A2δ ligands gabapentin and pregabalin: future implications in daily clinical practice

Hippokratia 2010; 14 (2): 71-75

TG. Tzellos, G. Papazisis, KA. Toulis, Ch. Sardeli, D. Kouvelas

Abstract

Gabapentin (GP) and pregabalin (PB) are structurally related compounds and their predominant mechanism of action is the inhibition of calcium currents via high-voltage-activated channels containing the a2d-1 subunit. A2ä ligands are approved for the treatment of pain of diabetic neuropathy and post-herpetic neuralgia in adults and as adjunctive therapy of partial seizures in children. Recently, pregabalin has been approved for treatment of anxiety disorders in Europe.Besides their already approved indications both drugs are promising treatment options for a number of different serious and debilitating diseases, as fibromyalgia, neuropathic pain of spinal cord injury, hot flushes, and essential tremor. In the present review, the unique mechanism of action of the above drugs is critically analyzed and evidence for their future use is provided. Gabapentin and pregabalin can be treatment options for these disorders, however, a clear comparison between the two drugs can not be performed, since there is no direct comparison study. The most common side effects are dizziness and somnolence which are also the most frequent reasons for withdrawal. Recommendations for future studies should include assessment of ideal titration period for GP and PB to reduce incidence of somnolence and dizziness and increase tolerability, cost-effectiveness and dose-response analysis of PB and GP and direct comparison of the two drugs.

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Preperitoneal repair (open posterior approach) for recurrent inguinal hernias previously treated with Lichtenstein tension-free hernioplasty

Hippokratia 2010; 14 (2): 119-121

O. Karatepe, E. Acet, M. Altiok, G. Adas, A. Cakir, S. Karahan

Abstract

Background: The repair of recurrent inguinal hernias after prosthetic mesh repair is usually diffucult due to considerable technical challenge and complications. There is also a greater risk of developing further recurrence. The aim of this study was to investigate the outcome of preperitoneal repair (open posterior approach) for recurrent inguinal hernias after Lichtenstein tension-free hernioplasty.
Methods: We performed a prospective clinical study in 44 patients having recurrent inguinal hernias the period 2002-2008. Preperitoneal repair was performed on all patients who have had Lichtenstein tension-free hernioplasty previously.The age, gender, operating time, hospital stay, postoperative complication rates and recurrence rates of patients were evaluated.
Results: There were no serious intraoperative complications. There were 36 men and 9 women in the study, whose average age was 38.45 (25-68) years. The average operative time and hospital stay were 44.56 (30-120) min and 1.6 (1-3) days, respectively. Complications included 4.5 % seromas, 4.5 % hematomas and urinary retention in 9.09 % patients.
Follow-up to date is 1-90 months (range, median 40 months).
Conclusions: We concluded that the preperitoneal repair (open posterior approach) in recurrent inguinal hernias after Lichtenstein tension-free hernioplasty is a safe and efficient method with low complication and rerecurrence rates.

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Multiple myeloma and bone disease: pathogenesis and current therapeutic approaches

Hippokratia 2010; 14 (2): 76-81

EC. Papadopoulou, S P. Batzios, M. Dimitriadou, V. Perifanis, V. Garipidou

Abstract

Multiple myeloma is a haematologic malignancy caused by clonal expansion of malignant plasma cells and associated with bone disease and hypercalcaemia. Myeloma cells are in close proximity to sites of active bone resorption and the interactions between those cells, osteoblasts and osteoclasts, are crucial not only for the bone distraction but for the proliferation of bone marrow cells as well. Recent studies have revealed that numerous regulating factors of osteoblast and osteoclast activity interfere with the pathogenesis of multiple myeloma?s bone disease and that the understanding of the pathophysiological pathways involved is the first step towards discovering novel potential therapeutic approaches.

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Hypothyroidism - new aspects of an old disease

