Long-range ordering of vibrated polar disks.

Vibrated polar disks have been used experimentally to investigate collective motion of driven particles, where fully ordered asymptotic regimes could not be reached. Here we present a model reproducing quantitatively the single, binary, and collective properties of this granular system. Using system sizes not accessible in the laboratory, we show in silico that true long-range order is possible in the experimental system. Exploring the model's parameter space, we find a phase diagram qualitatively different from that of dilute or pointlike particle systems.

Indication-specific 6-h systolic blood pressure thresholds can approximate 24-h determination of blood pressure control.

Ambulatory blood pressure monitoring (ABPM) is an accurate method for evaluating hypertension, yet its use in clinical practice may be limited by availability, cost and patient inconvenience. The objective of this study was to investigate the ability of a 6-h ABPM window to predict blood pressure control, judging by that of the full 24-h ABPM session across several clinical indications in a cohort of 486 patients referred for ABPM. Sensitivities and specificities of the 6-h systolic blood pressure mean to accurately classify patients as hypertensive were determined using a fixed reference point of 130 mm Hg for the 24-h mean. For four common indications, in which ABPM was ordered, prediction tables were constructed varying the thresholds for the 6-h mean to find the optimal value that best predicted the 24-h hypertensive status as determined from the full 24-h interval. Using a threshold of 137 mm Hg for the indications of borderline hypertension, evaluation of current antihypertensive regimen and suspected white-coat hypertension, sensitivity and specificity ranged from 0.83-0.88 to 0.80-0.88, respectively, for the ability of 6-h ABPM to correctly categorize hypertensive status. Using 133 mm Hg as the threshold for treatment resistance resulted in a sensitivity and specificity of 0.93 and 0.83, respectively. We conclude that a shortened ABPM session of 6 h can be used to accurately classify blood pressure as controlled or not, based on the results of a 24-h session. The optimal 6-h threshold for comparison depends upon indication for referral.

Do antibiotics affect the quality of life of patients with upper respiratory tract illnesses? It might depend on one's luck.

OBJECTIVE: Upper respiratory tract illnesses (URTI) are known to cause measurable decline in health-related quality of life (HRQL). We studied whether antibiotics impacted patients' HRQL after obtaining medical care for URTI. METHODS: Adults seeking care for URTI at a family medicine office were eligible for this study. Decisions to prescribe antibiotics were left to their physicians. Subjects completed the Quality of Well-Being questionnaire on enrolment and on days 3, 7, 14 and 28. Analysis of HRQL was undertaken using repeated measures ANOVA and ANCOVA. RESULTS: Seventy-three patients (mean age 35.8 years) were studied. Thirty-six of the subjects (50.7%) received prescriptions for antibiotics from their physicians at the index visit. By day 28, 78.4% of the subjects in the antibiotic group and 77.8% of the other group reported cure (p = 0.95). Receiving a prescription for an antibiotic at the initial visit did not influence subsequent HRQL reported by subjects (p = 0.98). However, when subjects receiving antibiotics were subgrouped by whether they reported an antibiotic adverse event we found significant differences in final HRQL. Subjects receiving antibiotics but not experiencing adverse events reported higher HRQL by day 28 than did subjects receiving an antibiotic but also reporting adverse events and subjects not receiving any antibiotics (p = 0.02). CONCLUSION: Providing patients experiencing URTIs with prescriptions for antibiotics does not, on average, positively impact HRQL over the following 28 days. However, the subgroup of patients who receive antibiotics and do not experience an adverse event may come out ahead.

Circulating microemboli in patients with myeloproliferative disorders.

Myeloproliferative disorders (MPD) are associated with an increased risk for thrombembolic events. In this study, we examined the prognostic value of transcranial Doppler (TCD) microemboli detection regarding clinical events and correlated TCD findings with results of blood cell counts and platelet flow cytometry to gain insight into the composition of circulating microemboli in these patients. In a cohort of 42 patients with MPD TCD microemboli detection was performed on a single occasion and correlated with thrombembolic events during a prospective follow up of 29.7 +/- 7.3 month. In all patients, a complete blood count and in 17 patients platelet flow cytometry were performed on the day of the TCD examination. Microembolic signals (MES) were recorded in 15 (35.7%) patients, however, without any correlation with the type of MPD, blood cell counts, or thrombembolic events [9 (21.4%)]. MES positive and negative patients did not differ regarding the levels of activated platelets, platelet microaggregates, or microparticles. We found a strong trend for higher rates of platelet-neutrophil conjugates in MES positive patients (P = 0.09). Detection of MES by TCD on a single occasion in MPD patients has only limited prognostic value. MES do not correlate with the type of MPD, nor blood cell counts. Flow cytometry suggests that MES in MPD may consist of platelet-neutrophil aggregates.

