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Biomedical subjects

M Welch

Publications and source records attributed to M Welch.

At least 73 records · Page 4Linked to original sources

Recent developments in psychiatric nurse education in the countries of central and eastern Europe.

Since the social and political revolutions of 1989 and the years that followed the countries of Central and Eastern Europe (CCEE) have undergone radical changes in their health care systems, and among the most radical of these has been the restructuring and reorganisation of the psychiatric nurse training and education, with a weather eye to the potential of mental health demands that may result from the socio-economic turmoil. This paper, much of which was compiled while on secondment to the WHO, attempts to give a brief overview of the main policy developments in selected countries and to place them within a philosophical, social and pedagogical context. It cannot escape notice that the way in which countries choose to educate their nurses and what they can be expected to achieve in their work, reflects a more global understanding of mental health--and that may be why we should all learn from this experience.

Commonwealth of Independent States↗

Systemic endotoxaemia and fibrinolysis during aortic surgery.

OBJECTIVE: To determine whether endotoxaemia and activation of the systemic fibrinolytic system occurs during and after aortic surgery. DESIGN: Prospective clinical study. SETTING: University Hospital. MATERIALS: 31 patients undergoing aortic surgery. CHIEF OUTCOME MEASURES: Venous blood assay for endotoxin and plasminogen activator inhibitor-1 (PAI-1). Samples were obtained preoperatively, immediately before and 5 minutes after cross-clamp application and removal, and at 2, 4, 6 and 24 hours postoperatively. Tonometric sigmoid intramural pH was monitored throughout this period as a means of detecting colonic mucosal ischaemia. MAIN RESULTS: Endotoxin levels increased after clamping of the aorta, peaking immediately before clamp removal, mean value 34.5 pg/ml, p < 0.01, but returning to preoperative levels by 24 hours. PAI-1 levels progressively increased after surgery, with persistently high levels remaining at 24 hours (p < 0.01). CONCLUSIONS: Endotoxaemia does occur during aortic surgery and appears to be associated with activation of the systemic fibrinolytic system.

Acidosis↗

Associations between serum lipids and indicators of adiposity in men with spinal cord injury.

Several reports indicate that dyslipidemia, primarily depressed high density lipoprotein cholesterol, is common in persons with spinal cord injury. The purpose of this study was to assess the relationships between anthropometric and near infrared interactance measurements to the serum lipoprotein profiles of 46 men with spinal cord injury of > 6 months duration. Mean age (+/- SD) was 49.5 +/- 15.0 y and duration of injury was 17.5 +/- 13.0 y. Forty-one percent of the subjects had low high density lipoprotein cholesterol (< 35 mg dl-1) and 57% had elevated total cholesterol to high density lipoprotein cholesterol ratios (> 4.5). Abdominal circumference was most closely associated with the overall lipid profile and abdominal circumference/height ratio was the second strongest correlate. Body mass index, conicity index, and percent body fat estimated by near infrared interactance were significantly related to some lipid parameters; however, the relationships were weaker than for abdominal circumference or abdominal circumference/height. Significant correlations were found between abdominal circumference and serum high density lipoprotein cholesterol (r = -0.421, P < 0.01) and log10 triglyceride (r = 0.587, P < 0.001) concentrations as well as the total cholesterol:high density lipoprotein cholesterol (r = 0.482, P < 0.01) and low density lipoprotein cholesterol-to-high density lipoprotein cholesterol (r = 0.387, P < 0.05) ratios. Based on these findings, the sample was partitioned by abdominal circumference into low (< 95 cm), moderate, and high (> or = 102 cm) risk subgroups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Human immunodeficiency virus type 1-infected cells in breast milk: association with immunosuppression and vitamin A deficiency.

