Host status and susceptibility of Cannabis sativa cultivars to root-knot nematodes.

Root-knot nematode host status of hemp cultivars of different uses (fiber, dual, CBD/CBG) and from different regions (Europe, China, US) were evaluated in five different greenhouse trials. None of the tested cultivars showed resistance to any of the tested root-knot nematode species, and all tested hemp cultivars were good hosts for root-knot nematodes, especially to mixed populations of M. javanica and M. incognita. Root gall symptoms on hemp were less severe than on cucumber (and tomato), but reproduction rates were similar. Lower infection and reproduction rates were noted for M. hapla and M. enterolobii, which were probably due to the colder temperatures at the time of the trial, as the same effect was noted for the cucumber control plants. While no negative impact on hemp shoot growth was seen in trials where nematodes were added to pasteurized soil, a significant and visible negative effect on hemp growth was noted when two CBG hemp cultivars were planted in heavily naturally root-knot infested soil. This result indicates that hemp is not only a good host to root-knot nematodes, but also that root-knot can be a limiting factor for hemp production in Florida and other places with high abundance and pressure of root-knot nematodes.

Plant-Parasitic Nematodes Associated with Cannabis sativa in Florida.

The subtropical climate of Florida allows for a wide range of crops to be grown. With the classification of hemp (Cannabis sativa L., <0.3% delta-9-tetrahydrocannabinol) as an agricultural commodity, hemp has become a potential alternative crop in Florida. Hemp cultivars of different geographies (Europe, China, and North America), and uses (fiber, oil and CBD), were evaluated in three field experiments. The field experiments evaluated a total of 26 cultivars and were conducted for two consecutive seasons at three different locations (soil types) in North (sandy loam), Central (fine sand), and South Florida (gravelly loam). Nematode soil populations were measured at the end of each season. A diverse population of plant-parasitic nematodes was found, with reniform nematodes (RN, Rotylenchulus reniformis) the dominant species in North and South Florida (up to 27.5 nematodes/cc soil), and RKN (Meloidogne javanica) the main species in central Florida (up to 4.7 nematodes/cc soil). Other nematodes that were commonly found in south Florida (and to a lesser extent north Florida) were spiral (Helicotylenchus spp.), stunt (Tylenchorhynchus spp.) and ring nematodes (Criconemoids), while in central Florida, stubby root (Nanidorus minor) and sting nematodes (Belonolaimus longicaduatus) were found. No significant difference among hemp cultivars was noted at any of the locations. RKN were found in all three regions and soils, while RN were only found in North and South Florida. This is the first report on plant-parasitic nematodes associated with hemp in Florida fields. Natural nematode populations varied greatly, depending on where in Florida hemp was grown. Growers who wish to include hemp in their crop rotation need to be aware of potential pest pressure from nematodes. More research is needed to determine to what extent nematodes, especially RKN and RN, can reduce hemp growth and yield.

Silk fibroin preserves beta cell function under inflammatory stress while stimulating islet cell surface GLUT2 expression.

Silk fibroin is a novel biomaterial for enhancing transplanted islet cell function and survival. This study investigated whether silk fibroin may have unique properties that improve islet function in the face of inflammatory-mediated stress during transplantation. Murine islet function was tested in vitro with either silk fibroin or alginate and challenged with inflammatory cytokines. The glucose-stimulated insulin secretion index for all conditions decreased with inflammatory cytokines, but was better preserved for islets exposed to silk compared to those exposed to alginate or medium. GLUT2 transporter expression on the cell surface of islets exposed to silk was increased compared to alginate or medium alone. Upon cytokine stress, a greater percentage of islet cells exposed to silk expressed GLUT2 on their surface. We conclude that preconditioning islets with silk fibroin stimulates islet cell surface GLUT2 expression, an increase, which persists under inflammatory stress, and may improve islet engraftment and function after transplantation.

Brain-computer interface devices for patients with paralysis and amputation: a meeting report.

