Resistance exercise training and alendronate reverse glucocorticoid-induced osteoporosis in heart transplant recipients.

BACKGROUND: Immunosuppression therapy with bolus glucocorticoids causes regional osteoporosis in the axial skeleton of heart transplant recipients (HTR). No preventive strategy is generally accepted for steroid-induced bone loss. METHODS: To determine the efficacy of an anti-osteoporosis regimen that combined a bisphosphonate agent (alendronate sodium) with the osteogenic stimulus of mechanical loading, 25 HTRs were randomly assigned either to a group that received alendronate (10 mg/day) for 6 months (ALEN; n = 8), a group that received alendronate (10 mg/day) and performed specific resistance exercises for 6 months (ALEN + TRN; n = 8) or to a non-intervention control group (CONTR; n = 9). Alendronate was initiated at 2 months after transplantation. Bone mineral density (BMD) of the total body, femur neck and lumbar spine (L-2 and L-3) was measured by dual-energy X-ray absorptiometry before and 2, 5 and 8 months after transplantation. Resistance training consisted of lumbar extension exercise (MedX) performed 1 day/week and 8 variable resistance exercises (MedX) performed 2 days/week. RESULTS: Pre-transplantation BMD values did not differ among the 3 groups. BMD of the total body, femur neck and lumbar vertebra were significantly decreased below baseline at 2 months after transplantation in CONTR (-2.6 +/- 0.9%, -5.1 +/- 1.8%, -12.5 +/- 4.2%, respectively), ALEN (-2.8 +/- 0.8%, -5.3 +/- 1.6%, -12.0 +/- 3.9%) and ALEN + TRN groups (-2.7 +/- 1.0%, -5.6 +/- 2.1%, -11.2 +/- 3.7%). CONTR had further significant losses of BMD after 3 and 6 months. ALEN had no further regional BMD losses after initiation of alendronate therapy. ALEN + TRN restored BMD of the whole body, femur neck and lumbar vertebra to within 0.9%, 2.1%, and 3.4% of pre-transplantation levels, respectively. CONCLUSIONS: Resistance exercise plus alendronate was more efficacious than alendronate alone in restoring BMD in HTRs. Our results indicate that anti-osteoporosis therapy in this population should include both an anti-resorptive agent as well as an osteogenic stimulus, such as mechanical loading.     

Effect of photodynamic therapy on blood flow in normal and tumor vessels

The aim of this series of experiments was to determine the dynamic blood flow changes that occur in normal and neoplastic tissues during photodynamic therapy. Mice bearing SMT-F tumors and rats with transplanted chondrosarcomas were injected with graded doses of dihematoporphyrin ether. Studies of changes in single-vessel and whole-tumor blood flow were carried out with 630 nm light activation. A helium neon laser Doppler velocimeter was used to stimulate dihematoporphyrin ether, as well as to measure changes in flow velocity in both single-vessel and whole-tumor models. There was a reduction of flow velocity in all vessels and tumors in animals injected with 1 to 40 mg/kg dihematoporphyrin ether intraperitoneally. The extent of flow reduction was related to drug dose administered. Decreases in blood flow began within 10 seconds of light stimulation and were maximal within 5 minutes. Both normal and tumor vessels responded similarly. We conclude that photodynamic therapy leads to significant microcirculatory changes that may be pertinent to the mechanism of tumor necrosis.     

Nicotine applied by transdermal patch induced HSV-1 reactivation and ocular shedding in latently infected rabbits.

