Fourth Week Of Therapy Research Articles

Sulfasalazinom indukovan DRESS (drug reaction with eosinophilia and systemic symptoms) sindrom sa teškim akutnim hepatitisom - prikaz slučaja

Introduction: Drug Reaction with Eosinophilia and Systemic Symptoms Syndrome is a rare and severe form of drug induced delayed-type hypersensitivity reaction with mortality rate up to 10%. It usually manifests with skin rash, fever, lymphadenopathy, hematological abnormalities and involvement of one or more internal organs. Establishing the diagnosis is sometimes late due to variable clinical presentation. Current recommendations for therapy rely mainly on expert opinions, retrospective studies, case reports and series. Sulfasalazine was firstly synthesized in 1930 and is currently being prescribed for various inflammatory and rheumatic diseases. Case report: We present a 45-year-old patient who was prescribed sulfasalazine tablets by a rheumatologist due to reactive arthritis. In the fourth week of therapy, he developed skin rash and fever up to 39.5°C. On admission, generalized maculopapular exanthema covering over 60% of the body surface area, edema of the lower eyelids and bilateral cervical and inguinal lymphadenomegaly were registered. Laboratory findings showed leukocytosis with significant eosinophilia, lymphocytosis, elevated bilirubin values, ALT <100 U/L, while ultrasonography of the upper abdomen confirmed hepatosplenomegaly. The patient was diagnosed with Drug Reaction with Eosinophilia and Systemic Symptoms Syndrome using RegiSCAR and J-SCAR diagnostic criteria and systemic therapy with methylprednisolone at a dose of 1.5 mg/kg and other supportive therapy was applied, which resulted in complete regression of the skin changes and normalization of laboratory values. Conclusion: The authors would like to recall the occurrence of Drug Reaction with Eosinophilia and Systemic Symptoms Syndrome as a rare and potentially fatal drug reaction in which awareness of this disease is of key importance for early recognition. Identification of the offending drug followed by a prompt withdrawal and subsequent treatment is essential for decreasing disease related morbidity and mortality and thus we wish to familiarize the sulfasalazine prescribers with this syndrome.

Prehabilitation to Improve Positioning Reproducibility in Patients Undergoing Pelvic Radiation Therapy

Reproducible patient positioning is essential for precision in radiation therapy (RT) delivery. However, a retrospective review of pre-treatment imaging demonstrated variability in daily patient set-up. We tested the hypothesis that a structured daily pre-treatment stretching regimen is both feasible and effective for minimizing variability in positioning, as measured by sacral slope angles (SSA). After obtaining IRB approval, we had 8 female patients undergoing pelvic radiotherapy perform a structured daily hip exercise regimen (extension and external rotation) immediately prior to both simulation and daily treatment, throughout the RT course. The control group of 20 patients (17 female and 3 male) had usual care. SSA measurements on daily pre-treatment imaging were compared to SSA measurements from the simulation CT for 5 weeks. The extent of SSA variability between two groups and over time was analyzed using a linear mixed model. The same two readers independently measured SSA of all subjects, comparing SSA on the day of simulation to SSA measured on each day of RT. The average variation in SSA among the intervention subjects was 0.913° (±0.582°), with a range among subjects of 0.57°-1.3°. The average variation for the control subjects was 2.27° (±1.43°), with range among subjects of 1.22° - 5.09°. The difference between the two groups was statistically significant (p=0.002). There was a statistically significant SSA variation between groups at each week of treatment (Week (wk) 1: p = 0.007, wk 2: p = 0.008, wk 3: p = 0.01, wk 4: p = 0.005, wk 5: p = 0.008). There was no significant variation among the intervention subjects between week 1 and later weeks (wk 2: p = 0.88, wk 3: p = 0.74, wk 4: p = 0.97, wk 5: p = 0.40), whereas subjects in the control group demonstrated significant SSA variation between week 1 and the fourth week of therapy (wk 2: p = 0.87, wk 3: p = 0.92, wk 4: p = 0.02, wk 5: p = 0.22). There were no reported adverse effects of the stretching regimen. We demonstrated a significant decrease in the variability of SSA by implementing a simple pre-treatment stretching program, whereas control subjects exhibited an increasing variability of SSA over the course of treatment. We conclude that there is a potential benefit for prehabilitation during pelvic RT. A larger clinical trial is required to determine whether a pre-treatment stretching program would result in clinical benefit.