OBJECTIVE: The Food and Drug Administration's (FDA) Center for Devices and Radiological Health (CDRH) believes it is important to help stakeholders (e.g., manufacturers, health-care professionals, patients, patient advocates, academia, and other government agencies) navigate the regulatory landscape for medical devices. For innovative devices involving brain-computer interfaces, this is particularly important. APPROACH: Towards this goal, on 21 November, 2014, CDRH held an open public workshop on its White Oak, MD campus with the aim of fostering an open discussion on the scientific and clinical considerations associated with the development of brain-computer interface (BCI) devices, defined for the purposes of this workshop as neuroprostheses that interface with the central or peripheral nervous system to restore lost motor or sensory capabilities. MAIN RESULTS: This paper summarizes the presentations and discussions from that workshop. SIGNIFICANCE: CDRH plans to use this information to develop regulatory considerations that will promote innovation while maintaining appropriate patient protections. FDA plans to build on advances in regulatory science and input provided in this workshop to develop guidance that provides recommendations for premarket submissions for BCI devices. These proceedings will be a resource for the BCI community during the development of medical devices for consumers.

Static stretching vs. dynamic warm-ups: a comparison of their effects on torque and electromyography output of the quadriceps and hamstring muscles.

AIM: The aim of this paper was to determine if two different warm-up protocols differently affect torque of the quadriceps and hamstrings, and electromyography (EMG) output of the rectus femoris (RF) and vastus lateralis (VL) when completing 30 maximal leg extensions and curls. METHODS: Twenty-one healthy male (N.=8) and female (N.=13) subjects volunteered to participate in a familiarization session and three testing sessions. The three testing sessions control, dynamic, and static were completed in a counterbalanced order on non-consecutive days. First, subjects warmed-up on a treadmill for five minutes before completing six dynamic movements, six static-stretches, or no stretches. They then rested for five minutes before completing 30 maximal leg extensions and curls at a speed of 60 s-1. RESULTS: A significant decrease in quadriceps torque output over time was determined for the dynamic protocol when compared to the control (P<0.01) and static (P<0.05) protocols. A significant decrease was found in peak quadriceps torque for the dynamic protocol (P<0.01) when compared to the static, and a significant increase was found for the static protocol (P<0.05) when compared to the control. A significant decrease in average quadriceps torque was found for the dynamic protocol when compared to the static (P<0.05) and control (P<0.01) protocols. No difference was found in hamstring torque or EMG output of the RF and VL. CONCLUSION: Short duration static-stretching has the ability to increase peak and average torque of the leg extensors, while some types of anaerobic exercise involving maximal contractions to fatigue may be hindered by performing dynamic movements as part of the warm-up.

Surgery combined with controlled-release doxorubicin silk films as a treatment strategy in an orthotopic neuroblastoma mouse model.

BACKGROUND: Neuroblastoma tumour resection goal is maximal tumour removal. We hypothesise that combining surgery with sustained, local doxorubicin application can control tumour growth. METHODS: We injected human neuroblastoma cells into immunocompromised mouse adrenal gland. When KELLY cell-induced tumour volume was >300 mm(3), 80-90% of tumour was resected and treated as follows: instantaneous-release silk film with 100 µg doxorubicin (100IR), controlled-release film with 200 µg (200CR) over residual tumour bed; and 100 and 200 µg intravenous doxorubicin (100IV and 200IV). Tumour volume was measured and histology analysed. RESULTS: Orthotopic tumours formed with KELLY, SK-N-AS, IMR-32, SH-SY5Y cells. Tumours reached 1800±180 mm(3) after 28 days, 2200±290 mm(3) after 35 days, 1280±260 mm(3) after 63 days, and 1700±360 mm(3) after 84 days, respectively. At 3 days post KELLY tumour resection, tumour volumes were similar across all groups (P=0.6210). Tumour growth rate was similar in untreated vs control film, 100IV vs 100IR, and 100IV vs 200IV. There was significant difference in 100IR vs 200CR (P=0.0004) and 200IV vs 200CR (P=0.0003). Tumour growth with all doxorubicin groups was slower than that of control (P: <0.0001-0.0069). At the interface of the 200CR film and tumour, there was cellular necrosis, surrounded by apoptotic cells before reaching viable tumour cells. CONCLUSIONS: Combining surgical resection and sustained local doxorubicin treatment is effective in tumour control. Administering doxorubicin in a local, controlled manner is superior to giving an equivalent intravenous dose in tumour control.

