A portable system for the assessment of neuromuscular diseases with electrical impedance myography.

PRIMARY OBJECTIVE: To create a system for the acquisition of multi-angle, multifrequency muscle impedance data. RESEARCH DESIGN: Device development and preliminary testing. METHODS AND PROCEDURES: The system presented here employs an interrogating signal composed of multiple tones with frequencies between 10 kHz and 300 kHz. The use of a composite signal makes possible measurement of impedance at multiple frequencies simultaneously. In addition, this system takes impedance measurements at multiple orientations with respect to the muscle fibres by means of an electronically reconfigurable electrode array. The required measurement time is reduced by taking advantage of muscle's linearity with respect to the flow of electrical current. MAIN OUTCOMES AND RESULTS: The system was tested in normal subjects, a patient with amyotrophic lateral sclerosis, and one with inclusion body myositis; unique impedance signatures were identified the two patients. CONCLUSIONS: Early data suggest that this system is capable of high-quality data collection and may detect changes in neuromuscular disease; study of additional normal subjects and patients with a variety of neuromuscular diseases is warranted.

The ovariectomized sheep as a model for human bone loss.

The aim of this study was to determine the effects of ovariectomy on the trabeculae of ovine iliac bone, with a view to the further development of a model for human osteoporosis. Seven ovariectomized (OVX) and five control Dorset ewes were observed for one year. Iliac crest bone samples were obtained at the time of ovariectomy ("time 0") and again when the animals were killed 12 months later. At "time 0" and at 3-month intervals thereafter samples of blood and urine were collected for the assay of serum 17beta-oestradiol and osteocalcin (OC) and urinary deoxypyridinium (D-PYR). One year after ovariectomy, trabecular bone volume and thickness were reduced (P<0.05) and trabecular separation was increased (P<0.05) as compared with the controls. In OVX sheep, serum 17beta-oestradiol concentrations were significantly lower at the end of the experiment than at "time 0", while serum OC and urinary D-PYR concentrations were significantly higher (P<0.001). The results suggest that the OVX sheep is a valid model for changes in trabecular bone architecture associated with oestrogen deficiency, especially in women experiencing early menopause.

Effect of estrogen deficiency on skeletal and alveolar bone density in sheep.

BACKGROUND: This study provides a longitudinal assessment of changes in alveolar and skeletal bone mineral density (BMD) in ovariectomized animals. METHODS: Following ovariectomy (OVX) (n = 6) or sham-operation (n = 6) intraoral radiographs were made at 4-month intervals and serum 17-beta-estradiol, osteocalcin, and interleukin (IL)-6, urinary deoxypyridinium, and salivary IL-6, deoxypyridinium, and osteocalcin concentrations were evaluated. Twelve months after surgery, animals were sacrificed and the mandible and radius/ulna removed. Bones were sectioned and radiographed. Mean BMD and cortical thicknesses were calculated from each region. RESULTS: OVX animals had a progressive decrease in serum 17-beta-estradiol, increased serum osteocalcin and IL-6, urinary deoxypyridinium and salivary IL-6, osteocalcin and deoxypyridinium (P < 0.001), suggesting that they were becoming osteoporotic. The BMD of the radius/ulna and mandibular alveolar bone was significantly reduced in OVX animals (P < 0.05 and P < 0.001, respectively). Reduced alveolar bone BMD became evident in OVX animals 6 months after surgery and became more severe during the subsequent 6 months. Alveolar crestal height was also significantly reduced in OVX animals (P < 0.001). These biochemical and density changes preceded a significant reduction in serum 17-beta-estradiol, which occurred between 4 and 8 months following surgery. CONCLUSIONS: Serial measurements of alveolar BMD predicts loss of skeletal BMD in OVX sheep. Changes in alveolar BMD precede estrogen deficiency, suggesting that early signs of reduced BMD may be detected in peri-menopausal women. The presence of biomarkers of bone metabolism within saliva and their correlation with reduced BMD suggests that saliva could be used as an adjunct screening method for assessment of skeletal bone density.

