Urinary protein patterns in patients with Balkan endemic nephropathy

Purpose

Urinary excretion of beta2-microglobulin (beta2-MG), albumin, immunoglobulin G (IgG) and protein was examined in patients with Balkan endemic nephropathy (BEN), glomerulonephritis (GN) and healthy controls.

Methods

The proteins were measured in morning urine samples from 74 patients with BEN, 50 healthy persons and 22 patients with GN.

Results

In BEN patients, median values for albumin, beta2-MG and protein were above upper normal limits, but median IgG was inside normal range. All patients with GN had microalbuminuria (MAU) and half of them had increased urinary beta2-MG, which was also found in eleven patients with increased urinary IgG. In BEN patients, there were significant negative correlations between eGFR and all measured urinary proteins, the composition of which changed during the course of BEN. In patients with eGFR > 60 ml/min/1.73 m² isolated beta2-MG was the most frequent finding (10/12 patients), but MAU was present in 4/12 patients. In BEN patients with eGFR between 30 and 59 ml/min/1.73 m², beta2-MG appeared as often as the combination of beta2-MG and albumin and isolated MAU. Out of 49 BEN patients with eGFR > 30 ml/min/1.73 m² 15 had increased urinary IgG either alone (1) or together with beta2-MG (3) or albumin (3) or beta2-MG and albumin (8). In BEN patients with GFR < 30 ml/min/1.73 m² only 1/25 had isolated beta2-MG but increased urinary IgG with increased beta2-MG, and albumin was the most frequent.

Conclusion

Although low-molecular weight proteinuria was the most frequent urinary finding in BEN patients, MAU was frequently detected in advanced stages of BEN but also in some patients with eGFR > 60 ml/min/1.73 m². IgG was increasingly found as eGFR decreased.     

Impact of triple pelvic osteotomy on contact stress pressure distribution in the hip joint

Purpose

We studied changes of contact stress distribution in the hip joint after Tonnis triple pelvic osteotomy applied in the treatment of dysplasia and hip joint incongruence in adolescents.

Methods

In a group of 75 patients, 54 (72 %) female, who underwent surgery by triple pelvic osteotomy in adolescence for developmental disorder of the hip and avascular necrosis of the femoral head, a three-dimensional hip joint model was used based on the radiography of the pelvis with hips. The following biomechanical parameters were calculated: resultant hip force normalised to body weight (R/Wb), inclination of the resultant hip force (θ−R), the position of the stress pole (θ), peak contact hip stress (Pmax), and peak contact hip stress normalised to body weight (Pmax/Wb). Gait quality was also assessed.

Results

After surgery the Wiberg CE angle was increased by 17.85° (114 %), resultant hip force normalised to body weight (R/Wb) was decreased by 0.107 (3.3 %), the position of the stress pole was shifted medially by 27.59° (63.5 %), and peak contact hip stress normalised to body weight (Pmax/Wb) was decreased by 2249.74 (55.9 %). Waddling gait was reduced from 17 (23.9 %) to four cases (5.6 %). All changes were statistically highly significant (p<0.01).

Conclusions

The effect of Tonnis triple pelvic osteotomy lies in the improvement of stress distribution across the acetabular cartilage of the hip joint, thus slowing down the degenerative damage of the hip joint.     

Risk factors for recurrence of diabetic foot ulcers: prospective follow‐up analysis in the Eurodiale subgroup