Effects of oral rehydration and external cooling on physiology, perception, and performance in hot, dry climates.

Only limited research evaluates possible benefits of combined drinking and external cooling (by pouring cold water over the body) during exercise. Therefore, this study examined cold water drinking and external cooling on physiological, perceptual, and performance variables in hot, dry environments. Ten male runners completed four trials of walking 90 min at 30% VO(2max) followed by running a 5-km time trial in 33 ± 1 °C and 30 ± 4% relative humidity. Trials examined no intervention (CON), oral rehydration (OR), external cooling (EC), and oral rehydration plus external cooling (OR + EC). Investigators measured rectal temperature, skin temperatures, heart rate, thirst, thermal sensation, and ratings of perceived exertion (RPE). Oral rehydration (OR and OR + EC) significantly lowered heart rate (P < 0.001) and thirst (P < 0.001) compared with nondrinking (CON and EC) during low-intensity exercise. External cooling (EC and OR + EC) significantly reduced chest and thigh temperature (P < 0.001), thermal sensation (P < 0.001), and RPE (P = 0.041) compared with non-external cooling (CON and OR) during low-intensity exercise. Performance exhibited no differences (CON = 23.86 ± 4.57 min, OR = 22.74 ± 3.20 min, EC = 22.96 ± 3.11 min, OR + EC = 22.64 ± 3.73 min, P = 0.379). Independent of OR, pouring cold water on the body benefited skin temperature, thermal sensation, and RPE during low-intensity exercise in hot, dry conditions but failed to influence high-intensity performance.

Postural orthostatic tachycardia syndrome: a clinical review.

Postural orthostatic tachycardia syndrome was defined in adult patients as an increase >30 beats per minute in heart rate of a symptomatic patient when moving from supine to upright position. Clinical signs may include postural tachycardia, headache, abdominal discomfort, dizziness/presyncope, nausea, and fatigue. The most common adolescent presentation involves teenagers within 1-3 years of their growth spurt who, after a period of inactivity from illness or injury, cannot return to normal activity levels because of symptoms induced by upright posture. Postural orthostatic tachycardia syndrome is complex and likely has numerous, concurrent pathophysiologic etiologies, presenting along a wide spectrum of potential symptoms. Nonpharmacologic treatment includes (1) increasing aerobic exercise, (2) lower-extremity strengthening, (3) increasing fluid/salt intake, (4) psychophysiologic training for management of pain/anxiety, and (5) family education. Pharmacologic treatment is recommended on a case-by-case basis, and can include beta-blocking agents to blunt orthostatic increases in heart rate, alpha-adrenergic agents to increase peripheral vascular resistance, mineralocorticoid agents to increase blood volume, and serotonin reuptake inhibitors. An interdisciplinary research approach may determine mechanistic root causes of symptoms, and is investigating novel management plans for affected patients.

An assessment of cinacalcet HCl effects on bone histology in dialysis patients with secondary hyperparathyroidism.

AIMS: Cinacalcet lowers plasma parathyroid hormone (PTH) levels in patients with secondary hyperparathyroidism (sHPT), but the bone histologic response has not been described. This prospective, double-blind, placebo-controlled trial assessed the effects of cinacalcet on bone histology and serum markers of bone metabolism in dialysis patients with sHPT. METHODS: Patients with intact PTH (iPTH) > or = 300 pg/ml were randomly assigned 2:1 to receive cinacalcet or placebo with concurrent vitamin D and/or phosphate binder therapy. Cinacalcet (30 - 180 mg/day) was used to achieve iPTH levels < or = 200 pg/ml. Bone biopsies were performed before and after one year of treatment. RESULTS: Baseline and end-of-study data were available from 32 patients (19 cinacalcet, 13 placebo). Baseline bone turnover was elevated in 27, reduced in 3 and normal in 2 patients. Serum bone-specific alkaline phosphatase (BSAP) and N-telopeptide (NTx) were elevated. Cinacalcet treatment decreased PTH and diminished activation frequency, bone formation rate/bone surface, and fibrosis surface/bone surface. Adynamic bone was observed in three patients receiving cinacalcet; in two of these, PTH levels were persistently low (< 100 pg/ml). The histomorphometric parameter changes in bone corresponded to PTH, BSAP and NTx reductions. Bone mineralization parameters remained normal. CONCLUSIONS: Treatment with cinacalcet lowered PTH and reduced bone turnover and tissue fibrosis among most dialysis patients with biochemical evidence of sHPT.