Zoledronic Acid Reduces Osteonecrosis and Anti-Leukemic Efficacy in Murine Models of Acute Lymphoblastic Leukemia Therapy

Background: Osteonecrosis and osteopenia frequently complicate acute lymphoblastic leukemia (ALL) therapy. Interventions which reduce these bony toxicities without impairing the anti-leukemic efficacy of therapy are lacking. Case reports suggest that bisphosphonates may reduce the pain associated with osteonecrosis; however, it is unclear if they are effective in preventing or reducing the progression of osteonecrosis or modifying bone density loss during therapy. Their impact on the anti-leukemic efficacy of therapy is also unknown.Methods: We tested the efficacy of the bisphosphonate zoledronic acid (ZA) in the murine model of osteonecrosis. Four-week-old Balb/c mice were treated with dexamethasone (2mg/L in drinking water) and PEGylated-asparaginase [1200IU/kg intraperitoneal (IP) weekly] for 6 weeks. To test whether ZA could prevent osteonecrosis, mice received ZA 100ug/kg IP weekly starting with therapy initiation (early zoledronic acid group, receiving 6 total doses). To test whether ZA could prevent the progression of osteonecrosis, ZA administration was delayed until the fourth week of therapy (late zoledronic acid group, receiving 2 total doses) after osteonecrosis processes have already begun. All mice were humanly euthanized at 10 weeks post-natal. At the end of the 6 week therapy, osteonecrosis was assessed histologically at the distal femur, while bone density and quality measurements were obtained from the proximal tibia using the Siemeons Inveon uCT system.To test the impact of zoledronic acid on the anti-leukemic efficacy of therapy, nine-week-old B6 mice were injected with 2000 Arf-/- Bcr/Abl+ syngeneic acute lymphoblastic leukemia cells. Mice received three weeks of therapy identical to the osteonecrosis studies (including zoledronic acid randomization), except dexamethasone was increased to 4mg/L in the drinking water. Mice were sacrificed when moribund and leukemia as cause of death was confirmed by peripheral white blood cell count and spleen weight.Results: Osteonecrosis was reduced in the early zoledronic acid group compared to the control group (12/69 limbs vs. 25/72 limbs, p=0.03). The incidence of osteonecrosis in the late zoledronic acid group (19/56 limbs) was identical to that in the control group (p=1). Both zoledronic acid interventions increased the cortical thickness of the tibia [median 0.12mm in therapy treated controls; 0.18mm in early zoledronic acid group (p=<0.001 vs. control); 0.15mm in late zoledronic acid group (p=<0.001 vs. control)]. Thinner cortical wall thickness was associated with an increased risk of osteonecrosis in univariate analysis (p=0.03) but not in multivariate analysis including treatment arm (p=0.32). Epiphyseal arteriopathy, the preceding vascular lesion in osteonecrosis, was less common in early zoledronic acid mice vs. controls (15/60 vs. 28/51, p=0.002). Late zoledronic acid administration resulted in a similar rate of arteriopathy (22/47) compared to controls (p=0.55). There was no difference in the incidence of asparaginase plasma concentrations <1u/mL (p=0.25) or in plasma dexamethasone levels (p=0.67) in mice receiving ZA vs. control treated mice.Because early zoledronic acid administration reduced the rate of osteonecrosis and improved bone density, we tested its effect on the anti-leukemic efficacy of therapy. Mice that received zoledronic acid and chemotherapy had a shorter survival than mice receiving chemotherapy alone (mean 36 vs. 41.6 days, log-rank p=0.046, Figure 1).Conclusion: Zoledronic acid administration early in acute lymphoblastic leukemia therapy reduces osteonecrosis and osteopenia. Zoledronic acid is ineffective in reducing osteonecrosis when given later in therapy. However, the use of zoledronic acid impairs the combined anti-leukemic efficacy of dexamethasone and asparaginase. Further studies are underway to understand this relationship. [Display omitted] DisclosuresRelling:Shire Pharmaceuticals: Research Funding.

Efficacy, safety and cost effectiveness of levocetrizine and ebastine in allergic rhinitis: a comparative study

