Experimental axonopathy induced by immunization with campylobacter jejuni lipopolysaccharide from a patient with guillain‐barré syndrome

Campylobacter jejuni (C. jejunj) infection is the most common antecedent in the axonal variant of Guillain‐Barré syndrome (GBS). Antibodies against nerve gangliosides found in GBS patients recognize cross‐reactive epitopes in the lipopolysaccharide (LPS) of C. jejuni. This led to the molecular mimicry hypothesis of GBS. We immunized eleven rabbits with a LPS extracted from HS:19 C. jejuni strain isolated from a patient with GBS and complete Freund's adjuvant (CFA)(group I). In a second experiment we immunized seven rabbits with LPS, CFA and keyhole limpet hemocyanin (KLH)(group II). All group I rabbits developed high titers of anti‐LPS, anti‐GM1, anti‐GD1b antibodies and lower titers of anti‐GD1a. One rabbit, 50 days after initial inoculation, showed tremor and weakness. All rabbits of group II developed high titres of antiganglioside antibodies and six animals showed weakness 59–113 days after initial inoculation. Two rabbits died. Pathology showed mild to moderate, tendentially grouped, axonal degeneration in sciatic nerves of four out of five animals. Control rabbits of group I (immunized with CFA only) did not develop antibodies, controls of group II (immunized with CFA + KLH) developed low titers of IgG anti‐GM1. None developed neurological signs or showed axonal degeneration. C. jejuni LPS is a potent B‐cell stimulator capable to induce a strong antiganglioside response in rabbits. However, to induce the neuropathy is crucial to employ KLH, a glycoprotein known to stimulate both humoral and cellular responses. This animal model reproduces the pathogenetic process hypothesized in axonal GBS with antiganglioside antibodies post C. jejuni infection.     

Disorders of perfusion of the anterior segment of the eye

Background: We have investigated the vascular perfusion of a wide variety of conditions of the anterior segment using fluorescein angiography.
Methods: The conditions were classified and findings reported according to the system set out below. Patients underwent full ocular examination. Fluorescein angiography of the anterior segment was carried out when indicated to investigate iris atrophy and neovascularisation. Specular microscopy of the corneal endothelium was used to detect changes in this tissue.
Results: The hypoperfusion was variable in degree and accompanied by varying degrees of iris hypoplasia and atrophy with neovascularisation. The degree of neovascularisation depended upon its rapidity of development, the pre-existing state of vascular perfusion and the underlying pathological condition.
Conclusions: Hypoperfusion with resultant ischaemia and neovascularisation is common in conditions of the anterior segment. An understanding of the changes is valuable in treating many conditions affecting the anterior segment. The changes observed may also occur elsewhere in the physical system and may be a significant part of the ageing process, either as scattered, disparate processes or as part of a general disease process.     

Postoperative radiation therapy in the management of lung cancer

Postoperative radiation therapy for lung cancer is still controversial. In a 9-year period, 69 patients with non-oat-cell carcinoma of the lung (16% stage I, 26% stage II, and 58% stage III) received such therapy. The radiation dose was less than 5,000 cGy in 42 patients, 5,000-5,900 cGy in 16, and 6,000 cGy or more in 11; follow-up ranged from 24 to 64 months. Actuarial survival at 2 and 4 years was 50% and 16%, respectively, for squamous cell carcinoma, and 40% and 26% for adenocarcinoma. The 5-year survival for stages I, II, and III cancer was 29%, 17%, and 19%, respectively. Histologic findings and type of surgery did not affect survival, but the radiation dose apparently did. The 3-year survival for patients who received less than 6,000 cGy was 35%, compared with 73% for patients who received higher doses. In eight patients, treatment failed within the irradiated volume: all had received doses of less than 6,000 cGy, and the volume in three was judged to be inadequate.     