Mechanomyographic responses of the superficial quadriceps femoris muscles to incremental isometric muscle actions.

The purpose of this study was to compare the composite and individual relationships for mechanomyographic (MMG) amplitude vs. torque during incremental isometric muscle actions. Ten women and six men (mean age +/- SD = 21.8 +/- 1.6 y) performed isometric leg extension muscle actions at 10-100% of peak isometric torque. Accelerometers were placed over the superficial quadriceps femoris muscles to detect the MMG signals. Polynomial regression analyses were used to determine the composite and individual patterns for MMG amplitude vs. isometric torque. The results indicated that the composite MMG amplitude vs. isometric torque relationships for all subjects combined were quadratic for the vastus lateralis and vastus medialis, and linear for the rectus femoris. The results of the individual analyses for the vastus lateralis revealed that the best fit model was linear for six subjects, quadratic for five subjects, cubic for three subjects, while two subjects exhibited no significant relationship. For the rectus femoris, eight subjects demonstrated linear patterns, six were quadratic, and two were cubic. For the vastus medialis, six subjects demonstrated linear patterns, four were quadratic, four were cubic, and two demonstrated no significant relationship. Examination of the patterns between muscles for each individual subject demonstrated that twelve of the sixteen subjects demonstrated different patterns for MMG amplitude vs. isometric torque for at least two of the three muscles examined. The results indicated there were differences in the patterns of responses for the composite MMG amplitude vs. isometric torque relationships for the three muscles. Furthermore, individual patterns for MMG amplitude frequently differed from the composite patterns, as well as between muscles. The results suggested that, in addition to using composite results of MMG responses, individual subject responses should be examined. Furthermore, caution should be used in generalizing the MMG responses of the quadriceps femoris muscles when examining a single muscle.

Severe hypokalaemic metabolic alkalosis following ingestion of gaviscon.

INTRODUCTION: Uncommon metabolic abnormalities in the emergency department could be a result of drug overdose due to uncommon agents. CASE REPORT: A 35-year-old male presented to the emergency department with a Glasgow Coma Scale (GCS) of 3/15 and a normal pulse rate and blood pressure. Subsequent questioning after recovery revealed he had ingested 2 L of Gaviscon over the preceding 48 hours. He had normal haematology, liver, and renal function during admission. The electrocardiogram showed T wave inversion in the inferior leads on admission. Arterial blood gas on air was: pH 7.54, HCO3 50 mmol/L (50 meq/L), Chloride 66 mmol/L, anion gap was 19, pO2 11 kPa (82.5 mmHg), and pCO2 8 kPa (60 mmHg). Serum sodium was 127 mmol/L and serum potassium was 1.6 mmol/L. His GCS improved within one hour of admission with supportive care, and his serum potassium and bicarbonate improved within 24 hours. He subsequently made a full recovery. Discussion. Bicarbonate ingestion in the form of Gaviscon(R) and vomiting made this patient alkalotic, and simple supportive care provided effective management with a complete recovery. CONCLUSION: This case illustrates how a severe metabolic alkalosis can result from a significant ingestion of Gaviscon, and that such presentations can give rise to diagnostic dilemma.

Comparison of Fourier and wavelet transform procedures for examining mechanomyographic and electromyographic frequency versus isokinetic torque relationships.

