Species-specific prevalence of vaginal candidiasis among patients with diabetes mellitus and its relation to their glycaemic status

OBJECTIVES: Non- C. albicans Candida species are increasingly being recognized as the cause of vulvo-vaginal candidiasis. These species are often less susceptible to antifungal agents. Patients with diabetes mellitus are at risk for vulvo-vaginal candidasis. We assessed the species-specific prevalence rate and risk of candidiasis in patients with diabetes mellitus and healthy controls. METHODS: Genital tract examination, direct microscopy and fungal cultures of discharge collected by high vaginal swab were undertaken among 78 consecutive patients with diabetes mellitus (mean (+/-sd) age 32+/-12 years and body mass index (BMI) 22.3+/-5.5kg/m(2)) and 88 age- and BMI-matched healthy females. Glycaemic control in the diabetic cohort was assessed by measuring total glycosylated haemoglobin. RESULTS: Candida species were isolated in 36 of 78 (46%) subjects with diabetes mellitus and in 21 of 88 (23%) healthy subjects (Chi-squared 9.11, P=0.0025). The predominant Candida species isolated in diabetics with vulvo-vaginal candidiasis were Candida glabrata (39%), C. albicans (26%) and C. tropicalis (17%). In contrast, in the control group, C. albicans, C. glabrata and C. hemulonii comprised 30% each, with none having C. tropicalis infection (for C. tropicalis: diabetic vs. control; 17% vs. nil, P=0. 05). Among the diabetic group, subjects with vulvo-vaginal candidiasis had significantly higher mean HbA1 when compared to those who had no such infection (12.8+/-2.6% vs. 9.7+/-1.7% respectively, P=0.001). The overall accuracy of direct microscopy and clinical examination for predicting vulvo-vaginal candidiasis was only 77% and 51%, respectively, in the diabetic group, and 83% and 65% in the control group. CONCLUSIONS: Patients with diabetes mellitus had a high prevalence rate (46%) of vulvo-vaginal candidiasis with relative risk of 2.45. The non- C. albicans species such as C. glabrata and C. tropicalis were the predominant species isolated among them. There seems to be a significant link between hyperglycaemia and vulvo-vaginal candidiasis.     

Biphasic intra-thoracic pressure regulation augments cardiac index during porcine peritonitis: a feasibility study

Preservation of cardiac output (CO) and pulmonary artery pressure (PAP) is vital to maintaining tissue oxygenation in sepsis. This feasibility study tested the hypothesis that therapeutic intra-thoracic pressure regulation (tIPR), delivered with a novel device, was designed to non-invasively enhance venous return by creating sub-atmospheric intra-thoracic pressure during the expiratory phase of mechanical ventilation, improves CO without fluid resuscitation in a porcine E. coli peritonitis model of sepsis. Seven pigs were intubated, anaesthetized and instrumented with a Swan-Ganz and femoral artery catheter. After a 30?min basal period, a fibrin clot containing 4–5?×?10⁹ cfu kg^?1 E. coli O111.B4 was implanted in the peritoneum. One hour after clot implantation, tIPR was utilized for 30?min and then removed from the ventilator circuit for 30?min. This tIPR cycle was repeated 4-times. Changes in haemodynamic parameters were calculated by comparing pre-tIPR values to peak values during tIPR administration. Following peritonitis, tIPR significantly increased the peak cardiac index (mean?±?SEM) (14.8?±?2.6 vs 7.9?±?2.3?ml kg^?1) and mean arterial pressure (10.2?±?1.5 vs 4.9?±?1.1?mmHg) and simultaneously decreased PAP (?7.7?±?1.5 vs ?2.7?±?0.8?mmHg). These results support the feasibility of the concept that therapeutic application of negative expiratory pressure may provide a non-invasive and complementary approach to increase cardiac output and organ perfusion in the setting of septic shock.     

