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Biomedical subjects

A Hawkins

Publications and source records attributed to A Hawkins.

At least 37 records · Page 2Linked to original sources

Antagonism of cyanide intoxication with murine carrier erythrocytes containing bovine rhodanese and sodium thiosulfate.

Murine carrier erythrocytes containing bovine rhodanese and sodium thiosulfate are being explored as a new approach to antagonize the lethal effects of potassium cyanide in mice. Prior studies indicated that these carrier erythrocytes persist in the vascular system for the same length of time as normal erythrocytes and can enhance metabolism of cyanide to thiocyanate. The present studies demonstrate the ability of these carrier red blood cells containing rhodanese and thiosulfate to antagonize the lethal effects of cyanide either alone or in various combinations with sodium nitrite and/or sodium thiosulfate. Potency ratios are compared in groups of mice treated with sodium nitrite, sodium thiosulfate, and carrier erythrocytes containing rhodanese and sodium thiosulfate either alone or in various combinations prior to the administration of potassium cyanide. These results indicate that the administration of carrier erythrocytes containing rhodanese and thiosulfate alone can provide significant protection against the lethal effects of cyanide. These carrier erythrocytes potentiate the antidotal effect of sodium thiosulfate alone or the combination of sodium nitrite and sodium thiosulfate. The mechanisms of cyanide antagonism by these carrier erythrocytes and their broader conceptual significance to the antagonism of other chemical toxicants are discussed.

Animals↗

The effects of changing prompted voiding schedules in the treatment of incontinence in nursing home residents.

OBJECTIVE: To determine the effects of different prompted voiding schedules on urinary incontinence on a continence unit (CU) and the maintenance of benefits on normal nursing units. DESIGN: Multiphase study with both intra- and inter-subject comparisons. PARTICIPANTS: Subjects were 41 consenting incontinent nursing home residents. Based on clinical criteria, subjects were assigned to one of four treatment groups that varied as to the schedule of prompted voiding received. MEASUREMENT: The study used chart review, Katz ADL, and MMSE. Urologic status, self-initiated toileting, urine volumes voided, and incontinence assessed by pad/pants checks were measured by research nurses. Baseline pad check data were collected on residents' normal nursing units. Residents were transferred to the CU where baseline measurement was repeated, and the effects of different prompted voiding schedules were then assessed. Indigenous staff were trained to use prompted voiding, and nurse supervisors were instructed in special procedures for enhancing maintenance of the intervention. Residents were returned to their normal units and the maintenance of improvements in continence status was assessed at 2 weeks and 3 months post-CU discharge. RESULTS: One of the four groups showed significant improvement on the CU in response to the 2-hour schedule; two groups improved on the less intensive 3-hour schedule (P < 0.05). Two groups maintained this improvement on their normal nursing units (P < 0.05); one group showed a non-significant trend toward improvement. Self-initiated toileting decreased (P < 0.05) and volume voids in an appropriate receptacle increased (P < 0.05) during training. CONCLUSIONS: Prompted voiding is an effective treatment for urinary incontinence, and a less intensive 3-hour schedule may be superior to the standard 2-hour schedule for some residents. These improvements in dryness can be maintained by normal nursing home staff if formal staff management procedures are utilized by nurse supervisors.

Aged↗

Patterns of hospital care for patients with HIV infection and AIDS.

