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Biomedical subjects

G Robinson

Publications and source records attributed to G Robinson.

At least 91 records · Page 5Linked to original sources

Cross-cultural perspectives on menopause.

Numerous physical and psychological symptoms have been attributed to the hormonal changes of menopause. Symptoms have also been attributed to loss of fertility, redefining of roles, empty nest syndrome, loss of femininity, and changes of status. Cross-cultural studies allow researchers to examine the contribution of physiological, psychological, and sociocultural influences to the experience of menopausal symptoms. Such research is complicated by differences between cultures in the definition of menopause, reproductive histories, symptom expression, and beliefs as to what constitutes status. A review of five important cross-cultural studies indicates that there are enormous differences in the experience of menopause among women in the same culture and among cultures. Menopausal symptoms seem to be caused by a combination of physical changes, cultural influences, and individual perceptions and expectations.

Aging↗

Cloning and mRNA expression of vascular endothelial growth factor in ischemic retinas of Macaca fascicularis.

PURPOSE: To identify and isolate cDNAs for the alternatively spliced vascular endothelial growth factor (VEGF) mRNAs present in retina and to compare the relative levels of the splice variants and localization of VEGF mRNA in nonischemic and ischemic adult simian retinas. METHODS: Retinas of cynomolgous monkeys were made ischemic by laser occlusion of the main branch retinal veins. Reverse transcription-polymerase chain reaction was used to amplify the VEGF coding region of RNA from ischemic and control retinas, and amplification products were analyzed by agarose gel electrophoresis, Southern blot, and nucleotide sequencing. Analysis of VEGF mRNA expression was accomplished by in situ hybridization. RESULTS: Control and ischemic retinas produce mRNAs that correspond to the 121 and 165 amino acid diffusible isoforms of VEGF, and relatively low levels of VEGF189, the heparin-binding isoform. There was no significant difference in the levels of the alternatively spliced VEGF transcripts between control and ischemic retinas. Cloning and sequencing revealed that simVEGF cDNAs are 99% identical to human VEGFs and are predicted to encode proteins identical to their respective human homologues. In situ hybridization of nonischemic retinas revealed a low level of VEGF mRNA in retinal ganglion cells and in the inner nuclear layer. VEGF mRNA levels were elevated in ischemic retinas as early as 1 day after laser vein occlusion, when there was a small but reproducible increase in signal. The expression peaked at approximately 13 days, coincident with maximal iris neovascularization, and was significantly reduced by 28 days, when the iris vessels largely regressed. CONCLUSIONS: The elevation of simVEGF121 and VEGF165 in ischemic retinas is consistent with a role for diffusible, retina-derived angiogenic factors in the development of ocular neovascularization.

Alternative Splicing↗

Inhibition of organ invasion by the matrix metalloproteinase inhibitor batimastat (BB-94) in two human colon carcinoma metastasis models.

The effect of the matrix metalloproteinase inhibitor batimastat was evaluated in two human colorectal cancer metastasis models involving: (a) the liver-invasive tumor C170HM2 and (b) the lung-invasive tumor AP5LV, both of which have been shown to express the M(r) 72,000 type IV collagenase. Batimastat at concentrations between 0.01 and 3.0 micrograms/ml had no direct cytotoxic effects on the in vitro growth of the cell lines. In the liver-invasive tumor model, batimastat administered i.p. from day 10 to termination of the therapy (day 39) at 40 mg/kg reduced both the mean number of liver tumors (35% of vehicle-treated control; P < 0.05) and the cross-sectional area of the tumors (43% of vehicle-treated control; P < 0.05). In the lung-invasive tumor model, batimastat administered daily (40 mg/kg i.p.) significantly reduced tumor weight within the lung (72% of vehicle-treated control; P < 0.05) but did not significantly affect nodule number. In the latter model, in which the take rate was unaffected, tumor cells were introduced into the lateral tail vein, and lung localization may have been a physical phenomenon not involving invasion. In the former model, tumor cells were introduced directly into the peritoneal cavity, and from there the cells adhered to and invaded the liver capsule. Because the take rate is significantly reduced, it may be that the matrix metalloproteinases are involved in this process. Batimastat may be a therapeutic modality for the treatment of colorectal cancer metastasis.

