Volumen 39 (2018): Heft 1 (July 2018)

Background: Osteoporosis is highly prevalent in CKD patients and is characterized by low bone mass leading to decreased bone strength. It is associated with an increased risk of fracture, thus increasing morbidity and mortality. Bisphosphonate administration decreases fracture risk in postmenopausal females with osteoporosis. There are limited studies showing effects of short term alendronate administration on BMD in predialysis osteoporotic patients with CKD.

Methods: This study was conducted on fifty adult patients with chronic kidney disease. Patients were divided into two groups. Group A consisted of seventeen patients with CKD stage 3 (eGFR 45-30 ml/min/1.73m²) and Group B comprised thirty three patients with CKD stage 4 (eGFR 30-15 ml/min/1.73m²). The study included male patients between age 18-75 years and premenopausal non pregnant females older than 18 years of age. All the patients were osteoporotic having T score < −2.5 on DEXA scan. The patients were administered 70 mg alendronate tablet once a week for 6 weeks. Renal parameters, parathyroid hormone, calcium, phosphorous and alkaline phosphatase levels were assayed at baseline for 6 months. Serum (iPTH) level (pg/ml) was measured by chemiluminescent immune assay (CLIA) method and serum 25 Hydroxy Vitamin D level (ng/ml) was measured by enzyme linked immunosorbent assay (ELISA) method. Bone Mineral Density (BMD) was measured at baseline for 6 months, by dual energy x-ray absorptiometry at lumbar spine and neck of femur and lowest values were included. The results were obtained for T score, Z score and bone mineral density (g/cm²).

Results: The BMD, T score and Z score increased in both groups after 6 months with a statistically significant difference in the treatment group. In Group A, T score, Z score and BMD (g/cm²) increased from −2.60±0.086, −2.13±0.28, and 0.80±0.008 at baseline to −2.57±0.097, −2.11±0.26 and 0.81±0.008 after six months. In Group B, the T score, Z score and BMD (g/cm²) increased from −3.17±0.24, −2.82±0.33 and 0.738±0.03 to −3.16±0.25, −2.66±0.95 and 0.743±0.03 after six months with a statistically significant difference. eGFR decreased in both groups but the difference was statistically non-significant (P>0.05). The serum iPTH levels increased after 6 months in both groups with a statistically insignificant difference. There was an increase in serum calcium and decrease in serum phosphate levels after six months, however the difference was statistically insignificant (p>0.05). The SAP values decreased in both groups after six months with a statistically insignificant difference. The main side-effect in the alendronate group was the occurrence of gastroesophageal reflux symptoms in two subjects.

Conclusion: Low-dose alendronate, administered for a limited duration, appears to be well tolerated in CKD patients. The BMD increased in both groups suggesting a bone-preserving effect of alendronate.

Background: The aim was to evaluate the Nt-proBNP discriminatory role between symptomatic and asymptomatic patients with severe aortic stenosis.

Methods: 187 patients with severe valvular aortic stenosis, with normal EF > 50%, were included, 61 asymptomatic and 126 symptomatic. We used clinical, laboratory (Nt-proBNP) and echocardiographic parameters. Endpoints of monitoring (occurrence of event) were: the onset of symptoms in asymptomatic patients and death in both groups.

Results: The symptomatic group with severe AS had a significantly higher means of Nt-proBNP, in comparison with the asymptomatic group. Nt-proBNP was a significant predictor for the risk of event occurrence (HR 1.4). In the group of severe AS without CAD (n = 101), the subgroup with Nt-proBNP above the cut-off value, took significantly higher percentage of patients with chest pain, fatigue and syncope. In the group with Nt-proBNP above the cut-off value, we had a significantly higher percentage of patients with severe AS without CAD, compared to those with CAD (n = 142). Nt-proBNP was negatively correlated with AVA and LVEF, whether the positive correlation was expressed for: LVEDd, LVEDs, IVSd, AV_Vmax, AV_MaxGrad, LVM and LA. Patients with Nt-proBNP above the cut-off, had a significantly lower event free survival, compared to patients with Nt-proBNP below the cut-off (n = 187; n = 101).

