The effects of exercise intensity on the cortisol response to a subsequent acute psychosocial stressor.

OBJECTIVE: The aim of this experimental study was to determine the extent to which the intensity of a single 30 min bout of exercise alters the salivary cortisol (sCort) response to a subsequently induced acute psychosocial stressor. The study further aimed to elucidate a physiological mechanism through which exercise intensity exerts stress-mitigating effects. METHODS: Eighty-three healthy men (Mage = 21.04 SD = 2.89) were randomly assigned to exercise on a treadmill at either 30%, 50% or 70% of their heart rate reserve (HRR) for 30 min and then underwent the Trier Social Stress Test 45 min later. sCort was measured repeatedly throughout and following the exercise bout and stressor task. RESULTS: ANCOVA and Multilevel Growth Curve Analysis determined that vigorous (70% HRR) exercise elicited dampened sCort responses to the stressor task, marked by lower total sCort levels, diminished sCort reactivity, and faster recovery to baseline values, as compared to less intense exercise. Moreover, exercise elicited a sCort response in proportion to the intensity at which it was performed, and this exercise-associated HPA-axis response was inversely proportional to the sCort response to the subsequent stressor task. CONCLUSIONS: This study revealed that exercise-intensity dampens the HPA-axis stress response in a dose-dependent manner, with evidence that the cortisol released from exercising intensely suppresses the subsequent cortisol response to a psychosocial stressor.

Effectiveness of an advanced practice nurse-led delirium education and training programme.

AIM: To develop an education and training programme to enhance bedside nurses' knowledge, competency and compliance in accurately performing delirium screening in intensive care units. BACKGROUND: Delirium in intensive care units is associated with several poor patient outcomes. Delirium detection can be improved by enhancing nurses' knowledge, competency and compliance in accurately performing delirium screening. METHODS: A descriptive quantitative study with pretest-post-test design was adopted. There were 245 nurses from five intensive care units who participated in the study. Multiple-choice questions were used to assess nurses' knowledge change before and after the education programme. Competency was assessed before and 2 months after the programme by simulation with a standardized patient, followed by real patients at the bedside. Compliance data on screening were collected from the documentation of the Richmond Agitation-Sedation Scale and the Confusion Assessment Method for the ICU before and 3 and 10 months after the programme. Data collection took 1 year, from June 2014 to May 2015. RESULTS: Despite nurses' improved knowledge and good competency, delirium screening documentations after 3 months were poor. However, screening documentations subsequently improved when measured at 10 months, following further emphasis by the senior nursing staff. IMPLICATIONS FOR NURSING PRACTICE AND POLICY: Nursing administrators and bedside nurses need to be involved in the policy-making process and plan a training programme for the new nursing staff in the high-risk areas. A short refreshment course should be offered to the nursing staff 3 months after the initial training programme. CONCLUSIONS: Improved knowledge and competency in assessment did not improve compliance and documentation of delirium screening. Therefore, it is important to reinforce nurses' compliance of delirium screening over time.

Detection in Malaysia of a Borrelia sp. From Haemaphysalis hystricis (Ixodida: Ixodidae).

Spirochetes from the Borrelia genus are known to cause diseases in humans, namely Lyme disease and relapsing fever. These organisms are commonly transmitted to humans by arthropod vectors including ticks, mite, and lice. Here, we report the molecular detection of a Borrelia sp. from a Haemaphysalis hystricis Supino tick collected from wildlife in an Orang Asli settlement in Selangor, Malaysia. Phylogenetic analyses of partial 16s rRNA and flaB gene sequences revealed that the Borrelia sp. is closely related to the relapsing fever group borreliae, Borrelia lonestari, Borrelia miyamotoi, and Borrelia theileri, as well as a number of uncharacterized Borrelia sp. from ticks in Portugal and Japan. To our knowledge, this is the first report of a Borrelia sp. detected in H. hystricis, and in Malaysia. The zoonotic potential of this Borrelia sp. merits further investigation.

Genetic modulation of oxytocin sensitivity: a pharmacogenetic approach.

