Evaluation inflammatory markers of hemogram parameters in primary ovarian insufficiency.

OBJECTIVE: In most of primary ovarian insufficiency (POI) cases, etiologic factors have not been fully elucidated. Recent studies have revealed that inflammatory agents play an important role in the etiopathogenesis of POI. Therefore, the aim of this study was to investigate the role of inflammatory markers of hemogram parameters in POI. MATERIALS AND METHODS: The study compared 47 healthy women and 47 women diagnosed as having POI retrospectively by scanning electronic and written recording systems. Complete blood counts, day-3 hormone profiles levels of all subjects were analyzed. The neutrophil-lymphocyte ratio (NLR), red cell distribution width (RDW), platelet ratio (RPR), platelet lymphocyte ratio (PLR), and mean platelet volume (MPV) mean platelet lymphocyte ratio (MPLR) were calculated from the complete blood count parameters. RESULTS: White blood cell and MPV values, platelet, and lymphocyte counts were significantly higher in the POI patients (p<0.001, p=0.042, p=0.038, p=0.049, respectively), RPR was significantly lower than the control group (p=0.011), but there were no significant differences in hemoglobin, RDW, NLR, PLR, and MPLR (p=0.454, p=0.057, p=0.635, p=0.780, p=0.126, respectively). The neutrophil count of the study group was higher than in the control group (p=0.057). Bivariate correlation analyses showed no correlations between blood parameters and hormone levels. The area under the receiver operating characteristic curve for RPR in POI was 0.652, with a threshold value 0.053, sensitivity=63% and specificity=63. CONCLUSION: Inflammatory markers of hemogram detected higher in patients with POI then control subjects.

An unusual case of cavernous hemangioma of the rib in a young man with lung tuberculosis: a brief review and case report.

Hemangiomas are benign vascular tumors that usually involve the liver, skin, eyes and central nervous system. Hemangioma of the bone is unusual and is generally observed in the vertebrae or skull while hemangioma of the costae is extremely rare. Hemangioma of the rib and chest wall tuberculosis may be misdiagnosed as chest wall tumors. We herein report a case of hemangioma of the rib with a tuberculosis infection of the pleura.

Tuberous sclerosis presented with polycystic kidney disease and acute renal failure.

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by hamartomatous involvement of multiple organs such as the skin, central nervous system, kidneys, lungs, and heart. A linkage has been found with a locus on the long arm of chromosome 9 (9q34) and with a locus on the short arm of chromosome 16 (16p13). TSC has a birth incidence of 1/6000. Children with TSC are almost universally born with normal kidneys, but cystic disease and angiomyolipomas develop with increasing age. Angiomyolipomas, renal cysts, and renal cell carcinoma are classical features of renal involvement in TSC. Renal complications are the most common cause of death in adult TSC patients, thus renal involvement has a crucial importance on the course of this disease. We present a 27-year-old patient previously diagnosed as tuberous sclerosis complex and referred with acute renal failure and polycystic kidney disease.

Screening for Celiac disease in Hodgkin and non-Hodgkin lymphoma patients.

BACKGROUND/AIMS: Celiac disease is an abnormal T cell-mediated immune response against dietary gluten in genetically predisposed individuals. The aim of our prospective study was to evaluate the frequency of Celiac disease in patients with lymphoma and to determine the usefulness of the anti-gliadin and anti-endomysial antibodies (EMA) for diagnosis of Celiac disease in this patient group. METHODS: We studied 119 patients with previously or newly diagnosed non-Hodgkin's lymphoma and 60 patients with Hodgkin's lymphoma who presented at the hematology and medical oncology divisions of Dicle University Hospital in Turkey between December 2002 and January 2006. Serological screening for Celiac disease was performed in all patients by searching for serum anti-gliadin immunoglobulin A and immunoglobulin G, and EMA immunoglobulin A and immunoglobulin G. RESULTS: In the Hodgkin's lymphoma group, anti-gliadin immunoglobulin A was detected in 9 (15%) patients (3 male, 6 female), and antigliadin immunoglobulin G was detected in 21 (35%) patients (15 male, 6 female). In the non-Hodgkin's lymphoma group, antigliadin immunoglobulin A was detected in 6 (5%) patients (2 M male 4 female), and anti-gliadin immunoglobulin G was detected in 30 (25.2%) patients (18 male, 12 female). EMA immunoglobulin A and immunoglobulin G were not detected in the Hodgkin's lymphoma and non-Hodgkin's lymphoma groups. CONCLUSIONS: Our report is the first to describe the frequency of Celiac disease in patients with lymphoma in the southeast region of Turkey. In our study, there was no evidence that Celiac disease is a pre-malignant condition for lymphoma. Serological screening for Celiac disease in lymphoma patients does not seem to be necessary.

