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Interactive relations of central versus total obesity and blood pressure to cognitive function.

OBJECTIVE: To examine the potential interactive relations of central versus total obesity and blood pressure (BP) to cognitive function. METHOD: In all, 90 healthy, stroke, and dementia-free middle-aged and older adults (ages 54-81 years; 63% male; 93% White) underwent biomedical and neuropsychological assessment. Relations of central obesity (assessed by waist circumference (WC)) and systolic or diastolic BP to cognitive function were examined in multiple regression models. Next, body mass index (BMI) was substituted for WC in the models. RESULTS: After statistical adjustment for age, education, gender, and other potential confounders including components of the metabolic syndrome (depending on the model), significant interactions of WC and systolic (or diastolic) BP were noted for the Grooved Pegboard - Dominant Hand and Stroop Interference scores, with marginally significant results for Grooved Pegboard - Nondominant Hand. In general, individuals with greater WC and higher BP performed most poorly on these measures. Similar results were obtained for BMI. CONCLUSION: Independent of other confounders including facets of the metabolic syndrome, the combination of greater WC (or BMI) and higher (systolic or diastolic) BP was associated with diminished performance on tests of motor speed and manual dexterity, and executive function (i.e. response inhibition) accounting for 3-13% of the variance in these measures. In healthy older adults, there are similar, negative relations of central and total obesity to cognitive function that are potentiated by higher BP levels.

Aged↗

Preferential expression of the vasoactive intestinal peptide (VIP) receptor VPAC1 in human cord blood-derived CD34+CD38- cells: possible role of VIP as a growth-promoting factor for hematopoietic stem/progenitor cells.

Primitive hematopoietic progenitor cells such as severe combined immunodeficiency- repopulating cells and long-term culture-initiating cells are enriched in CD34+CD38- cells derived from various stem cell sources. In this study, to elucidate the features of such primitive cells at the molecular level, we tried to isolate genes that were preferentially expressed in umbilical cord blood (CB)-derived CD34+CD38- cells by subtractive hybridization. The gene for VPAC1 receptor, a receptor for the neuropeptide vasoactive intestinal peptide (VIP), was thereby isolated and it was shown that this gene was expressed in both CD34+CD38- and CD34+CD38+ CB cells and that the expression levels were higher in CD34+CD38- CB cells. Next, we assessed the effects of VIP on the proliferation of CD34+ CB cells using in vitro culture systems. In serum-free single-cell suspension culture, VIP enhanced clonal growth of CD34+ CB cells in synergy with FLT3 ligand (FL), stem cell factor (SCF), and thrombopoietin (TPO). In serum-free clonogenic assays, VIP promoted myeloid (colony-forming unit-granulocyte/macrophage (CFU-GM)) and mixed (CFU-Mix) colony formations. Furthermore, in Dexter-type long-term cultures, VIP increased colony-forming cells at week 5 of culture. These results suggest that VIP functions as a growth-promoting factor of CB-derived hematopoetic progenitor cells.

ADP-ribosyl Cyclase↗

Enforced expression of HOXB7 promotes hematopoietic stem cell proliferation and myeloid-restricted progenitor differentiation.

Hematopoietic progenitor/stem cells (HPCs/HSCs) purified from human adult peripheral blood (PB) were triggered into cycling, retrovirally transduced with HOXB7 and then functionally assayed in vitro. HPCs were assayed in multi- and unilineage differentiation cultures in either liquid phase or semisolid medium, primitive HPCs in the high proliferative potential colony-forming cell (HPP-CFC) evaluation system and putative HSCs in Dexter type long-term culture (LTC) as LTC initiating cells (LTC-ICs). Control experiments ensured that the exogenous HOXB7 gene was constantly expressed, while the endogenous one was barely or not transcribed. Enforced expression of the gene markedly modulated the proliferation/differentiation program of the entire HSC/HPC population. Enforced HOXB7 expression exerted a potent stimulatory effect on the proliferation of the primitive HPC and putative HSC subsets, assayed as HPP-CFCs and LTC-ICs respectively. While not modifying the total number of HPCs, exogenous HOXB7 induced an increase of the number of granulo-monocytic (GM) HPCs [colony-forming unit GM (CFU-GM) CFU-GM, CFU-G and CFU-M, as evaluated by clonogenic assays] and markedly amplified the progeny of both CFU-G and CFU-M, which showed a sustained proliferation through at least 1-2 months (as evaluated in liquid suspension culture). The prolonged proliferative stimulus induced by HOXB7 transfer into LTC, primitive and GM oriented HPC culture was characterized by persistent proliferation of a discrete population of blast cells and a large pool of differentiated myeloid precursors. Altogether, these results suggest the hypothesis that the proliferative stimulus exerted by exogenous HOXB7 in primitive and GM-oriented HPCs may represent a preleukemic immortalization step. Consistent with the functional role of HOXB7 in the initial ontogenetic phase, these studies indicate that ectopic HOXB7 expression in early HPCs and HSCs from adult PB stimulates their self renewal, sustained proliferation and myeloid differentiation.

