Management of Iatrogenic Direct Carotid Cavernous Fistula Occurring During Endovascular Treatment of Stroke.

Traumatic carotid cavernous fistula may occur as a complication of endovascular treatment of acute stroke. We report 3 cases of such lesions. All patients were initially managed conservatively. Two patients have remained asymptomatic. One patient became symptomatic with right eye proptosis, chemosis, and right lateral gaze diplopia 3 weeks post thrombectomy. He underwent endovascular embolization via transfemoral transvenous approach via the inferior ophthalmic vein.

Development, Validation, and Field-Testing of an Instrument for Clinical Assessment of HIV-Associated Neuropathy and Neuropathic Pain in Resource-Restricted and Large Population Study Settings.

HIV-associated sensory peripheral neuropathy (HIV-SN) afflicts approximately 50% of patients on antiretroviral therapy, and is associated with significant neuropathic pain. Simple accurate diagnostic instruments are required for clinical research and daily practice in both high- and low-resource setting. A 4-item clinical tool (CHANT: Clinical HIV-associated Neuropathy Tool) assessing symptoms (pain and numbness) and signs (ankle reflexes and vibration sense) was developed by selecting and combining the most accurate measurands from a deep phenotyping study of HIV positive people (Pain In Neuropathy Study-HIV-PINS). CHANT was alpha-tested in silico against the HIV-PINS dataset and then clinically validated and field-tested in HIV-positive cohorts in London, UK and Johannesburg, South Africa. The Utah Early Neuropathy Score (UENS) was used as the reference standard in both settings. In a second step, neuropathic pain in the presence of HIV-SN was assessed using the Douleur Neuropathique en 4 Questions (DN4)-interview and a body map. CHANT achieved high accuracy on alpha-testing with sensitivity and specificity of 82% and 90%, respectively. In 30 patients in London, CHANT diagnosed 43.3% (13/30) HIV-SN (66.7% with neuropathic pain); sensitivity = 100%, specificity = 85%, and likelihood ratio = 6.7 versus UENS, internal consistency = 0.88 (Cronbach alpha), average item-total correlation = 0.73 (Spearman's Rho), and inter-tester concordance > 0.93 (Spearman's Rho). In 50 patients in Johannesburg, CHANT diagnosed 66% (33/50) HIV-SN (78.8% neuropathic pain); sensitivity = 74.4%, specificity = 85.7%, and likelihood ratio = 5.29 versus UENS. A positive CHANT score markedly increased of pre- to post-test clinical certainty of HIV-SN from 43% to 83% in London, and from 66% to 92% in Johannesburg. In conclusion, a combination of four easily and quickly assessed clinical items can be used to accurately diagnose HIV-SN. DN4-interview used in the context of bilateral feet pain can be used to identify those with neuropathic pain.

Feedback control of electrical stimulation electrode arrays.

Electrical stimulation electrode arrays are an emerging technology that enables muscles to be artificially contracted through the activation of their associated motor neurons. A principal application of electrical stimulation is to assist human motion for orthotic or therapeutic purposes. This paper develops a framework for the design of model-based electrode array feedback controllers that balance joint angle tracking performance with the degree of disturbance and modeling mismatch that can exist in the true underlying biomechanical system. This framework is used to develop a simplified control design procedure that is suitable for application in a clinical setting. Experimental results evaluate the feasibility of the control design approach through tests on ten participants using both fabric and polycarbonate electrode arrays.

Sensory, psychological, and metabolic dysfunction in HIV-associated peripheral neuropathy: A cross-sectional deep profiling study.

HIV-associated sensory neuropathy (HIV-SN) is a frequent complication of HIV infection and a major source of morbidity. A cross-sectional deep profiling study examining HIV-SN was conducted in people living with HIV in a high resource setting using a battery of measures which included the following: parameters of pain and sensory symptoms (7day pain diary, Neuropathic Pain Symptom Inventory [NPSI] and Brief Pain Inventory [BPI]), sensory innervation (structured neurological examination, quantitative sensory testing [QST] and intraepidermal nerve fibre density [IENFD]), psychological state (Pain Anxiety Symptoms Scale-20 [PASS-20], Depression Anxiety and Positive Outlook Scale [DAPOS], and Pain Catastrophizing Scale [PCS], insomnia (Insomnia Severity Index [ISI]), and quality of life (Short Form (36) Health Survey [SF-36]). The diagnostic utility of the Brief Peripheral Neuropathy Screen (BPNS), Utah Early Neuropathy Scale (UENS), and Toronto Clinical Scoring System (TCSS) were evaluated. Thirty-six healthy volunteers and 66 HIV infected participants were recruited. A novel triumvirate case definition for HIV-SN was used that required 2 out of 3 of the following: 2 or more abnormal QST findings, reduced IENFD, and signs of a peripheral neuropathy on a structured neurological examination. Of those with HIV, 42% fulfilled the case definition for HIV-SN (n=28), of whom 75% (n=21) reported pain. The most frequent QST abnormalities in HIV-SN were loss of function in mechanical and vibration detection. Structured clinical examination was superior to QST or IENFD in HIV-SN diagnosis. HIV-SN participants had higher plasma triglyceride, concentrations depression, anxiety and catastrophizing scores, and prevalence of insomnia than HIV participants without HIV-SN.

