The essence of alternative medicine. A dermatologist''s view from Germany

BACKGROUND: A microemulsion formulation of cyclosporine, Neoral, has been developed to overcome the problems associated with the poor and variable absorption of the traditional oil-based oral formulation, Sandimmune. The present study was conducted to compare the safety and tolerability of Neoral versus Sandimmune in maintenance renal transplant recipients over 1 year, and to assess the number of dose adjustments necessary to maintain trough cyclosporine concentrations within the desired therapeutic range. METHODS. Patients on Sandimmune were randomized to be converted to Neoral (n=373) or remain on Sandimmune (n=93) for 12 months. RESULTS: The proportion of patients needing dose increases to maintain cyclosporine trough levels within the desired range was significantly higher in the Sandimmune group during the first 3 months of the study, whereas the number of patients needing dose reductions was similar in both groups throughout the study period. There were no differences between the groups in terms of changes in blood pressure, serum creatinine levels, or other laboratory parameters. No significant differences in the incidence of adverse events known to be related to cyclosporine were observed between the treatment groups. More adverse events were causally related to Neoral than to Sandimmune by the investigators. However, overall, there were no clinically relevant differences between the treatment groups in the main safety and tolerability variables. CONCLUSIONS: The results of this study in maintenance renal transplant patients suggest that the improved pharmacokinetic characteristics of the microemulsion formulation of cyclosporine, Neoral, may facilitate the clinical management of cyclosporine immunosuppression, compared with the traditional formulation, Sandimmune. Furthermore, there is no evidence that the average improved bioavailability of Neoral has a negative impact on the main safety and tolerability variables, as no significant differences in graft function, the incidence of rejections, and most adverse events were seen.     

Impact of Sandimmune, Neoral, and Prograf on rejection incidence and renal function in primary liver transplant recipients

Following primary liver transplantation, immunosuppressive efficacy of Neoral and Prograf was similar and superior to that of Sandimmune. Rejection incidence was statistically increased with Sandimmune therapy. Incidence of hypertension, posttransplant diabetes mellitus, and infectious complications was not statistically different. Although early compromise in renal function was associated with Sandimmune, Neoral, and Prograf immunosuppression, no progressive renal dysfunction was identified.     

Drug delivery systems for cyclosporine: achievements and complications

The review deals with the preparation, properties, and analysis of different kinds of cyclosporine delivery systems, such as solid formulations, liposomes, emulsions and microemulsions and targeted cyclosporine formulations. The review points out a key role of delivery systems in increasing the therapeutic effectiveness of cyclosporine. Comparative studies of the prior marketed formulation, Sandimmune, with a new microemulsion formulation, Neoral, are discussed including some data on clinical development of Neoral.     

Mycophenolate mofetil decreases rejection in simultaneous pancreas-kidney transplantation when combined with tacrolimus or cyclosporine

BACKGROUND: Historically, the acute rejection rates in simultaneous pancreas-kidney (SPK) recipients have been extremely high (50-80%), with many second and third rejection episodes despite the use of quadruple immunosuppression (antibody induction and cyclosporine [CsA]-azathioprine [AZA]-based maintenance immunosuppression). Although this acute rejection has rarely led to graft loss, it has been a great cause of morbidity and of significantly increased cost. In an attempt to decrease the acute rejection rate and related morbidity in SPK transplant recipients, we compared two "state-of-the-art" immunosuppression regimens in a prospective, randomized, single-center study. METHODS: Patients who received SPK transplants were randomized to receive either tacrolimus (TAC) and mycophenolate mofetil (MMF, n=18) or CsA (Neoral formulation) and MMF (n=18). All patients received OKT3 induction and prednisone, which was tapered to 5 mg/day by 6 months after transplantation. All rejection episodes were biopsy proven. In addition, metabolic control (HgbA1C, hypertension, serum cholesterol), drug toxicity, and infection also were measured. Data were compared with that of a historical group (n=18) who received conventional CsA (Sandimmune formulation) and AZA-based immunosuppression. RESULTS: The incidence of biopsy-proven acute rejection was 11% in both the TAC-MMF and CsA-MMF groups with only two patients in each group experiencing a rejection episode. This rejection rate was significantly decreased from that of the CsA-AZA historical group (77%, P<0.01). There were no significant differences in infection rates, including cytomegalovirus, or in metabolic control (HgbA1C, hypertension, and cholesterol levels). All patients remained on their initial immunosuppression regimen for the first 3 months after transplantation. Between 3 and 6 months after transplantation, three patients were switched from TAC to CsA for recurrent migraine headaches, posttransplant diabetes, and chronic cytomegalovirus infection. Two patients in the CsA-MMF group died of nonimmunologic causes (aspiration pneumonia and arrhythmia) between 3 and 6 months after transplantation. CONCLUSIONS: The data from this study show that MMF treatment significantly decreases the incidence of biopsy-proven acute rejection in SPK transplant recipients compared with AZA-treated historical controls. In addition, we conclude that TAC and CsA (Neoral), when combined with MMF, yield similar, low acute rejection rates with similar graft function and metabolic control.     

