitutes. Fibrin glue has been shown to improve the percentage of skin graft take, especially when associated with difficult grafting sites or sites associated with unavoidable movement. Evidence also suggests improved hemostasis and a protective effect resulting in reduced bacterial infection. Fibrin, associated with fibronectin, has been shown to support keratinocyte and fibroblast growth both in vitro and in vivo, and may enhance cellular motility in the wound. When used as a delivery system for cultured keratinocytes and fibroblasts, fibrin glue may provide similar advantages to those proven with conventional skin grafts. Fibrin glue has also been shown to be a suitable delivery vehicle for exogenous growth factors that may in the future be used to accelerate wound healing.

Genome-wide scan for Parkinson's disease: the GenePD Study.

A genome-wide scan for idiopathic PD in a sample of 113 PD-affected sibling pairs is reported. Suggestive evidence for linkage was found for chromosomes 1 (214 cM, lod = 1.20), 9 (136 cM, lod = 1.30), 10 (88 cM, lod = 1.07), and 16 (114 cM, lod = 0.93). The chromosome 9 region overlaps the genes for dopamine beta-hydroxylase and torsion dystonia. Although no strong evidence for linkage was found for any locus, these results may be of value in comparison with similar studies by others.

Cranial distraction osteogenesis in sheep using a totally implantable hydraulic mechanism: early results.

Conventional distraction osteogenesis has been performed by using either percutaneous pins attached to a thread and screw mechanism, or a thread and screw mechanism that is implanted but still requires turning by a percutaneous instrument or device. In these situations there is always the risk of infection passing to the bone via the percutaneous connection. We have developed a totally implantable hydraulic mechanism, which is activated in much the same way as injection into the port of a tissue expander. Preliminary in vitro testing has suggested that our mechanism can produce sufficient force at appropriate rates of distraction to have a promising role in distraction osteogenesis. We examined the effect of osseous distraction on the cranial vault. Expansion of the cranial vault by distraction osteogenesis is not widespread in clinical practice, in part because of the risk of infective complications of the extra-dural space. We were, therefore, presented with an ideal opportunity both to test the new distraction device and to examine the effect of distraction osteogenesis on the cranial vault. A sheep animal model was used in a pilot study to test the plausibility and examine the physiology of cranial-vault distraction osteogenesis using a totally implantable hydraulic device. Two sheep had a device implanted in the temporal fossa so as to push the craniotomised cranial cap upwards. Distraction was performed for 13 days beginning 1 week after craniotomy. After 9 weeks of consolidation, 5.5 mm and 7.4 mm of new woven bone of normal cranial thickness were demonstrated.

Gender ratio differences between Parkinson's disease patients and their affected relatives.

Mitochondrial dysfunction in Parkinson's disease (PD) is suspected to arise from either acquired or inherited mutation of mitochondrial DNA (mtDNA). If inherited, epidemiologic analysis may reveal maternal transmission. We looked for maternal inheritance bias in our PD clinical database. About 13% of 600 PD probands reported an affected parent. Although 60% of the PD probands were male, only 42% of the affected parents were. The gender ratios for the proband and affected parent generations were dissimilar (p<0.005), indicating an underrepresentation of affected fathers or an overrepresentation of affected mothers. To address these possibilities we analyzed a non-PD control cohort. Four percent of the controls had a PD affected parent, and 75% of these affected parents were male. Apparent maternal inheritance bias in our PD cohort is therefore more likely due to overrepresentation of affected mothers, and is consistent with mitochondrial inheritance in some of our ascertained cases.

Induction by dopamine D1 receptor agonist ABT-431 of dyskinesia similar to levodopa in patients with Parkinson disease.

BACKGROUND: Dyskinesias are a frequent adverse effect of long-term levodopa therapy. The relative contribution of dopamine D(1) and D(2) receptor function to the pathophysiology of levodopa-induced dyskinesias remains a matter of controversy. OBJECTIVE: To establish whether a selective D(1) dopamine agonist induces more or less dyskinesia than levodopa in primed dyskinetic patients with Parkinson disease. METHODS: We studied ABT-431, the prodrug of a fully selective D(1) agonist, in 20 subjects with advanced Parkinson disease and a fluctuating response to levodopa complicated by dyskinesias. Eight patients were studied in a double-blind, randomized design (French centers); 12, in an open, randomized design (US centers). We assessed and compared the antiparkinsonian (Unified Parkinson's Disease Rating Scale) and dyskinetic (response induced by an acute challenge of a suprathreshold dose of levodopa and by 4 different ascending doses (5, 10, 20, and 40 mg) of ABT-431 during the 6 hours after the challenge. RESULTS: The separate analysis of the double-blind and open data led to the same findings, ie, the antiparkinsonian and dyskinetic responses induced by ABT-431 were dose related. At the most effective doses (20 and 40 mg), ABT-431 exhibited similar antiparkinsonian benefit and produced similar dyskinesias as levodopa. CONCLUSION: Dopamine D(1) agonists can induce a full antiparkinsonian response but do not support previous hypotheses suggesting that D(1) agonists are more or less likely to produce dyskinesias than levodopa.