Adult↗

Improvements in activities of daily living following functional hand surgery for treatment of lesions to the cervical spinal cord: self-assessment by patients.

STUDY DESIGN: Tetraplegic patients were tested for hand strength before and after hand surgery. They also answered questions about how they rated the results of surgery. OBJECTIVES: Presentation of the efficacy of reconstruction of hand raising, lateral grip, and cylindrical grip in the tetraplegic hand. SETTING: The study was conducted in the Werner Wicker Clinic, Bad Wildungen, Germany, from 1991 to 1998. METHODS: The results of reconstruction surgery performed on 23 tetraplegic hands, as reflected in lifting the hand (n=3), lateral grip (n=21), and cylindrical grip (n=14), are presented. In a follow-up study in 22 patients, their management of activities of daily living 34.1 months (9-51 months) after the surgery is compared with the preoperative situation. Subjective satisfaction levels were elicited for each of the 22 patients by means of a questionnaire. RESULTS: The gain in force corresponded to 893 g (150-1500 g) for cyclindrical grip and 488 g (100-1200 g) for lateral grip, while they were able to develop grade 4 force for lifting the hand. After the operation 28 aids/appliances that patients had formerly used regularly were no longer necessary. There were 75 separate activities listed in the questionnaire, and on average the 22 patients were able to perform 8.7 (0-20) more of these. Most patients (19) said they would advise others to have the operation and 18, that they would have the operation again. There were 12 complications in nine patients. CONCLUSION: Reconstructive surgery on the hands of tetraplegic patients leads to gains in both cylindrical grip and lateral grip force and to increased manual dexterity. Patient satisfaction with the procedure is high.

Activities of Daily Living↗

Professor Heinrich Sebastian Frenkel: a forgotten founder of rehabilitation medicine.

Frenkel was born and later on practiced medicine in Heiden, Swizerland. This small town became, by his vigilant and innovative work, a place of pilgrimage for neurologists. He was the first to introduce the concept of exercise to restore dexterity and to improve ambulation and so pioneered the specialty of physical medicine and rehabilitation. Frenkel's method and philosophy became the foundation of treatment for many chronic neurological disabling diseases. His personality and work influenced many famous neurologists, worldwide.

History, 19th Century↗

An unusual energy transfer process from free-base porphyrin guests to a zinc porphyrin host in self-assembled systems.

The "V" shaped bis-porphyrinic host ZnH can complex the dipyridyl free-base porphyrin guests FBP and FBE with an association constant of 10(8) M(-1). Complexation by ZnH of a reference photo-inactive guest, MN, occurs with a similar association constant and induces a perturbation in the luminescence properties of the host i.e. lower energy and decreased intensity and lifetime of the excited state localized on ZnH. A comparison of the effect of MN complexation by ZnH with those occurring in the complexes of FBP and FBE with ZnH, allowed us to establish the occurrence of an efficient energy transfer from each guest to the host ZnH. The rate constants are 2.5 x 10(10) s(-1) (deltaG0 = -0.2 eV) and 6.5 x 10(9) s(-1) (deltaG0 = -0.13 eV) for FBE and FBP respectively. The results are consistent with a Förster type process with a very low orientation factor (kappa2), even if a Dexter type mechanism with a weak intercomponent electronic interaction term (H), cannot be excluded.

Journal Article↗

Rapid method for design and fabrication of passive micromixers in microfluidic devices using a direct-printing process.

We developed a facile and rapid one-step technique for design and fabrication of passive micromixers in microfluidic devices using a direct-printing process. A laser printing mechanism was dexterously adopted to pattern the microchannels with different gray levels using vector graphic software. With the present method, periodically ordered specific bas-relief microstructures can be easily fabricated on transparencies by a simple printing process. The size and shape of the resultant microstructures are determined by the gray level of the graphic software and the resolution of the laser printer. Patterns of specific bas-relief microstructures on the floor of a channel act as obstacles in the flow path for advection mixing, which can be used as efficient mixing elements. The mixing effect of the resultant micromixer in microfluidic devices was evaluated using CCD fluorescence spectroscopy. We found that the mixing performance depends strongly on the gray level values. Under optimal conditions, fast passive mixing with our periodic ordered patterns in microfluidic devices has been achieved at the very early stages of the laminar flow. In addition, fabrication of micromixers using the present versatile technique requires less than an hour. The present method is promising for fabrication of micromixers in microfluidic devices at low cost and without complicated devices and environment, providing a simple solution to mixing problems in the micro-total-analysis-systems field.