Animals↗

A 30-amino acid truncation of the microsomal triglyceride transfer protein large subunit disrupts its interaction with protein disulfide-isomerase and causes abetalipoproteinemia.

The microsomal triglyceride transfer protein (MTP) is a heterodimer composed of the multifunctional enzyme, protein disulfide-isomerase, and a unique large, 97 kDa, subunit. It is found as a soluble protein within the lumen of the endoplasmic reticulum of liver and intestine and is required for the assembly of very low density lipoproteins and chylomicrons. Mutations in MTP which result in an absence of MTP function have been shown to cause abetalipoproteinemia. Here, the gene encoding the MTP 97-kDa subunit of an abetalipoproteinemic subject, which we have previously demonstrated lacks MTP activity and protein (Wetterau, J. R., Aggerbeck, L. P., Bouma, M.-E., Eisenberg, C., Munck, A., Hermier, M., Schmitz, J., Gay, G., Rader, D. J., and Gregg, R. E. (1992) Science 258, 999-1001), was isolated and sequenced. A nonsense mutation, which predicts the truncation of the protein by 30 amino acids, was identified. To investigate if this apparently subtle change in MTP could explain the observed absence of MTP, protein disulfide-isomerase was co-expressed with either the normal or mutant MTP 97-kDa subunit in Sf9 insect cells using a baculovirus expression system. Although there were high levels of expression of both the normal and mutant forms of the MTP 97-kDa subunit, only the normal subunit was able to form a stable, soluble complex with protein disulfide-isomerase. These results indicate that the carboxyl-terminal 30 amino acids of the MTP 97-kDa subunit plays an important role in its interaction with protein disulfide-isomerase.

Abetalipoproteinemia↗

Anti-gastrin antibodies raised by gastrimmune inhibit growth of the human colorectal tumour AP5.

The neutralising ability of rabbit anti-gastrin-17 (G17) antiserum raised by Gastrimmune, an immunogen constructed of the N-terminal portion of human G17 conjugated to diptheria toxoid (DT), was evaluated. The anti-serum (denoted anti-G17: DT) was shown to displace 125[I] G17 from the gastrin receptors on AR42J cells. The therapeutic effect of the rabbit anti-G17:DT anti-serum was evaluated on a freshly derived human colorectal cancer cell line, AP5, which was shown to express both gastrin receptors and gastrin immunoreactivity as assessed by immunocytochemistry. Rabbit anti-G17:DT anti-serum was shown to block basal in vitro growth of AP5 cells when used at an antigen binding capacity of 3.75 x 10(-9) M. The same dilution of anti-serum completely reversed growth stimulated by human G17 at concentrations of 1 x 10(-10) and 1 x 10(-9) M but did not inhibit growth at 1 x 10(-8) M G17. When AP5 was grown as a xenograft in nude mice, the sensitivity to the proliferative effect of human G17 was maintained. In addition, the basal growth of AP5 xenografts was significantly reduced by i.v. infusion of rabbit anti-G17:DT anti-serum when compared to treatment with rabbit anti:DT control anti-serum. Thus anti-G17:DT antibodies raised by Gastrimmune may be of clinical value in gastrin-sensitive tumours.

3T3 Cells↗

Clinical indicators associated with unintentional weight loss and pressure ulcers in elderly residents of nursing facilities.

