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Biomedical subjects

S Holmberg

Publications and source records attributed to S Holmberg.

At least 73 records · Page 4Linked to original sources

Locus-specific suppression of ilv1 in Saccharomyces cerevisiae by deregulation of CHA1 transcription.

The ILV1 gene of Saccharomyces cerevisiae encodes the anabolic threonine deaminase, which catalyzes the first committed step in isoleucine biosynthesis. Strains devoid of a functional Ilv1p have a requirement for isoleucine. Threonine can also be deaminated by a second serine/threonine deaminase encoded by the CHA1 gene. CHA1 is regulated by transcriptional induction by serine and threonine, and enables yeast to utilize the hydroxyamino acids as sole nitrogen source. Phenotypic suppression of ilv1 can occur by inducer-mediated transcriptional activation of the CHA1 gene. To identify mutations in putative trnas-acting factors regulating CHA1 expression, we have isolated and characterized three extragenic suppressors of ilv1. A dominant mutation, SIL4 (suppressor of ilv1), is allelic to HOM3. It increases the size of the threonine pool, by 15- to 20-fold, which is sufficient to induce CHA1 transcription, thereby creating a metabolic bypass of ilv1. A second dominant mutation, SIL3, and a recessive mutation, sil2, both suppress ilv1 by causing inducer-independent, constitutive transcription of CHA1. Importantly, sil2 and SIL3 increase the expression of a CHA1p-lacZ translational gene fusion, demonstrating that they exert their action through the CHA1 promoter. Genetic analysis showed that both SIL3 and sil2 are alleles of CHA4, a positive regulator of CHA1, i.e., they convert Cha4p to a constitutive activator.

Chromosome Mapping↗

Continuation of CPR on admission to emergency department after out-of-hospital cardiac arrest. Occurrence, characteristics and outcome.

AIM: To describe the occurrence, characteristics and outcome among patients with out-of-hospital cardiac arrest who required continuation of cardiopulmonary resuscitation (CPR) on admission to the emergency department. PATIENTS: all patients in the municipality of Göteborg who suffered out-of-hospital cardiac arrest, were reached by the emergency medical service (EMS) system and in whom CPR was initiated. Period for inclusion in study: 1 Oct. 1980-31 Dec. 1992. RESULTS: of 334 out-of-hospital cardiac arrests, 2,319 (68%) were receiving on-going CPR at the time of admission to hospital. Of these, 137 patients (6%) were hospitalized alive and 28 (1.2%) could be discharged from hospital. Of these patients, 39% had a cerebral performance categories (CPC) score of 1 (no cerebral deficiency), 18% had a CPC score of 2 (moderate cerebral deficiency), 36% had a CPC score of 3 (severe cerebral deficiency) and 7% had a CPC score of 4 (coma) at discharge. Among patients discharged. 76% were alive after 1 year. CONCLUSION: among consecutive patients with out-of-hospital cardiac arrest, CPR was ongoing in 68% of them on admission to hospital. Among these patients, 6% were hospitalized alive and 1.2% were discharged from hospital. Thus, among patients with ongoing CPR on admission to hospital, survivors can be found but they are few in numbers and extensive cerebral damage is frequently present.

Adolescent↗

Lidocaine in out-of-hospital ventricular fibrillation. Does it improve survival?

BACKGROUND: A large proportion of cardiac arrests outside hospital are caused by ventricular fibrillation. Although it is frequently used, the exact role for treatment with lidocaine in these patients remains to be determined. AIM: To describe the proportion of patients with witnessed out-of-hospital cardiac arrest found in ventricular fibrillation who survived and were discharged from hospital in relation to whether they were treated with lidocaine prior to hospital admission. PATIENTS AND TREATMENT: All the patients with out-of-hospital cardiac arrest found in ventricular fibrillation in Göteborg between 1980 and 1992 in whom cardiopulmonary resuscitation (CPR) was initiated by our emergency medical service (EMS). During the observation period, some of the EMS staff were authorized to give medication and some were not. RESULTS: In all, 1,360 patients were found in ventricular fibrillation, with detailed information being available in 1,212 cases (89%). Lidocaine was given in 405 of these cases (33%). Among patients with sustained ventricular fibrillation, those who received lidocaine had a return of spontaneous circulation (ROSC) more frequently (P < 0.001) and were hospitalized alive more frequently (38% vs. 18%, P < 0.01). However, the rate of discharge from hospital did not significantly differ between the two groups. Among patients who were converted to a pulse-generating rhythm, those who received lidocaine on that indication were more frequently alive than those who did not receive such treatment (94% vs. 84%; P < 0.05). However, the rate of discharge did not significantly differ between the two groups. CONCLUSION: In a retrospective analysis comparing patients who received lidocaine with those who did not in sustained ventricular fibrillation and after conversion to a pulse-generating rhythm, such treatment was associated with a higher rate at ROSC and hospitalization but was not associated with an increased rate of discharge from hospital.

