bluuebunny/crossref_metadata_2025 huggingface dataset:
Testing an ecophysiological mechanism of morphological plasticity in pupfish and its relevance to conservation efforts for endangered Devils Hole pupfish
Authors: Lema Sean C. , Nevitt Gabrielle A.
Published: August 2006

Imperiled species that have been translocated or established in captivity can show rapid alterations in morphology and behavior, but the proximate mechanisms of such phenotypic changes are rarely known. Devils Hole pupfish(Cyprinodon diabolis) are endemic to a single desert pool and are characterized by a small body, large head and eyes, and lack of pelvic fins. To lessen the risk of extinction, additional populations of C. diabolis were established in artificial refuges. Yet, pupfish in these refuges rapidly shifted to a larger body, smaller head and eyes, and greater body depth. Here we examined how food availability and temperature, which differ between these habitats, influence morphological development in closely related Amargosa River pupfish (Cyprinodon nevadensis amargosae). We were interested in knowing whether these environmental factors could developmentally shift Amargosa River pupfish toward the morphology typical of pupfish in Devil's Hole. By regulating food ration, we created groups of pupfish with low, medium and high growth rates. Pupfish with low growth showed proportionally larger head and eyes, smaller body depth, and reduction in pelvic fin development. Elevated temperature further inhibited pelvic fin development in all treatments. Pupfish in the low growth group also showed reduced levels of thyroid hormone, suggesting a possible physiological mechanism underlying these morphological changes. To test this mechanism further, pupfish were reared with goitrogens to pharmacologically inhibit endogenous thyroid hormone production. Pupfish given goitrogens developed larger heads and eyes, shallower bodies, and reduced pelvic fins. Taken together, our results suggest that changes in environmental factors affecting the growth and thyroid hormone status of juvenile pupfish may play a developmental role in generating the morphological differences between C. diabolis in Devil's Hole and the refuges. These findings illustrate the need to incorporate a mechanistic understanding of phenotypic plasticity into conservation strategies to preserve imperiled fishes.
Perturbation of auditory feedback causes systematic perturbation in vocal structure in adult cotton-top tamarins
Authors: Egnor S. E. Roian , Iguina Carmen G. , Hauser Marc D.
Published: August 2006

Auditory feedback is critical for the development and maintenance of speech in humans. In contrast, studies of nonhuman primate vocal production generally report that subjects show little reliance on auditory input. We examined the extent to which cotton-top tamarin (Saguinus oedipus) vocal production is sensitive to perturbation of auditory feedback by manipulating the predictability of presentation of a 1 s burst of white noise during the production of the species-specific contact call, the combination long call(CLC). We used three experimental conditions: the Begin condition, in which white noise was presented only during the first half of a recording session,the End condition, in which white noise was presented only in the last half,and the Random condition, in which each call had a 50% probability of receiving white noise playback throughout the recording session, making the auditory feedback unpredictable. In addition we recorded calls before and after the experimental series (Baseline condition) to determine whether any changes induced by modification of auditory feedback persisted. Results showed that playback of white noise during the production of the CLC produced changes in the temporal structure of the CLC: calls were shorter and had fewer pulses,indicating that modification of auditory feedback can interrupt vocal production. In addition, calls that received modified feedback were louder and had longer inter-pulse intervals than those that did not, consistent with an adaptive response to the masking effect of white noise playback. The magnitude of this compensatory effect and the interruption rate were both sensitive to whether the feedback modification occurred at the beginning or end of the experimental session: early feedback produced less interruption and more compensation. Finally, when auditory feedback modification was unpredictable,adaptive changes were observed in both calls that received modified feedback and those that received normal feedback, suggesting that tamarins can generate an expectation of noise playback and increase vocal amplitude in anticipation of masking.
Odour-evoked responses to queen pheromone components and to plant odours using optical imaging in the antennal lobe of the honey bee droneApis melliferaL.
Authors: Sandoz Jean-Christophe
Published: August 2006

The primordial functional role of honey bee males (drones) is to mate with virgin queens, a behaviour relying heavily on the olfactory detection of queen pheromone. In the present work I studied olfactory processing in the drone antennal lobe (AL), the primary olfactory centre of the insect brain. In drones, the AL consists of about 103 ordinary glomeruli and four enlarged glomeruli, the macroglomeruli (MG). Two macroglomeruli (MG1 and MG2) and approximately 20 ordinary glomeruli occupy the anterior surface of the antennal lobe and are thus accessible to optical recordings. Calcium imaging was used to measure odour-evoked responses to queen pheromonal components and plant odours. MG2 responded specifically to the main component of the queen mandibular pheromone, 9-ODA. The secondary components HOB and HVA each triggered activity in one, but not the same, ordinary glomerulus. MG1 did not respond to any of the tested stimuli. Plant odours induced signals only in ordinary glomeruli in a combinatorial manner, as in workers. This study thus shows that the major queen pheromonal component is processed in the most voluminous macroglomerulus of the drone antennal lobe, and that plant odours,as well as some queen pheromonal components, are processed in ordinary glomeruli.
Correlation between thermotolerance and membrane properties inParamecium aurelia
Authors: Sasaki Toshiaki , Konoha Yoshimi , Toyoda Taichi , Yasaka Yuta , Przybos Eva , Nakaoka Yasuo
Published: August 2006