Conclusion: The Nt-proBNP cut-off> 460 pg/ml was confirmed as a useful tool in the determination of event free survival in patients with severe AS. Nt-proBNP not only had relevance in the assessment of the severity of the disease, but also was a significant predictor for the risk of event occurrence.

Background: Benign esophageal strictures are complications resulting from various causes. They can be structurally categorized in two groups: simple and complex. Treatment is similar in most cases that require dilatation and means use of three general types of dilators that are currently in use. However, despite the last guidelines on esophageal dilatation, the therapeutic response, optimal timing of treatment and interval between sessions may vary and there is no strong consensus in the literature regarding this fact.

Aims: To analyzethe first 4 year experience of Digestive Endoscopy Unit at the University Clinic of Gastroenterohepatology of the Medical Faculty, Skopje, Republic of Macedonia in treating benign esophageal strictures, since the Savary-Gilliard technique of “bougienage” was introduced for the first time in Republic of Macedonia, at our Institution, in December 2013, by assessing etiology, length of stricture, number of dilations required to achieve satisfactory therapeutic response, as well as the relationship between the type, extent of stenosis and therapeutic response.

Methods: One hundred and forty five dilations, during a period from 20th December 2013, until March 2017, have been analyzed in 31 patients

Results: The caustic strictures were the most prevalent, occurring in 15 (48%) of patients, followed by peptic stenosis presenting 26% of patients. The long and corrosive strictures needed more sessions to the absence of dysphagia. Peptic and short stenoses best respondedon treatment and needed fewer dilatation sessions per patient.

Conclusion: Caustic stricture is the most common type of benign esophageal stenosis and the most refractory to treatment, especially the long one. Peptic stenosis is the second cause of benign esophageal strictures and responded well to endoscopic therapy. The higher the extent of stenosis, the greater the number of sessions required. Short strictures have good prognoses in most cases. The number of dilations depended directly on the cause and extent of stenosis. Bouginage using Savary-Gilliard or American type of technique, irrespective of the type and the extent of esophageal stenosis, is safe and purposeful procedure.

Objective: The aim of the study was to assess the prevalence of newly diagnosed diabetes in patients with acute coronary syndrome and estimate the relationship between stress hyperglycemia, glyco-regulation and newly diagnosed diabetes with hospital morbidity and mortality.

Methods: This was an observational study which included all patients hospitalized due to acute coronary syndrome (January 2015 until April 2017) at the University Clinic of Cardiology in Skopje, Macedonia. We analyzed demographic, clinical, biochemical variables and hospital morbidity and mortality. Five investigated groups were compared using a single biochemical parameter glycated hemoglobin (HgbA1c) depending on the presence of known diabetes before the acute event: 0-without DM (HgbA1c <5.6%), 1-newly diagnosed pre-diabetes (HgbA1c 5.6-6.5%), 2-newly diagnosed diabetes (HgbA1c ≥ 6.5%), 3-known well controlled diabetes (HgbA1c <7%) and 4-known un-controlled diabetes (HgbA1c ≥7%).

Results: 860 patients were analyzed. Impaired glucose metabolism was confirmed in 35% of patients, 9% of which were with newly diagnosed diabetes. Stress hyperglycemia was reported in 27.3% (3.6% were without diabetes). The highest values of stress hyperglycemia were reported in newly diagnosed and known un-controlled diabetes. In-hospital morbidity and mortality were 15% and 5% accordingly and the rate was highest in patients with newly diagnosed and known, but un-controlled diabetes. HgbA1c, stress hyperglycemia, and poor glycemic control have emerged as significant independent predictors of hospital morbidity and mortality in patients with acute coronary syndrome.