Adult↗

Rhythm changes during resuscitation from ventricular fibrillation in relation to delay until defibrillation, number of shocks delivered and survival.

AIM: To describe rhythm changes during the initial phase of resuscitation from ventricular fibrillation in relation to the interval between collapse and defibrillation, to survival and to bystander-initiated cardiopulmonary resuscitation (CPR). PATIENTS: All patients who suffered out-of-hospital cardiac arrest between 1980 and 1992, who were reached by the emergency medical service system (EMS), in whom resuscitation attempts were initiated and who were found in ventricular fibrillation. RESULTS: In all, 1216 patients were included in the study. Among patients who converted to a pulse-generating rhythm after the first defibrillation (n = 119) were 56% discharged from hospital as compared with 6% among patients who converted to asystole. The corresponding figures after the third defibrillation were 49% and 2%, respectively, and after the fifth defibrillation 28% and 7%, respectively. Among patients in whom the first defibrillation took place less than 5 min after collapse, 28% directly converted to a pulse-generating rhythm as compared with 3% when the first defibrillation took place 12 min or more after collapse. CONCLUSION: Among patients who suffer out-of-hospital cardiac arrest and are found in ventricular fibrillation, there is a strong relationship between survival and initial rhythm changes after defibrillation. These rhythm changes are directly related to the interval between collapse and the first defibrillation.

Adolescent↗

Survivors of out of hospital cardiac arrest: their prognosis, longevity and functional status.

This paper reports, consistent with Utstein Style definitions, 13 years experience observing out-of-hospital cardiac arrest survivors' prognosis, longevity and functional status. We report for all patients, available outcome information for out-of-hospital cardiac arrest survivors in Göteborg Sweden between 1980 and 1993. Patients were followed for at least 1 year and some for over 14 years. From 1980 to 1993 Göteborg EMS treated 3754 out-of-hospital cardiac arrests. 9% (n = 324) were discharged from the hospital alive. Survivors' median age was 67 and 21% (n = 67) were women. Mortality rate was: 21% (n = 61) at 1 year; 56% (n = 78) by 5 years; and 82% (n = 32) by 10 years following the arrest. During the first 3 years, 16% (n = 46) experienced another cardiac arrest, 19% (n = 53) had an acute myocardial infraction and a total of 81% (n = 232) were rehospitalized for various conditions. 14% (n = 40) returned to previous employment, and 74% (n = 229) had retired before their arrest occurred. Cerebral performance categories (CPC) scores were: At hospital discharge N = 324; Data available for 320-1 = 53% (n = 171), 2 = 21% (n = 66), 3 = 24% (n = 77), 4 = 2% (n = 6). One year post arrest N = 263; Data available for 212-1 = 73% (n = 156), 2 = 9% (n = 18), 3 = 17% (n = 36), 4 = 1% (n = 2). Overall, 21% (n = 61) of cardiac arrest survivors died during the first year, and an additional 16% (n = 46) experienced another arrest. 73% of those patients who were still alive after 1 year returned to pre-arrest function.

Adolescent↗

Experience of an emergency mobile asthma treatment programme.

In order to reduce mortality and the need for hospital care for patients suffering from acute asthma, an emergency programme was set up. An ambulance crew, trained in coronary-pulmonary resuscitation was instructed in dealing with acute asthma and delegated to give 24 h treatment with bronchodilators (inhaled salbutamol and ipratropium bromide). If there was no, or only slight, improvement with this therapy, nurses (daytime) were delegated to give injections with corticosteroids (terbutaline and theophylline). Over a period of 2 years, 240 patients, 115 women and 125 men, were treated on 367 occasions. In 127 patients (53%), two or more treatments were given. The number of times treatment was given, as well as the proportion of females to males, increased the younger the patients were. Out of all the cases, more than 70% improved after treatment. On arrival, 21 patients (6%) were unconscious. After therapy, 15/21 patients (71%) survived. This may correspond to a similar reduction in mortality (population about 350,000 inhabitants), as it is unlikely that unconscious patients can survive without intensive care.

