Biomedical subjects

J Hall

Publications and source records attributed to J Hall.

At least 55 records · Page 3Linked to original sources

PubMed2003

Use of perioperative mupirocin to prevent methicillin-resistant Staphylococcus aureus (MRSA) orthopaedic surgical site infections.

We have examined whether topical perioperative prophylaxis can reduce the incidence of methicillin-resistant Staphylococcus aureus (MRSA) surgical site infections (SSIs). Using a controlled before and after approach on patients from four orthopaedic wards, undergoing orthopaedic surgery involving insertion of metal prostheses and/or fixation, received perioperative prophylaxis with nasal mupirocin for five days, and a shower or bath with 2% (v/v) triclosan before surgery (PPNMT). After introduction of PPNMT there was a marked decrease in incidence of MRSA SSIs (per 1000 operations) from 23 in the six months beforehand (period A) to 3.3 (P<0.001) and 4 (P<0.001) in subsequent consecutive six-month periods (B and C, respectively). Of 11 MRSA SSI cases that occurred during periods B and C, only one had actually received PPNMT, and 10 occurred after acute, as opposed to elective, surgery (P<0.001). Point prevalence nasal MRSA carriage decreased from 38% before PPNMT to 23% immediately after, and 20%, 7%, 10% and 8% (P<0.001) at six-monthly intervals post-intervention. Conversely, the prevalence of nasal MRSA carriage in a control elderly medicine ward did not change significantly. Vancomycin usage, in terms of defined daily doses, declined by 23%. Low-level mupirocin resistance was found in 2.3% of S. aureus isolates from orthopaedic patients before PPNMT, and in 3.9%, 6.1%, 10% and 0% in subsequent six month periods. No S. aureus isolates with high-level mupirocin resistance were found. PPNMT can reduce the incidence of MRSA SSls after orthopaedic surgery, probably by reducing nasal MRSA carriage in the endemic setting, without selecting for mupirocin resistance.

Anti-Bacterial Agents↗

PubMed2003

Altered expression of DNA double-strand break detection and repair proteins in breast carcinomas.

AIMS: To determine whether the expression of DNA damage detection and repair proteins is frequently altered in breast carcinomas. METHODS AND RESULTS: The expression profiles of five such proteins: ATM, p53, NBS1, MRE11 and Rad50 were analysed in 99 in-situ and invasive ductal breast carcinomas of different grades using an immunohistochemical approach, and compared with those seen in eight independent non-cancer (normal) breast samples and in the surrounding normal tissues of the breast carcinomas examined. ATM protein expression was reduced in 75% of the tumours compared with the levels found in normal tissues. Fewer tumours had reduced protein levels of the members of the MRE11, NBS1 and Rad50 (MNR) complex (31%, 46% and 28%, respectively) with p53 being over-expressed in 30%. In the majority of tumours (92%) we observed a good correlation between the expression of the three proteins of the MNR complex with low NBS1, MRE11 or Rad50 expression rarely found alone, suggesting that this event occurs subsequently to the deregulation in expression of other DNA repair proteins. CONCLUSION: The pattern of protein changes observed supports our hypothesis that alterations in DNA double-strand break repair capacity are involved in mammary carcinogenesis.

Breast Neoplasms↗

PubMed2003

The effect of urethral instrumentation on uroflowmetry.

