Treatment of mild-to-moderate hypertension with calcium channel blockers: a multicentre comparison of once-daily nifedipine GITS with once-daily amlodipine

BACKGROUND: Hypertension is one of the most important causes of cardiovascular disease, and treatment of hypertension leads to a significant reduction in cardiovascular mortality and morbidity. Although calcium channel blockers are regarded as an important part of the therapeutic armamentarium against cardiovascular diseases, and are among the most frequently prescribed antihypertensive medications, concern has been aroused about these drugs, particularly the short-acting dihydropyrldine derivatives. However, the value of nifedipine GITS(Adalat-Crono), the long-acting dihydropyrldine, is in need of being re-established. OBJECTIVE: To compare the effectiveness, safety and tolerability of once-daily nifedipine and amlodipine treatment in patients with mild-to-moderate essential hypertension. DESIGN: Randomised multicentre trial with an open comparison of treatments for 12 weeks, with a preceding placebo run-in period of 2 weeks (patients on beta-blockers at the time of enrollment entered a mandatory 2-week wash-out period before being allowed In the placebo run-in period;this wash-out period was one week for patients using any antihypertensive medication other than beta-blockers). SETTING: Nine centres (all university hospitals) in Turkey. PATIENTS: 155 patients with essential hypertension(diastolic blood pressure 95-109 mmHg). INTERVENTIONS: Initial treatment (step 1) consisted of 30 mg nifedipine GlTS (n = 76; (Adalat-Crono tablets), or 5 mg amlodipine (n = 79; Norvasct5-mg tablets), either administered once daily, as a morning dose, or f the blood pressure was not below 140/90 mmHg, or the reduction In diastolic blood pressure was lower than 10 mmHg after a treatment period of 6 weeks, the dose was increased (Step 2) to 60 mg once daily in the nifedipine group, or 10 mg once daily in the amlodipine group. MAIN EFFICACY PARAMETER: Diastolic blood pressure at trough after 12 weeks of active compound therapy adjusted to baseline. RESULTS: After 12 weeks of treatment, the mean diastolic blood pressure was 83.1 and 81.9 mmHg,in the nifedipine and amlodipine groups, respectively (p = 0.436). The mean decrease in systolic blood pressure (28.5 +/- 11.9 and 28.2 +/- 11.2 mmHg in the nifadipine and amlodipine groups, respectively) and the mean decrease in diastolic blood pressure (16.4A +/- 7.0 and 17.5 +/- 6.9 mmHg in the nifedipine and amlodipine groups, respectively), as well as the responder rates (88.1%and 92.1%, in the nifediplne and amlodipine groups, respectively) were comparable at the end of the study. No significant differences between groups were detected In the efficacy parameters assessed in this study. Both drugs were well tolerated. The overall incidence of adverse events was 7.9% in the nifadipine group and 10.1% In the amlodipine group. However, more patients discontinued treatment prematurely in the amlodipine group (13 patients; 19.7%), than in the nifedipine group (four patients; 5.6%). CONCLUSIONS: The results of this study demonstrated that once-daily nifedipine in GITS formation and amlodipine are comparably safe and effective treatment options in patients with mild-to-moderate essential hypertension.     

Assessment of the effectiveness of postmenopausal tibolone therapy on neural functions by measuring visual evoked potentials: a placebo-controlled study

OBJECTIVE: To assess the effect of hormone replacement therapy on neural transmission in postmenopausal women using tibolone by a non-invasive, objective way. STUDY DESIGN: In a randomised, 3 cycle, placebo-controlled study, neurovisual transmission in optic pathways were evaluated by measuring visual evoked potentials (VEP). After neuroophtalmologic examination, eligible subjects were randomised into two groups. Treatment group (n=38) were given tibolone 2.5mg daily continuously for 3 months and control group (n=20) were treated with placebo. A baseline VEP measurement before the treatment and then at the end of first, second and third month were obtained by the EMG-evoked system in the Department of Neurology, University of Celal Bayar, Manisa, Turkey. RESULTS: Data from 31 women from treatment group and 16 from control group were available for evaluation. The mean P(100) latency values, which indicate the transition time period between the optic stimuli and electrical change recorded on the occipital area by the skin electrodes, have showed a significant decrease for the study group (from 100.39+/-0.58 to 97.90+/-0.65 ms, P<0.01) at the end of the first month of treatment according to the baseline values. This difference between two groups has remained constant during the study period. CONCLUSION: The change in latency measurements of VEP, reflecting the functional status in optic pathways from retina to occipital cortex were significantly different in the treatment group than in that of control. We concluded that a facilitating effect of tibolone was observed on neurovisual transmission.     