Pharmacological treatment of painful HIV-associated sensory neuropathy: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Significant pain from HIV-associated sensory neuropathy (HIV-SN) affects ∼40% of HIV infected individuals treated with antiretroviral therapy (ART). The prevalence of HIV-SN has increased despite the more widespread use of ART. With the global HIV prevalence estimated at 33 million, and with infected individuals gaining increased access to ART, painful HIV-SN represents a large and expanding world health problem. There is an urgent need to develop effective pain management strategies for this condition. OBJECTIVE: To evaluate the clinical effectiveness of analgesics in treating painful HIV-SN. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Medline, Cochrane central register of controlled trials, www.clinicaltrials.gov, www.controlled-trials.com and the reference lists of retrieved articles. SELECTION CRITERIA: Prospective, double-blinded, randomised controlled trials (RCTs) investigating the pharmacological treatment of painful HIV-SN with sufficient quality assessed using a modified Jadad scoring method. REVIEW METHODS: Four authors assessed the eligibility of articles for inclusion. Agreement of inclusion was reached by consensus and arbitration. Two authors conducted data extraction and analysis. Dichotomous outcome measures (≥ 30% and ≥ 50% pain reduction) were sought from RCTs reporting interventions with statistically significant efficacies greater than placebo. These data were used to calculate RR and NNT values. RESULTS: Of 44 studies identified, 19 were RCTs. Of these, 14 fulfilled the inclusion criteria. Interventions demonstrating greater efficacy than placebo were smoked cannabis NNT 3.38 95%CI(1.38 to 4.10), topical capsaicin 8%, and recombinant human nerve growth factor (rhNGF). No superiority over placebo was reported in RCTs that examined amitriptyline (100mg/day), gabapentin (2.4 g/day), pregabalin (1200 mg/day), prosaptide (16 mg/day), peptide-T (6 mg/day), acetyl-L-carnitine (1g/day), mexilitine (600 mg/day), lamotrigine (600 mg/day) and topical capsaicin (0.075% q.d.s.). CONCLUSIONS: Evidence of efficacy exists only for capsaicin 8%, smoked cannabis and rhNGF. However,rhNGF is clinically unavailable and smoked cannabis cannot be recommended as routine therapy. Evaluation of novel management strategies for painful HIV-SN is urgently needed.

A helical capping motif in ShK toxin and its role in helix stabilization.

ShK toxin, a 35-residue polypeptide cross-linked by three disulfides, is a potent blocker of voltage-gated potassium channels and is of interest as a lead in the development of new immunosuppressant agents. ShK toxin contains two short stretches of alpha-helix, the first of which is preceded by a putative N-capping box encompassing residues Thr13 and Gln16. (1)H and (13)C NMR data support the presence of this structural motif, but the hydrogen bonds involving residues 13 and 16 in the solution structure of ShK toxin do not match the pattern expected for a conventional N-cap motif. They do, however, fit the pattern for the recently described ST-motif, class 4a (Wan and Milner-White (1999) Journal of Molecular Biology, 1999, Vol. 286, pp. 1651-1662). The (1)H NMR chemical shifts, nuclear Overhauser effects, and amide exchange rates of native ShK toxin are compared with those of three synthetic analogues with the substitutions Thr13 to Ala and Gln16 to Glu and Ala in order to determine the contribution of this motif to the structure and stability of ShK toxin. Disruption of the capping interactions destabilizes the helices, with the Thr13 to Ala substitution being much more disruptive than Gln16 to Ala, consistent with the lack of hydrogen bonding to the side chain of residue i + 4 in a class 4a ST-motif. Mutation of residues 13 and 16 has only a minor effect on potassium channel binding, probably because the disulfide bonding network minimizes the effect of loss of the capping motif on the overall structure. The implications of these findings for the design of ShK analogues are discussed.

Ionisation behaviour and solution properties of the potassium-channel blocker ShK toxin.