Prevalence of urinary tract infection and renal scars in patients with diabetes mellitus

Insulin resistance is known as an important risk factor for coronary artery disease (CAD). However, CAD-related mortality in Japanese type 2 diabetics is lower than in Caucasians. To investigate whether insulin resistance is related to CAD in Japanese type 2 diabetics, we measured insulin sensitivity and several coronary risk factors in Japanese patients with type 2 diabetes with and without CAD. Thirty-three patients with definite CAD and 33 age- and sex-matched patients without CAD (control) were studied. Insulin sensitivity was assessed by the K index of insulin tolerance test (KITT). Clinical characteristics, classical risk factors, lipoprotein (a), and insulin sensitivity were compared between the two groups. Patients with CAD had a significantly longer duration of diabetes (9.0 +/- 1.4 vs. 5.5 +/- 0.9 years, P < 0.05, respectively), were mostly hypertensive (69.7 vs. 39.4%, P < 0.05), and more likely to be treated with insulin (45.5 vs. 18.2%, P < 0.05) compared with the control. Concerning the metabolic parameters, patients with CAD had a significantly higher insulin resistance than control (2.40 +/- 0.15 vs. 3.23 +/- 0.17%/min, P < 0.01, respectively), higher triglyceride (1.39 +/- 0.10 vs. 1.05 +/- 0.05 mmol/l, P < 0.05), lower HDL cholesterol (1.05 +/- 0.05 vs. 1.28 +/- 0.06 mmol/l, P < 0.05), and higher lipoprotein (a) (27.5 +/- 4.3 vs. 17.4 +/- 2.0 mg/dl, P < 0.05). Multiple logistic regression analysis indicated that hypertension, insulin resistance, high lipoprotein (a) and triglyceride, and low HDL cholesterol were independently related to CAD. Our results suggest that insulin resistance per se is a significant risk factor for CAD in Japanese patients with type 2 diabetes.     

Progression of Ulcerative Dermatitis Lesions in C57BL/6Crl Mice and the Development of a Scoring System for Dermatitis Lesions