Conclusion: High prevalence of newly diagnosed diabetes was observed in patients with acute coronary syndrome. Stress hyperglycemia and failure to achieve glycemic control are independent predictors of hospital morbidity and mortality.

The assessment of liver fibrosis in patients with chronic hepatitis B (CHB) is of great importance in evaluating the phases of chronic hepatitis B viral infection, prompt administration of antiviral therapy, prevention of disease progression and late complications of CHB infection. Aim: to investigate the clinical significance of quantitative HBs antigen as a predictor for liver fibrosis in patients with HBe antigen negative chronic hepatitis B and inactive carriers. Material and Methods: the study included 44 treatment naïve patients with chronic hepatitis B, divided into two groups, HBeAg negative chronic HBV infection or inactive carriers (IC) and HBeAg negative chronic hepatitis B patients. All patients underwent laboratory, serologic testing, ultrasound and transient elastography (TE). In both patient groups, quantitative HBs antigen (HBsQ), alanine aminotransferase (ALT), hepatitis B virus deoxyribonucleic acid (HBV DNA) and liver fibrosis were analyzed. Results: The value of HBsQ is significantly higher in patients with HBeAg negative CHB 2477.02±4535.44 IU/ml than in the IC group 8791±11891 IU/ml; Z=3.32, p<0.001 (p=0.0009). In IC patients, 1 (4.76%) had fibrosis and 20 (95.24%)) did not have fibrosis. Out of 23 patients with HBeAg negative chronic hepatitis B, 8 (34.78%) had fibrosis and 15 (65.22%) did not have fibrosis. Patients with HBeAg negative hepatitis B had significantly higher liver fibrosis than IC; Fisher Exact Test p<0.05 (p=0.02). The increase of HBsQ for one single unit (IU/ml) does not have predictive value for fibrosis (Ext (B) =1.00), 95% C.I. for EXP (B): 1.00-1.00 / p>0.05. Conclusion: Quantitative hepatitis B surface antigen has intermediate weak statistically insignificant prediction for liver fibrosis R=0.25 (p<0.10).

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to an infection and it is a major cause of morbidity and mortality worldwide. The aim of this study is to describe epidemiology of community-acquired sepsis in the Intensive care unit (ICU) of the Macedonian tertiary care University Clinic for Infectious Diseases. A prospective observational study was conducted over a 6-year period from January, 2011 to December, 2016. All consecutive adults with community-acquired sepsis or septic shock were included in the study. Variables measured were incidence of sepsis, age, gender, comorbidities, season, source of infection, complications, interventions, severity indexes, length of stay, laboratory findings, blood cultures, 28-day and in hospital mortality. Of 1348 admissions, 277 (20.5%) had sepsis and septic shock. The most common chronic condition was heart failure (26.4%), and the most frequent site of infection was the respiratory tract (57.4%). Median Simplified Acute Physiology Score (SAPS II) was 50.0, and median Sequential Organ Failure Assessment (SOFA) score was 8.0. Blood cultures were positive in 22% of the cases. Gram-positive bacteria were isolated in 13% and Gram-negatives in 9.7% of patients with sepsis. The overall 28-day and in hospital mortality was 50.5% and 56.3% respectively. The presence of chronic heart failure, occurrence of ARDS, septic shock and the winter period may influence an unfavorable outcome. Mortality compared to previous years is unchanged but patients that we have been treating these last 6 years have had more severe illnesses. Better adherence to the Surviving Sepsis guidelines will reduce mortality in this group of severely ill patients.

The notion that personality impacts health is not new. According to Grossarth-Maticek and Eysenck’s theoretical approach, the main factor for health is the ability for self-regulation, which seems to moderate the effects of some physical risk factors.

The aim of this study was to evaluate personality characteristics of patients hospitalized for traumatic limb’s fractures which have been operatively treated. To our knowledge, it is the first study of this type in the region.

The evaluated sample comprises two groups of examinees: patients hospitalized at the Traumatology Clinic for surgery after fractured limbs (N=30) and healthy people (N=120) as control, previously examined. Two psychometric tests were used: Grossarth-Maticek questionnaire and Eysenck Personality Questionnaire (EPQ).