Catheter-directed thrombolysis for thromboembolic disease during pregnancy: a viable option.

Anticoagulation with intravenous heparin has been the standard treatment for the management of gestational thromboembolic complications. Catheter-directed thrombolysis is an encouraging approach for the treatment of thromboembolic disease and has not been previously reported during pregnancy. One gravid woman with pulmonary embolism, critically ill, and hemodynamically compromised, and two gravid women with iliofemoral venous thrombosis, who failed to respond to standard treatment with intravenous heparin, were treated with catheter-directed urokinase. All three patients experienced rapid resolution of symptoms and successful pregnancy outcomes. In our three patients, catheter-directed thrombolysis for thromboembolic disease during pregnancy allowed rapid resolution of hemodynamic abnormalities and/or resolution of thrombus. Catheter-directed thrombolysis offered a reasonably safe alternative to prolonged medical management in these young, otherwise healthy, patients. Long-term, it may prevent the postphlebitic syndrome.

Molecular analysis of ERCC2 mutations in the repair deficient hamster mutants UVL-1 and V-H1.

The cDNA sequence of the Chinese hamster ERCC2 nucleotide excision repair and transcription gene from the UVL-1 Chinese hamster ovary (CHO) mutant cell line and the V-H1 Chinese hamster V79 mutant line was analyzed. ERCC2 encodes a presumed ATP-dependent DNA helicase and is single copy in CHO lines due to the structural hemizygosity of chromosome 9. Both UVL-1 and V-H1 have intermediate levels of (6-4) photoproduct repair but are as highly UV sensitive as the group 2 mutants that have no detectable repair. Deficiency in cyclobutane dimer removal has also been shown for V-H1. In UVL-1, a single base substitution resulting in an Arg75-->Trp substitution in helicase domain Ia was identified. The equivalent amino acid position is also Arg in the human, mouse, Xiphophorus maculatus, Saccharomyces cerevisiae, and Schizosaccharomyces pombe homologs. In V-H1, a single base substitution resulting in a Thr46-->Ile substitution in helicase domain I (the ATP-binding domain) was identified in both alleles. The equivalent amino acid position is also Thr in the five homologs. Analysis of three V-H1 partial revertants revealed that they still have the original V-H1 mutation in both alleles, indicating that these are second site reversion events. Site-specific mutagenesis was used to introduce the Thr46-->Ile, Arg75-->Trp, and Lys48-->Arg (helicase domain I) mutations into a hamster ERCC2 expression plasmid. These plasmids each failed to confer UV resistance to group 2 mutant cells, further demonstrating that the changes identified are the causative mutations in V-H1 and UVL-1. Correlations between specific mutations, biochemical activities, and repair phenotype are discussed.

Restoration of preferential and strand specific gene repair in group 2 Chinese hamster ovary mutants (UV5) by the XPD (ERCC2) gene.

It has recently been reported that the XPD (ERCC2) gene is an integral component of the basal transcription factor TFIIH. We have studied the direct role of this repair gene on the fine structure of DNA repair in hamster cells. The gene and strand specific DNA repair of UV induced pyrimidine dimers was determined in wild-type hamster cells, in hamster cells harboring a mutation in the gene homologous to the XPD gene and in mutant cells transfected with the human XPD gene. In the mutant cells, strand specific repair was severely deficient. In the transfected cells, preferential and strand specific gene repair were restored to wild-type levels. The results of the current study clearly demonstrate a direct role for the XPD gene product both in the preferential repair and bulk repair of pyrimidine dimers as well as its high functional conservation between rodent and human cells. An in vitro transcription assay was employed to investigate whether RNA polymerase II mediated transcription was also affected by the transfection with the XPD gene. No change in transcription between the mutant and transfected cells was observed. This suggests that the role of XPD in repair can be distinguished from its role in TFIIH dependent transcription initiation. Different functional domains of XPD appear to be necessary for repair versus transcription.

DNA repair characteristics and mutations in the ERCC2 DNA repair and transcription gene in a trichothiodystrophy patient.