Intranasal administration of the neuropeptide oxytocin has been shown to influence a range of complex social cognitions and social behaviors, and it holds therapeutic potential for the treatment of mental disorders characterized by social functioning deficits such as autism, social phobia and borderline personality disorder. However, considerable variability exists in individual responses to oxytocin administration. Here, we undertook a study to investigate the role of genetic variation in sensitivity to exogenous oxytocin using a socioemotional task. In a randomized, double-blind, placebo-controlled experiment with a repeated-measures (crossover) design, we assessed the performance of 203 men on an emotion recognition task under oxytocin and placebo. We took a haplotype-based approach to investigate the association between oxytocin receptor gene variation and oxytocin sensitivity. We identified a six-marker haplotype block spanning the promoter region and intron 3 that was significantly associated with our measure of oxytocin sensitivity. Specifically, the TTCGGG haplotype comprising single-nucleotide polymorphisms rs237917-rs2268498-rs4564970-rs237897-rs2268495-rs53576 is associated with increased emotion recognition performance under oxytocin versus placebo, and the CCGAGA haplotype with the opposite pattern. These results on the genetic modulation of sensitivity to oxytocin document a significant source of individual differences with implications for personalized treatment approaches using oxytocin administration.

Replacing the rod with the cone transducin subunit decreases sensitivity and accelerates response decay.

Cone vision is less sensitive than rod vision. Much of this difference can be attributed to the photoreceptors themselves, but the reason why the cones are less sensitive is still unknown. Recent recordings indicate that one important factor may be a difference in the rate of activation of cone transduction; that is, the rising phase of the cone response per bleached rhodopsin molecule (Rh*) has a smaller slope than the rising phase of the rod response per Rh*, perhaps because some step between Rh* and activation of the phosphodiesterase 6 (PDE6) effector molecule occurs with less gain. Since rods and cones have different G-protein alpha subunits, and since this subunit (Talpha) plays a key role both in the interaction of G-protein with Rh* and the activation of PDE6, we investigated the mechanism of the amplification difference by expressing cone Talpha in rod Talpha-knockout rods to produce so-called GNAT2C mice. We show that rods in GNAT2C mice have decreased sensitivity and a rate of activation half that of wild-type (WT) mouse rods. Furthermore, GNAT2C responses recover more rapidly than WT responses with kinetic parameters resembling those of native mouse cones. Our results show for the first time that part of the difference in sensitivity and response kinetics between rods and cones may be the result of a difference in the G-protein alpha subunit. They also indicate more generally that the molecular nature of G-protein alpha may play an important role in the kinetics of G-protein cascades for metabotropic receptors throughout the body.

Cavitary acetabular defects treated with morselized cancellous bone graft and cementless cups.

The use of impacted morselized cancellous bone grafts in conjunction with cementless hemispherical acetabular cups for treatment of AAOS type II acetabular cavitary deficiencies was evaluated in a retrospective study of 23 primary and 24 revision total hip arthroplasties, at a mean follow-up of 7.9 and 8.1 years, respectively. All primary hips received autografts, while all revision hips received allografts. Modified Harris Hip Scores for primary and revision hip replacements increased from a pre-operative mean of 37 and 47 to a postoperative mean of 90 and 86, respectively. All 23 autografts and 23 out of 24 cancellous allografts were radiographically incorporated without evidence of resorption. There were no instances of infection, component migration, or cases requiring subsequent acetabular revision. We conclude that impacted morselized cancellous bone-graft augmentation of cementless cups is a viable surgical option for AAOS type II cavitary acetabular defects.

Fatal hemolytic transfusion reaction due to anti-Ku in a Knull patient.

A fatal transfusion reaction due to anti-Ku in a Knull (Ko) patient is reported. The patient was transfused with 34 units of incompatible RBCs during 44 days of hospitalization. Apart from the first transfusion, all subsequent transfusions failed to raise the patient's Hb. No serum antibody was identified until he was transferred to another hospital for dialysis. A compatibility test demonstrated a weak antibody and autocontrol reacting at room temperature by a manual polybrene method. The antibody was considered to be a "cold agglutinin." A blood sample was sent to a reference laboratory where the patient was found to be Knull and the antibody was identified as anti-Ku.

Medial elbow problems in the overhead-throwing athlete.