Thrombosis of temporal artery and renal vein in Kimura-disease-related nephrotic syndrome.

Kimura disease (KD) is an angiolymphoid proliferative disorder of unknown etiology, occurs mainly in Asian patients, presenting with subcutaneous slowly growing masses, with a predilection for preauricular and submandibular regions. The clinical course of the disease is thought to be benign. Concomitant peripheral blood eosinophilia and elevated serum immunoglobulin E levels are often observed. Main systemic manifestation of the KD is renal involvement. Renal abnormalities, notably proteinuria and nephrotic syndrome have been found to be associated with KD. We report a 42-year-old man with KD and a steroid-sensitive membraneous nephrotic syndrome with bilaterally temporal artery and renal vein thrombosis. This is the first reported case of KD associated nephrotic syndrome complicated with wide arterial and venous thrombosis from Anatolia.

A case of essential mixed cryoglobulinemia and associated acquired von-Willebrand disease treated with rituximab.

Current treatment options of essential mixed cryoglobulinemia (EMC); include immunosuppressive approaches, such as corticosteroids, cyclophosphamide, plasma exchange, other cytotoxic drugs in moderate to severe manifestations. Some controlled studies have been carried out to assess the efficacy of anti-CD20 monoclonal antibody, rituximab in patients with hepatitis C (HCV) related cryoglobulinemia (CG) and in patients with autoimmune disorders. Recent trials and some case reports demonstrate a beneficial role for rituximab in HCV related mixed CG. Although, the published evidence for treatment of EMC with rituximab is restricted to case reports, which have shown positive results. Several diseases include lymphoproliferative and myeloproliferative disorders, solid tumors, immunological disorders, cardiovascular disorders and some drugs associated with acquired von Willebrand disease (avWD). CG, which is a kind of immune complex disease, may be related with development of autoantibodies to various autoantigens. In this present case report, we showed the efficacy of rituximab in a 21-year-old female patient, suffered from neuropathy and arthralgia related with EMC, and developed avWD, presented with mucosal bleeding associated with CG. von Willebrand factor activity of our patient also increased with controlling the underlying disease, EMC by rituximab. This case demonstrate that rituximab may be an effective treatment option in EMC and avWD mainly related to CG.

The effects of nonsteroidal anti-inflammatory drugs on platelet function and severity of upper gastrointestinal haemorrhage.

Nonsteroidal anti-inflammatory drugs (NSAIDs) cause gastrointestinal (GI) damage primarily due to the inhibition of prostaglandin synthesis in gastric mucosa, which is an important factor in mucosa protection. Platelets are a cardinal feature of vascular repair. A variety of angiogenic stimulators are stored in platelets and are released during clotting at the wound. When there is a defect in any of these functions and/or platelet number, haemostasis is usually impaired and there may be an associated increased risk and severity of bleeding. While the mechanism of mucosal injury and bleeding are well documented with the use of NSAIDs, very little is known about the platelet function abnormalities and their effects on severity of upper GI bleedings. We performed a prospective analysis of 49 patients who had a history of NSAIDs use to investigate the association between the platelet function impairment associated with NSAIDs and severity of upper GI haemorrhages. Thirty-six of 49 patients (73.5%) had deteriorated platelet function. Mean severity score of patients with deteriorated platelet functions was 3.39, and that of patients with normal platelet functions was 2.46. Mean severity score was statistically significantly higher in patients with deteriorated platelet functions. In conclusion, impaired platelet functions associated with NSAIDs may cause more severe upper GI bleeding. Clinicians should be alert for GI complications especially in older patients and in those with a history of ulcer bleeding.