Breast milk samples from human immunodeficiency virus type 1 (HIV-1)-seropositive women were analyzed by polymerase chain reaction to determine the prevalence and determinants of HIV-1-infected cells in breast milk. Breast milk samples (212) were collected from 107 women, and 58% of the samples had detectable HIV-1 DNA. The proportion of HIV-1-infected cells in the milk samples ranged from 1 to 3255/10(4) cells. Breast milk samples with detectable HIV-1 DNA were more likely to be from women with absolute CD4 cell counts of < 400 (odds ratio, 3.1; 95% confidence interval [CI], 1.5-7.0). Severe vitamin A deficiency (< 20 micrograms/dL) was associated with a 20-fold increased risk of having HIV-1 DNA in breast milk among women with < 400 CD4 cells/mm3 (95% CI, 2.1-188.5). Women with CD4 cell depletion, especially those with vitamin A deficiency, may be at increased risk of transmitting HIV-1 to their infants through breast milk.

Adolescent↗

Human immunodeficiency virus DNA in urethral secretions in men: association with gonococcal urethritis and CD4 cell depletion.

To evaluate the prevalence and correlates of human immunodeficiency virus (HIV)-infected cells in urethral secretions, samples were collected from 106 HIV-seropositive men with and without urethritis. HIV DNA was detected by polymerase chain reaction in 27% of 184 urethral specimens and was associated with CD4 cell depletion (P for trend, .03) and with urethritis (odds ratio [OR], 2.4; 95% confidence interval [CI], 1.2-4.6) or gonorrhea (OR, 2.9; 95% CI, 1.5-5.8). Two multivariate models were constructed that included age, CD4 cell count < 200/mm3, and either urethritis or gonococcal infection. Detection of HIV-infected cells in urethral secretions was independently associated with < 200 CD4 cells/mm3 (OR, 2.2; 95% CI, 0.9-5.2; P = .05) and urethritis (OR, 2.7; 95% CI, 1.3-5.3; P = .003) in the first model and with gonococcal infection (OR, 3.2; 95% CI, 1.6-6.4; P < .001) in the second model. Successful treatment of gonococcal urethritis was associated with a 2-fold reduction in urethral HIV DNA (44% vs. 21%; P = .02). Thus, treatment of gonococcal urethritis may be an effective strategy for reducing HIV transmission.

Adult↗

Clients' experiences of depression during recovery from traumatic injury.

The purpose of this study was to examine experiences and coping strategies of 30 patients who had experienced traumatic injury. A prospective design documented the process of change that occurred over 14 months and identified factors that facilitated and impeded recovery. Seventeen of the informants viewed themselves as recovered. This group did not experience any permanent disabilities or scars and resumed their preaccident activities, including return to work. Thirteen of the informants did not describe themselves as recovered; they all experienced episodes of depression and had more severe injuries. Several had permanent disabilities. The experience of depression was identified as a serious impediment to recovery. CNSs working with trauma patients can help them recover by organizing support groups and discussing with them the possible experience of depression and how to seek treatment.

Adaptation, Psychological↗

The effect of nedocromil sodium on childhood asthma during the viral season.

Viral-induced symptomatic respiratory infections (SRI) frequently cause exacerbations of asthma in children. This study investigated the protective effects of 0.5% nedocromil sodium nebulizer solution given three times a day in preventing asthma exacerbations associated with SRI. Ninety-three mild-moderate asthmatic children (6 to 12 yr of age) received either 0.5% nedocromil sodium or placebo for 24 wk during the viral season. The nedocromil sodium group was symptom-free 58% of the days, and the placebo-treated patients were symptom-free 45% of the days (p = 0.027). During Weeks 1-12, significant differences favored nedocromil sodium for asthma summary score (means: nedocromil sodium = 0.61, placebo = 0.92; p = 0.026), and daytime asthma (nedocromil sodium = 0.78, placebo = 1.22; p = 0.03). Significant differences were noted during monthly intervals for cough (Weeks 1-4: nedocromil sodium = 0.61, placebo = 0.92, p = 0.027) and peak expiratory flow rate (PEFR) (nedocromil sodium 262, placebo = 254 L/min, p = 0.041 Weeks 9-12). Patients in the active treatment group reduced their need for rescue inhaled beta 2-agonist by 10%, whereas patients treated with placebo demonstrated a 24% increase. There was a strong correlation between asthma symptoms and SRI symptoms (r = 0.47; p < 0.001). During SRIs, patients in the nedocromil sodium group demonstrated more rapid resolution of asthma symptoms immediately following infection (p = 0.033 summary score, p = 0.039 sleep difficulty). No serious adverse events were noted. Nedocromil sodium did not prevent the infection or exacerbation of asthma symptoms during SRI.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Asthmatic Agents↗

Inflammatory linear verrucous epidermal nevus in patients with positive results of tests for human immunodeficiency virus 1.