Patient TTD183ME is male and has typical trichothiodystrophy characteristics, including brittle hair, ichthyosis, characteristic face with receding chin and protruding ears, sun sensitivity, and mental and growth retardation. The relative amount of NER carried out by a TTD183ME fibroblast cell strain after ultraviolet (UV) exposure was approximately 65% of normal as determined by a method that converts repair patches into quantifiable DNA breaks. UV survival curves show a reduction in survival only at doses greater than 4 J/m2. Nucleotide sequence analysis of the ERCC2 (XPD) DNA repair and transcription gene cDNA revealed both a Leu461-to-Val substitution and a deletion of amino acids 716-730 in one allele and an Ala725-to-Pro substitution in the other allele. The first allele has also been reported in one xeroderma pigmentosum group D patient and two other trichothiodystrophy patients, while the second allele has not been previously reported. Comparisons suggest that the mutation of Ala725 to Pro correlates with TTD with intermediate UV sensitivity.

Construction of a functional cDNA clone of the hamster ERCC2 DNA repair and transcription gene.

The complete hamster ERCC2 cDNA was constructed in a plasmid vector from clones of three overlapping reverse transcribed/polymerase chain reaction amplified fragments using unique restriction enzyme recognition sites within the regions of overlap. This complete cDNA insert was then cloned into a mammalian expression vector, pcD2E, and tested for function by the ability to confer UV resistance to the ERCC2 mutant CHO cell line UV5. Site-specific mutagenesis was used to introduce the G347-->A and G1844-->A changes resulting in the Cys116-->Tyr and Gly615-->Glu mutations previously identified in UV5 and UVL-13 (also an ERCC2 mutant CHO cell line), respectively. The 116Tyr and 615Glu plasmids each failed to confer UV resistance to UV5 or UVL-13 cells, respectively, demonstrating that the changes identified are indeed the causative mutations in UV5 and UVL-13.

Defects in the DNA repair and transcription gene ERCC2(XPD) in trichothiodystrophy.

Trichothiodystrophy (TTD) is a rare autosomal recessive disorder characterized by brittle hair with reduced sulfur content, ichthyosis, peculiar face, and mental and growth retardation. Clinical photosensitivity is present in approximately 50% of TTD patients but is not associated with an elevated frequency of cancers. Previous complementation studies show that the photosensitivity in nearly all of the studied patients is due to a defect in the same genetic locus that underlies the cancer-prone genetic disorder xeroderma pigmentosum group D (XP-D). Nucleotide-sequence analysis of the ERCC2 cDNA from three TTD cell strains (TTD1V1, TTD3VI, and TTD1RO) revealed mutations within the region from amino acid 713-730 and within previously identified helicase functional domains. The various clinical presentations and DNA repair characteristics of the cell strains can be correlated with the particular mutations found in the ERCC2 locus. Mutations of Arg658 to either His or Cys correlate with TTD cell strains with intermediate UV-sensitivity, mutation of Arg722 to Trp correlates with highly UV-sensitive TTD cell strains, and mutation of Arg683 to Trp correlates with XP-D. Alleles with mutation of Arg616 to Pro or with the combined mutation of Leu461 to Val and deletion of 716-730 are found in both XP-D and TTD cell strains.

Defects in the DNA repair and transcription gene ERCC2 in the cancer-prone disorder xeroderma pigmentosum group D.

Xeroderma pigmentosum (XP) is a sun-sensitive, cancer-prone genetic disorder characterized by a defect in nucleotide excision repair. The human nucleotide excision repair and transcription gene ERCC2 is able to restore survival to normal levels after exposure to UV light in XP complementation group D cells. No enhancement of UV survival is seen in groups C, E, F, or G. XP-CS-2 cells are complemented by ERCC2, confirming the reassignment to group D of this combined XP/Cockayne's syndrome patient. Nucleotide sequence analysis of the ERCC2 cDNA from five XP group D cell strains [XP6BE(SV40), XP17PV, XP102LO, A31-27 (a HeLa/XP102LO hybrid), and XP-CS-2] revealed mutations predominantly affecting previously identified functional domains. The mutations include base substitutions resulting in amino acid substitutions, deletions due to splicing alterations, and defects in expression. XP6BE(SV40), XP17PV, XP102LO, and A31-27 all have one allele with an Arg683 to Trp substitution within the putative nuclear location signal. The genetic disorder trichothiodystrophy (which is not cancer-prone) can also result from mutations in the ERCC2 gene, some of which are the same as those found in XP-D. The various clinical presentations can be correlated with the particular mutations found in the ERCC2 locus.