The purpose of this study was to compare the isokinetic torque-related patterns for mechanomyographic (MMG) and electromyographic (EMG) center frequency [wavelet center frequency (CF), mean power frequency (MPF), and median frequency (MDF)] determined by the fast Fourier transform (FFT) and discrete wavelet transform (DWT). Ten adults [mean +/- SD age = 22.0 +/- 3.4 yrs] performed submaximal to maximal, isokinetic muscle actions of the biceps brachii on a Cybex II dynamometer. For both MMG and EMG, the CF, MPF, and MDF values were intercorrelated at (r = 0.91-0.98). Quadratic models provided the best fit for the absolute and normalized CF, MPF, and MDF versus isokinetic torque relationships for MMG (R2 = 0.67-0.83) and EMG (R2 = 0.72-0.90). The similarities among the CF, MPF, and MDF patterns suggested that Fourier or wavelet transform procedures can be used to examine the patterns of MMG and EMG responses during dynamic muscle actions.

The acute effects of static stretching on peak torque, mean power output, electromyography, and mechanomyography.

The purpose of this study was to examine the acute effects of static stretching on peak torque (PT), the joint angle at PT, mean power output (MP), electromyographic (EMG) amplitude, and mechanomyographic (MMG) amplitude of the vastus lateralis (VL) and rectus femoris (RF) muscles during maximal, voluntary concentric isokinetic leg extensions at 60 and 240 degrees x s(-1) of the stretched and unstretched limbs. Twenty-one volunteers [mean age (SD) 21.5 (1.3) years] performed maximal, voluntary concentric isokinetic leg extensions for the dominant and non-dominant limbs at 60 and 240 degrees x s(-1). Surface EMG (muVrms) and MMG (mVrms) signals were recorded from the VL and RF muscles during the isokinetic tests. PT (Nm), the joint angle at PT, and MP (W) were calculated by a dynamometer. Following the initial isokinetic tests, the dominant leg extensors were stretched using four static stretching exercises. After the stretching, the isokinetic tests were repeated. PT decreased (P< or =0.05) from pre- to post-stretching for the stretched limb at 60 and 240 degrees x s(-1) and for the unstretched limb at 60 degrees x s(-1). EMG amplitude of the VL and RF also decreased (P< or =0.05) from pre- to post-stretching for the stretched and unstretched limbs. There were no stretching-induced changes (P>0.05) for the joint angle at PT, MP, or MMG amplitude. These findings indicated stretching-induced decreases in force production and muscle activation. The decreases in PT and EMG amplitude for the unstretched limb suggested that the stretching-induced decreases may be due to a central nervous system inhibitory mechanism.

Supraventricular tachyarrhythmias in Ebstein anomaly: management and outcome.

OBJECTIVE: This study was undertaken to review the role of electrophysiology testing and to determine the early and late results of medical and surgical management of supraventricular tachyarrhythmias in Ebstein anomaly. METHODS: We reviewed 130 patients between 1990 and 2001 with Ebstein anomaly and history of tachyarrhythmia with a median age of 25 years (mean age 27.5 years); 106 underwent electrophysiologic testing and 24 had documented atrial flutter or fibrillation. We excluded 21 patients: negative results of testing (n = 18), ventricular tachycardia (n = 2), and junctional tachycardia (n = 1). The remaining 109 patients had more than one mechanism: accessory pathway-mediated tachycardia (n = 49), atrioventricular nodal reentrant tachycardia (n = 10), and atrial flutter/fibrillation (n = 70). RESULTS: Eighty-three patients underwent at least one arrhythmia procedure combined with surgery for Ebstein anomaly. Early mortality was 4.8%. Forty-one patients underwent surgical ablation of an accessory pathway without recurrent accessory pathway-mediated tachycardia at a mean follow-up of 48 months. Seven patients underwent surgical perinodal cryoablation for atrioventricular nodal reentrant tachycardia without recurrence at a mean follow-up of 57 months. Forty-eight patients underwent surgical intervention for atrial flutter or fibrillation (right-sided maze procedure, n = 38, and cryoablation of the atrial isthmus, n = 10). Freedom from recurrent atrial flutter or fibrillation was 75% at a mean follow-up of 34 months. CONCLUSION: Concomitant arrhythmia procedures can be performed without increase in early mortality and should be added to Ebstein repairs for all patients who have supraventricular tachyarrhythmias. Surgical procedures for accessory pathway-mediated tachycardia and atrioventricular nodal reentrant tachycardia give excellent (100%) freedom from recurrence of those arrhythmias. Surgical intervention for atrial flutter/fibrillation yields freedom from late recurrence in 75% of cases.

