Chemotherapy-Induced Peripheral Neuropathy (CIPN) in Patients Receiving 4-6 Cycles of Platinum-Based and Taxane-Based Chemotherapy: A Prospective, Single-Center Study from Kosovo.

BACKGROUND Chemotherapy-induced peripheral neuropathy (CIPN) is most commonly associated with platinum-based drugs, taxanes, and vinca alkaloids. This prospective study from a single center in Kosovo aimed to evaluate CIPN in 120 patients receiving 4-6 cycles of platinum-based and taxane-based chemotherapy. MATERIAL AND METHODS One hundred twenty patients underwent neurological examination and nerve conduction studies (NCS) before chemotherapy, and after 4 to 6 cycles of treatment. Sixty patients were treated with platinum-based chemotherapy, 30 were treated with taxane-based chemotherapy, and 22 patients received a combination of platinum- and taxane-based chemotherapy. The most commonly used platinum-based compounds were oxaliplatin and carboplatin, whereas the most commonly used taxane medications were paclitaxel and docetaxel. Presence of neuropathy was confirmed with neurological examination of electrophysiological criteria applicable for polyneuropathies. Total Neuropathy Score (TNSr) was used to combine clinical and electrophysiological values. RESULTS Around 90% of patients self-reported neuropathic symptoms, and in 60% of them polyneuropathy was present in NCS. All sensory and motor nerves had significantly lower amplitudes (P<0.01). Platinum-based agents caused more pronounced decrease in ulnar nerve compound motor action potential (CMAP) (P<0.05); when used solely or in combination with taxanes, they caused significant decrease in tibial nerve CMAP (P<0.01). TNSr did not reach statistical significance between groups; only clinical muscle strength showed pronounced weakness in the combined protocol (P<0.05). CONCLUSIONS These findings support previous studies and show that CIPN, including sensory and motor symptoms, is commonly associated with chemotherapy. Platinum-based chemotherapy agents were more commonly associated with ulnar and tibial nerve damage in this study population.

Availability of technology for managing cancer patients in the Southeast European (SEE) region.

Background: The Southeast European (SEE) region of 10 countries and about 43 million people differs from Western Europe in that most SEE countries lack active cancer registries and have fewer diagnostic imaging devices and radiotherapy (RT) units. The main objective of this research is to initiate a common platform for gathering SEE regional cancer data from the ground up to help these countries develop common cancer management strategies. Methods: To obtain detailed on-the-ground information, we developed separate questionnaires for two SEE groups: a) ONCO - oncologists regarding cancer treatment modalities and the availability of diagnostic imaging and radiotherapy equipment; and b) REG - national radiation protection and safety regulatory bodies regarding diagnostic imaging and radiotherapy equipment in SEE facilities. Results: Based on responses from 13/17 ONCO participants (at least one from each country) and from 9/10 REG participants (all countries but Albania), cancer incidence rates are higher in those SEE countries that have greater access to diagnostic imaging equipment while cancer mortality-to-incidence (MIR) ratios are higher in countries that lack radiotherapy equipment. Conclusion: By combining unique SEE region information with data available from major global databases, we demonstrated that the availability of diagnostic imaging and radiotherapy equipment in the SEE countries is related to their economic development. While immediate diagnostic imaging and radiation therapy capacity building is necessary, it is also essential to develop both national and SEE-regional cancer registries in order to understand the heterogeneity of each country's needs and to establish regional collaborative strategies for combating cancer.

Dermatoglyphics and Reproductive Risk in a Family with Robertsonian Translocation 14q;21q.

AIM: The present study is carried out to evaluate the risk of giving birth to children with Down syndrome in a family with Robertsonian translocation 14q;21q, and to find the dermatoglyphic changes present in carriers of this translocation. METHODS: Cytogenetics diagnosis has been made according to Moorhead and Seabright method, while the analysis of prints (dermatoglyphics analysis) was made with the Cummins and Midlo method. RESULTS: Cytogenetic diagnosis has been made in a couple who suffered the spontaneous miscarriages and children with Down syndrome. Robertsonian translocation between chromosomes 14 and 21 (45, XX, der (14; 21) (q10; q10)) was found in a female partner who had four pregnancies, in two of which was found fetus karyotype with trisomy in chromosome 21 and pregnancies were terminated. The outcome of fourth pregnancy was twin birth, one of them with normal karyotype and another with Down syndrome due to Robertsonian translocation inherited by mother side. Specific dermatoglyphics traits are found in the child carrying Down syndrome, whereas several traits of dermatoglyphics characteristic of Down syndrome have been displayed among the silent carriers of Robertsonian translocation 14q;21q. CONCLUSION: Robertsonian translocation found in female partner was the cause of spontaneous miscarriages, of giving birth to a child with Down syndrome, and of trisomy of chromosome 21 due to translocation in two pregnancies.