Short-termin vivo stability of endothelial-lined polyester elastomer and polytetrafluoroethylene grafts

A fibronectin substrate will significantly enhance the strength of endothelial cell attachment on grafts constructed of polyester elastomer (PE) and polytetrafluoroethylene (e-PTFE). This experiment was undertaken to determine the short-termin vivo stability of endothellum on these fibronectin coated surfaces. Eight mongrel dogs underwent bilateral carotid artery replacement with both graft materlals. All grafts were inoculated with 2,000 cells/mm² using cultured autogenous venous endothelium labelled with Indium-111-oxine. The Indium-111 label in the grafts was measured immediately prior to implantation, after 1 hour ofin vivo perfusion, and at explantation after 24 hours. The percentage of inoculated cells attached to the grafts before perfusion was simillar for both materials, 93.3±3.0% versus 92.2±7.2%, for PE and e-PTFE respectively. All grafts were patent at one hour after implantation. PE grafts were found to have 93.8±3.9 % of the attached cells present at one hour while e-PTFE grafts had only 54.5 ± 10.8 % remaining, p<.001. After 24 hours, 5/8 (62.5%) e-PTFE grafts and 2/8 (25.0 %) PE grafts remained patent, p=.13. Of the patent grafts however, endothelial cell retention was still superior on the PE grafts with 78.0±0.6% of the attached cells remaining compared to only 24.5±6.1% on e-PTFE, p<.001. Occluded PE grafts had fewer cells remaining at 24 hours than patent ones, 78.0±0.6% versus 31.1±32.8%, respectively, p=.13. Histologically, patent PE grafts demonstrated nearly confluent endothelial monolayers while e-PTFE had patches of endothelial cells surrounded by, a platelet-fibrin carpet. We conclude that short-term patency appears to be determined by the extent of endothelial retention on PE but not e-PTFE.     

Remote intervention engagement and outcomes in the Clinical Trials in Organ Transplantation in Children consortium multisite trial

Remote interventions are increasingly used in transplant medicine but have rarely been rigorously evaluated. We investigated a remote intervention targeting immunosuppressant management in pediatric lung transplant recipients. Patients were recruited from a larger multisite trial if they had a Medication Level Variability Index (MLVI) ≥2.0, indicating worrisome tacrolimus level fluctuation. The manualized intervention included three weekly phone calls and regular follow-up calls. A comparison group included patients who met enrollment criteria after the subprotocol ended. Outcomes were defined before the intent-to-treat analysis. Feasibility was defined as ≥50% of participants completing the weekly calls. MLVI was compared pre- and 180 days postenrollment and between intervention and comparison groups. Of 18 eligible patients, 15 enrolled. Seven additional patients served as the comparison. Seventy-five percent of participants completed ≥3 weekly calls; average time on protocol was 257.7 days. Average intervention group MLVI was significantly lower (indicating improved blood level stability) at 180 days postenrollment (2.9 ± 1.29) compared with pre-enrollment (4.6 ± 2.10), p = .02. At 180 days, MLVI decreased by 1.6 points in the intervention group but increased by 0.6 in the comparison group (p = .054). Participants successfully engaged in a long-term remote intervention, and their medication blood levels stabilized. NCT02266888.     

Intropin (dopamine hydrochloride) intravenous admixture compatibility. Part 2: stability with some commonly used antibiotics in 5% dextrose injection.

The stability of dopamine hydrochloride (Intropin) and several commonly used antibiotics was studied as admixtures in 5% Dextrose Injection USP. The antibiotic-dopamine-dextrose 5% admixtures were assayed for dopamine by colorimetric and chromatographic procedures. The antibiotics were assayed by standard microbiological methods. Kanamycin sulfate, tetracycline hydrochloride, carbenicillin disodium and chloramphenicol sodium succinate were stable in the Intropin-5% dextrose admixture for a period of 24 hours at room temperature in fluorescent and natural (western exposure) light. Gentamicin sulfate, penicillin G potassium and cephalothin sodium were stable in Intropin-5% dextrose admixture for six hours. Ampicillin sodium was stable in the Intropin admixture for only one hour. Amphotericin B was physically unstable in the Intropin-dextrose 5% solution upon admixture. The potency of dopamine hydrochloride remained substantially unchanged in the presence of the above antibiotics. It is recommended that dopamine not be added to amphotericin B or ampicillin sodium admixtures. Further, in order to avoid a fixed combination of potent drugs, it is recommended that a "piggyback" administration set or administration into a second injection site be employed when another drug is to be administered with dopamine hydrochloride.     