Cyclosporine disposition and metabolite profiles in renal transplant patients receiving a microemulsion formulation

Several lines of evidence suggest that cyclosporine may undergo prehepatic metabolism, the possible contribution of which to the overall biotransformation of the drug is, however, unclear. A recently developed oral formulation of cyclosporine, Sandimmune Neoral, which incorporates the drug in a microemulsion preconcentrate, exhibits a faster rate of absorption and a shorter residence time in the gastrointestinal tract compared to the currently marketed formulation, Sandimmune. If prehepatic metabolism plays an important role, this could, theoretically, have an impact on the metabolite profile from the microemulsion formulation. Therefore, the pharmacokinetics of cyclosporine and its major metabolites were assessed in 13 clinically stable renal transplant patients receiving the commercial and the new formulations at steady state. Whole blood samples were collected over a dosing interval and analyzed by high-performance liquid chromatography (HPLC). Model-fitting of the concentration-time profiles of the parent compound indicated that while the systemic disposition was similar between formulations, absorption-related pharmacokinetic differences were evident. This was manifested in patients at steady state as shorter lag time and faster rate of absorption of the parent compound from the microemulsion formulation. The metabolite-to-parent area under the curve (AUC) ratios for the major metabolites AM1, AM4N, and AM9 were comparable between formulations. Specifically for metabolites AM1 and AM9, which predominated in whole blood and could, therefore, be fully characterized, the area ratios were bioequivalent when comparing the two formulations. Hence, absorption-related differences between the two oral formulations does not affect the systemic metabolite profile during steady-state administration in patients.     

Anti-F(ab'')2 antibody in HIV type 1 infection: relationship to hypergammaglobulinemia and to antibody specific to the V3 loop region of glycoprotein 120

Cyclosporine (Sandimmune) is an effective immunosuppressive drug but may be poorly absorbed in the early postoperative period after liver transplantation, exposing the recipient to an increased risk for rejection. Neoral is a new oral formulation of cyclosporine that uses a mixture of surfactant, lipophilic, and hydrophilic solvents to permit microemulsification that leads to potentially better absorption. This oral drug has not been evaluated in children immediately posttransplantation. The aim of this study was to evaluate the pharmacokinetics, bioavailability, and safety of Neoral during the first week post-liver transplantation in children. Twelve children, 8 boys and 4 girls, with a median age of 2.6 years (range, 1 to 8 years) were administered Neoral within 12 hours posttransplantation. Pharmacokinetic profiles were performed over a 12-hour period on each child on days 1, 3, and 5 and twice-daily trough levels were obtained on days 2, 4, 6, and 7. The maximum concentration (Cmax), time to reach Cmax (Tmax), 12-hour trough levels, and area under the curve were calculated, and rejection episodes and adverse events were documented over a 12-week period. Neoral was well absorbed, even on the first postoperative day. After the introduction of enteral feeding, the peak levels increased (Cmax, 655 ng/mL) and were achieved significantly sooner (Tmax, 2 hours). There was no significant difference in drug exposure between days 1, 3, and 5 (P > .05). The incidence of acute rejection was 25% and hypertension was reported in 4 of 12 patients during the first week. Neoral was well absorbed in the early post-liver transplantation period, provided effective immunosuppression, and was not associated with a high incidence of adverse events or toxicity. The introduction of enteral feeding improved absorption.     