The effects of pH, temperature and polypeptide concentration on the solution structure and side chain interactions of ShK toxin, a potassium-channel-blocking polypeptide from the sea anemone Stichodactyla helianthus, have been investigated by means of one-dimensional and two-dimensional 1H-NMR spectroscopy. Resonance assignments have been obtained for most protons in the molecule, and for the alpha and beta carbon atoms. The lack of concentration dependence of the 1H chemical shifts and linewidths indicates that self-association is not significant and cannot account for the sheet-like structure near the N terminus. The structure is stable to high temperature, showing little change even at 353 K. This stability allowed backbone-amide temperature coefficients to be interpreted, and the correlation of these values with hydrogen bonds observed in the structures and with solvent exchange rates is discussed. pKa values have been measured for Asp5, His19 and Tyr23, and the contributions to these pKa values from other residues investigated using the analogues R11Q (denoting substitution of Argll with Gln), R11E, H19K, K22A, Y23A and K30A. These results show that Asp5 (pKa 2.8) makes an electrostatic interaction with Lys30, which may be partially responsible for the importance of these side chains in the folding of synthetic toxin. The phenolic pKa of Tyr23 is reduced to 8.7 in the native toxin, as a result of interactions with the positively charged side chains of Arg11 and to a lesser extent Lys22. Several hydrogen bonds between the Arg11 guanidino group and the Tyr23 phenolic group are found in the solution structures. As these three residues are implicated in the tight binding of ShK toxin to the T-lymphocyte voltage-gated potassium channel Kv1.3, their close interactions should be taken into account in models of binding of this toxin to the pore and vestibule of this and other potassium channels.

Defining the need for faculty in family medicine: results of a national survey.

BACKGROUND: Although numerous anecdotal reports are being offered about the growing number of unfilled faculty positions in US family medicine departments, virtually no literature exists on faculty recruitment. The objective of this study was to define the scope and nature of current faculty recruitment needs in family medicine. METHODS: A national survey was sent to all family medicine department chairs and family practice residency program directors concerning faculty positions unfilled at their sites and positions for which recruitment would occur within the next 5 years. The survey asked for information on currently available positions; academic title of position; percentage of time to be devoted to clinical, educational, administrative, and research activities; primary focus of the position; date when the position became available; and the length of time the position has been unfilled. Similar information was collected on positions anticipated to be available within the next 5 years. RESULTS: A total of 364 surveys were returned, for an overall response rate of 70%. Information from the survey revealed a current, substantial demand for family medicine faculty throughout the country, with an even greater demand anticipated for the near future. Respondents reported 496 currently unfilled positions for family medicine faculty and another 677 positions anticipated to be available within the next 19.5 months on average. A total of 89.7% of those anticipated positions were reported as either "certain" or "somewhat certain," in terms of likelihood of availability. CONCLUSIONS: The demand for family medicine faculty is increasing, and much of the demand is financially motivated. Clinical expectations appear to be higher among departments than for residencies. Finally, it was revealed that most positions had minimal allotments for research time. Family medicine must recommit itself to the development of a scholarly agenda as it recruits new faculty.

Extracorporeal shock wave lithotripsy: multicenter study of kidney and upper ureter versus middle and lower ureter treatments.

Six institutions throughout the United States participated in this study. Each center used a multifunctional flat table lithotriptor (Dornier MFL-5000) to treat 658 patients with kidney and upper ureteral stones (766 treatments) and 323 with middle and lower ureteral stones (391 treatments), for a total of 925 patients (1,157 treatments). Some patients received more than 1 treatment (that is the kidney and ureter), for a total of 981 patient events. Complete followup was available for 81% of the patients. The overall stone-free rate at followup of approximately 90 days was greater in the middle and lower ureter group (83%) than in the kidney and upper ureter group (67%). The proportion of single stones treated was greater for the former group (89.5%) than for the latter group (72%). A larger proportion (18%) of the middle and lower ureter group required 2 or more treatments to the targeted stone than did the kidney and upper ureter group (13%). Anesthesia was required or selected in only 26.7% of the kidney and upper ureteral stone patients and in 18.5% of those with middle and lower ureteral calculi, usually at the request of the patient or physician, or for performance of an adjunctive procedure. The relative safety of this treatment is demonstrated by a low overall rate of complications reported during and after treatment, including a ureteral obstruction rate of 2.1% for kidney and upper ureteral stones and 2.5% for middle and lower ureteral stones. There were no demonstrated trends in a review of laboratory data to suggest significant treatment side effects. The diastolic blood pressure increased to more than 95 mm. Hg after extracorporeal shock wave lithotripsy (ESWL*) in 6% of the kidney and upper ureteral and 4% of the middle and lower ureteral stone patients, while pretreatment hypertension resolved after ESWL in 11% of both groups. The results of this clinical evaluation indicate somewhat greater effectiveness for the specified indications of ESWL of stones in the ureter below the upper rim of the bony pelvis, as opposed to those in the kidney and upper ureter, with a low incidence of complications and side effects.

