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Biomedical subjects

D Milicić

Publications and source records attributed to D Milicić.

At least 19 recordsLinked to original sources

A method for the repair of vesicovaginal fistulas.

OBJECTIVE: To determine the efficacy of the sliding layers method for repairing vesicovaginal fistulas caused by surgical trauma. METHOD: Twenty one women suffering from vesicovaginal fistulas after surgical trauma, operated on between 1990 and 1995 using the sliding layers method, were included in an uncontrolled prospective study and followed 24 months after the procedure. Patient outcome was assessed according to subjective estimation, gynecological examination and objectively by instillation of diluted methylene blue to the urinary bladder. RESULTS: Sixteen out of 21 patients suffered vesicovaginal fistulas after being subjected to abdominal hysterectomy and five patients after vaginal surgery. Fourteen fistulas were located 5 to 10 mm over the interureteric edge, five fistulas were in the trigone and two fistulas were in the bladder neck region. Fistula size ranged from 5 to 35 mm in diameter but 72.1% of patient fistulas were less than 10 mm in diameter. Only one patient had a large bladder defect of 35 mm in diameter. According to subjective estimation and objective assessment the overall success rate of the procedure after 2 years was 95.2%. Only one patient had to be subjected to a second successful attempt for fistula closure. CONCLUSION: The sliding layers method is a safe and reliable vaginal surgical approach for the repair of vesicovaginal fistulas after surgical trauma.

Adult↗

Glutathione and glutathione S-transferases as early markers for ovarian carcinomas: case series.

AIM: To determine the activity of glutathione (GSH) and concentrations of glutathione S-transferases (GST), urokinase type plasminogen activator (uPA), and plasminogen activator inhibitor type 1 (PAI-1), and to evaluate their diagnostic and prognostic value and possible correlation with clinical and histopathological prognostic factors for ovarian carcinomas. METHODS: The concentrations of GSH, uPA, PAI-1, and activity of GST were analyzed in 35 tissue samples taken from 10 normal ovaries, 10 benign, 10 primary malignant, and 5 metastatic ovarian tumors. The GSH level and GST activity were determined by spectrophotometric methods, and uPA and PAI-1 concentrations by ELISA commercial kits. RESULTS: GSH concentrations were significantly higher in primary malignant (126.3+/-12.8 nmol/mg protein) and metastatic (160.5+/-24.3 nmol/mg protein) ovarian tumor specimens than in normal ovarian tissue (48.9+/-8.1 nmol/mg protein, p<0.003 for both carcinoma groups) or benign ovarian tumor samples (35.2+/-5.0 nmol/mg protein, p=0.001). The GST activity was significantly higher in primary malignant (245.8+/-22.7 nmol/min/mg protein) and metastatic (303.7+/-48.8 nmol/min/mg protein) ovarian tumor tissues than in benign tumor specimens (105.9+/-16.2 nmol/min/mg protein, p<0.004 for both carcinoma groups) or normal ovarian tissue samples (133.2+/-32.0 nmol/min/mg protein, p<0.044 for both carcinoma groups). There were no statistical differences in uPA and PAI-1 concentrations between normal, benign, and malignant tumor samples. Concentrations of GSH, uPA and PAI-1, and activity of GST were independent from histopathological and clinical prognostic factors. CONCLUSION: Increased GSH concentration and GST activity found in primary malignant and metastatic ovarian tumor samples were independent of histopathological and clinical prognostic factors, suggesting that they could be early markers for ovarian carcinomas.

Analysis of Variance↗

Plasminogen activator inhibitor type 2: potential prognostic factor for endometrial carcinomas.