Inflammatory linear verrucous epidermal nevi are rare lesions that have many similarities to psoriasis on histologic examination, and are resistant to therapy. The two lesions reported occurred in patients with positive results of tests for human immunodeficiency virus 1 and showed features consistent with psoriasis. Results of tests for immunohistochemical markers were also consistent with previous findings and expected staining patterns in lesions of psoriasis. Our findings suggest that inflammatory linear verrucous epidermal nevi represent a clonal dysregulation in growth, probably secondary to an inflammatory stimulus. Since human immunodeficiency virus 1 has been associated with onset and exacerbation of psoriasis, perhaps this virus or another secondary infection associated with human immunodeficiency virus 1 infection could also play a role in the onset of this rare lesion.

Adult↗

Effects of phosphorylation, Mg2+, and conformation of the chemotaxis protein CheY on its binding to the flagellar switch protein FliM.

CheY is the response regulator of bacterial chemotaxis. Previously, we showed that CheY binds to the flagellar switch protein FliM and that this binding is increased upon phosphorylation of CheY [Welch, M., Oosawa, K., Aizawa, S.-I., & Eisenbach, M. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 8787-8791]. Here, we demonstrate that it is the phosphorylated conformation of CheY, rather than the phosphate group itself, that is recognized and bound by FliM. We found that subsequent to the phosphorylation of CheY, Mg2+ was not required for the binding of CheY to FliM. However, phosphorylation of CheY did cause a change in the coordination properties of Mg2+ in the acid pocket of the protein. This change in the coordination of Mg2+ required the presence of the absolutely conserved residue Lys109. When Lys109 was substituted by arginine, the resulting CheY protein was unable to adopt an active conformation upon phosphorylation, and the protein was not bound by FliM. Surprisingly, the CheY13DK mutant protein, which is active in vivo but cannot be phosphorylated in vitro, exhibited only a low level of FliM binding activity, suggesting that its ability to cause clockwise rotation in the cell is not due to a constitutively high level of FliM binding. On the basis of these findings, we propose a mechanism for CheY activation by phosphorylation.

Bacterial Proteins↗

Precursors of the neurosteroids.

In addition to the neurosteroids pregnenolone and dehydroepiandrosterone, organic solvent extracts of rat brains contain related compounds that react with various reagents to yield additional amounts of these ketosteroids. Among the chemicals producing these increments are triethylamine, HCl, FeCl3, and Pb(OAc)4. Most revealing is the action of FeSO4 on these extracts. This reducing agent also converts components of the extract into the two neurosteroids, suggesting the presence of sterol hydroperoxides or peroxides in brain. The clues provided by this study indicate that the chemical nature of the steroidal constituents existing in extracts of mammalian brains remains to be determined. It is likely that their association with neurological functions will be better understood when the structures of these substances are established.

Animals↗

Hypofibrinolysis: a common, major cause of osteonecrosis.

In 30 patients with osteonecrosis of the hip (12 idiopathic, 18 secondary), we assessed the role of hypofibrinolysis mediated by high levels of plasminogen activator inhibitor (PAI). We evaluated hypofibrinolysis as a common, potentially reversible, pathophysiologic cause of idiopathic osteonecrosis. In all 18 patients with secondary osteonecrosis, PAI was normal, as was the ability to activate fibrinolysis. Nine of the 12 patients with idiopathic osteonecrosis had exceptionally high PAI levels and could not normally elevate tissue plasminogen activator (tPA-Fx), the major stimulator of fibrinolysis, after 10 min of venous occlusion at 100 mm Hg. The group of 12 patients with idiopathic osteonecrosis, compared to the 18 with secondary osteonecrosis, had low mean stimulated tPA-Fx (1.92 vs. 7.6 IU/ml, P < or = .001) and very high stimulated PAI-Fx (70 vs. 7.6 U/ml, P < or = .01). Three of the 12 patients with idiopathic osteonecrosis had both normal PAI and normal stimulated tPA-Fx. These three patients and 14 of the 18 with secondary osteonecrosis had high lipoprotein (a) [Lp(a)] (> 20 mg/dl). Mean Lp(a) was much higher (60 mg/dl) in the patients with secondary osteonecrosis than Lp(a) (16 mg/dl, P < or = .001) in the 12 patients with idiopathic osteonecrosis. These findings suggest that hypofibrinolysis mediated by high PAI is a common cause of idiopathic osteonecrosis, whereas high Lp(a) may play an etiologic role in secondary osteonecrosis. Prospective studies of patients with high PAI and/or high Lp(a) should be carried out to assess further their apparently causal roles in osteonecrosis.