MRI screening for acoustic neuroma: a comparison of fast spin echo and contrast enhanced imaging in 1233 patients.

Gadolinium enhanced MRI is the gold standard investigation for the detection of acoustic neuroma. Non-contrast MRI sequences have been suggested as an alternative for screening examinations. In order to determine the utility of fast spin echo imaging, both gadolinium enhanced T1 weighted images and fast spin echo T2 weighted images were acquired in 1233 consecutive patients referred for exclusion of acoustic neuroma. Two radiologists independently recorded their findings. Fast spin echo T2 weighted images were evaluated with respect to the visibility of nerves within the internal auditory canals and allocated a confidence score for the presence or absence of acoustic neuroma. 33 acoustic neuromas were identified. Only 56% were confidently identified on fast spin echo T2 weighted images alone; gadolinium enhanced T1 weighted images were required to confirm the diagnosis in 44% of the cases, including 9 of the 10 intracanalicular tumours. However, when identification of two normal intracanalicular nerves is employed as the criterion of normality, the single fast spin echo T2 weighted sequence excluded acoustic neuroma in 59% of this screened population. It is concluded that an imaging strategy intended to identify small intracanalicular acoustic neuromas cannot rely on fast spin echo T2 weighted imaging alone. Gadolinium enhanced T1 weighted imaging could be restricted to patients where fast spin echo images do not exclude acoustic neuroma but this strategy requires continuous supervision by an experienced radiologist. In most practices the screening examination should continue to include a gadolinium enhanced sequence in order to optimize the detection of small acoustic neuromas.

Mini review of canine stifle joint anatomy.

The stifle is a complex, condylar, synovial joint that allows motion in three planes. The complexity of the normal motion is directly related to the structure and functions of the anatomical components that form the joint. Alteration in any one of these components often leads to dysfunction as well as an increased risk of damage to other structures in the joint. Thus understanding of the normal anatomy and function of each stifle joint component is essential for proper diagnosis and treatment of any stifle joint injury. This review highlights the basic anatomy and function of the stifle joint components.

Preliminary evaluation of a new dental implant design in canine models.

Problems with crestal bone resorption and bone adaptation to dental implants in compromised and weak bone present clinical challenges due to insufficient bone volume. Mathematical models have shown that a new, square-thread, dental implant design increases functional surface area and reduces shear loading at the implant interface. The aim of this investigation was to evaluate the ability of bone to grow between the threads of the new implant and its general biocompatibility in a canine model. Test implants were placed in the mandibles of four beagle dogs after posterior partial edentulism. Three months after implantation, the animals received independent fixed partial dentures, were followed for an additional 6 months, and then euthanized for histological analyses. Analyses revealed that bone grew between the threads and closely apposed the new implant design. Histological observations also revealed that the inferior aspect of the test implant threads were apposed by more bone than the coronal aspect, suggesting a biological advantage for the compressive load transfer mechanism of the new implant design. The results of this study revealed that the new implant design became osseointegrated with bone growing between the threads of the device.

A swine model for the evaluation of efficacy of anti-microbial catheter coatings.