The clinical determination of proteases which are involved in carcinogenesis, invasion and metastasis may contribute to the detection of the early stage of disease, and to the prognostic assessment of patients with the cancer. The aim of the present study was to determine the level of urokinase plasminogen activator (uPA), plasminogen activator inhibitor type 1 (PAI-1) and plasminogen activator inhibitor type 2 (PAI-2) in normal and malignant tissues of corpus uteri and to evaluate the possible correlation with clinical and histopathological prognostic factors. UPA, PA-I and PAI-2 were determined by the ELISA assay in tissue cytosol of matched pair samples from 27 patients with endometrial carcinoma. Results show that significantly higher levels of these proteins were found in malignant than in normal tissue samples (uPA: 1.266 versus 0.633 ng/mg protein, PAI-1:4.468 versus 1.958 ng/mg protein, and PAI-2:3.428 versus 0.483 ng/ml protein). The levels of uPA and PAI-1 did not correlate with clinical staging or pathohistological grading. However, in tumor tissues with clinical stages II and III, myometrial invasion > 50%, and lymphovascular invasion, increased levels of PAI-2 were determined. Our results indicate that components of the plasminogen activation cascade are up-regulated in endometrial cancer and suggest the role of PAI-2 in determining invasive potential of endometrial carcinomas.

Disease Progression↗

Clinical variability and molecular diagnosis in a four-generation family with X-linked Emery-Dreifuss muscular dystrophy.

AIM: To describe the clinical variability of X-linked Emery-Dreifuss muscular dystrophy (X-EDMD) with cardiac involvement in a four-generation family with a novel mutation in the STA gene. METHODS: Clinical data were provided for 4 affected males and a female carrier. The Western blot analysis of emerin was performed on lymphoblastoid cell lines and followed by sequencing of the emerin gene. RESULTS: A thymine insertion at nucleotide 417 in exon 2, resulting in a frameshift with a premature stop codon at position 62 and absence of functional protein, was found in one of the three available patients. In ten-year-old proband's dizygotic twin-nephews the intermittent first-degree A-V block, atrial and ventricular ectopy, atrial runs, and exit sinus block were found, although the echocardiographic findings were normal. One of the twins also had short episodes of atrial fibrillation, idioventricular rhythm, and junctional rhythm. CONCLUSION: Cardiac abnormalities in the proband's ten-year-old dizygotic twins without evident clinical features suggestive of EDMD were remarkable in contrast to the oldest patient in the family, who lived to the age of 63 without a pacemaker, and to the proband who had a very early onset of muscle wasting and weakness, and a pacemaker implantation at the age of 27. This striking intra-familial variability in cardiac involvement associated with specific null mutation (417 ins T) has practical early diagnostic and possibly preventive implications. It also points at genetic and environmental factors as causes of clinical features in X-EDMD.

Adult↗

Intravesically administered ketoprofen in treatment of detrusor instability: cross-over study.

AIM: To evaluate the therapeutic efficacy of intravesically administered ketoprofen in patients with urodynamically verified detrusor instability. METHODS: This double-blind randomized placebo-controlled cross-over study included 30 patients with urodynamically verified detrusor instability. Their mean age was 44+/-3.6 years (range 37-49) and the median of the parity was 2 years (1-3). The mean duration of symptoms was 18.3+/-3.1 months (range 14-23). After a 6-week screening, patients were randomized to receive ketoprofen or placebo once a day for 4 weeks. Out of 30 patients, 16 started with ketoprofen, and 14 received placebo. After a week of washing period, 16 patients received placebo, and 14 received ketoprofen. The solution for intravesical application was 50 mL of saline with 2 mL (100 mg) of ketoprofen warmed to 37 degrees C. The placebo solution contained 2 mL of distilled water instead of ketoprofen. The assessment including micturition diaries, cystometric measurements, and bacteriological analysis of urine specimens was performed at the beginning of the study and after the treatment. RESULTS: The subjective cure rate was 18/30 after ketoprofen. The instability index was lower after ketoprofen than before treatment or after placebo (p<0.001). Maximal cystometric capacity and the urinary bladder volume at which the patients felt urgency to void were larger after ketoprofen than before it (p<0.001) or after placebo (p<0.001). The number of patients with uninhibited bladder contractions decreased significantly after ketoprofen, but not after placebo (p<0.001). No side effects were observed. CONCLUSION: Intravesically administrated ketoprofen is a feasible and effective treatment for detrusor instability.

Administration, Intravesical↗

Prognostic factors in carcinoma of the larynx: relevance of DNA ploidy, S-fractions and localization of the tumour.

