Antiviral therapy with ganciclovir for cytomegalovirus retinitis and bilateral exudative retinal detachments in an immunocompromised child

A child with bilateral cytomegalovirus (CMV) retinitis, vitritis, and exudative retinal detachments, who was in remission from stage IV neuroblastoma and status post-chemotherapy and autologous bone marrow transplantation, was treated with ganciclovir. The drug is a new acyclic nucleoside antiviral drug with potent antiCMV activity. There was bilateral retinal reattachment, clearing of vitritis and regression of retinal exudates and hemorrhages, with concomitant resolution of viral shedding in urine and blood, on ganciclovir 7.5 mg/kg per day. There was recurrence of exudative detachments, vitritis and retinitis when the dose was reduced to 2.5 mg/kg per day, and regression of these findings when the dose was again increased to 7.5 mg/kg per day. Despite continued therapy at this dose, a relapse occurred. When the dose of drug was doubled to 15 mg/kg per day, there initially was a partial therapeutic response, followed by a subsequent relapse. No further response was seen when the dose was increased to 19.5 mg/kg per day. This patient was treated with ganciclovir for a total of 192 days. No adverse reactions to ganciclovir were seen. On the last day of drug administration, there were persistent bilateral exudative retinal detachments and progressive optic nerve head involvement with optic disc pallor, despite quiescence of the retinitis.     

Aspirin resistance: possible roles of cardiovascular risk factors, previous disease history, concomitant medications and haemorrheological variables

BACKGROUND AND OBJECTIVE: Recent studies have described the incidence (approximately one in eight high-risk patients will experience a further atherothrombotic event over a 2-year period) of aspirin (acetylsalicylic acid) resistance and its possible background. The aim of this study was to compare the characteristics (risk profile, previous diseases, medications and haemorrheological variables) of patients in whom aspirin provided effective platelet inhibition with those in whom aspirin was not effective in providing platelet inhibition. METHODS: 599 patients with chronic cardio- and cerebrovascular diseases (355 men, mean age 64 +/- 11 years; 244 women, mean age 63 +/- 10 years) taking aspirin 100-325 mg/day were included in the study. Blood was collected between 8:00am and 9:00am from these patients after an overnight fast. The cardiovascular risk profiles, history of previous diseases, medication history and haemorrheological parameters of patients who responded to aspirin and those who did not were compared. Platelet and red blood cell (RBC) aggregation were measured by aggregometry, haematocrit by a microhaematocrit centrifuge, and plasma fibrinogen by Clauss' method. Plasma and whole blood viscosities were measured using a capillary viscosimeter. RESULTS: Compared with aspirin-resistant patients, patients who demonstrated effective aspirin inhibition had a significantly lower plasma fibrinogen level (3.3 g/L vs 3.8 g/L; p < 0.05) and significantly lower RBC aggregation values (24.3 vs 28.2; p < 0.01). In addition, significantly more patients with effective aspirin inhibition were hypertensive (80% vs 62%; p < 0.05). Patients who had effective platelet aggregation were significantly more likely to be taking beta-adrenoceptor antagonists (75% vs 55%; p < 0.05) and ACE inhibitors (70% vs 50%; p < 0.05), whereas patients with ineffective platelet aggregation were significantly more likely to be taking HMG-CoA reductase inhibitors (statins) [52% vs 38%; p < 0.05]. Use of statins remained an independent predictor of aspirin resistance even after adjustment for risk factors and medication use (odds ratio 5.92; 95% CI 1.83, 16.9; p < 0.001). CONCLUSIONS: The mechanisms underlying aspirin resistance are multifactorial. Higher fibrinogen concentrations increase RBC aggregation and can also result in increased platelet aggregation. The higher rate of hypertension in patients with effective platelet aggregation on aspirin could explain the differences in beta-adrenoceptor antagonist and ACE inhibitor use between these patients and aspirin-resistant patients. Furthermore, an additive effect of these drugs may contribute to effective antiplatelet therapy. It is also possible that drug interactions with statins might reduce aspirin bioavailability and/or activity, thereby reducing platelet inhibition in aspirin-resistant patients.     