The elbow is subjected to enormous valgus stresses during the throwing motion, which places the overhead-throwing athlete at considerable risk for injury. Injuries involving the structures of the medial elbow occur in distinct patterns. Although acute injuries of the medial elbow can occur, the majority are overuse injuries as a result of the repetitive forces imparted to the elbow by throwing. Injury to the ulnar collateral ligament complex results in valgus instability. Valgus extension overload leads to diffuse osseous changes within the elbow joint and secondary posteromedial impingement. Overuse of the flexor-pronator musculature may result in medial epicondylitis and occasional muscle tears and ruptures. Ulnar neuropathy is a common finding that may be due to a variety of factors, including traction, friction, and compression of the ulnar nerve. Advances in nonoperative and operative treatment regimens specific to each injury pattern have resulted in the restoration of elbow function and the successful return of most injured overhead athletes to competitive activities. With further insight into the relevant anatomy, biomechanics, and pathophysiology involved in overhead activities and their associated injuries, significant contributions can continue to be made toward prevention and treatment of these injuries.

Efficacy of preoperative skin traction in hip fracture patients: a prospective, randomized study.

OBJECTIVE: To compare the analgesic benefit of preoperative skin traction with the placement of a pillow under the injured extremity in patients with hip fractures. DESIGN: Prospective, randomized clinical study. SETTING: University-affiliated teaching institution. PATIENTS AND PARTICIPANTS: One hundred consecutive patients with hip fractures admitted to the authors' institution who met inclusion criteria were enrolled. Fifty-five patients had femoral neck fractures, and forty-five patients had intertrochanteric fractures. The average patient age was seventy-eight years. INTERVENTION: All patients were preoperatively randomized into two intervention groups. One group underwent placement of five pounds of skin traction on the injured extremity, whereas the second underwent placement of a pillow under the injured extremity. Fifty patients were enrolled in each intervention group. RESULTS: With respect to immediate postintervention pain levels, patients treated with a pillow showed a trend toward better pain relief, as compared with patients treated with skin traction; however, this was not statistically significant. On the morning after admission, patients treated with a pillow had a statistically significant greater reduction in pain (p = 0.04). These patients also requested a statistically significant lower amount of pain medication (p < 0.01). CONCLUSIONS: The authors think that preoperative skin traction in patients with hip fractures does not provide significant pain relief, as compared with pillow placement under the injured extremity, and thus should not be routinely performed in this patient population for analgesia.

Characterization of chicken antisera raised against Aspergillus spp. by enzyme linked immunosorbent assay.

Enzyme linked immunosorbent assays of three Aspergillus species have been developed. Laying hens were immunized with the exoantigens from Asp. flavus, Asp. ochreaus and Asp. versicolor. All test chickens except for one produced antisera raised against the exoantigens. The antisera production process and ELISA titer were analysed. Fourteen days after the first injection, the antisera began to produce largely, on the 35th day reached to the peak, and maintained a stable level until the 42nd day. The maximum ELISA titer of the antisera to the exoantigens from Asp. flavus, Asp. ochreaus and Asp. versicolor was 1:8,000, 1:10,000 and 1:10,000, respectively. The cross-reactivities of antisera were determined with seventeen species of Aspergillus, ten species of fungi from other genera and the buffer-extracts of grain. The antisera did not cross-react with the exoantigens from other genera and the buffer-extracts of grain. The antiserum to exoantigen from Asp. ochreaus was species-specific, whereas the antisera against Asp. flavus and Asp. versicolor tended to cross-react with other Aspergillus species to varying degrees. The results suggest that exoantigens immunoassays can be developed to indentify and detect Aspergillus genus in grains.

Acute and chronic posterolateral rotatory instability of the knee.

Isolated posterolateral rotatory instability of the knee is an uncommon injury pattern that may result in significant degrees of functional disability. This injury complex can be a challenging diagnostic and therapeutic problem for the orthopaedic surgeon. The presence of associated ligamentous and soft-tissue injuries, resulting in combined instability patterns, further complicates management. The results of recent research have enhanced our understanding of the complex anatomy and biomechanics of the posterolateral aspect of the knee. Numerous surgical techniques have been described for both repair and reconstruction of the injured posterolateral structures; however, long-term functional results have been only moderately successful.

[Experience of application of skin flap in repairing 112 patients with severe thermo pressure injury of hand].

