Mariusz Gadzicki

Switching to Sulphonylureas in Children With iDEND Syndrome Caused by KCNJ11 Mutations Results in Improved Cerebellar Perfusion

OBJECTIVE Activating mutations in the KCNJ11 gene, encoding the Kir6.2 subunit of the KATP channel, result in permanent neonatal diabetes mellitus. They also may cause neurologic symptoms such as mental retardation and motor problems (iDEND syndrome) and epilepsy (DEND syndrome). Sulphonylurea (SU) treatment is reported to alleviate both the neurologic symptoms and diabetes in such cases. The study aimed to establish the magnitude and functional basis of the effect of SUs on the neurologic phenotype in children with iDEND using neuroimaging before and after insulin replacement with glibenclamide. RESEARCH DESIGN AND METHODS To localize and quantify the effect of glibenclamide administration, we performed single-photon emission computed tomography in seven patients with different mutations in KCNJ11. In five patients, measurements before and after initiation of SU treatment were performed. RESULTS Significant changes in single-photon emission computed tomography signal intensity after transfer to SU therapy were restricted to the cerebellum, consistent with previous data showing high Kir6.2 expression in this brain region. Cerebellar perfusion improved for both left (P = 0.006) and right (P = 0.01) hemispheres, with the mean improvement being 26.7 ± 7.1% (n = 5). No patients showed deterioration of cerebellar perfusion on SU therapy. Electrophysiological studies revealed a good correlation between the magnitude of KATP channel dysfunction and the clinical phenotype; mutant channels with the greatest reduction in adenosine 5′-triphosphate inhibition were associated with the most severe neurologic symptoms. CONCLUSIONS We conclude it is likely that at least some of the beneficial effects of SU treatment on neurodevelopment in iDEND patients result from improved cerebellar perfusion.

Progression of diabetic retinopathy correlated with muscle perfusion disturbances of the lower limbs, with clinically important diagnostic recommendations

Introduction The objective of this study was to investigate the relationship between microvascular and macrovascular disturbances in patients with type 2 diabetes, as shown by results of ophthalmological examination and by vascular and perfusion examinations of the lower limbs. Material and methods A total of 85 patients with type 2 diabetes and an additional cardiovascular risk factor were enrolled in the study. All patients underwent complex ophthalmological examination, including fundus colour photography and fluorescein angiography, and were divided into two groups: group I with signs of diabetic non-proliferative retinopathy (NPDR), and group II with signs of diabetic proliferative retinopathy (P/PDR). After collection of the general medical history and analysis of medical data, patients underwent vascular and muscle perfusion examination of the lower limbs. Results In the P/PDR group, disturbances of lower-limb perfusion were more frequent than in the NPDR group. Analysis of the blood flow and results of lower-limb muscle perfusion for the two groups showed a significant relationship with the severity of microvascular complications observed in examination of the fundus. Conclusions Ophthalmological assessment of the progression of diabetic retinopathy in patients with type 2 diabetes is a reliable indicator of the changes in peripheral vessel systems and perfusion defects in the lower limbs.

Bone metabolism assessment, bone metabolism index designation and the determination of its normal values range in young healthy women.

Summary Background Bone metabolism assessment requires the determination of bone mass and quality. The bone metabolism was assessed with the modified bone scintigraphy using 99mTc-MDP. The elaboration of radioisotopic method and program allowed for the assessment of bone metabolism, index of bone metabolism assay and definition of its normal values range with the possibility of clinical application. Material/Methods We examined 70 healthy young women with normal BMI, in which bone system was assessed with scintigraphic and densitometric examinations, and bone turnover markers definition together with hormonal and biochemical blood tests were performed. Group exclusion examinations were also performed, including basic, biochemical and hormonal blood tests, bone turnover markers and densitometric examinations with DXA technique. The scintigraphic examinations were performed using a gamma camera after 99mTc-MDP injection. After the application of the BONS method and program, the normal values range was determined with the STATISTICA 8 program. Results The normal results of basic, biochemical, hormonal and vascular tests were obtained. The examinations of bone turnover markers confirmed the balance between bone formation and bone resorption processes. The normal results of densitometric examinations excluded osteopeny or osteoporosis. The normal values range of IBM in young healthy women was between 84.08 and 105. Conclusions The elaborated BONS program and method allow for the quantitative assessment of bone quality and definition of IBM normal values range. The quantitative scintigraphic bone examinations provide an alternative to the bone markers examination for obtaining information about bone metabolism.

