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Biomedical subjects

H Johnson

Publications and source records attributed to H Johnson.

At least 37 records · Page 2Linked to original sources

Regulation of neurotrophin signaling in aging sensory and motoneurons: dissipation of target support?

A hallmark of senescence is sensorimotor impairment, involving locomotion and postural control as well as fine-tuned movements. Sensory and motoneurons are not lost to any significant degree with advancing age, but do show characteristic changes in gene-expression pattern, morphology, and connectivity. This review covers recent experimental findings corroborating that alterations in trophic signaling may induce several of the phenotypic changes seen in primary sensory and motoneurons during aging. Furthermore, the data suggests that target failure, and/or breakdown of neuron-target interaction, is a critical event in the aging process of sensory and motoneurons.

Aging↗

Economic impact of febrile morbidity and use of permethrin-impregnated bed-nets in a malarious area I. Study of demographics, morbidity, and household expenditures associated with febrile morbidity in the Republic of Benin.

In preparation for a study on the effect of bed net use on malaria, this article describes febrile morbidity and malaria expenditures in a sub-Saharan area (Benin) of hyperendemic malaria. The 325 randomly selected households were visited weekly between April 1994 and March 1995 to determine febrile morbidity and household expenditures for prevention and treatment. The results indicate that rural children had two febrile episodes annually compared with 0.3 episodes among children living in the city. There was no difference in mean annual febrile episodes between adults and children (adults = 1.5, children = 1.5; P = 0.48) and in the expenditures per febrile episode (adults = US$1.85, children = US$1.62; P = 0.45). Annual prevention expenditures were higher for adults than for children (US$1.73 and US$1.28, respectively; P < 0.001), although there was no significant difference in expenditures for annual treatment for adults and children (US$2.15 and US$2.34, respectively). These and other findings are analyzed further and discussed.

Adult↗

Economic impact of febrile morbidity and use of permethrin-impregnated bed nets in a malarious area II. Determinants of febrile episodes and the cost of their treatment and malaria prevention.

The objective of this study is to determine the effect of permethrin insecticide-treated bed net (PITN) use on the incidence of febrile episodes and on household malaria expenses in Benin. Over the course of one year, 208 randomly selected PITN user and non-user households were visited weekly to determine expenditures on febrile morbidity and its treatment, and to monitor spending on malaria prevention. Multivariate analyses were performed to distinguish the effects of PITN use from other important determinants of morbidity, such as malaria-related beliefs and practices, income, and other socio-economic variables. Results from the logistic regression analysis show that the use of PITNs decreases the risk of febrile episodes by 34% in children living in the rural zone. Multiple regression analysis reveals that PITN use does not reduce prevention and treatment expenses. These expenses are significantly associated with women's income. This report also discusses other factors associated with febrile morbidity and malaria-related expenditures.

Adult↗

Restoration of Th1 cytokine synthesis by T cells of patients with chronic myelogenous leukemia in cytogenetic and hematologic remission with interferon-alpha.

Chronic myelogenous leukemia (CML) is a disorder of the hematopoietic stem cell that results in malignant expansion of myeloid cells with a cytogenetic abnormality, the translocation between chromosomes 9 and 22 known as the Philadelphia chromosome. Treatment with IFN-alpha has proven to be an effective therapy, inducing cytogenetic remission in CML patients. However, it is unknown whether IFN-alpha can restore normal immune function for patients who achieve a complete cytogenetic remission. To address this question, we used a method of intracellular staining and flow cytometric analysis to ascribe the syntheses of Th1 or Th2 cytokines to T-cell subsets of patients in chronic, in accelerated, and in blast crisis phases as well as patients who had achieved a complete cytogenetic remission with IFN-alpha. We assessed the cytoplasmic synthesis of cytokine in phorbol ester (phorbol 12-myristate 13-acetate)-activated CD4+ and CD8+ T-cell subsets of 81 patients with various stages of CML and 21 normal controls. The percentages of CD4+ and CD8+ T cells from patients in chronic, in accelerated, and in blast crisis phases that synthesized Th1 cytokines interleukin (IL)-2, IFN-gamma, and tumor necrosis factor-alpha were significantly lower than those of remission patients and normal controls. Conversely, the percentages of CD4+ and CD8+ T cells of patients in chronic, in accelerated, and in blast crisis phases of CML preferentially synthesized the Th2 cytokine IL-10. Patients who achieved a durable complete cytogenetic remission for >2 years without maintenance IFN-alpha therapy restored their preference for a Th1 cytokine profile that is necessary for efficient cytotoxic T-cell function.

