Cardiovascular disease risk prediction in scleroderma

SUMMARY OBJECTIVE: Cardiovascular disease risk prediction in scleroderma is important. In this study of scleroderma patients, the aim was to investigate the relationship between cardiac myosin-binding protein-C, sensitive troponin T, and trimethylamine N-oxide and cardiovascular disease risk with the Systematic COronary Risk Evaluation 2 model of the European Society of Cardiology. METHODS: Systematic COronary Risk Evaluation 2 risk groups of 38 healthy controls and 52 women with scleroderma were evaluated. Cardiac myosin-binding protein-C, sensitive troponin T, and trimethylamine N-oxide levels were analyzed with commercial ELISA kits. RESULTS: In scleroderma patients, cardiac myosin-binding protein-C and trimethylamine N-oxide levels were higher than healthy controls but sensitive troponin T was not (p<0.001, p<0.001, and p=0.274, respectively). Out of 52 patients, 36 (69.2%) were at low risk, and the other 16 (30.8%) patients were at high-moderate risk with the Systematic COronary Risk Evaluation 2 model. At the optimal cutoff values, trimethylamine N-oxide could discriminate high-moderate risk with sensitivity 76%, specificity 86% and cardiac myosin-binding protein-C with sensitivity 75%, specificity 83%. Patients with high trimethylamine N-oxide levels (≥10.28 ng/mL) could predict high-moderate- Systematic COronary Risk Evaluation 2 risk 15 times higher than those with low trimethylamine N-oxide (<10.28 ng/mL) levels (odds ratio [OR]: 15.00, 95%CI 3.585-62.765, p<0.001). Similarly, high cardiac myosin-binding protein-C (≥8.29 ng/mL) levels could predict significantly higher Systematic COronary Risk Evaluation 2 risk than low cardiac myosin-binding protein-C (<8.29 ng/mL) levels (OR: 11.00, 95%CI 2.786-43.430). CONCLUSION: Noninvasive cardiovascular disease risk prediction indicators in scleroderma, cardiac myosin-binding protein-C, and trimethylamine N-oxide could be recommended to distinguish between high-moderate risk and low risk with the Systematic COronary Risk Evaluation 2 model.

A case of chronic lymphocytic leukemia still taking etanercept for ankylosing spondylitis.

The possible risk of hematologic malignancies in anti TNF users is a matter of debate. Whether associated with the drug or not, how to behave when a hematologic malignancy is discovered in the course of anti TNF treatment remains unanswered. Here we present a 66 year old male patient who had AS for 30 years and had been on etanercept for the last two years and who is diagnosed with B cell chronic lymphocytic leukemia (CLL) stage 1. The patient is still on etanercept for 5 years after the diagnosis without any progression in CLL.

Progression to the blastocyst stage of embryos derived from testicular round spermatids.

Progression to the blastocyst stage of embryos derived from testicular round spermatids in men with non-obstructive azoospermia was studied. A total of 56 men were studied in whom partial spermatogenesis failure had occurred where only very few spermatozoa (fewer than the number of oocytes retrieved) were extracted from multiple testicular biopsy specimens. Oocytes remaining after intracytoplasmic injection of testicular spermatozoa (group 1) were injected with round spermatids (ROSI, group 2). Only embryos derived from group 1 were transferred. Remaining embryos were observed under culture for 8 days and their progression to the blastocyst stage was recorded. Of the 546 oocytes injected with testicular spermatozoa, 404 (73.9%) showed evidence of 2-pronuclear (2PN) fertilization. Injection of testicular round spermatids resulted in 2PN fertilization rate of 50% (P < 0.05). Using a four-point grading system, 53% of the good quality embryos (grade 1 or 2) in group 1 reached the blastocyst stage compared with 25% in group 2 (P < 0.05). The rate of progression to the blastocyst stage of grade 3 and grade 4 embryos was 46 and 8.5% in the two groups respectively (P < 0.05). Using a different three-point grading system for the blastocysts, 75.3% of the blastocysts in group 1 were either grade 1 or grade 2 and 24.7% were grade 3. However, in group 2 all blastocysts were grade 3. All embryos observed in group 1 reached the blastocyst stage by day 5 or 6 compared with 25% of the embryos reaching the blastocyst stage by this time in group 2. While 31.2% of the blastocysts in group 1 showed evidence of spontaneous hatching in vitro, none of the blastocysts in group 2 hatched. In conclusion, progression to the blastocyst stage occurred at a much lower and slower rate in embryos derived from testicular round spermatids. Furthermore, all blastocysts resulting from ROSI were of poor quality and none showed spontaneous hatching. These results may explain the dismal outcome associated with ROSI.

Outcome of testicular sperm retrieval procedures in non-obstructive azoospermia: percutaneous aspiration versus open biopsy.