OBJECTIVE: To evaluate in a prospective study the effect of urethral instrumentation (flexible cystoscopy) on uroflowmetry, and in particular the peak urinary flow rate (Qmax). PATIENTS AND METHODS: Thirty-two consecutive patients (median age 61.8 years, range 24-80) undergoing flexible cystoscopy were included in the analysis. Patients with active urethral stricture disease or urinary infection were excluded. The indications for cystoscopy included haematuria (44%), voiding symptoms (66%), history of bladder cancer (19%), and history of perineal trauma (3%). Patients underwent uroflowmetry immediately before instrumentation. The postvoid residual volume (PVR) was measured by bladder catheterization. After cystoscopy the bladder was completely emptied and then filled with the same volume of sterile normal saline (bladder volume = voided volume + PVR), and the patient underwent a second uroflowmetry. RESULTS: Patients with voiding symptoms (21, 66%) had a median (range) American Urological Association symptom score of 17 (4-34), a Bother score of 16 (1-23), and Quality of Life score of 3 (1-6). The mean Qmax was 16.9 (4.5-36.9) and 13.3 (4.5-39.4) mL/s before and after cystoscopy, respectively (P = 0.029). The mean percentage difference in Qmax was + 27 (- 23 to 139)% higher before than after cystoscopy. After cystoscopy, up to 25% (eight) and 21% (seven) patients had a lower Qmax, from > 15 to < 15 mL/s and from > 12 to < 12 mL/s, respectively. There were no significant differences in the bladder volume and PVR (P = 0.914 and 0.984, respectively). CONCLUSIONS: Urethral instrumentation by flexible cystoscopy significantly alters Qmax. A 'false' mean change in Qmax (favouring improvement) of +27% would result if uroflowmetry data after instrumentation were used at baseline. Therefore, study protocols for benign prostatic obstruction should exclude uroflowmetry data obtained after urethral instrumentation; failure to exclude such data will lead to disproportionately greater improvements in Qmax that are independent of the therapy delivered.

Adult↗

PubMed2003

E-Selectin mediates pathogenic effects of antiphospholipid antibodies.

Antiphospholipid (aPL) antibodies, detected in patients with antiphospholipid syndrome (APS) are associated with thrombosis, pregnancy loss and thrombocytopenia. Studies have shown that aPL are thrombogenic in vivo, but the mechanism(s) involved are not completely understood. Several studies have demonstrated that aPL antibodies activate endothelial cells (ECs) in vitro, as determined by up-regulation of adhesion molecules: E-selectin (E-sel); intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), and in vivo. The objectives of these study were to determine the effects of aPL antibodies on the expression of E-selectin on ECs, on the adhesion of monocytes to ECs and to study the role of E-selectin on aPL antibodies enhanced thrombus formation and activation of ECs in vivo. We demonstrated that the surface expression of E-selectin on HUVEC by ELISA was increased 400-fold when treated with tumor necrosis factor-alpha (TNF-alpha) and 421-fold when treated with aPL antibodies during 4 h. APL antibodies also induced activation of the nuclear factor-kappa B (NF-kappaB). APL antibodies increased significantly the number of adhering leukocytes to ECs in vivo in C57BL/6 J mice when compared to IgG-NHS treated mice. This effect was abrogated in E-selectin-deficient mice. The thrombus size was significantly increased in C57BL/6 J mice treated with aPL antibodies when compared to mice treated with IgG-NHS. This enhancement in thrombus size by aPL antibodies was abrogated in E-selectin-deficient mice treated with aPL antibodies.

Animals↗

PubMed2003

Variation in radiation-induced apoptosis in ataxia telangiectasia lymphoblastoid cell lines.

PURPOSE: To investigate and compare the ability of Epstein-Barr virus-transformed lymphoblastoid cell lines (LCL) from healthy individuals (normals) and ataxia telangiectasia (A-T) patients to undergo apoptosis after exposure to ionizing radiation. MATERIALS AND METHODS: Four normal and eight A-T LCL were exposed to doses of up to 20 Gy ionizing radiation. Apoptosis induction was studied 24 h after irradiation using three different methods: measurement of caspase-3 activity, PARP-1 cleavage and estimation of the sub-G(1) cell fraction. RESULTS: Of the eight A-T LCL tested, all harbouring truncating ATM mutations, five had a higher level of spontaneous apoptosis than the normal LCL as assessed by the sub-G(1) cell fraction. Four of the eight A-T LCLs showed a similar level of radiation-induced apoptosis after exposure to 5 Gy as the normal LCL. The other four A-T LCL showed a greater radiation-induced apoptotic response, as assessed by at least one of the three techniques. CONCLUSIONS: LCL from A-T patients can undergo ionizing radiation-induced apoptosis in spite of a defect in ATM-p53-dependent signalling pathways. However, the apoptotic response is characterized by a large degree of variability between the A-T cell lines, the causes of which remain to be established.