Aeromonas hydrophila--its implications in freshwater injuries.

Lacerations or puncture wounds sustained in freshwater environments are susceptible to contamination by Aeromonas hydrophila. Numerous cases have been reported of cellulitis secondary to water-related injuries requiring hospitalization where A. hydrophila was the isolated organism. The typical presentation of an infection of A. hydrophila mimics a streptococcal soft tissue infection, which may result in delay in administration of appropriate antibiotics. A case is presented of a nonimmunocompromised patient who developed an A. hydrophila infection following freshwater-related injuries.

Molecular and cellular analysis of the DNA repair defect in a patient in xeroderma pigmentosum complementation group D who has the clinical features of xeroderma pigmentosum and Cockayne syndrome.

Xeroderma pigmentosum (XP) and Cockayne syndrome (CS) are quite distinct genetic disorders that are associated with defects in excision repair of UV-induced DNA damage. A few patients have been described previously with the clinical features of both disorders. In this paper we describe an individual in this category who has unusual cellular responses to UV light. We show that his cultured fibroblasts and lymphocytes are extremely sensitive to irradiation with UV-C, despite a level of nucleotide excision repair that is 30%-40% that of normal cells. The deficiency is assigned to the XP-D complementation group, and we have identified two causative mutations in the XPD gene: a gly-->arg change at amino acid 675 in the allele inherited from the patient's mother and a -1 frameshift at amino acid 669 in the allele inherited from his father. These mutations are in the C-terminal 20% of the 760-amino-acid XPD protein, in a region where we have recently identified several mutations in patients with trichothiodystrophy.

The role of endoscopy in treatment of stenosing posterior tibial tenosynovitis.

Some foot and ankle pathologic conditions can be treated by an endoscopic approach. Its effectiveness has been reported in the treatment of plantar fasciitis. The authors have used an endoscopic approach in the treatment of posterior tibial tenosynovitis resistant to nonsurgical treatment. A review of the pathology, terminology and the diagnosis of tenosynovitis is provided. The case report demonstrates a technique using an endoscope to incise the posterior tibial tendon sheath.

Trichothiodystrophy: clinical spectrum, central nervous system imaging, and biochemical characterization of two siblings.

Trichothiodystrophy (TTD), an autosomal recessive disorder characterized by sulfur-deficient brittle hair, identifies a group of genetic disorders with an altered synthesis of high-sulfur matrix proteins and a defect in excision repair of ultraviolet damage in fibroblasts of most TTD patients. In contrast to patients with xeroderma pigmentosum (XP), TTD patients do not have an increased frequency of skin cancers. TTD patients may be grouped into four categories: 1) those without photosensitivity and without a defect in excision repair of UV damage; 2) those without photosensitivity and with an excision-repair defect in the same gene as in XP-D (complementation group D); 3) those with photosensitivity and with the XP-D repair defect; 4) those with photosensitivity and with a repair defect distinct from that in XP-D. We present a brother and sister in the third category of TTD. Clinically, the patients have brittle hair, short stature, ichthyosis, photosensitivity, nail and dental dysplasias, cataracts, mental retardation, and pyramidal tract abnormalities. Diagnosis was made by hair mount, which shows the characteristic banding pattern with polarizing microscopy, and by hair amino acid analysis, which demonstrated decreased high-sulfur matrix proteins. Fibroblasts cultured from skin biopsies had a marked DNA excision repair defect similar to the repair defect seen in XP-D. We have documented a unique dysmyelinating disorder on magnetic resonance imaging of the brain that might explain their mental retardation, marked hyperactivity, and neurologic deficits. Following the discovery that the human excision repair cross complementing rodent ultraviolet group 2 (ERCC2) gene is able to correct the ultraviolet sensitivity of XP-D cell strains, the ERCC2 cDNA from previous TTD patients was sequenced and shows frameshifts, deletions and point mutations in the ERCC2 gene. Molecular analysis of our patients is in progress. Molecular analysis of the defects in ERCC2 in clinically distinct patients with XP,XP/Cockayne's syndrome, and TTD may provide insight into the molecular mechanisms of these genetically related but clinically distinct disorders.