Two cases of bacterial meningitis accompanied by thalidomide therapy in patients with multiple myeloma: is thalidomide associated with bacterial meningitis?

Morbidity and mortality in multiple myeloma is often attributed to life-threatening infections. A defect in humoral immunity has been proposed for the predisposition to bacterial infections. Most of the infections are of bacterial origin, and the most serious are septicemia, meningitis, and pneumonia. Thalidomide is a drug with pleiotropic effects. The immunomodulatory effects of thalidomide are at least partially mediated through its ability to down-regulate the pathogenic over-production of tumor necrosis factor-alpha (TNF-alpha). TNF-alpha is a cytokine that plays a central role in the regulation of the host immune and inflammatory response to infection. In the central nervous system, TNF-alpha is involved in induction of a fever response and triggers the release of other cytokines, and may also influence transport of compounds into the brain, leading to cerebrospinal fluid leukocytosis, increased protein influx, and lactate accumulation. Thalidomide has been shown to down-regulate the production of TNF-alpha. On the other hand, knowledge of the effects of thalidomide on granulocyte functions is limited. Thalidomide has been shown to attenuate neutrophil adhesion and chemotaxis. We present herein two cases of Streptococcus pneumoniae bacterial meningitis that developed soon after the initiation of thalidomide treatment, and discuss the effect of thalidomide on the immune system. Although, it is not clear whether thalidomide caused the development of the bacterial infections and meningitis, or what its pathogenetic mechanisms are, physicians should be alert for signs and symptoms of meningitis in patients with multiple myeloma who are treated with thalidomide, especially those in neutropenic states.

The efficacy of rituximab in patients with splenectomized refractory chronic idiopathic thrombocythopenic purpura.

The most difficult problem a physician encounters is the management of patients with idiopathic thrombocytopenic purpura (ITP), who has persistent severe thrombocytopenia after failure of initial treatment with glucocorticoids and splenectomy. Most of the patients refractory to corticosteroids and splenectomy will become refractory to other available agents, such as intravenous immunoglobulin (IVIg), danazol or chemotherapy. In this study, we investigated the effect of rituximab on 17 splenectomized refractory chronic ITP patients. Here, we showed that the anti-CD20 antibody, rituximab, induces a clinically significant response in severe chronic ITP patients, who are unresponsive to other therapeutic options. After sixth month, 10 out of 14 responders were still maintaining their durable and significant platelet responses (platelet counts >50 x 10(9)/l), without requirement to any other ITP medication. Therefore, we suggest that, rituximab is an effective treatment option in splenectomized refractory or relapsed ITP patients. Rituximab was well tolerated without severe side effects.

Sheehan's syndrome as a rare cause of anaemia secondary to hypopituitarism.