Apoptosis↗

PubMed2003

Definitive radiotherapy for extramedullary plasmacytomas of the head and neck.

Extramedullary plasmacytoma of the head and neck region (EMPHN) is an uncommon malignant plasma cell neoplasm. In this study we conducted a retrospective analysis of our experience of EMPHN with particular emphasis on the role of definitive radiotherapy. From 1982 to 2001, 10 patients (6 males, 4 females) with EMPHN were treated in our institution. Of nine patients treated at initial diagnosis, all received definitive radiotherapy. One patient treated at relapse underwent surgical resection followed by post-operative radiotherapy. The median age at diagnosis was 55 years (range 35-84 years). The disease was most frequently localized in the paranasal sinuses (50%). All nine patients who received definitive radiotherapy at a dose of 40-50 Gy achieved a complete response. The median follow up period was 29 months (range 7-67 months). Four patients (40%) relapsed, three have died of their disease. Two patients (20%) with paranasal sinus disease subsequently relapsed with multiple myeloma at 10 months and 24 months, respectively. Our results indicate that treatment of EMPHN with radiotherapy achieves excellent rates of local control. The relapse rate in neck nodes of 10% does not justify elective irradiation of the uninvolved neck.

Adult↗

PubMed2003

Interpreting CSF lactic acidosis: effect of erythrocytes and air exposure.

OBJECTIVE: Elevated cerebrospinal fluid (CSF) lactate concentrations in neurotrauma and sub-arachnoid haemorrhage are associated with a poor prognosis. However, in blood-stained CSF, elevated lactate levels may arise from red cell metabolism, even without ischaemia, potentially reducing specificity. This study was undertaken to quantify the erythrocyte contribution to CSF lactate measurements, with and without, exposure to room air. METHODS: Blood was added to CSF to achieve three different red cell concentrations. The CSF was then exposed at 37 degrees C to either room air or 5% CO2 and 95% oxygen. Vancomycin and gentamycin were added to inhibit bacterial growth. Lactate concentrations and red cell concentrations were measured prior to the addition of blood and 10 minutes, 6 hours and 24 hours later. CSF without the addition of blood was used as a control. RESULTS: In the control specimens there were no increases in CSF lactate concentrations over time, either in air or CO2, whereas all specimens with blood added demonstrated significant increases in lactate at 6 and 24 hours (P < 0.01). The lactate increases in both air and CO2 were correlated directly with red cell counts (R2 = 0.62 to 0.87). At all red cell concentrations, the mean lactate increase was greater in air. CONCLUSIONS: Red cells in CSF cause significant increases in lactate concentrations, more so when exposed to air. This should be considered when interpreting lactate in blood stained CSF. Blood-stained CSF specimens for lactate assay should be collected directly from an external ventricular drain rather than a reservoir bag.

Journal Article↗

PubMed2002

Inhibition of CD40-mediated endothelial cell activation with antisense oligonucleotides.