Adolescent↗

A 5-year prospective clinical study of Astra Tech dental implants supporting fixed bridges or overdentures in the edentulous mandible.

In a 5-year prospective clinical study, 155 endosseous implants were installed in the mandible anterior to the mental foramina in 33 edentulous patients (13 males and 20 females). Usually 6 implants were installed for fixed prostheses (FP), 13 patients with 77 implants, and 4 implants for overdentures (OD) with a Dolder bar, 20 patients with 78 implants. At the time of abutment connection 1 implant in 2 patients was found to be loose and removed. However, in both these patients overdentures were successfully placed on the remaining 3 implants. Narrow-beam radiography was used for radiological evaluation. The mean (SD) total marginal bone loss in 5 years was 0.48 (0.38) mm (0.36 (0.22) mm in the FP group and 0.56 (0.45) mm in the OD group). Very few complications were reported during the 5 years, most of them being related to the superstructures. The overall cumulative implant survival rate was 98.7% (100% in the FP group and 97.4% in the OD group). The survival rate of the superstructures was 100%. The present study has demonstrated that Astra Tech implants offer reliable and predictable medium-term support for fixed prostheses and overdentures in the edentulous mandible.

Adult↗

Comparative amino acid sequence analysis of the C6 zinc cluster family of transcriptional regulators.

The C6 zinc cluster family of fungal regulatory proteins shares as DNA-binding motif the C6 zinc cluster, also known as the Zn(II)2Cys6 binuclear cluster. This family includes transcriptional activators like Gal4p, Leu3p, Hap1p, Put3p and Cha4p from Saccharomyces cerevisiae, qutA and amdR from Aspergillus, nit4 from Neurospora and Ntf1 from Schizosaccharomyces pombe. Seventy-nine proteins were retrieved from databases by homology to the C6 zinc cluster. All were fungal and 56 were found in the entire genome sequence of S.cerevisiae. Sequence analysis suggests that 60 of the 79 proteins possess one or more coiled-coil dimerization regions succeeding the C6 zinc cluster. Previous comparisons of Gal4p and seven other C6 zinc cluster proteins identified an additional region with weak homology. This region, designated the middle homology region (MHR), was shown to be present in 50 of the 79 proteins. Although reported mutation and deletion analyses suggest a role of MHR in regulation of protein activity, no function has yet been assigned specifically to this region. We find that the family of MHR sequences is confined to C6 zinc cluster proteins and hypothesize that one MHR function is to assist the C6 zinc cluster in DNA target discrimination.

Amino Acid Sequence↗

Prognosis among patients with out-of-hospital cardiac arrest judged as being caused by deterioration of obstructive pulmonary disease.

AIM: To describe the prognosis of patients with out-of-hospital cardiac arrest judged to be caused by the deterioration of obstructive pulmonary disease. PATIENTS: All patients in the community of Göteborg Sweden who suffered out-of-hospital cardiac arrest between 1980 and 1992 attended by our emergency medical service and in whom cardiopulmonary resuscitation was initiated. METHODS: The etiology of cardiac arrest was determined according to clinical history, observations at resuscitation and findings at autopsy. RESULTS: There were 3434 cardiac arrests of which 130 (4%) were judged to have been caused by deterioration of obstructive pulmonary disease. Of these patients 50% were found in asystole, 40% in pulseless electrical activity, and only 7% in ventricular fibrillation. Among patients with cardiac arrest caused by obstructive pulmonary disease 21 (16%) were hospitalized alive and six (5%) were discharged from hospital. Among patients who developed cardiac arrest after arrival of the ambulance, 16% were discharged from hospital versus 0% among patients who had arrest prior to arrival of the ambulance. CONCLUSION: Among patients with out-of-hospital cardiac arrest caused by deterioration of obstructive pulmonary disease, half were found in asystole. Overall, the survival rate was low. This highlights the importance of effective treatment early in the course of deterioration of obstructive pulmonary disease in order to avoid cardiac arrest.

Adult↗

Bystander-initiated cardiopulmonary resuscitation out-of-hospital. A first description of the bystanders and their experiences.