The aim of this study was to evaluate whether the extraction of testicular spermatozoa with percutaneous versus open biopsy has an effect on the treatment outcome with intracytoplasmic sperm injection (ICSI) in men with non-obstructive azoospermia. Regardless of testicular size, follicle stimulating hormone concentration, and previous biopsy result, percutaneous testicular sperm aspiration (PTSA) using a 21-gauge butterfly needle was attempted first and if this failed testicular sperm extraction (TESE) was performed. In 63 men spermatozoa were found with PTSA whereas in 228 men TESE had to be undertaken. More men in the PTSA group had previously been diagnosed with hypospermatogenesis (82 versus 50%). Compared with the PTSA group, more men in the TESE group had germ cell aplasia (27 versus 10%) or maturation arrest (22 versus 8%). There was no difference between the groups regarding mean age of men and their partners, duration of stimulation, oestradiol concentration on the day of human chorionic gonadotrophin, number of oocytes retrieved, fertilization rate, and embryo quality between the two groups. The number of embryos transferred (4.38 versus 3.90) was significantly higher in the PTSA group (P < 0.05), reflecting the increased number of embryos available for transfer. Implantation rate per embryo was 20.7% in the PTSA and 13.3% in the TESE group (P < 0.05). Clinical pregnancy rates were 46 and 29% in the PTSA and TESE groups respectively (P < 0.05). Clinical abortion rates were similar (21.2 versus 24%). It is concluded that in men with non-obstructive azoospermia, easier sperm retrieval, which is most likely indicative of a more favourable histopathology, is associated with higher implantation rates per embryo.

Elevated serum progesterone level on the day of human chorionic gonadotropin administration does not adversely affect implantation rates after intracytoplasmic sperm injection and embryo transfer.

OBJECTIVE: To evaluate the association between serum P levels on the day of hCG administration and the outcome of intracytoplasmic sperm injection (ICSI). DESIGN: Retrospective case study. SETTING: Assisted reproduction unit of a tertiary care private hospital. PATIENT(S): Nine hundred eleven ICSI cycles that proceeded to ET were studied. INTERVENTION(S): The decision to administer hCG was based on serum E2 levels and follicle size. Serum P was measured from frozen sera obtained on the day of hCG administration. Cycles were stratified according to serum P levels of <0.9 ng/mL (n = 298) or > or =0.9 ng/mL (n = 613). This cutoff level was selected because it yielded the highest sensitivity and specificity according to a receiver operator characteristic curve. MAIN OUTCOME MEASURE(S): Implantation and clinical pregnancy rates. RESULT(S): In cycles with high serum P levels, more oocytes were retrieved and more embryos were available for transfer. Clinical pregnancy rates per ET in the low and high P groups were 36.9% and 45.4%, respectively (P<.05). The implantation rate per embryo was similar in the two groups (14.9% and 16.4%, respectively, in cycles with P levels <0.9 vs > or =0.9 ng/mL). Abortion rates were 22.7 and 25.8%, respectively (P>.05). CONCLUSION(S): Our data showed no adverse effect of high serum P levels on the day of hCG administration on implantation rates after ICSI and ET.

Intra- and inter-laboratory variability in the assessment of sperm morphology by strict criteria: impact of semen preparation, staining techniques and manual versus computerized analysis.

We designed prospective studies to compare manual and computerized analysis of sperm morphology by strict criteria using different semen processing and staining techniques. A total of 54 semen samples were studied; slides were prepared from each subject from liquefied semen and after washing, and stained with Diff-Quik or Papanicolaou. An intra-laboratory, blind assessment was performed manually (two observers) and using a computerized analyser (two readings). This demonstrated a very good correlation between manual analysis of liquefied and washed samples with both staining techniques [intraclass coefficient (ICC) = 0.93 and 0.83]. Greater agreement was observed between computerized readings (washed samples) of Diff-Quik (ICC = 0.93) than of Papanicolaou-stained slides (ICC = 0.66). An excellent intra-laboratory correlation was observed for within-computer readings (ICC = 0.93). There was moderate agreement between inter-laboratory computer readings (two centres, ICC = 0.72). Although there was lower inter-laboratory agreement for manual and manual versus computer readings, overall results of all manual and computer analyses showed good agreement (ICC = 0.73). Diff-Quik staining is reliable for both manual (liquefied) and computer (washed) analysis of strict sperm morphology. Intra- and inter-computer analyses using this method reached satisfactory levels of agreement. There is still high inter-laboratory variability for the manual method.

Evaluation of uterine cavity by sonohysterography in women scheduled for intracytoplasmic sperm injection.

A prospective study was performed to determine the feasibility of evaluating the uterine cavity by sonohysterography (SHG) in women who were scheduled for intracytoplasmic sperm injection (ICSI) due to severe male factor infertility and who had not had a previous hysterosalpingography (HSG). Sonohysterography was performed in 80 women scheduled for ICSI. A subsequent hysteroscopy was undertaken in patients with intracavitary lesions. The outcome of ICSI for the women undergoing SHG was compared with that of 240 cycles performed (during the same time period) in patients who had a normal HSG before admission to the clinic. There were no complications attributable to the SHG procedure. Hysteroscopy correctly identified all lesions depicted by SHG. SHG and HSG groups were comparable with regard to female age and duration of infertility. Clinical pregnancy rates per transfer were 40.2% and 42.5% in the SHG and HSG groups, respectively. Abortion rates in the two groups were also similar (14.8 and 11.0%, respectively). In conclusion, sonohysterography appears to be a simple, inexpensive, and safe alternative to HSG for evaluation of the uterine cavity in women scheduled for ICSI.