Colchicine-induced myopathy with myotonia in a patient with chronic renal failure

Although colchicine induced myopathy has been described in patients with chronic renal failure, colchicine induced myopathy with myotonia has been reported very rarely. A 49-year-old man with chronic renal failure was hospitalised for investigation of fatigue, malaise and severe pain in all extremities. He was on colchicine therapy for 5 months. Neurological examination showed mildly decreased sensation in a distal symmetric pattern in lower extremities, moderate proximal limb weakness, hyporeflexia and severe myalgia on palpation. No clinical evidence of myotonia was present. Laboratory studies showed elevated creatine phosphokinase (CK), lactic dehydrogenase (LDH), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. Electromyographic (EMG) findings were compatible with myopathy and abundant, widespread myotonic discharges were determined. Muscle biopsy was consistent with vacuolar myopathy. After withdrawal of colchicine, CK, LDH, AST and ALT levels were normalised and the symptoms were disappeared gradually. In conclusion, the detection of myopathic motor unit potentials with myotonic discharges on EMG in patients on colchicine therapy is an important finding and it is possible to suggest that this clue may lead to the invasive procedure of muscle biopsy unnecessary.     

Apoptosis and proliferation in childhood acute proliferative glomerulonephritis

Acute proliferative glomerulonephritis is characterized by glomerular hypercellularity that can be caused by many different etiologies and pathogenetic mechanisms. A balance between cell birth by mitosis and cell death by apoptosis is crucial. In this study, apoptosis and the regenerative activity (Ki67/apoptosis index) were investigated in acute proliferative glomerulonephritis. Thirty-five children with biopsy-proven acute proliferative glomerulonephritis and five controls with MCD were studied retrospectively. According to the clinical outcome, patients were divided into 2 groups: group 1 (n =21) were patients with normal renal functions at follow-up; group 2 (n =8) were patients with end-stage renal failure or those who died. Immunohistochemical staining of proliferating cells (Ki67) was done. In situ end labeling of DNA was used to evaluate apoptosis. Glomerular cell apoptosis was 45% in the patients with acute proliferative glomerulonephritis and 3% in controls ( p <0.001). Apoptotic cells were identified in the tubulointerstitial compartment with higher and heavier immunostaining in patients than controls (p =0.001). Tubular proliferative index (= tubular proliferation/tubular apoptosis ratio) was significantly higher in group 1 patients than in group 2 patients (2.03±2% versus 0.32±0.6%, p =0.002). Tubulointerstitial regenerative ratio (=tubular proliferation/interstitial proliferation ratio) was significantly higher in controls than in patients (3.4±1.9 versus 1.52±0.8, p =0.01). In addition, it was significantly increased in group 1 patients when compared with those in group 2 patients (1.89±0.8 versus 0.73±0.2, p =0.001). Since 17 patients presented with postinfectious proliferative glomerulonephritis, which is known to exhibit better course, we also evaluated those parameters in patients with postinfectious proliferative glomerulonephritis separately. We found statistically significant differences only in the tubulointerstitial regenerative ratio, which was higher in postinfectious cases when compared with those in other cases [1.60 interquartile range (IQR) 1.54 versus 1.22 IQR 1.26, respectively, p =0.003]. In conclusion, tubular proliferative index and tubulointerstitial regenerative ratio might be useful parameters for predicting final functional outcome in acute proliferative glomerulonephritis. Further studies, however, are still needed to clarify the importance of these histopathological parameters.     

Field evaluation of an area repellent system (Thermacell) against Phlebotomus papatasi (Diptera: Psychodidae) and Ochlerotatus caspius (Diptera: Culicidae) in Sanliurfa Province, Turkey

