Core content for venous and Lymphatic Medicine: 2022 revision.

The core content for a medical specialty outlines the scope of the discipline as well as the categories of knowledge considered essential to practice in the field. It provides a template for the development of curricula for medical school, graduate, and postgraduate education, as well as for creating certification standards. Venous and Lymphatic Medicine (VLM) is a specialty that has benefitted from contributions from specialists from several medical disciplines. Optimally, the societies, boards, and residency review committees representing these disciplines would uniformly recognize the scope of VLM to develop education and assessment standards to allow training and identification of qualified practitioners. In order to inform the standard setting bodies and other stakeholders of the current scope of VLM, a task force of VLM experts from cardiology, dermatology, emergency medicine, general surgery, interventional radiology, vascular medicine, and vascular surgery was formed to revise a 2014 consensus document defining the core content of the specialty of VLM.

Evaluation of the Genetic Association and Expressions of Notch-2 /Jagged-1 in Patients with Type 2 Diabetes Mellitus.

BACKGROUND: Diabetes mellitus (DM) is the world's most common cause of chronic kidney diseases (CKD), with approximately 1 in 4 adults with DM having CKD and 1 out of 10 to 20% of DM patients die from CKD. OBJECTIVE: The current study aims to investigate the correlation between Notch-2 and Jag-1expressions and specific inflammation biomarkers IL-1ß and IL-6 with different stages of diabetic nephropathy. METHODS: From August 2018 to January 2019, three hundred subjects were recruited for this study. One hundred and fifty subjects were healthy and age-matched to the diabetic group and selected as a control group. Another 150 patients with an established diagnosis of type 2 diabetes (T2DM) according to the criteria of the American Diabetes Association (ADA) were also recruited. Blood specimens were eventually used to identify the expressions Notch-2 and Jagged-1 and the levels of inflammatory biomarkers IL-1ß and IL-6. RESULT: The current study shows a significant increase in gene expression and inflammatory biomarkers in patients with moderate and severe diabetic nephropathy compared to the control group. However, there was no significant difference between healthy control and mild diabetic nephropathy patients. This study shows a close association between the increase in the levels of inflammatory biomarkers IL-1ß and IL-6 as well as the gene expressions levels of both Notch-2 and Jag-1 with human diabetic nephropathy. CONCLUSION: According to our findings, we emphasize the use of Notch-2 and Jag-1 expressions and IL-1ß and IL-6 levels as potential biomarkers for different stages of diabetic nephropathy.

End-stage renal disease and African American race are independent predictors of mild liver fibrosis in patients with chronic hepatitis C infection.

Recipients of haemodialysis for end-stage renal disease (ESRD) have a higher prevalence of hepatitis C virus (HCV) infection relative to the general US population. However, the natural course of HCV infection in patients with renal failure, including African Americans (AAs) and Caucasian Americans (CAs), is not well known. We compared the degree of liver inflammation and fibrosis in AA and CA patients with HCV infection, with and without ESRD. This was a cross-sectional study of 156 HCV patients with ESRD (130 AAs and 26 CAs) with a liver biopsy between 1992 and 2005. The control group consisted of 138 patients (50 AAs; 88 CAs) with HCV infections and a serum creatinine <1.5 mg/dL with a liver biopsy between 1995 and 1998. Specimens were graded for inflammation and fibrosis using Knodell histological activity index. Compared to patients without renal impairment, HCV patients with renal failure were older and more likely to be AA. Patients with renal impairment had lower mean serum transaminases, a higher mean serum alkaline phosphatase levels (all P < 0.0001) and less hepatic necro-inflammation (Knodell histological activity index -I, II and III; P < 0.05) and fibrosis (Knodell histological activity index -IV; P < 0.0001). There were no racial differences in serum liver chemistry and histology scores among patients with renal failure. In a multivariate analysis, younger age, ESRD, AA race and a lower serum alkaline phosphatase were associated with lower odds for advanced liver fibrosis. Thus, HCV patients with ESRD had a lower degree of hepatic inflammation and fibrosis compared to those without renal disease, independent of race.

Radiation-induced esophageal squamous cell carcinoma in situ.

A report of radiation-induced squamous cell carcinoma in situ of the esophagus is presented. This report indicates that the patient developed the carcinoma in situ many years after chest wall irradiation for breast cancer treatment. A review of the literature with respect to carcinogenesis after radiotherapy is included and recommendations for the follow-up of patients having mediastinal radiation are suggested.

Acute bacterial endocarditis following burns: case report and review.

Acute bacterial endocarditis (ABE) is a rare but deadly complication following major thermal injury. Typically the presentation is silent, with persistent fever and positive blood cultures being the only consistent findings. Fibrin-platelet vegetations on the valvular endocardium are thought to be seeded during bacteremic episodes. Manipulation of the burn wound is probably the most likely source of bacteremia, with Staphylococcus aureus and Gram-negative bacilli being the most commonly implicated bacteria. In addition to causing local damage to a valve or the myocardium, infected vegetations may dislodge septic emboli systemically. Diagnosis is most easily obtained by echocardiography. Treatment usually involves prolonged administration of intravenous antibiotics. In rare circumstances, valvular resection and replacement may be indicated.