Background: Allergic rhinitis is a ubiquitous aliment affecting a large population of individuals. The mainstay of treatment includes antihistamines and topical steroids. With a large assortment available, the choice of the drugs needs to be non-random and evidenced based. Hence this study was undertaken to compare Levocetrezine and Ebastine in terms of efficacy, safety and cost effectiveness in treatment of allergic rhinitis.Methods: Newly diagnosed patients with allergic rhinitis were categorized into two groups and treated with Levocetrizine 5mg and Ebastine 20mg per day respectively. Severity of the symptoms at the commencement and at the end of second and the fourth weeks of therapy were assessed using a four-point Likert scale and assigning a Total Nasal Symptoms Score (TNSS). The primary efficacy measure was mean change from baseline TNSS at each follow up visit. Change in TNSS was compared using Independent sample test. Adverse effects in both the groups were compared using Chi square test. Cost effectiveness was inferred by calculation of the Average Cost Effectiveness Ratio.Results: A total of 159 patients 84 from Levocetrizine group (L group) and 75 from the Ebastine group (E group) were available for study. At the end of second week, the E group showed a better reduction in TNSS(p-0.04). However, both the groups showed similar reduction in TNSS at the concluding visit (p-value of 0.09). The incidence of adverse effects was significantly higher in the L than in E. Levocetrezine was found to be more cost effective than Ebastine.Conclusions: Levocterezine and Ebastine are equally efficacious in treatment of allergic rhinitis. Hence treatment will have to be personalized to the individual patients based on other factors such as adverse drug effects and cost effectiveness.

Clinical differentiation of psychopathological symptomatics in depressive, maniacal and mixed types of schizoaffective disorder in dynamics

Aim of the research: conducting a comparative analysis of clinical and psychopathological features of depressive, manic and mixed types of schizoaffective disorder during active therapy at the time of the exacerbation of the disease.Materials and methods. In the course of the study, 110 patients with schizoaffective disorder (F 25 for MIC-10) who were treated at the 1 psychiatric department of the State Institution Institute of Neurology, Psychiatry and Narcology of the National Academy of Medical Sciences of Ukraine for the period from 2000 to 2017 were examined. The average age of the surveyed patients was 26.0 ± 7.1, the mean duration of the disease was 5.0 ± 0.8 years.The first group consisted of 60 patients with schizoaffective disorder, depression type MKH-10 (F25.1) and the second group - 50 patients with manic and mixed type of schizoaffective disorder for MKH-10 (F25.0, F25.2).For the purpose of standardized assessment of psychiatric disorders and treatment effect, the PANSS scale, the Young Mania Rating Scale, and the Calgary Depression Scale (CDSS) were used. The assessment of the severity of psychopathological symptoms through these scales was performed four times during treatment in a hospital: at the first, second, third and fourth weeks of therapy. The analysis of the results was carried out with the help of methods of mathematical statistics (Student-Fisher test (t)). The data is given in the format M ± m, where M is the average value, and m is the standard error.Results. It was found that in patients with both depressive and manic and mixed types of SAD at the time of the 4th week of active treatment of exacerbation, which actually corresponds to the discharge from the hospital, there remain certain psychopathological manifestations that are revealed by the use of assessment techniques such as the PANSS scale, Young Manic Scale, Calgary Depression Scale. In the course of the study, presented in this article, it has been shown that the depressive type of SAD on the one hand, and manic and mixed on the other, have quite distinct differences in the dynamics of symptoms at the clinico-psychopathological level.Conclusions. Therefore, patients with schizoaffective disorder (SAD) after the quenching of acute psychotic symptoms need continued support therapy, aimed at both psychotic and affective residual manifestations

PD Associated Recurrent Peritonitis

If patient's immunity impairs due to the first episode of peritonitis, leads in some cases to another episode of peritonitis from a completely different organism, implying a different cause is known as Recurrent Peritonitis. Method: The study is based on the analysis of our data over a period of 16 years. The sample size was of 402 ESRD patients on CAPD. We retrospectively identified 20 cases of recurrent peritonitis, examined the demographic features, spectrum of pathogens and the outcome. Result: We analyzed 20 patients of recurrent peritonitis in which 11 (55%) patients developed aerobic peritonitis, 6 (30%) developed anaerobic peritonitis and 3 (15%) patients developed fungal peritonitis. We observed that all the three categories of recurrent peritonitis were predominantly found in the cases of diabetic nephropathy. Data were significant at 0.05 levels. When analysis was done between primary diagnosis and outcome, p value was 0.094 which was very near to significance; it might become significant if sample size would high. Aggressive combination therapy was given to the patients to avoid relapse and recurrent peritonitis. Outcome of anaerobic Recurrent Peritonitis is more dreaded than outcome of aerobic Recurrent Peritonitis. Worst outcome was observed when both the primary and Recurrent Peritonitis were due to fungal pathogens.Conclusion: The study illustrates that if, any symptom of peritonitis reappears after initial positive response within the fourth week of therapy of a prior episode, we should think of recurrent peritonitis. Hence, we should advice repeat counts and culture testing of dialysate, to avoid further recurrence and relapse.

Photodynamic Sensory Neuropathy in a Patient Treated With St John's Wort.