A trial of reducing adhesion formation in a uterine horn model.

For the prevention of postoperative adhesion formation, one of the most common causes of infertility, none of the adjuvants had been proven uniformly effective. In this study we evaluated the effectiveness of sodium carboxymethylcellulose (SCMC) and disodium cromoglycate (DSCG) in postoperative adhesion prevention in a rat uterine horn model. Thirty female Sprague-Dawley rats were used. After uterine horn abrasion, in 10 rats 10 ml 0.9% saline, in 10 rats 10 ml of 2% SCMC, and in 10 rats 10 ml DSCG were administered intraperitoneally. Two weeks later, all animals were sacrificed and adhesion formation was assessed. All the pieces of the peritoneum biopsies were stained with Luna's mast cell stain to assess the mast cell degranulation. The mean adhesion scores were 2.1, 2.0 and 1.5 for saline, SCMC and DSCG groups respectively. There were no significant differences among all groups. In the pathologic examination, mast cell degranulation was less in the DSCG group than the other groups.

Improved oocyte quality is obtained with follicle stimulating hormone alone than with follicle stimulating hormone/human menopausal gonadotrophin combination.

The aim of this study was to compare the efficacy of pure follicle stimulating hormone (FSH) with that of FSH/human menopausal gonadotrophin (HMG) combination in downregulated cycles. A total of 357 patients was evaluated retrospectively. Sixty percent of patients in the FSH group and 55% in the FSH/HMG group were new; the others were repeat patients. Ovulation was suppressed with leuprolide acetate in all patients, followed by either FSH (n = 218) or FSH/HMG (n = 119). There was no difference in patients' age, infertility factors, number of ampoules used, length of stimulation, oestradiol levels on day of human chorionic gonadotrophin (HCG) administration, number of oocytes recovered or the number of embryos transferred. Also, nuclear maturity at aspiration and fertilization rates were not different between the two groups. FSH stimulation resulted in a significantly higher percentage of mature oocytes that showed the typical 'mature' morphological characteristics (P < 0.0001). The clinical pregnancy rates per transfer were 40 and 28% in patients stimulated with pure FSH and FSH/HMG respectively (P < 0.05). The significantly higher number of immature oocytes matured in vitro in the FSH/HMG group (P = 0.001) suggests a possible effect on in-vitro maturation, due to luteinizing hormone present in HMG. The difference in mature oocyte quality may be an important determinant in the higher pregnancy rates for the FSH-stimulated patients.

Granulosa cell tumor of the ovary. A clinicopathological evaluation of 60 cases.

The patients with granulosa cell tumor of the ovary constituted 7.6% (60/780) of all ovarian malignancies treated at our Institution. The mean age of patients at diagnosis was 53.1. The most frequent symptom was abnormal vaginal bleeding. Of the 60 patients, 36 had stage I, 2 had stage II, 16 had stage III and 6 had stage IV disease. Endometrial hyperplasia and adenocarcinoma were detected in 18 and 3 patients, respectively. Lymph node metastasis was detected in only one of 18 patients subjected to lymphadenectomy. Recurrent disease was observed in 3 of 36 patients with stage I disease. The overall 5-year survival was found to be 85.0% (51/60). This figure varied from 100.0% to 63.6% according to the stage. In patients with stage I disease, surgery with and without adjuvant therapy achieved the same 5-year survival rate. In advanced stage, 5-year survival rate dropped from 90.0% with no gross residual disease to 25.0% with residual disease more than 2 cm. In patients with stage I disease, surgery only seems to be the treatment of choice. In advanced stage, since residual disease after surgery effects survival significantly, an aggressive surgical approach is advocated.

Immature teratoma of the ovary.

The clinicopathologic experience of 10 patients with immature ovarian teratoma is presented. The mean age of the patients was 22.1. Abdominopelvic mass was the presenting symptom in the majority of cases. Immature ovarian teratomas accounted for 4.0% of germ cell tumors and 2.1% of all ovarian neoplasms diagnosed in our institution. Of the patients, 6 had Stage I disease and 7 had grade I tumor. Unilateral tumor was encountered in the majority of patients. Adequate primary surgical-pathologic staging and multiagent chemotherapy seem to be the treatment of choice.

Complications of radical vulvectomy and inguinal lymphadenectomy for the treatment of carcinoma of the vulva.

Forty-two patients with invasive carcinoma of the vulva, subjected to radical vulvectomy and inguinal lymphadenectomy, were evaluated retrospectively. The mean age of patients was 61.6 years. Fifteen patients (35.7%) had complicating medical diseases, the histopathological diagnoses were squamous carcinoma (n = 39), undifferentiated carcinoma (n = 1), and malignant melanoma (n = 2). The postoperative morbidity and mortality rates were found to be 73.8% and 11.6%, respectively.