New potent sensitizers for photodynamic therapy: 21-oxaporphyrin, 21-thiaporphyrin and 21,23-dithiaporphyrin induce extensive tumor necrosis

New sensitizers for photodynamic therapy (PDT) are reported. These compounds, namely 21-thiaporphyrin, 21,23-dithiaporphyrin and 21-oxaporphyrin, reveal some of the properties required for such therapy. Their physicochemical, chemical and pharmacological features meant that we could use them in the treatment of transplantable BFS1 fibrosarcoma in Balb/c mice. New sensitizers and the well-known chlorin e6 (Ce6) were used in doses of 2.5, 5.0, 7.5 and 10.0 mg/kg body weight, given intraperitoneally and followed by light irradiation, the total light doses being 50, 100 and 150 J/cm² within 24 h after injection. The effectiveness of new sensitizers in PDT was evaluated with in terms of tumor necrosis intensity, the survival time of treated animals, the rate of tumor response (complete/partial/no response), and skin photosensitivity. These results were compared to results obtained in analogous conditions after Ce6-PDT. Distribution studies revealed that the highest concentration of new compounds occurred within 24 h after injection. The results of these experiments confirmed that 21-thiaporphyrin, 21,23-dithiaporphyrin and 21-oxaporphyrin can be considered as potent tumor photosensitizers that do not exert any unwanted effects, primarily skin photosensitization. We suggest that these porphyrins are possible sensitizers to be applied in clinical PDT. Received: 17 December 1998 / Accepted: 12 April 1999     

Interindividual variability in the response to oral antiplatelet drugs: a position paper of the Working Group on antiplatelet drugs resistance appointed by the Section of Cardiovascular Interventions of the Polish Cardiac Society, endorsed by the Working Group on Thrombosis of the European Society of Cardiology

Oral antiplatelet drugs are a cornerstone of modern pharmacotherapyin cardiovascular atherothrombotic diseases. The efficacy ofacetylsalicylic acid (ASA, aspirin) and clopidogrel in decreasingthe risk of adverse events in coronary heart disease patientshas been well established in the past 20 years. Despite chronicoral antiplatelet therapy, a number of atherothombotic eventscontinue to occur. In recent years, a number of reports in theliterature have shown possible relationships between residualplatelet activity, as measured with a variety of laboratorytests, and clinical outcome, raising the possibility that ‘resistance’to oral antiplatelet drugs may underlie many such clinical adverseevents. The present position paper, conveyed within a groupof clinical cardiologists with expertise in thrombosis appointedby the Section of Cardiovascular Interventions of the PolishCardiac Society, has been further elaborated and endorsed bythe Working Group on Thrombosis of the European Society of Cardiology.It aims at summarizing the main findings in this complex area,issuing opinions in cases of high controversy, and fosteringfuture research in this area to obtain reliable laboratory andclinical data for the resolution of the many problems stillopen.     

Nutrition in pediatric patients before liver transplantation

Malnutrition leading to growth failure is one of the main problems in maintainig children with chronic liver diseases. The pathogenesis of malnutrition is complex and includes reduced calorie intake, fat malabsorption, impaired protein metabolism and increased energy expenditure. The nutritional status is an important risk factor for survival post liver transplantation. Aggressive nutritional support with careful monitoring is essential, particularly where liver transplantation is considered. When the oral nutrition is inadequate, the enteral feeding with nocturnal intragastric tube should be started. In case of gastrointestinal intolerance, severe malnutrition and gastrointestinal bleeding, parenteral nutrition should be considered.     

Energy and nutritional value of diets used in patients alimentation and their assessment by patients of selected clinical department in the Military Medical Institute in Warsaw

The aim of the work was laboratory assessment of energy and nutritional value of general and light diets used in patients of selected clinical department in the Military Medical Institute in Warsaw alimentation. Using questionnaire method the assessment of diets was done by patients too. Meals given to patients in hospital not always fulfilled nutritional requirements. Additional consumption of supplementary products did not always meet the requirements of proper nutrition. Half of examined patients appraised nutrition variety as good but at the same time claimed the there was not enough fruits and vegetables.     

