Proteinuria and other renal functions in Wilson’s disease

Renal lesions have repeatedly been described in Wilson’s disease (WD). We investigated the excretion of total protein, albumin, low (LMW) and high molecular weight (HMW) proteins, N-acetyl-β-D-glucosaminidase (NAG), and calcium, as well as creatinine clearance, in 24-h urine samples of 41 patients with WD aged 6 – 37 (mean 17) years who had been treated for a period of 0 – 15 (mean 4.5) years with D-penicillamine (900 mg/day). The amount of all protein excreted was significantly increased compared with controls, 39% of patients presenting with total proteinuria more than two standard deviations from the mean of controls. The changes in protein excretion depended on the duration of treatment. LMW proteinuria was elevated almost exclusively in the first 2 years after the start of treatment, indicating early tubular damage. This is supported by an initially high excretion of β₂-microglobulin, NAG, and calcium. Increased excretion of HMW proteins, including albumin, persisted over longer periods, which suggests glomerular injury in some patients, possibly related to the use of D-penicillamine. Creatinine clearance remained roughly within normal limits. We propose that renal function should regularly be checked in patients with WD. Received October 26, 1995; received in revised form August 27, 1996; accepted September 20, 1996     

Stature estimation based on hand length and foot length

This study was carried out to estimate the relationship between hand length, foot length and stature using multiple linear regression analyses based on a sample of male and female adult Turks residing in Adana. Measurements of hand length, foot length and stature were taken from 155 adult Turks (80 male, 75 female) aged 17-23 years. The participants were students of the Medical Faculty of Cukurova University. A multiple linear regression model was fitted to the observed data. Stature was taken as the response or dependent variable, hand length and foot length were taken as explanatory variables or regressors. All possible (simple and multiple) linear regression models for each of males, females and both genders together were tested for the best model. The multiple linear regression model for both genders together was found to be the best model with the highest values for the coefficients of determination R2 = 0.861 and R2adjusted = 0.859, and multiple correlation coefficient R = 0.928.     

Survivin expression in non-small-cell lung carcinomas: correlation with apoptosis and other apoptosis-related proteins, clinicopathologic prognostic factors and prognosis.

The role of survivin that regulates the biological behavior of non-small-cell lung carcinoma (NSCLC) is still controversial. We aimed to investigate survivin expression in NSCLC and to define any correlation with expressions of p53, bcl-2, bax, apoptotic index (AI), tumor cell proliferation, clinicopathologic variables, and overall survival. Tumors of 63 patients with NSCLC were examined for expressions of survivin, p53, bcl-2, bax, and Ki-67 by immunohistochemistry. AI was also evaluated. Results for each antibody were correlated with each other, and with clinicopathologic variables including age, sex, histologic subtype, TNM (T: primary tumor, N: regional lymph node metastasis, M: distant metastasis) stage, lymph node status, smoking history, and prognosis. Nuclear survivin expression was inversely correlated with p53 expression (P = 0.04, r = - 0.367), and tumor stage (P = 0.03, r = - 0.273), and positively correlated with tumor cell proliferation (P = 0.009, r = 0.329). Cytoplasmic survivin expression positively correlated with smoking history (P = 0.02, r = 0.282). Survivin/bax ratio was inversely correlated with AI (r: - 0.004). By Kaplan-Meier analysis, TNM stage (P < or = 0.001), lymph node metastasis (P = 0.04), and Ki-67 index (P < or = 0.001) were associated with survival, whereas survivin was not. In multivariate analysis, only TNM stage was an independent predictor. Although survivin and other apoptosis-related protein expressions fail to predict the clinical outcome, the present findings suggest that survivin is involved in tumor cell apoptosis and proliferation and may play a role in critical steps of cancer progression in NSCLC.     

The “vaccine” hubbub: Viral load comparisons of SARS-CoV-2 Delta and Omicron variants against different vaccine–booster vaccine combinations

There is a significant body of evidence showing that efficient vaccination schemes against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is helping control the coronavirus disease 2019 (COVID-19) pandemic. However, this goal cannot be achieved without real world data highlighting the impact of vaccines against viral spread. In this study, we have aimed at differentially investigating the impact of COVID-19 vaccines (CoronaVac, Pfizer/BioNTech, Astra/Zeneca Oxford, Janssen) used in North Cyprus in limiting the viral load of Delta and Omicron variants of SARS-COV-2. We have utilized real-time quantitative polymerase chain reaction cycle threshold values (Ct values) as a proxy of viral load of the two SARS-CoV-2 variants. Our results indicate that the administration of at least two doses of the messenger RNA-based Pfizer/BioNTech vaccine leads to the lowest viral load (highest Ct values) obtained for both Omicron and Delta variants. Interestingly, regardless of the vaccine type used, our study revealed that Delta variant produced significantly higher viral loads (lower Ct values) compared with the Omicron variant, where the latter was more commonly associated with younger patients. Viral spread is a crucial factor that can help determine the future of the pandemic. Thus, prioritizing vaccines that will play a role in not only preventing severe disease but also in limiting viral load and spread may contribute to infection control strategies.     