Antineoplastic Agents↗

Efficacy, safety and patient acceptance of sildenafil citrate as treatment for erectile dysfunction.

PURPOSE: We assessed the efficacy and safety of sildenafil citrate as treatment for erectile dysfunction. MATERIALS AND METHODS: A total of 433 completely evaluated men with chronic erectile dysfunction were treated with sildenafil citrate. Response was assessed prospectively by baseline and followup physician interviews, and by a patient self-administered 15-item questionnaire on the domains of patient treatment response and satisfaction, partner treatment satisfaction, comparative previous treatment satisfaction, adverse effects, and patient and partner quality of life. RESULTS: Of the 304 men (70.2%) who completed the questionnaire 278 received sildenafil, including 186 who previously had undergone treatment for erectile dysfunction, principally involving intracavernous injection therapy. A response was elicited by a median dose of 100 mg. in 188 patients (67.6%) who achieved erection suitable for sexual intercourse. Those with psychogenic erectile dysfunction responded significantly better than those with organic dysfunction (p <0.001). Erection suitable for intercourse was attained by 30.8% of patients with erectile dysfunction after radical prostatectomy and 80% with cavernous veno-occlusive dysfunction. Of previous intracavernous injection responders 29.9% were refractory to sildenafil, while 33. 3% of previous intracavernous injection nonresponders responded to sildenafil. The sildenafil response was considered inferior to the intracavernous injection response by 43.6% of the men who previously responded to intracavernous injection, of whom 51.5% continued to receive intracavernous injection as the only treatment (19.5%) or as an alternative to sildenafil (32%). Adverse effects in 53.6% of cases were assessed as mild in 56.4%, moderate in 38.3% and severe in 5.3%. Multiple adverse effects were reported by 62.4% of patients, while 17 (6.1%) discontinued sildenafil as a direct result of intolerable adverse effects. The most common adverse effects were facial flushing in 33.5% of cases, headaches in 23.4%, nasal congestion in 12.6%, dyspepsia in 10.1% and dizziness in 10.8%. Baseline patient and partner quality of life scores significantly improved after sildenafil treatment (p <0.001), while significantly improved quality of life was noticed by 51.5% and 43.1%, respectively. CONCLUSIONS: Sildenafil citrate is effective oral first line treatment for erectile dysfunction. Although more than 50% of men reported adverse effects, most were considered mild and rarely resulted in treatment cessation. There was a trend in those on intracavernous injection who responded to sildenafil to continue intracavernous injection as the only therapy or as an alternative to sildenafil. Also, we noted that some cases refractory to sildenafil responded to intracavernous injection. These findings imply that intracavernous injection remains an effective erectile dysfunction treatment option.

Adult↗

Adult service refusers in the greater Dublin area.

The reclusive behaviour and living conditions of people living in the community can be a source of concern to others, especially when statutory and voluntary support are refused. A cross-sectional observational study of service providers was carried out to profile 'service refusers' in the greater Dublin area and to describe the support offered. Two hundred and thirty three subjects were identified. Most were female (127, 54.5%) and 65 years of age or older (162, 69.5%). Approximately 50% (117, 50.2%) were living in private accommodation. The majority of subjects were considered to exhibit traits of poor personal hygiene (171, 73.4%), suspiciousness (160, 68.7%), secrecy (144, 61.8%) or hoarding (126, 54.1%). Forty-seven per cent of subjects (110) identified met the criteria for 'Diogenes Syndrome'. A wide variety supports had been offered including meals-on-wheels, home-helps and house cleaning. Respondents considered that 51.9% (121) of subjects had not been offered a service which proved successful. Despite the best efforts of agencies, service refusers can remain steadfast in not availing of the help that is on offer.

Adult↗

Seasonal patterns of morbidity and mortality in the elderly in Ireland.

