Bone Mineral Density in the Proximal Femur and Contralateral Knee After Total Knee Arthroplasty

Osteoarthrosis (OA) is often associated with pain and disability, which are relieved after total knee arthroplasty (TKA), but the nature of bone changes associated with OA is controversial. We examined preoperative hip and contralateral knee bone mineral density (BMD) in patients requiring TKA and monitored the BMD changes postoperatively. Sixty-nine patients, scheduled to have TKA for osteoarthrotic knees, had both hips and contralateral knee BMD measured by dual-energy X-ray absorptiometry (DXA) at the time of operation (baseline) and at 1 yr after operation. X-rays of the knee joints were also taken to evaluate the severity of OA. Preoperatively, 27% and 38% of the patients had total hip BMD Z-score more than 1 SD in the operated side and contralateral hips, respectively. In all regions of interest (ROI), the mean baseline BMD of the affected side proximal femur was significantly lower than that of the contralateral side (p < 0.0005-0.019). The severity of OA was not associated with BMD. During 1-yr follow-up, the postoperative knee status and the physical activity of the patients (AKS score) improved. However, neither the hip nor the nonoperated knee BMDs increased. Knee OA is associated with significantly lower BMD values in the affected side compared with the contralateral hip, and these levels remained similar or decreased during a 1-yr follow-up. We conclude that improved mobility after TKA does not improve the effects of preoperative disuse-associated bone loss in the short term.     

Depression-executive dysfunction syndrome in stroke patients.

OBJECTIVE: It has been suggested that executive dysfunction could be the core defect in patients with geriatric or vascular depression, and that this depression-dysexecutive syndrome (DES) might be related to frontal-subcortical circuit dysfunction. The authors tested this hypothesis in 158 poststroke patients, of whom 21 had both depression and executive dysfunction. Methods: In this cross-sectional cohort study, a neurological, psychiatric, and neuropsychological examination was carried out 3 months after ischemic stroke, and brain infarcts, white-matter changes, and brain atrophy were recorded by MRI. RESULTS: The 21 patients with DES had significantly more brain infarcts affecting their frontal-subcortical circuit structures than the 137 patients without DES, or the 41 patients with depression but without executive dysfunction. Patients with DES also had more severe depressive symptoms and worse psychosocial functioning, and they coped less well in complex activities of daily living. CONCLUSIONS: DES is a valid concept and may define a subgroup of poststroke patients with frontal-subcortical pathology and with distinct prognosis and treatment options.     

Chromosome 2q terminal deletion: report of 6 new patients and review of phenotype-breakpoint correlations in 66 individuals

We report a new patient with terminal deletion of chromosome 2 with breakpoint at 2q36 and five additional new patients with 2q terminal deletion with breakpoint at 2q37. Hemidiaphragmatic hernia is a novel finding in one patient with a breakpoint at 2q37.1. In comparing these patients to 60 previously reported individuals with 2q terminal deletions, certain physical abnormalities are loosely associated with positions of breakpoint. For example, facial features (e.g., prominent forehead, depressed nasal bridge, and dysmorphic ears and nose), short stature, and short hands and feet were frequent in patients with breakpoints at or proximal to 2q37.3. Reports of horseshoe kidney and Wilms tumor were limited to patients with a breakpoint at 2q37.1, and structural brain anomalies and tracheal anomalies were reported only in patients with breakpoints at or proximal to 2q37.1. Cleft palate was reported only in patients with the most proximal breakpoints (2q36 or 2q35). Neurological effects including developmental delay, mental retardation, autistic-like behavior, and hypotonia were typical in this patient population but did not stratify in severity according to breakpoint. Terminal deletion of the long arm of chromosome 2 should be considered in the infant with marked hypotonia, poor feeding, gastroesophageal reflux, and growth delay, and the older child with developmental delay, autistic behavior, and the characteristic facial and integumentary features described herein. Assignment of clinical features to specific breakpoints and refinement of predictive value may be useful in counseling.     

Sleep and its homeostatic regulation in mice lacking the adenosine A1 receptor

Sleep deprivation (SD) increases extracellular adenosine levels in the basal forebrain, and pharmacological manipulations that increase extracellular adenosine in the same area promote sleep. As pharmacological evidence indicates that the effect is mediated through adenosine A1 receptors (A1R), we expected A1R knockout (KO) mice to have reduced rebound sleep after SD. Male homozygous A1R KO mice, wild-type (WT) mice, and heterozygotes (HET) from a mixed 129/C57BL background were implanted during anesthesia with electrodes for electroencephalography (EEG) and electromyography (EMG). After 1 week of recovery, they were allowed to adapt to recording leads for 2 weeks. EEG and EMG were recorded continuously. All genotypes had a pronounced diurnal sleep/wake rhythm after 2 weeks of adaptation. We then analyzed 24 h of baseline recording, 6 h of SD starting at light onset, and 42 h of recovery recording. Neither rapid eye movement sleep (REM sleep) nor non-REM sleep (NREMS) amounts differed significantly between the groups. SD for 6 h induced a strong NREMS rebound in all three groups. NREMS time and accumulated EEG delta power were equal in WT, HET and KO. Systemic administration of the selective A1R antagonist 8-cyclopentyltheophylline (8-CPT) inhibited sleep for 30 min in WT, whereas saline and 8-CPT both inhibited sleep in KO. We conclude that constitutional lack of adenosine A1R does not prevent the homeostatic regulation of sleep.     