The relationship between thermotolerance and membrane properties was studied by using a ciliated protozoan, Paramecium aurelia. P. aurelia is a complex of sibling species termed `syngens' whose cell morphology appear similar on microscopic examination. From the comparison of tolerance to increasing temperature among 14 syngens of P. aurelia,we selected syngens 2 and 3 as low thermotolerant examples, and syngens 8 and 10 as high thermotolerant examples. The membrane resistance of high thermotolerant syngens measured by injection of a constant inward current was greater than that of low thermotolerant syngens. Membrane fluidity measurements of living cells using the fluorescent dye,6-lauroyl-2-dimethylaminonaphtalene (laurdan) showed that the fluidity at the cultured temperature was decreased in high thermotolerant syngens compared to that of low thermotolerant syngens. However, when the temperature was increased to the killing temperature of each syngens, the fluidity was increased to almost the same level irrespective of syngen. Furthermore,analysis of fatty acids extracted from whole cells showed that the ratios of unsaturated to saturated fatty acids was smaller in high thermotolerant syngens than in low thermotolerant syngens. These results suggest that the thermotolerance of P. aurelia syngens is determined by the membrane fluidity which is related to the fatty acids composition.
Effective elastic modulus of isolated gecko setal arrays
Authors: Autumn K. , Majidi C. , Groff R. E. , Dittmore A. , Fearing R.
Published: August 2006

Conventional pressure sensitive adhesives (PSAs) are fabricated from soft viscoelastic materials that satisfy Dahlquist's criterion for tack with a Young's modulus (E) of 100 kPa or less at room temperature and 1 Hz. In contrast, the adhesive on the toes of geckos is made of β-keratin, a stiff material with E at least four orders of magnitude greater than the upper limit of Dahlquist's criterion. Therefore, one would not expect aβ-keratin structure to function as a PSA by deforming readily to make intimate molecular contact with a variety of surface profiles. However, since the gecko adhesive is a microstructure in the form of an array of millions of high aspect ratio shafts (setae), the effective elastic modulus(Eeff) is much lower than E of bulkβ-keratin. In the first test of the Eeff of a gecko setal adhesive, we measured the forces resulting from deformation of isolated arrays of tokay gecko (Gekko gecko) setae during vertical compression, and during tangential compression at angles of +45° and-45°. We tested the hypothesis that Eeff of gecko setae falls within Dahlquist's criterion for tack, and evaluated the validity of a model of setae as cantilever beams. Highly linear forces of deformation under all compression conditions support the cantilever model. Eeff of setal arrays during vertical and +45°compression (along the natural path of drag of the setae) were 83±4.0 kPa and 86±4.4 kPa (means ± s.e.m.), respectively. Consistent with the predictions of the cantilever model, setae became significantly stiffer when compressed against the natural path of drag: Eeff during -45° compression was 110±4.7 kPa. Unlike synthetic PSAs, setal arrays act as Hookean elastic solids; setal arrays function as a bed of springs with a directional stiffness, assisting alignment of the adhesive spatular tips with the contact surface during shear loading.
How Often Should Reputation Mechanisms Update a Trader's Reputation Profile?
Authors: Dellarocas Chrysanthos
Published: August 2006

Reputation mechanisms have become an important component of electronic markets, helping to build trust and elicit cooperation among loosely connected and geographically dispersed economic agents. Understanding the impact of different reputation mechanism design parameters on the resulting market efficiency has thus emerged as a question of theoretical and practical interest. Along these lines, this note studies the impact of the frequency of reputation profile updates on cooperation and efficiency. The principal finding is that, in trading settings with pure moral hazard and noisy ratings, if the per-period profit margin of cooperating sellers is sufficiently high, a mechanism that does not publish every single rating it receives but rather only updates a trader's public reputation profile every k transactions with a summary statistic of a trader's most recent k ratings can induce higher average levels of cooperation and market efficiency than a mechanism that publishes all ratings as soon as they are posted. This paper derives expressions for calculating the optimal profile updating interval k, discusses the implications of this finding for existing systems, such as eBay, and proposes alternative reputation mechanism architectures that attain higher maximum efficiency than the, currently popular, reputation mechanisms that publish summaries of a trader's recent ratings.
Reconceptualizing System Usage: An Approach and Empirical Test
Authors: Burton-Jones Andrew , Straub Detmar W.
Published: August 2006

Although DeLone, McLean, and others insist that system usage is a key variable in information systems research, the system usage construct has received little theoretical scrutiny, boasts no widely accepted definition, and has been operationalized by a diverse set of unsystematized measures. In this article, we present a systematic approach for reconceptualizing the system usage construct in particular nomological contexts. Comprising two stages, definition and selection, the approach enables researchers to develop clear and valid measures of system usage for a given theoretical and substantive context. The definition stage requires that researchers define system usage and explicate its underlying assumptions. In the selection stage, we suggest that system usage be conceptualized in terms of its structure and function. The structure of system usage is tripartite, comprising a user, system, and task, and researchers need to justify which elements of usage are most relevant for their study. In terms of function, researchers should choose measures for each element (i.e., user, system, and/or task) that tie closely to the other constructs in the researcher's nomological network.

