Prospective diagnostic test accuracy of transvaginal ultrasound posterior approach for uterosacral ligament and torus uterinus deep endometriosis.

OBJECTIVE: To determine the diagnostic test accuracy of transvaginal ultrasound (TVS) using a standardized technique for the diagnosis of deep endometriosis (DE) of the uterosacral ligaments (USLs) and adjacent torus uterinus (TU). METHODS: This was a prospective diagnostic test accuracy study conducted at the McMaster University Medical Center Tertiary Endometriosis Clinic, Hamilton, ON, Canada. Consecutive participants were enrolled if they successfully underwent TVS and surgery by our team from 10 August 2020 to 31 October 2021. The index test was TVS using a standardized posterior approach performed and interpreted by an expert sonologist. The reference standard included direct surgical visualization on laparoscopy by the same person who performed and interpreted the ultrasound scans. Accuracy, sensitivity, specificity, positive and negative predictive values (PPV and NPV) and positive and negative likelihood ratios were calculated for the TVS posterior approach for each location using the reference standard. RESULTS: There were 54 consecutive participants included upon completion of laparoscopy and histological assessment. The prevalence of DE for the left USL, right USL and TU was 42.6%, 22.2% and 14.8%, respectively. Based on surgical visualization as the reference standard, TVS demonstrated an accuracy of 92.6% (95% CI, 82.1-97.9%), sensitivity of 82.6% (95% CI, 61.2-95.1%), specificity of 100% (95% CI, 88.8-100%), PPV of 100% and NPV of 88.6% (95% CI, 76.1-95.0%) for diagnosing DE in the left USL. For DE of the right USL, TVS demonstrated an accuracy of 94.4% (95% CI, 84.6-98.8%), sensitivity of 75.0% (95% CI, 42.8-94.5%), specificity of 100% (95% CI, 91.6-100%), PPV of 100% and NPV of 93.3% (95% CI, 84.0-97.4%). For DE of the TU, TVS demonstrated an accuracy of 100% (95% CI, 93.4-100%), sensitivity of 100% (95% CI, 63.1-100%), specificity of 100% (95% CI, 92.3-100%), PPV of 100% and NPV of 100%. CONCLUSIONS: We observed high diagnostic test accuracy of the evaluated standardized TVS technique for assessing DE of the USLs and TU. Further studies evaluating this technique should be performed, particularly with less experienced observers, before considering this technique as the standard approach. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

The roles of proteolysis and nuclear localisation in the toxicity of the polyglutamine diseases. A review.

The polyglutamine disorders consist of a group of nine neurodegenerative diseases with overlapping phenotypes, but which affect distinct neuronal subsets, causing neuronal dysfunction and death. In the majority of these, the causative proteins share no homology to other known proteins, or to each other apart from the polyglutamine tract. The polyglutamine tracts themselves are toxic over a disease-specific threshold, and this common feature has suggested a common pathogenesis. The pathogenic mechanism(s) of this group of diseases is hotly debated, with proteolytic cleavage and nuclear accumulation both popular hypotheses. Such cleavage is thought to release toxic fragments containing an expanded polyglutamine tract, and may itself facilitate entry of cytoplasmic polyglutamine proteins to the nucleus. Numerous downstream effects including accumulation and apoptotic activation, misfolding, aggregation, and sequestration of other proteins including transcription factors and chaperones may then be initiated. It is uncertain whether all of the polyglutamine proteins undergo cleavage in vivo. Even in those in which proteolysis has been demonstrated, it remains unclear to what extent this also occurs in the wild-type proteins, or whether it is dependent on, or increased by, the expanded polyglutamine tract. Similarly, in at least one of these disorders (spinocerebellar ataxia type 6), nuclear localisation has not been demonstrated. The contradictory evidence for the production and role of proteolytic fragments and for nuclear localisation in toxicity, reviewed in this article, suggests that neither may be uniformly necessary steps in the pathogenesis of this group of diseases, and that, for all their apparent similarities, the exact pathogenic mechanisms may not be identical in each.

Variable galactocerebroside expression by human Schwann cells in dissociated and peripheral nerve explant cultures.

It has been well established that rat Schwann cells down regulate their cell-surface expression of galactocerebroside (GalC) in vitro under normal cell culture conditions. To determine whether human Schwann cells exhibit a similar down-regulation of GalC in vitro we examined GalC expression in dissociated human Schwann cell cultures derived from normal adult peripheral nerve. Twenty-four hours post-dissociation up to 63% of human Schwann cells were found to express detectable levels of GalC on their surface whereas less than 8% of the Schwann cells expressed detectable levels of GalC at 14 days post-dissociation. In contrast, after nearly 3 months of peripheral nerve explant culture, greater than 30% of human Schwann cells still retained their GalC expression. A similar pattern was also observed when analyzing Schwann cell purity with dissociated cultures exhibiting a rapid decrease in Schwann cell purity under normal culturing conditions although Schwann cell purity was found to be largely unaffected during the period of peripheral nerve explant culture. In summary, we found there was less variation in both GalC expression and Schwann cell purity with time in peripheral nerve explant cultures than dissociated cultures.

High-titre IgM anti-sulfatide antibodies in individuals with IgM paraproteinaemia and associated peripheral neuropathy.