Adaptive cytoprotection against ethanol-induced small intestinal mucosal injury.

Exposure of the small intestinal mucose to 6% ethanol (which is found in human jejunum during alcohol consumption) causes morphological alterations, and increased permeability of the mucosa and histamine release from intestinal mast cells. The released histamine is shown to mediate a significant component of the increased mucosal permeability (i.e., mucosal injury). In the present study, we have investigated whether adaptive cytoprotection occurs against the increased mucosal permeability and histamine release induced by 6% ethanol. Rabbits were used. In each animal, three adjacent segments of upper small intestine were pre-perfused for 30 min, and then perfused for 90 min in the following order control solution followed by control solution (control segment); control solution followed by 6% ethanol (ethanol segment); 1% ethanol followed by 6% ethanol (pretreated ethanol segment). During the 90-min perfusion, mucosal permeability of each segment was measured by analyzing the effluent for intraluminal clearance of i.v. administered 51Cr-labelled ethylenediaminetetraacetic acid (51Cr-EDTA) and 125I-labelled bovine serum albumin (125I-BSA). Mast cell histamine release was assessed by determining histamine concentration of the gut effluent. All measurements were higher in the ethanol segments than in the controls. These ethanol effects were significantly lower in the pretreated ethanol segments, indicating that adaptive cytoprotection occurs against the mucosal injury induced by 6% ethanol. These findings are discussed in relation to the literature on mucosal effects of intestinal intraluminal ethanol.

Responsiveness of mutants of NHE1 isoform of Na+/H+ antiport to osmotic stress.

Hypertonic activation of NHE1, the ubiquitous Na+/H+ exchanger, plays a central role in cell volume regulation, yet little is known about the underlying mechanism. We probed the osmotic responsiveness of full-length and truncated constructs of NHE1 transfected into cells lacking endogenous antiport activity. The hypertonic stimulation of NHE1 was preserved after heterologous transfection of the full-length NHE1 or of constructs truncated at positions 698 or 703. In contrast, mutants truncated at position 635 (delta 635) failed to respond to osmotic challenge. Transfectants (delta 635) behaved as if constitutively activated, having a permanently elevated cytosolic pH (pHi) under isotonic, unstimulated conditions. The delta 635 mutant displayed H+ binding with high affinity and low cooperativity. Constructs delta 582 or delta 566 had a reduced H+ sensitivity and were therefore inactive at resting pHi. Such cells were unresponsive to osmotic stress near physiological pHi but could be activated by shrinking after an acid load. Jointly, these results suggest that the H+ affinity and high cooperativity of the antiporter, earlier attributed to a single "modifier site," can be varied independently and are probably controlled by different regions of the molecule. The data indicate that volume or osmolarity-sensitive site(s) exist between the NH2-terminus and residue 566. This putative volume-sensitive site is therefore different from the site(s) postulated to mediate the stimulatory effects of calcium and growth factors.

Functional characterization of three isoforms of the Na+/H+ exchanger stably expressed in Chinese hamster ovary cells. ATP dependence, osmotic sensitivity, and role in cell proliferation.

Four distinct isoforms of the mammalian Na+/H+ exchanger (NHE) have been identified by molecular cloning. Three of these (NHE-1, NHE-2, and NHE-3) have been shown to be functionally active by heterologous expression. Their kinetic and pharmacological properties are well documented, yet comparatively little is known about their regulation. In this report, rat NHE-1, NHE-2, and NHE-3 were stably transfected into antiporter-deficient Chinese hamster ovary cells to study their role in cellular proliferation and their regulation by nucleotides and cell volume. Their ability to influence cell proliferation was assessed by measuring the growth of antiporter-deficient cells and of the different transfectants in media of varying pH. While antiporter-deficient cells were unable to grow at acidic pH levels, all three isoforms supported proliferation under these conditions. Therefore, while the epithelia-specific isoforms (NHE-2 and NHE-3) are thought to play primarily a role in transcellular ion transport, they can also contribute to intracellular pH (pHi) homeostasis and have a permissive role in cell growth. The activity of the three isoforms was markedly inhibited by depletion of cellular ATP. In the pHi 6.0-7.2 range, decreases in the affinity for internal H+ and/or the maximal rate of transport accounted for the inhibitory effect, depending on the isoform. The osmotic responsiveness of the three isoforms was also compared. As reported earlier, NHE-1 was stimulated by hypertonicity. Under similar conditions, NHE-2 was also stimulated to a comparable extent. Conversely, both isoforms were inhibited in hypotonic media. In contrast, NHE-3 was markedly inhibited by hypertonic cell shrinking but was unaffected by hypotonicity. Osmotic inhibition of NHE-3 was rapid, reversible, and apparent throughout the pH range studied. Osmotic inhibition of NHE-3 may play a role in the physiology and pathophysiology of epithelia.