Probiotics in Experimental Ulcerative Colitis: Mast Cell Density and Neuronal Hypertrophy

Background:Probiotics such as Lactobacillus and Bifidobacterium are among the supportive treatment methods to achieve effective results in ulcerative colitis. This study was established to investigate the effect of probiotics in experimental ulcerative colitis and to detect changes in mast cell and neuronal structures in this treatment method.Methods:A total of 48 adult male rats were used to study the effects of probiotics on ulcerative colitis. The animals were divided into 6 groups as control, experimental colitis, and four probiotic protective groups. Three different bacterial strains were administered to the protective groups individually and in combination by gavage. PGP 9.5 antibody and mast cell tryptase were used for the detection of neuronal structures and mast cells. The number of Schwann cells and ganglia, size measurements of ganglia, and density of mast cells were evaluated.Results:Compared to the control, an increase in the number of mast cells was detected in all groups. Especially the increase in the number of mast cells was found to be statistically significant in combined probiotic administration. In the detection of neuronal structures, a significant increase in the number of Schwann cells and ganglia was detected in groups where probiotics were administered combined and individually.Conclusion:These results suggest that probiotics may play a role in the supporting effect of increasing the number of mast cells and neuronal structures, protecting the intestinal wall. We think that more specific and detailed studies should be conducted to evaluate the protective/therapeutic effect of probiotics in future studies.     

Intraocular pressure measurement over soft contact lens by rebound tonometer:a comparative study

AIM: To evaluate the intraocular pressure (IOP) measurements by Icare rebound tonometer over a contact lens in comparison with Goldmann applanation tonometry (GAT).METHODS: Fifty patients using contact lens were included in this study. One of the eyes of the patients was selected randomly and their IOP were measured by rebound tonometer with and without contact lens (RTCL, RT respectively) and by GAT, as well as their central corneal thickness (CCT) by optical pachymeter. The results of both methods were compared by correlation analysis, general linear method repeated measure and Bland-Altman analysis.RESULTS: Mean IOP values measured by RTCL, RT and GAT were 15.68±3.7, 14.50±3.4 and 14.16±2.8 (P<0.001), respectively. Mean IOP by RTCL was significantly higher than the measurements implemented by RT and GAT (P<0.001), while there was no difference between the measurements by GAT and RT (P=0.629). There was a good level of positive correlation between GAT and RTCL as well as RT (r=0.786 P<0.001, r=0.833 P<0.001, respectively). We have observed that CCT increase did not show any correlation with the differences of the measurements between RTCL and RT (P=0.329), RTCL and GAT (P=0.07) as well as RT and GAT (P=0.189) in linear regression model.CONCLUSION: The average of the measurements over contact lens by rebound tonometer was found to be higher than what was measured by GAT. Although this difference is statistically significant, it may be clinically negligible in the normal population.     

Differential Diagnosis of Acromegaly: Pachydermoperiostosis Two New Cases from Turkey

Pachydermoperiostosis (PDP), also known as primary hypertrophic osteoarthropathy, is a rare genetic disorder characterized by pachyderma and periostosis. Acromegaly is a condition caused by excessive secretion of growth hormone (GH) leading to elevated insulin-like growth factor 1 levels, and is characterised by somatic overgrowth and physical disfigurement, notably affecting hands and feet. We present two cases referred with an initial diagnosis of acromegaly that were ultimately diagnosed as PDP. Case 1: A 17 year-old boy presented with enlargement in both feet and hands, finger clubbing, swelling in knee joints, knee pain, coarsening of facial skin lines and forehead skin, and excessive sweating which increased gradually over five years. There were prominent skin folds on the forehead, face, and eyelids. Also, there was an enlargement in both hands and clubbing of the fingers. There was marked swelling in the knee joints and ankles. Genetic analysis revealed a novel homozygous variant {"type":"entrez-nucleotide","attrs":{"text":"NM_005630","term_id":"1673110479","term_text":"NM_005630"}}NM_005630: c.31C>T (p.Q11*) in the SLCO2A1 gene. Case 2: A 16 year-old boy presented with coarsening of forehead skin and scalp, excessive sweating, and pain in the elbow and knee over three years. Skin folds were prominent on the forehead and scalp. Genetic analysis revealed a homozygous variant {"type":"entrez-nucleotide","attrs":{"text":"NM_005630.2","term_id":"188528662","term_text":"NM_005630.2"}}NM_005630.2:c.86delG (p.G29Afs*48) in the SLCO2A1 gene. Such clinical presentation contemporaneous with normal GH level and prominent radiological abnormalities prompted the diagnosis of PDP. In conclusion, PDP is a very rare osteoarthrodermopathic disorder with clinical and radiographic presentation that may mimic acromegaly. In the evaluation of patients with acromegaloid appearance, PDP should be considered as a differential diagnosis.     