The influence of the cell cycle profile and the site of the primary tumour on the overall survival were examined in 36 patients with squamous cell carcinoma of the larynx. DNA ploidy (p = 0.0091), the overall proliferative activity (p = 0.0001), the overall proliferative activity of diploid tumour cells (p = 0.0017) and primary tumour site (p = 0.0008) were found to be significant single prognostic factors of the overall survival. Multivariate analysis showed that only the overall proliferative activity was prognostically significant (p = 0.013). The results of the study show that the supraglottic site of the tumours correlates significantly with DNA ploidy (p = 0.0334) and the overall proliferative activity of tumour cells (p = 0.0159), whereas the correlation with proliferative activity of diploid tumour cells (p = 0.1416) has not been confirmed by this study. Glottic tumours showed a prognostically significant correlation with the overall proliferative activity (p = 0.0037) and proliferative activity of diploid tumour (p = 0.0054). Such a prognostic correlation was not found for DNA ploidy (p = 0.6542).

Adult↗

[Acute renal insufficiency in children].

Acute renal failure (ARF) is not rare in hospitalized children, especially in newborns and infants. Sudden disorganization of a glomerular and tubular function is the most often transitory and require a quick make of diagnosis and early therapy in order to obtain a adequate kidney function recovery and to reduce mortality. In this article 51 children with ARF were included from newborn period to 16 years of age (25 female: 26 male). We described the most often causes of ARF, diagnosis procedures and nondialytic treatments. The diagnosis was made by history, physical examination, laboratory and radiology findings. Causes of ARF were divided on prerenal, renal and postrenal. The treatment of ARF in all cases was conservative with good success in 45 patients and in 6 children followed death because of the nature of primary diseases. The results of study show that the accent is on the prevention, early diagnosis and early therapy of diseases which lead to ARF. We conclude that a multidisciplinary therapeutic approach is imperative for successful management of ARF.

Acute Kidney Injury↗

[Remission of nephrotic syndrome in children treated with corticosteroids and other immunosuppressive therapy].

Hypoproteinaemia, proteinuria and edema are the main features of Nephrotic syndrome (NS) and are the result of greater permeability of glomerular basal membrane for proteins. It is difficult to predict course of disease and outcome. During 1989-1998 year 18 children were followed up, 9 boys and 9 girls, at the age of 2 to 14 years and diagnosis of NS. Therapy with pronison was initiated in all children according to the protocol of ISKDC. Children were then divided in two groups, depending on success of therapy. In the first group (13 patients, 72.22%) were the patients that had remission, and the second group consisted of 5 patients that did not have remission. In the first group relapses occurred in 7 patients (53.84%), because of side effect of pronison therapy was discontinued in 3 patients. Those 3 patients along with 5 patients from second group were then turned to immuno-suppressive therapy. One patient responded well to cyclophosphamide, rest of them with regular follow up. Two years latter two of them had relapse but responded well on pronisone therapy in the full dose. Biopsies that were done showed that 2 had minimal changes, 2 had focal segmental sclerosis and one membranous proliferative glomerulonephritis. One patient developed chronic renal insufficiency. We conclude that our experience shows that if there is not favorable effect of corticosteroid therapy cyclosporine A is the first choice in NS, without regarding of the patho-hystological findings.

Adolescent↗

A study of auditory afferent organization in children with dyslalia.