OBJECTIVE: To monitor adults older than 65 years living in nursing facilities and who experience unintentional weight loss of more than 10% of actual body weight in 6 months or more than 5% in 1 month or who have stage II, III, or IV pressure ulcers. SUBJECTS: We reviewed 290 medical records for unintentional weight loss and 265 for pressure ulcers. DESIGN: Two data-collecting instruments were used: one for pressure ulcers and one for unintentional weight loss. Indicators for each instrument were selected to monitor clinical conditions that tend to be problem-prone areas for these two populations. STATISTICAL ANALYSIS: Descriptive statistics were used to calculate the frequency of each indicator for each population. RESULTS: Of the 24 indicators for unintentional weight loss, the 6 indicators present most often, in descending order, were reduced functional ability, intake of 50% or less of food served for the past 3 consecutive days, chewing problems, serum albumin level less than 35 g/l with normal hydration status, cholesterol level less than 4.1 mmol/L, and refusal of 50% or more of food replacement for the past 7 days. For the residents with pressure ulcers, the indicator present most often was serum albumin level less than 35 g/L with normal hydration status. The three highest intervention indicators were receives 1.2 g protein per kilogram of actual body weight, receives 120 mg or more of vitamin C daily, and receives 1 1/2 times the energy required based on goal body weight. When serum albumin level was documented in the medical record, it was a valid indicator for both diagnoses. CONCLUSIONS: Inappropriate dietary intake, disease, and disability place residents in nursing facilities at risk for malnutrition. Thus, it is important to obtain laboratory values when assessing elderly residents and determining their nutritional status.

Aged↗

Technique and results of laparoscopic choledochotomy for the management of bile duct calculi.

Laparoscopic choledochotomy has been performed in 50 patients to remove common bile duct calculi demonstrated on routine operative cholangiography at the time of laparoscopic cholecystectomy. The patients ranged from 16 to 91 years old. One patient died, giving a mortality of 2%. At postoperative T-tube cholangiography, retained stones were demonstrated in three patients (6%) with all stones being removed using a choledochoscope via the T-tube track. Laparoscopic common bile duct exploration via a choledochotomy is a feasible and effective method to manage common bile duct calculi demonstrated during laparoscopic cholecystectomy.

Adolescent↗

Mental health services: critical component of integrated primary care and substance abuse treatment.

The documented high incidence of mental health disorders among individuals in substance abuse treatment argues for the importance of studying the provision of mental health services to this population. This survey documents how the Linkage Programs assembled an array of mental health services based on the assessed health care needs of clients. Specialty and nonspecialty personnel addressed the extensive mental health needs of ethnically diverse, multiproblem clients with substance abuse problems. The innovative use of nonconventional providers, however, did not eliminate the shortfall between the number of clients with mental health problems and the number who were referred to and received mental health services; nor did it enable all Linkage Programs to address the mental health needs of the most severely ill clients. There is a continuing need to forge relationships between mental health providers and integrated providers of primary care and substance abuse treatment.

Community Mental Health Services↗

Persistence of an activating N-RAS oncogene mutation in clonogenic progenitor cells from an acute myeloid leukaemia patient in remission.

A patient with acute myeloid leukaemia (AML) with an activating N-RAS oncogene mutation was studied in a haemopoietic clonogenic progenitor cell assay. Individual colonies and clusters were analysed by polymerase chain reaction and oligonucleotide hybridization for the original mutation. The mutation was detected in a majority of leukaemic clusters, but also in almost half of the differentiated colonies. After chemotherapy the patient entered clinical remission. However, the mutation could still be detected in the bone marrow. Only differentiated colonies and no leukaemic clusters were grown from the remission bone marrow, but the original mutation was still detectable in almost half of the colonies.

Aged↗

The 12-hour shift: the views of nurse educators and students.

Interest in 12-hour nursing shifts has been renewed in response to demands for improved cost-effectiveness in the UK National Health Service. But the effects of the shift on nursing education are unclear. We report surveys of the attitudes of student nurses and nurse educators towards 12-hour shifts. Learners are reasonably positive about 12-hour shifts, but this preference is based on social rather than professional benefits. A reported effect of fatigue on home study is evident. Very negative views about the 12-hour shift are held by the group of educators. Their criticisms appear to be primarily organizational, but they are unequivocal that learning is detrimentally affected. Thus, even if students appear to like this shift pattern, serious concerns are raised by these findings about the impact of the shift on nursing education.

Adult↗

Abdominal aortic aneurysm and associated colorectal carcinoma: a management problem.