Outcome in the treatment of discopathy by interbody fusion with the posterior approach using metal cages

Background. Discopathy most often occurs in persons from 20 to 50 years old, in the period of greatest physical and intellectual capacity, and thus poses a major social problem. The goal of our research was to evaluation the outcome of interbody fusion performed with metal cages. Material and methods. We operated 52 patients ranging in age from 29 to 60, who presented with prolapse of the nucleus pulposus (21 patients), instability (8 patients), lumbar stenosis (11 patients), and recurrent discopathy with spondylolisthesis (12 patients). Interbody fusion was performed on these patients from the posterior approach using metal implants. Results. Applying both subjective and radiological criteria, we obtained good outcome in 36 cases, satisfactory in 12 cases, and unsatisfactory in 4 cases. A follow-up at 4 years after surgery showed that the solution was effective in preventing lumbar stenosis and intervertebral instability. However, there were still difficulties in the assessment of bone union. Conclusions. Maintaining or expanding the height of the interbody space by using implants is indicated by radiography in our material to be the most important surgical intervention justifying the use of this method. Interbody fusion in discopathy using metal implants is a logical solution to prevent secondary stenosis of the vertebral canal and intervertebral instability. The outcomes obtained at 4-year follow-up should be regarded as satisfactory.     

Effect of salmon calcitonin on bone mineral density and calcium-phosphate metabolism in chronic hemodialysis patients with secondary hyperparathyroidism

The aim of the study was to evaluate the effect of salmon calcitonin on bone mineral density, parathyroid and thyroid C cells, and calcium-phosphate metabolism in chronic hemodialysis patients with uremic hyperparathyroidism. Forty five patients with serum 1-84 PTH >220 pg/ml were divided into 2 groups: group I (n = 25), treated with intranasal salmon calcitonin (200 IU, thrice a week) and control group II (n = 20). Patients received calcium carbonate (up to 6 g/d) alone or with aluminum hydroxide (up to 3 g/d) as phosphate binders; dialysate calcium was 1.75-2 mmol/l. The observation period was 12 months. The following parameters were measured: bone mineral density (BMD) with dual-energy X-ray absorptiometry in: lumbar spine (L2-L4), femoral neck and total body, before and after the study; serum endogenous calcitonin, before and after the study; serum PTH, alkaline phosphatase and total hydroxyproline, before and after 1, 3, 6, and 12 months; and serum calcium and phosphate monthly. During 12 months of the study, a substantial reduction in BMD was observed in all examined regions in group II (-2.8 +/- 2.1%; p<0.01 in L2-L4, -2.4 +/- 2.0%; p<0.01 in femoral neck, and -1.9 +/- 1.4%; p<0.01 in total body), whereas in group I a slight increase of bone mineral was noted, however insignificant. The inhibition of bone resorption was accompanied by a marked decrease in serum hydroxyproline. No changes in parathyroid activity were noted nor any decrease in serum phosphate. The treatment had no influence on serum endogenous calcitonin; initial concentrations were elevated in 47% of patients. CONCLUSION: Intranasal salmon calcitonin: 1) has no influence on bone mineralization in dialysis patients with uremic hyperparathyroidism; 2) has no significant effect on serum phosphate concentration; 3) provided adequate calcium supplementation doesn't stimulate parathyroid glands; 4) has no influence on endogenous calcitonin secretion.     

Incidence and clinical correlates of ruptured plaques in saphenous vein grafts: an intravascular ultrasound study

OBJECTIVES: The goal of this study was to assess the incidence, clinical correlates, and angiographic appearance of ruptured atherosclerotic plaques detected in saphenous vein grafts (SVGs). BACKGROUND: Ruptured atherosclerotic plaques in native coronary arteries but not in SVGs have been well described with intravascular ultrasound (IVUS). METHODS: We reviewed 791 pre-intervention IVUS SVG studies and identified 95 ruptured plaques in 76 SVGs in 73 patients. Standard clinical, angiographic, and IVUS measurements were collected and/or measured. Ruptured plaques were compared with nonruptured plaques in 276 randomly selected patients. RESULTS: The IVUS-detected ruptured plaques had angiographically complex morphology (95%) with ulceration (79%), intimal flap (71%), and sometimes aneurysm formation (14%). Compared with control SVG lesions, ruptured plaques occurred more often in patients with acute coronary syndromes, in older SVGs (12.3 +/- 5.0 years vs. 8.6 +/- 5.2 years, p < 0.001), and in patients with hypercholesterolemia (92% vs. 81%, p = 0.021) and hypertension (78% vs. 63%, p = 0.015). Multiple ruptured plaques were identified in 22 patients in 19 grafts, more often in diabetic patients (55% vs. 29%, p = 0.054). A tear in the fibrous cap could be identified in 59% of plaques; in 70% it occurred at the shoulder of the plaque and in 30% at the center of the plaque. The IVUS features of ruptured plaques included positive remodeling in 71%, which was more common than in control plaques (40%, p < 0.001). CONCLUSIONS: Ruptured atherosclerotic plaques occur in old SVGs with an incidence of 9.7%. These lesions have a complex angiographic appearance and positive remodeling characteristics. This is similar to ruptured plaques in native arteries.     