SPECT, MR and quantitative MR imaging: correlates with neuropsychological and psychological outcome in traumatic brain injury

This study examined the relative effectiveness of magnetic resonance (MR) imaging, single photon emission tomography (SPECT) and quantitative magnetic resonance (QMR) imaging in detecting brain abnormalities in 52 traumatically brain injured patients. The relationship between brain abnormalities and neuropsychological and psychological testing results was also investigated. Sixty-two per cent of patients had abnormal clinical MR findings, 57% had abnormal SPECT and 51% had abnormal QMR. Each neuroimaging modality detected brain abnormalities that the other two did not. Neuropsychological and psychological testing indicated significant memory impairments and subjective emotional distress even several years post-injury. Memory and intellectual impairments modestly but significantly correlated with the number of brain abnormalities indicated by all three imaging studies combined, as well as those detected individually by QMR and MR. SPECT abnormalities alone were not correlated with intellectual and memory outcome. Psychological distress was also related to the number of MR abnormalities, with most brain abnormalities being in the frontal areas.     

Idiopathic intracranial hypertension and anticardiolipin antibodies

The association of idiopathic intracranial hypertension (IIH) or pseudotumour cerebri (PTC) with anticardiolipin antibodies (aCL-Abs) has been only acknowledged recently. However, its true incidence is as yet unknown. In this retrospective study, the co-occurrence of IIH and aCL-Abs was looked for among a relatively large group of patients diagnosed with IIH or PTC in the neuro-ophthalmology clinic during the years of 1992-8. All patients underwent routine blood tests and the presence of activated protein C resistance and protein S and protein C deficiency were recorded. ACL-Abs were determined in all patients. The co-occurrence of IIH and aCL-Abs was found in three out of 37 patients (8.1%), which is higher than the incidence of aCL-Abs in the general population but considerably lower than that reported in two previously published studies. The aCL-Ab positive patients in our series were significantly older and thinner than those in whom antibodies were undetected. In conclusion, it seems that patients with this association should be considered as a unique subgroup of IIH.     

Outcome results of transurethral collagen injection for female stress incontinence: assessment by urinary incontinence score

PURPOSE: We assessed the results of collagen injection for female sphincteric incontinence using strict subjective and objective criteria. MATERIALS AND METHODS: We evaluated 63 consecutive women with sphincteric incontinence who underwent a total of 131 transurethral collagen injections. Sphincteric incontinence was confirmed by urodynamics. All patients were treated with 1 to 5 transurethral collagen injections and treatment outcome was classified according to a new outcome score. Cure was defined as no urinary loss due to urge or stress incontinence documented by a 24-hour diary and pad test, and patient assessment that cure was achieved. Failure was defined as poor objective results and patient assessment that treatment failed. Cases that did not fulfill these cure and failure criteria were considered improved and further classified as a good, fair or poor response. RESULTS: Mean patient age plus or minus standard deviation was 67.7 +/- 12.8 years. All women had a long history of severe stress urinary incontinence, 18 (29%) underwent previous anti-incontinence surgery, and 41% had combined stress and urge incontinence. Preoperatively diary and pad tests revealed a mean of 7.5 +/- 4.6 incontinence episodes and 152 +/- 172 gm. of urine lost per 24 hours. Overall 1 to 5 injections were given in 26, 17, 13, 3 and 4 patients, respectively. Mean interval between injections was 4.4 +/- 5.7 months, mean followup was 12 +/- 9.6 months, and mean interval between the final injection and outcome assessment was 6.4 +/- 4.9 months. There was a statistically significant decrease in the total number of incontinence episodes per 24-hour voiding diary after each injection session. Although there was a clear trend toward decreased urinary loss per 24-hour pad test, statistical significance was not established. Using the strict criteria of our outcome score overall 13% of procedures were classified as cure, 10%, 17% and 42% as good, fair and poor, respectively, and 18% as failure. CONCLUSIONS: As defined by strict subjective and objective criteria, we noted a low short-term cure rate after collagen injection in women with severe sphincteric incontinence. It remains to be determined how patients with less severe incontinence would fare using our outcome assessment instruments.