Treatment of hypogonadal adolescent boys with long acting subcutaneous testosterone pellets

AIMS: Long acting subcutaneous testosterone pellets are of proved efficacy for the treatment of hypogonadal men, but have not been reported as a treatment modality in adolescent boys. Pharmacodynamic studies of subcutaneous testosterone release have shown prolonged normalisation of testosterone levels for at least four months. Administration of a long acting, safe, effective, and convenient form of treatment is desirable when life-long treatment is indicated. PATIENTS AND METHODS: Eighteen boys (aged 13.9-17.5 years at the start of treatment)-seven with primary hypogonadism, nine with secondary hypogonadism, and two boys being treated with testosterone for tall stature--were given testosterone pellets (8-10 mg/kg) every six months for 18 months. Height, weight, pubertal status, and psychosocial parameters were assessed and follicle stimulating hormone, luteinising hormone, testosterone, prolactin, and lipids were measured at 0, 1, 3, 6, 12, and 18 months. Bone age was measured at 0 and 12 months. RESULTS: In all boys growth velocity continued appropriately for bone age. Puberty continued to progress in all boys and in two boys the amount of virilisation exceeded that seen with previous treatment with intramuscular testosterone. After testosterone administration, follicle stimulating hormone and luteinising hormone suppressed incompletely in the boys with primary hypogonadism. Serum testosterone ranged from 4.3 to 26.7 nmol/l at three months to less than 10 nmol/l at six months after implantation. Prolactin and lipid levels were normal throughout the study. By report, there was an improvement in mood and emotional wellbeing. No pellet extrusions occurred in a total of 156 pellet insertions. CONCLUSIONS: All boys preferred this mode of testosterone administration to intramuscular injections. Long acting subcutaneous testosterone pellets are safe, efficacious, well tolerated, and convenient, and result in normal physical growth and improved psychological outlook in adolescent hypogonadal boys.     

Balo病同心圆硬化的MRI分析

目的：探讨Balo病同心圆硬化（BCS）的磁共振表现特征及其病理基础.方法：回顾性分析4例Balo病同心圆硬化患者的MRI表现,均经激素治疗临床症状好转后行MRI复查.结果：4例患者中,1例单发,3例多发,最多者病灶5个.病变主要累及大脑半球皮层下和深部白质区,共发现11个病灶,其中顶叶半卵圆中心和颞叶的发病比例高.典型同心圆样病灶8个,直径1～2.3cm,同心圆层数为3～5个.在T1WI加权像呈等、低信号相间;T2WI,FLAIR像上呈等、高信号交替环,病灶周围有轻度水肿表现,上述表现与镜下脱髓鞘区与髓鞘保留区相间相对应.其余3个不典型的病灶呈斑片状或煎蛋样改变;增强后1例病灶呈点状或边缘线状强化.结论：Balo病同心圆性硬化的MRI及其增强扫描具有特征性表现,可作为本病诊断的主要方法,并可用于疗效的观察.     

Does the publication of NICE guidelines for venous thromboembolism chemical prophylaxis influence the prescribing patterns of UK hip and knee surgeons?

IntroductionWe assessed the practice of surgeons regarding venous thromboembolism (VTE) chemical prophylaxis for total hip replacement (THR) and total knee replacement (TKR), before and after issuing of updated National Institute for Health and Care Excellence (NICE) guidance in 2018.MethodsA survey, circulated through the British Hip Society and regional trainee networks/collaboratives, was completed by 306 UK surgeons at 187 units. VTE chemical prophylaxis prescribing patterns for surgeons carrying out primary THR (n=258) and TKR (n=253) in low-risk patients was assessed after publication of 2018 NICE recommendations. Prescribing patterns before and after the NICE publication were subsequently explored.ResultsFollowing the new guidance, 34% (n=87) used low-molecular-weight heparin (LMWH) alone, 33% (n=85) aspirin (commonly preceded by LMWH) and 31% (n=81) direct oral anticoagulants (DOACs: with/without preceding LMWH) for THR. For TKR, 42% (n=105) used aspirin (usually monotherapy), 31% (n=78) LMWH alone and 27% (n=68) DOAC (with/without preceding LMWH). NICE guidance changed the practice of 34% of hip surgeons and 41% of knee surgeons, with significantly increased use of aspirin preceded by LMWH for THR (before=25% vs after=73%; p<0.001), and aspirin for TKR (before=18% vs after=84%; p<0.001). Significantly more regimens were NICE guidance compliant after the 2018 update for THR (before=85.7% vs after=92.6%; p=0.011) and TKR (before=87.0% vs after=98.8%; p<0.001).ConclusionOver one-third of surveyed surgeons changed their VTE chemical prophylaxis in response to 2018 NICE recommendations, with more THR and TKR surgeons now compliant with latest NICE guidance. The major change in practice was an increased use of aspirin for VTE chemical prophylaxis.     