To provide evidence of the viability of the approach, we undertook an empirical investigation of the relationship between system usage and short-run task performance in cognitively engaging tasks. The results support the benefits of the approach and show how an inappropriate choice of usage measures can lead researchers to draw opposite conclusions in an empirical study. Together, the approach and the results of the empirical investigation suggest new directions for research into the nature of system usage, its antecedents, and its consequences.
On the Optimality of Fixed-up-to Tariff for Telecommunications Service
Authors: Masuda Yasushi , Whang Seungjin
Published: August 2006

A tariff is the total charge payable by a customer for services provided. We study the design of tariffs for a telecommunications service provider. We develop an economic model that captures the negative externalities of the network and the diversity of customers. The tariff is designed so that it reflects the expected response of different customers and the system congestion it would induce. We study a simple tariff structure in wide use by mobile phone carriers—a menu of “fixed-up-to (FUT)” plans like “fixed access fee $35 up to 300 minutes, and $0.40 per minute beyond the limit.” We derive the optimal menu of FUT plans and show that such a simple FUT menu structure delivers as good performance to the monopolistic carrier as any nonlinear pricing schedule.
Editorial Notes
Authors: Sambamurthy Vallabh
Published: August 2006

Information Systems Research continues to grow with submission increases, in no small part due to greater interest in the journal from Asian academics. The journal welcomes manuscripts on important and interesting phenomena from the global community of IS scholars. A new special issue on “Flexible and Distributed Information Systems Development” is announced.
Bertolotti’s syndrome
Authors: Quinlan J. F. , Duke D. , Eustace S.
Published: August 2006

Bertolotti’s syndrome is characterised by anomalous enlargement of the transverse process(es) of the most caudal lumbar vertebra which may articulate or fuse with the sacrum or ilium and cause isolated L4/5 disc disease.

We analysed the elective MR scans of the lumbosacral spine of 769 consecutive patients with low back pain taken between July 2003 and November 2004. Of these 568 showed disc degeneration. Bertolotti’s syndrome was present in 35 patients with a mean age of 32.7 years (15 to 60). This was a younger age than that of patients with multiple disc degeneration, single-level disease and isolated disc degeneration at the L4/5 level (p ≤ 0.05). The overall incidence of Bertolotti’s syndrome in our study was 4.6% (35 of 769). It was present in 11.4% (20 patients) of the under-30 age group.

Our findings suggest that Bertolotti’s syndrome must form part of a list of differential diagnoses in the investigation of low back pain in young people.
Is secondary radiological follow-up of infants with a family history of developmental dysplasia of the hip necessary?
Authors: Arumilli B. R. B. , Koneru P. , Garg N. K. , Davies R. , Saville S. , Sampath J. , Bruce C.
Published: August 2006

The practice of regular radiological follow-up of infants with a positive family history of developmental dysplasia of the hip is based on the widespread belief that primary acetabular dysplasia is a genetic disorder which can occur in the absence of frank subluxation or dislocation. We reviewed all infants who were involved in our screening programme for developmental dysplasia of the hip, between November 2002 and January 2004, and who had a normal clinical and ultrasound examination of the hip at six to eight weeks of age, but who, because of a family history of developmental dysplasia of the hip, had undergone further radiography after an interval of 6 to 12 months. The radiographs of 89 infants were analysed for signs of late dysplasia of the hip and assessed independently by three observers to allow for variability of measurement. There were 11 infants (11%) lost to follow-up.

All the patients had normal radiographs at the final follow-up and none required any intervention. We therefore question the need for routine radiological follow-up of infants with a positive family history of developmental dysplasia of the hip, but who are normal on clinical examination and assessment by ultrasound screening when six to eight weeks old.
Iontophoresis of antibiotics into segmental allografts
Authors: Khoo P. P. C. , Michalak K. A. , Yates P. J. , Megson S. M. , Day R. E. , Wood D. J.
Published: August 2006

Iontophoresis is a novel technique which may be used to facilitate the movement of antibiotics into the substance of bone using an electrical potential applied externally. We have examined the rate of early infection in allografts following application of this technique in clinical practice. A total of 31 patients undergoing revision arthroplasty or surgery for limb salvage received 34 iontophoresed sequential allografts, of which 26 survived for a minimum of two years. The mean serum antibiotic levels after operation were low (gentamicin 0.37 mg/l (0.2 to 0.5); flucloxacillin 1 mg/l (0 to 1) and the levels in the drains were high (gentamicin 40 mg/l (2.5 to 131); flucloxacillin 17 mg/l (1 to 43). There were no early deep infections. Two late infections were presumed to be haemotogenous; 28 of the 34 allografts were retained. In 12 patients with pre-existing proven infection further infection has not occurred at a mean follow-up of 51 months (24 to 82).
Does salvage and tranexamic acid reduce the need for blood transfusion in revision hip surgery?
Authors: Phillips S. J. , Chavan R. , Porter M. L. , Kay P. R. , Hodgkinson J. P. , Purbach B. , Reddick A. Hoad , Frayne J. M.
Published: August 2006

We carried out a retrospective case-control study in 80 patients who underwent a revision total hip replacement. Group A (40 patients) received tranexamic acid and intra-operative cell salvage. Group B (40 patients) was a matched control group and did not receive this management. Each group was divided into four subgroups: revision of both components, revision of both components with bone grafting, revision of the acetabular component with or without bone graft, and revision of the femoral component with or without bone graft.