Mechanomyographic and electromyographic amplitude and frequency responses during fatiguing isokinetic muscle actions of the biceps brachii.

The purpose of this investigation was to examine the mechanomyographic (MMG) and electromyographic (EMG) amplitude and mean power frequency (MPF) patterns during fatiguing isokinetic muscle actions of the biceps brachii. Ten adults [three women (mean +/- SD age = 20 +/- 2 yrs) and seven men (mean +/- SD age = 23 +/- 3 yrs) ] volunteered to perform 50 consecutive maximal, concentric isokinetic muscle actions of the biceps brachii at 180 degrees x s(-1). The percent decline (mean +/- SD) in isokinetic peak torque (PT) was 70 +/- 17% and polynomial regression analyses indicated a cubic relationship (R2 = 0.994) between PT and repetition number. Both MMG amplitude and MMG MPF decreased linearly (r2 = 0. 774 and 0.238, respectively) across repetitions. The results for EMG amplitude demonstrated a cubic (R2 = 0.707) pattern across repetitions, where EMG amplitude increased during repetitions 1-20, remained stable during repetitions 20-40, and increased during repetitions 40-50. There was a quadratic (R2 = 0. 939) reduction in EMG MPF throughout the test. The decreases in MMG amplitude and MMG MPF may have been due to de-recruitment of fast fatiguing motor units, a reduction in muscular compliance, or the effects of "muscle wisdom." The results for EMG amplitude may have reflected nonmaximal efforts by the subjects and/or peripheral fatigue. The factor(s) determining the decrease in EMG MPF are unclear, although a reduction in muscle fiber action potential conduction velocity may have been partially responsible.

Mechanomyographic time and frequency domain responses of the vastus medialis muscle during submaximal to maximal isometric and isokinetic muscle actions.

The purpose of this study was to examine the patterns for the mechanomyographic (MMG) amplitude and mean power frequency (MPF) versus torque relationships during isometric and isokinetic muscle actions. Ten adults (mean age +/- SD = 22 +/- 1 y) volunteered to perform isometric and isokinetic leg extension muscle actions at 10, 20, 30, 40, 50, 60, 70, 80, 90, and 100% of peak torque on a Cybex II dynamometer. A piezoelectric crystal contact sensor was placed on the vastus medialis to detect the MMG signal. Regression analyses indicated that for the isometric muscle actions, the relationships for MMG amplitude (R2 = 0.998) and MPF (R2 = 0.987) versus torque were cubic. For the isokinetic muscle actions, the relationships for MMG amplitude (r2 = 0.927) and MPF (r2 = 0.769) versus torque were linear. The different patterns for MMG amplitude and frequency may reflect differences in the motor control strategies that modulate torque production for isometric versus dynamic muscle actions.

Delineation of Borrelia burgdorferi p66 sequences required for integrin alpha(IIb)beta(3) recognition.

The outer membrane protein p66 of the Lyme disease agent, Borrelia burgdorferi, has been identified as a candidate ligand for beta(3)-chain integrins. To identify portions of p66 required for integrin recognition, fusions of maltose-binding protein to fragments of p66 were tested for binding to integrin alpha(IIb)beta(3), and synthetic peptides derived from the p66 amino acid sequence were tested for the ability to inhibit B. burgdorferi attachment to the same integrin. The data identify two noncontiguous segments of p66 that are important for alpha(IIb)beta(3) recognition, suggesting that, as is true for other integrin ligands, the tertiary structure of p66 is important for receptor recognition.

Efficacy and side effects of intermittent intravenous and oral doxercalciferol (1alpha-hydroxyvitamin D(2)) in dialysis patients with secondary hyperparathyroidism: a sequential comparison.