A swine model was developed to investigate the efficacy of percutaneous venous catheters with anti-microbial coatings. The catheters used in the study consisted of silver-coated and uncoated catheters, both designed for percutaneous venous access. Five commercial pigs were each implanted with three venous catheters and followed for a period of 90 days. Two of the three catheters were coated and one was uncoated. To evaluate the percutaneous aspects of the catheters in the model, two venous access catheters were implanted percutaneously, parallel to the dorsal midline. These catheters were just caudal to the region that is dorsal to the scapula in each animal. In each case, the catheter to the left of the dorsal midline was silver-coated while the catheter to the right of the dorsal midline was uncoated. A silver-coated catheter was also implanted in the left external jugular vein of each animal and buried subcutaneously in order to evaluate the elution of the coating through the body under venous contact. Over the 90 day period, the concentration of silver in the blood rose to a mean peak level of 23.2 ppb following implantation of the catheters and then decreased after the second post-surgery week. The histological evaluation and macroscopic inspection at necropsy revealed minimal tissue response to both coated and uncoated materials. Data on bacterial growth indicated that bacteria were present at the terminal subcutaneous end of two of the uncoated percutaneous catheters. Based upon serum silver levels, exudate formation, histological examination, and bacterial growth information, the swine model was deemed to be suitable for testing the efficacy of catheters containing anti-microbial coatings.

Alveolar bone loss one year following ovariectomy in sheep.

There is little information concerning the incidence of alveolar bone loss in estrogen-deficient women. Ovariectomized sheep are valid models for study of the effects of estrogen deficiency on bone metabolism. The objective of this study was to compare alveolar bone loss in control (C) and ovariectomized sheep (OVX) at 3 and 12 months following surgery. OVX animals had decreased serum levels of 17-beta-estradiol and increased serum levels of osteocalcin, IL-6, and urinary levels of deoxypyridinoline which, taken together, suggest development of osteoporosis. The mean probing depths and percentage of sites with pocket depths 4 to 6 mm and > 6 mm were significantly greater in OVX than C at each time period and in OVX were significantly greater at 12 months that at 3 months. Gingival tissue interleukin-6 (IL-6) levels (but not the number of IL-6(+) cells) were elevated adjacent to deep periodontal pockets; however, there was no significant elevation of levels of the proinflammatory cytokines IL-1 beta and IL-8 within gingiva. Taken together, the data suggest a systemic contribution for progression of periodontal disease associated with estrogen deficiency. This may involve upregulation of systemic IL-6 synthesis and transfer to gingiva in serum, resulting in enhanced IL-6 accumulation within the gingival tissues or reduced bone density allowing for a greater amount of alveolar bone loss.

DNA haplotypes of the complement C6 and C7 genes associated with deficiencies of the seventh component; and a new DNA polymorphism in C7 exon 13.

Eight common DNA polymorphisms have been described for the linked C6 and C7 genes. We now describe a ninth polymorphism in C7 exon 13 which is located in a tight cluster with two previously reported markers. We have used all these markers to investigate the heterogeneity of C7 deficiency. Five of the nine C7 deficient probands (resident in Ireland, South Africa, Russia and Israel) are heterozygous for C6/C7 haplotypes. Seven different C7 deficient haplotypes were found for C7 markers alone, but all the four Israelis share one and three out of four Irish haplotypes share another. The markers appear to be a good guide to the heterogeneity of C7 deficiency and have been useful in choosing homozygous subjects for the investigation of molecular defects.

A natural mutant of plasmid RP4 that confers phage resistance and reduced conjugative transfer.

A natural isolate of RP4 (PRC#116) acquired from the Stanford University Plasmid Reference Center differed from the wild-type Incompatibility Group P plasmid in several respects. Cells of Escherichia coli harboring PRC#116 were resistant to the IncP pili-specific bacteriophage PRD1 and GU5, and transferred this plasmid at a lower efficiency than the wild-type RP4. Phage sensitivity was restored, and transfer considerably improved in PRC#116+ bacteria transformed with plasmid constructs containing the origin of transfer (oriT region) of RP4. Mutant RP4 plasmids equivalent to PRC#116 were selected at a high frequency from an RP4+ E. coli population infected with PRD1 indicating that this RP4 variant may be the product of a very common mutation of the wild-type plasmid.

Differential cardiovascular effects of propranolol, atenolol, and pindolol measured by impedance cardiography.