Hippokratia 2010; 14 (2): 82-87

I. Kostoglou-Athanassiou, K. Ntalles

Abstract

hypothyroidism is divided in primary, caused by failure of thyroid function and secondary (central) due to the failure of adequate thyroid-stimulating hormone (TSH) secretion from the pituitary gland or thyrotrophin-releasing hormone (TRH) from the hypothalamus. Secondary hypothyroidism can be differentiated in pituitary and hypothalamic by the use of TRH test. In some cases, failure of hormone action in peripheral tissues can be recognized. Primary hypothyroidism may be clinical, where free T4 (FT4) is decreased and TSH is increased or subclinical where FT4 is normal and TSH is increased. In secondary hypothyroidism FT4 is decreased and TSH is normal or decreased. Primary hypothyroidism is most commonly caused by chronic autoimmune thyroiditis, less common causes being radioiodine treatment and thyroidectomy. Salt iodination, which is performed routinely in many countries, may increase the incidence of overt hypothyroidism. The incidence of clinical hypothyroidism is 0.5-1.9% in women and <1% in men and of subclinical 3-13.6% in women and 0.7-5.7% in men. It is important to differentiate between clinical and subclinical hypothyroidism as in clinical symptoms are serious, even coma may occur, while in subclinical symptoms are less and may even be absent. Subclinical hypothyroidism may be transformed to clinical and as recent research has shown it may have various consequences, such as hyperlipidemia and increased risk for the development of cardiovascular disease, even heart failure, somatic and neuromuscular symptoms, reproductive and other consequences. The administration of novel tyrosine kinase inhibitors for the treatment of neoplastic diseases may induce hypothyroidism. Hypothyroidism is treated by the administration of thyroxine and the prognosis is excellent.

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The role of endothelium and endogenous vasoactive substances in sepsis

Hippokratia 2010; 14 (2): 88-93

G. Kotsovolis, K. Kallaras

Abstract

Sepsis and septic shock are great challenges for the doctors who treat critically ill patients. A big part of the scientific community is performing researches about the pathophysiology and treatment of this clinical problem. The endothelium has a very significant role in the alterations that sepsis causes especially to the circulatory system. The disorders of the normal function of the endothelium include derangement of the vascular tone, increase of endothelium permeability, activation of the endothelial cells, production of various regulators and disorders of coagulation. Nitric oxide is the modulator that mediates the action of most vasodilators. The overproduction of nitric oxide during sepsis is possibly the most important cause of the vasopressor-resistant hypotension which characterizes septic shock. The levels of natriuretic peptides are also increased. These peptides act through several ways on the circulatory system both peripherally and directly on the myocardium. Endothelin, vasopressin, adrenomedullin and prostacyclin are vasoactive substances that have their own role in the regulation of the circulatory system during sepsis.

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The level of teamwork as an index of quality in ICU performance

Hippokratia 2010; 14 (2): 94-97

Ch K. Kydona, G. Malamis, T. Giasnetsova, V. Tsiora, N. Gritsi-Gerogianni

Abstract

Background: The benefits of improved interdisciplinary collaboration in the health care section are well documented in the literature, including fewer errors and shorter delays and thus enhanced effectiveness and maximised patient safety.Given that the first step in improving teamwork involves uncovering individual team member?s attitudes, this study was planned to investigate the level of collaboration, as part of organizational culture in the environment of ICU in Hippokratio Hospital.
Methods: Considering as team all the medical and nursing stuff necessary for the integraded care of the ICU-patient, all the ICU personnel was included in the study, as well as that of other cooperating clinical departments and labs of Hippokratio hospital. For the purpose of the study a questionnaire was adopted and was given to 250 individuals, 196 of which responded (response rate 78.4%).
Results: Responders, in general, valued teamwork as crucial for the performance of ICU. However, the study revealed a relative low consensus regarding the level of teamwork within each unit and inadequate collaboration between certain departments and ICU. Interestingly enough, most of the responders were willing to share responsibility but unwilling to share decision making or accept questioning of their actions. Finally, low consensus was also observed regarding the composition of the team, some responders (mostly clinicians) undervaluing the contribution of labs. Certain differences were detected across departments, as well as between physicians and nurses, the statistical significance of which is indicated.
Conclusion: Although the benefits of teamwork are well understood, realization of effective cooperation seems to be yet too far from our interdisciplinary practice. Teaching of teamwork skills and team concepts should become part of our medical or nursing education and training, if we should want to achieve a substantial improvement of quality of healthcare services, especially in high risk areas such as the ICUs.

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Comparison of estimated creatinine clearance among five formulae (Cockroft?Gault, Jelliffe, Sanaka, simplified 4-variable MDRD and DAF) and the 24hours-urine-collection creatinine clearance

Hippokratia 2010; 14 (2): 98-104

A. Diamandopoulos, P. Goudas, A. Arvanitis

Abstract

Background: GFR estimation is of major importance in everyday clinical practice. Usually it is done using one of the many eGFR equations available. In this study we compared in our population four widespread eGFR equations and our own empirical eGFR, with creatinine clearance calculated through a timed urine collection.
Patients and methods: We collected laboratory data of 907 patients from our clinic and outpatient department through a ten-year period and statistically compared the eGFR results between them and with the timed urine collection creatinine clearances.
Results: All eGFR equations gave acceptable approximations to the timed urine collection creatinine clearances. However, in different subpopulations some equations did better than others, without any clear advantage of any equation overall. Surprisingly, our empirical equation named DAF also gave acceptable approximations regardless of age, weight and sex of the patient.
Conclusions: In our population our empirical eGFR method (DAF) gave satisfactory results regarding the monitoring of renal function, compared with four other eGFR methods. We suggest that it could provide a very fast and easy to use means of eGFR calculation.