A Long-Term Comparison of Presenting Characteristics of Children with Newly Diagnosed Type 1 Diabetes Before and During the COVID-19 Pandemic

Objective:Diabetic ketoacidosis (DKA) - a potentially preventable complication of type 1 diabetes mellitus (T1D) - is one of the most common chronic childhood diseases, and is associated with a significant risk of morbidity and mortality. The limited use of healthcare services due to fear of Coronavirus disease-2019 (COVID-19) transmission during the pandemic has raised concerns of delays in T1D diagnosis, among other diseases. This study investigated the presenting characteristics of newly diagnosed T1D patients assessed in a single clinic during the pandemic and compares them with the pre-pandemic period.Methods:For the purpose of this study, the first year of the pandemic is referred to as the “pandemic period”, and the previous three years as the “pre-pandemic period”. Patient files were reviewed retrospectively, the demographic and clinical characteristics and laboratory findings of the patients were recorded, and the findings from both periods were compared.Results:The number of patients diagnosed with T1D in the pandemic period was 44, and in the pre-pandemic period 39 in 2017, 22 in 2018 and 18 in 2019. The two groups had similar age, sex, pubertal stage and anthropometric characteristics (p>0.05). Regarding the type of presentation, the frequency of DKA was significantly higher in the pandemic period (68.2%) than in the pre-pandemic period (40.5%) (p=0.006), and this difference was also observed in the comparison by years (p=0.016). The duration of symptoms (16.5±10.7 vs. 23.5±17.6 days) and the length of hospital stay (10±3.9 vs. 15.2±5.5 days) were significantly shorter in the pandemic period (p=0.032, and p<0.001, respectively). There was no difference in the frequency of severe DKA between the pandemic (46.7%) and the pre-pandemic (37.5%) periods (p>0.05). However, pH (7.17±0.16 vs. 7.26±0.14) and bicarbonate (12.8±6.3 vs. 16.6±6.3) levels were significantly lower in the pandemic period (p<0.005). Additional signs of infection on admission were less frequent in the pandemic period (9.1%) than in the pre-pandemic period (27.8%) (p=0.027). The groups did not differ in terms of hemoglobin A1c, C-peptide, concurrent thyroid autoantibodies and tissue transglutaminase antibodies (p>0.05). The rate of anti-glutamic acid decarboxylase positivity was higher in the pandemic period (73.8% vs. 39.2%) (p=0.001) while the frequency of other diabetes-associated autoantibodies was similar between the groups (p>0.05). The polymerase chain reaction test for COVID-19 was negative in six patients with a history of contact.Conclusion:There was an increased frequency and severity of DKA in children with newly diagnosed T1D in the pandemic period, and these findings justify concerns related to the diagnosis of other diseases during the pandemic. Studies to raise awareness of diabetes symptoms during the pandemic should be continued regularly to reach all segments of society. Our study provides an additional contribution to the literature in its coverage of the one-year period during the pandemic and its comparison with the previous three years.     

Use of Antiandrogens as Therapeutic Agents in COVID-19 Patients

COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), is estimated to have caused over 6.5 million deaths worldwide. The emergence of fast-evolving SARS-CoV-2 variants of concern alongside increased transmissibility and/or virulence, as well as immune and vaccine escape capabilities, highlight the urgent need for more effective antivirals to combat the disease in the long run along with regularly updated vaccine boosters. One of the early risk factors identified during the COVID-19 pandemic was that men are more likely to become infected by the virus, more likely to develop severe disease and exhibit a higher likelihood of hospitalisation and mortality rates compared to women. An association exists between SARS-CoV-2 infectiveness and disease severity with sex steroid hormones and, in particular, androgens. Several studies underlined the importance of the androgen-mediated regulation of the host protease TMPRSS2 and the cell entry protein ACE2, as well as the key role of these factors in the entry of the virus into target cells. In this context, modulating androgen signalling is a promising strategy to block viral infection, and antiandrogens could be used as a preventative measure at the pre- or early hospitalisation stage of COVID-19 disease. Different antiandrogens, including commercial drugs used to treat metastatic castration-sensitive prostate cancer and other conditions, have been tested as antivirals with varying success. In this review, we summarise the most recent updates concerning the use of antiandrogens as prophylactic and therapeutic options for COVID-19.