To the Editor: The popular herbal preparation St John’s wort is widely used to treat mild to moderate depression. The chemical composition of St John’s wort has been well studied.1 Hypericin, an active ingredient in St John’s wort, has many psychoactive and photodynamic properties, and photosensitivity is one of its possible side effects.2 This report highlights a case of allodynia induced by St John’s wort following sun exposure. Case report: Ms A, a 40-year-old woman, presented to a private family practice office with depressive symptoms. She was diagnosed with mild to moderate depression after scoring 5 on the 9-item Patient Health Questionnaire.3 Ms A had read about some over-the-counter supplements and decided to try the herbal medication St John’s wort 500 mg twice daily before starting any other treatment options. During the follow-up visit 4 weeks after initiating therapy with St John’s wort, Ms A noted improvement of her depressive symptoms but complained of a tingling sensation in her hands whenever she washed them with cold water. This sensation began during the fourth week of therapy after she started working long hours in the sun. The physical examination revealed no skin erythema or burning. The use of a cold tuning fork on the hands produced a tingling sensation and discomfort; light touch did not provoke pain. The symptoms were restricted to the hands. There were no motor or other sensory disturbances, and she had normal peripheral reflexes. Following a review of the literature, Ms A was diagnosed with subacute toxic neuropathy on the basis of a report by Bove,4 who described a patient who experienced similar symptoms following ingestion of St John’s wort. St John’s wort was discontinued, and Ms A’s symptoms started improving after 1 week, with complete resolution of symptoms within 3 weeks of stopping the herb. In a case report, Bove4 suggested that possible demyelination of cutaneous axons caused a patient’s symptoms, but the lack of any other motor or sensory involvement might suggest a different etiology. One possible suggestion would be the activation of the transient receptor potential cation channel, subfamily A, member 1 (TRPA1), a nociceptive ion channel expressed in the unmyelinated c fibers in the sensory neurons in the skin. TRPA1 is considered a key player in acute and chronic (neuropathic) pain, and it is activated by noxious cold and chemical compounds.5 Hypericin activation occurs when the substance is exposed to ultraviolet A. This exposure leads to the release of reactive oxygen radicals,6 which have the potential to activate TRPA1, leading to painful or burning sensations in the light-exposed areas, mimicking symptoms occurring during photodynamic therapy.5 Photosensitivity can occur with the use of St John’s wort, but clinicians also should be aware of possible photodynamic activation of sensory neurons with sunlight exposure.

Early Prediction by 18F-FDG PET/CT for Progression-Free Survival and Overall Survival in Patients With Metastatic Colorectal Cancer Receiving Third-Line Cetuximab-Based Therapy

In metastatic colorectal cancer (mCRC) with wild-type K-ras, cetuximab-based regimen is an option for third-line therapy. The objective of this study was to assess if early response evaluation by 18F-FDG PET/CT can predict progression-free survival (PFS) and overall survival (OS) in these patients. Patients with mCRC going to receive third-line cetuximab-based therapy were enrolled. 18F-FDG PET/CT studies were arranged at baseline and at the ends of the first and fourth weeks of therapy. Treatment response was evaluated with 2 methods: method 1 based on PET response criteria in solid tumors 1.0 and method 2 based on the assumption that an increase in peak tumor metabolism implies nonresponse. Progression-free survival was counted to tumor progression based on the Response Evaluation Criteria in Solid Tumors 1.1 or death. The predictive powers for PFS and OS were analyzed using the Kaplan-Meier method and the log-rank test. Twenty-seven patients were eligible with a median PFS of 5.8 months and a median OS of 9.1 months. Method 2 predicts PFS (P = 0.001) and OS (P < 0.001) at the end of the first week, whereas method 1 does not. Both methods predict PFS and OS at the end of the fourth week. Early response evaluation by 18F-FDG PET/CT predicts PFS and OS in patients with mCRC receiving third-line cetuximab-based therapy. Early therapeutic change may be possible for nonresponsive patients after 1 week of treatment.