OBJECTIVE: The aims were to describe the use of inpatient resources by patients with HIV infection and patients with AIDS; to examine trends in service use over time; and to provide data for planners concerned with service provision for HIV infection. SETTING: An inner London health district reporting 9% of AIDS cases nationally. DESIGN: Data on survival times and inpatient and day care use of resources were derived from existing patient records or collected prospectively between 1983 (when the first case of AIDS was diagnosed in the district) and 31 March 1990. SUBJECTS: A total of 488 HIV positive patients of whom 396 had been diagnosed as having AIDS were studied. MEASUREMENTS AND MAIN RESULTS: Inpatient days consumed per annum; trends in the number of bed days per person year with AIDS; the lifetime inpatient use per AIDS patient; and the influence of survival on service use estimates were determined. Altogether 16.4% of a total 17,785 hospital inpatient days were attributable to HIV positive patients who did not fulfil the criteria for AIDS. For patients with AIDS, there was an initial increase in the intensity of inpatient use in 1987 when a dedicated HIV ward was opened. After 1988, however, inpatient use fell to 30.8 bed days per person year with AIDS. Patients diagnosed after April 1987 had noticeably longer survival times than those diagnosed earlier (a median of 17-18 months compared with a median of 10-11 months). From 214 lifetime service use records, it was estimated that patients with short survival (less than six months) would consume 36 days of inpatient care, while those expected to survive longer would consume approximately twice that number of days, irrespective of how much longer they survived. CONCLUSIONS: The data indicate less intensive use of inpatient care by AIDS patients over time, and hence the apparent ability to manage an increasing AIDS patient workload without a comparable increase in occupied bed days. Increases in the size of that workload and changes in the survival profile of patients, together with a relatively constant rate of service demand by longer survivors, however, will continue to place increasing strains on finite inpatient resources. Further research is needed to establish the extent to which the greater use of outpatient and community services can offset this.

Acquired Immunodeficiency Syndrome↗

Chromosomal band assignments of the genes encoding human FKBP12 and FKBP13.

Human FKBP12 and FKBP13 are encoded by distinct genes designated FKBP1 and FKBP2, respectively. Human FKBP1 was previously characterized. The characterization of human FKBP2 is described. FKBP2 is three kb in length and contains six exons. Fluorescence in situ hybridization of FKBP1 and FKBP2 genomic probes to metaphase chromosomes localized FKBP1 to human chromosome 20 band p13 and FKBP2 to human chromosome 11 band q13.1-q13.3.

Amino Acid Sequence↗

In vivo studies on rhodanese encapsulation in mouse carrier erythrocytes.

Resealed erythrocytes containing sodium thiosulfate and rhodanese (CRBC) are being employed as a new approach in the antagonism of cyanide intoxication. In earlier in vitro studies, the behavior of red blood cells containing rhodanese and sodium thiosulfate was investigated with regard to their properties and their capability of metabolizing cyanide to thiocyanate. The present studies are concerned with the properties of these rhodanese-containing carrier erythrocytes in the intact animal. These carrier erythrocytes were administered intravenously and the survival of the encapsulated enzyme was compared with the administration (iv) of free exogenous enzyme. Also, the amount of leakage of the encapsulated rhodanese from the red blood cell was determined. The survival of the carrier red blood cell. prepared by hypotonic dialysis, was found to be characterized by a biphasic curve. There was an initial rapid loss of approximately 40 to 50% of the carrier cells with a t1/2 = 2.5 hr. Subsequently the remaining resealed annealed carrier erythrocytes persisted in the vascular system with a t1/2 = 8.5 days. When free exogenous rhodanese was administered directly into the vascular system, it was rapidly eliminated with a t1/2 = 53 min. Red blood cells containing sodium thiosulfate and rhodanese apparently are effective in vivo in the biotransformation of cyanide. In animals pretreated with encapsulated rhodanese and sodium thiosulfate, blood cyanide concentrations are appreciably decreased with a concomitant increase in thiocyanate ion, a metabolite of cyanide. When erythrocytes, which contained no rhodanese or sodium thiosulfate, were subjected to hypotonic dialysis, cyanide was not metabolized to any appreciable extent. Furthermore, carrier erythrocytes containing rhodanese and sodium thiosulfate were found to increase the protection against the lethal effects of cyanide by approximately twofold. The ability of these carrier erythrocytes alone to metabolize cyanide and to antagonize the lethal effects of cyanide reflects the potential of this new antidotal approach in the antagonism of chemical toxicants.

Animals↗

The Mycobacterium tuberculosis shikimate pathway genes: evolutionary relationship between biosynthetic and catabolic 3-dehydroquinases.