Adult↗

Vaccinating guinea pigs with recombinant glycoprotein D of herpes simplex virus in an efficacious adjuvant formulation elicits protection against vaginal infection.

Guinea pigs were immunized with glycoprotein gD-2t in SAF-m or saline, then challenged with herpes simplex virus, type 2 (HSV-2). Animals given gD-2t in SAF-m had higher anti-gD-2t antibodies, fewer and less severe vaginal lesions, and decreased ganglionic latency compared to animals given gD-2t in saline. Leucocytes from animals vaccinated with gD-2t in SAF-m had greater proliferative responses to gD-2t in vitro than cells from control animals. MHC II-restricted, gD-2t-specific cytotoxic T cells were induced in guinea pigs vaccinated with gD-2t in SAF-m. Thus, immunization of guinea pigs with gD-2t in SAF-m markedly reduced the incidence and severity of primary HSV-2 by eliciting both humoral and cell-mediated responses.

Acetylmuramyl-Alanyl-Isoglutamine↗

Syringolymphoid hyperplasia with alopecia. A case report.

Syringolymphoid hyperplasia with alopecia is an uncommon skin disorder described in 1969 by Sarkany. Since then only three additional cases have been reported, all in the European literature. We present a 59-year-old man with two persistent hyperpigmented hairless patches of 13 years duration. Biopsy specimens revealed characteristic hyperplastic changes of the eccrine glands and ducts and a dense lymphocytic infiltrate surrounding eccrine structures with "syringotropism". Perifollicular lymphocytic infiltration and changes consistent with follicular mucinosis and mycosis fungoides were also present. Imunophenotyping and gene rearrangement studies showed the cells to be primarily of the T helper phenotype with rearrangement of the surface receptor gene.

Adult↗

Antiepiligrin cicatricial pemphigoid. A subepithelial bullous disorder.

BACKGROUND: Epiligrin is a glycoprotein complex deposited in extracellular matrix by cultured human keratinocytes that serves as the major integrin ligand of these cells. In human skin, epiligrin is found at the interface of the lamina lucida and lamina densa in epidermal basement membrane where it is believed to be associated with anchoring filaments and plays an important role in keratinocyte adhesion. METHODS AND RESULTS: We have identified six patients with a subepithelial bullous disorder of mucous membranes and skin who have IgG anti-basement membrane autoantibodies that immunoprecipitate epiligrin from human keratinocyte extracts and culture media. These patients' IgG autoantibodies also bind epiligrin in human keratinocyte extracellular matrix and epidermal basement membrane as determined by immunofluorescence and immunoelectron microscopy. Studies of 10 patients who are clinically indistinguishable from subjects with anti-epiligrin autoantibodies (ie, cicatricial pemphigoid patients) found that while seven had anti-basement membrane autoantibodies, the latter are directed exclusively against a region of epidermal basement membrane that does not contain epiligrin, are present in low titer (ie, < or = 1:10), do not react with keratinocyte extracellular matrix, and do not bind epiligrin (or any other specific antigen) in immunoprecipitation studies of human keratinocyte extracts or media. Antiepiligrin autoantibodies were also not detected in studies of 36 additional patients with bullous diseases or six normal volunteers. CONCLUSIONS: Cicatricial pemphigoid is a disease phenotype in which patients' autoantibodies may target different constituents of epidermal basement membrane. Antiepiligrin autoantibodies are a specific immunologic marker for a group of patients with a disease entity that we propose to designate antiepiligrin cicatricial pemphigoid.