Few studies have examined factors associated with diabetic foot ulcer (DFU) recurrence. Using data from patients enrolled in the prospective Eurodiale DFU study, we investigated the frequency of and risk factors for DFU recurrence after healing during a 3‐year follow‐up period. At our site, 93 Eurodiale‐enrolled patients had a healed DFU. Among these, 14 were not alive; of the remaining 79 patients we enrolled 73 in this study. On entry to the Eurodiale study, we assessed demographic factors (age, sex and distance from hospital); diabetes‐related factors [duration, and glycated haemoglobin (HbA1c) levels]; comorbidities (obesity, renal failure, smoking and alcohol abuse) and DFU‐related factors [peripheral arterial disease, ulcer infection, C‐reactive protein (CRP) and; foot deformities]. During the 3‐year follow‐up period, a DFU had recurred in 42 patients (57·5%). By stepwise logistic regression of findings at initial DFU presentation, the significant independent predictors for recurrence were plantar ulcer location [odds ratio (OR) 8·62, 95% confidence interval (CI) 2·2–33·2]; presence of osteomyelitis (OR 5·17, 95% CI 1·4–18·7); HbA1c > 7·5% ([DCCT], OR 4·07, 95% CI 1·1–15·6) and CRP > 5 mg/l (OR 4·27, 95% CI 1·2–15·7). In these patients with a healed DFU, the majority had a recurrence of DFU during a 3‐year follow‐up period, despite intensive foot care. The findings at diagnosis of the initial DFU were independent risk factors associated with ulcer recurrence (plantar location, bone infection, poor diabetes control and elevated CRP) and define those at high risk for recurrence, but may be amenable to targeted interventions.     

Pannexin‐1 and P2X7‐Receptor Are Required for Apoptotic Osteocytes in Fatigued Bone to Trigger RANKL Production in Neighboring Bystander Osteocytes

Osteocyte apoptosis is required to induce intracortical bone remodeling after microdamage in animal models, but how apoptotic osteocytes signal neighboring “bystander” cells to initiate the remodeling process is unknown. Apoptosis has been shown to open pannexin‐1 (Panx1) channels to release adenosine diphosphate (ATP) as a “find‐me” signal for phagocytic cells. To address whether apoptotic osteocytes use this signaling mechanism, we adapted the rat ulnar fatigue‐loading model to reproducibly introduce microdamage into mouse cortical bone and measured subsequent changes in osteocyte apoptosis, receptor activator of NF‐κB ligand (RANKL) expression and osteoclastic bone resorption in wild‐type (WT; C57Bl/6) mice and in mice genetically deficient in Panx1 (Panx1KO). Mouse ulnar loading produced linear microcracks comparable in number and location to the rat model. WT mice showed increased osteocyte apoptosis and RANKL expression at microdamage sites at 3 days after loading and increased intracortical remodeling and endocortical tunneling at day 14. With fatigue, Panx1KO mice exhibited levels of microdamage and osteocyte apoptosis identical to WT mice. However, they did not upregulate RANKL in bystander osteocytes or initiate resorption. Panx1 interacts with P2X₇R in ATP release; thus, we examined P2X₇R‐deficient mice and WT mice treated with P2X₇R antagonist Brilliant Blue G (BBG) to test the possible role of ATP as a find‐me signal. P2X₇RKO mice failed to upregulate RANKL in osteocytes or induce resorption despite normally elevated osteocyte apoptosis after fatigue loading. Similarly, treatment of fatigued C57Bl/6 mice with BBG mimicked behavior of both Panx1KO and P2X₇RKO mice; BBG had no effect on osteocyte apoptosis in fatigued bone but completely prevented increases in bystander osteocyte RANKL expression and attenuated activation of resorption by more than 50%. These results indicate that activation of Panx1 and P2X₇R are required for apoptotic osteocytes in fatigued bone to trigger RANKL production in neighboring bystander osteocytes and implicate ATP as an essential signal mediating this process. © 2016 American Society for Bone and Mineral Research.     

Pituitary tumors in MEN1: do not be misled by borderline elevated prolactin levels

Purpose

The objective of this case report is to demonstrate that the simple expedient of measuring periodic prolactin levels in patients with MEN1 who have modest hyperprolactinemia and normal pituitary MRI scans is insufficient to monitor for the development of pituitary adenomas.

Methods

Review of relevant literature and chart review.