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Oral supplementation of folic acid for two months reduces total serum homocysteine levels in hyperhomocysteinemic Greek children

Hippokratia 2010; 14 (2): 105-108

D. Papandreou, P. Malindretos, M. Arvanitidou, A. Makedou, I. Rousso

Abstract

Background & Aim: Hyperhomocysteimemia is a cardiovascular risk factor even among children. Supplementation of oral folic acid may reduce homocysteine levels to normal. However, data is limited at this point for healthy children and adolescents.
Methods: Five hundre and twenty four children participated in the study; Twenty six of them were found to be hyperho mocysteinemic(>95th percentile for age). Twenty of them received 5 mg of folic acid twice per week for two consecutive months while the other six received a diet rich in dietary folate.
Results: Serum homocysteine levels were statistically significantly decreased from 13.1 (10-24.2 ìmol/L ) to 7.7 (4.9-15.2 ìmol/L), p<0.001. Serum folate levels were significantly rose from 4.3 (3-20 ng/mL) to 16.8 (7-20 ng/mL), p<0.001.On the contrary, no important changes were observed in the above parameters in children to whom a diet rich in folic acid was recommended. Homocysteine levels were found to be positively associated with age (r=0.314, p<0.001), BMI (r=0.192, p<0.001), WC (r = 0.215, p<0.001), simple sugars (r= 0.182, p<0.001 ) and negatively associated with folic acid (r = -0.331, p95th percentile for age). Hyperhomocysteinemia in childhood may be a predictive factor of cardiovascular disease. In addition, these results may offer more help to health practioners in order to establish more prospective studies to elucidate the relationship between homocysteine, folic acid and heart disease in children.

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Bronchoalveolar lavage in children with inflammatory and non inflammatory lung disease

Hippokratia 2010; 14 (2): 109-114

D. Gidaris, F. Kanakoudi - Tsakalidou, D. Papakosta, V. Tzimouli, A. Taparkou, M. Ventouri, I. Tsanakas

Abstract

Background: Bronchoalveolar lavage (BAL) is a useful bronchoscopic technique. Studies in ?normal? children are limited.
Aim: To provide data on BAL reference values from Greek children and compare BAL cellular and noncellular components in children with inflammatory and non-inflammatory lung diseases.
Methods: Seventy two children, aged 2.5 months to 16 years, underwent diagnostic bronchoscopy and BAL. Patients were divided in two groups whether lung inflammation was absent or present. Differential cytology, flow cytometry for lymphocyte subsets and cytokine and chemokine measurements were performed on BAL fluid.
Results: Alveolar macrophages were the predominant cellular population in normal children. Patients with inflammatory pneumonopathies had significantly more neutrophils. There was no difference in lymphocyte subpopulations.Values of CD4+/CD8+ ratio in BAL was similar to that reported in adults. Levels of IL-8 and TNF- á were significantly higher in children with inflammatory lung diseases.
Conclusion: This study provides the first data on BAL of ?normal? Greek children. BAL from patients with pulmonary inflammation was characterised by neutrophilia. Finally, we propose that measurement of IL-8 and TNF-a levels in BAL could help in early identification of inflammation in the tracheobronchial tree.

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Re-vascularization may not increase graft survival after hepatic artery thrombosis in liver transplant recipients