The Mycobacterium tuberculosis shikimate pathway genes designated aroB and aroQ encoding 3-dehydroquinate synthase and 3-dehydroquinase, respectively were isolated by molecular cloning and their nucleotide sequences determined. The deduced dehydroquinate synthase amino acid sequence from M. tuberculosis showed high similarity to those of equivalent enzymes from prokaryotes and filamentous fungi. Surprisingly, the deduced M. tuberculosis 3-dehydroquinase amino acid sequence showed no similarity to other characterised prokaryotic biosynthetic 3-dehydroquinases (bDHQases). A high degree of similarity was observed, however, to the fungal catabolic 3-dehydroquinases (cDHQases) which are active in the quinic acid utilisation pathway and are isozymes of the fungal bDHQases. This finding indicates a common ancestral origin for genes encoding the catabolic dehydroquinases of fungi and the biosynthetic dehydroquinases present in some prokaryotes. Deletion of genes encoding shikimate pathway enzymes represents a possible approach to generation of rationally attenuated strains of M. tuberculosis for use as live vaccines.

Amino Acid Sequence↗

The Gospel Oak Study: prevalence rates of dementia, depression and activity limitation among elderly residents in inner London.

The steps to setting up a population register of elderly residents are described. Based upon this, 87.2% of the elderly residents of an inner-city electoral area were screened for memory disorder, depression and activity limitation using the Short CARE. Contact with medical and social agencies was also recorded; 4.7% were classed as cases by the dementia diagnostic scale, sufferers being older and not living alone. Of the residents 15.9% were classed as depressed, this state being more prevalent in those not currently married. The depressed were, in contrast to the demented residents, likely to be in recent contact with hospital and general practitioner. Thirty-two per cent of the population showed impairment in daily activity, these individuals were usually older, not married and receiving hospital care. Sleep disorder and complaint of many somatic symptoms were associated with a diagnosis of depression. In contrast, most respondents with a subjective complaint of memory disorder, which was common in this population, were neither suffering from depression nor dementia. With this accurate sampling frame and a good response rate, the prevalence rate of clinical depression must be seen as disturbingly high. The prevalence rate of dementia approximated to that of other surveys. This study also indicated that general practitioners' lists may be inaccurate and that non-responders to first approaches for interview, although similar in demographic features to those responding, may contain among them many suffering from dementia.

Activities of Daily Living↗

A descriptive analysis of nursing staff behaviors in a teaching nursing home: differences among NAs, LPNs, and RNs.

Various staff behaviors in a nursing home were sampled seven times a day, 5 days a week over 37 months and were coded separately for LPNs, RNs, and NAs. The behavior most frequently observed was patient care, which occurred during 56.9% of the samples. We observed staff interacting with patients during 10.7% and with other staff during 19.5% of the samples. The LPNs displayed significantly more patient care behaviors and NAs significantly more nonwork behaviors than other nursing staff. RNs displayed the least nonwork behavior. We conclude that nursing staff devote most of their time to patient needs and relatively little time to nonproductive activities.

Behavior↗

A staff management system for maintaining improvements in continence with elderly nursing home residents.

We developed a staff management system for maintaining treatment gains achieved on a specialized continence unit located in a geriatric nursing home. Geriatric assistants learned to use a prompted voiding procedure to maintain improved dryness for 4 elderly residents. The staff management system included self-monitoring and recording of prompted voiding activities and supervisory monitoring and feedback based on group performance of these activities. Results show that the system was effective in maintaining prompted voiding activities with corresponding maintenance of improved patient continence. However, a gradual decline in staff performance was noted 4 to 5 months after the initiation of the system. During a subsequent phase of the study, provision of individual feedback restored staff performance to previous levels. Results are discussed in relation to the practicality of prompted voiding interventions in nursing home environments and the applicability of staff management systems in this setting.

Aged↗

Human immunodeficiency viruses in patients attending a sexually transmitted disease clinic in London, 1982-7.