A field evaluation of a new area repellent system, Thermacell Mosquito Repellent (TMR, cis-trans allethrin), was conducted against phlebotomine sand flies and mosquitoes in Cunpolat village, Sanliurfa Province, in southeastern Anatolia, Turkey, an area historically endemic for cutaneous leishmaniasis and high sand fly populations. The objective of this study was to determine the efficacy, duration of protection, and spatial characteristics of protection (downwind distance from point of release), of the TMR. Twelve adult volunteers (nine in the treatment and three controls) made collections from ankle to knee for 25 min every hour from 2100 to 0300 on six consecutive nights in August 2002. Treatment consisted of placing a TMR unit at the middle of the village and then placing human bait collectors at 2.3, 4.6, and 7.6 m away from the repellent unit. Results from the field tests showed highly significant protection provided by the TMR from attack by Phlebotomus papatasi (Scopoli) (P < 0.001) and Ochlerotatus caspius (Pallas) (P < 0.001) for up to 4 h postapplication. In the six nights that tests were done, a total of 949 sand flies and 1095 mosquitoes were collected from the untreated control sites. Only 86 sand flies and 83 mosquitoes were collected at all distances from the places treated with TMR. These results indicated that reduction in sand fly and mosquito biting rates in treated groups ranged from 87.5 to 97.7% (mean protection 92%) and 90.2-97.4% (mean protection 93%), respectively. The percentage reduction values were maintained above 90.0% for 6 h of the assessment period. Overall, the number of bites by the cutaneous leishmaniasis vector Ph. papatasi and also Oc. caspius was reduced > 11-fold and 13-fold, respectively, by the TMR.     

Prospective trial of cisplatin, adriamycin, and dacarbazine in metastatic mixed mesodermal sarcomas of the uterus and ovary

Twenty-four patients with advanced or recurrent uterine (13) and ovarian (11) mixed mesodermal sarcomas received a combination of cisplatin. Adriamycin and dacarbazine (PAD) as initial therapy after surgical debulking. Of the 13 patients with metastatic uterine sarcoma, six (46.1%) remained without evidence of disease (NED) from 8 to 36 months from the start of PAD. The estimated 1-, 2-, and 3-year survivals for these patients were 68%, 68%, and 51%, respectively. Of the 11 ovarian sarcoma patients, five (45.4%) were NED at 5, 7, 32, 56, and 59 months from the start of PAD. The estimated 1-, 2-, and 3-year survivals for these patients were 70%, 35%, and 35%, respectively. The PAD regimen is an active regimen in patients with metastatic uterine and ovarian mixed mesodermal sarcomas and progression-free survival may be improved by maximum debulking surgery prior to the initiation of PAD chemotherapy.     

Antibacterial effects of electrically activated vertebral implants

Bio-implants in the human body act as passive surfaces that are prone to bacterial adhesion potentially leading to deep body infections. Pedicle screws made of uncoated or silver-coated titanium alloy were used both in vitro and in vivo to determine whether silver-coated materials have antimicrobial properties when they are anodized. Twenty-four New Zealand Albino rabbits were divided into four groups with six in each. In Group 1, the rabbits were exposed to 8 muA direct current (DC) via silver-coated screws. In Group 2, the rabbits were not exposed to any electrical current, but silver-coated screws were used. In Group 3, the rabbits were exposed to 8 muA DC using uncoated screws. In Group 4, the rabbits were not exposed to any electrical current, but uncoated screws were used. Staphylococcus aureus (106 cfu) was inoculated into the rabbits before any electrical current was applied. All the animals were killed, and the areas surrounding the screws were histologically and microbiologically examined. Silver-coated titanium screws prevented implant-associated deep bone infections when they were polarized anodically. The antibacterial effects of the same screws with the same bacterium were confirmed in in vitro experiments on agar plates. When the screws were anodized with the same electrical parameters in vitro, a marked inhibition zone was detected around the silver-coated screws but not around the uncoated screws. Our findings suggest that silver-coated titanium implants can be used to prevent implant-associated deep bone infections when they are polarized anodically.     

Pyridoxine in the treatment of tetanus neonatorum

A prospective study has been conducted to assess the efficacy of oral pyridoxine in the treatment of neonatal tetanus. A little reduction in mortality was observed by adding pyridoxine to the conventional therapy. The mortality in this group was 50.0% as compared to 62.5% in controls. This result did not confirm the ones in the literature. This could be sourced from the fact that additional infection was 50.0%.     

On the pathogenesis of hyperparathyroidism in chronic experimental renal insufficiency in the dog

Healthy adult dogs were subjected to stepwise reduction of nephron population so as to create the transition from normal renal function to advanced renal insufficiency. Studies were performed at each level of renal function. Glomerular filtration rate (GFR), renal phosphate clearance, and serum radioimmunoassayable parathyroid hormone (PTH) levels were measured. Two groups of animals were studied. In one, phosphorous intake was maintained at 1200 mg/day. As GFR declined, fractional phosphate excretion rose reciprocally, and PTH levels increased over 20-fold. In the second group, phosphorous intake was maintained at less than 100 mg/day. As GFR fell, fractional phosphate excretion changed little, and no increment in PTH levels occurred. The data suggest that the control system regulating phosphate excretion contributes importantly to the pathogenesis of secondary hyperparathyroidism in advancing renal insufficiency.