Controlled trial of thyrotropin releasing hormone in amyotrophic lateral sclerosis

A double-blind controlled trial of thyrotropin releasing hormone (TRH) 150 mg IM daily in 30 patients with amyotrophic lateral sclerosis is reported. The drug/placebo was administered for 2 months, followed by a 2-month "wash-out". Evaluation of strength, functional ability, and respiratory functions was performed. A temporary increase in the strength of some muscles was detected following the administration of TRH, but no change in functional performance was noted. Neither the patients nor the investigators believed the effects were of any marked clinical significance. The course of the illness was not altered.     

Influence of ageing on aerobic parameters determined from a ramp test

Summary The purpose of this study was to examine the four parameters of aerobic function, the maximum oxygen uptake ( O_2max), ventilation threshold (Th _VE), efficiency, and the effective time constant for oxygen consumption ( 0₂), across age. In particular, the study was designed to observe whether there may be accelerated declines in aerobic function beyond 60 years of age. Seventy-nine sedentary men aged 30–84 years were studied. Each subject performed two maximal cycle ramp function tests, and data were collected on a breath-by-breath basis. The O_2max, from a plateau in 0₂, was achieved in 87% of the subjects using the ramp test. The O_2max showed a significant decrease with increasing age (from linear regression,r = –0.81) at a rate averaging 0.037 l·min^–1·year^–1. The Th _VE also declined with increasing age, but at a slower rate (0.013 l·min^–1·year^–1). The O₂ was significantly increased across the age groups from 69 s for those aged 30–40 years to 98s for those aged 60 years or more. There was no evidence of accelerated decline in these aerobic parameters beyond age 60 years, and there were no differences in efficiency (27.5–29.9%) across age. Although other forcing functions should be used to confirm this characterization of the oxygen kinetics, this slowed response with age would result in greater oxygen deficit and possibly earlier fatigue in response to even light exercise in older individuals.     

Alterations of neutrophil responses to tumor necrosis factor alpha and interleukin-8 following human endotoxemia.

Interleukin-8 (IL-8), a neutrophil chemoattractant and activating cytokine, has been implicated as a proinflammatory mediator in gram-negative sepsis. In vitro data support the notion of IL-8 as an endothelial adherence inhibitor. To evaluate this issue, we infused six volunteers with reference endotoxin and measured plasma levels of IL-8, neutrophil tumor necrosis factor alpha (TNF-alpha) receptors, TNF-alpha-induced adherence to fibronectin, and neutrophil chemotaxis to IL-8 and other attractants. We found that, at 3 h postinfusion, IL-8 but not TNF-alpha plasma levels were elevated. Neutrophils had shed L-selectin (mean channel fluorescence decrease, 79 +/- 9 to 49 +/- 7; P = 0.0625) and TNF-alpha receptors (decrease in number of receptors per cell, 1,596 +/- 340 to 574 +/- 93; P = 0.004). Cells were chemotactically desensitized to IL-8. TNF-alpha-induced adherence to fibronectin was suppressed from 69% +/- 5% of the phorbol myristate acetate response to 38% +/- 7% (P = 0.0154). These findings support the notion that release of IL-8 into the vascular space may be an in vivo mechanism for suppression of neutrophil accumulation at extravascular sites. L-Selectin loss would reduce the ability of neutrophils to adhere to activated endothelial cells. The specific loss of migratory response to IL-8 would impair neutrophil delivery to areas where IL-8 was the predominant chemoattractant. Loss of TNF-alpha-induced adherence to fibronectin would blunt those responses, including production of oxidants, capacitated by adherence.     

The induction of immunologic hyporesponsiveness by preoperative donor-specific transfusions and cyclosporine in human cadaveric transplants. A preliminary trial.

A prospective randomized preliminary trial was performed in patients undergoing cadaveric renal transplantation to determine the potential benefits, disadvantages, and logistic problems associated with the administration of donor-specific transfusions and cyclosporine initiated 24 hr before transplantation. Ten patients received DST followed by continuous intravenous CsA approximately 24 hr before cadaveric renal transplantation from the same donor. Twelve patients receiving sequential therapy with Minnesota antilymphoblast globulin, azathioprine, and steroids with subsequent conversion to CsA served as controls. Patient demographics and the donor characteristics were evenly matched in the two groups. While the study group had longer cold ischemia time and more evidence of renal dysfunction within the first two weeks, subsequent renal function was identical in the groups and there were fewer episodes of severe rejection requiring treatment with OKT3 within the first six months in the DST group (5 vs. 0, P less than 0.05), which also had less reactivity in mixed lymphocyte cultures against preserved donor-specific lymphocytes than did the control group (stimulation index 9.0 +/- 3.0 vs. 25.3 +/- 6.0, respectively, P less than 0.05). The need for dialysis, incidence of infections and other complications, and subsequent immunosuppressive therapy were not different in the two groups. It is concluded that DSTs and intravenous CsA initiated 24 hr prior to transplantation are capable of inducing reduced immunologic responsiveness against the specific donor. Patients treated with this therapy should receive organs from "ideal" donors without risk factors and cold ischemia time should not exceed 30 hr. Further clinical studies of this approach are warranted.     