Results

A 25 year old man with known MEN1 manifested by hyperparathyroidism and a gastrin-producing neuroendocrine tumor was found to have a prolactin [PRL] level of 20.0 ng/mL [1.6–16 ng/mL] but a normal pituitary MRI scan. The impression then was that he had prolactinoma too small to be visualized on the MRI. Over the next 3.5 years his PRL levels remained in this mildly elevated range but he then presented with severe headaches and visual field defects. An MRI showed a 3.1 × 1.7 × 1.9 cm pituitary adenoma with compression of the optic chiasm and invasion of the left cavernous sinus. Surgery revealed a gonadotroph adenoma and he subsequently required gamma knife radiotherapy for residual tumor. Postoperative PRL levels were normal.

Conclusions

Small, intrasellar microadenomas may be associated with elevated PRL levels due to possible direct hormone production [prolactinoma] or possibly to interference with portal vessel blood flow. In monitoring hyperprolactinemic MEN1 patients for the development of pituitary adenomas, measurement of PRL levels is insufficient and periodic MRI scans are necessary at a more frequent interval than every 3–5 years. This may also pertain to patients with “idiopathic” hyperprolactinemia.

     

Tie – an Accessory Fashion Detail or a Symbol?

Aim

The first aim of this study was to establish the frequency of wearing a tie or business neckerchief on different occasions and in relation to age and educational level. The second aim was to establish whether men who frequently wear a tie were attributed certain characteristics more often than men who rarely wear a tie and to establish whether there were differences in the attribution of these characteristics according to sex, age, educational level, and the frequency of wearing a tie.

Method

Data were collected in 2005 by a method of face to face interview on a national representative sample (n = 1007). Participants estimated how often they wore a tie or business neckerchief on 9 different occasions. They also estimated whether each of 14 characteristics was more pronounced in men who frequently wear a tie.

Results

Tie was most frequently worn on festive and formal occasions, such as weddings and festive gatherings, and least frequently on family gatherings and when traveling. On all occasions, tie was more often worn by men of higher educational level and of older and middle age. A relatively small proportion of Croatian citizens based their conclusions on men’s characteristics on the frequency of wearing a tie. Men who frequently wear a tie were relatively most often attributed the characteristics of ambition, politeness, and respectability, with significant differences found between persons who attributed these characteristics according to sex, age, educational level, and the frequency of wearing a tie by the participants themselves.