Matrilineal inheritance of complex I dysfunction in a multigenerational Parkinson's disease family.

Recent data suggesting complex I dysfunction in Parkinson's disease (PD) arises from mitochondrial DNA (mtDNA) mutation does not conclusively answer whether the responsible genetic lesion is inherited (primary) or somatic (secondary). To address this question, we identified a family in which multiple members over three generations are affected with PD through exclusively maternal lines. Cytoplasmic hybrids (cybrids) were created for 15 family members over two generations by transferring each individual's mtDNA to mtDNA-depleted human neuroblastoma cells. Eight of the 15 cybrid lines contained mtDNA obtained from maternally descended family members and seven contained mtDNA from paternally descended family members. After 6 weeks of culture, cybrid cell lines were assayed for complex I activity and oxidative stress, and mitochondrial morphology was analyzed by electron microscopy. Compared with the cybrid lines containing mtDNA from paternal descendants, cybrid lines containing mtDNA from maternal descendants had lower complex I activity, increased reactive oxygen species production, increased radical scavenging enzyme activities, and more abnormal mitochondrial morphologic features. These findings were present in cybrid lines containing mtDNA from maternal descendants with PD as well as in currently asymptomatic young maternal descendants, and support a precedent for inherited mtDNA mutation in some persons with PD.

Early morning dystonia in Parkinson's disease.

We interviewed 383 patients with PD regarding disease onset and medication history and evaluated them using the Unified Parkinson's Disease Rating Scale. Sixteen percent of the sample reported the occurrence of early morning dystonia (EMD). Patients with EMD had been taking levodopa for a longer time, were taking higher daily levodopa doses, demonstrated more disability in carrying out their activities of daily living, exhibited dystonia more often before initiation of levodopa treatment, and experienced more peak-dose and diphasic dyskinesias with levodopa therapy.

Clinical correlates of sleep benefit in Parkinson's disease.

The phenomenon of sleep benefit, a period of lessened disability or feeling "on" upon awakening from sleep in the morning, has received scant attention in the literature on Parkinson's disease. We interviewed 162 consecutive patients regarding disease onset, medication history, and symptoms, evaluated them using the Unified Parkinson's Disease Rating Scale, and assessed them as to the presence or absence of sleep benefit. Thirty-three percent reported experiencing sleep benefit. Compared with patients not having sleep benefit, patients with sleep benefit tended to be younger at disease onset, have longer disease duration, take higher total daily doses of levodopa, have longer duration of levodopa treatment, and exhibit less cognitive and physical disability. The findings of this study suggest that sleep benefit is a common phenomenon that may be anticipated in a subgroup of patients with Parkinson's disease. The mechanisms underlying sleep benefit do not appear to be simple and may be multifactorial. Clinicians need to be aware of the authenticity of patients' reports of sleep benefit and consider the existence of this phenomenon when prescribing or adjusting patients' medication schedules.

Maternal inheritance in Parkinson's disease.

To evaluate possible matrilineal factors in the inheritance of Parkinson's disease, we prospectively identified families in which a parent and multiple siblings had Parkinson's disease. In each of the 5 families identified, the affected parent was the mother (p < 0.03). The age at onset in the offspring generation in these 5 families was younger than the age at onset in the parental generation (p < 0.001). In addition, the age at onset in all patients with an affected mother (n = 18) was younger than the age at onset in the affected mothers (p < 0.001). No difference was found between the age at onset in patients with an affected father (n = 14) and the age at onset in the affected fathers. These results are consistent with a role for inherited abnormalities of mitochondrial DNA in the pathogenesis of at least some cases of Parkinson's disease.

Risk profiles for nursing home placement of rural elderly: a cluster analysis of psychogeriatric indicators.

In an effort to better understand the clinical and functional status of patients served by our Rural Elder Outreach Program, more effectively identify risk groups, and more efficiently target services, we performed a cluster analysis on 92 older adults served by our program. The first cluster included patients with very poor health, mild cognitive impairment, very high care demands, and migrating toward active risk for institutionalization. The second cluster included patients with poor physical but good mental health, intact cognition, high care demands, and at passive risk. The third cluster comprised patients with high functional, physical, and cognitive impairment, intensive care demands, moderate mental health problems, poor insight into their situation, and at active risk for institutionalization.

Effects of group interventions on cognition and depression in nursing home residents.

The effects of cognitive-behavioral group therapy, focused visual imagery group therapy, and education-discussion groups on cognition, depression, hopelessness, and dissatisfaction with life were studied among depressed nursing home residents. Seventy-six depressed subjects with mild to moderate cognitive decline participated in nurse-led 24-week protocols. Data were collected 4 weeks before the interventions, 8 and 20 weeks after treatment initiation, and 4 weeks after treatment termination. There were no significant changes in depression, hopelessness, or life satisfaction scores for any of the three conditions. Participants in the cognitive-behavioral and focused visual imagery groups showed a significant improvement beginning 8 weeks after treatment initiation on cognitive scores. These findings are encouraging indications that cognitive-behavioral and focused visual imagery group therapies may reduce cognitive impairment in depressed nursing home residents with mild to moderate cognitive decline.