Gonadotropin treatment restores in vitro interleukin-1beta and tumour necrosis factor-alpha production by stimulated peripheral blood mononuclear cells from patients with idiopathic hypogonadotropic hypogonadism

In the present study, we aimed to investigate the effects of testosterone deficiency and gonadotropin therapy on the in vitro production of tumour necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) by peripheral blood mononuclear cells (PBMCs) from patients with idiopathic hypogonadotropic hypogonadism (IHH) in order to elucidate the modulatory role of androgen in cytokine production. Fifteen male patients with untreated IHH and 15 age-matched healthy male subjects were enrolled in the study. Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), free testosterone (FT), sex hormone binding globulin (SHBG), prolactin, and IL-2 and IL-4 levels were also measured. In unstimulated cultures, IL-1beta and TNF-alpha secretion were not significantly different between patient and control groups. However, after stimulation with lipopolysaccharide (LPS), secretion of IL-1beta and TNF-alpha was significantly higher in cultures from untreated patients with IHH than in control subjects. Mean FSH, LH and FT levels were significantly lower, whereas SHBG, IL-2 and IL-4 levels were significantly higher in patients with IHH compared than in controls. In patients with IHH, FT negatively affected the serum levels of IL-4 and in vitro secretion of IL-1beta and TNF-alpha. In addition, IL-2 and IL-4 affected the in vitro secretion of IL-1beta in a positive manner. Gonadotropin therapy decreased both TNF-alpha and IL-1beta in PBMCs from patients with IHH. The levels of serum IL-2 and IL-4 were also decreased by therapy. In conclusion, in the present study, gonadotropin treatment restored the in vitro production of IL-1beta and TNF-alpha by PBMCs from patients with IHH, suggesting that androgen modulates proinflammatory cytokine production, at least directly through its effects on PBMCs. It seems probable that this effect plays an important role in the immunosuppressive action of androgens.     

Musculotopic organization of the motor neurons supplying forelimb and shoulder girdle muscles in the mouse

We identified the motor neurons (MNs) supplying the shoulder girdle and forelimb muscles in the C57BL/6J mouse spinal cord using Fluoro-Gold retrograde tracer injections. In spinal cord transverse sections from C2 to T2, we observed two MN columns (medial and lateral) both with ventral and dorsal subdivisions. The dorsolateral column consisted of the biceps brachii, forearm extensors, forearm flexors, and hand MNs, and the ventrolateral column consisted of the latissimus dorsi, trapezius, teres major, deltoid, and triceps MNs. The supraspinatus muscle MNs were located in the dorsomedial column, and pectoralis major and serratus anterior MNs were located in the ventromedial columns. MNs of the dorsolateral column innervated the biceps brachii in mid-C4 to mid-C7, forearm extensors in caudal C4 to mid-T1, forearm flexors in rostral C5 to mid-T1, and hand muscles in mid-C8 to mid-T2 segments. The MNs innervating the trapezius were located in mid-C2 to mid-C4, triceps brachii in mid-C6 to rostral T1, deltoid in rostral C4 to mid-C6, teres major in rostral C5 to mid-C8, and latissimus dorsi in mid-C5 to caudal C8. In addition, MNs innervating the supraspinatus were located from rostral C4 to caudal C8, pectoralis major in mid-C6 to mid-T2, and serratus anterior in rostral C5 to caudal C7/rostral C8 segments. While the musculotopic pattern of MN groups was very similar to that documented for other species, we found differences in the position and cranio-caudal extent of some MN pools compared with previous reports. The identification of mouse forelimb MNs can serve as an anatomical reference for studying degenerative MN diseases, spinal cord injury, and developmental gene expression.     

Thrombophilia and avascular necrosis of femoral head in kidney allograft recipients.

BACKGROUND: Thrombophilia has been implicated in the development of avascular necrosis (AVN) in various diseases. We aimed to search for the relation of both prothrombin gene G20210A mutation and factor V G1691A (factor V Leiden) mutation with AVN among kidney transplant recipients. METHODS: Nineteen patients with AVN and 38 control patients without AVN were included. Clinical information was collected, and gender, age, type of renal allograft, duration and type of dialysis, presence of acute rejection, and cumulative doses of ciclosporin and corticosteroid administration were taken into consideration. Genotypes of factor V G1691A and prothrombin G20210A were determined by direct sequencing of genomic DNA. RESULTS: Factor V Leiden mutation was detected in six patients (31.6%) among patients with AVN and in only three patients (7.9%) in the control group (P = 0.048). Two patients (10.5%) in the AVN group were determined to have prothrombin G20210A mutation, while no prothrombin G20210A mutation was detected in the control group. When both of the mutations causing thrombophilia were considered, a total of eight patients (42.1%) in the AVN group and three patients (7.9%) in the control group were identified (P = 0.004). CONCLUSION: Thrombophilia seems to be an important risk factor for development of AVN. More studies are needed to clarify the role of factor V G1691A and prothrombin G20210A mutation for AVN.     

Klebsiella pneumoniae peritonitis shortly after kidney transplantation

We report a case of spontaneous bacterial peritonitis caused by Klebsiella pneumoniae in a 34-year-old male recipient shortly after kidney transplantation. On posttransplant day 10, the patient started complaining of severe abdominal pain and nausea. Body temperature was 38.4°C. The abdomen was diffusely tender with rigidity and rebound. Laboratory data showed a normal erythrocyte sedimentation rate and serum creatinine level but a slightly elevated C-reactive protein concentration and leukocytosis of 36,200 cells/mm³ with 88% neutrophils. Explorative laparotomy revealed diffuse purulent peritonitis without an intraabdominal source of infection, such as intestinal perforation. The peritoneal fluid revealed greater than 1000/mm³ white blood cells and many gram-negative bacilli. Fluid cultures yielded growth of Klebsiella pneumoniae. The patient responded to antibiotic therapy; he was discharged in good condition. This case report draws attention to the impaired host defense that may predispose to spontaneous bacterial peritonitis in renal transplant recipients and alerts the clinician to the possibility of this rare disease.     

