[Importance of mathematical analysis of the retinal image in diabetic retinopathy]. / Význam matematického zpracování obrazu sítnice u diabetické retinopatie.

The authors test whether for evaluation of the severity of diabetic retinopathy it is possible to use the method of computer assisted mathematical processing of the retinal image. This method is based on the identification of vascular endings in the visualized part of the retina. It is assumed that with the severity of the finding the number of vascular endings increases in conjunction with the process of neogenesis. For assessment of the number of vascular endings the authors use the Adaptive Contrast Control (ACC) method. By a special procedure the vascular endings are identified and their number is assessed in the investigated area of the retina. The method makes it possible to assess in addition to the number of vascular endings also the total length of the vessels, their volume, surface, area they cover and the histogram of the diameter of the vessels. The authors examined 19 patients (38 eyes) with a quite normal finding on the retina. The mean age of the group was 37.3 years. Moreover they examined 10 patients (20 eyes) with middle advanced and advanced non-proliferative diabetic retinopathy and 10 patients (20 eyes) with risk proliferative diabetic retinopathy. In every patient a standard digital photograph of the fundus of both eyes size "tif" was made and each picture was subjected to mathematical analysis. The group of patients was divided into three sub-groups (patients with a normal finding, a non-proliferative finding and a finding of proliferative diabetic retinopathy). In the conclusion the authors provide evidence that with increasing severity of the finding on the retina also the number of vascular endings increases.

Duration of non-Insulin-dependent diabetes mellitus and the TNF-beta NcoI genotype as predictive factors in proliferative diabetic retinopathy.

The object of the study was to investigate the share of the polymorphisms I/D ACE, endothelin 1 4127G/A and TNF-beta NcoI in the susceptibility to proliferative diabetic retinopathy (PDR) in non-insulin-dependent diabetes mellitus (NIDDM). Genotypes were detected by polymerase chain reactions and determined in a set of 246 Caucasian NIDDM subjects with defined PDR status. The relevance of genotypes and clinical characteristics to the PDR occurrence was tested using multiple linear regression models and discrimination analysis. The best predictive value for PDR was given by a combination of two parameters - NIDDM duration and the TNF-beta genotype (p < 1.10(-6) and p = 1.10(-2), respectively) with a correct retrograde prediction of 82.6%. A comparison of the TNF-beta NcoI allele frequencies revealed no difference between NIDDM and nondiabetic subjects (n = 176), but a statistically significant difference was found between PDR and non-PDR NIDDM subjects (after a correction for the number of comparisons p = 0.03), allele beta2 being associated with PDR. Our results identified the allele variant TNF-beta2 being associated with PDR in NIDDM. Diabetes duration and the TNF-beta NcoI genotype were proven to significantly predict PDR occurrence. The TNF-beta2 allele could be regarded as a separate genetic risk factor that increases the relative incidence of PDR in patients with NIDDM.

Association analysis of 24-h blood pressure records with I/D ACE gene polymorphism and ABO blood group system.

The purpose of this study was to analyze the association between 24-h blood pressure parameters, insertion/deletion polymorphism of the angiotensin I converting enzyme gene and the ABO blood group system in a sample of the general Czech population. Fourteen parameters describing the 24-h blood pressure readings were obtained by analyzing blood pressure records in 243 volunteers, 119 men and 124 women. These parameters were adjusted for sex and body mass index (BMI) by means of multiple regression test. All subjects were genotyped for the insertion/deletion polymorphism of angiotensin I converting enzyme (I/D ACE) gene and routinely examined for the blood group phenotype in the ABO system. An association was found between the interaction of I/D ACE gene polymorphism and ABO blood group system on the one hand and mean values of systolic (p=0.016) or mean arterial (p=0.027) blood pressures and the phase shift of 24-h BP rhythm (p=0.036) on the other hand. Among three I/D ACE variants the DD genotype was associated with the highest values of mean blood pressure in blood group A and AB carriers. The same genotype was associated with the lowest blood pressures in blood group B and O carriers. In subjects with the DD genotype, the earlier daily position of the maximum of 24-h BP rhythm was found in blood group B, AB and O carriers. On the contrary, blood group A was associated with the latest position of maximum of the 24-h BP rhythm in the DD genotypes.

Bone marrow as multidimensional orbit oscillator after autologous bone marrow transplantation.