In group A the total number of units transfused was 52, compared with 139 in group B, representing a reduction in blood usage of 62.5%. The mean amount of blood transfused from cell salvage in each group was 858 ml (113 to 2100), 477 ml (0 to 2680), 228 ml (75 to 315) and 464 ml (120 to 1125), respectively. There was a significant difference in the amount of blood returned between the groups (p < 0.0001).

In group A, 22 patients needed transfusion and in group B, 37 (p < 0.0001). A cost analysis calculation showed a total revenue saving of £70 000 and a potential saving throughout our facility of £318 288 per year.

Our results show that a significant reduction in blood transfusion can be made using combined cell salvage and tranexamic acid in revision surgery of the hip.
Exposure of the head of the radius using the Wrightington approach
Authors: Stanley J. K. , Penn D. S. , Wasseem M.
Published: August 2006

Surgical access to the head of the radius is usually performed through a lateral approach. We present an alternative technique through a modified posterior approach which was developed following dissections of 22 human cadavers. An osteotomy of the supinator tuberosity was performed and reflected as a single unit with the attached annular ligament. Excellent exposure of the head of the radius was achieved, replacement of the head was undertaken and the osteotomy site repaired. The elbows were stable and had a full range of movement. The approach was then carried out on 13 patients for elective replacement of the head and was found to be safe and reproducible. In the patient group all osteotomies united, the elbows were stable and had an improved range of supination and pronation. There was no change in flexion and extension of the elbow. Complications included a haematoma and a reflex sympathetic dystrophy.

The modified posterior approach provides excellent access to the head and neck of the radius, gives good stability of the elbow and allows early mobilisation of the joint.
Homologous blood transfusion is not required in surgery for adolescent idiopathic scoliosis
Authors: Verma R. R. , Williamson J. B. , Dashti H. , Patel D. , Oxborrow N. J.
Published: August 2006

We studied 70 consecutive patients with adolescent idiopathic scoliosis who underwent corrective surgery. They were divided into two groups. In the study group of 38 patients one or more modern blood-conservation measures was used peri-operatively. The 32 patients in the control group did not have these measures. Both groups were similar in regard to age, body-weight, the number of levels fused and the type of surgery.

Only two patients in the study group were transfused with homologous blood and these transfusions were ‘off-protocol’. Wastage of autologous pre-donated units was minimal (6 of 83 units). By contrast, all patients in the control group were transfused with homologous blood. In the study group there was a significant decrease (p = 0.005) in the estimated blood loss when all the blood-conservation methods were used.

The use of blood-conservation measures, the lowering of the haemoglobin trigger for transfusion and the education of the entire team involved in the care of the patient can prevent the need for homologous blood transfusion in patients undergoing surgery for adolescent idiopathic scoliosis.
The novel use of resorbable Vicryl mesh for in vivo tendon reconstruction to a metal prosthesis
Authors: Pendegrass C. J. , Oddy M. J. , Sundar S. , Cannon S. R. , Goodship A. E. , Blunn G. W.
Published: August 2006

We examined the mechanical properties of Vicryl (polyglactin 910) mesh in vitro and assessed its use in vivo as a novel biomaterial to attach tendon to a hydroxyapatite-coated metal implant, the interface of which was augmented with autogenous bone and marrow graft. This was compared with tendon re-attachment using a compressive clamp device in an identical animal model. Two- and four-ply sleeves of Vicryl mesh tested to failure under tension reached 5.13% and 28.35% of the normal ovine patellar tendon, respectively. Four-ply sleeves supported gait in an ovine model with 67.05% weight-bearing through the operated limb at 12 weeks, without evidence of mechanical failure.

Mesh fibres were visible at six weeks but had been completely resorbed by 12 weeks, with no evidence of chronic inflammation. The tendon-implant neoenthesis was predominantly an indirect type, with tendon attached to the bone-hydroxyapatite surface by perforating collagen fibres.
Delays in definitive reconstruction of complex pelvic and acetabular fractures
Authors: Bircher M. , Lewis A. , Halder S.
Published: August 2006

There are unacceptable delays in the management of pelvic trauma in the United Kingdom. In 2003 this became a political issue after TV and radio coverage. Changes to the service were introduced, including trauma coordinators and a special tariff, but has it made a difference?
Five- to 12-year follow-up of a hydroxyapatite-coated, cementless total knee replacement in young, active patients
Authors: Tai C. C. , Cross M. J.
Published: August 2006

We carried out a prospective study of 118 hydroxyapatite-coated, cementless total knee replacements in patients who were ≤ 55 years of age and who had primary (92; 78%) or post-traumatic (26; 22%) osteoarthritis. The mean period of follow-up was 7.9 years (5 to 12.5). The Knee Society clinical scores improved from a pre-operative mean of 98 (0 to 137) to a mean of 185 (135 to 200) at five years, and 173 (137 to 200) at ten years. There were two revisions of the tibial component because of aseptic loosening, and one case of polyethylene wear requiring further surgery. There was no osteolysis or progressive radiological loosening of any other component. At 12 years, the overall rate of implant survival was 97.5% (excluding exchange of spacer) and 92.1% (including exchange of spacer).