Baseline anti-NS4a antibodies in combination with on-treatment quantitative HCV-RNA reliably identifies nonresponders to pegylated interferon–ribavirin combination therapy after 4 weeks of treatment

Early detection of nonresponders to hepatitis C therapy limits unnecessary exposure to treatment and its side-effects. A recent algorithm combining baseline anti-NS4a antibodies and on-treatment quantitative PCR identified nonresponders to a combination of interferon and ribavirin after 1 week of treatment. To validate a stopping rule based on baseline anti-NS4a antibody levels and early on-treatment virological response in treatment-naive genotype 1 chronic hepatitis C patients treated with the current standard pegylated interferon and ribavirin combination therapy. Eighty-nine genotype 1 patients from the Dynamically Individualized Treatment of hepatitis C Infection and Correlates of Viral/Host dynamics Study treated for 48 weeks with standard 180 μg pegylated interferon (PEG-IFN)-α-2a (weekly) and ribavirin 1000-1200 mg (daily) were analysed. Baseline anti-NS4a antibody enzyme-linked immunosorbent assay (NS4a AA 1687-1718) was performed on pretreatment serum. Hepatitis C virus-RNA was assessed at days 0, 1, 4, 7, 8, 15, 22, 29, weeks 6, 7, 8, 10, 12 and 6 weekly thereafter until end of treatment. Multiple regression logistic analysis was performed. Overall 54 of 89 (61%) patients achieved sustained virological response. A baseline anti-NS4a antibody titre less than 1/1250 correlated with absence of favourable initial viral decline according to variable response types (P = 0.015). The optimal algorithm was developed using the combination of the absence of anti-NS4a Ab (<1/1250) at baseline and the presence of a viral load ≥ 100.000 IU/ml at week 4. This algorithm has a specificity of 43% and negative predictive value of 100% to detect nonresponse to standard PEG-IFN-α-2a and ribavirin therapy at fourth week of therapy (intention-to-treat analysis). The decision to stop the therapy in genotype 1 chronic hepatitis C patients treated with PEG-IFN-α-2a and ribavirin can be confidently made after 4 weeks of treatment based on the absence of baseline anti-NS4a Ab and a week-4 hepatitis C virus-RNA above 100.000 IU/ml.

ATRA enhances bystander effect of suicide gene therapy in the treatment of prostate cancer

Objectives All-trans retinoic acid (ATRA) has been shown to inhibit the growth of many malignancies by altering gap junctional intercellular communication (GJIC) and the expression of connexin (Cx) 43. Here, we report that the alteration of GJIC by ATRA may directly enhance the bystander effect (BE) of suicide gene therapy against prostate cancer in vitro and in vivo. Methods PC-3 cells were exposed to different concentrations of ATRA for varying lengths of time in culture. Flow cytometry was performed to measure Cx43-positive cells and the GJIC function of the cells was examined with the scrape-loading dye transfer assay. Cells were treated with ATRA in combination with an adenovirus/ganciclovir (Ad-TK/GCV) system encoding herpes simplex virus-thymidine kinase, and the BE was assessed in the treatment of androgen-independent prostate cancer both in vitro and in vivo. Semiquantitative reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry were performed to assess the expression of Cx43 mRNA and protein in tumor tissues. Results ATRA significantly increased the amount of Cx43-positive cells in a time- and dose-dependent manner ( P < 0.05). GJIC functions were enhanced 3- to 5-fold in the presence of ATRA, although ATRA did not augment GCV toxicity of PC-3 cells. In the mixing assay, ATRA significantly increased cell killing when the ratio of TK-positive cells in the coculture ranged from 30% to 60% compared with ATRA-untreated cell ( P < 0.05), and attained 50% cell killing cells when the ratio of TK-positive cell was 30%, but the same result did not appear until the ratio of TK-positive cell was up to 60% in the ATRA-untreated cell. Mice treated with a combination of ATRA and GCV had significantly smaller Ad-TK infected tumors than those treated with GCV or ATRA alone after 3-weeks of therapy ( P < 0.05). However, from the fourth-week of therapy, there was no difference in tumor growth inhibition between GCV treatment and GCV + ATRA treatment ( P > 0.05), as two tumors in the latter group started to grow more quickly than tumors in the control group. This phenomenon was not found in other groups. Conclusions ATRA could enhance the efficiency of cell killing in suicide gene therapy against prostate cancer by strengthening the BE in vitro and in vivo. Induction of Cxs and GJIC by ATRA might provide an element of selectivity to suicide gene therapy. Future studies should focus on safety and tailoring this cooperative therapy to the patient.