The assessment of testosterone and radioisotopic index of bone metabolism and bone mineral density in men with testosterone deficiency after one year of testosterone therapy

BACKGROUND Testosterone deficiency in men is characterized by typical symptoms of hypogonadism and negative influence on the preservation of bone mass. In this study, we analysed the relationship between testosterone concentration and bone metabolism. Moreover, we assessed the impact of one-year compensation of testosterone deficiency in elderly men on bone metabolism and bone mineral density. Radioisotopic methods of bone metabolism assessment provide new research opportunities. MATERIALS AND METHODS Men with total testosterone concentration (TT) ≤ 3 ng/ml were included into this study. Patients with disorders or injuries of bone system, elevated prostate-specific antigen (PSA), enlarged prostate, disorders of thyroid and liver, diabetes mellitus or a history of chemotherapy as well as those treated for a long time with antibiotics were excluded from this study. The results of 50 men aged 57.52 ± 6.71 years obtained before the treatment (I test) and after one year of oral testosterone supplementation (test II) were analysed in this study. The following examinations and analyses were performed: interview and physical examination, orthopaedic, neurological and urological consultations, blood biochemistry, determination of hormones levels, assessment of Testosterone Deficiency Syndrome (TDS), densitometric and radioisotope assessment of bone metabolism. Moreover, radioisotopic index of bone metabolism was calculated. Testosterone therapy with oral preparation Undestor Testo Caps (Organon) containing 40 mg of testosterone lasted for 12 months. Statistical analysis was performed using Statistica 12 and Excel 2010 programs. Correlations between results before and after treatment were analysed. RESULTS After 12 months of treatment, testosterone concentration increased by mean 78% and the level of luteinizing hormone (LH) decreased by 62%. TDS index increased from 0.53 ± 0.21 (in test I) to 1.91 ± 0.60 (in test II). After the therapy this index was significantly higher in all men (p < 0.0001). Moreover, BMD was also improved following therapy, however, the difference between test I and II was statistically insignificant. The greatest change was found in case of IBM (Index of Bone Metabolism). We observed a positive correlation between IBM and BMD before treatment (r = 0.7991), however, its strength decreased after one-year therapy (r = 0.6757). CONCLUSIONS In our opinion, IBM is more sensitive than other methods of the assessment of changes occurring in bone system under the influence of testosterone therapy. The observed changes in IBM were proportional to changes in testosterone concentration. Testosterone level, TDS and radioisotopic assessment of bone metabolism may be used as prognostic and therapeutic factors of osteoporosis and bone fractures in elderly men.

Radioisotopic assessment of bone metabolism of the operated vertebra after inter-process stabilizer implantation in the lumbar segment of the spine

Introduction Lack of efficacy of pharmacotherapy and physiotherapy in spinal pain syndrome is an indication for intervertebral stabilizer implantation between the processes in the lumbar segment of the spine. Material and methods The group consisted of 32 patients qualified after radioisotopic single-photon emission computed tomography/computed tomography (SPECT/CT) examinations with assessment of bone metabolism and mineral density. For comparative purposes, the L2 vertebra was defined as normal. Parameters defined in the area of operated vertebrae were comparable to L2. Imaging examinations and a pain intensity test were performed before and 12 months after the procedure. Results In SPECT, osteotropic isotope (OI) activity in spinous bodies and processes was close to L2 values. Density assessed in CT of analysed vertebrae was close to L2. In the control examination, activity of OI in spinous bodies and processes was higher in the procedure area. Under the stabilizer, there was a strong positive correlation with the L2 parameters. The differences were statistically significant (p = 0.0002). The increase of OI activity in the elements above the stabilizer was variable. In the control examination, there was higher density of spinous processes and bodies above and under the stabilizer. The difference, compared to the L2 density, was statistically significant. Conclusions The radioisotopic method with SPECT/CT allows for the precise assessment of bone metabolism in the spine. After the procedure, a negative correlation was observed between bone metabolism changes and pain intensity test results.

The Influence of the Water Baths with or Without ozone Associated with Kinesitherapy on Lower Limbs Muscles Perfusion in Patients with Gonarthrosis

Introduction: Ozone therapy is a frequently applied physiotherapy method. There are reports that ozone has a wide spectrum of possible effects. Aim: The aim of the study was to examine a possible influence of the water baths with ozone on lower limbs muscles perfusion in patients with gonarthrosis. Materials and methods: 30 patients (mean age 62,3±11,0 years) with gonarthrosis (II-III degree according to Seyfried’s scale) were included in the study. The patients were assigned to three groups: • Group A (10pts) – water massages with ozone + exercises (kinesitherapy) were applied in this group • Group B (9pts) – water massages without ozone + exercises (kinesitherapy) were applied • Group C (11pts) – kinesitherapy alone was applied. All the patients realized the same kinesitherapy program. Radioisotopic examinations of the lower limbs muscles perfusion in rest were performed before and after the treatment. Results: the study revealed a significant lower limbs muscles perfusion increase in the group A (water massages with ozone were applied in this group). A slight perfusion increase was also observed in other groups (B and C) but the differences were not statistically significant. No patient had any adverse reaction after the applied treatment. Conclusions: The study revealed a significant lower limbs muscles perfusion increase after hydrotherapy with ozone procedures. The results confirm that ozone has a positive influence on microcirculation. Ozonetherapy can be recognized as a safe method as no adverse reactions during and after the treatment were observed in the study.