The effect of Opisthorchis on the manifestations of herpesvirus type 2 in an experiment and their possible participation in the mechanism of the occurrence of primary liver cancer

In a 4 month study, a group of 16 patients with stable renal graft function receiving triple immunosuppressive therapy including cyclosporin A (Cy A) were investigated for the levels of calcium, magnesium and zinc in erythrocytes. The patients were randomized to be converted to the new microemulsion formulation (Sandimmun Neoral) in a 1:1 fashion (n = 8) or to continue with the classical formulation (Sandimmun) (n = 8). The concentrations of creatinine, phosphate, alkaline phosphatase activity, calcium, magnesium and zinc were measured twice a month in blood plasma. The concentration of calcium, magnesium and zinc in erythrocytes was also measured. The concentration of magnesium in blood plasma and erythrocytes during the study showed no deviation from normal values. The level of zinc in erythrocytes was almost twice as high as in normal healthy controls and was not dependent on Cy A formulation. Calcium content in erythrocytes of patients receiving Sandimmun was 27.6% higher than in healthy persons. Conversion of the patients to Sandimmun Neoral normalized the calcium concentration in erythrocytes and caused a transient increase of calcium levels in blood plasma.     

Salvage of urea-nitrogen in the large bowel: functional significance in metabolic control and adaptation

OBJECTIVE: To assess the safety, tolerability and efficacy of a new cyclosporin A (CyA) microemulsion formulation, Sandimmun Neoral (Neoral), in patients with severe psoriasis that was stable on CyA administered as Sandimmun (SIM). METHODS: In this 24-week, open, randomized, prospective, multicentre trial, 28 patients continued on the same dosage of SIM, while 30 converted to Neoral at 2.5 mg/kg/day or a dosage equivalent to their pre-conversion SIM dosage. During the study, dosages could be adjusted to maintain efficacy, because of adverse events or after disease stabilization. The maximum permitted dosage for either formulation was 5.0 mg/kg/day. Primary efficacy criteria were change in Psoriasis Area and Severity Index (PASI) from baseline and time to relapse. RESULTS: The dosage was increased to maintain efficacy in 22 patients (Neoral 13; SIM 9) and 20 dose reductions for safety were required (Neoral 14, SIM 6). In both groups, PASI scores remained stable throughout and relapses were primarily a result of dosage reduction after disease stabilization. No significant difference was found between groups in the proportion of patients remaining relapse-free. Adverse events were recorded in 20 patients receiving Neoral and 14 receiving SIM. Most drug-related events were of mild or moderate severity and reflected the known CyA side-effect profile. Dose titration guidelines ensured that mean blood pressure and serum creatinine concentrations remained stable in both groups. CONCLUSIONS: If the guidelines for CyA use are followed and the Neoral dosage does not exceed 5 mg/kg/day, conversion of stable patients with severe psoriasis from SIM to Neoral should present no clinically relevant safety or tolerability problems and efficacy of treatment is maintained.     

Neoral--new cyclosporin for old?

Cyclosporin A is now well established as an effective second-line drug to treat rheumatoid arthritis. In April 1995, the microemulsion-based formulation of cyclosporin (Neoral) was introduced based on its increased bioavailability at 'no extra cost'. There may have been concerns that with increased bioavailability of Neoral, some patients might experience increased toxicity, particularly if transferring from Sandimmun to Neoral at the same dose. We describe our experience of 51 patients treated with Neoral--39 with rheumatoid arthritis, six with psoriatic arthritis and the remainder with a variety of diseases, including Beh?et's, systemic lupus erythematosus and juvenile chronic arthritis. All patients continued their other medication including non-steroidal anti-inflammatory drugs and analgesics. Five continued low dose prednisolone (average 7.5 mg per day) all patients were monitored for safety and efficacy throughout their treatment according to standard protocol. Five patients were enrolled in a study of efficacy and safety where the dose of cyclosporin was reduced to 2.5 mg/kg/day at the time of conversion, i.e. to Neoral 2.5 mg/kg/day; 19 patients were converted dose for dose, cyclosporin A dose range 2.5-4 mg/kg/day converted to Neoral dose range 2.5-4 mg/kg/day and 27 patients started Neoral de novo. We conclude that cyclosporin is a useful disease modifying anti-rheumatic agent, and our experience suggests that the new formulation, Neoral, has a similar safety and efficacy profile to the original preparation (Sandimmun). Neoral was relatively easy to manage and we noted a slight reduction in dose when compared to Sandimmun. With dose adjustments over 18 months the mean dose for patients with RA fell from 3.2 to 2.7 mg/kg/day and of the 27 patients starting Neoral de novo only seven required an increased dose above 2.5 mg/kg/day in order to establish efficacy.     