The identification of factors involved in herpes virus latency and reactivation is critical to a better understanding of the mechanisms essential to viral neuroinvasiveness and neurovirulence. Recurrent episodes of ocular herpes infections cause irreversible corneal scarring and are the primary cause of loss of vision due to an infectious agent in industrialized countries. In this study, we examined the ability of nicotine, a compound known to be involved in stress-associated immunomodulation and recognized as one of the most frequently used addictive agents, to induce ocular shedding in rabbits latently infected with herpes simplex virus type 1 (HSV-1) strain McKrae. New Zealand white rabbits latently infected with HSV-1 at 3-4 weeks post-inoculation were randomly divided into two groups. The corneas of all rabbits were free of lesions as verified by slit lamp biomicroscopy. One group received nicotine by transdermal patch (21 mg/day) for 20 days and the other group served as the control. Reactivation data were obtained by detection of virus in tear film collected by ocular swabbing performed concurrently with the administration of nicotine. Compilation of data from three separate experiments demonstrated that 16.5% (258/1560) of the swabs taken from rabbits treated with nicotine were positive for virus, compared with 8.3% (53/639) of swabs taken from controls. Rabbits receiving nicotine exhibited a significantly (P < 0.0001) higher rate of ocular shedding than controls. The concentration of nicotine in the serum was determined at various times (0-24 hrs) after new patch replacement. Peak (average) serum level of nicotine was obtained 8 hours after patch replacement and exhibited a broad range of values (0.233 microg/mL-6.21 microg/mL). These results suggest that an initial systemic exposure to nicotine significantly increases HSV-1 reactivation. Further studies are needed to reveal any effects of nicotine dependency and nicotine withdrawal on herpesvirus reactivation.     

Congenital absence of the inferior rectus muscle--diagnosis and management.

BACKGROUND: Congenital absence of the inferior rectus muscle is a rare cause of apparent inferior rectus palsy especially in the absence of associated cranial facial anomalies. METHODS: We report three cases of isolated congenital absence of the inferior rectus muscle and its successful surgical management. RESULTS: Failure of the normal embryologic development of the mesodermal complex around the eye can lead to agenesis of the extraocular muscles. In apparent palsies of the inferior rectus muscle and no definite cause, a high index of suspicion and orbital imaging can confirm the diagnosis of congenitally absent inferior rectus preoperatively. Surgical correction may involve inferior transposition of the horizontal rectus muscles. CONCLUSIONS: Although rare, congenital absence of the inferior rectus muscle is a possible cause of apparent inferior rectus muscle palsy particularly in the absence of another identifiable cause. Strabismus surgery in conjunction with intramuscular botulinum toxin injection can offer significant improvement in function and cosmesis of these patients.     

Subclavian vein thrombosis: a continuing challenge

Subclavian vein thrombosis is a relatively uncommon but potentially morbid disease entity. To determine the frequency, cause, and best mode of treatment of this problem, we performed a chart review of all patients with a diagnosis of subclavian vein thrombosis at two major metropolitan hospitals during a 6-year period. A total of 40 patients were identified with subclavian vein thrombosis, which represented 3.5% of all venous thromboses detected during the 6-year period. No side or sex predilection was noted and the majority of patients were outpatients. The cause was fairly evenly divided among intravenous catheters (32%), anatomic abnormalities (45%), and carcinoma with postoperative radiation (22.5%). Despite the increasing use of the subclavian veins for pacemaker leads, hyperalimentation, and permanent intravenous access for chemotherapy, there has not been an increase in diagnosed subclavian vein thrombosis. Anatomic abnormalities with compression of the vein respond well to either heparinization or lytic therapy but require surgery if the venous abnormality persists. Treatment consisted of lytic therapy in 20%, heparinization in 55%, and elevation with removal of the central line in 25% of patients. All patients responded well to treatment, with a decrease in swelling and symptoms; no patient progressed to venous gangrene and only one (2.5%) had a documented pulmonary embolus. Medical treatment provides excellent long-term benefit in most cases unless complicated by an anatomic abnormality.     

Mechanisms associated with the expression of cisplatin resistance in a human ovarian tumor cell line following exposure to fractionated X-irradiation in vitro.