The effect of aerobic exercise on quality of life among breast cancer survivors: a randomized controlled trial.

OBJECTIVE: To determine the effect of moderate-intensity aerobic exercise on the quality of life (QOL) and physical functioning in breast cancer survivors. MATERIALS AND METHODS: We randomly assigned 62 breast cancer survivors to an exercise (N = 30) or control group (N = 32). The exercise group trained at a moderate intensity progressing from 25 to 40 min over a 10-week period. The control group did not train. Outcomes were assessed at baseline and postintervention. The primary outcomes were overall QOL--as assessed by the functional assessment of cancer therapy-breast (FACT-B) scale. Secondary outcomes were changes in various subscales of overall QOL, and changes in body composition outcomes: body weight, body mass index, and changes in performance in a 12 min walk test (12MWT). RESULTS: Sixty-two of 73 women randomized (84.9%) completed the study. There were no significant differences amongst the two groups at baseline for any variable. In the exercise group significant improvements were demonstrated for the FACT-B (13.4 points, P < 0.003), functional assessment of cancer therapy-general (FACT-G) (9.16 points, P < 0.008), the functional well-being subscale (P < 0.010), and the emotional well-being subscale (P < 0.035) compared to the control group. No significant changes in body weight or BMI were observed. Exercise group showed a significant increase in 12MWT (P < 0.009). CONCLUSION: We conclude that 10 week of moderate-intensity aerobic exercise program significantly improves QOL and physical functioning in breast cancer survivors. Future studies are needed to evaluate the effectiveness of similar exercise programs over longer periods of time and involving a greater number of breast cancer survivors.

Gender related predictors of limited exercise capacity in heart failure.

AIM: The aim of this study was to investigate the impact of gender on the prediction of limited exercise capacity in heart failure (HF) patients assessed by 6 minute walk test (6-MWT). METHODS: In 147 HF patients (mean age 61 ± 11 years, 50.3% male), a 6-MWT and a Doppler echocardiographic study were performed in the same day. Conventional cardiac measurements were obtained and global LV dyssynchrony was indirectly assessed using total isovolumic time - t-IVT [in s/min; calculated as: 60 - (total ejection time - total filling time)] and Tei index (t-IVT/ejection time). Patients were divided into two groups according to gender, which were again divided into two subgroups based on the 6-MWT distance (Group I: ≤ 300 m, and Group II: > 300 m). RESULTS: Female patients were younger (p = 0.02), and had higher left ventricular (LV) ejection fraction - EF (p = 0.007) but with similar 6-MWT distance to male patients (p = 68). Group I male patients had lower hemoglobin level (p = 0.02) and lower EF (p = 0.03), compared with Group II, but none of the clinical or echocardiographic variables differed between groups in female patients. In multivariate analysis, only t-IVT [0.699 (0.552-0.886), p = 0.003], and LV EF [0.908 (0.835-0.987), p = 0.02] in males, and NYHA functional class [4.439 (2.213-16.24), p = 0.02] in females independently predicted poor 6-MWT distance (< 300 m). CONCLUSION: Despite similar limited exercise capacity, gender determines the pattern of underlying cardiac disturbances; ventricular dysfunction in males and subjective NYHA class in female heart failure patients.

Research on alteration of neurons in vagal nuclei in medulla oblongata in newborns with respiratory distress.