Obtained results showed that the personality characteristics of patients with traumatic limb fractures belong generally to the “healthy type 4” of Grossarth-Maticek typology, similarly as the control. It correlates to the low N (neuroticism) and moderate E (extraversion) scales in the Eysenck typology.

We showed that gender and age highly influence the scores obtained from the questionnaire.

The type of personality could influence reactions in life situations, coping with stress and consequently to be a trigger for any disorder, even traumatic fractures

The potential use of modern mobile devices for medical purposes is huge. Digital mental health tools have mostly tended to use psycho-educational strategies based on treatment orientations developed and validated outside digital health.

The aim of this study was to test the availability of our own original app named “Neuro-game” for evaluation of reaction time in different neuropsychiatric patients. Reaction time is strongly related to the executive brain functions.

The examined sample comprised of 135 neuropsychiatric patients (with epilepsy, depression, general anxiety, psychosis and ADHD) compared with matched 50 healthy persons.

We showed that the average reaction time in neuropsychiatric patients compared with healthy people is not notably different. However, we found significant differences in total hits, total misses and total tries in the performances of ill persons.

The crucial differences in obtained scores are confirmed for age and gender issues.

The most important differences are found in the number of hits, misses and tries in the group of depressed, followed by psychotic and ADHD patients, while anxious ones showed pretty normal parameters.

All tested parameters are remarkably different for the epileptic group vs. healthy people.

The T-test for epileptic vs. healthy people showed noteworthy differences for total tries, total misses, and total hits, but the average time reaction did not differ significantly.

In comparison with other psychometric assessments, this approach by using mobile phones seemed more practical, available anywhere (not only in medical settings), less time consuming and quite interesting for all ages.

Introduction: Children born small for gestational age (SGA) have increased prevalence of metabolic syndrome, diabetes mellitus type 2 (DM2), hypertension and cardiovascular and cerebrovascular events in adulthood.

Patients and Methods: In 100 children born SGA, and in second cohort having 32 obese children born in term with normal birth weight and height, anthropometric measurements and biochemical metabolic profiles were analysed. The Homeostasis Model Assessment - Insulin Resistance and Sensitivity (HOMA-IR and IS) were calculated.

Results: Four overweight/obese children (M:F=3:1) with normal height were found among 100 SGA children. The body mass index (BMI) in all 4 children was above the 98th percentile and the mean BMI z-score was (2.04±0.30 SDS). The HOMA-IR index in all four children was increased: 1.26-2.65 (>1). Two teenagers had significant hyperinsulinemia (198.00 uIU/ml and 275 uIU/ml) and were treated with metformin. Two girls needed only a diet and increased physical activity. The mean values of HOMA-IR (1.26-2.65; N< 1) and IS (58 ±17.12) in fo-ur SGA overweight/obese children who caught-up growth had indistinguishable values with the group of 32 (M: F=21:11) obese children (HOMA-IR 1.83±1.2 SDS; IS 82.99±64.53 SDS) born in term with normal birth weight and height.

Conclusions: SGA born children are usually thin; nevertheless we found overweight and obesity in 4% of the patients. Two of those children have metabolic syndrome. Excess weight, obesity and metabolic syndrome in SGA children result with increase of their inherent risk for DM2, cardiovascular and cerebrovascular diseases in adulthood.