Cementless total knee replacement can achieve excellent long-term results in young, active patients with osteoarthritis. In contrast to total hip replacement, polyethylene wear, osteolysis and loosening of the prosthesis were not major problems for these patients, although it is possible that this observation could change with longer periods of follow-up.
Repair of chronic osteochondral defects in the rat
Authors: Nishimori M. , Deie M. , Kanaya A. , Exham H. , Adachi N. , Ochi M.
Published: August 2006

Bone marrow mesenchymal stromal cells were aspirated from immature male green fluorescent protein transgenic rats and cultured in a monolayer. Four weeks after the creation of the osteochondral defect, the rats were divided into three groups of 18: the control group, treated with an intra-articular injection of phosphate-buffered saline only; the drilling group, treated with an intra-articular injection of phosphate-buffered saline with a bone marrow-stimulating procedure; and the bone marrow mesenchymal stromal cells group, treated with an intra-articular injection of bone marrow mesenchymal stromal cells plus a bone marrow-stimulating procedure. The rats were then killed at 4, 8 and 12 weeks after treatment and examined.

The histological scores were significantly better in the bone marrow mesenchymal stromal cells group than in the control and drilling groups at all time points (p < 0.05). The fluorescence of the green fluorescent protein-positive cells could be observed in specimens four weeks after treatment.
Polyaxially-locked plate screws increase stability of fracture fixation in an experimental model of calcaneal fracture
Authors: Richter M. , Droste P. , Goesling T. , Zech S. , Krettek C.
Published: August 2006

Different calcaneal plates with locked screws were compared in an experimental model of a calcaneal fracture. Four plate models were tested, three with uniaxially-locked screws (Synthes, Newdeal, Darco), and one with polyaxially-locked screws (90° ± 15°) (Rimbus). Synthetic calcanei were osteotomised to create a fracture model and then fixed with the plates and screws. Seven specimens for each plate model were subjected to cyclic loading (preload 20 N, 1000 cycles at 800 N, 0.75 mm/s), and load to failure (0.75 mm/s).

During cyclic loading, the plate with polyaxially-locked screws (Rimbus) showed significantly lower displacement in the primary loading direction than the plates with uniaxially-locked screws (mean values of maximum displacement during cyclic loading: Rimbus, 3.13 mm (sd 0.68); Synthes, 3.46 mm (sd 1.25); Darco, 4.48 mm (sd 3.17); Newdeal, 5.02 mm (sd 3.79); one-way analysis of variance, p < 0.001).

The increased stability of a plate with polyaxially-locked screws demonstrated during cyclic loading compared with plates with uniaxially-locked screws may be beneficial for clinical use.
Extra-axial chordoma
Authors: van Akkooi A. C. J. , van Geel A. N. , Bessems J. H. J. M. , den Bakker M. A.
Published: August 2006

A chordoma which occurs as a primary tumour outside the axial skeleton is known as an extra-axial chordoma, parachordoma or chordoma periphericum. It is extremely rare and therefore survival, recurrence and the rates of metastasis are not known. Whilst few recurrences have been described, the extra-axial chordoma has the potential for late recurrence at up to 12 years. Metastases are even less frequent.

We report the case of a 56-year-old woman who developed an extra-axial chordoma of the right thoracic wall in close relationship with the tenth rib. The tumour was completely removed and the prognosis is excellent.
Statistics in orthopaedic papers
Authors: Petrie A.
Published: August 2006

Although the importance of sound statistical principles in the design and analysis of data has gained prominence in recent years, biostatistics, the application of statistics to the analysis of biological and medical data, is still a subject which is poorly understood and often mishandled. This review introduces, in the context of orthopaedic research, the terminology and the principles involved in simple data analysis, and outlines areas of medical statistics that have gained prominence in recent years. It also lists and provides an insight into some of the more common errors that occur in published orthopaedic journals and which are frequently encountered at the review stage in papers submitted to the Journal of Bone and Joint Surgery.
Simvastatin-Induced Decline in Cognition
Authors: Padala Kalpana P , Padala Prasad R , Potter Jane F
Published: August 2006

Objective:

To describe a case of new-onset cognitive difficulties in an older patient after initiation of simvastatin therapy.

Case Summary:

A 64-year-old man developed cognitive difficulties within one week after starting simvastatin 40 mg/day. There was a 3 point decline from baseline in the Mini-Mental State Exam (MMSE) score 2 weeks after simvastatin was initiated, as well as declines in the Activities of Daily Living and Instrumental Activities of Daily Living scales. Simvastatin was discontinued, and the patient's cognition improved to baseline within 6 weeks. Rechallenge with simvastatin at half the original dose was attempted. His cognition deteriorated over a 2 week period. Simvastatin was stopped, and the patient's MMSE scores returned to baseline within 4 weeks.

Discussion:

This patient developed new-onset problems with short-term memory, long-term memory, and item misplacement in addition to the baseline problems with names and word-finding that had been present prior to beginning statin therapy. Decreased cognition identified with neuropsychological tests has been shown in clinical trials with simvastatin; however, as of August 23, 2006, this is the first report of cognitive and functional problems that have been documented using standardized instruments. The Naranjo probability scale revealed a highly probable adverse reaction of cognitive decline associated with simvastatin therapy.