Ulcerative dermatitis (UD) is a common, spontaneous condition in mice with a C57BL/6 background. Although initial lesions may be mild, UD is a progressive disease that often results in ulcerations or debilitating fibrotic contractures. In addition, lesions typically are unresponsive to treatment. Euthanasia is often warranted in severe cases, thereby affecting study outcomes through the loss of research subjects. Because the clinical assessment of UD can be subjective, a quantitative scoring method and documentation of the likely time-frame of progression may be helpful in predicting when animals that develop dermatitis should be removed from a study. Such a system may also be helpful in quantitatively assessing success of various treatment strategies and be valuable to clinical laboratory animal veterinarians. In this 1.5-y, prospective cohort study, we followed 200 mice to monitor the development and course of UD. Mice were examined every 2 wk. A clinical sign (alopecia, pruritus, or peripheral lymphadenopathy) was not identified that predicted development of UD lesions in the subsequent 2-wk period. Once UD developed, pruritus, the character of the lesion (single or multiple crust, coalescing crust, erosion, or ulceration), and the size of the lesion were the only parameters that changed (increased) over the course of the disease. Pruritus was a factor in the rapid progression of UD lesions. We used these findings to develop a quantitative scoring system for the severity of UD. This enhanced understanding of the progression of UD and the quantitative scoring system will enhance the monitoring of UD.Abbreviation: UD, ulcerative dermatitis; S number, scratching number; COL, character of lesionsUlcerative dermatitis (UD) is an idiopathic, spontaneous, debilitating syndrome of laboratory mice that is typically a disease of aged^1,19,43,46 C57BL/6 mice or genetically engineered mice on a C57BL/6 background.^1,19,43,44 Some reports discuss a similar condition in young, weanling mice that presents initially as alopecia.^24,42,44,45 Prevalence rates of UD between 4.1% to 21% have been reported.^1,6,19 Although no etiology has been identified, environmental factors,^{6,19,41,42,44} diet,^{5,29,41,42,46} season,^19,41,43,44 age at weaning,⁴² alopecia,^24,42,44,45 sex,^19,39,41,43 immune complex vasculitis,¹ follicular dysplasia,⁴⁴ lesion location,²⁰ and deficiencies in vitamin A metabolism⁴⁴ have all been implicated as predisposing factors for disease development. In addition, oronasal pain and chronic inflammation may lead to self-mutilation as a result of, initiating an “itch” response.¹⁰ UD is diagnosed by ruling out other causes of dermatitis in laboratory mice, such as fur mites,⁹ infections, fight wounds,¹⁷ strain phenotype,^15,35,40,49 and experimentally induced dermatitis.^4,50 Other diagnostic criteria are based on professional judgment and may include strain (C57BL/6 background),^1,19,44 lesion location (head and dorsal thorax),^1,19,43,44 intense pruritus,^1,19,44 peripheral lymphadenopathy,^6,19,39 and failure to respond to treatment.¹⁹ The rapid progression of UD lesions results in significant morbidity in laboratory mice.^6,19,44 Typically, the lesions progress to large, irregularly shaped, confluent ulcerations on the dorsal cervical and thoracic region.^1,19,39,44 As the lesions heal, contracted scar tissue forms, which can impair species-typical behaviors and mobility.^39,41,43,44 The presence of large dermal ulcerations or debilitating contractures affect animal welfare and typically necessitate euthanasia of affected mice. Although reports on the later stages of UD have been consistent,^{1,19,39,41,43,44} information on the initiation and progression of UD lesions is conflicting. Pruritus,^1,19,44 pain,¹⁰ and genetic predisposition^1,19,43,44 have been implicated as initiators of the disease. Alopecia, pruritus, erythema, and single or multiple(s) crust have all been reported as early signs of the disease.^{1,19,39,42-44} However, the majority of this information has been collected retrospectively, at timed necropsies, or based on anecdotal reports.Scoring systems are useful tools to evaluate clinical diseases in laboratory animals. For example, scoring systems have been published for tumors,^14,28 body condition,^14,28,47 and neurologic phenotype¹³ in mice to aid in assessment of clinical disease severity. Even though the progressive and severe nature of UD typically warrants eventual euthanasia, determining the severity of disease has typically been based on professional judgment,^1,39 subjective scoring,^{12,15,19,40,43,48,49} or postmortem histology.^40,44 A quantitative scoring system for UD in live mice has not been described and could greatly aid laboratory animal veterinarians and researchers in determining the severity of the disease and response to treatment.The purpose of the current study is to investigate clinical parameters that reflect the progression of UD to facilitate management and veterinary care of mice with UD. We followed 200 mice from 3 wk of age until the development of UD to determine the initial signs and progression of UD lesions. We hypothesized that mice will first develop signs of pruritus prior to any clinical lesion. From there, we predicted that clinical lesions will progress stepwise though the following stages of severity, with or without alopecia: (1) excoriations; (2) a single, small punctuate crust; (3) multiple, small punctuate crusts; (4) coalescing crust; (5) erosion; and (6) ulceration. In addition, we hypothesized that a quantitative, validated, and reliable UD scoring system can be created that is based on physical examination parameters that do, in fact, predict development and progression of UD. Having a more thorough understanding of the initiation and progression of ulcerative lesions likely will enhance our ability to predict the outcome for a given mouse and develop earlier end-points for that mouse. Furthermore, use of this scoring system will enable accurate monitoring of UD lesions.     

Multimodal quantitative examination of nerve function in colorectal cancer patients prior to chemotherapy

Introduction: Given recent findings of subclinical sensory deficits in colorectal cancer patients before oxaliplatin treatment, in the current study we aimed to identify evidence of subclinical peripheral neuropathy on multimodal testing before chemotherapy commencement. Methods: Clinical, functional, and neurophysiological assessments were undertaken in 93 colorectal cancer patients before chemotherapy. Results: There was no neurophysiological evidence of neuropathy, with 92 of 93 sural sensory values within normative reference values for age and no significant abnormalities detected in nerve conduction or nerve excitability studies. Clinical neurological assessment revealed 75.9% of patients with no signs or symptoms, 10.3% with reduction in distal vibration or pinprick sensitivity, and 6.9% with reduction in ankle reflexes only. There was no difference in manual dexterity (using the 9‐hole peg‐board test) compared with normative data. Discussion: The present study has established a low likelihood of significant distal symmetrical polyneuropathy in colorectal cancer patients before initiation of chemotherapy. Muscle Nerve 57 : 615–621, 2018