Multiple orbital venous malformations presenting with enophthalmos in a patient with presumed blue rubber bleb nevus syndrome

A 27-year-old white woman presented with enophthalmos in the right eye. The visual acuity was 20/20 in both eyes. External examination showed 7 mm of enophthalmos of the right eye with deepened superior palpebral sulcus compared with the left eye. After Valsalva maneuver, the right eye became 4-mm exophthalmic compared with the left eye. Extraocular movements were full. There was no palpable orbital mass or diplopia. MRI showed diffuse enhancing intraconal orbital and nasopharyngeal masses consistent with venous malformations in the right orbit. Systemic evaluation revealed bluish vascular lesions on the hard and soft palates, and the pretibial area of her right leg. These findings were suggestive of blue rubber bleb nevus syndrome. The patient was observed, and her clinical findings remained stable for 12 months. Enophthalmos can be a rare initial presentation of blue rubber bleb nevus syndrome and patients with ophthalmic involvement should undergo systemic evaluation including gastrointestinal, dermatologic, and otorhinolaryngologic examination.     

Biweekly administration of gemcitabine and cisplatin chemotherapy in patients with anthracycline and taxane-pretreated metastatic breast cancer

Gemcitabine and cisplatin are the active agents in metastatic breast cancer pretreated with anthracycline and/or taxane as a second line treatment. The present study was designed to assess the efficacy and safety of this regimen given biweekly schedule in these patients. Twenty-seven women, median age 57, with metastatic breast cancer previously treated with anthracycline and taxane were eligible for enrollment. Gemcitabine was administered intravenously on days 1 and 15 at a dose of 2,000 mg/m(2) and Cisplatin was given intravenously on day 1 and 15 at a dose of 50 mg/m(2). Treatment cycles were repeated on an outpatient basis every 28 days. Of all 27 evaluable patients, the overall response rate was 26% (7 of 27; 95% CI: 11-46%) with seven all partial responses. The stable diseases were found in 9 (33%) patients. At the time of last follow-up, 11 (41%) of the patients died of their disease progression. The median overall survival duration was 7.4 +/- 2.8 months. The 1-year overall survival rate was 46.9% +/- 12.3. Hematological toxicity was not found as the principal dose-limiting toxicity. Severe (grade III/IV) neutropenia was observed only one (4%) patients. No patient was complicated by febrile neutropenia and G-CSF usage was not performed. Grade III and IV anemia were seen in only 4 (15%) and thrombocytopenia was noted only one (4%) patients. Severe hepatic (n = 2) and renal toxicity (n = 1) were observed and these all recovered completely without complication. Several other severe non-hematological side effects were managed easily. Permanent dose reductions were necessary in 9 (33%) patients and chemotherapy administration was also delayed in 7 (26%) patients because of delayed both hematological and non-hematological toxicity recovery. Treatment was discontinued in one (4%) patient due to severe fatigue and deteriorating performance status. In conclusion, gemcitabine and cisplatin combination therapy with this biweekly schedule and dosage is moderately active and extremely safe in patients with metastatic breast cancer previously treated with anthracycline and taxanes.     