Distal renal tubular acidosis (dRTA) (MIM #267300, #602722 and #179800) is a rare inherited tubulopathy characterized by the inability of the distal tubule to acidify the urine with consecutive systemic acidosis. The clinical features include polyuria, polydipsia, poor appetite, failure to thrive, short stature and rickets. Prominent biochemical features are hypokalemia, hypercalciuria and hypocitraturia. There are reports on patients who presented with unusual biochemical features such as low molecular proteinuria, hypophosphatemia, hypouricemia, generalized hyperaminioaciduria, hyperoxaluria and other making diagnostic confusion to the clinicians. In this work, we report on a series of 8 children with clinically, biochemically and genetically proven dRTA who present with low molecular proteinuria at the disease onset. With metabolic compensation of the disease, there was complete resolution of the low molecular weight protenuria and other proximal tubular abnormalities in all children. Late recognition of the disease with long standing hypokalemia and acidosis may result in abnormal expression and function of the transporters in the proximal tubules. Sodium dodecyl sulphate polyacrylamide gel electrophoeresis is an accurate method for detection and follow up of patients with low molecular weight proteinuria.

The ability to adapt to stress and adversity is a central facet of human development. Coping can be defined as a set of cognitive and affective actions that arise in response to a particular disquiet.

The aim of this research was to evaluate coping patterns used to mediate anxiety and stress level in two groups of patients: orthodontic and dental.

Psychometric instruments applied in the research are: Sarason’s anxiety questionnaire, Stress-test for children, as well as A-Cope questionnaire.

Obtained scores confirmed important level of anxiety, and moderate stress level. It was shown that coping mechanisms used for moderate stress and anxiety were productive and influenced the scores for the stress level and anxiety to be diminished.

As far as our knowledge is concerned, this is the first study for coping styles in children in our country.

Background: Obesity is the most common chronic metabolic disease in children and adolescents. It has reached epidemic ranges and is a significant global problem.

Objective: This study aimed to investigate the possible metabolic disturbances in children and adolescents with obesity and severe obesity.

Subjects and methods: This cross-sectional study included 158 (82 boys, 76 girls) obese children and adolescents between ages of 0 and 17years (10.43 ± 3.11 years). The obesity was defined according to the sex- and age-specific growth charts proposed by the Centers for Disease Control and Prevention as BMI ≥ 95th percentile. Severe obesity was classified as 120% of the 95th percentile for age and sex. Study participants underwent medical assessment and analysis of: ALT, AST, fasting serum triglycerides, total serum cholesterol, fasting plasma glucose and plasma glucose from oral glucose tolerance test.

Results: The majority of study participants were severely obese (69.92%). The highest distribution of abnormal biochemical results was seen in elevated ALT (53.91%) followed by elevated triglycerides (34.75%). The prevalence of abnormal total cholesterol level was significantly higher (p=0.04) in the group of obese children compared to the severely obese children. The levels of total cholesterol were also statistically higher in the group of adolescents compared to preadolescents (p=0.02). An important number of obese patients (2.5%) and even higher number of severely obese patients (5.26%) had carbohydrate intolerance.

Conclusion: There was a significant elevation of ALT, total serum cholesterol and triglycerides in all study participants. High serum lipids and high hepatic enzymes (as introduction in non-alcoholic fatty liver disease) are alarming. Strikingly, there was carbohydrate intolerance in an important number of patients. Treatment and education of patients and parents is mandatory. Preventive measures in the society concerning childhood obesity are necessary.

Background: Multiple sclerosis (MS) treatment aims not only to prevent the rate of relapse, but also to slow down patient’s disability progression. Monoclonal antibodies constitute a new class of therapeutic agents and are administered by intravenous (IV) infusion. Treatment satisfaction and incidence of adverse drug events influence the patient’s treatment adherence which is essential to ensure patients obtain the best treatment outcomes and also to make that treatment cost-effective. Our primary objective was to assess the current IV treatment satisfaction among MS patients.

Methods: A standard questionnaire was developed which contained 20 questions about patient’s disease, IV treatment satisfaction and drug safety awareness. Analyzed data was presented as a percent of the respondents.

Results: The cross-sectional study included 13 MS patients on IV treatment, with mean age of 35 years. 54% of them had relapse-remitting MS, while 46% had secondary progressive MS. The most common onset symptoms were tingling reported in 46% and numbness in 31% patients. 70% of patients were satisfied, while 23% were not satisfied with the conditions under which they were receiving their IV treatment that lasts in average 2 hours. Well-established pharmacovigilance practice enhanced the patient’s knowledge that was reflected through 100% reporting of adverse drug reactions in the past.

