Background: Phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome (PHTS) is caused by germ line mutations in the PTEN gene. Symptoms include cancer pre- disposition, immune deviations, and lipomas/lipomatosis. No causal standard therapy is available. We describe a therapeutic attempt with the mammalian target of rapamycin (mTOR) inhibitor sirolimus for a PHTS patient suffering from thymus hyperplasia and lipomatosis. We furthermore assessed the in vitro effects of sirolimus and other inhibitors on lipoma cells of the patient. Methods: The patient underwent clinical and blood examinations and whole-body magnetic resonance imaging to assess tumor sizes. Lipoma cells of the patient were incubated with inhibitors of the phosphoinositide3-kinase (PI3K)/AKT/ mTOR signaling pathway to analyze the effects on proliferation, adipocyte differentiation, and survival in vitro. Results: Sirolimus treatment improved somatic growth and reduced thymus volume. These effects diminished over the treatment period of 19 mo. Sirolimus decreased lipoma cell proliferation and adipocyte differentiation in vitro but did not cause apoptosis. PI3K and AKT inhibitors induced apoptosis significantly. Conclusion: Sirolimus treatment led to an improvement of the patient’s clinical status and a transient reduction of the thymus. Our in vitro findings point to PI3K and AKT inhibitors as potential treatment options for patients with severe forms of PHTS.

Combination antiviral drug therapy improves the survival rates of patients chronically infected with hepatitis B virus by controlling viral replication and enhancing immune responses. Some of these drugs have side effects that make them unsuitable for long-term administration. To address the trade-off between the positive and negative effects of the combination therapy, we investigated an optimal control problem for a delay differential equation model of immune responses to hepatitis virus B infection. Our optimal control problem investigates the interplay between virological and immunomodulatory effects of therapy, the control of viremia and the administration of the minimal dosage over a short period of time. Our numerical results show that the high drug levels that induce immune modulation rather than suppression of virological factors are essential for the clearance of hepatitis B virus.

With the increase in recent years in the prevalence of malaria, and in drug resistance of Plasmodium falciparum, there has been much interest in natural plant products for new antimalarials with novel modes of action against Plasmodium. Artemisinin or Qinghaosu is one such antimalarial isolated from a Chinese herb, Anemisia annua (Asteraceae) and it is currently undergoing phase I and II clinical trials. The Southern African species, Artemisia afra (African wormwood, wildeals, lengana) is commonly used by local traditional healers for symptoms of malaria, in particular fever. Thus it seemed appropriate to investigate this species for antimalarial activity. Crude petroleum ether soxhlet extracts of Anemisia afra had demonstrated antimalarial activity against Plasmodium falciparum, FCR-3, cultured in vitro. The IC₅₀ values ranged from 5-13μg/ml. The extract from leaves and flowers was then screened against D10 (chloroquine-sensitive) and FAC8 (chloroquineresistant) P. falciparum, in vitro, with IC₅₀ values of 1.03μg/ml and l.5μg/ml respectively. This extract was fractionated by column chromatography using silica gel-60 and the fractions obtained were screened for antimalarial activity. The most active fraction had an IC₅₀ of 0.5μg/ml against D10 and FAC8. Using TLC and HPLC-UV analysis with pure artemisinin as a standard, no artemisinin could be detected in this fraction. This result was confirmed by thermospray LC-MS analyses. Purification of this fraction yielded ultimately a single pure compound; a clear colourless oil identified by MS and NMR analyses as hydroxydavanone. The compound was screened against a variety of P. falciparum strains with varying degrees of sensitivity and resistance to both chloroquine and mefloquine. Their sensitivity against artemisinin was also established. IC₅₀ values obtained for the isolated pure compound against P. falciparum ranged from 0.87 to 2.54μg/ml. The IC₅₀ values obtained for general cytotoxicity of the crude extract and isolated pure compound against RAT-I fibroblast cells were 34.78 ± 8.23 and 6.29 ± 0.95 μg/ml (n=4) respectively. Thus the crude extract and isolated pure compound exhibited a greater antimalarial than cytotoxic effect. Hence, there are implications for A. afra to be used as a phytomedicine for the treatment of malaria. In vivo studies are recommended for hydroxydavanone in order to fully assess its potential for clinical use.

No description available.

The aims of this research were to establish the drug use patterns of an elderly population in the southern suburbs of the Cape peninsula and to determine the extent of knowledge with respect to their medicines. In addition, the relationship between drug use patterns and medication knowledge and the socioeconomic status of the elderly, the health care services utilised by them and the amount of information conveyed on medicine container labels was assessed. Two hundred and sixty non-institutionalised Caucasian elderly over the age of 65 years and living in old age residences were interviewed. The interviews were structured with 4 major components: 1. a questionnaire designed to collect participant particulars; 2. an interview schedule to collect information on drug use patterns and to assess participant knowledge of medicines used (Knowledge score). 3. a container label assessment schedule (Label score); 4. a cognitive function test to identify and exclude severely cognitively impaired elderly from the study population. Analysis of the data showed the majority of the participants were English-speaking women of social class 1 or 2. Approximately one fifth of all participants were male. The State-run health care services were utilised by 38% of the participants whilst 73% retained their own general practitioner. A total of 843 medicines were used with an average of 3.2 medicines per capita. Ninety-five percent of all participants took prescribed medicines, with diuretics, non-narcotic analgesics/antipyretics, and tranquillisers the 3 most frequently prescribed classes. A smaller percentage - 41.5% - of participants used self-prescribed medicines, of which non-narcotic analgesics, homeopathic and herbal medicines, and vitamins were taken most frequently. When assessed against container label directions approximitely one third of participants were non-compliant with their dosage regimens. The majority of all medicines had been used on a continuous basis for 1 to 10 years. Average knowledge score was 58%. The majority of participants had very little knowledge about interactions, side effects, and maximum permissible dose for their medicines. Just over one fifth of all participants could correctly state both the name and the strength of their medicine. Average knowledge score was found to decline with increasing age, but no relationships were found to exist with the other patient characteristics. Similarly, no relationship was found to exist between knowledge score and label score. Participants utilising the public health care services tended to have a lower knowledge score than those receiving treatment from the private sector. Twenty-six percent of all labels did not have specific usage directions. The private sector suppliers were most frequently culpable of omitting instructions. Label legibility also proved to be a problem for the elderly participants. The drug use patterns identified in this study are similar to those of the American and British elderly and should be of value in compiling a health care plan for the South African elderly, although further research involving other race and cultural groups is needed.