Weather conditions have been shown to have a strong association with health Status. (1,2) In this study we examined the relationship between meteorological conditions (average daily temperature, humidity, precipitation, and wind strength) and the seasonal morbidity (emergency hospital admissions and drug prescribing) and mortality patterns in the elderly (over 65 years) over a four year period in Ireland. Temperature (summer/winter variation of 10 degrees C) had the strongest (inverse) association with total mortality (correlation coefficient of 0.895). Circulatory diseases showed the strongest seasonal trend in mortality and a weaker trend for admissions. For respiratory diseases, the morbidity and admission seasonal patterns were similar. Circulatory and respiratory drug prescribing showed no strong seasonal pattern. On examination of the excess winter mortality in four different regions, it was found that the smallest summer/winter temperature difference (9.96 degrees C) occurred in Cork and was associated with the highest percentage difference in total mortality. The highest temperature difference (10.80 degrees C) occurred in Monaghan and this area was associated with the lowest percentage difference in total mortality.

Aged↗

Tumor necrosis factor-related apoptosis-inducing ligand receptors signal NF-kappaB and JNK activation and apoptosis through distinct pathways.

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF family that interacts with several receptors, including TRAIL-R1, TRAIL-R2, and TRAIL-R4. TRAIL-R1 and TRAIL-R2 can induce apoptosis of cancer cells and activate the transcription factor NF-kappaB. TRAIL-R4 can activate NF-kappaB and protect cells from TRAIL-induced apoptosis. Here we show that TRAIL-R1-, TRAIL-R2-, and TRAIL-R4-induced NF-kappaB activation are mediated by a TRAF2-NIK-IkappaB kinase alpha/beta signaling cascade but is MEKK1 independent. TRAIL receptors also activate the protein kinase JNK. JNK activation by TRAIL-R1 is mediated by a TRAF2-MEKK1-MKK4 but not the TRAF2-NIK/IkappaB kinase alpha/beta signaling pathway. We also show that activation of NF-kappaB or overexpression of TRAIL-R4 does not protect TRAIL-R1-induced apoptosis. Moreover, inhibition of NF-kappaB by IkappaBalpha sensitizes cells to tumor necrosis factor- but not TRAIL-induced apoptosis. These findings suggest that TRAIL receptors induce apoptosis, NF-kappaB and JNK activation through distinct signaling pathways, and activation of NF-kappaB is not sufficient for protecting cells from TRAIL-induced apoptosis.

Apoptosis↗

Expression of p75(NTR), trkB and trkC in nonmanipulated and axotomized motoneurons of aged rats.

Several lines of evidence indicate that adult neurons remain dependent on neurotrophins and that changes in tissue expression of neurotrophins and/or their receptors may play a role in senile neurodegeneration. We have studied the expression of p75NTR, trkB and trkC, respectively, in lumbar motoneurons of young adult (2-3 months) and aged (30 months) rats subjected to sciatic transection using in situ hybridization and immunohistochemistry. Nonmanipulated age-matched animals were processed in parallel. In nonmanipulated aged rats, high levels of p75NTR could be seen in a number of motoneurons (10-15%), while in young adult animals no p75NTR could be detected. Seven days following sciatic axotomy, a conspicuous ipsilateral upregulation p75NTR was observed in young adult rats. Also in aged rats there was a marked ipsilateral increase in number of p75NTR expressing neurons ( approximately 100%). In comparison to young adult rats, aged rats showed a decreased expression of both trkB (5/6 animals) and trkC (6/6 animals). Furthermore, in response to sciatic transection, 3 out of 5 aged rats did not show an increased expression of trkB. In aged rats, axotomy did not induce any significant change in trkC expression. In the young adult rats, we recorded a side-to-side effect with lower values ipsilaterally, however, it cannot be excluded that this difference was caused by an upregulation in the contralateral motoneurons. Oligonucleotide probes against BDNF and NT3 mRNA showed only very few faintly positive neurons in both age groups. Our results indicate that the pattern of regulatory changes of NT receptors in response to axotomy is different in aged and young adult rats. The lack of covariation between p75NTR and trkB and trkC regulation in aged rats indicates a changed role for p75NTR in senescent motoneurons.

Aging↗

Treatment of intracorporeal injection nonresponse with sildenafil alone or in combination with triple agent intracorporeal injection therapy.