OBJECTIVE: To determine the prevalence of infection with the human immunodeficiency virus (HIV) in all patients attending a London sexually transmitted disease clinic over four weeks at the end of 1987 and to see how it varied from that in similar samples studied between 1982 and 1986. DESIGN: Anonymous testing of serum samples from consecutive heterosexual and homosexual patients having routine serological investigations for syphilis. Testing was for anti-HIV-I, anti-HIV-II, and hepatitis B core antibody (anti-HBc) and P24 antigen. Age, nationality, sexual orientation, and past sexually transmitted diseases were recorded for each patient. Gonorrhoea rates by quarters were analysed among homosexual and bisexual men and heterosexual men and women from 1981 to 1987. SETTING: Outpatient department of genitourinary medicine. PATIENTS: A total of 1074 patients attending consecutively for syphilis serology. Thirty five homosexual and bisexual men were excluded (these were regular attenders as part of a prospective study of the natural course of HIV infection). MEASUREMENTS AND MAIN RESULTS: The prevalence of anti-HIV-I in homosexual and bisexual men in 1987 was 25.6% (64/250). Results in the same clinic population between 1982 and 1984 had shown a rise in prevalence, which flattened out in 1985-6 and continued at that level. Among heterosexual attenders in 1987 the prevalence of anti-HIV-I was 1% (women 4/412; men 4/377), which contrasted with a prevalence of 0.5% (women 2/395; men 3/757) in January 1986. One homosexual man was seropositive for anti-HIV-II and seronegative for anti-HIV-I. Among homosexual and bisexual men the rate of gonorrhoea had declined by an average of 2.7% a year since 1981, such that by 1987--and for the first time in the clinic--there was no significant difference in the rates between these men and heterosexual men and women. CONCLUSIONS: The appearance of HIV-I infection among heterosexuals indicates a need for more aggressive education programmes and intervention strategies along the lines adopted for homosexual men. Surveillance for HIV-II infection is needed to provide information for future policy in national screening programmes.

Acquired Immunodeficiency Syndrome↗

Excessive burden of end-state renal disease among Canadian Indians: a national survey.

Analysis of data from the Canadian National Renal Failure Register indicates that Canadian Natives are at much higher risk for end-stage renal disease (ESRD) than the Canadian population in general. Using two population estimates for the total Native population, the age-standardized incidence rate of newly registered ESRD cases between 1981 and 1986 among Natives was at least 2.5 times (and may be as high as four times) the national rate. Natives were particularly at higher risk for ESRD to diabetes, glomerulonephritis, and pyelonephritis, whereas for the other causes the risk was no different from that of other Canadians. As technologically sophisticated treatment facilities are only available in major urban centers, Native ESRD patients and their families living in remote areas of Canada are faced with major psychosocial disruptions of relocation.

Canada↗

Hepatitis B virus reactivation or reinfection associated with HIV-1 infection.

Following acute hepatitis B virus (HBV) infection, most individuals develop antibodies to HBV surface (anti-HBs) and core antigen (anti-HBc). Prevalence studies have shown that 10-18% develop anti-HBc in the absence of detectable anti-HBs. We report four such cases, all with persistence of serum anti-HBc, who had evidence of a second period of active HBV replication as demonstrated by the reappearance of serum hepatitis B surface antigen (HBsAg). In one patient, an HBsAg subtype difference indicated that the second period of HBsAg-positivity was due to a reinfection. In the other cases, reactivation may also explain the findings. All cases were anti-HIV-1 seropositive at the time of reappearance of HBsAg. There is experimental evidence that anti-HBc has a protective effect against HBV infection; however, this may require intact cell-mediated immunity to be effective. HIV-1 infection may render such patients susceptible to reinfection. Alternatively, some patients with anti-HBc, but without detectable anti-HBs may have latent HBV infection. Immunosuppression associated with HIV-1 infection may allow reactivation.

Acquired Immunodeficiency Syndrome↗

Prevalence of antibodies to human immunodeficiency virus, gonorrhoea rates, and changed sexual behaviour in homosexual men in London.

The prevalence of antibody against human immunodeficiency virus (anti-HIV), which rose among British homosexual/bisexual men attending a London sexually-transmitted-disease clinic from 3.7% (4/107) in March, 1982, to 21% (26/124) in July, 1984, was 18.1% (17/94) in April/May 1985, 24.5% (61/249) in January, 1986, and 25.3% (25/99) in November/December, 1986. This slower rise in anti-HIV prevalence coincided with a fall in the annual gonorrhoea rate from 15.3% in 1982 to 5.1% in the first half of 1986 in the same male homosexual clinic population. Over the same period a reduction in the number of sexual partners and a change to safer sexual practices has been documented among homosexual and bisexual men taking part in a prospective study of the natural history of HIV infection. These data support the value of continuing preventive efforts to control viral spread in the absence of an effective vaccine or therapy.