Interactions between cisplatin (CDDP) and irradiation are of potential significance for the combined modality treatment of cancer. Previous data have indicated that following in vitro exposure to X-irradiation certain tumour cells expressed resistance to CDDP. To identify parameters associated with this CDDP resistance, the human ovarian carcinoma cell line SK-OV-3/P was pre-exposed to fractionated X-irradiation (total dose: 50 Gy) in vitro. The resultant subline (SK-OV-3/DKR-10) proved 2-fold resistant to CDDP, but not to acute X-irradiation. Consistent with unaltered dihydrofolate reductase and thymidylate synthase activities, SK-OV-3/DXR-10 cells were neither cross-resistant to methotrexate nor to 5-fluorouracil. Verapamil (6.6 microM) significantly (P less than 0.05) enhanced CDDP-induced cytotoxicity in the resistant DXR-10 subline, but not in the parental cells. Total glutathione levels were significantly (P less than 0.01) lower in the resistant subline and BSO pretreatment failed to influence cytotoxicity, whilst related enzyme activities were not consistently modified in the SK-OV-3/DXR-10 cells. Resistance in these cells was associated with significantly decreased cisplatin uptake (P less than 0.002). Immediately following drug exposure the total platination level of the DNA, quantitated immunochemically, was higher (P less than 0.05) in the resistant subline indicative of increased tolerance to DNA damage. After an 18 h post-treatment incubation the parental cell line appeared proficient in the removal of the intrastrand adduct Pt-AG, but deficient in removing the major adduct Pt-GG and the difunctional Pt-(GMP)2 lesion, whilst the DXR-10 resistant subline appeared proficient in removal of all four Pt-DNA adducts. DNA polymerases alpha and beta activities, however, were comparable in both cell lines. These data implicate both enhanced repair and increased tolerance of DNA damage as mechanisms of resistance to CDDP resulting from in vitro exposure of a human ovarian carcinoma cell line to fractionated X-irradiation.     

Segmental intestinal muscular thinning: a possible cause of intestinal obstruction in the newborn

Intestinal obstruction proximal to a transition zone without an interposed physical barrier usually indicates Hirschsprung disease. The authors report one case of focal small bowel muscular thinning just distal to a transition zone that produced clinical and radiographic findings that simulated long-segment Hirschsprung disease in a 2-day-old infant.     

Very low versus undetectable maternal serum alpha-fetoprotein values and fetal death

Very low maternal serum alpha-fetoprotein (MSAFP) levels (less than 10 ng/mL) are known to be associated with non-viable pregnancies, including conditions such as fetal death, molar pregnancies, and non-pregnancies. There has not been agreement, however, as to whether very low MSAFP levels indicate already existing fetal deaths or are actually predictive. We analysed 230 pregnancies with MSAFP levels less than 10 ng/mL from among 15,807 women (1.5 per cent) screened consecutively during a three-year period and identified 26 non-viable pregnancies, 22 of which were diagnosed sonographically as part of the screening process (17 missed abortions, 3 blighted ova, 2 non-pregnancies). Furthermore, 20 of these 22 pregnancies were associated with essentially undetectable MSAFP levels (less than 5 ng/mL). Our data indicate that pregnancies with MSAFP values less than 5 ng/mL are the group most strongly associated with fetal non-viability and that very low MSAFP values are not strongly predictive for fetal death.     

Gender difference in anaerobic capacity: role of aerobic contribution.

The purpose of this study was to evaluate effects of gender on anaerobic and aerobic contributions to high-intensity exercise. A group of 38 subjects (22 women, 16 men) performed modified Wingate tests against resistances of 0.086 kg kg-1 body mass (0.844 N kg-1) for women and 0.095 kg kg-1 body mass (0.932 N kg-1) for men. The aerobic contribution to total work performed was determined from breath-by-breath analyses of expired gases during each test. Total work in 30 s was 30% lower (Student's t test; P < 0.01) in women than men (211 +/- 5 J kg-1 versus 299 +/- 14 J kg-1). Aerobic contribution was only 7% lower (P = 0.12) in women than men (53 +/- 1 J kg-1 versus 57 +/- 2 J kg-1). The anaerobic component of the work performed, determined by subtraction of the aerobic component from total work in 30 s, was 35% lower (P < 0.01) in women than men (158 +/- 5 J kg-1 versus 242 +/- 15 J kg-1). It is concluded that, because women provide a relatively higher (P < 0.01) portion of the energy for a 30-s test aerobically than men (25% versus 20%), total work during a Wingate test actually underestimates the gender difference in anaerobic capacity between women and men.     

Cigarette smoking increases white blood cell aggregation in whole blood.

We studied the effect of chronic cigarette smoking on white blood cell aggregation, increased aggregation predisposes to microvascular occlusion and damage. Current smokers had significantly increased white blood cell aggregation when compared with non smokers. The presence of chronically activated white blood cells in current smokers may be relevant in the pathogenesis of ischaemic vascular disease.