BACKGROUND: CD40-CD154 interactions play a pivotal role in the amplification of immune responses and, as such, represent an attractive target for immune intervention in a number of disease indications. We have previously shown that binding of human CD154 expressed on the Jurkat D1.1 cell line to porcine CD40 on pig aortic endothelial cells (PAECs) can lead to up-regulation of vascular cell adhesion molecule (VCAM)-1 and MHC class II. This activation can be completely inhibited by the addition of a monoclonal antibody (mAb) to human CD154. In this study, we explore an alternative approach to blocking this pathway with antisense oligonucleotides (ASOs). METHODS: Ten ASOs were generated on the basis of the porcine CD40 cDNA sequence. The ASOs that were found to reduce CD40 expression on PAECs were analyzed for their ability to reduce CD40-mediated PAEC activation. RESULTS: Four ASOs were found to significantly lower surface expression of porcine CD40 on PAECs 48 hr after transfection. Eight of the ASOs were seen to lead to mRNA cleavage products by ribonuclease protection assay. Of the four ASOs tested in the PAEC activation assay, one (ASO-9) showed a dramatic inhibition of PAEC activation (IC50 approximately 1 nM) results comparable to the use of a blocking mAb. Furthermore, we compared the effect of CD40 ASO on tumor necrosis factor alpha receptor signaling, in which we observed no effect, which confirmed ASO specificity. CONCLUSIONS: These results indicate that a CD40-dependent activation pathway can be inhibited with an ASO with high potency and specificity. ASO could be an attractive alternative therapy to the use of mAbs.

Animals↗

PubMed2002

Immunofluorescent patterns produced by antineutrophil cytoplasmic antibodies (ANCA) vary depending on neutrophil substrate and conjugate.

BACKGROUND: The "International consensus statement on testing and reporting antineutrophil cytoplasmic antibodies (ANCA)" advocates screening by indirect immunofluorescence (IIF), but external quality assessment programmes often demonstrate different IIF patterns for a single serum. AIM: To determine whether the variation in IIF patterns can be attributed solely to errors in interpretation. METHODS: This study compared the IIF patterns produced by four sera (two with cytoplasmic or C-ANCA; one with perinuclear or P-ANCA with myeloperoxidase (MPO) specificity; and one P-ANCA without MPO specificity) that were tested in 11 different laboratories. The sera were examined according to individual laboratory protocols at dilutions of 1/10 to 1/40 using P1 (n = 4), P2 (n = 2), P3 (n = 2), or in house (n=3) neutrophil preparations and conjugates from manufacturers C1 (n = 3), C2 (n = 1), C3 (n = 2), C4 (n = 1), C5 (n = 2), and C6 (n = 2). The IIF patterns were noted in each laboratory, the testing repeated, and the fluorescent patterns photographed and subsequently discussed at a meeting of the Australian ANCA study group. RESULTS: All IIF patterns described in individual laboratories were confirmed on retesting and by the ANCA study group. Neutrophil substrates produced commercially or in house varied in their ability to demonstrate cytoplasmic granularity and interlobular accentuation, which distinguish between "C-ANCA" and "C-ANCA (atypical)". All commercial and in house neutrophil substrates demonstrated neutrophil nuclear extension of P-ANCA fluorescence, which correlates with MPO specificity. However, eight assays (eight of 43) from eight laboratories resulted in IIF patterns different from those usually seen. One of these produced a C-ANCA (atypical) rather than a C-ANCA pattern. The other seven resulted in at least some cytoplasmic fluorescence when the consensus pattern was P-ANCA with (n = 4) or without (n = 3) MPO specificity. These assays used three different commercial and one in house neutrophil substrate, and six different conjugates, with anti-IgG, anti-(Fab)'(2), anti-Ig (heavy and light chain), and anti-G, A, and M activity. Four of the seven assays tested on commercial substrates had used the manufacturer's conjugates. CONCLUSIONS: This study indicates that the variation in IIF patterns seen with ANCA positive sera tested in different laboratories does not necessarily result from errors in the interpretation of patterns and cannot be attributed solely to the use of a particular neutrophil substrate or conjugate, or to the use of substrate from one manufacturer and conjugate from another.

Antibodies, Antineutrophil Cytoplasmic↗

PubMed2001

Increased expression of unmethylated CDKN2D by 5-aza-2'-deoxycytidine in human lung cancer cells.