OBJECTIVE: To investigate the clinical effect of skin flaps repairing severe thermopressure injury of hand. METHODS: From January 1989 to December 1998, 112 patients with severe thermopressure injury of hand were repaired by various skin flaps transfer, the size of skin flaps was 6 cm x 8 cm to 12 cm x 18 cm. Postoperative patients were treated by combined rehabilitation in early stage. RESULTS: All the flaps were survived with satisfactory effect. Sixty-six patients were followed up 6 to 12 months, skin flaps all showed better colour and texture, and function of the hand was satisfactory. CONCLUSION: Different skin flaps are adopted to repair severe thermopressure injury of the hand according to different skin defects of the hand, combined early rehabilitation treatment, to achieve good recovery of function and appearance of the hand to the greatest extent.

In vitro and in vivo activation of polymorphonuclear leukocytes in response to particulate debris.

The host inflammatory response to particulate wear debris has been implicated as a principal cause of osteolysis and aseptic loosening following total joint arthroplasty. While it has long been assumed that this inflammatory response is mediated solely by a chronic process, there has been evidence to suggest that an acute response to particulate debris may be important in initiating the chronic response. We studied the in vitro and in vivo acute inflammatory responses mediated by polymorphonuclear leukocytes (PMNs) to both retrieved particulate from a catastrophically failed uncemented metal-backed acetabular component and to commercially pure particulate (polyethylene, cobalt-chrome, and titanium). Isolated, nonactivated human PMNs in vitro exhibited both a dose- and time-dependent degranulation response to opsonized particulate debris, as evidenced by release of both specific (increased lysozyme activity) and azurophilic (increased beta-glucuronidase activity) granule contents. In the rat subcutaneous pouch model in vivo, PMNs were recruited within 3-6 h after exposure to particulate debris and were noted to phagocytize particulate and subsequently degranulate, as evidenced by increased beta-glucuronidase and PMN-specific myeloperoxidase (azurophilic granule enzymes) activities. This response peaked within the first 6 h and gradually declined by 24 h. The results of this study demonstrate the presence of an acute inflammatory response mediated by PMNs both in vitro and in vivo to particulate debris, which may be important in the sequence of events that lead to the macrophage-dominated chronic inflammatory process culminating in osteolysis and aseptic loosening of total joint arthroplasties.

Effects of propofol on contractile response and electrophysiological properties in single guinea-pig ventricular myocyte.

Effects of propofol on contractile response, action potential, resting membrane potential and L-type voltage-dependent calcium channel current were examined in guinea-pig single cardiac myocyte. Propofol (10(-4) M) inhibited contractile response induced by electrical stimulation (83.6% of control, n = 5), but did not change the resting membrane potential. On the other hand, propofol reduced the overshoot of action potential (10(-4) M), and shortened the duration of action potential (10(-5) and 10(-4) M). Whole-cell voltage clamp experiment showed inhibition of L-type calcium channel current (ICa, 10(-5) M: 90.8+/-1.39, 10(-4) M: 83.4+/-1.53% of control, n = 5). In addition, propofol showed use-dependent block of ICa. It is concluded that negative inotropic effect of propofol is caused by suppression of action potential, and that inhibition of ICa plays a role in shortening of the duration of action potential.

Wear rates of ceramic-on-ceramic bearing surfaces in total hip implants: a 12-year follow-up study.

A retrospective clinical and radiographic analysis was performed on 58 patients (60 hips; mean age at time of surgery, 45.2 years) at a minimum of 10-year follow-up (mean, 12.7 years) after total hip replacement using a ceramic-on-ceramic hearing total hip implant (Autophor, Smith and Nephew, Memphis, TN). Mean wear rate at final follow-up was 0.21 mim, averaging 0.016 mm/y. There were no cases of periprosthetic osteolysis in the acetabuulum or femur. For the unrevised components, there were 3 (5%) cases of protrusio acetabuli and 4 (7%) cases of acetabular component loosening. On the femoral side, 78.3% had distal pedestal formation, and 83% had greater than 2 mm implant-bone radiolucencies in more than 5 Gruen zones as a result of gross motion of the stem. Despite radiographic evidence of implant loosening, this hard bearing articulation functioned well in vivo for more than 12 years with remarkably low wear--approximately one tenth the rate reported for metal-on-polyethylene total hip bearings.