Neuronal and axonal degenerative changes in motor vagal neurons (DMNV) and sensory vagal neurons (nTS) in the medulla oblongata in newborns were studied. Material was taken from the autopsies of newborns, live and dead newborns, in different gestational weeks (aborted, immature, premature and mature). 46 cases were studied. Material for research was taken from the medulla oblongata and lung tissue. Serial horizontal incisions were made in the medulla oblongata (± 4 mm), commencing from the obex, where the DMNV and nTS vagal nuclei were explored. Fixed cuttings in buffered formalin (10%) were used for histochemical staining. Serial cuttings were done with a microtome (7 µm). Pulmonary infections, being significant (p < 0.05), have an important place when studying respiratory distress (RD) in newborns. Morphological changes of nerve cells in DMNV and nTS nuclei in the medulla oblongata in newborns in different gestational weeks are more emphasized in matures in comparison to aborted and immature (p < 0.05). Depending on the lifetime of dead newborns, neuronal morphological changes in vagus nerve nuclei are significant (p < 0.05). Therefore, it can be concluded that pulmonary infections are often caused due to dramatic respiratory distress in newborns, while hypoxaemic changes in the population of vagus nerve neurons in respiratory distress are more emphasized in matures.

Phentolamine action in permeability of airways at patients with bronchial asthma.

In this work, effect of phentolamine as antagonist of alpha-1 adrenergic receptor in patients with bronchial asthma and with obstructive chronic bronchitis was studied. Parameters of the lung function are determined by body plethysmography. Raw and ITGV were registered and SRaw was calculated as well. Aerosolization is done with standard aerosolizing machines--Asthma with a possibility of aerosolization of 0.5 ml per minute. Results gained by this research shows that blockage of alpha-1 adrenergic receptor with phentolamine (10 mg by inhalator and intravenous ways and 20 mg by inhalator ways) has not changed significantly (p > 0.1) the bronchomotor tonus of tracheobronchial tree, by comparing it with the inhalation of natrium chloride solution with percentage of 0.9% (p > 0.1), or of hexoprenaline (2 inh x 0.2 mg) and atropine 1 mg/ml (p < 0.01). This suggests that the activity of alpha-1 adrenergic receptor in the smooth musculature is not a primary mechanism that causes reaction in patients with increased bronchial reactibility, in comparison to agonists of beta2--adrenergic receptor and cholinergic antagonists that expresses their significant action in reduction of specific resistance of airways.

The study of volume density of tracheal ganglions in vitro in new born babies with respiratory distress syndrome.

Volume density of respiratory organs was studied in vitro in newborn babies at different age of gestation (abort, immature, premature and mature) using stereometric method. The total of 23 cases was subject to this study. The respiratory organs (trachea, lungs) were taken from autopsies of newborn babies exited from different causes. For this purpose the tissues were fixed in formalin (10%) solution, cut serially in 7micro and 10micro slabs. Volume density of the respiratory system was assessed stereometricaly using Universal testing system Weibel M 42. We observed that volume density of epithelia, musculature and glands were proportionally present in the tracheal tissue. Cellular interstitial tissue is consistently increasing and corresponds to the developmental stages of the newborn babies. The density of tracheal ganglions is greater in premature ages of immature and premature newborns (p<0,05). Decreased number of ganglion cells is observed in mature ages (p<0,05). This is caused by intensive ramification of ganglions from serosa to deeper layers of trachea right to epithelium. Medium diameter of tracheal ganglions is greater in mature newborn babies and corresponds to developmental ages of babies.

Role of meconium in the reaction of airways smooth musculature in the newborn with meconium aspiration syndrome (MAS).

The role of meconium in the respiratory system was studied in newborns, who died from various causes (250 up to 3000 g of weight). We monitored tracheal rings response to dopamine, serotonin and ethanol in different concentrations (dopamine: 0,05 mg/ml, 0,5 mg/ml, 5 mg/ml; serotonin (5-HT): 10-4, 10-3, 10-2, 10-1 mol/dm3; ethanol: 0,02 ml, 0,5 ml, 1,0 ml; 96%). Tracheal smooth musculature tonus (TSM) was examined in 48 tracheal preparations taken after the newborn exitus due to different reasons. Based on functional researche of isolated preparations of tracheas, it may be concluded that: aspiration of meconium has not changed the response of TSM to dopamine, serotonin and ethanol (p>0,1) in comparison with the control group, which have died due to different lung inflammatory processes (e.g. pneumonia, bronchopneumonia, atelectasis, cerebral hemorrhage). The results suggest that meconium does not potentiate the constricting action of dopamine, serotonin and ethanol in tracheobronchial system. Meconium causes mild relaxation of the TSM through a mechanism that is not intermediated by the products of cyclooxygenases (prostaglandins, prostacyclins) from the tracheal epithelium or proteins. Also, as it seems, the direct activity of many tested acids in the smooth musculature has no significant impact on increase of the airways tonus in MAS syndrome.