Continuous subcutaneous insulin infusion (CSII) of insulin aspart versus multiple daily injection of insulin aspart/insulin glargine in type 1 diabetic patients previously treated with CSII

OBJECTIVE: Multiple daily injection (MDI) therapy of bolus insulin aspart and basal insulin glargine was compared with continuous subcutaneous insulin infusion (CSII) with aspart in type 1 diabetic patients previously treated with CSII. RESEARCH DESIGN AND METHODS: One hundred patients were enrolled in a randomized, multicenter, open-label, crossover study. After a 1-week run-in period with aspart by CSII, 50 subjects were randomly assigned to MDI therapy (aspart immediately before each meal and glargine at bedtime) and 50 subjects continued CSII. After 5 weeks of the first treatment, subjects crossed over to the alternate treatment for 5 weeks. During the last week of each treatment period, subjects wore a continuous glucose monitoring system for 48-72 h. RESULTS: Mean serum fructosamine levels were significantly lower after CSII therapy than after MDI therapy (343 +/- 47 vs. 355 +/- 50 micromol/l, respectively; P = 0.0001). Continuous glucose monitoring profiles over a 24-h time period showed that glucose exposure was 24 and 40% lower for CSII than MDI as measured by area under the curve (AUC) glucose >/=80 mg/dl (1,270 +/- 742 vs. 1,664 +/- 1,039 mg . h . dl(-1); P < 0.001) and AUC glucose >/=140 mg/dl (464 +/- 452 vs. 777 +/- 746 mg . h . dl(-1), CSII vs. MDI, respectively; P < 0.001). Similar percentages of subjects reported hypoglycemic episodes (CSII: 92%, MDI: 94%) and nocturnal (12:00 a.m. to 8:00 a.m.) hypoglycemic episodes (CSII: 73%, MDI: 72%). Major hypoglycemia was infrequent (CSII: two episodes, MDI: five episodes). CONCLUSIONS: In a trial of short duration, CSII therapy with insulin aspart resulted in lower glycemic exposure without increased risk of hypoglycemia, as compared with MDI with insulin aspart and glargine.     

The importance of verifying diagnosis in patients with spinal cord injury hospitalized in a rehabilitation department

Background. According to Annex 7 to Resolution no. 226/2003, the National Health Fund does not cover the costs of diagnostic procedures performed in rehabilitation departments. Everyday clinical practice shows that the availability of imaging studies and specialized laboratory tests is often crucial for effective and safe patient management. The purpose of our research was to analyze the need for diagnostic procedures and verification of referral diagnosis in patients with spinal cord injury admitted to a rehabilitation department. Material and methods. We studied 175 patients (134 males and 41 females, 16 to 75 years of age, mean age 35.2 years) admitted with a diagnosis of spinal cord injury to the Rehabilitation Department of the Warsaw Medical University in the period from 1998 to 2004. Referral diagnoses were compared to the diagnoses established after examination on admission to our Department (verified diagnoses). Results. In 67 patients (38.3%) the referral diagnosis differed from the verified diagnosis. The most frequent new diagnoses included: myositis ossificans: 22 cases (12.6%), decubitus ulcers: 14 cases (8.0%); other trophic skin lesions: 9 cases (5.4%) and undiagnosed concomitant injuries: 5 cases (2.9%). 13 patients (7.5%) were disqualified from further rehabilitation and referred for surgical treatment. Conclusions. 38.3% of our patients with spinal cord injury admitted for rehabilitation had an incorrect referral diagnosis. Legislative decisions limiting the availability of diagnostic procedures at rehabilitation departments lead to decreased health care quality. Spinal cord injury patients admitted for rehabilitation require verification of the referral diagnoses, preferably by the staff of the rehabilitation department.