Although its exact mechanism is unclear, anaemia is well recognised as a feature of hypopituitarism; and anaemia is associated with Sheehan's syndrome (SS). We aimed to evaluate the frequency and severity of anaemia and other haematological changes among patients with Sheehan's syndrome, in comparison with healthy controls. Sixty-five SS patients and 55 age-matched female healthy controls were included. Biochemical and hormonal assessments and haematological evaluations were carried out, and groups were compared. The mean number of red blood cells, as well as mean haemoglobin, iron and erythropoietin levels, total iron-binding capacity and transferrin saturation were all significantly lower in SS patients compared to controls. SS patients had significantly higher rates of anaemia (80.0% vs. 25.5%, p = 0.0001), iron deficiency (44.6% vs. 5.4%, p = 0.001), leukopenia (20.0% vs. 5.4%, p = 0.015), thrombocytopenia (9.2% vs. 0.0%, p = 0.028) and bicytopenia (21.5% vs. 1.8%, p = 0.001) compared to controls. Anaemic SS patients had normochromic-normocytic anaemia (55%) or hypochromic-microcytic anaemia (45%). Anaemia is frequently associated with Sheehan's syndrome and responds to appropriate replacement therapy. Hypopituitarism should be considered as a possible cause of anaemia, and a hormone examination should be undertaken promptly, particularly in patients with anaemia resistant to therapy and/or with a history suggestive of Sheehan's syndrome.

Thyroid and celiac diseases autoantibodies in patients with adult chronic idiopathic thrombocytopenic purpura.

The association of chronic idiopathic thrombocytopenic purpura (cITP) and thyroid autoimmune diseases (TAD) is a known but an uncommon condition. Celiac disease (CD), which is characterized by malabsorption and villous atrophy that occur as a consequence of the ingestion of wheat gluten may also be related to other autoimmune disorders. In this study, we investigated the prevalence of thyroid anti-microsomal (TAMA) and anti-thyroglobulin (TATA) auto antibodies, anti-gliadin (AGA) IgG, IgA, anti-endomisium (EMA) IgG and IgA antibodies in 74 patients with cITP and in 162 healthy controls. TATA positivity was found in 29, and TAMA positivity in 19 out of 74 patients; and in 16 and 18 out of 162 controls respectively (p < 0.0001 and p = 0.005, respectively). TAD was diagnosed in 29 of cITP patients. AGA IgG positivity was found in 17, and IgA was present in five out of 74 patients; and AGA IgG was found in 19, and IgA was detected in 4 out of 162 controls (p = 0.032 and p = 0.143, respectively). EMA IgG positivity was found in six out of 74 patients and in nine out of 162 control subjects (p = 0.566). EMA IgA positivity was found in two out of 74 patients and in one out of 162 controls (p = 0.232). We showed that the prevalence of TAD and related autoantibodies are higher in patients with cITP. We suggest that, patients with cITP should be followed up for development of TAD. In addition, all CD related auto antibodies were found to be more frequent in patients with cITP, but only the AGA IgG reached to the clinical significance. None of the CD related auto antibody positive patients developed clinically manifested CD. Large-scale designed studies are needed to clarify the long-term impact and importance of these CD related auto antibodies in patients with cITP.

Lamivudine for the prevention of hepatitis B virus reactivation in hepatitis-B surface antigen (HBSAG) seropositive cancer patients undergoing cytotoxic chemotherapy.

Hepatitis B virus (HBV) is one of the major causes of chronic liver disease worldwide. Cancer patients who are chronic carriers of HBV have a higher hepatic complication rate while receiving cytotoxic chemotherapy (CT) and this has mainly been attributed to HBV reactivation. In this study, cancer patients who have solid and hematological malignancies with chronic HBV infection received the antiviral agent lamivudine prior and during CT compared with historical control group who did not receive lamivudine. The objectives were to assess the efficacy of lamivudine in reducing the incidence of HBV reactivation, and diminishing morbidity and mortality during CT. Two groups were compared in this study. The prophylactic lamivudin group consisted of 37 patients who received prophylactic lamivudine treatment. The historical controls consisted of 50 consecutive patients who underwent CT without prophylactic lamivudine. They were followed up during and for 8 weeks after CT. The outcomes were compared for both groups. Of our control group (n= 50), 21 patients (42%) were established hepatitis. Twelve (24%) of them were evaluated as severe hepatitis. In the prophylactic lamivudine group severe hepatitis were observed only in 1 patient (2.7%) of 37 patients (p < 0.006). Comparison of the mean ALT values revealed significantly higher mean alanine aminotransferase (ALT) values in the control group than the prophylactic lamivudine group; 154:64 (p < 0.32). Our study suggests that prophylactic lamivudine significantly decreases the incidence of HBV reactivation and overall morbidity in cancer patients during and after immunosuppressive therapy. Further studies are needed to determine the most appropriate nucleoside or nucleotide analogue for antiviral prophylaxis during CT and the optimal duration of administration after completion of CT.