Conclusion: High level of satisfaction from the current IV treatment conditions and high drug safety awareness among MS patients was shown. Establishment of infusion centre as a proposed strategy by MS patients would substantially increase their IV treatment satisfaction and adherence.

Introduction: Patients undergoing laparoscopic cholecystectomy do experience postoperative pain, especially in the abdomen. Postoperative pain management remains a major challenge after laparoscopic procedures. Administration of intraperitoneal local anesthetic (IPLA) after surgery is used as a method of reducing postoperative pain. In this study, we evaluated the effect of intraperitoneal infiltration of local anesthetic (bupivacaine) for pain relief after laparoscopic cholecystectomy.

Material and methods: In this prospective, controlled, and randomized study were included 50 patients aged 25-60 years (35 female and 15 male), scheduled to laparoscopic cholecystectomy with ASA classification 1 and 2. Patients were classified randomly into two groups: group A, which included 25 patients who received intraperitoneal instillation of bupivacaine 0.5% 20 ml; and group B, which included 25 patients who didn’t receive any intraperitoneal instillation. Postoperative pain was recorded using the visual analogue scale (VAS) for 24 hours after laparoscopic cholecystectomy.

Results: There was no significant difference with respect to age, weight, and sex; duration of surgery; and anesthesia time. VAS scores at different time intervals were statistically significantly lower at all times in group A compared to group B. There were statistically significant differences in VAS scores between group A and group B at all postoperative time points - 1hr,4 hr,8 hr,12hr and 24hr (p < 0.00001).

Conclusion: Intraperitoneal instillation of bupivacaine provides good analgesia in the postoperative period after laparoscopic cholecystectomy.

Introduction: Parapneumonic effusions, as a complication of community-acquired pneumonia (CAP), usually have a good course, but they sometimes progress into complicated parapneumonic effusion (CPPE) and empyema, thus becoming a significant clinical problem.

Aim: To review clinical and radiological features, as well as diagnostic and therapeutic options in parapneumonic effusions.

Material and methods: The analysis included 94 patients with parapneumonic effusion hospitalized at the University Infectious Diseases Clinic in Skopje during a 4 year period. Out of 755 patients with CAP, 175 (23.18%), had parapneumonic effusion. Thoracentesis was performed in 94 (53.71%) patients, 50 patients were with uncomplicated parapneumonic effusions (UCPPE) and 44 with complicated parapneumonic effusions (CPPE).

Results: More patients (59.57%) were male; the average age was 53.82±17.5 years. The most common symptoms included: fever (91; 96.81%), cough (80; 85.11%), pleuritic chest pain (68; 72.34%), dyspnea (65; 69.15%). Alcoholism was the most common comorbidity registered in 12 (12.77%) patients. Macroscopically, effusion was yellow and clear in most cases (36; 38.29%). Localization of pleural effusion was often in the left costophrenic angle (53; 56.38%) and ultrasonographic non-septated complex. Between the two groups of effusions there was a significant difference between the ERS, WBC and CRP in serum and CRP in pleural fluid. Statistical difference existed in terms of days of hospitalization with a longer hospital stay for patients with CPPE (p <0.0001).

Conclusion: Patients with parapneumonic effusion have the symptoms of acute respiratory infection and frequent accompanying diseases. Future diagnostic and therapeutic treatment depends on pleural fluid features and imaging lung findings.

Introduction: Growth failure is a common consequence in small for gestational age (SGA) children.

Patients and Methods: The growth patterns and serum insulin like growth factor 1 (IGF1) concentrations before and after the 1st year under growth hormone treatment of 32 short stature SGA born children have been evaluated. In addition, we investigated the insulin like growth factor 1 receptor (IGF1R) exon 2 as a hotspot for IGF1R genetic alterations. It is of note that no dysmorphic features were observed in this group of children.