Repair of articular cartilage defects: part II. Treatment options.

Articular cartilage injuries result in numerous clinical symptoms, such as pain and decreased functional levels. Current therapeutic options being used include articular surface debridement, such as chondral shaving, abrasion chondroplasty, and subchondral perforation; soft-tissue arthroplasties, such as perichondrial and periosteal grafts; and osteochondral transplantation. None of these therapies, however, has resulted in the successful regeneration of a hyaline-like tissue that withstands normal joint loading and activity over prolonged periods. As a result, research is also being conducted on alternative therapeutic procedures to enhance the repair process and to stimulate the regeneration of a repair tissue with hyaline-like structural and biologic properties. Part I of this paper, which was published in January, discussed the basic science of cartilage healing. Part II presents the treatment options.

Repair of articular cartilage defects: part I. Basic Science of cartilage healing.

Articular cartilage injuries result in numerous clinical symptoms, such as pain and decreased functional levels. The limited reparative capabilities of hyaline cartilage results in the generation of repair tissue that lacks the structure and biomechanical properties of normal cartilage. Chondrocytes are unable to adequately proliferate, migrate, and synthesize high-quality repair tissue in response to blunt, superficial, or deep penetrating trauma. Extensive research has been conducted to understand the healing process and devise techniques that would enhance this response. Part I of this paper will discuss the basic science of cartilage repair. Part II, which will be published in the February issue, will present the treatment options.

The 1997 Stevenson Award Lecture. Cardiac K+ channel gating: cloned delayed rectifier mechanisms and drug modulation.

K+ channels are ubiquitous membrane proteins, which have a central role in the control of cell excitability. In the heart, voltage-gated delayed rectifier K+ channels, like Kv1.5, determine repolarization and the cardiac action potential plateau duration. Here we review the broader properties of cloned voltage-gated K+ channels with specific reference to the hKv1.5 channel in heart. We discuss the basic structural components of K+ channels such as the pore, voltage sensor, and fast inactivation, all of which have been extensively studied. Slow, or C-type, inactivation and the structural features that control pore opening are less well understood, although recent studies have given new insight into these problems. Information about channel transitions that occur prior to opening is provided by gating currents, which reflect charge-carrying transitions between kinetic closed states. By studying modulation of the gating properties of K+ channels by cations and with drugs, we can make a more complete interpretation of the state dependence of drug and ion interactions with the channel. In this way we can uncover the detailed mechanisms of action of K+ channel blockers such as tetraethylammonium ions and 4-aminopyridine, and antiarrhythmic agents such as nifedipine and quinidine.

On the mechanism by which 4-Aminopyridine occludes quinidine block of the cardiac K+ channel, hKv1.5.

4-Aminopyridine (4-AP) binds to potassium channels at a site or sites in the inner mouth of the pore and is thought to prevent channel opening. The return of hKv1.5 off-gating charge upon repolarization is accelerated by 4-AP and it has been suggested that 4-AP blocks slow conformational rearrangements during late closed states that are necessary for channel opening. On the other hand, quinidine, an open channel blocker, slows the return or immobilizes off-gating charge only at opening potentials (>-25 mV). The aim of this study was to use quinidine as a probe of open channels to test the kinetic state of 4-AP-blocked channels. In the presence of 0.2-1 mM 4-AP, quinidine slowed charge return and caused partial charge immobilization, corresponding to an increase in the Kd of approximately 20-fold. Peak off-gating currents were reduced and decay was slowed approximately 2- to 2.5-fold at potentials negative to the threshold of channel activation and during depolarizations shorter than normally required for channel activation. This demonstrated access of quinidine to 4-AP-blocked channels, a lack of competition between the two drugs, and implied allosteric modulation of the quinidine binding site by 4-AP resident within the channel. Single channel recordings also showed that quinidine could modulate the 4-AP-induced closure of the channels, with the result that frequent channel reopenings were observed when both drugs were present. We propose that 4-AP-blocked channels exist in a partially open, nonconducting state that allows access to quinidine, even at more negative potentials and during shorter depolarizations than those required for channel activation.