Conclusions:

Statins are commonly used in the older population. Simvastatin appeared to be associated with worsened cognition in our patient, an older person with preexisting memory problems. Statins should be used with caution in this vulnerable population.
Pharmacokinetics of Oseltamivir in Young and Very Elderly Subjects
Authors: Abe Masaichi , Smith James , Urae Akinori , Barrett Joanne , Kinoshita Haruki , Rayner Craig R
Published: August 2006

Background:

Pharmacokinetic studies of oseltamivir in very elderly patients (≥80 y) have not previously been performed.

Objective:

To compare the pharmacokinetics of oseltamivir and the active carboxylate metabolite in healthy young and very elderly Japanese subjects.

Methods:

Young (20–35 y, fasting, n = 7) and very elderly subjects (≥80 y, fed, n = 5) were enrolled in single-center studies and received a single oral dose of oseltamivir 75 mg. Plasma and urine samples were collected (24 h) for pharmacokinetic analysis, and safety was assessed.

Results:

The time to maximum plasma concentration (tmax for oseltamivir was delayed in the very elderly compared with the young subjects (2.30 vs 0.71 h, respectively). Furthermore, oseltamivir maximum plasma concentration (Cmax) and AUCinf were 52% and 80% higher, respectively, in the very elderly compared with the young subjects. Oral clearance was 45% lower in elderly patients, possibly due to the effects of administration of oseltamivir with a meal. For the active metabolite, oseltamivir carboxylate, Cmax and AUCinf values were, respectively, 22% and 91% higher in the very elderly subjects than in the young subjects, while oral clearance was 50% lower in the elderly population. The increased exposure of the active metabolite is likely to correlate with an age-related decline in renal function. For both oseltamivir and the active metabolite, there was large interpatient variability in the Cmax values. The data reported here indicate that oseltamivir would be effective in both of these populations, as trough concentrations for the active metabolite at 12 and 24 hours exceeded the 50% inhibitory concentration against the neuraminidase of influenza A and B isolates by more than 50-fold. Oseltamivir was well tolerated in both groups.

Conclusions:

Exposures (AUCinf) to both the parent drug and active metabolite were increased by more than 80% in the small number of very elderly subjects presented here. However, oseltamivir was well tolerated by these subjects.
Paroxetine Useful for Palmar–Plantar Hyperhidrosis
Authors: Praharaj Samir Kumar , Arora Manu
Published: August 2006

Objective:

To report a case of palmar–plantar hyperhidrosis (PPH) In which paroxetine was found to be helpful.

Case Summary:

A 32-year-old man with a history of excessive sweating of the palms and soles since childhood was diagnosed with PPH and was prescribed paroxetine 10 mg/day, which was increased to 20 mg/day. After one month, he experienced a marked reduction in sweating and improvement in socio-occupational functioning, which were sustained during follow-up at 6 months without any emergent adverse effects.

Discussion:

Paroxetine's anticholinergic action may be responsible for its beneficial effect in PPH, as it may override the adrenergic mechanism, which has a minor effect on sweating from eccrine glands. Alternatively, paroxetine's beneficial effect in PPH may be secondary to its antianxiety effect, through central mechanisms.

Conclusions:

Paroxetine may be a useful option in the treatment of PPH.
Obesity: Low-Dose Orlistat Effects on Body Weight of Mildly to Moderately Overweight Individuals: A 16 Week, Double-Blind, Placebo-Controlled Trial
Authors: Anderson James W , Schwartz Susan M , Hauptman Jonathan , Boldrin Mark , Rossi Maureen , Bansal Vidhu , Hale Cecilia A
Published: August 2006

Background:

Lifestyle measures are considered the first line of therapy for treating overweight individuals, but many are unable to achieve a meaningful weight loss.

Objective:

To determine the efficacy and safety of orlistat 60 mg, given 3 times daily, for weight loss in mildly to moderately overweight individuals.

Methods:

A multicenter, 16 week, randomized, double-blind, placebo-controlled study was conducted in 391 overweight subjects at 20 US centers. The main outcome measure was change in weight from baseline to week 16; secondary measures included changes in body mass index, waist circumference, blood pressure, and fasting lipoprotein and glucose levels.

Results:

Subjects in both groups lost weight over the treatment period; however, orlistat-treated subjects lost significantly more weight than placebo-treated subjects beyond 2 weeks of treatment. Weight loss from baseline to week 16 was significantly greater in participants receiving orlistat versus those receiving placebo (3.05 vs 1.90 kg; p < 0.001, intent-to-treat analysis). Orlistat-treated subjects who completed 16 weeks of treatment lost 4.8 ± 0.35% (mean ± SE) of baseline weight compared with 3.1 ± 0.38% for the placebo group (p < 0.001). Orlistat-treated subjects, compared with those receiving placebo, also demonstrated a greater relative reduction in total (–4.4% vs 0.0%; p = 0.004) and low-density lipoprotein cholesterol (–7.2% vs -0.6%; p = 0.005) and both diastolic (-3.9% vs -0.5%; p = 0.001) and systolic blood pressure (-4.7% vs -1.8%; p = 0.004). Both groups showed a similar safety profile; gastrointestinal events were significantly more common in the orlistat-treated subjects.