The auditory afferent (AA) control is an important feedback mechanism in the speech generation. A different organization of AA pathways in children with speech alterations is suggested. In order to investigate this possibility we recorded the auditory brainstem responses (ABR) and middle latency responses (MLR) on monoaural and binaural click stimulation in a group of 17 normal children with no alteration of the speech (N) and in 16 children with dyslalia (eight with systematic (S) and eight with non-systematic errors of the speech (NS)). All of children were normal hearing, with normal ORL and neurological status, right-handed and with the age approximately 7 years old. A lateralization effect was found in the S group. Normally, it was only found for wave I. The efficiency of both AA pathways was the same in NS group, indicating a more effective right pathway in more rostral areas. A prolonged latency (X = 0.25 ms) of wave III was registered on the right side in the NS group compared to normals, as well for wave V (X = 0.175 ms) with increased sweep rate (21 vs. 51 and 71). The effect of sweep rate augmentation was also studied (21-51-71) on latency values and inter-wave differences in these groups. A successive latency prolongation (X = 2.97 ms) of MLR wave Na was registered between the N-S-NS groups. In the S group a latency binaural interaction (BI) of MLR left wave Na was prolonged for 3.52 ms and in the NS group for a further 1.32 ms compared to normals. Only in the NS group was a prolongation of the BI of the right wave Pa detected (6.76 ms) compared to normals. Results suggest a different AA organization in children with dyslalia. Possible locations of alterations in functioning could be pons, and thalamocortical projections. ABR and MLR could evaluate the auditory-speech capability of children.

Auditory Pathways↗

Dipeptidyl peptidase III in malignant and non-malignant gynaecological tissue.

Exopeptidases, in contrast to endopeptidases (proteinases) have been much less studied in relation to cancer. The aim of this study was to investigate one such enzyme, dipeptidyl peptidase III (DPP III), in gynaecological tissues, by measuring both the enzyme activity and enzyme content. DPP III activity was assessed in normal (n = 65), benign (n = 9) and malignant (n = 51) gynaecological tissues. A statistically significant higher DPP III activity was observed in endometrial (n = 40, P = 4.6 x 10(-7)) and ovarian (n = 11, P = 8.1 x 10(-4)) malignant tumours, whereas no significant difference was detected for leiomyomas (n = 8), if compared to the activity in normal tissue. A matched pair analysis of normal and cancerous endometrial tissue confirmed the significance of the DPP III activity increase in the transformed tissue (n = 7, P = 0.022). Western blot analysis revealed a significantly (P = 0.014) increased level of DPP III in endometrial cancer. Further, regression analysis showed a positive correlation between the activity and the content of DPP III in normal tissue (r = 0.637, P = 0.047) and in endometrial cancer (r = 0.574, P < 0.007). The increase of the DPP III activity was observed in the endometrial carcinomas of various histological types, grade or the depth of myometrial invasion. The easy-to-perform determination of this exopeptidase activity may serve as a potential indicator of endometrial and ovarian malignancies.

Adolescent↗

War injuries to the head and neck.

During the 1991-1992 war in Croatia, 7,043 wounded persons were treated at Dr Josip Bencević General Hospital in Slavonski Brod. Among them, 728 (580 soldiers and 148 civilians) had war injuries to the head and neck and were admitted to the Department of Otorhinolaryngology and Cervicofacial Surgery. There were 541 (74.3%) patients with head injuries, 117 (16.0%) with neck injuries, and 70 (9.6%) with a combination of head and neck injuries. The wounds were mostly inflicted by shell and bomb fragments (542 wounds, or 74.5%). War injuries of the facial bones were preliminarily or definitively treated. Preliminary treatment was used for the wounds with multifragmentary fractures and extensive soft-tissue defects. Definitive treatment was used in lesions of cervical structures. Immediate exploration of the neck was performed on 84 patients with penetrating neck wounds. Exploration was positive in 49 patients. Concerning long-term complications, two cases of partial paralysis of the cranial plexus and one case each of quadriplegia, hemiplegia, and glottic paralysis were recorded. To our knowledge, primary closure of war wounds to the head and neck (supported by antibiotic therapy) and reconstruction of extensive laryngotracheal injuries with the medial layer of the cervical deep fascia were used for the first time as war surgery procedures.

Blast Injuries↗

Mortality caused by war wounds to the head and neck encountered at the Slavonski Brod Hospital during the 1991-1992 war in Croatia.