DNA hypermethylation of CpG islands in the promoter region of genes is associated with transcriptional silencing. Treatment with hypo-methylating agents can lead to expression of these silenced genes. However, whether inhibition of DNA methylation influences the expression of unmethylated genes has not been extensively studied. We analysed the methylation status of CDKN2A and CDKN2D in human lung cancer cell lines and demonstrated that the CDKN2A CpG island is methylated, whereas CDKN2D is unmethylated. Treatment of cells with 5-aza-2'-deoxycytidine (5-Aza-CdR), an inhibitor of DNA methyltransferase 1, induced a dose and duration dependent increased expression of both p16(INK4a) and p19(INK4d), the products of CDKN2A and CDKN2D, respectively. These data indicate that global DNA demethylation not only influences the expression of methylated genes but also of unmethylated genes. Histone acetylation is linked to methylation induced transcriptional silencing. Depsipeptide, an inhibitor of histone deacetylase, acts synergistically with 5-Aza-CdR in inducing expression of p16(INK4a) and p19(INK4d). However, when cells were treated with higher concentrations of 5-Aza-CdR and depsipeptide, p16(INK4a) expression was decreased together with significant suppression of cell growth. Interestingly, p19(INK4d) expression was enhanced even more by the higher concentrations of 5-Aza-CdR and depsipeptide. Our data suggest that p19(INK4d) plays a distinct role from other INK4 family members in response to the cytotoxicity induced by inhibition of DNA methylation and histone deacetylation.

Azacitidine↗

PubMed2001

Biogeography and ecological setting of Indian Ocean hydrothermal vents.

Within the endemic invertebrate faunas of hydrothermal vents, five biogeographic provinces are recognized. Invertebrates at two Indian Ocean vent fields (Kairei and Edmond) belong to a sixth province, despite ecological settings and invertebrate-bacterial symbioses similar to those of both western Pacific and Atlantic vents. Most organisms found at these Indian Ocean vent fields have evolutionary affinities with western Pacific vent faunas, but a shrimp that ecologically dominates Indian Ocean vents closely resembles its Mid-Atlantic counterpart. These findings contribute to a global assessment of the biogeography of chemosynthetic faunas and indicate that the Indian Ocean vent community follows asymmetric assembly rules biased toward Pacific evolutionary alliances.

Animals↗

PubMed2001

A pilot longitudinal study of hippocampal volumes in pediatric maltreatment-related posttraumatic stress disorder.

BACKGROUND: Adult posttraumatic stress disorder (PTSD) is associated with decreased hippocampal volumes; however, decreased hippocampal volumes were not seen in pediatric maltreatment-related PTSD. We examined hippocampal volumes longitudinally to determine if a history of childhood traumatic stress alters hippocampal growth during puberty. METHODS: Magnetic resonance imaging was used to measure temporal lobes, amygdala, and hippocampal volumes in nine prepubertal maltreated subjects with pediatric maltreatment-related PTSD and nine sociodemographically matched healthy nonmaltreated yoked control subjects at baseline and after at least 2 years follow-up (during the later stages of pubertal development) using identical equipment and measurement methodology. RESULTS: Temporal lobe, amygdala and hippocampal volumes did not differ between groups at baseline, follow-up, or across time. CONCLUSIONS: Whereas these data are from a small sample, the results do not support hippocampal changes in pediatric maltreatment-related PTSD.

Amygdala↗

PubMed2001

Right amygdala volume in adolescent and young adult offspring from families at high risk for developing alcoholism.

BACKGROUND: Neurobiological factors have been implicated in the increased susceptibility for developing alcohol dependence that offspring from alcoholic families exhibit. The P300 component of the event-related potential shows developmental changes during childhood and adolescence that appear to be related to risk status. The underlying structural changes that accompany these neurophysiological changes are not well understood. METHODS: Magnetic resonance imaging was used to measure cerebral, amygdala, and hippocampal volumes in 17 high-risk adolescent and young adult offspring from multiplex alcoholism families and 17 age-, gender-, and IQ-matched control subjects without a family history for alcoholism or other substance dependence. Twenty-two of the subjects are part of a longitudinal prospective study and have been followed an average of 7.3 years, making it possible to relate P300 developmental trajectories to structural volumes. RESULTS: High-risk adolescents and young adults showed reduced right amygdala volume in comparison with control subjects. Right amygdala volume was significantly correlated with visual P300 amplitude. CONCLUSIONS: Offspring from families having a high density of alcoholism differ in both neurophysiological and neuroanatomical characteristics that could not be explained by personal drinking history or particular childhood and adolescent psychopathology. Because the amygdala tends to increase in volume during childhood and adolescence, smaller volumes in high-risk children may indicate a developmental delay that parallels delays seen in visual P300 amplitude.