The increasing age of the population has led to the more common occurrence of multi-organ disease. Colorectal cancer (CRC) and abdominal aortic aneurysm (AAA) in the same patient is a difficult management problem. Over 10 years, 23 patients with CRC and AAA were treated at Concord Hospital. The management and outcome of these patients was reviewed to identify an optimum plan for patients with both conditions. The average age of patients was 71 years, ranging from 52 to 90 years. There was only one female patient in the series. In 19 of the patients, the AAA and CRC were synchronous, while in the other four patients the AAA and CRC were remote events. Within the group of patients with synchronous AAA and CRC. 12 had the diagnosis of both conditions made pre-operatively. However, in seven cases an unexpected AAA or CRC was found at operation for the other condition. Sixteen patients underwent resection of the CRC, while only eight underwent repair of the AAA. There were three deaths following CRC resection, two following AAA resection, and one following simultaneous CRC resection and AAA repair. Two of 10 patients with large (> 6 cm) AAA, who underwent CRC resection, ruptured the AAA in the postoperative period. A further patient ruptured 10 months following CRC resection. Colorectal cancer was given priority over AAA when these conditions were found simultaneously. The present study suggests that a large AAA (> 6 cm) should be either given preferential treatment, or resected simultaneously, in view of the high risk of rupture.

Aged↗

Naturally occurring antibodies devoid of light chains.

Random association of VL and VH repertoires contributes considerably to antibody diversity. The diversity and the affinity are then increased by hypermutation in B cells located in germinal centres. Except in the case of 'heavy chain' disease, naturally occurring heavy-chain antibodies have not been described, although antigen binding has been demonstrated for separated heavy chains or cloned VH domains. Here we investigate the presence of considerable amounts of IgG-like material of M(r) 100K in the serum of the camel (Camelus dromedarius). These molecules are composed of heavy-chain dimers and are devoid of light chains, but nevertheless have an extensive antigen-binding repertoire, a finding that calls into question the role of light chains in the camel. Camel heavy-chain IgGs lack CH1, which in one IgG class might be structurally replaced by an extended hinge. Heavy-chain IgGs are a feature of all camelids. These findings open new perspectives in the engineering of antibodies.

Amino Acid Sequence↗

Effect of four combined oral contraceptives on blood pressure in the pill-free interval.

OBJECTIVE: To evaluate blood pressure changes in the pill-free interval and from baseline among women taking four different low-dose monophasic oral contraceptives. DESIGN: 131 women were randomized to four different oral contraceptives. Pressures were obtained at baseline, at the end of treatment cycles and at the end of the 7 pill-free days, during 6 months of treatment. Pressures were obtained at 4 and 8 weeks after discontinuation. Group 1 received norethisterone acetate 1000 micrograms, group 2 received levonorgestrel 150 micrograms, group 3 received desogestrel 150 micrograms, and group 4 received gestodene 75 micrograms, all combined with ethinyloestradiol 30 micrograms. RESULTS: All four groups showed an increase in pressure during treatment, with return to baseline levels four weeks after treatment. At the end of the pill-free interval, the readings did not differ significantly from on treatment except for women in Group 4, who experienced an increase in diastolic pressure. CONCLUSIONS: Use of the four oral contraceptives was associated with a small increase in systolic and diastolic pressure. Whatever mechanism causes the increase is not entirely reversible by 7 days without treatment.

Adolescent↗

The quantity of nursing care on wards working 8- and 12-hour shifts.

Interest in 12-hour nursing shifts has been renewed in response to demands for improved cost-effectiveness in the NHS, but the effects of this shift on the delivery of patient care have been unclear. This paper describes the results of a repeated-measures study of 10 wards, using activity analysis to describe patterns of care under an 8-hour compared to a 12-hour shift system. Significant reductions in the amount of direct patient care were found under the 12-hour shift, with corresponding increases in unofficial work-breaks. It is suggested that these findings, which were consistent over all study wards and throughout the whole 12-hour day, demonstrate a "pacing" effect by nurses who face 12 hours on duty. Such a detrimental effect should be a major consideration when coming to any decision to implement a 12-hour shift.

Hospital Units↗