Safety and tolerability of conversion from stable Sandimmun maintenance treatment to Sandimmun Neoral in patients with rheumatoid arthritis

OBJECTIVE: To assess the safety and tolerability of converting patients with rheumatoid arthritis (RA) taking a stable dose of cyclosporin A (CyA) maintenance treatment (Sandimmun, SIM) to a new microemulsion capsule formulation, Sandimmun Neoral (Neoral), at an initial dose of 2.5 mg/kg/day. METHODS: In this single arm, open multicenter study, 28 patients were recruited to enter a 6 week pre-conversion period; of these, 22 patients completed 12 weeks' treatment with Neoral. RESULTS: During the 12 week post-conversion period, 11 patients experienced adverse events considered to be drug related; most were mild to moderate in severity and reflected the known safety profile for CyA. Only slight differences in efficacy variables were observed after conversion. The mean Neoral dose at Week 12 (2.84 mg/kg/day) was lower than the mean SIM pre-conversion dose (3.38 mg/kg/day). The study showed that, in patients with RA undergoing stable SIM maintenance treatment, conversion to an initial Neoral dose of 2.5 mg/kg/day did not give rise to any clinically relevant safety and tolerability concerns, and efficacy of the treatment was maintained compared with SIM. CONCLUSION: This conversion strategy constitutes a clinically acceptable alternative to a 1:1 dose conversion.     

Enhanced insulin response to oral glucose load in patients with angina pectoris associated with ST segment elevation in the absence of epicardial coronary arterial obstruction

The authors treated 10 patients with microvascular angina (MVA) manifesting angina pectoris, ST segment elevation suggestive of transmural myocardial ischemia, and no epicardial arterial obstruction. Since such patients frequently showed abnormal responses to oral glucose loading, the authors investigated the glucose and insulin responses to glucose loading in 10 MVA patients, 25 patients with vasospastic angina (VAP), 25 patients with effort angina (EAP), and 25 control subjects. Insulinogenic index, peripheral insulin activity [= 10(4)/(peak glucose x insulin at glucose peak)], glucose area, and insulin area were calculated. The MVA group included two patients with impaired glucose tolerance and two newly diagnosed diabetic patients. These proportions were similar to those in the VAP and EAP groups. Glucose levels at 30 to 180 min and insulin levels at 90 to 120 min in the MVA group were higher than in the control group. Peak glucose, glucose area, peak insulin, and insulin area were higher in the MVA group than in the control group (p<0.01). Those in the VAP and EAP groups were also higher. Insulin/glucose ratio at 120 min was higher, peripheral insulin activity, lower, in the disease groups than in the control group (p<0.05). The MVA patients showed a hyperglycemic and hyperinsulinemic response to oral glucose loading, as did the patients with EAP and VAP. Enhanced insulin response to oral glucose loading may also contribute to the pathogenesis of MVA.     

An experimental model of the effect of uremia on cyclosporin A availability

BACKGROUND: The aim of the study was to determine whether or not uraemia has an effect on cyclosporine A intestinal resorption. METHODS AND RESULTS: Model experiments were conducted in rats to monitor the effect of acute uraemia (bilateral nephrectomy) on the kinetics of cyclosporine A. Using intragastric tube, Cyclosporine A was administered to one group of rats in the form of Consupren (Galena, Czech Republic) and to another group in the form of Sandimmune (Sandoz, Switzerland), at a dose of 10 mg/kg/24 h either case. Blood levels of cyclosporine A were determined using RIA and specific and non-specific antibodies (cyclosporine and its metabolites). Cyclosporine A kinetics in nephrectomized rats was compared with that in control rats and in rats undergoing sham nephrectomy. The blood levels of cyclosporine A were significantly lower, and the area under the curve (AUC) of blood cyclosporine A in nephrectomized rats significantly smaller than in control rats. No significant differences in the evaluated parameters after Consupren or Sandimmune were observed. CONCLUSIONS: Our findings support the hypothesis that uraemia decreases cyclosporine A availability. The results suggest that the changes in cyclosporine A kinetics in nephrectomized rats following Consupren and Sandimmune administration are of the same character.     