From July 1, 1991, until January 1, 1993, a total of 7,720 patients (soldiers and civilians) with war wounds were treated at Dr. Josip Bencević General Hospital in Slavonski Brod, Croatia. Treatment was provided for 7,043 patients, whereas 677 individuals (8.8%) killed in action (KIA) were examined at the Forensic Department. There were 1,456 patients (18.9%) with head and neck wounds: 1,176 soldiers and 280 civilians. The mortality rate was significantly greater in patients with head and neck wounds (N = 271, 40.0%) than in those with injuries to the thorax (N = 163, 24.1%) and abdomen (N = 62, 9.2%; p < 0.01 for both). During treatment, 188 patients (2.4%) died of wounds (DOW). The DOW mortality was 5.2% (61 of 1,185), 4.0% (41 of 1,026), and 2.9% (25 of 867) for wounds of the head and neck, thorax, and abdomen, respectively. There was no significant difference in the mortality rate between head and neck and thorax wounds: however, the former exceeded the mortality rate recorded for abdominal wounds (p < 0.05). No significant differences were observed between soldiers and civilians with head and neck injuries either in the KIA (205 of 1,176, 17.4% vs. 66 of 280, 23.5%, respectively) or the DOW group (51 of 971, 5.3% vs. 10 of 214, 4.7%, respectively. According to the mechanism of head and neck wounding, there were 1,046 explosive (71.9%), 226 gunshot (15.5%), and 184 other (12.6%) wounds. Lethal outcome was significantly more common in gushot than in explosive wounds (79 of 226, 35% vs. 243 of 1,046, 23.2%; p < 0.01). The proportion of head and neck injuries did not differ significantly from literature reports on recent conventional wars. The site of wounding, i.e., at the battlefield or elsewhere, had no effect on the prognosis of wounds to the head and neck. Gunshot head and neck injuries showed a significantly higher mortality rate.

Abdominal Injuries↗

Influence of nasal fontanel receptors on the regulation of tracheobronchal vagal tone.

AIM: To test the hypothesis according that the receptors located in the nasal fontanels influence the regulation of the tracheobronchial tree vagus tone. METHODS: Changes in respiratory parameters (forced expiratory volume in the first second- FEV1 and total resistance- Rt) occurring consequentially to light mechanical nasal stimulation were determined in healthy volunteer, non-smokers using spirometric and body plethysmographic measurements. The parameters were measured before and at 15 and 60 min after mechanical stimulation with cotton pledge. RESULTS: In subjects in whom the middle nasal meatus was stimulated by a cotton pledge soaked in saline, FEV1 decreased (p=0.01) and Rt increased (p=0.03). In subjects in whom the middle nasal meatus was stimulated by a cotton pledge soaked in 5% cocaine solution, no change was observed. In the control group of subjects, in whom the inferior nasal concha was stimulated by a cotton pledge soaked in saline, only a statistically significant decrease for FEV1 (p=0.04) was found. CONCLUSION: There is a reflex communication between the nasal fontanel receptors and lungs, which is regulating the tracheobronchial vagal tone and resistance in lung airways. Further studies of this important physiologic relation are needed.

Administration, Intranasal↗

Glutathione S-transferase activity as an early marker for malignant tumors of corpus uteri.

Glutathione (GSH) concentrations and glutathione S-transferase (GST) activities were determined in 30 paired malignant human corpus uteri tumor samples and in samples of adjacent normal tissues. For GSH concentrations no difference was found between normal (126.0 +/- 52.4 nmol/mg protein) and tumor tissues (110.1 +/- 46.4 nmol/min/mg protein; p = 0.219). The GST activities were significantly higher in tumor tissues (322.4 +/- 135.54 nmol/min/mg protein) than in corresponding normal tissues (224.6 +/- 95.64 nmol/min/mg protein; p = 0.005). This activities were independent on the pathohistological and clinical factors, except for positive lymphovascular invasion and myometrial invasion (over 50%), where significantly lower GST activities were found. For normal tissues the positive correlation between GSH concentrations and GST activities was found (correlation coefficient = 0.50, p = 0.005), but not for tumor tissue (correlation coefficient = 0.20, p = 0.281). The prognosis of patients (according to the well established prognostic factors, such as tumor type, myometrial invasion and grades) who had lower GSH concentration and GST activity in normal tissue was similar to those with higher GSH concentration and GST activity. In conclusion, higher GST activities found in tumor of corpus uteri suggest, that GST activity could be used as a tumor marker for the early stages of these malignant tumors.