Adult↗

Familial idiopathic osteonecrosis mediated by familial hypofibrinolysis with high levels of plasminogen activator inhibitor.

Familial hypofibrinolysis with 3 generation, autosomal dominant, very high levels of plasminogen activator inhibitor activity (PAI-Fx) and antigen (PAI-Ag) was etiologically associated with bilateral idiopathic osteonecrosis in 2 brothers. They, their mother, 2 brothers, sister, and all 4 of her children (none of whom had yet developed osteonecrosis), all had very high PAI and could not elevate tissue plasminogen activator after 10 minutes of venous occlusion at 100 mmHg. Familial high PAI levels with concurrent hypofibrinolysis co-segregated with familial combined hyperlipidemia, both being independent risk factors for premature coronary heart disease. If thrombi block venous drainage in the femur, familial hypofibrinolysis mediated by familial high PAI with inability to lyse thrombi would contribute to venous hypertension of bone, bone anoxia, and bone death characteristic of osteonecrosis.

Adolescent↗

Influence of renal artery blood flow on renal function during aortic surgery.

BACKGROUND: This study was undertaken to determine the true incidence of renal impairment after aortic surgery and its association with intraoperative fluctuations in renal artery blood flow and cardiac output. METHODS: Direct measurements of renal artery blood flow were undertaken with electromagnetic flowmetry in 19 patients undergoing elective infrarenal aortic surgery. Renal function was assessed before and after operation by measurement of creatinine clearance. RESULTS: Twelve patients (63%) had renal impairment as defined by a 40% or greater reduction in creatinine clearance after operation. This group of patients had significantly lower renal artery blood flow during the period of aortic cross-clamping than had those who preserved their renal function (p < 0.001). CONCLUSIONS: Renal impairment is common after infrarenal aortic surgery and may be a result of intraoperative ischemia secondary to reduced renal artery blood flow.

Adult↗

Phosphorylation-dependent binding of a signal molecule to the flagellar switch of bacteria.

Regulation of the direction of flagellar rotation is central to the mechanism of bacterial chemotaxis. The transitions between counterclockwise and clockwise rotation are controlled by a "switch complex" composed of three proteins (FliG, FliM, and FliN) and located at the base of the flagellar motor. The mechanism of function of the switch is unknown. Here we demonstrate that the diffusible clockwise-signal molecule, the CheY protein, binds to the switch, that the primary docking site is FliM, that the extent of CheY binding to FliM is dependent upon the phosphorylation level of CheY, and that it is unaffected by the other two switch proteins. This study provides a biochemical demonstration of binding of a signal molecule to the bacterial switch and demonstrates directly that phosphorylation regulates the activity of this molecule.

Amides↗

Steroids and their conjugates in the mammalian brain.

Five steroids--3 beta-hydroxypregn-5-en-20-one (pregnenolone; P), 3 beta-hydroxy-5 alpha-pregnan-20-one (3 beta-AP), 3 alpha-hydroxy-5 alpha-pregnan-20-one (3 alpha-AP), 3 beta-hydroxyandrost-5-en-17-one (dehydroepiandrosterone; D), and 3 beta-hydroxy-5 alpha-androstan-17-one (EpiA)--were extracted from the brains of adult male rats, rabbits, and dogs. The steroids exist in this organ as unconjugated compounds and as sulfates, lipoidal esters, and sulfolipids. The techniques for separating these four classes of steroids from each other and for separating the five steroids from each other are described. In all cases, the steroids were identified by their retention time (Rt) on HPLC, their Rt by gas chromatography, and by selected ion monitoring of their mass spectra. The latter were also used for quantification. In their reaction toward organic bases, the sulfolipid conjugates resemble previously described sulfolipids of cholesterol and sitosterol. These conjugates are relatively abundant in brain, particularly those of P and D, and this suggests that, in the search for the physiological significance of these brain constituents, these conjugates warrant attention.

Animals↗