Activation of multiple pH-regulatory pathways in granulocytes by a phosphotyrosine phosphatase antagonist.

Activated phagocytes undergo a massive burst of metabolic acid generation, yet must be able to maintain their cytosolic pH (pHi) within physiological limits. Peroxides of vanadate (V(4+)-OOH), potent inhibitors of phosphotyrosine phosphatases, have recently been shown to produce activation of the respiratory burst in HL60 granulocytes. We therefore investigated the effects of V(4+)-OOH on pHi homoeostasis in HL60 granulocytes, using a pH-sensitive fluorescent dye. V(4+)-OOH stimulation induced a biphasic pH change: a transient cytosolic acidification followed by a significant alkalinization. The initial acidification was prevented by inhibition of the NADPH oxidase and was absent in undifferentiated cells lacking oxidase activity. Analysis of the alkalinization phase demonstrated the involvement of the Na+/H+ antiporter, and also provided evidence for activation of two alternative H(+)-extrusion pathways: a bafilomycin-sensitive component, likely reflecting vacuolar-type H(+)-ATPase activity, and a Zn(2+)-sensitive H(+)-conductive pathway. Our results indicate that V(4+)-OOH stimulation not only activated the NADPH oxidase but concomitantly stimulated H(+)-extrusion pathways, enabling the cells to compensate for the massive production of intracellular H+ associated with the respiratory burst.

Sodium loading treatment for amphotericin B-induced nephrotoxicity.

The increased frequency and duration of antifungal treatment with amphotericin B in immunocompromised patients has stimulated a great deal of research into the mechanisms of its nephrotoxic effects and treatment modalities designed to attenuate these effects. A review of amphotericin B-induced nephrotoxicity, the underlying pathophysiologic mechanisms, and the role of salt loading as a means of minimizing renal impairment are described. Both animal and human studies regarding the efficacy of sodium loading are presented as well as a case report describing the use of salt supplementation over a prolonged course of therapy.

Ultrastructural effects of topical timolol on the rabbit cornea. Outcome alone and in conjunction with a gas permeable contact lens.

Corneal epithelial erosions developed in two patients wearing gas permeable contact lenses (Boston) soon after commencing topical timolol maleate therapy. This prompted the following investigation. Forty rabbit corneas were examined by scanning and transmission electron microscopy after treatment for one month with one of the following: timolol ophthalmic solution, preservative-free timolol, contact lens, contact lens and timolol, contact lens and preservative-free timolol, contact lens and saline, or no treatment. Corneas treated with either timolol or contact lens alone showed mild to moderate edema or degeneration of epithelial and endothelial cells. However, the combined use of a contact lens and timolol produced marked alterations in both the corneal epithelium and endothelium.

Corneal epithelial dysplasia and carcinoma in situ.

Corneal epithelial dysplasia and carcinoma in situ have not been emphasized as distinct clinical conditions in the literature. Seven cases are presented with their clinicopathological correlation. Six of the patients presented primarily with corneal signs and symptoms consisting of notable visual blurring or foreign body sensations, or both. Biomicroscopic examination revealed a geographic, diffuse, greyish-white haze involving the corneal epithelium, often with; subtle thickening and irregularity of the involved areas and overlying superficial punctate keratitis. Histologic examination showed all degree of corneal epithelial dysplasia up to carcinoma in situ. The diagnosis, course and management of these conditions is discussed.

Renal oncocytomas: clinical, radiological and histological features.

Proximal renal tubular adenomas with oncocytic features, also known as renal oncocytomas, are rare, probably benign, tumors of the kidney. They are easily misdiagnosed as carcinomas. However, radiological, histological and ultrastructural characteristics allow their differentiation from adenomas and adenocarcinomas. We report 4 cases of renal oncocytomas and review the literature.

Glucose substrate in myocardial protection.

Glucose-insulin-potassium (GIK) was infused preoperatively in 30 patients scheduled for coronary artery operation. Before cardiopulmonary bypass (CPB) each patient received an intravenous infusion of 50% glucose. Myocardial protection was achieved with a cardioplegic solution containing glucose. A similar group of 30 patients received an equal volume of NaCl infused preoperatively and before CPB, and their cardioplegic solution contained no glucose. Clinically and by hemodynamic evaluation postoperatively one could not separate the two groups. Glycogen grading of the myocardium prior to bypass demonstrated no difference in glycogen levels in patients receiving glucose and those receiving NaCl. However, at the end of cardioplegic arrest only the group receiving glucose maintained normal grading of myocardial glycogen.

Prosepctive analysis of heart biopsies in coronary artery surgery.

In a prospective analysis of 36 biopsies from human hearts performed at the time of elective coronary operation, several morphological changes were identified in the myocardium. Some of these changes (fibrosis, vacuolation, edema, and amyloid deposition) are of clinical signficance and may affect the long-term prognosis for patients undergoing revascularization procedures. It appears, therefore, that knowledge of the morphological state of the myocardium at the time of operation can prove useful in elucidating further the long-term effects of coronary artery bypass on the left ventricular myocardium.