Hippokratia 2010; 14 (2): 115-118

D. Vrochides, M. Hassanain, P. Metrakos, J. Barkun, S. Paraskevas, P. Chaudhury, M. Cantarovich, J. Tchervenkov

Abstract

Background and aim: Hepatic artery thrombosis (HAT) occurs in 3% to 11% of all liver transplantations.Some authors have reported good outcomes with early thrombectomy. To investgate the impact of re-vascularization on graft survival.
Methods: A total of 566 primary, cadaveric, single organ, adult liver transplants were performed. Hepatic arterial Doppler was performed routinely and patients with abnormal findings during the first two post-operative weeks were reexplored. Abnormal findings after this time-point were verified by non-invasive angiogram. The 47 patients that were diagnosed with arterial thrombosis, either intra operatively or by angiogram, were divided into three groups. No further action was taken for group A, thrombectomy alone was performed for group B1, thrombectomy and anastomotic revision was employed for group B2.
Results: Arterial thrombosis was diagnosed in 47 (8.3%) patients. Mean patient survival was 42, 62 and 98 months for groups A, B1 and B2 respectively (p: 0.0629). Mean graft survival was 24, 29 and 60 months for groups A, B1 and B2 respectively (p:0.3386). Re-transplant incidence was 8.7%, 40% and 28.6% for groups A, B1, and B2 respectively (p:0.035).
Conclusions: Early diagnosis of HAT by surveillance Doppler may lead to improved recipient survival secondary to earlier re-transplantation and not because of successful graft re-vascularization.

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Health-related quality of life in Greek chronic hepatitis C patients during pegylated interferon and ribavirin treatment

Hippokratia 2010; 14 (2): 122-125

E. Sinakos, E. Gigi, T. Lalla, A-L. Bellou, A. Sykja, E. Orphanou, E. Vrettou, V. Tsapas, M. Raptopoulou

Abstract

Background - Aims: Chronic hepatitis C (CHC) can cause a series of neuropsychiatric symptoms, whereas the currently approved treatment for this disease often induces similar symptoms as well. The aim of the present study was to compare Greek CHC patients? health-related quality of life (HRQoL) with that of healthy controls, to identify any possible relationships
between HRQoL and demographic and laboratory parameters and to study the fluctuation of HRQoL during therapy and follow-up.
Patients and Methods: Ninty nine patients with CHC and 91 healthy controls were enrolled in the study. ALT, viral load, HCV genotype, fibrosis stage by liver biopsy and BMI, were determined at baseline. All patients completed the SF-36 quality of life questionnaire, which was self-administered, before treatment. They were treated with pegylated interferon á2-a or á-2b and ribavirin for 24 or 48 weeks and evaluated in the middle of therapy, at the end and six months after treatment cessation. SF-36 questionnaire was also completed in each evaluation.
Results: Patients? HRQoL was found to be below that of healthy controls in all SF-36 scales before treatment. There was a significant negative association between history of drug abuse and general health and a positive association between age and mental health. Multivariate analysis revealed that history of drug abuse seemed to play a significant role in bodily pain and general health of patients, as well as age did in vitality and mental health. The course of patients? HRQoL showed that in the middle of treatment values in all SF-36 scales were below those of baseline and they returned to pretreatment levels at the end of therapy. However, at the end of the six month follow-up period, an improvement in almost all scales compared to baseline was noted. Conclusion: Our results showed that a) Greek CHC patients? HRQoL was worse than that of healthy individuals and fluctuated significantly during treatment b) A history of drug abuse and age can independently affect HRQoL c) During treatment values of HRQoL are worsened possibly due to interferon-a treatment and d) In the long-term treatment results in improvement of HRQoL

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Skeletal muscle hydatid cysts presenting as soft tissue masses

Hippokratia 2010; 14 (2):126-130

NE. Gougoulias, SE. Varitimidis, KA. ` Bargiotas, TN. Dovas, G. Karydakis, ZH. Dailiana

Abstract

Muscle hydatidosis is rare, accounting only for 3?5% of all cases. We present a case series of 9 patients (8 male, one female, mean age 59.3 years, range 48-75 years) with primary echinococcosis of skeletal muscles. The cysts presented as soft tissue masses in 8 patients, whereas in one, the cyst was an incidental finding on a CT scan performed for investigation of a lung problem. All hydatid cysts were confined into muscles, without affecting the bone. The location was the thigh region in 6 patients (quadriceps in 4, biceps in 2), the popliteal fossa (gastrocnemius) in one, the humerus (triceps branchii) in one and the shoulder (infraspinatus) in one patient. MRI showed multi vesicular cysts in all patients. Indirect hemagglutination serological test was positive in 6 out of 9 cases. En block surgical excision of the cysts was undertaken in all patients. Two patients received antihelminthic chemotherapy preoperatively. Histopathologic findings confirmed the diagnosis. No recurrence occurred during the follow-up period (1-8 years). Skeletal muscle echinococcosis should be considered in the differential diagnosis of limb masses, especially in endemic countries. A meticulous history taking and MRI imaging are essential, while pericystectomy is an effective method of treatment.