Immunoglobulin deficiency in kidney allograft recipients: comparative effects of mycophenolate mofetil and azathioprine

Mycophenolate mofetil (MMF) has commonly been substituted for azathioprine (AZA) in kidney transplantation and has been shown to have a greater effect on T cell function and also B cell function than AZA. Although immunoglobulin deficiency has been investigated in patients treated with protocols that include AZA, it has not extensively been studied in MMF-based immunosuppressive protocols. To evaluate this effect, we conducted a prospective study and recruited 49 patients. The patients received either AZA- (group 1) or MMF- (group 2) based therapy. A total of 17 patients in group 1 and 24 patients in group 2 completed the study. Immunoglobulin levels were evaluated before and in every month after transplantation for a 6-month period. Total infectious episodes were recorded and evaluated after 6 months in both groups. While no significant differences have been found in group 1, there were significant decreases in IgG, M, and A levels in group 2 after 6 months (IgG: 11.6+/-1.5-6.8+/-2.0 g/L, P<0.0001; IgM: 2.20+/-1.40-1.40+/-1.16 g/L, P=0.02; IgA: 1.40+/-0.70-1.07+/-0.86 g/L P=0.03). Two patients (11.7%) in group 1 and 11 patients in group 2 (45.8%) were found to have at least one low level of immunoglobulin (P=0.03). When the infectious complications were evaluated, the mean number of infection episodes in each patient was 1.3+/-1.6 and 0.5+/-0.7 for the MMF and AZA groups, respectively (P=0.06). Recurrent urinary tract infection developed in eight patients and seven of those were in group 2. In group 2, 7 of 11 patients with low immunoglobulin levels had recurrent urinary tract infection (63%), while no patient who had normal immunoglobulin levels developed any recurrent urinary tract infections (P<0.001). After 6 months, MMF was changed to AZA in these seven patients, who had both recurrent urinary tract infections and low immunoglobulin levels. All but one patient was found to have normal immunoglobulin levels after 3 months of conversion and only two episodes of infection were recorded during this period. We suggest that serum immunoglobulin levels can be monitored in patients taking MMF, and conversion from MMF to AZA may be an alternative for patients with low immunoglobulin levels and recurrent urinary tract infections.     

Tuberculosis of the breast in a patient undergoing hemodialysis

A 61-year-old female patient with diabetes undergoing maintenance hemodialysis presented with fever and swelling of her right breast. She had been unresponsive to nonspecific antimicrobial therapies. Breast tuberculosis and tuberculous lymphadenitis were diagnosed by excision biopsy and tissue culture. A combination antituberculous treatment including isoniazid, rifampin, ethambutol, and pyrazinamide was started and resulted in the remission of the lesions by the end of the first month of therapy.     

Systemic and local antibiotic prophylaxis in the prevention of <Emphasis Type="Italic">Staphylococcus epidermidis</Emphasis>graft infection

Background  

The aim of the study was to investigate the in vivo efficacy of local and systemic antibiotic prophylaxis in the prevention of Staphylococcus (S.) epidermidis graft infection in a rat model and to evaluate the bacterial adherence to frequently used prosthetic graft materials.     

Thyroid cancer in hyperthyroidism: incidence rates and value of ultrasound-guided fine-needle aspiration biopsy in this patient group

Three hundred and thirty-three hyperthyroidism cases were retrospectively investigated to provide information about the association between hyperthyroidism and thyroid cancer. There were 112 cases of toxic multinodular goiter (TMNG), 77 cases of toxic nodular goiter (TNG) and 144 cases of Graves' disease (GD). All nodules detected in GD patients, all nodules greater than 1 cm diameter in nodular goiter patients, nodules 5-10 mm size diameter if they had calcification were fine-needle biopsied (FNAB) under ultrasound guidance (US-guided), and a total of 612 such biopsies were performed. The biopsy samples were cytologically assessed as benign (no.=552; 90.2%), suspicious (no.=6; 1.1%), malignant (no.=13; 2.1%), or inadequate for diagnosis (no.=41; 6.7%). All patients with a biopsy diagnosis of malignant or suspicious nodules underwent surgery. Histological examination confirmed the diagnosis of thyroid cancer in all 13 (2.1%) patients with malignant FNAB findings. Papillary thyroid carcinoma (PTC) was identified in 2 patients with TMNG (%1.8), 5 with TNG (%6.5) and 5 with GD (%3.5). Metastatic follicular thyroid carcinoma (FTC) was identified in a patient with TNG. Thyroid malignancy (micro- or macrocarcinoma) was diagnosed pre-operatively in all 13 cases by US-guided FNAB. Thyroid cancer was diagnosed in 6 (5.5%) of the 109 nodules detected in the TNG group, 2 (0.44%) of the 452 nodules detected in the TMNG group, and 5 (9.8%) of the 51 nodules detected in the GD group. Two (2.6%) of the 77 functioning nodules in the TNG patients were malignant, but none of the 402 functioning nodules in the TMNG patients was malignant. In patients with hyperthyroidism, US-guided FNAB is useful for detecting thyroid cancer in nodules greater than 5 mm diameter before radioiodine therapy or surgery.