We have evaluated Sramek's method of impedance cardiography as a non-invasive way of detecting the cardiovascular effects of drugs. We made cardiovascular measurements using the method during passive tilting and exercise 2 h after the oral administration of atenolol (50 and 100 mg), propranolol (40 and 80 mg), pindolol (5 and 10 mg), and placebo in seven separate studies involving eight healthy male volunteers. Equivalent doses of the pure antagonists atenolol (beta 1) and propranolol (beta 1, beta 2) produced similar reductions in heart rate, systolic blood pressure, and cardiac index, and increases in stroke volume and total peripheral resistance, particularly during exercise. In contrast the partial agonist pindolol produced increases in heart rate and cardiac index, and reductions in peripheral resistance at rest. During passive tilting and exercise pindolol reduced heart rate, but cardiac output and total peripheral resistance were unchanged except at the highest levels of exercise. The similar cardiovascular effects of atenolol and propranolol, but differing effects of pindolol, are consistent with reports using other methods of measurement. This suggests that impedance cardiography may have a place in the non-invasive assessment of the cardiovascular effects of drugs.

The hygienic aspects of wastewater reuse.

Historically drinking water contaminated with wastewater discharged from nearby communities has been a major public health problem whose solution was directed towards the treatment of drinking water rather than of the source of contamination. The increased need for deliberate wastewater reuse has stimulated greater interest in the ability of wastewater treatment processes to produce a product in which the risk of infection, upon reuse, is reduced to an acceptable level. A brief overview of the disease agents involved, human dose-response considerations, microbial standards, and treatment plant reliability is presented. Selected experiences with the question as to how our terrestrial experience can be applicable to advanced life support systems is addressed.

A study of immune responses to myelin and cardiolipin in patients with systemic lupus erythematosus (SLE).

Sera from 39 patients with SLE, 20 patients with cerebrovascular disease with no evidence of SLE, and 20 normal controls were tested for antibodies to cardiolipin (CL), brain total upper (UPG) and lower phase (LPG) glycolipids, myelin basic protein (MBP), myelin, and single strand DNA (ssDNA) by ELISA. Binding to the glycolipids and MBP was negative or negligible in all the groups, but significant binding was observed against CL, myelin and ssDNA in some of the SLE patients. Many sera from SLE patients with cerebral disorders and high CL binding also demonstrated high binding to myelin. These sera also labelled cell surface antigens on neonatal mouse neurons and astrocytes by immunofluorescence in tissue culture. A correlation was found to exist between anti-CL and antimyelin antibodies in SLE patients with cerebral lesions, but not between anti-ssDNA and anti-CL antibodies. As much as 80-90% of the specific activity of these antibodies could be absorbed out by the relevant antigens but only partially by the other antigens. In the control groups binding was low and no specific absorption could be demonstrated.

Deficiency of the seventh component of complement. A case report.

Deficiency of the 7th component of the complement cascade was diagnosed in a white male with recurrent meningococcal infections. This deficiency has not previously been reported in South Africa.

Prophylaxis against Neisseria meningitidis infections and antibody responses in patients with deficiency of the sixth component of complement.

Forty South African patients with homozygous deficiency of the sixth component of complement (C6) have been identified in an area where group B meningococcal meningitis is endemic; 22 of the 24 proband cases presented with recurrent meningococcal meningitis. In a 2- to 4-year prospective study, patients with recurrent infections who received monthly prophylactic long-acting penicillin were significantly protected from subsequent neisserial infection compared with those who did not receive penicillin (P = .02, Fisher's exact test). Heterogeneous susceptibility to neisserial infection was confirmed by following C6-deficient patients who presented with one or no Neisseria meningitidis infections. These patients, on no prophylaxis, had significantly fewer infections (P = .004) than did patients who presented with recurrent disease. Functional C6 activity was restored by transfusion of fresh frozen plasma in a C6-deficient patient resistant to conventional antibiotic treatment. Antibody levels to the serotype 2 outer membrane proteins were significantly elevated in C6-deficient patients compared with control groups (P = .001).