Neurologic status and intracranial hemorrhage in very-low-birth-weight preterm infants. Outcome at 1 year and 5 years

Twenty-six very-low-birth-weight preterm infants with and without intracranial hemorrhage (ICH) were followed up prospectively from birth to school age to determine the relationship between ICH and subsequent neurologic and cognitive outcomes. All children had sequential cranial ultrasound examinations at birth and neurologic assessments at 3-month intervals during the first year, at 1 year of age, and at 5 to 6 years; psychometric assessments were done at 5 to 6 years. Seventeen children had no ICH, 3 had grade 1 ICH, 1 had grade 3 ICH, and 5 had grade 4 ICH. The 1-year Amiel-Tison neurologic assessment in 25 infants demonstrated that 14 were normal, 3 were suspect, and 8 were abnormal. By 5 to 6 years of age, 5 of 8 children neurologically abnormal at 1 year remained abnormal, 2 of 3 children neurologically suspect at 1 year remained suspect; while 9 of 15 children neurologically normal at 1 year remained normal, the remaining 6 had become suspect. The predominant neurologic abnormality at 5 to 6 years was subtle neurologic dysfunctioning. The Wechsler Preschool and Primary Scale of Intelligence at 5 to 6 years revealed a mean group IQ score of 92.1. The Beery Visual Motor Integration Test results demonstrated that 18 of 26 children had mild to severe visual motor perceptual difficulties. Severe ICH (grades 3 and 4) correlated with abnormal neurologic performances at 1 and 5 to 6 years. Mild ICH (grade 1) and no ICH did not correlate with any one of the 1-year neurologic classifications. The 1-year status correlated with the 5- to 6-year neurologic outcome best for children who were either neurologically suspect or abnormal at age 1 year. The 1-year neurologic score did not correlate with 5- to 6-year IQ and Beery Visual Motor Integration Test scores.     

Physical and Psychological Abuse in Breast Cancer Survivors and Cancer-Free Women

The purpose of this study was to provide a preliminary examination of intimate partner abuse in survivors of breast cancer relative to women who have never been diagnosed with cancer. The current study retrospectively evaluated the presence of physical or severe psychological abuse before cancer diagnosis, during treatment, and after remission of cancer in a sample of 206 ethnically diverse breast cancer survivors and 206 age- and ethnicity-matched control participants. Breast cancer survivors were less likely than controls to report abuse and did not report significant changes in frequency of abuse after cancer diagnosis or treatment.     

Indium-cadmium-oxide films having exceptional electrical conductivity and optical transparency: Clues for optimizing transparent conductors

Materials with high electrical conductivity and optical transparency are needed for future flat panel display, solar energy, and other opto-electronic technologies. In(x)Cd(1-x)O films having a simple cubic microstructure have been grown on amorphous glass substrates by a straightforward chemical vapor deposition process. The x = 0.05 film conductivity of 17,000 S/cm, carrier mobility of 70 cm2/Vs, and visible region optical transparency window considerably exceed the corresponding parameters for commercial indium-tin oxide. Ab initio electronic structure calculations reveal small conduction electron effective masses, a dramatic shift of the CdO band gap with doping, and a conduction band hybridization gap caused by extensive Cd 5s + In 5s mixing.     

Epidermal keratinocytes from light vs. dark skin exhibit differential degradation of melanosomes

Modification of skin complexion coloration has traditionally been accomplished by interruption or attenuation of melanogenesis and/or melanosome transfer. Post-transfer modification of pigmented melanosomes provides an attractive and distinct avenue of modulating skin pigmentation. The processing of melanosomes during keratinocyte (KC) terminal differentiation and the degradative variability observed between light and dark skin (LS and DS) remains enigmatic. To evaluate this, we developed a model system to investigate the loss of fluorescently labeled and isolated melanosomes by cultured human KCs. The extent of melanosome loss has been qualitatively assessed using transmission electron microscopy and indirect immunofluorescence with confocal microscopy, and quantitatively assessed using flow cytometry analysis. Results show that melanosomes are incorporated into the cytoplasm of both light and dark keratinocytes (LKCs and DKCs) and trafficked to a perinuclear region. Within 48 hours, confocal microscopy images suggest that LKCs display accelerated melanosome loss. This time-dependent decrease in carboxyfluorescein diacetate (CFDA) fluorescence was then quantitatively analyzed using flow cytometry. Consistent with the results of the confocal analysis, over a 48-hour time frame, LKCs appear to lose melanosomes more efficiently than DKCs. These experiments show that melanosomes are more rapidly lost in KCs derived from LS as opposed to DS.