Conclusions:

The use of orlistat 60 mg by mildly to moderately overweight individuals produced significant weight loss in conjunction with a reduced calorie diet and self-instructional materials. This amount of weight loss was associated with improvements in several weight-related risk factors. Orlistat 60 mg may be a useful adjunct to lifestyle measures and has the potential to contribute significantly to weight and risk factor improvement for overweight individuals.
Age- and Sex-Specific Differences in the Factor of Risk for Vertebral Fracture: A Population-Based Study Using QCT
Authors: Bouxsein Mary L , Melton L Joseph , Riggs B Lawrence , Muller John , Atkinson Elizabeth J , Oberg Ann L , Robb Richard A , Camp Jon J , Rouleau Peggy A , McCollough Cynthia H , Khosla Sundeep
Published: August 2006

We used QCT scans obtained in 687 men and women, 21–97 years of age, to estimate the factor of risk for vertebral fracture, Φvert, defined as the ratio of spinal loading to vertebral strength. With age, vertebral strength declined and Φvert increased significantly more in women than men. Age- and sex-specific differences in Φvert closely resembled previously reported vertebral fracture incidence.

Introduction: Despite the high prevalence of vertebral fractures, little is known about the interaction between spinal loading and vertebral fragility.

Materials and Methods: We assessed the ratio of spinal loading to vertebral strength (i.e., the factor of risk, Φvert) in an age- and sex-stratified population-based sample of 700 women and men 21–97 years of age. We measured volumetric BMD (vBMD, mg/cm3) and cross-sectional area (CSA, cm2) of the midvertebral bodies of L1–L3 using QCT and computed vertebral compressive strength from these data using engineering beam theory. A biomechanical model of the trunk was used to estimate compressive forces applied to the L3 vertebral body during standing, bending forward, and bending forward while lifting 10 kg. The factor of risk for fracture, Φvert, was computed as the ratio of spinal compressive force to vertebral strength for each activity.

Results: Men had a higher vertebral strength at all ages, largely because of their greater CSA. Whereas both sexes exhibited a marked decline in vertebral compressive strength with age (p < 0.001), the decline was greater in women than men (−43% versus −31%, p = 0.008). Compressive forces on L3 were greater in men than women, because of their greater body weight and height. For both sexes, forces during bending and lifting were 8-fold higher than those experienced during upright standing. For all activities, Φvert increased with age, but significantly more so in women than men (p < 0.001). For bending and lifting, Φvert-bending exceeded 1.0 in 30% of women and 12% of men ≥50 years of age, values that are similar to the reported frequency of vertebral fracture.

Conclusion: These findings illustrate potential mechanisms underlying vertebral fractures and provide strong rationale for further evaluation of this QCT-based biomechanical approach for assessment of fracture risk.
Vitamin D–Mediated Hypercalcemia in Slack Skin Disease: Evidence for Involvement of Extrarenal 25-Hydroxyvitamin D 1α-Hydroxylase
Authors: Karakelides Helen , Geller Jordan L , Schroeter Arnold L , Chen Hong , Behn Philip S , Adams John S , Hewison Martin , Wermers Robert A
Published: August 2006

A case of granulomatous slack skin disease is presented in which we studied the possible involvement of extrarenal 1,25(OH)2D in the pathogenesis of the patient's hypercalcemia. Immunolocalization of 1α-OH in skin showed simultaneous dysregulation in epithelial and granulomatous cells.

Introduction: Granuloma-forming diseases such as sarcoidosis are associated with extrarenal synthesis of active 1,25-dihydroxyvitamin D [1,25(OH)2D]. Here we describe a case of granulomatous slack skin disease in which we have studied the possible involvement of extrarenal synthesis of 1,25(OH)2D in the pathogenesis of the patient's hypercalcemia. The aim of the study was to clarify the etiology of hypercalcemia in this patient.

Materials and Methods: This was a case study of a 19-year-old man with a T-cell lymphoproliferative disorder diagnosed as granulomatous slack skin disease who presented with hypercalcemia and raised serum 1,25(OH)2D. Analysis of expression of the enzyme 25-hydroxyvitamin D 1α-hydroxylase (1α-hydroxylase), which catalyzes synthesis of 1,25(OH)2D, was carried out by immunohistochemical analysis of involved and uninvolved skin. Approval was granted by the Mayo Foundation Institutional Review Board and Biospecimens Subcommittee.

Results: In uninvolved skin, expression of 1α-hydroxylase was confined to the basal layer of the epidermis, whereas slack skin showed overexpression of the enzyme in dermal granulomata and basal cells of the epidermis.

Conclusions: Hypercalcemia associated with granulomatous slack skin syndrome seems to be caused by dysregulation of 1α-hydroxylase expression in both epidermal and dermal granulomatous cells. This contrasts with psoriasis and sarcoidosis of the skin, in which overexpression of the enzyme is restricted to keratinocytes and granulomata, respectively.
Role of IGF-I Signaling in Regulating Osteoclastogenesis
Authors: Wang Yongmei , Nishida Shigeki , Elalieh Hashem Z , Long Roger K , Halloran Bernard P , Bikle Daniel D
Published: August 2006

We showed that IGF-I deficiency impaired osteoclastogenesis directly and/or indirectly by altering the interaction between stromal/osteoblastic cells and osteoclast precursors, reducing RANKL and M-CSF production. These changes lead to impaired bone resorption, resulting in high BV/TV in IGF-I null mice.