MAP-2 Expression in the Human Adenohypophysis and in Pituitary Adenomas. An Immunohistochemical Study

MAP-2, a well characterized member of the microtubule associated protein (MAP) family, binds to and stabilizes microtubules and is involved in cell proliferation as well as neuronal differentiation. The aim of the present work was to study MAP-2 expression in human adenohypophyses and pituitary adenomas. To our knowledge, data regarding MAP-2 expression in human pituitaries has not been reported to date. For immunohistochemistry, the streptavidin-biotin-peroxidase complex method was used. Nine non-tumorous adenohypophyses and 77 adenomas (GH-, PRL-, ACTH-, TSH-, FSH/LH- and/or alpha subunit- producing or immunonegative tumors) were investigated. The results show that MAP-2 is expressed in the cytoplasm of non-tumorous adenohypophysial cells as well as of various pituitary adenoma types. No significant correlation was found between MAP-2 expression and gender, patient age, mitotic activity, MIB-1 labelling indices, hormone immunoprofile, and endocrine status, ie. hormonal activity or lack thereof. Thus MAP-2 expression cannot be used to estimate cell proliferation rate, growth potential, endocrine activity or biologic behaviour of an adenoma. Immunopositivity appeared to be stronger in the cytoplasm of adenoma cells than in that of non-tumorous adenohypophysial cells, implying that the adenoma cells contain larger quantities of MAP-2. It can be concluded that the functional activity of MAP-2 is not associated with the manufacture of any specific adenohypophysial hormone(s) and is not limited to one specific cell type.     

Injuries from biologic material of suicide bombers

BACKGROUND: The management of penetrating wounds caused by suicide bomber bone fragments, contaminated by infectious viruses such as hepatitis or human immunodeficiency virus, is a new medical challenge. The aim of this study was to review the literature and add our experience in the treatment of such wounds. PATIENTS AND METHODS: The files of 94 patients with multiple penetrating fragment injuries of the musculoskeletal system were reviewed. Following any necessary life-saving procedures, the patients underwent wound debridement with delayed wound closure. Broad-spectrum antibiotic treatment was started immediately on admission, and all patients were inoculated with antitetanus toxin and hepatitis B vaccine. RESULTS: The most common injuries were multiple lacerations caused by penetration of small metal fragments. Those that were not removed on initial debridement and continued to cause pain were removed during follow-up. Twenty-three patients presented with 49 open fractures caused by the penetrating nails or impact against other objects. Three cases were complicated by chronic osteomyelitis. Three patients presented with injuries caused by bone fragments from the suicide bomber. Samples of bone from one suicide bomber tested positive for hepatitis B virus. None of the patients developed clinical signs of hepatitis B, human immunodeficiency virus or other severe infections during follow-up. CONCLUSIONS: The penetration of biologic material may transmit severe incurable infectious disease.     

Pituitary carcinoma: a clinicopathological review

Pituitary carcinomas are rare tumors; less than 100 well-documented cases have been reported to date. Such tumors are aggressive and associated with a high mortality rate. The molecular events leading to the development of pituitary carcinomas are largely unknown. Recent studies have only begun to shed light on the probable mechanisms of tumor initiation and progression. A review of the clinicopathological and molecular genetic characteristics of pituitary carcinomas is presented.     

Four pregnancies and two deliveries after unilateral orchidectomy and chemotherapy for testicular embryonal carcinoma

This case report describes a 33-year-old patient diagnosed with left-sided testicular embryonic carcinoma with vascular invasion. Unilateral orchiectomy was performed and the patient subsequently underwent chemotherapy. He retained fertility and later fathered healthy children.     

The use of the distal Syme's procedure for treating onychopathy

There are many procedures available to the podiatric surgeon to deal with a painful, deformed nail. The Syme's procedure should not be overlooked, though more conservative options should be attempted before this procedure. With the proper surgical candidate (ie, intact neurovascular status), this is a successful, safe procedure easy to perform under local anesthesia.     

Vitamin D receptor gene polymorphism in hypercalciuric children

Idiopathic hypercalciuria is a complex disease resulting from an interaction between environmental and genetic factors. Recently, the relationship between vitamin D receptor (VDR) alleles and calcium homeostasis has been investigated. This study was conducted to explore the association of VDR gene polymorphism with the risk of absorptive hypercalciuria (AH). We investigated the VDR gene polymorphisms, ApaI, BsmI, and TaqI, in relation to intact parathormone (PTH), osteocalcin, and 25-hydroxyvitamin D in 80 children (42 males, 38 girls) with AH and in 86 healthy children without hypercalciuria. A significant difference in the ApaI genotype was observed between the AH group and the control group (²=7.21, P=0.027). The AA genotype was associated with a 3.5-fold increased risk for idiopathic hypercalciuria compared with the Aa/aa genotype (odds ratio 3.5, 95% confidence interval 1.1–11). The BsmI and TaqI polymorphisms did not show any significant association with AH. Serum osteocalcin levels were significantly higher in the group with the AA genotype compared with those with the Aa or aa genotype (P=0.02, P=0.05, respectively). The results indicate that the ApaI AA genotype of the VDR gene is not only associated with AH but is also related to differences in serum osteocalcin.