Effect of the function of polymorphonuclear leukocytes and interleukin-1 beta on wound healing in patients with diabetic foot infections

This study was carried out prospectively to determine the effect on prognosis of phagocytic activity index (PAI) and intracellular killing activity (IKA) of polymorphonuclear leukocytes (PMNL), and the levels of interleukin-1 beta (IL-1beta) on prognosis in patients with diabetic foot infection (DFI). The evaluation of PAI and IKA in PMNL and the levels of IL-1beta were performed at the beginning and in the second and fourth weeks of therapy in all diabetic patients, who were categorized into a healing group (HG) and a non-healing group (NHG) on the basis of therapy results. Sixty-six cases (38 diabetic patients and 28 non-diabetic controls) were included in the study. Full recovery was observed in 23 HG patients, whereas 15 (NHG) patients were unresponsive to treatment and nine patients were subjected to amputation at the end. At the baseline, PAI, IKA and IL-1beta levels in HG were not significantly different compared to those of NHG, but at weeks 2 and 4, PAI and IKA levels were significantly higher and IL-1beta levels were significantly lower than those in NHG. On the other hand, at the baseline, PAI and IKA values in HG were significantly lower and IL-1beta levels were significantly higher in comparison with the controls. However, no significant difference was observed at week 2 or 4. Our results suggest that the PMNL functions and IL-1beta regulation deteriorated in patients with DFI, and that such deteriorations might indicate inefficient therapeutic responses in patients with diabetes mellitus.

Noninvasive diffuse optical measurement of blood flow and blood oxygenation for monitoring radiation therapy in patients with head and neck tumors: a pilot study

This pilot study explores the potential of noninvasive diffuse correlation spectroscopy (DCS) and diffuse reflectance spectroscopy (DRS) for monitoring early relative blood flow (rBF), tissue oxygen saturation (StO(2)), and total hemoglobin concentration (THC) responses to chemo-radiation therapy in patients with head and neck tumors. rBF, StO(2), and THC in superficial neck tumor nodes of eight patients are measured before and during the chemo-radiation therapy period. The weekly rBF, StO(2), and THC kinetics exhibit different patterns for different individuals, including significant early blood flow changes during the first two weeks. Averaged blood flow increases (52.7+/-9.7)% in the first week and decreases (42.4+/-7.0)% in the second week. Averaged StO(2) increases from (62.9+/-3.4)% baseline value to (70.4+/-3.2)% at the end of the second week, and averaged THC exhibits a continuous decrease from pretreatment value of (80.7+/-7.0) [microM] to (73.3+/-8.3) [microM] at the end of the second week and to (63.0+/-8.1) [microM] at the end of the fourth week of therapy. These preliminary results suggest daily diffuse-optics-based therapy monitoring is feasible during the first two weeks and may have clinical promise.

The use of ceftriaxone impregnated beads in the management of chronic osteomyelitis

Up to now, orthopaedic management of chronic osteomyelitis is still problematic. Debridement and antibiotic administration is still a widely practiced management. However, oral or parenteral antibiotics often cannot reach the infection site well. Some experts have developed a system to administer local antibiotic in the form of antibiotic beads. Antibiotic beads on the market are still very expensive. Therefore, we made efforts to make our own antibiotic beads by using Ceftriaxone as the antibiotic. Ceftriaxone impregnated beads were made by mixing 2 grams of Ceftriaxone powder with 40 grams of polymethyl methacrylate (PMMA) bone cement sterilely. The size of the beads was 3 x 5 mm. Thirty male rabbits that were induced to get osteomyelitis by inoculating Staphylococcus aureus to their left radius bones were used. In the fourth week, clinical, radiological, histological examination and bacterial culture were performed to prove the presence of osteomyelitis. Then, the samples were divided into 3 groups of ten. The first group only underwent debridement. The second group underwent debridement followed by intravenous Ceftriaxone administration. The third group underwent debridement followed by intravenous Ceftriaxone and Ceftriaxone-impregnated beads administration. After four weeks, clinical, radiological, histological examination and bacterial culture were repeated. In the first group, the incidence rate of osteomyelitis at the end of the fourth week of therapy was 60% (success rate 40%). In the second group, after four weeks of therapy the incidence rate of osteomyelitis after treatment was 20% (success rate 80%), whereas that of the third group was 0% (success rate 100%). In conclusion, the efficacy of combination of systemic antibiotic therapy and ceftriaxone impregnated beads in the therapy of chronic osteomyelitis is better than systemic antibiotic therapy. (Med J Indones 2005; 14: 157-62)

Use of angiotensin-converting enzyme inhibitors in patients with heart failure and renal insufficiency: how concerned should we be by the rise in serum creatinine?

Use of angiotensin-converting enzyme inhibitors in patients with heart failure and renal insufficiency: how concerned should we be by the rise in serum creatinine?

Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting, April 29???May 4, 2001

Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting, April 29???May 4, 2001

Pioglitazone hydrochloride in combination with metformin in the treatment of type 2 diabetes mellitus: A randomized, placebo-controlled study

Background: Their complimentary mechanisms of action suggest that a combination of pioglitazone hydrochloride and metformin may have clinically beneficial effects in the treatment of patients with type 2 diabetes. Objective: This study was undertaken to assess the efficacy and tolerability of pioglitazone in combination with metformin in patients with type 2 diabetes mellitus. Methods: This was a 16-week, double-blind study with the option of enrollment in a separate open-ended, open-label study. It included patients with poorly controlled diabetes mellitus (glycated hemoglobin [HbA 1c] ≥8.0%, fasting C-peptide >1.0 ng/mL) who had been receiving a stable regimen of metformin for ≥30 days. Patients with diabetic retinopathy, nephropathy, or neuropathy; impaired liver or kidney function; or unstable cardiovascular or cerebrovascular conditions were excluded. Patients were randomized to receive once-daily pioglitazone 30 mg + metformin or placebo + metformin. Patients in the open-label extension received pioglitazone 30 mg (with optional titration to 45 mg) + metformin. Results: Three hundred twenty-eight patients were randomized to treatment (168 pioglitazone + metformin, 160 placebo + metformin), and 249 completed the study. Of these, 154 elected to enter the open-label extension study. Patients' mean age was 56 years; most (84%) were white and slightly more than half (57%) were male. Patients receiving pioglitazone 30 mg + metformin had statistically significant mean decreases in HbA 1c (−0.83%) and fasting plasma glucose (FPG) levels (−37.7 mg/dL) compared with placebo + metformin ( P ≤ 0.05). Decreases in FPG levels occurred as early as the fourth week of therapy, the first time point at which FPG was measured. The pioglitazone + metformin group had significant mean percentage changes in levels of triglycerides (−18.2%) and high-density lipoprotein cholesterol (+8.7%) compared with placebo + metformin ( P ≤ 0.05). Mean percentage increases were noted in low-density lipoprotein cholesterol levels (7.7%, pioglitazone + metformin; 11.9%, placebo + metformin) and total cholesterol (4.1%, pioglitazone + metformin; 1.1%, placebo + metformin), with no significant differences between groups. In the extension study, patients treated with open-label pioglitazone + metformin for 72 weeks had mean changes from baseline of −1.36% in HbA 1c and −63.0 mg/dL in FPG. The incidence of adverse events was similar in both groups. Throughout the study, no patient in either treatment group had an alanine aminotransferase (ALT) value ≥3 times the upper limit of normal, a commonly used marker of potential liver damage. Thus, no evidence of drug-induced hepatotoxicity or drug-induced elevations in serum ALT was observed. Conclusions: In this study in patients with type 2 diabetes mellitus, pioglitazone + metformin significantly improved HbA 1c and FPG levels, with positive effects on serum lipid levels and no evidence of drug-induced hepatotoxicity. These effects were maintained for >1.5 years, including the open-label extension.

Treatment of Porphyria cutanea tarda with Oral Thalidomide

Eight male patients with overt clinical and biochemical features of porphyria cutanea tarda (PCT) were orally treated with 300 mg/day thalidomide for 1 week and with 200 mg/day for 3 more weeks. Already after the first week of treatment no new vesicles and/or bullae could be observed. Spontaneous blisters completely disappeared, increased skin fragility subsided and skin hyperpigmentation receded about 2 months after completion of therapy, whereas hypertrichosis persisted. There was a rapid decrease in the urinary total porphyrin excretion which reached normal levels in all patients by the end of the fourth week of therapy, whereas the posttreament chromatographic pattern of urinary porphyrins revealed a slight reduction of higher carboxylated porphyrin metabolites and an increase in the amount of the excreted coproporphyrin, as compared to the pretreatment period. Somnolence, intermittent constipation and dry mouth occurred in all patients, 2 patients additionally experienced dizziness. No evidence of peripheral neuropathy could be detected and laboratory investigations revealed no abnormalities, as compared to the pretreatment period. During the 16- to 28-month follow-up of the patients, no clinical or biochemical relapse was observed. In view of the encouraging results of the present investigation, further studies are now warranted in order to definitely answer the question whether oral thalidomide may be regarded as an effective alternative approach to the treatment of PCT.