At present there are about 1 million trained cardiopulmonary resuscitation (CPR) rescuers in Sweden. CPR out-of-hospital is initiated about 2000 times a year in Sweden. However, very little is known about the bystanders' experiences and reactions. The aim of this study was to describe bystander-initiated CPR, the circumstances, the bystander and his experiences. All CPR bystanders in Sweden who reported their resuscitation attempts between 1990 and 1994 were approached with a phone interview and a postal questionnaire, resulting in 742 questionnaires. Bystander-initiated CPR most frequently took place in public places such as the street. The rescuer most frequently had problems with mouth-to-mouth ventilation (20%) and vomiting (18%). More than half (53%) of the rescuers experienced CPR without problems. Ninety-two percent of the bystanders had no hesitation because of fear of contracting the acquired immunodeficiency syndrome (AIDS) virus. Ninety-three percent of the rescuers regarded their intervention as a mainly positive experience. Of 425 interviewed rescuers, 99.5% were prepared to start CPR again.

Adolescent↗

Type of arrhythmia at EMS arrival on scene in out-of-hospital cardiac arrest in relation to interval from collapse and whether a bystander initiated CPR.

Outcome after cardiac arrest is strongly related to whether the patient has ventricular fibrillation at the time the emergency medical service (EMS) arrives on the scene. The occurrence of various arrhythmias at the time of EMS arrival among patients with out-of-hospital cardiac arrest was studied in relation to the interval from collapse and whether cardiopulmonary resuscitation (CPR) was initiated by a bystander. The patients studied were all those with out-of-hospital cardiac arrest in Goteborg, Sweden, between 1980 and 1992 in whom CPR was attempted by the arriving EMS and for whom the interval between collapse and the arrival of EMS was known. In all, information on the time of collapse and the arrival of EMS was available for 1,737 patients. Among patients for whom EMS arrived within 4 minutes of collapse, 53% were found in ventricular fibrillation/tachycardia. There was a successive decline in occurrence of such arrhythmias with time. However, when the interval exceeded 20 minutes, ventricular fibrillation/tachycardia was still observed in 27% of cases. Bystander CPR increased the occurrence of such arrhythmias regardless of the interval between collapse and EMS arrival.

Adolescent↗

Exploring the interface between first and second level of care: referrals in rural Africa.

The studies aimed to determine the referral rate, the characteristics of patients referred, the reasons for referral and, in a sub-sample, its outcome. Study I recorded data on 602 patients referred to hospital from 13 rural clinics; follow-up interviews were conducted with a sub-sample of 57 referred patients. Study II interviewed 97 consecutive outpatients seeking care at Meru District Hospital. Both studies were carried out in a rural area of Meru district in central Kenya. The 602 referred cases represent between 0.3 and 1.8% of all new patients at the respective clinic with a mean of 0.5%, or 8.7 referrals annually per 1000 catchment area population. More than half of the referrals were for treatment only while 13% were for investigation, 63% were considered urgent, and 85% were referred in writing. Of the 57 subsequently interviewed, all except one had complied, and 52 patients, mostly with infections, injuries or obstetric disorders, reported improvement at the time of interview. The second study found that only 19 (20%) of the 97 outpatients had been referred (II in writing and 8 verbally). Rates of formal clinic-to-hospital referral were very low. Reasons included poor access to transport; patient inability to pay user fees, transport outlays, and other expenses; time constraints in emergency situations; and lack of feedback information from hospital to clinic. Verbal referral was common. Further research should focus on the selection of patients for referral, on follow-up of cases referred, on the communication between institutions involved, and on options for the financing of emergency transport to hospital.

Adolescent↗

Rates of major surgery by age and sex in a rural district in Kenya.

All major surgical operations performed during 1 year in Meru district, Kenya, were recorded. The district, with a population of 1.3 million, had five hospitals and two nursing homes where major surgery was performed. Over 3400 major operations were recorded: Caesarean section (129.0 operations/100,000 population), tubal ligation (39.4), laparotomy (14.0), hysterectomy (5.0), open reduction of fracture (4.3) and hernia repair (6.3). The total major surgery rate was 263/100,000 year: 88/100,000 males and 434/100,000 females. Of all major operations, 83.5% were performed on females, the most common being Caesarean section, tubal ligation, laparotomy, eye or lens removal and hysterectomy. Most frequent major operations on males were laparotomy, eye or lens removal, hernia repair, gastro-intestinal surgery and prostatectomy. Most major surgery (68.1%) was on young and middle-aged adults; only 7.7% was performed on children aged < 15 years even though these made up half of the population. Rates increased with age, and there were modest male/female differences except for very high rates of obstetrical surgery on young women. There is need to expand the district's capacity for major surgery and also to prevent more conditions requiring surgery, for example by improving sexual- and reproductive-health education, making family planning services more easily available among sexually active adolescents, and by initiating more aggressive prevention programmes against injuries. Although population-based operation rates, totally and by sex and age-group, are useful indicators for monitoring service output, current reporting is inadequate. One step towards improvement would be to require that every hospital reports, annually to the district level, all major operations by kind and by age and sex of the patient.