The local renin-angiotensin system (RAS) in bone marrow is probably involved in the control of hematopoiesis. Earlier observations suggest the relationship between the frequency of sodium and potassium concentration changes in urine and bone marrow recovery after chemotherapy. The purpose of this study was to prove the relationship between sodium and potassium excretion changes in urine and granulocyte counts in peripheral blood after autologous bone marrow and peripheral blood stem cell transplantation. The correlation between amplitude maximum FFmax of F=d[Na]/d[K], where d[Na] and d[K] are changes of sodium and potassium excretions in 24 h, and granulocytes, recorded k days later, was found in 12 patients with autologous bone marrow transplantation (BMT) and/or PBSCT. In patients with successful engraftment, k ranged from 4 to 7 days. In the patient with unsuccessful BMT, k was 12 days. The results imply the interaction between systemic and bone marrow RAS.

Angiotensin I-converting enzyme and angiotensinogen gene interaction and prediction of essential hypertension.

To prove whether the interaction between insertion/deletion (I/D) angiotensin I converting enzyme (ACE) and M235T angiotensinogen (AGT) gene polymorphic alleles could contribute to causing essential hypertension, we examined subjects from the Czech Republic (365 Caucasians total; 202 normotensives and 163 hypertensives). Subjects were genotyped for insertion/deletion polymorphism of ACE (I/D ACE, intron 16) and for M235T polymorphism of angiotensinogen gene (AGT, exon 2) by means of the polymerase chain reaction (PCR) method. The case-control approach was used. Fisher's exact test followed by Holmes's test to overcome the problem of multiple comparisons were used for the statistical analysis of data. No association of single gene allelic variants with essential hypertension was found in our population. Having compared only double homozygote combinations, the association of the DDMM genotype with essential hypertension was proven (P = 0.0081). To the contrary, IITT (P = 0.0086) was found more frequently in normotensive subjects. We conclude that the interaction of the I/D ACE and M235T AGT polymorphic alleles can contribute to essential hypertension, despite the absence of single gene associations with the condition.

Lung diffusion estimated by oxygen and carbon monoxide.

The study was objected to the comparison of the results of lung diffusion estimated by oxygen to those of routinely used single breath carbon monoxide method. The method described is based on the analysis of the speed of response of arterial partial oxygen pressure (paO2) to increasing inspiratory fraction of oxygen (Fi). The transcutaneous oximetry was used to follow paO2 by means of transcutaneous oxygen pressure (ptCO2). The study was performed on 35 patients of both sexes with interstitial lung involvement with normal or only slightly decreased FVC and FEV1. The close correlation between the results of both methods was proved (r = 0.848, p < 0.0001).

[The effect of clodronate on bone density in patients with multiple myeloma--a 2-year follow-up of therapeutic effects]. / Vliv clodronátu na kostní denzitu pacientu s mnohocetným myelomem--dvouleté sledování lécebného úcinku.

Biphosphonates are used for the treatment of hypercalcaemia as well as in normocalcaemic patients for the long-term inhibition of malignant osteolytic bone processes. In patients with multiple myelomas treated with biphosphonates in randomized studies a reduction of the number of new osteolytic foci was proved and improvement of the quality of life. The objective of the present study was to evaluate the effect of clodronat on the development of bone density in patients with multiple myeloma. In the study since 1993 27 patients were included. In August 1995 22 patients were evaluated who were treated for more than 12 months with clodronat (Bonefos Leiras). The patients were given clodronat in i.v. infusions (five infusions à 600 mg) in three-month intervals. After six-month intervals the amount of hydroxyapatite in the lumbar vertebrae was evaluated by CT densitometry. Statistical testing of trends of assessed bone density values revealed that not even after two years of the disease a statistically significant reduction of the bone density occurs. Treatment was very well tolerated, gastrointestinal problems were an exception. At the onset of the investigation three patients had symptoms of mild tetany, and a decline of the calcaemia below normal values was recorded. As soon as regular administration of calcium preparations was started during clodronat administration, the calcaemia did not decline below normal levels and enhanced neuromuscular irritability did not develop. Clodronat stabilizes the amount of bone mass, reduces pain and also improves the quality of the patients life. It should be included among standard treatment of patients with multiple myeloma.

Increasing bone density in myeloma patients after the administration of clodronate.