Adolescent↗

PubMed2001

Human twinning is not linked to the region of chromosome 4 syntenic with the sheep twinning gene FecB.

The tendency to dizygotic (DZ) twinning is inherited in both humans and sheep, and a fecundity gene in sheep (FecB) maps to sheep chromosome 6, syntenic with human 4q21-25. Our aim was to see whether a gene predisposing to human DZ twinning mapped to this region. DNA was collected from 169 pairs and 17 sets of 3 sisters (trios) from Australia and New Zealand who had each had spontaneous DZ twins, mostly before the age of 35, and from a replication sample of 111 families (92 affected sister pairs) from The Netherlands. Exclusion mapping was carried out after typing 26 markers on chromosome 4, of which 8 spanned the region likely to contain the human homologue of the sheep FecB gene. We used nonparametric affected sib pair methods for linkage analysis [ASPEX 2.2, Hinds and Risch, 1999]. Complete exclusion of linkage (lod < -2) of a gene conferring a relative risk for sibs as low as 1.5 (lambda(s) > 1.5) was obtained for all but the p terminus region on chromosome 4. Exclusion in the syntenic region was stronger, down to lambda(s) = 1.3. We concluded that if there is a gene influencing DZ twinning on chromosome 4, its effect must be minor.

Adult↗

PubMed2001

Activity of a novel bcl-2/bcl-xL-bispecific antisense oligonucleotide against tumors of diverse histologic origins.

BACKGROUND: Increased expression of the anti-apoptotic proteins Bcl-2 and Bcl-xL is involved in the development and progression of many tumors. We recently reported that the bcl-2/bcl-xL-bispecific antisense oligonucleotide 4625 induces apoptosis in lung carcinoma cells. To further assess the therapeutic potential of oligonucleotide 4625, we investigated its effect on a series of human tumor cell lines of diverse histologic origins in vitro and in vivo. METHODS: Oligonucleotide 4625-mediated inhibition of bcl-2 and bcl-xL expression in vitro was measured in breast carcinoma cells with the use of reverse transcription-polymerase chain reaction (PCR), real-time PCR, and western blotting. Cytotoxicity was assessed in several different cell lines by measurement of tumor cell growth, propidium iodide uptake, and nuclear apoptosis. The in vivo activity of oligonucleotide 4625 was determined by the inhibition of growth of established tumor xenografts in nude mice, immunohistochemical staining of Bcl-2 and Bcl-x proteins in the tumors, and western blotting of tumor lysates. Apoptosis in tumor xenografts was detected with the use of in situ TUNEL (i.e., terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-digoxigenin nick end labeling) staining. All statistical tests are two-sided. RESULTS: In breast carcinoma cells, oligonucleotide 4625 treatment reduced bcl-2 and bcl-xL messenger RNA levels in a dose-dependent manner. At 600 nM:, oligonucleotide 4625 reduced Bcl-2 and Bcl-xL protein levels to 25% (95% confidence interval [CI] = 16% to 34%) and 20% (95% CI = 14% to 26%), respectively, of the levels in untreated cells and it decreased viability in all cell lines mainly by inducing apoptosis. In vivo, oligonucleotide 4625 statistically significantly inhibited the growth of breast and colorectal carcinoma xenografts by 51% (95% CI = 28% to 74%) and 59% (95% CI = 44% to 74%), respectively, relative to those treated with control oligonucleotide 4626; it also reduced Bcl-2 and Bcl-xL protein levels and induced tumor cell apoptosis. CONCLUSION: The bcl-2/bcl-xL-bispecific antisense oligonucleotide 4625 merits further study as a novel compound for cancer therapy.