Biomedical Technology↗

Rapid energy transfer in bichromophoric tris-bipyridyl/cyclometallated ruthenium(II) complexes.

The synthesis, characterization, and photophysical properties of the N6-N5C bichromophoric [(bpy)2Ru(I)Ru(ttpy)][PF6]3 (bpy is 2,2'-bipyridine and ttpy is 4'-p-tolyl-2,2':6',2''-terpyridine) and [(bpy)2Ru(II)Ru(ttpy)][PF6]3 (I and II are bpy-dipyridylbenzene ditopic ligands bridged by an ethynyl and phenyl unit, respectively) complexes are reported together with the model mononuclear complexes [(bpy)2Ru(I)][PF6]2, [(bpy)2Ru(II)][PF6]2, [Ru(VI)(ttpy)][PF6] (VI is 3,5-di(2-pyridyl)-biphenyl) and [Ru(dpb)(ttpy)][PF(6)] (Hdpb is 1,3-di(2-pyridyl)-benzene). The electrochemical data show that there is little ground state electronic communication between the metal centers in the bimetallic complexes. Selective excitation of the N(5)C unit in the bichromophoric systems leads to luminescence typical for a bis-tridentate cyclometallated ruthenium complex and is similar to the [Ru(VI)(ttpy)][PF6] model complex. In contrast, the luminescence from the tris-bidentate N6 unit is efficiently quenched by energy transfer to the N5C unit. The energy transfer rate has been determined by femtosecond pump-probe measurements to 0.7 ps in the ethynyl-linked [(bpy)2Ru(I)Ru(ttpy)][PF6]3 and to 1.5 ps in the phenyl-linked [(bpy)2Ru(II)Ru(ttpy)][PF6]3 (in acetonitrile solution at 298 K), and is inferred to occur via a Dexter mechanism.

Journal Article↗

Intramolecular energy-transfer processes in a bis(porphyrin)-ruthenium(II) bis(2,2':6',2''-terpyridine) molecular array.

A molecular triad has been synthesized comprising two free-base porphyrin terminals linked to a central ruthenium(II) bis(2,2':6',2''-terpyridine) subunit via meso-phenylene groups. Illumination into the ruthenium(II) complex is accompanied by rapid intramolecular energy transfer from the metal-to-ligand, charge-transfer (MLCT) triplet to the lowest-energy pi-pi* triplet state localized on one of the porphyrin subunits. Transfer takes place from a vibrationally excited level which lowers the activation energy. The electronic coupling matrix element for this process is 73 cm(-1). Selective illumination into the lowest-energy singlet excited state (S1) localized on the porphyrin leads to fast singlet-triplet energy transfer that populates the MLCT triplet state with high efficiency. This latter process occurs via Dexter-type electron exchange at room temperature, but the activation energy is high and the reaction is prohibited at low temperature. For this latter process, the electronic coupling matrix element is only 8 cm(-1).

Journal Article↗

A high-performance elastomeric patch clamp chip.

Ion channels play key roles in cell physiology and underlie a broad spectrum of disorders. To this day, the gold standard for studying ion channels is the patch clamp technique. Patch clamping involves careful positioning of a fine-tipped glass micropipette onto the surface of the cell to form a high-resistance (>1 Gohms) seal ("gigaseal"), a procedure that is laborious, vibration-sensitive, and not easily amenable to automation. In addition, the solution inside the pipette cannot be easily exchanged. Recently reported patch clamp chips offer the potential of increased throughput, but to date the overall per-cell performance of most designs has been very low when compared to pipettes, and/or the fabrication process is prohibitively expensive. Here we demonstrate a replica-molded elastomeric patch clamp chip incorporating nanofabricated constrictions, which delivers high-stability gigaseals, with success rates comparable to those of pipettes, using rat basophilic leukemia (RBL) cells. The high stability enables exchanges of both the extracellular and intracellular solution during whole-cell recordings. In a sample of 103 experiments, 66 cells (64%) were successfully immobilized at the patch aperture; 38 cells (58% of immobilized cells, 37% of all cells) were successfully gigasealed; and 25 cells (65% of gigasealed cells, 34% of immobilized cells, 24% of all cells) were successfully perforated for whole-cell access. In the last group of 27 experiments, 79% of the cells could be immobilized, of which 68% could be gigasealed and 46% perforated for whole-cell access, indicating that dexterity is important.