PURPOSE: We assess the efficacy of sildenafil as salvage therapy for intracorporeal injection therapy nonresponse. MATERIALS AND METHODS: The study group comprised 93 patients with a mean age of 53.6 years (range 24 to 77) with chronic erectile dysfunction. In all cases a home trial of intracavernosal injection of high dose alprostadil and triple agent intracavernosal injection therapy had failed. Patients were treated with sildenafil citrate alone or in combination with intracavernosal injection therapy. RESULTS: The etiology of erectile dysfunction was arteriogenic in 29 cases, cavernosal venous leakage in 36, mixed vasculogenic in 24, psychogenic in 3 and post-priapism intracavernous fibrosis in 1. Of the 32 sildenafil responders (34% of the study group) 30 required 100 and 2 required 50 mg. The 29 sildenafil intracavernosal injection (combined therapy) responders (31% of the study group) required 100 mg. sildenafil. There were 32 nonresponders (34% of the study group). Mean International Index of Erectile Function questions 3 and 4 scores were 1.7 and 1.5 at baseline, 2.3 and 1.9 with intracavernosal injection, 4.6 and 42.2 with sildenafil, and 4.1 and 4.10 with combined therapy, respectively. Of the 93 patients 29 (31%) treated with intracavernosal injection reported adverse effects, including penile pain in 27, dizziness in 5 and headache in 2. Of the patients treated with sildenafil 34 (37%) reported side effects, including headache in 30, facial flushing in 25, dyspepsia in 12, nasal congestion in 9, dizziness in 5 and visual disturbances in 1. Of the 41 patients given combined therapy 20 (49%) reported adverse effects, including penile pain in 15, headache in 15, facial flushing in 12, dyspepsia in 7, nasal congestion in 3, dizziness in 12 and syncope in 1. CONCLUSIONS: Sildenafil alone or sildenafil plus intracavernosal injection is effective salvage therapy for intracavernosal injection nonresponse. Sildenafil in combination with intracavernosal injection is associated with a 33% incidence of adverse effects, including a 20% incidence of dizziness.

Adult↗

Determinants of the Permethrin Impregnated Bednets (PIB) in the Republic of Benin: the role of women in the acquisition and utilization of PIBs.

An important aspect of malaria control strategies has been the use of prophylactic measures such as impregnated bednets; however, adoption of this strategy has been slow and uneven. This study considers the factors determining Permethrin Impregnated Bednets (PIB) use in the context of a PIB promotion project in a rural area of Benin undertaken between 1992 and 1995. Quantitative data, on socio-demographic characteristics, malaria knowledge, attitudes, and practices, were gathered from 191 households of PIB users and non-users for comparative purposes using a questionnaire format. Qualitative data were collected from 23 focus group discussion sessions and 16 semi structured interviews. Women's income, men's educational level, and women's participation in communal organizations were the principal variables distinguishing user households from non-user households. Recourse to non-western medicine and, in particular, to medicinal teas which are considered preventive or curative correlates negatively with PIB use. The qualitative data shows that informants consider exposure to the sun, especially while engaged in agriculture work, a principal cause of malaria, and that PIB adoption is not considered justified in a context where there is a quasi chronic shortage of financial resources and where confidence in the efficacy of non-western medicine prevails. Because they have primary responsibility for the health of their families and are more aware of children's vulnerability to malaria, women are more inclined than men to want to buy PIBs. However, because the household head, who is most often male, sets family consumption priorities using family income, women often have to resort to using their own income, which is often considerably lower than that of men, to buy PIBs. Support for community initiatives which are directed to women's work, linked with intensive effort to sensitize men to the mechanisms of malaria transmission and the principal groups at risk, is seen as a means to increase PIB acquisition and use.

Bedding and Linens↗

TALL-1 is a novel member of the TNF family that is down-regulated by mitogens.

Members of the tumor necrosis factor (TNF) family play important roles in modulation of immune responses. We describe the identification and cloning of a novel TNF family member that has been designated as TALL-1. TALL-1 is a 285-amino acid type II transmembrane protein. Its carboxy terminus shares approximately 35% sequence identity with the recently identified APRIL and approximately 20-25% with TNF, FasL, TRAIL, and lymphotoxin-alpha, suggesting that TALL-1 and APRIL belong to a subfamily of the TNF family of ligands. Northern blot analysis suggests that TALL-1 is expressed abundantly in peripheral blood leukocytes and weakly in spleen but is barely detectable in all other tissues examined. Reverse transcriptase-polymerase chain reaction analysis indicates that TALL-1 is specifically expressed in monocytes and macrophages but is undetectable in T and B lymphocytes. Furthermore, TALL-1 expression is dramatically down-regulated by phorbol myristate acetate/ionomycin.