Most reports on the effectiveness and side effects of oral versus parenteral calcitriol or alfacalcidol in hemodialysis patients with secondary hyperparathyroidism show no advantage of parenteral treatment. The efficacy and safety of intravenous doxercalciferol (1alphaD(2)) were studied in hemodialysis patients with secondary hyperparathyroidism (plasma intact parathyroid hormone [iPTH]: range, 266 to 3,644 pg/mL; median, 707 pg/mL). These results were compared with those of a previous trial using intermittent oral 1alphaD(2); the same 70 patients were entered onto both trials, and 64 patients completed both trials per protocol. Twelve weeks of open-label treatment in both trials were preceded by identical 8-week washout periods. Degrees of iPTH suppression from baseline were similar in the two trials, with iPTH level reductions less than 50% in 89% and 78% of patients during oral and intravenous treatment, respectively. Grouping patients according to entry iPTH levels (<750 and >/=750 pg/mL) showed similar but more rapid iPTH suppression in the low-iPTH groups, whereas longer treatment and larger doses were required by the high-iPTH groups. Highest serum calcium levels averaged 9.82 +/- 0.14 and 9.67 +/- 0.11 mg/dL during oral and intravenous 1alphaD(2) treatment, respectively (P: = not significant [NS]). Prevalences of serum calcium levels greater than 11.2 mg/dL during oral and intravenous treatment were 3.62% and 0.86% of calcium measurements, respectively (P: < 0.001). Highest serum phosphorus levels during oral and intravenous treatment averaged 5.82 +/- 0.21 and 5.60 +/- 0.21 mg/dL, respectively (P: = NS). The percentage of increments in serum phosphorus levels during oral treatment exceeded that during intravenous treatment during 5 of 12 treatment weeks. Thus, intermittent oral and intravenous therapy with 1alphaD(2) reduced iPTH levels effectively and similarly, hypercalcemia was less frequent, and serum phosphorus levels increased less during intravenous than oral 1alphaD(2) therapy, suggesting that intravenous 1alphaD(2) therapy may be advantageous in patients prone to hypercalcemia or hyperphosphatemia.

Recognition of multiple antibody epitopes throughout Borrelia burgdorferi p66, a candidate adhesin, in patients with early or late manifestations of Lyme disease.

Antibody responses to p66, a candidate integrin ligand of Borrelia burgdorferi, were studied in 79 patients with early or late manifestations of Lyme disease. The central portion of p66 was previously shown to contain all of the information required for specific recognition of beta3-chain integrins, but work by others had suggested that the C-terminal portion of the protein contains a single surface-exposed, immunodominant loop. In examining antibody responses to full-length p66 and to three overlapping fragments of the protein, we found that the majority of Lyme disease patients had immunoglobulin M (IgM) and/or IgG responses to p66 and that, particularly early in the disease, epitopes throughout p66 were recognized. Among patients with later manifestations of the illness, antibody responses to the C-terminal portion of the protein were more prominent. These results demonstrate that Lyme disease patient sera recognize epitopes throughout p66.

Platelet activation by a relapsing fever spirochaete results in enhanced bacterium-platelet interaction via integrin alphaIIbbeta3 activation.

Borrelia hermsii, a spirochaete responsible for relapsing fever in humans, grows to high density in the bloodstream and causes thrombocytopenia. We show here that B. hermsii binds to human platelets. Extended culture in bacteriological medium resulted in both diminished infectivity in vivo and diminished platelet binding in vitro. Platelet binding was promoted by the platelet integrin alphaIIbbeta3: the bacterium bound to purified integrin alphaIIbbeta3, and bacterial binding to platelets was diminished by alphaIIbbeta3 antagonists or by a genetic defect in this integrin. Integrin alphaIIbbeta3 undergoes a conformational change upon platelet activation, and bacteria bound more efficiently to activated rather than resting platelets. Nevertheless, B. hermsii bound at detectable levels to preparations of resting platelets. The bacterium did not recognize a point mutant of alphaIIbbeta3 that cannot acquire an active conformation. Rather, B. hermsii was capable of triggering platelet and integrin alphaIIbbeta3 activation, as indicated by the expression of the platelet activation marker P-selectin and integrin alphaIIbbeta3 in its active conformation. The degree of platelet activation varied depending upon bacterial strain and growth conditions. Prostacyclin I2, an inhibitor of platelet activation, diminished bacterial attachment, indicating that activation enhanced bacterial binding. Thus, B. hermsii signals the host cell to activate a critical receptor for the bacterium, thereby promoting high-level bacterial attachment.