Effect of oral administration of kefir on serum proinflammatory cytokines on 5-FU induced oral mucositis in patients with colorectal cancer

Summary  In order to investigate the effect of kefir consumption on mucositis induced by 5-FU based chemotherapy (CT), we monitored the systemic immune response by measurement of the serum proinflammatory cytokine levels and we evaluated the anti-microbial effect of kefir with an agar diffusion method. Forty patients with colorectal cancer were included in this randomized prospective study. On the first 5 days of each CT cycle, the study group received oral lavage with kefir and then swallowed 250 ml of kefir while control group received oral lavage with 0.09% NaCl twice a day. Before and after every cycle of CT, the oral mucosa was assessed. Serum proinflammatory cytokine levels were evaluated before the initiation and after the third and the sixth cycle. Kefir was administered in 99 out of 205 courses. Mucositis developed in 27.3% of the courses given with kefir administration and in 21.7% of the courses given with 0.9% NaCl oral rinses. The difference between the two groups was not statistically significant (p > 0.05). When we compared the serum proinflammatory cytokine levels of the two groups at the baseline and following the third and the sixth cycles, we again found no statistically significant difference (p > 0.05). Kefir consumption at the mentioned doses made no statistically significant effect on serum proinflammatory cytokine levels and on the incidence of mucositis development in cancer patients. Under in vitro conditions, kefir inhibits only Staphylococcus epidermidis.     

Molecular Epidemiology of Cryptosporidiosis in Iranian Children,Tehran, Iran

Background

Cryptosporidium is a worldwide protozoan parasite and one of the most common causes of infection and diarrhea in humans and cattle. The aim of the present study was determination of subtypes of Cryptosporidium among children with diarrhea in Tehran by sequence analysis of the highly polymorphic 60-kDa glycoprotein (GP60) gene.

Methods

Fecal samples were collected from 794 diarrheic children. Initial identification of Cryptosporidium was carried out on stool samples by Ziehl-Neelsen acid-fast staining method. DNA was extracted from positive microscopically samples and Cryptosporidium genotypes and subtypes were determined, accordingly.

Results

Out of 794 collected samples, 19 (2.40%) were positive for Cryptosporidium oocysts. Sequences analysis of GP60 gene showed that 17 (89.47%) of the positive isolates were Cryptosporidium parvum and 2 (10.52%) were C. hominis. All subtypes of C. parvum isolates belonged to allele families IIa (6/17) and IId (11/17). The most common allele in all 17 isolates belonged to IId A20G1a (41.18%). A22G1 (IF) subtype was detected in two C. hominis isolates of the children.

Conclusion

The predominancy of C. parvum species (specially, IId A20G1a subtype) in current study underlines the importance of zoonotic Cryptosporidium transmission in Iran.     

Monarch-1 Activation in Murine Macrophage Cell Line (J774 A.1) Infected with Iranian Strain of Leishmania major

Background

Leishmania major is an intracellular parasite transmitted through the bite of the female phlebotomine sand flies. Leishmania major is able to escape the host immune defense and survive within macrophages. Modulation of the NF-κB (Nuclear Factor-Kappa B) activation and suppression of the pro-inflammatory cytokines by L. major are the main evasion mechanisms that remain to be explored. This study aims to examine the expression level of the Monarch-1 in L. major-infected macrophages, as a negative regulator of the NF-κB activation.

Methods

Murine macrophage cell line (J774 A.1) was infected by metacyclic form of Leishmania promastigotes at macrophage/parasite ratio of 1:10. After harvesting infected cells at different times, total RNA was extracted and converted to cDNA. Semi-quantitative RT-PCR was performed for Monarch-1 by specific primers. Hypoxanthine Phospho-Ribosyl Transferase (HPRT) was used as an internal control to adjust the amount of mRNA in each sample.

Results

Semiquantitive analysis of Monarch-1 mRNA expression level showed a significant expression increase within 6 to 30 hours after L. major infection of macrophages when compared to the control macrophages.

Conclusion

Monarch-1 expression level reveals a significant increase in the early phase of macrophage infection with L. major, which in turn may suppress IL-12 production in Leishmania infected macrophages and deeply influence the relationship between host and parasite.