Characterization of GPRA, a novel G protein-coupled receptor related to asthma

We recently identified a novel positional asthma susceptibility gene, GPRA, which belongs to the G protein-coupled receptor family. In the present studies, we show that isoform specific activation of GPRA-A with its agonist, Neuropeptide S (NPS) resulted in significant inhibition of cell growth. GPRA has several variants due to extensive alternative splicing. We observed that only the full-length variants, GPRA-A and GPRA-B, with 7 transmembrane topology are transported into the plasma membrane, while the truncated proteins retain intracellular compartments. To clarify disease mechanism, we studied co-expression of the variants without finding any indication that truncated variants would inhibit the receptor transport into the plasma membrane. By using in situ hybridization and immunohistochemistry, we detected ubiquitous expression of GPRA-B, and frequent expression of GPRA-A in the epithelia of several organs including bronchi and gastrointestinal tract. Furthermore, we observed aberrant mRNA and protein expression levels of GPRA in the asthmatic bronchi. Finally, we demonstrate that GPRA and NPS are co-expressed in bronchial epithelium. In summary, this study provides evidence that GPRA might have functional relevance in modulating asthma by increased expression levels in the relevant tissues under diseased state and by potential inhibitory effect of GPRA-A activation on cell growth.     

Coding haplotype analysis supports HCR as the putative susceptibility gene for psoriasis at the MHC PSORS1 locus

PSORS1, near HLA-C, is the major genetic determinant of psoriasis. We present genetic and structural evidence suggesting a major role for the HCR gene at the PSORS1 locus. Genotyping of 419 families from six populations revealed that coding single-nucleotide polymorphisms of HCR formed a conserved allele HCR*WWCC that associated highly significantly with psoriasis and with the HLA-Cw6 allele in all populations. Because of strong linkage disequilibrium between HLA-Cw6 and HCR*WWCC, the two genes could not be genetically distinguished by this sample size. However, the variant HCR allele was predicted to differ in secondary structure from the wild-type protein. HCR protein expression in lesional psoriatic skin differed considerably from that observed in normal skin. These results provide strong evidence for the HCR*WWCC allele as a major genetic determinant for psoriasis, probably by a mechanism impacting on keratinocyte proliferation.     

Estrogen receptor genotype modulates myocardial perfusion in young men

Most of the effects of estrogens are mediated by estrogen receptors. Vascular endothelial cells and smooth muscle cells express estrogen receptor (ESR1) in both genders. A long genotype group of a common thymine-adenine (TA) dinucleotide repeat polymorphism in the regulatory region of this gene has previously been related to coronary artery disease. The present study examined whether coronary blood flow is affected by this genotype. A total of 49 healthy men were genotyped by PCR and divided into three groups according to median number of the ESR1 promoter TA repeat (=19), i.e., in the short allele genotype group both alleles were of fewer than 19 repeats whereas in the long allele group both alleles were 19 repeats or more. The intermediate group comprised men who had one short and one long allele. Myocardial blood flow was measured by positron emission tomography using [¹⁵O]water, performed at rest and during adenosine stimulation. Men with long alleles had lower adenosine-stimulated coronary flow than those with short alleles and those with one short and one long allelle. Our results suggest that adenosine-stimulated myocardial perfusion is lower in subjects with ESR1 long alleles than the other TA repeat genotypes.     

Levodopa, bromocriptine and selegiline modify cardiovascular responses in Parkinson's disease

Autonomic nervous system (ANS) involvement is frequently found in Parkinson's disease (PD), but its causal relationship to the disease itself and its medication is unclear. We evaluated the effects of PD medications on cardiovascular ANS functions. Heart rate (HR) responses to normal and deep breathing, the Valsalva manoeuvre and tilting, and blood pressure (BP) responses to tilting and isometric work were measured prospectively in 60 untreated PD patients randomised to receive either levodopa (n=20), bromocriptine (n=20) or selegiline (n=20) as their initial treatment. The results were compared with those of 28 healthy controls. The responses were recorded at baseline, after 6 months on medication and following a 6-week washout period. At baseline HR responses to normal breathing, deep breathing and tilting were already lower and the fall in the systolic BP immediately and at 5 min after tilting was more pronounced in the PD patients than in the controls. Six months' levodopa treatment diminished the systolic BP fall after tilting when compared to baseline, whereas bromocriptine and selegiline increased the fall in systolic BP after tilting and selegiline diminished the BP responses to isometric work. The BP responses returned to the baseline values during the washout period. The drugs induced no change in the HR responses. Thus PD itself causes autonomic dysfunction leading to abnormalities in HR and BP regulation and the PD medications seem to modify ANS responses further. Bromocriptine and selegiline, in contrast to levodopa, increase the orthostatic BP fall and supress the BP response to isometric exercise reflecting mainly impairment of the sympathetic regulation. Received: 17 February 2000 / Received in revised form: 25 May 2000 / Accepted: 15 June 2000