Introduction: Although IGF-I has been clearly identified as an important growth factor in regulating osteoblast function, information regarding its role in osteoclastogenesis is limited. Our study was designed to analyze the role of IGF-I in modulating osteoclastogenesis using IGF-I knockout mice (IGF-I−/−).

Materials and Methods: Trabecular bone volume (BV/TV), osteoclast number, and morphology of IGF-I−/− or wildtype mice (IGF-I+/+) were evaluated in vivo by histological analysis. Osteoclast precursors from these mice were cultured in the presence of RANKL and macrophage-colony stimulating factor (M-CSF) or co-cultured with stromal/osteoblastic cells from either genotype. Osteoclast formation was assessed by measuring the number of multinucleated TRACP+ cells and pit formation. The mRNA levels of osteoclast regulation markers were determined by quantitative RT-PCR.

Results: In vivo, IGF-I−/− mice have higher BV/TV and fewer (76% of IGF-I+/+) and smaller osteoclasts with fewer nuclei. In vitro, in the presence of RANKL and M-CSF, osteoclast number (55% of IGF-I+/+) and resorptive area (30% of IGF-I+/+) in osteoclast precursor cultures from IGF-I−/− mice were significantly fewer and smaller than that from the IGF-I+/+ mice. IGF-I (10 ng/ml) increased the size, number (2.6-fold), and function (resorptive area, 2.7-fold) of osteoclasts in cultures from IGF-I+/+ mice, with weaker stimulation in cultures from IGF-I−/− mice. In co-cultures of IGF-I−/− osteoblasts with IGF-I+/+ osteoclast precursors, or IGF-I+/+ osteoblasts with IGF-I−/− osteoclast precursors, the number of osteoclasts formed was only 11% and 48%, respectively, of that from co-cultures of IGF-I+/+ osteoblasts and IGF-I+/+ osteoclast precursors. In the long bones from IGF-I−/− mice, mRNA levels of RANKL, RANK, M-CSF, and c-fms were 55%, 33%, 60%, and 35% of that from IGF-I+/+ mice, respectively.

Conclusions: Our results indicate that IGF-I regulates osteoclastogenesis by promoting their differentiation. IGF-I is required for maintaining the normal interaction between the osteoblast and osteoclast to support osteoclastogenesis through its regulation of RANKL and RANK expression.
Low-Level, High-Frequency Mechanical Signals Enhance Musculoskeletal Development of Young Women With Low BMD
Authors: Gilsanz Vicente , Wren Tishya AL , Sanchez Monique , Dorey Frederick , Judex Stefan , Rubin Clinton
Published: August 2006

The potential for brief periods of low-magnitude, high-frequency mechanical signals to enhance the musculoskeletal system was evaluated in young women with low BMD. Twelve months of this noninvasive signal, induced as whole body vibration for at least 2 minutes each day, increased bone and muscle mass in the axial skeleton and lower extremities compared with controls.

Introduction: The incidence of osteoporosis, a disease that manifests in the elderly, may be reduced by increasing peak bone mass in the young. Preliminary data indicate that extremely low-level mechanical signals are anabolic to bone tissue, and their ability to enhance bone and muscle mass in young women was investigated in this study.

Materials and Methods: A 12-month trial was conducted in 48 young women (15–20 years) with low BMD and a history of at least one skeletal fracture. One half of the subjects underwent brief (10 minutes requested), daily, low-level whole body vibration (30 Hz, 0.3g); the remaining women served as controls. Quantitative CT performed at baseline and at the end of study was used to establish changes in muscle and bone mass in the weight-bearing skeleton.

Results: Using an intention-to-treat (ITT) analysis, cancellous bone in the lumbar vertebrae and cortical bone in the femoral midshaft of the experimental group increased by 2.1% (p = 0.025) and 3.4% (p < 0.001), respectively, compared with 0.1% (p = 0.74) and 1.1% (p = 0.14), in controls. Increases in cancellous and cortical bone were 2.0% (p = 0.06) and 2.3% (p = 0.04) greater, respectively, in the experimental group compared with controls. Cross-sectional area of paraspinous musculature was 4.9% greater (p = 0.002) in the experimental group versus controls. When a per protocol analysis was considered, gains in both muscle and bone were strongly correlated to a threshold in compliance, where the benefit of the mechanical intervention compared with controls was realized once subjects used the device for at least 2 minute/day (n = 18), as reflected by a 3.9% increase in cancellous bone of the spine (p = 0.007), 2.9% increase in cortical bone of the femur (p = 0.009), and 7.2% increase in musculature of the spine (p = 0.001) compared with controls and low compliers (n = 30).

Conclusions: Short bouts of extremely low-level mechanical signals, several orders of magnitude below that associated with vigorous exercise, increased bone and muscle mass in the weight-bearing skeleton of young adult females with low BMD. Should these musculoskeletal enhancements be preserved through adulthood, this intervention may prove to be a deterrent to osteoporosis in the elderly.