Animals↗

An earmold for the geriatric patient.

This article describes a rehabilitation innovation for the elderly hearing-impaired patient. To minimize the problem of lack of fine finger dexterity in the elderly, an earmold was designed with a small handle. A brief description of the design is provided. A case study describes the usefulness of this earmold.

Aged↗

Loose anagen syndrome as a severity factor for trichotillomania.

Loose anagen syndrome (LAS) is a condition of childhood where anagen hairs are easily and painlessly extracted. The condition is due to poor adhesion between the cuticle of the hair shaft and the inner root sheath. A 4-year-old girl presented with patches of hair loss and a clinical diagnosis of trichotillomania was made. A hair pull test extracted multiple hairs easily and painlessly. Light microscopic examination was consistent with LAS. A biopsy was performed, which showed features of trichotillomania. However, on request the child did not display sufficient dexterity to pull out her own hair. It was subsequently determined that her hair loss was likely to be due to a third person plucking out her hair. It appears that in this case the LAS was not the cause of her hair loss, but rather acted as a severity factor for trichotillomania by proxy in that the lack of pain on plucking the hairs removed the principle deterrent.

Child Abuse↗

Cultured autografting for juvenile myelomonocytic leukaemia.

A case of juvenile myelomonocytic leukaemia (JMML) associated with a chromosomal translocation (1;5) is described. Initial cytoreductive therapy failed to control the disease. In the absence of a matched family or unrelated donor, a Dexter-type long-term bone marrow culture (LTBMC) was established. The LTBMC showed preferential growth of normal stem cells over the abnormal clone, allowing a cultured autologous stem cell transplantation to be performed. Despite detection of the t(1;5) from 5 months to 7 years following cultured autograft, the patient remained in haematological remission. Currently the patient is alive and well at 10 years in full cytogenetic remission.

Bone Marrow Cells↗

Circadian rhythms in human performance and mood under constant conditions.

UNLABELLED: This study explored the relationship between circadian performance rhythms and rhythms in rectal temperature, plasma cortisol, plasma melatonin, subjective alertness and well-being. Seventeen healthy young adults were studied under 36 h of 'unmasking' conditions (constant wakeful bedrest, temporal isolation, homogenized 'meals') during which rectal temperatures were measured every minute, and plasma cortisol and plasma melatonin measured every 20 min. Hourly subjective ratings of global vigour (alertness) and affect (well-being) were obtained followed by one of two performance batteries. On odd-numbered hours performance (speed and accuracy) of serial search, verbal reasoning and manual dexterity tasks was assessed. On even-numbered hours, performance (% hits, response speed) was measured at a 25-30 min visual vigilance task. Performance of all tasks (except search accuracy) showed a significant time of day variation usually with a nocturnal trough close to the trough in rectal temperature. Performance rhythms appeared not to reliably differ with working memory load. Within subjects, predominantly positive correlations emerged between good performance and higher temperatures and better subjective alertness; predominantly negative correlations between good performance and higher plasma levels of cortisol and melatonin. Temperature and cortisol rhythms correlated with slightly more performance measures (5/7) than did melatonin rhythms (4/7). Global vigour correlated about as well with performance (5/7) as did temperature, and considerably better than global affect (1/7). IN CONCLUSION: (1) between-task heterogeneity in circadian performance rhythms appeared to be absent when the sleep/wake cycle was suspended; (2) temperature (positively), cortisol and melatonin (negatively) appeared equally good as circadian correlates of performance, and (3) subjective alertness correlated with performance rhythms as well as (but not better than) body temperature, suggesting that performance rhythms were not directly mediated by rhythms in subjective alertness.

Adult↗

Cusum analysis of trends in operative selection and conversion rates for laparoscopic cholecystectomy.