Translocation of an outer membrane protein into prey cytoplasmic membranes by bdellovibrios.

Within minutes of Bdellovibrio bacteriovorus attack on prey cells, such as Escherichia coli, the cytoplasmic membrane of the prey is altered. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of purified invaded prey cell (bdelloplast) membranes revealed the appearance of a noncytoplasmic membrane protein. This protein is not observed in preparations of noninvaded E. coli membranes and migrates in a manner similar to that of E. coli OmpF. Isoelectric focusing and two-dimensional gel electrophoresis of bdelloplast cytoplasmic membrane preparations also revealed the presence of a protein with electrophoretic properties similar to those of OmpF and the major Bdellovibrio outer membrane proteins. The protein appears in cytoplasmic membrane preparations within minutes of attack and persists throughout most of the intraperiplasmic developmental cycle. The appearance of this protein is consistent with our hypothesis that bdellovibrios translocate a pore protein into the bdelloplast cytoplasmic membrane to kill their prey and to gain access to the cytoplasmic contents for growth.

A search for sonoluminescence in vivo in the human cheek.

In a previous experiment, sonoluminescence was observed in aerated water, especially at the pressure antinodes in the standing-wave field of a physiotherapeutic ultrasound device (Therasonic 1030). Mammalian cells in vitro showed growth inhibition when placed at the pressure antinodes but not at adjacent pressure nodes. In the light of these results, we looked for sonoluminescence in vivo when a similar standing-wave field was set up. To detect luminescence, a light guide was held against the inner surface of the human cheek. This would channel any luminescence photons to a cooled, red-sensitive photomultiplier which would quantify the light. Direct insonation of the cheek produced no detectable luminescence. Similarly when a water bag was placed against the outer surface of the cheek, and the latter was insonated through the bag, no luminescence was detected. Sonoluminescence from the water bag was, however, detected when the bag was placed against the inner surface of the cheek, showing that absorption of sound by the cheek tissue was not preventing cavitation. Further analysis showed that if cavitation had been occurring in the cheek without detection using the system employed, then the resulting sonoluminescence would have to be at most 0.025 times as intense as that produced by an equivalent volume of aerated water.

A new model for the penetration of prey cells by bdellovibrios.

Bdellovibrio bacteriovorus 109J and most other bdellovibrios cause prey cells to round following penetration. Bdellovibrio sp. strain W does not cause rounding of the prey. Analysis of enzyme activities during the early stages of bdellovibrio attack indicated that strain W differs from most other bdellovibrios in that there is no glycanase activity produced during penetration. Likewise, heat-killed prey were penetrated normally by strain 109J, but the resulting bdelloplast did not become round and no glycanase was detected, indicating that glycanase is not essential for penetration. Peptidoglycan from prey cells penetrated by strain W was sensitive to lysozyme, but these cells were not susceptible to attack and penetration by strain 109J, indicating that peptidoglycan deacetylation is not the primary exclusion mechanism. We propose a model in which it is the peptidase activity of the bdellovibrios which allows them to breach the peptidoglycan of their prey and in which the glycanase activity exhibited by strain 109J and other bdellovibrios is responsible for the rounding of the bdelloplast.

Size of the Streptococcus mutans GS-5 chromosome as determined by pulsed-field gel electrophoresis.

Rare cutting restriction endonucleases were used to cut the Streptococcus mutans chromosome into large fragments. Restriction enzymes utilizing recognition sites containing 6-, 7-, or 8-base-pair sequences with only G and C nucleotides produced few fragments, most of which were greater than 100 kilobase pairs in size. Addition of the fragments from digests of SmaI, NotI, ApaI, RsrII, and EagI yielded a molecular size for the S. mutans GS-5 genome of 2,819 +/- 60 kilobase pairs.

Rarity of synovitis in polymyalgia rheumatica.

The joints of 56 patients with polymyalgia rheumatica were examined for evidence of inflammatory synovitis. x Rays, isotope scans, and thermography supplemented clinical examination. Control sternoclavicular joints were examined at necropsy. Peripheral and axial synovitis were uncommon and the results contrast with the findings of several recent studies.

Maps for diagnosis and management of antenatal urinary tract dilatation.

Despite advances in radiological imaging techniques, the ideal management of antenatally diagnosed hydronephrosis remains controversial. A map, showing diagnostic and management pathways, has been designed in an attempt to provide maximum information from the most appropriate and minimum number of investigations.