Results: The tests for pituitary reserve were within normal ranges for all 32 patients. Growth hormone (GH) treatment (0.037 mg/kg/day) was initiated at the mean age of 9.32±3.19 years. Growth velocity increased yearly from −1.80 SDS after the first year to −0.03 SDS in the sixth year of treatment. Their IGF1 serum concentrations before treatment were age and sex appropriate, while during treatment a significant increase was observed fitting in the upper third of the normal range: before the treatment IGF1 SDS was 0.84±1.78 after 1st year the concentrations increased to IGF1 SDS 0.94±2.23. No genetic alterations were found in the IGF1R exon 2 by PCR analysis.

Conclusions: Herein we present 32 short stature SGA children with no dysmorphic features treated with GH. They all had increased growth velocity and entered the normal growth range on their growth charts. No side-effects were observed. GH treatment in children with no genetic alterations on the IGF1R exon 2 is safe and efficient in treating SGA children with short stature.

One of the most important CF-related conditions is the bone disease, which is nowadays acknowledged as a significant clinical complication of CF. Imbalance between bone formation and degradation in cystic fibrosis (CF) has become an important issue for developing osteopenia. The aim of the study was to assess bone formation and resorption process with bone markers in children with cystic fibrosis (CF). Materials and methods: The study included 35 clinically stable children with CF who regularly attended the Cystic fibrosis center at the University Pediatric Clinic in Skopje, R. Macedonia. The control group was presented with 21 healthy children at the same age. Serum osteocalcin (OC), β cross laps, 25OHD and PTH were determined by ELISA assays in the CF group (mean age 8.25±SD1.9 y.) and in age-match controls (7.5±1.9 y.). Results: Vitamin D in the CF group was (23.83±10.9 ng/ml versus 25.6±11.53 in the control group, p=0.57), OC (70.88±34.24 ng/ml v.100.02±47.98, p=0.01) βcrosslaps (1.35±0.72 ng/ml v.1.54±0.73, p=0.37) and PTH (37.39±25.5 pg/ml v. 36.76±25.73, p=0.92). In the study, we did not find a significant difference for 25OHD between CF and healthy controls. OC in children with CF correlates significantly with the control and indicates a decreased formation rate whereas resorption rate is normal. Conclusion: Our results suggest that bone turnover in CF is impaired in childhood. Serum markers for bone formation can be used for predicting osteopenia in children with CF.

Aim: To present a group of young doctors from R. Macedonia who were elected as lecturers at the Faculty of Medicine (FM) in Skopje, R. Macedonia, in the period 1961-63.

Method: A retrospective study based on archive materials, encyclopaedias and jubilee publications of the FM and Faculty of Dentistry in Skopje, other relevant sources of information, and a review of the relevant literature.

Results: The Skopje FM was founded in 1947 and the first meeting of the Teachers’ Council of the Faculty was held on March 17, 1947. The first generation of 153 students was enrolled in the autumn of 1947 and the first lecture was delivered on November 3, 1947.

Besides 15 doctors from R. Macedonia - faculty staff, who had been appointed in the period from 1947-54, and a group of 24 lecturers from R. Macedonia who had been elected assistant professors in the period from 1955-60, an additional group of 17 Macedonian lecturers had been elected for the first time in the period from 1961-63. Those 56 pioneers and coryphaei of medicine in R. Macedonia played important roles in the establishing and/or initial and further development of a number of the faculty departments/chairs, institutes and clinics within the newly established FM in Skopje in 1947 and in the first 15-20 years of its initial development, until 1960s and later.

Conclusion: The Skopje FM, founded in 1947, played a crucial role in the education of medical professionals, in improving the poor health status of the population and the overall further development of the health system and provision of health care to the population of R. Macedonia. The contribution of the third group of 17 lecturers from R. Macedonia in furthering the development of the Skopje FM, during the 1960s and later, was very important.