The common association between monoclonal gammopathy and peripheral neuropathy was studied in seven patients with demyelinating polyneuropathy and IgM paraproteinaemia. Plasma samples from these individuals were thoroughly tested for antiperipheral nerve myelin (PNM) antibodies and then screened for glycoprotein and glycolipid reactivity by western immunoblotting and thin-layer chromatography (TLC) immunostaining. Three of the seven samples showed strong IgM anti-PNM and antisulfatide (GalS) antibody reactivity. Two of these three plasma samples showed extraordinarily high antisulfatide IgM antibody titres, ranging from 1 x 104 to 1 x 106 arbitrary units/L. These same samples also showed intense myelin staining of sciatic nerve sections (paraffin and cryostat) and teased nerve fibres. No axonal immunoreactivity was observed. These results suggest that high titre IgM antisulfatide antibodies may play a pathogenetic role in the immune demyelination associated with IgM paraproteinaemia.

High titre anti-sulphatide antibodies in HIV-infected individuals.

Plasma samples from 35 individuals with human immunodeficiency virus (HIV) infection but without peripheral neuropathy were screened by enzyme linked immunosorbent assay (ELISA) for IgM and IgG antibodies against sulphatide (GalS). Five of these were shown to contain raised anti-GalS IgM antibody titres, while six had raised IgG titres. All plasma samples screened were compared to an internal neurological disease control which contained raised anti-GalS IgM antibody titres. Anti-GalS IgM antibody titres in the HIV cohort ranged between 200 and 2000 arbitrary units/litre (AU/l), whereas, IgG titres were between 200 and 10,000 AU/l. Two of four plasma samples from HIV-infected individuals with neuropathy (HIV+PN) also showed IgM reactivity with GalS; one also binding to the gangliosides GM1, GD1a, GD1b and GT1b. The other two samples showed IgG reactivity against GalS. These data indicate that antibodies against GalS occur more frequently in HIV infection than in HIV-seronegative individuals with and without neurological disease and may participate in the pathogenesis of neuropathies associated with HIV infection.

Peripheral nerve binding patterns of anti-sulphatide antibodies in HIV-infected individuals.

HIV-positive plasma samples from patients with and without neuropathy and with high titre anti-GalS antibodies showed strong binding to the myelin membrane of both fixed and unfixed human sciatic nerve specimens. This staining pattern was also seen with a plasma sample from a patient with IgM paraproteinaemic inflammatory demyelinating neuropathy with anti-GalS IgM antibody. Teased nerve fibres incubated with these anti-GalS antibodies from both HIV and non-HIV plasma samples showed immunofluorescence at the paranodal regions and Schmidt-Lanterman incisures. These data support a potential role for these antibodies in the aetiology of HIV-associated immune mediated neuropathies.

Antibodies against peripheral myelin glycolipids in people with HIV infection.

Plasma samples from 35 individuals with HIV infection but without clinical peripheral neuropathy were screened by ELISA for IgM and IgG antibodies against peripheral myelin. Eighteen of the 35 samples (51%) showed IgM reactivity and 11 (31%) showed IgG reactivity. By comparison, none of 48 samples from healthy blood donors showed IgM or IgG reactivity. Epitopes reacting with these antibodies were identified by TLC immunostaining as sulphatide (GalS) and the gangliosides GM1, GD1a and GD1b. Plasma samples from four people with HIV infection and neuropathy (HIV+PN), six HIV-seronegative individuals with IgM paraproteinaemic demyelinating neuropathy (IgMPDN) and 12 HIV-seronegative individuals with a variety of other neurological disorders (HIV-OND) were also investigated. Two of the four HIV+PN samples showed IgM reactivity with GalS; and two showed IgG reactivity against GalS. Of the six IgMPDN samples, three showed IgM reactivity with GalS. These data indicate that antibodies against peripheral myelin glycolipids, in particular GalS, occur more frequently in HIV infection than in HIV-seronegative individuals with and without neurological disease, and may contribute to subclinical neuropathy in HIV infection.

Pharmacokinetics of a new skin wound cleanser.

Iodophors are effective germicidal agents that have prolonged antiseptic activity in contaminated wounds. A nontoxic surfactant, Pluronic F-68, has been used to formulate a safe and effective iodophor. The parameters necessary to regulate the activity of the iodophor were studied to develop a potent, yet safe bactericidal solution for use in human subjects. The parameters found to be most important were the pH of the solution and the concentration of sodium iodide. Lowering the pH of iodophors increased their stability and antiseptic activity. The free iodine in iodophor solutions prepared with a low pH is predominantly the highly biocidal diatomic iodine (I2). The concentration of iodide regulated the equilbrium of the dissolved iodine between its free and complexed form. Increasing the concentration of iodide in the iodophor lowered the amount of free iodine in solution and enhanced the concentration of the complexed iodide. It is the level of free iodine in an iodophor that determines its antiseptic activity. Low levels of free iodine yielded iodophors that had a slow bacterial kill rate but a prolonged duration of action. Manipulation of these variables permitted the generation of iodophors that varied considerably in their kill rates of bacteria and their duration of antibacterial activity. Iodophors tested in this study demonstrated a distinct superiority to noncomplexed iodine solutions (tincture and aqueous iodine solutions) as wound and skin cleansers.