Amino Acid Sequence↗

Gerontological social work and the UN International Year of Older Persons. Interview by Stanley L. Witkin.

To highlight the United Nations International Year of Older Persons and to increase awareness of social work issues related to older people, the editor of Social Work conducted an interview with four distinguished social workers involved in gerontological social work. The interviewees identified professional needs and various policy and practice issues for social work education and practice.

Aged↗

Alterations in heart failure of cyclic AMP-dependent inotropic and lusitropic properties of cardiac and skeletal muscle.

A central working hypothesis in our laboratory is that deficient cellular cyclic AMP concentrations may be responsible, at least in part, for striated muscle dysfunction, both cardiac and skeletal, in heart failure. These results suggest that therapy aimed at restoring cyclic AMP to normal levels may be effective with regard to improving systolic and diastolic function in the heart and may decrease the development of fatigue in skeletal muscle of patients with failure. The use of cyclic AMP-dependent drugs in clinical practice has been limited by side effects associated with raising total cellular content of this cyclic nucleotide. However, evidence suggesting that separate pools of cyclic AMP may exist within the cell raises the possibility that those pools associated with excitation/contraction coupling could serve as more specific therapeutic targets.

Animals↗

Obstetric events leading to anal sphincter damage.

OBJECTIVE: To identify the obstetric factors relating to anal sphincter injury at first vaginal delivery by prospective cohort study of primiparous women. METHODS: We compared the results of a bowel function questionnaire and anal vector manometry before and 6 weeks after delivery in 184 primiparous women. Postpartum, pudendal nerve conduction latency was measured in all women, and anal endosonography was performed in 81 with altered fecal continence or abnormal physiology. RESULTS: Sixteen (9%) women, none of whom had altered fecal continence, were delivered by cesarean. After vaginal delivery, 42 of 168 (25%) women had impairment of fecal continence and 76 of 168 (45%) women had abnormal anal physiology. Instrumental vaginal delivery was associated with an 8.1-fold (95% confidence interval [CI] 2.7, 24.0; P < .001) risk of anal sphincter injury and a 7.2-fold (95% CI 2.8, 18.6; P < .001) risk of symptoms. Duration of the second stage of labor beyond 60 minutes led to a 1.7-fold (95% CI 1.14, 2.48; P;< .01) risk of anal sphincter injury and a 1.6-fold (95% CI 1.03, 2.6, P = .01) risk of symptoms. Epidural analgesia, used in 58% of vaginal deliveries, prolonged the second stage of labor (P = .004; odds ratio [OR] 7.7; 95% CI 4.0, 14.7) and was associated with increased risk of sphincter injury (P = .02; OR 2.1; 95% CI 1.1, 4.0) and of symptoms (P = .02; OR 2.0; 95% CI 1.1, 3.7). CONCLUSION: Instrumental delivery and a second stage of labor prolonged by epidural analgesia are the obstetric factors that pose the greatest risk of injury to the anal sphincter mechanism in primiparous vaginal delivery.

Anal Canal↗

Seroprevalence of Borrelia burgdorferi sensu lato infection in blood donors and park rangers in relation to local habitat.

Serum samples were obtained from blood donors in eleven selected locations in Ireland and tested for antibodies to Borrelia burgdorferi s.l. by enzyme immunoassay (EIA) and immunoblot (IB). The highest seroprevalence (8.7%) was found in Portumna, an area rated as high risk because of the presence of public access woodland harbouring both ticks and spirochaete reservoir hosts. The lowest seroprevalence (0.0%) was found in Ballina, an area where there is no suitable woodland though ticks are common on pastures grazed by cattle and sheep. These results support the findings of an earlier less extensive study and suggest that infection with B. burgdorferi s.l. in Ireland is mainly associated with mixed woodland containing deer and a variety of spirochaete reservoir hosts. The lack of association of tick-infested farmland with seropositive samples suggests that exposure to ticks alone is not a reliable indicator of risk of Lyme borreliosis. This is supported by the fact that none of 38 park rangers, all of whom are regularly bitten by ticks, were seropositive for B. burgdorferi s.l. The low overall seroprevalence of 3.4% in Ireland correlates with the rarity of clinical cases compared with continental European countries, and is due in part to the scarcity of high risk Lyme borreliosis habitat.

Animals↗