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Sympathetic ophthalmia following postoperative endophthalmitis and evisceration

Hippokratia 2010; 14 (2): 131-132

S. Androudi, A. Theodoridou, A. Praidou, P D. Brazitikos

Abstract

Purpose: To report a case of sympathetic ophthalmia (SO) following purulent postoperative endophthalmitis and final evisceration of the affected eye.
Methods-Results: A 64-year-old male underwent phacoemulsification complicated by endophthalmitis. Five months latter the eye was painful and had no light perception so an evisceration was performed. Two weeks latter granulomatous posterior uveitis developed in the fellow eye. SO was diagnosed and the patient was started on prednisone and cyclosporine.The inflammation subsided and visual acuity improved to 20/30.
Conclusions: Bacterial endophthalmitis cannot prevent the development of SO. Prompt diagnosis and management is the most important factor for visual prognosis.

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Severe dyspnea as atypical presenting symptom of Madelung's disease

Hippokratia 2010;14 (2): 133-135

D. Milisavljevic, M. Zivic, Z. Radovanovic, P. Stankovic

Abstract

Madelung's disease (benign symmetrical lipomatosis) is a rare disease of unknown etiology manifesting as symmetric abnormal deposits of adipose tissue in the head, neck and upper trunk. We report a case of a 58-year-old man with a long lasting Madelung?s disease in whom progressive fatty tissue accumulation caused a severe inspiratory dyspnea as atypical presenting symptom. The etiopathogenetic, clinico-diagnostic and therapeutic aspects of this rare disease are discussed. Due to its progressive but not so easily predictable enlarging behavior Madelung?s disease has not only aesthetic but also functional and sometimes life threatening consequences which need to be treated. Hippokratia 2010;14 (2): 133-135

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Breast tumor developed in a pregnant rat after treatment with the teratogen Cycloheximide

Hippokratia 2010; 14 (2): 136-138

EN. Emmanouil - Nikoloussi, E. Nikoloussis, ME. Manthou, O CH. Goula, Ch. Likartsis, Th. Papamitsou, H. Frangou, S. Massouridou, Ch. Lazaridis, A. Manthos

Abstract

Aim: To describe histochemically and immunohistochemically a breast tumor presented in a pregnant rat given Cycloheximide to examine its teratogenic and embryotoxic effect on the embryos. Methods: Cyclïheximide was injected in pregnant Wistar rats at a dose of 3 mg/kg.b.w. on both 10th and 11th gestational days. In one of the rats, a large breast tumor developed rapidly. Histochemical staining with Hematoxylin-Eosin and Masson Trichrome and immunohistochemical identification with mouse monoclonal antibodies: a) Estrogen Receptor A and b) Estrogen Receptor B was performed.
Results: Analysis with A-receptor and B-receptor showed that the breast tumor which was developed after treatment with Cycloheximide was malignant. Positive immunohistochemical reaction was evident especially with A-receptor indicating the malignancy of the tumor.
Conclusions: Cycloheximide is a known toxic and teratogenic agent and potentially a carcinogenic drug. Thus it should be used with extreme caution as a pesticide.

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Emergence of Klebsiella pneumoniae carrying blaVIM and blaKPC genes

Hippokratia 2010; 14 (2): 139-140

G. Meletis, E. Tzampaz, E. Protonotariou, D. Sofianou

Abstract

A Klebsiella pneumoniae clinical isolate resistant to imipenem was recovered from a wound sample. The patient, a 57-year-old man, underwent a surgical resection of small bowel and sigmoid colon and was treated with multiple courses of antimicrobials. PCR analysis revealed that the clinical isolate was carrying simultaneously blaVIM-1, blaKPC-2, blaSHV and blaTEM genes. The concomitant presence of these genes is alarming and poses therapeutic as well as infection control problems.

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Carcinosarcoma of the thyroid: a case report

Hippokratia 2010; 14 (2): 141-142

I. Naqiyah, A N. Zulkarnaen, M. Rohaizak, S. Das

Abstract

Thyroid carcinosarcoma (TC) is a very rare, aggressive thyroid malignancy with a clinical course similar to anaplastic carcinoma. A thorough search of the literature reveals limited information regarding its behavior and treatment modalities. TC has a high mortality rate despite the multi-modal approach. A 54-year-old Chinese gentleman with a long history of a nodule in the right lobe of the thyroid presented with recent history of hemoptysis and shortness of breath. Cytology was suggestive of follicular neoplasm. However, histopathological examination of the total thyroidectomy specimen confirmed TC. This case reports discusses the clinical course and management of TC, which can cause a diagnostic dilemma.

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