BACKGROUND: Laparoscopic cholecystectomy (LC) requires a high degree of technical ability, spatial resolution and dexterity. Assessing trainees and competent operators is an important aspect of quality assurance in patient care. Most institutions quote mean conversion rate as a method of comparing operators' performance. The purpose of the present study was to use the technique of cumulative sum (cusum) analysis to determine whether a learning curve phenomenon exists in operators performing LC. METHODS: Data were obtained retrospectively by reviewing the operative records of all patients undergoing elective and acute cholecystectomy for a 30-month period coinciding with the commencement of LC at North Shore Hospital. Patients' age and gender, date and type of operative procedure, duration of operation, and name of operator were recorded. Mean and cusum-transformed data were derived for all operations as well as for four individual operators' performances. RESULTS: Over the study period a total of 614 cholecystectomies was performed, with 85% attempted laparoscopically. A total of 9.8% required conversion to the open technique. Time trend analysis with the cusum technique for all surgeons revealed an inverse relationship between selection rate and conversion rate. Analysis of four individual surgeons revealed three different time trend profiles. CONCLUSION: There was a direct inverse relationship between conversion rate and selection rate, in that careful selection is associated with a low conversion rate. Comparison of individual surgeons' performance showed wide variation, with only one surgeon exhibiting the phenomenon of a learning curve. Contrary to other reports, we found that performance on LC was not always related to operative experience. This highlights the need for a more objective method to analyse operator competence than operator experience alone.

Adolescent↗

Long-term effect of a single dose of flunarizine in Huntington's disease.

We report a preliminary pilot study on the clinical efficacy of flunarizine (FNZ), a calcium-entry blocker that causes extrapyramidal side-effects, in 10 patients with Huntington's disease (HD). FNZ (20 mg) administered by the sublingual route resulted in a decrease in choreic movements and improved dexterity in performing several tests. These effects lasted for at least 7 days after a single dose. Therefore, FNZ seems to exert the same effect as a long-acting neuroleptic agent in our HD patients.Copyright Lippincott-Raven Publishers

Journal Article↗

Efficacy and safety of botulinum toxin type a in the treatment of palmar hyperhidrosis: a double-blind, randomized, placebo-controlled study.

BACKGROUND: Recent studies demonstrate that botulinum toxin type A (BTX-A) decreases palmar hyperhidrosis. OBJECTIVE: To evaluate the efficacy and safety of BTX-A for palmar hyperhidrosis. METHODS: Patients (n = 19) received injections of placebo (normal saline) in one hand and BTX-A in the other. Assessments included gravimetric measurement of sweat production and physician's and patient's rating of severity. Safety evaluations included measuring grip strength. Preliminary 28-day results are reported. RESULTS: The mean percentage decrease in gravimetric measurement at day 28 was significantly greater with BTX-A versus placebo. One hundred percent of 17 patients rated the treatment as successful, while only 12% (2/17) rated placebo injection successful. Grip and hand strength were unchanged with either treatment. Only 21% (4/19) reported mild adverse events. CONCLUSION: BTX-A injections produce significant improvements in palmar hyperhidrosis without a concomitant decrease in grip or dexterity, or the occurrence of serious adverse events.

Adolescent↗

Scar quality and physiologic barrier function restoration after moist and moist-exposed dressings of partial-thickness wounds.

BACKGROUND: There is growing evidence of improved healing of full- and partial-thickness cutaneous wounds in wet and moist environments. Retention of biologic fluids over the wound prevents desiccation of denuded dermis or deeper tissues and allows faster and unimpeded migration of keratinocytes over the wound surface. It allows also the naturally occurring cytokines and growth factors to exert their beneficial effect on wound contracture and re-epithelialization. Despite all of these documented benefits, applying the moist healing principles to large surface areas, in particular to large burns, is hindered by the major technical handicap of creating and maintaining a sealed moist environment over these areas. METHODS: From January to September 2001, healing of partial-thickness skin graft donor sites was studied in a prospective comparative study of two types of moist dressings, Tegaderm (3M Health Care, St. Paul, MN), a semipermeable membrane occlusive dressing, and moist exposed burn ointment (MEBO) (Julphar; Gulf Pharmaceutical Industries, United Arab of Emirates), an ointment that can provide a moist environment without the need of an overlying occlusive dressing. Healing was assessed both clinically and with serial measurements of transepidermal water loss (TEWL) and moisture. Following healing, scar quality was evaluated by two members of the team separately using a visual analog scale. Results were statistically analyzed. RESULTS: Faster healing was observed clinically with MEBO application. Physiologic healing as determined by TEWL measurements occurred at an extremely significant earlier stage for MEBO, and this was associated with better scar quality, demonstrating a positive relationship between function and cosmetic appearance. Moreover, the ointment is definitely easier to apply than the occlusive self-adhesive membrane, which requires some degree of dexterity and expertise. CONCLUSION: MEBO application is an effective and valid alternative to conventional occlusive dressings. Moreover, the observed improved anatomic and physiologic healing indicates that MEBO may have a positive effect on healing more that the mere fact of passive moisture retention.

Adult↗