The use of bisphosphonates in hypercalcemia is fully accepted, but the long term therapy with bisphosphonates is still controversial. The aim of our study was to evaluate the influence of clodronate on the bone density of myeloma patients. 20 patients were included in the study. A total dose of 3000 mg clodronate was administered in 4 to 6 hourly infusions of 600 mg a day, once in 3 months. The effect of clodronate on bone density was evaluated by CT-densitometry over a period of 6 months. At the beginning of May 1994, 15 patients had completed at least 2 estimations of bone density. The amount of hydroxyapatite had increased in 9 patients, remained unchanged in 1 of them, and decreased in 4 of them during the 6 months. The mean bone density before the administration of clodronate was -2.6 SD (standard deviation of European standard bone density for the respective age and sex). After 6 months of therapy, bone density had increased to -2.3 SD. The mean amount of hydroxyapatite in spongiosa rose from the mean value of 32.71 mg/ml before clodronate administration to 38.91 mg/ml after the 6-month treatment period. The mean increase in calciumhydroxyapatite in trabecular bone mass was 6.2 mg. Clodronate contributed to alleviating bone pain in the majority of patients, but this effect is difficult to evaluate because of other treatment modalities administered concomitantly. The tolerance of clodronate was very good. No impairments of renal function, nor other adverse effects were observed. Only in 2 patients the decrease in calcium concentration caused slight tetania.(ABSTRACT TRUNCATED AT 250 WORDS)

[Increased bone density in patients with multiple myeloma treated with clodronate]. / Vzestup kostní denzity u nemocných s mnohocetným myelomem lécených clodronátem.

The indication of bisphosphonates in hypercalcemia is fully accepted, the long term therapy with bisphosphonates is still controversial. The aim of our study was to evaluate the influence of clodronate on the bone density of myeloma patients. Twenty patients were included in the study. Clodronate is administered in the total dose of 3,000 mg, which is delivered in 4-6 hour infusions, 600 mg/day, once in tree 3 months. The effect of clodronate on bone density is evaluated by CT-densitometry in a period of 6 months. At the beginning of May 1994, 15 patients had completed at least two estimations of bone density. The amount of hydroxyapatite in these six months increased in 9 patients, in one of them there was no change and in 4 of them decreasing bone density was detected. The mean bone density before the administration of clodronate was -2.6 SD (standard deviation of European standard of bone density for age and sex). After 6 months of therapy the bone density increased to -2.3 SD. The mean amount of hydroxyapatite in spongiosa was raised from the mean value 32.71 mg/ml before clodronate administration to 38.91 mg/ml after the 6 month treatment period. The mean increase in calciumhydroxyapatite in trabecular bone mass was 6.2 mg. Clodronate contributed to the amelioration of bone pain in the majority of patients, but this effect is difficult to evaluate because of other treatment modalities administered concomitantly. The tolerance of clodronate was good. No impairments of renal function or other adverse effects were observed. Only in 2 patients the decrease in calcium concentration caused slight tetania. Therefore close monitoring of the calcium level is recommended and in the case of its decrease below the physiological level peroral substitution of calcium was started.

Treatment of refractory multiple myeloma with vincristine, adriamycin, dexamethasone, and with repeated application of cyclophosphamide (C-VAD).

The quick reduction of differentiated myeloma cells by VAD chemotherapy (vincristine, adriamycin, dexamethasone) causes, according to the investigation by Bell et al., the acceleration of the proliferation of myeloma stem cells. In 1990 Bell demonstrated that this proliferation could be stopped by administering 500 mg of cyclophosphamide in 1-week intervals. We therefore modified the classical VAD scheme to the following "C-VAD" scheme:vincristine 0.5 mg/day in continuous infusion on the first to the 4th day, adriamycin 9 mg/m2/day in continual infusion on the 1st to the 4th day, dexamethasone 40 mg p.o. or i.v. always on 4 days starting with the 1st, 10th and 20th days, cyclophosphamide 600 mg i.v. on the 5th, 10th and 20th days). A further cycle follows on the 28th day. In the present paper the effect and the tolerance of this C-VAD scheme is evaluated: In the group of 21 patients with refractory myeloma 9 remissions were achieved, 5 partial remissions, in 6 patients the disease progressed, 1 patient died after the 2nd cycle without the possibility of evaluating the therapeutic response. The mean remission length was 10.2 months. The tolerance of chemotherapy was satisfactory, C-VAD chemotherapy did not cause any serious drop in the number of leucocytes and thrombocytes. Echocardiographically lower adriamycin cardiotoxicity was demonstrated in continual administration in comparison with the bolus administration. The C-VAD scheme is considered to be suitable for comparison with the VAD chemotherapy in a randomized study.