Animals↗

PubMed2001

Cellular imaging of zif268 expression in the hippocampus and amygdala during contextual and cued fear memory retrieval: selective activation of hippocampal CA1 neurons during the recall of contextual memories.

The neuroanatomical and molecular basis of fear memory retrieval was studied by analyzing the expression of the plasticity-associated immediate early gene zif268. Cellular quantitative in situ hybridization revealed that zif268 is expressed within specific regions of the hippocampus and amygdala during fear memory retrieval. Within the hippocampus, increased expression of zif268 was observed within CA1 neurons, but not dentate gyrus neurons, during the retrieval of contextual, but not cued, fear associations. In contrast, zif268 expression was increased within neurons of the amygdala (lateral, basal, and central nuclei) during the retrieval of both contextual and cued fear memories. These results demonstrate activation of hippocampal CA1 neurons in contextual fear memory retrieval that was not merely a correlate of the behavioral expression of fear itself, because it was limited to the retrieval of contextual, and not cued, fear memories. Further studies revealed that the selective increase in hippocampal CA1 zif268 expression seen after contextual fear memory retrieval was limited to the retrieval of recent (24 hr) but not older (28 d) memories. These experiments represent the first demonstration that zif268 expression in specific neuronal populations is associated with memory retrieval and suggest that this gene may contribute to plasticity and reconsolidation accompanying the retrieval process.

Acoustic Stimulation↗

PubMed2001

Mutations in the follicle-stimulating hormone receptor and familial dizygotic twinning.

Concentrations of follicle-stimulating hormone (FSH) have an important role in multiple ovulation. An association has been reported between mutations in the FSH receptor (FSHR) in a family with increased twinning frequency. We sequenced the transmembrane region of FSHR (located on chromosome 2) in 21 unrelated mothers of dizygotic twins and found no differences to the published sequence. A linkage study of 183 sister pairs and trios, in which all sisters had given birth to spontaneous dizygotic twins, excluded linkage to this region of chromosome 2. We conclude that mutations in FSHR are not a common cause of familial dizygotic twinning.

Chromosomes, Human, Pair 2↗

PubMed2001

A randomized, controlled trial of remacemide for motor fluctuations in Parkinson's disease.

BACKGROUND: Preclinical studies suggest that glutamate antagonists help ameliorate motor fluctuations in patients with PD treated with levodopa. METHODS: In a multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging study, the authors assessed the safety, tolerability, and efficacy of the glutamate receptor blocker remacemide hydrochloride in 279 patients with motor fluctuations treated with levodopa. The primary objective was to assess the short-term tolerability and safety of four dosage levels of remacemide during 7 weeks of treatment. Patients were also monitored with home diaries and the Unified PD Rating Scale (UPDRS) to collect preliminary data on treatment efficacy. RESULTS: Remacemide was well tolerated up to a dosage of 300 mg/d on a twice daily schedule and 600 mg/d on a four times daily schedule. The most common dosage-related adverse events were dizziness and nausea, as observed in previous studies of remacemide. The percent "on" time and motor UPDRS scores showed trends toward improvement in the patients treated with 150 and 300 mg/d remacemide compared with placebo-treated patients, although these improvements were not significant. CONCLUSION: Remacemide is a safe and tolerable adjunct to dopaminergic therapy for patients with PD and motor fluctuations. Although this study had limited power to detect therapeutic effects, the observed improvement is consistent with studies of non-human primates with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonian signs and symptoms. Additional studies are warranted to confirm these results over an extended period of observation, and to explore the potential neuroprotective effects of remacemide in slowing the progression of PD.

Acetamides↗