Lamivudine is effective in suppressing hepatitis B virus DNA in Chinese hepatitis B surface antigen carriers: A placebo-controlled trial

Lamivudine is a novel 2',3'-dideoxy cytosine analogue that has potent inhibitory effects on hepatitis B virus replication in vitro and in vivo. We performed a single-blind, placebo-controlled study to assess its effectiveness and safety in Chinese hepatitis B surface antigen (HBsAg) carriers. Forty-two Chinese HBsAg carriers were randomized to receive placebo (6 patients) or lamivudine orally in dosages of 25 mg, 100 mg, or 300 mg daily (12 patients for each dosage). The drug was given for 4 weeks. The patients were closely monitored clinically, biochemically, and serologically up to 4 weeks after drug treatment. All 36 patients receiving lamivudine had a decrease in hepatitis B virus (HBV) DNA values of >90% (P < .001 compared with placebo). Although 25 mg of lamivudine was slightly less effective than 100 mg (P = .011) and 300 mg (P = .005), it still induced 94% suppression of HBV DNA after the fourth week of therapy. HBV DNA values returned to pretreatment levels within 4 weeks of cessation of therapy. There was no change in the hepatitis B e antigen status or in aminotransferase levels. No serious adverse events were observed. In conclusion, a 4-week course of lamivudine was safe and effective in suppression of HBV DNA in Chinese HBsAg carriers. The suppression was >90% but reversible. Studies with long-term lamivudine administration should be performed to determine if prolonged suppression of HBV DNA can be achieved.(Hepatology 1997 Jan;25(1):241-4)

Concentrations of interferon gamma, tumor necrosis factor alpha, and interleukin-1 beta in the cerebrospinal fluid of children treated for tuberculous meningitis.

Concentrations of interferon gamma (IFN-gamma) in the lumbar cerebrospinal fluid (CSF) of 30 children (mean age, 27 months) being treated for stage III (16 children) and stage II (14 children) tuberculosis meningitis (TBM) were determined by ELISA. Nine children with stage III TBM and six with stage II TBM received prednisone (4 mg/kg). Concentrations of IFN-gamma in 73 CSF specimens (18 from the first week of therapy, 20 from the second, 19 from the third, and 16 from the fourth) were determined. The mean concentrations were 780 pg/mL in the first week of therapy and 554 pg/mL, 529 pg/mL, and 269 pg/mL in the second, third, and fourth weeks, respectively. Tumor necrosis factor alpha (TNF-alpha) and interleukin-1beta (IL-1beta) concentrations in 56 specimens from 23 of these same children were determined by ELISA. The mean CSF TNF-alpha concentration in 12 specimens obtained during the first week of therapy was 17 pg/mL, and the mean was 11 pg/mL during each of the subsequent weeks (14 specimens were evaluated in the second week and 15 specimens in the third and fourth weeks of therapy). Mean IL-1beta concentrations in these same groups of specimens were 52 pg/mL, 43 pg/mL, 42 pg/mL, and 18 pg/mL. No correlation could be shown between cytokine concentration and stage of disease, and no differences existed between those who did and those who did not receive prednisone. A significant decline in IL-1beta concentrations was shown during the 4-week period, but none in TNF-alpha or IFN-gamma concentrations was noted. Persistently high CSF INF-gamma concentrations in cases of TBM (as in cases of aseptic meningitis but not bacterial meningitis) at the time of diagnosis suggest an immune response fundamentally different from that in bacterial meningitis.

Oral cyclosporine for the treatment of alopecia areata: A clinical and immunohistochemical analysis

Cyclosporine inhibits the activation of helper T cells that may be pathogenic in alopecia areata. Therefore we treated six patients with alopecia areata (five men, one woman) with oral cyclosporine, 6 mg/kg/day for 12 weeks. Three patients had alopecia universalis, one had alopecia totalis, and two had patchy alopecia areata of the scalp. Hair regrowth in the scalp of all patients occurred within the second and fourth weeks of therapy, followed by hair regrowth of the face and chest (in the male patients), pubic area, extremities, and axillae. Overall, the site of best response was the scalp. Cosmetically acceptable terminal hair regrowth on the scalp occurred in three of six patients. Significant hair loss, however, occurred in all patients within 3 months of discontinuation of cyclosporine treatment. Clinical response correlated with changes in immune cell infiltration of the hair follicles. The number of leukocytes per hair follicle was quantified in transverse scalp biopsy sections stained with a panel of monoclonal antibodies. The degree of terminal hair regrowth correlated significantly with decreases in follicular epithelial human lymphocyte antigen-DR and intercellular adhesion molecule-1 expression, T cells, helper/inducer (CD4) T cells, suppressor/cytotoxic (CD8) T cells and Langerhans cells (CD1+DR+) from the hair follicles during cyclosporine therapy. A significant decrease in the CD4/CD8 ratio occurred early in the course of treatment and was maintained throughout the therapy. This decrease suggests that cyclosporine not only cleared immune cells from the hair follicles but also altered the balance of regulatory lymphocytes.(ABSTRACT TRUNCATED AT 250 WORDS)