Automated information system for controlling the sociopsychological adaptation of junior grade schoolchildren during learning activities

Acute graft rejection and delayed function are considered to be the major risk factors of short-term as well as long-term graft survival. We studied the impact of these factors on graft outcome among 109 renal transplant recipients. All recipients were treated with triple drug protocol. The recipients were divided into two groups: I group included 57 patients with delayed graft function (DGF), II group included 52 patients with immediate graft function (IGF). We studied graft survival, incidence of acute rejection, serum creatinine levels and the cause of graft loss for patients in both groups. Acute rejection episodes occurred in 49% of patients from DGF group and 45% of patients from IGF group. Graft survival in IGF group was better than in DGF group. Actuarial graft survival at 1, 2, 3 and 4 years in examined groups was 84%, 82%, 72%, 65% vs. 92%, 86%, 84%, 84%, respectively. One-year graft survival in patients with acute rejection from DGF group and IGF group was significantly lower than in patients who remained rejection free (69%, 74% vs. 94%, 96%). We concluded that delayed graft function decreases long-term graft survival, while immediate graft function has an excellent impact on graft outcome. Acute graft rejection is the strongest risk factor of graft loss.     

Anterior knee pain syndrome: a historical review]

The aim of this study was to determine whether advances in angioplasty techniques have improved results in multiple vessel coronary disease and to compare present results with those reported in randomised trials comparing angioplasty and surgery. The hospital results of two cohorts of multivessel coronary patients treated by angioplasty during two different periods were compared (group 1: 1990-1991. group 2: 1994-1995). The first period corresponded to the inclusion period of randomised trials comparing surgery and angioplasty. The patients in group 2 (n = 449) were older than those in group 1 (n = 424), had more triple vessel disease, more severe angina and more previous angioplasty attempts. Moreover, there were more cases of unfavourable lesions. Nevertheless, the clinical success rate was high in group 2 (92% vs 84%; p < 0.001) and the major complication rate (death, myocardial infarction or emergency bypass surgery) was lower (2.9% vs 6.1%; p = 0.02). The main technical difference between the two periods concerned the use of coronary stents (12% vs 8%; p < 0.001). The fact of being in group 2 was identified by multivariate analysis as an independent predictor for clinical success and a lower major complication rate. The authors conclude that, since the publication of randomised trials comparing angioplasty with coronary surgery, the hospital results of angioplasty have significantly improved. This should be taken into account in considering the clinical applications of the results of these trials.     

Plasma norepinephrine, epinephrine, and thyroid hormone interactions in severely burned patients

In this prospective study of thyroid catecholamine interactions, 15 severely burned patients were divided into two groups. Nine patients receiving 200 micrograms/day of triiodothyronine constituted the T3-treated group. Eight additional patients constituted the untreated group. Mean serum concentrations of T3 were significantly lower in the untreated group than in the treated group. Mean serum thyroxine (T4) concentrations were significantly higher in the untreated group than in the treated group. The mean plasma norepinephrine concentration in the untreated group was significantly greater than that of the treated group. In the untreated group, log plasma norepinephrine correlated inversely with serum T3. Similarly, in the untreated group, log plasma epinephrine correlated inversely with serum T3. Metabolic rates were not different between groups. These data suggest that a reciprocal relationship exists between plasma concentration of T3 and both norepinephrine and epinephrine in untreated burn patients and that treatment with the metabolically active hormone, triiodothyronine, does not alter the level of hypermetabolism accompanying thermal injury.     

Nomenclature and classification of the rheumatic diseases

BACKGROUND: A pilot study was performed to prospectively evaluate the safety and efficacy of "low-dose" OKT3 induction after liver transplantation. METHODS: Sixteen patients received a 5- to 10-day course of OKT3 (2.5 mg i.v. daily) along with azathioprine, prednisone, and the delayed introduction of cyclosporine (Neoral). RESULTS: Patient and graft survival rates at 1 year were 88% and 82%. Five patients (31%) had biopsy-proven rejection; all five were treated successfully with steroids. There were 15 infections in 12 patients, including 5 cytomegalovirus infections. Adverse events attributed to OKT3 consisted of low-grade fever (five patients), transient hypoxemia (three patients), and transient hypotension (two patients). Pharmacy acquisition costs for OKT3 averaged $2,139 less as compared to a group of historical controls receiving full-dose therapy. CONCLUSIONS: Low-dose OKT3 induction appears to be a safe and useful method of postoperative immunosuppression after liver transplantation. Its ultimate clinical, immunologic, and economic efficacy awaits determination by randomized trial.     