Adult↗

Acute laryngeal trauma: a comparison between peace time and war injuries.

Thirty-six patients with acute laryngeal trauma are presented. Sixteen patients had peace-time and 20 had war injuries. Peace-time injuries were mostly due to car accidents, violence and suicide using a knife, whereas the war injuries were caused by shell and mine fragments. Nine patients were treated conservatively (eight peace-time and one war-time) and 27 by surgery (eight peace-time and 19 war-time). Surgical experience showed that acute laryngeal trauma must be treated within the first 24 hours after injury. Primary treatment must be a definite one. In that way complications and uncontrolled healing can be successfully avoided.

Accidents, Traffic↗

Cardiac myxoma: diagnostic approach, surgical treatment and follow-up. A twenty years experience.

At the University Department of Cardiovascular Surgery in Zagreb, Croatia, we treated 81 patients with primary intracardiac myxoma, in a period from January 1975 to December 1994. There were 55 female and 26 male pts, in age from 1 month to 80 years, mean 46+/-15 years. Clinical manifestations varied from no symptoms and very poor or no clinical signs to various manifestations of chronic or acute congestive heart failure, syncope and arrhythmias with or without systemic findings such as high erythrocyte sedimentation rate, anaemia, leucocytosis, elevated gamma globulin, thrombocytopenia or low grade fever, as well as cerebrovascular accidents due to tumour embolization. Cardiac symptoms were predominant in 54 pts (66.6%) and cerebrovascular in 20 pts (24.7%). Seven pts (8.6%) were symptomless and discovered accidentally, mostly regarding on an unexplained heart murmur. In almost all the patients preoperative diagnosis of intracardiac myxoma was sufficiently established by echocardiography. The tumour was located in the left atrium in 62 pts (76.5%) and in the right atrium in 19 pts (23.5%). Delay from the onset of symptoms to the diagnosis was 6 months in average (range 10 days to 25 months). The average waiting for the operation was 9 days (range from 1 to 60 days). The echocardiographic diagnosis was confirmed during intraoperative examination followed by histological analysis. All pts underwent excision of myxoma using cardiopulmonary bypass with core and topical hypothermia and cold crystaloid cardioplegia. According to the additional preoperative and intraoperative findings, in 6 pts sinchronous mitral valve reconstruction, in 3 pts artificial mitral valve implantation and in 2 pts atrial wall reconstruction was performed. There was no perioperative mortality. After the operation, we could not evaluate all the patients long enough, mostly because of some paramedical circumstancies, such as war, migrations, etc. Twenty two pts undevent evaluation for at least 5 years after the operation. Among them there was no evidence of the tumour recurrence, 15 pts were asymptomatic and 7 had NYHA II class symptoms. For 17 pts with a left atrial myxoma preoperative and postoperative echocardiographic data were available for comparison, showing a significant reduction of the left atrial diameter (p<0.001) during the postoperative follow-up. Our data, presenting one of the biggest reports concerning cardiac myxomas, showed a broad spectrum of their clinical presentation, importance of echocardiography in diagnosing and postoperative follow-up and efficacy of a proper surgical intervention as a definite, curative therapy since there were no deaths and no significant cardiac dysfunction neither tumour reccurrence as well.

Croatia↗

Reconstruction of laryngotracheal war injuries with the median layer of the deep cervical fascia.

Surgical exploration and immediate reconstruction with the median layer of the deep cervical fascia (MLDCF) was performed in 8 of 22 patients with exogenous war injuries of larynx and cervical trachea. A surgical technique of reconstruction with the median layer of the deep cervical fascia is described. The 7 surviving patients had good respiration without signs of stenosis of the larynx and/or the trachea. Four had good and 3 satisfactory, phonation, and none had swallowing difficulties. Owing to the simplicity of the surgical approach, its size and biological properties, the median layer of deep cervical fascia proved itself to be a suitable material in the immediate reconstruction of exogenerous war injuries of the larynx and cervical trachea.

Adolescent↗