Conclusion

Wearing a tie or neckerchief is an exception rather than a rule for most of the Croatian population, and is associated only with specific, primarily festive and formal occasions. Such use of the tie suggests that people adapt their style of clothing to the expectations of others and use it as a specific symbol of the occasion.Clothing is a form of non-verbal communication and represents a systematic way of conscious or unconscious information transmission (1). What distinguishes clothing from other forms of non-verbal communication is that it is the first thing we notice when we meet a person for the first time. Clothing can influence our first impression of a person, create stereotypes, and influence our behavior toward that person (2,3). Therefore, we use clothing as a channel of non-verbal communication for self-presentation and impression management (4). Clothing is also important for our self-concept, since it allows us to feel safer, more assertive, more powerful, and more comfortable in a given situation (4,5). Besides that, the clothes we wear are an example of normative social influence (6), ie the influence we conform to in order to be accepted by a desired social group.More systematic investigation on the influence of clothes on interpersonal relations began in the 1970s and by now a large number of studies have confirmed that people form the impressions on other people on the basis of their physical appearance, especially clothes (7). For example, Damhorst (8), in his review, concluded that 94% of the analyzed experimental studies showed an influence of clothes on the impression formation. Research showed that the way a person is dressed influences the conclusions other people make on their traits and characteristics, such as reliability, competence, power/status, or their workplace (9-13). People not only base their conclusions on clothes itself but also on the appropriateness of clothes to the occasion (7). Different roles or social positions and different occupations or work places are often related to different social norms, including the clothing norm (4,14-16). Even when we do not place much importance on social roles, we still use clothing to adapt to the situation because we care about the reactions of others. Also, appropriate clothing facilitates social interaction and helps us feel more comfortable (4,5). People use clothes to demonstrate similarities in values and beliefs with members of their own group, as well as differences from the groups they do not belong to (17-19). The choice of clothes can show our disagreement with certain norms or terminate unwanted social interactions.The greatest part of the research on the influence of clothes on impression formation and management was conducted in business situations and is related to conventional or classic clothing style (14-16,20). These studies have shown that the applicant’s clothing at interview has an influence on whether he or she will get a job, and that classically or conventionally dressed people are more positively evaluated. Classic or conventional clothing includes a suit for both men and women and a tie for men. It has been proven that this style of clothing is associated with competence and authority in both men and women, not only in business situations (15,21-25).According to the available data, 600-700 million people across the world wear a tie every day, and more than two billion Euro is spent on ties every year, which is more than a yearly budget of some smaller states (26). According to Johnson (27), the earliest known version of the tie was found in the mausoleum of the first emperor of China, Shih Huang Ti, who was buried in 210 BC. Tie’s modern history began in the 17th century, when Croatian soldiers fighting in the Thirty Years'' War spread its forerunner, known as the cravat, all over Europe. In his monograph Le grande histoire de la cravate, Francois Chaille confirms and discusses the Croatian origin of the cravat (Figure 1), while the Encyclopćdia Britannica states that the noun “cravat” originated from the words Crabata, Cravata, and Croatian, mentioning the year 1656 as the year of its appearance (26). The French readily accepted the special way of tying a piece of cloth around the neck “a la Croate” and citizens of Paris soon took it to be a symbol of progress (26). During the French revolution, black cravats were worn as a sign of protest against reactionary ideas, and the cravat soon became a symbol of culture and elegance (26). While the French saw the cravat as a decoration and a symbol of progress, for the Croatian it was primarily a symbol of fidelity. According to the popular tradition, wives and girlfriends would give cravats to soldiers as a token of their love, to give them courage and comfort in difficulties and danger. On the other hand, by wearing a cravat, the soldier would show the respect for his beloved. This custom symbolized a man''s loyalty to a woman, as well as established loyalty as a virtue (28). Therefore, through the history, the tie has symbolized loyalty, culture, refinement, style, and elegance; according to Johnson (27) the tie has symbolized social status, occupation/work place, identity, as well as group belonging.Open in a separate windowFigure 1Tie with a traditional Croatian pattern called pleter.In order to examine contemporary symbolical connotations of the tie, we analyzed the frequency of wearing a tie on various occasions among the citizens of Croatia of different age and educational level, as well as the characteristics attributed to men who frequently wear a tie. Since tie is a garment worn usually by men, we analyzed the frequency of wearing a business neckerchief among women.Specific aims of the study were: 1) to establish the frequency of wearing a tie orbusiness neckerchief on different occasions among people of different age and educational levels; 2) to establish whether men who frequently wear a tie were attributed certain characteristics more often than men who wear a tie rarely and to establish whether there were differences in the attribution of these characteristics according to age and educational levels; and 3) to establish whether there are differences between men in the attribution of characteristics to other men who frequently wear a tie with regard to the number of different situations in which men themselves frequently wear a tie.     

D-Optimal Design in the Development of Rheologically Improved In Situ Forming Ophthalmic Gel

In situ forming ophthalmic gels need to be fine tuned considering all the biopharmaceutical challenges of the front of the eye in order to increase drug residence time at the application site resulting in its improved bioavailability and efficacy. The aim of this study was to develop in situ forming ophthalmic poloxamer P407/poloxamer P188/chitosan gel fine tuned in terms of polymer content, temperature of gelation, and viscosity. Minimizing the total polymer content while retaining the advantageous rheological properties has been achieved by means of D-optimal statistical design. The optimal in situ forming gel was selected based on minimal polymer content (P407, P188, and chitosan concentration of 14.2%, 1.7%, and 0.25% w/w, respectively), favorable rheological characteristics, and in vitro resistance to tear dilution. The optimal in situ forming gel was proved to be robust against entrapment of active pharmaceutical ingredients making it a suitable platform for ophthalmic delivery of active pharmaceutical ingredients with diverse physicochemical properties.