Vibrations as an experimental factor affecting intestinal resorption

The authors treated white rats daily at one and the same time for a period of one hour with vibrations. One of the groups of animals were treated with vibrations and examined after that, but the other two groups were treated respectively for 45 and 90 days. Examination was carried out during vibration, immediately after that and three hours after the vibrations. They used the method of the turned bags of Wilson and Waisman, by means of which they checked the resorption of glucose through the intestinal wall in vitro, it was established that during continuous vibration action the values of the resorption glucose were statistically lower than those of the control group. There were statistically significant differences in the values of the resorbed glucose in the subgroups examined during the vibration immediately and there hours after that. The authors discuss the obtained results in the light of the current concepts for the action of vibrations as a stress factor and their influence on intestinal resorption.     

Genotypically dependent effects of cyromazine on reproduction and offspring development in the Australian Lucilia cuprina (Diptera: Calliphoridae)

Various factors may influence bioavailability and blood concentrations of cyclosporine, a problem that may be compounded by diseases such as cystic fibrosis in which impaired absorption through the gastrointestinal tract is common. Neoral, a microemulsion formulation of cyclosporine, has improved bioavailability and more stable blood concentrations than earlier formulations. We conducted a prospective, open, crossover study to examine whether these findings held true in 12 clinically stable patients with cystic fibrosis who had undergone lung transplantation at least 6 months earlier. In the first arm, patients continued their usual dosage of cyclosporine twice/day. In the second arm they received Neoral for at least 1 week before having blood studies. For each arm whole blood trough concentrations were drawn for 7-10 successive days, together with a pharmacokinetic study with concentrations drawn at times zero, 1, 2, 3, 4, 6, 12, and 24 hours. Variance was assessed from morning concentrations. Area under the curve from zero to 12 hours (AUC12), maximum concentration (Cmax), and time to Cmax (Tmax) were calculated for each arm. Eleven subjects completed the protocol. The daily variance for Neoral was significantly less than for cyclosporine (p=0.04). The AUC12 for Neoral and cyclosporine were 4164+/-1467 and 5318+/-1670 microg x L/hour (p=0.09), respectively. Respective Cmax were 613+/-242 and 931 +/-458 microg/L (p=0.08) and relative Cmax and AUC12 were 1.91 and 1.47 (p<0.05). Thus Neoral had a superior pharmacokinetic profile and less day-to-day variability in patients with cystic fibrosis who had undergone lung transplantation.     

Sympathectomy by phenol infiltration in the treatment of chronic obliterative arteriopathies of the lower limbs. Comparison between 60 statistical cases and 35 surgical sympathectomies (author's transl)

The authors compare the results obtained by the use of two different lumbar sympathectomy techniques in patients with chronic obliterative arterial disease of the lower limbs. Surgical resection was employed in 35 cases, and infiltration with phenol under radiological control in 60 cases. The proportion of successful results was about the same in both groups, best results being obtained in younger patients with less advanced disease. No mortality occurred in the group treated by phenol infiltration. Transient neuralgia was reported in some cases, but hospital stay was reduced by an average of 10 days, and many cases could be treated as out-patients. More than half of the patients did not require operation or amputation after phenol infiltration, which is, therefore, a very valuable associated therapeutic measure, especially in the elderly.     

Discrimination of apoptotic thymocytes by forward light scatter

Gingival overgrowth induced by nifedipine has been extensively reported. This finding, however, does not apply to gingival size changes caused by other calcium antagonists such as diltiazem. We studied the gingiva of 13 subjects with ischemic cardiopathy who had been treated with diltiazem and established two control groups: (1) a healthy group of 12 patients and (2) a group of 10 patients with ischemic cardiopathy and concomitant treatment similar to that applied to the diltiazem group except that they had not been administered any type of calcium antagonists. The size of the gingiva around the six anterior teeth was measured on plaster models of the upper and lower jaws. Significantly higher scores of the size of the gingiva were found when patients treated with diltiazem were compared with the patients in the other two groups (p < 0.05) gingiva were found when patients treated with diltiazem were compared with the patients in the other two groups (p < 0.05) and also when interproximal (p < 0.05) and vestibular (p < 0.05) sites were considered. We did not observe any significant difference in the plaque index of each group (p < 0.05); only bleeding after probing was found statistically different between the diltiazem and the nondiltiazem groups.