Acquired Immunodeficiency Syndrome↗

Spontaneous loss of HBeAg and the prevalence of HTLV-III/LAV infection in a cohort of homosexual hepatitis B virus carriers and the implications for antiviral therapy.

The future design of controlled trials of antiviral therapy which might include homosexual hepatitis B virus (HBV) carriers requires base-line data on the spontaneous rate of loss of HBeAg and the prevalence of human T-lymphotropic virus III (HTLV-III/LAV) infection. Fifty-one untreated HBsAg and HBeAg-positive homosexual HBV carriers were followed for a median HBeAg-positive time of 23.5 months (range 6-85.5). Ten lost HBeAg, giving an annual rate of spontaneous loss of HBeAg of 10%. This rate is considerably higher than the apparent rate in a previous report and has considerable implications for the interpretation of previous, and the design of future, controlled trials in this population. A rapid rise in the prevalence of anti-HTLV-III/LAV amongst HBV carriers was demonstrated from 1981 such that by 1984 over 60% of HBV carriers were anti-HTLV-III-positive. HBV-DNA polymerase levels were not significantly different in asymptomatic anti-HTLV-III/LAV-positive compared to anti-HTLV-III/LAV-negative HBV carriers. Nevertheless, since chronic HTLV-III/LAV infection in its later stages may potentiate HBV replication, it is a factor that will need to be considered together with many others in any trial stratification procedure.

Acquired Immunodeficiency Syndrome↗

Two pathographies: a study in illness and literature.

This study compares two autobiographical descriptions of illness--the seventeenth-century John Donne's Devotions Upon Emergent Occasions and the twentieth-century Cornelius and Kathryn Ryan's A Private Battle. I begin by identifying the basic structure in both narratives as parallel to that of the case history, and then show how each individual's experience is shaped by the conditions of illness appropriate to their respective cultures. Lastly, I discuss the way in which both authors understand and represent sickness, as well as their respective therapies, in terms of a particular metaphoric construct: for Donne, it is the analogy between illness of the body and illness of the soul; for Ryan it is the analogy between illness and war. The stance of each towards his illness is conditioned by this metaphoric model: Donne's is one of acceptance, of conforming to the will of God; Ryan's is one of resistance, of fighting heroically until the very end. Thus these metaphors are functional as well as aesthetic: they serve as figural modalities whereby the patient/author hopes to transcend his illness.

England↗

Tumour cellularity, oestrogen receptors and prognosis in breast cancer.

One hundred and thirty-seven patients with operable breast cancer have been treated by mastectomy and node sampling. At the time of operation, portions of tumour were taken for determination of oestrogen receptor activity. In 91 cases adjacent tissue was taken for fixation and histological assessment of malignant epithelial cell content ('cellularity index'). The patients were followed for two years or more, or until first recurrence or death. Prognosis (probability of staying disease-free) was significantly better in patients whose tumours contained receptors than in those whose tumours were receptor-negative (p less than 0.03). However, the best prognosis was in patients with low receptor positive tumours. Those with highest values had a prognosis almost as poor as patients with receptor-negative tumours. In addition, a new finding emerged: prognosis was better in patients with tumours of low cellularity than in those with tumours of high cellularity (p less than 0.04). Since, for receptor-positive tumours, receptor level was also significantly correlated with cellularity (R = +0.35, p less than 0.01), the relationship between prognosis and receptor level was re-examined after 'correction' of the latter quantity for differences in cellularity: on this basis, again prognosis was better in patients with receptor-positive tumours (p less than 0.02), but there was no longer a tendency for any one sub-group of patients with receptor-positive tumours to fare better than the rest. It is concluded that prognosis in operable breast cancer is related to oestrogen receptor activity (either per mg weight, or per cell) and to cellularity.

Age Factors↗