Familial Mediterranean fever gene mutations in the Southeastern region of Turkey and their phenotypical features.

Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by recurrent inflammatory attacks of serosal membranes. Several studies have focused on the differences between frequency of the mutations and their phenotypical manifestations. The aim of this study was to evaluate whether or not this phenotypical variation is associated with the existence of particular mutations. Twelve MEFV (Mediterranean fever) gene mutations were investigated in 119 patients suffering from FMF. Heterozygote M694V (21/119), heterozygote E148Q (21/119), homozygote M694V (17/119) and heterozygote V726A (12/119) mutations were the most common mutations. Patients were grouped according to the presence of the M694V mutation: group I was M694V/M694V, group II was M694V/others, and group III was other/other. Mean severity scores for the groups were 13.94 +/- 4.10, 10.79 +/- 3.01 and 8.31 +/- 2.26, respectively. There were statistically significant differences between the mean severity scores of groups I and II (p = 0.029), groups I and III (p < 0.0001), and groups II and III (p < 0.0001). Diagnosis of amyloidosis was established in four (23%) patients of group I, and three (8%) patients of group II, but in none of the patients in group III. There was also a statistically significant difference between groups I and III (p = 0.046), but not between groups II and III (p = 0.083) and groups I and II (p = 0.317) in terms of amyloidosis development. In conclusion, we found a higher disease severity score and higher prevalence of amyloidosis in FMF patients who were M694V mutation carriers. Many ethnic groups live in Anatolia and more ethnic origin-based studies are needed to determine the real effect of these mutations on disease severity and amyloidosis.

Primary Spindle Cell Sarcoma of the Breast.

BACKGROUND: Primary pure breast sarcoma is a rare disease and constitutes 0.2-1.0% of all mammary malignancies. The establishment of a diagnosis of soft tissue sarcoma is difficult in adults. Immunohistochemical analysis usually proves to be helpful in indistinguishable cases. The simplistic step is to classify sarcomas on a simple descriptive basis as spindle cell sarcomas, myxoid sarcomas, pleomorphic sarcomas, and small round cell sarcomas. CASE REPORT: Here, we present a rare case of primary spindle cell sarcoma of the breast. A 43-year-old woman was admitted to our clinic with a 2-month history of a left breast lump. Histopathological examination showed a tumor of 2.5 cm in diameter and of nuclear and histological grade 2. In the immunohistochemical examination, vimentin positivity, high nuclear overexpression of P53, high Ki-67 and S-100, desmin, leukocyte common antigen, keratin, and smooth muscle antigen, CD34, HMB45 and EMA negativity were detected. CONCLUSION: Most invasive breast neoplasms are epithelial tumors, and mesenchymal breast tumors are rarely seen. In primary breast sarcoma, adequate surgical tumor excision, tumor grade, and tumor diameter seem to be the most important prognostic factors.

Serum nitric oxide levels and flow-mediated dilatation in patients with Sheehan syndrome and the effect of combination therapy consisting of L-thyroxine, prednisolone, and conjugated estrogen/medroxyprogesterone acetate.

Baseline and stimulated nitric oxide (NO) levels were higher, whereas baseline arterial diameter, FMD-stimulated NO increment, and arterial dilatation ratio were lower in Sheehan syndrome (SS) patients than in control subjects. After combination therapy consisting of prednisolone, L-thyroxine, and conjugated estrogen, baseline and stimulated NO levels of SS remained as high, but FMD-stimulated NO, NO increment ratio, and arterial dilatation ratio increased with treatment.