Adolescent↗

Cha4p of Saccharomyces cerevisiae activates transcription via serine/threonine response elements.

The CHA1 gene of Saccharomyces cerevisiae encodes the catabolic L-serine (L-threonine) deaminase responsible for the utilization of serine/threonine as nitrogen sources. Previously, we identified two serine/threonine response elements in the CHA1 promoter, UASCHA. We report isolation of a mutation, cha4-1, that impairs serine/threonine induction of CHA1 transcription. The cha4-1 allele causes noninducibility of a CHA1 p-lacZ translational gene fusion, indicating that Cha4p exerts its action through the CHA1 promoter. Molecular and genetic mapping positioned the cha4 locus 17 cM centromere proximal to put1 on chromosome XII. The coding region of CHA4 predicts a 648-amino acid protein with a DNA-binding motif (residues 43-70) belonging to the Cys6 zinc cluster class. Gel retardation employing a recombinant peptide, Cha4p1-174, demonstrated that the peptide in vitro specifically binds UASCHA. Binding is abolished by a G-C to T-A mutation in the middle bases of the two CEZ-elements in UASCHA. The transcriptional activating ability of UASCHA derivatives in vivo correlates with their ability to bind Cha4p1-174 in vitro. We conclude that Cha4p is a positive regulator of CHA1 transcription and that Cha4p alone, or as part of a complex, is binding UASCHA.

Alleles↗

Patient attitudes to major surgery in rural Kenya.

In this Kenyan study of patient perceptions of major surgery and involvement in decisions to operate, the attitudes of 89 female and 23 male patients who had undergone major surgery at a district hospital were studied. Semi-structured interviews were conducted in the wards by a social worker who had no employment or other relationship with the hospital. In 48 cases the decision about the operation was taken jointly by patient and doctor, while in 49 cases the decision was reportedly taken by the doctor alone. In 81 cases (64 female and 17 male) a relative or friend accompanied the patient to hospital. Only 21 patients reported being told details about the operation before the event. One quarter of the patients (housewives and school children) admitted feeling afraid or nervous prior to the operation while two-thirds reported having felt either confident or resigned about it. Ninety-eight patients characterized the care as good while seven felt it was poor.

Adult↗

Effect of eicosanoid inhibition on the development of pulmonary edema after acute lung injury.

In experimental models of acute lung injury, cyclooxygenase inhibition improves oxygenation, presumably by causing a redistribution of blood flow away from edematous lung regions. This effect on perfusion pattern could also reduce alveolar edema formation. On the other hand, pulmonary pressures usually increase after cyclooxygenase inhibition, an effect that could exacerbate edema accumulation. Therefore we tested the following hypothesis: the total accumulation of pulmonary edema in dogs during a 24- to 28-h period of observation after acute lung injury caused by oleic acid will be less in a group of animals treated with meclofenamate (n = 6) or with the thromboxane-receptor blocker ONO-3708 (n = 5) than in a group of animals treated with oleic acid alone (placebo, n = 6). Lung water concentrations (LWC), the regional pattern of pulmonary perfusion, and protein permeability were measured with the nuclear medicine imaging technique of positron emission tomography. After 24-28 h, LWC was significantly less (P < 0.05) in the ONO-3708 group than in the meclofenamate group (a similar trend was seen compared with the placebo group, P = 0.12). After 24-28 h, pulmonary arterial pressures were highest in the meclofenamate group. Regardless of group, the only significant correlation with the change in LWC was with the integral of pulmonary pressures over the 24- to 28-h period. The data suggest that thromboxane inhibition will reduce edema accumulation in acute lung injury but that this effect depends on reducing as much as possible the simultaneous development of pulmonary hypertension from other causes.

Animals↗