The current recommendations by the American Heart Association for health promotion are that all persons should partake in regular physical activity in order to reduce the risk of cardiovascular disease. Regular physical exercise reduces blood pressure and is an important component of the management of hypertension. It is therefore important that patients with hypertension participate in habitual physical exercise. Many hypertensive patients who exercise will require anti-hypertensive medication. However, some antihypertensive agents cause fatigue during exercise. In order for patients to gain the full benefits of an active lifestyle, it is important that the prescribed antihypertensive agent does not prevent them performing and enjoying sustained exercise. It has been well documented that β-blockers cause premature fatigue during physical exercise. The effects on exercise performance of other first line antihypertensive medications, such as calcium channel antagonists have not been extensively investigated. In particular, the effects of these agents on prolonged submaximal exercise endurance have not been well studied. The object of this thesis was to compare the effects of isradipine, a dihydropyridine calcium channel antagonist, to those of atenolol, a β₁-selective antagonist, on maximal and submaximal exercise performance and on short duration high-intensity exercise in physically active hypertensive patients. The study design was a crossover trial where drug treatments were double blinded and randomised. Physically active volunteers with mild to moderate hypertension were recruited. 11 subjects performed i) progressive exercise to exhaustion for determination of maximal oxygen consumption (VO₂max), maximal work load and cardiorespiratory responses to maximal exercise, ii) prolonged submaximal exercise for determination of exercise endurance, cardiorespiratory responses and ratings of perceived exertion (APE), and iii) short duration, high intensity exercise consisting of a 30 second maximal exercise test (Wingate test) to determine skeletal muscle power output, following 4 weeks ingestion of isradipine (2.5mg bd), atenolol (50mg bd) or placebo. Diastolic blood pressure at rest was reduced by both atenolol and isradipine, but was lowered to a greater extent by atenolol (83.3 vs 89.0 vs 96.1 mmHg, atenolol vs isradipine vs placebo, p<.0005). Systolic blood pressure at rest tended to be similarly reduced by both agents, but was significantly reduced during maximal and submaximal exercise by atenolol only (p<.001, atenolol vs isradipine, placebo). Heart rate at rest and during maximal and submaximal exercise was decreased by atenolol only (p<.0005, atenolol vs isradipine, placebo). Maximal exercise performance was reduced after atenolol ingestion compared to placebo but not after isradipine ingestion. Peak workload achieved during the maximal exercise test was decreased after atenolol but unchanged after isradipine ingestion (214 vs 243 W, atenolol vs placebo, p<.01). Similarly, VO₂max was reduced after atenolol compared to placebo but was unchanged after isradipine ingestion (33.6 vs 36.4, 33.6 vs 36.1 mlO₂/kg/min, atenolol vs placebo, atenolol vs isradipine, p<.05). Both atenolol and isradipine ingestion reduced submaximal endurance time compared to placebo (27.8 vs 46.4, 34.4 vs 46.4 min, atenolol vs placebo, isradipine vs placebo, p<.005), and increased rating of perceived exertion (APE) after 30 min of submaximal exercise (p<.05). Submaximal oxygen consumption (VO₂), ventilation, respiratory exchange ratio (REA) and blood lactate, glucose and free fatty acid concentrations were not altered after the ingestion of either agent. Neither agent influenced peak skeletal muscle power, total work done, or rate of fatigue during the Wingate test compared to placebo. The results of these studies indicate that impaired performance and increased RPE during submaximal exercise after ingestion of either atenolol or isradipine is not due to alterations of ventilation, VO₂, RER, or blood lactate, glucose and free fatty acid concentrations during prolonged submaximal exercise. Similarly, reduced submaximal exercise performance after atenolol or isradipine ingestion is not due to factors which would also limit the ability of skeletal muscle to perform short duration, high intensity exercise before a bout of prolonged exercise. This study demonstrates that prolonged submaximal exercise testing can reveal an impairment in exercise performance after ingestion of antihypertensive medication which is not evident during maximal exercise testing. This finding is important as prolonged submaximal exercise is the form of exercise which most hypertensive patients actually perform. Further research is required on the effects of anti-hypertensive medications on submaximal exercise performance before firm recommendations can be made regarding medications most suitable for the physically active hypertensive patient. The results of these and other studies indicate that it is not yet possible to make claims that the calcium channel antagonist agents are without effect on physical exercise performance in physically active hypertensive patients.

År 2018 drabbades cirka 24 800 personer i Sverige av hjärtinfarkt, och cirka 5800 av dem avled. Sekundärprevention kan minska risken för återinsjuknande i hjärtinfarkt. Medicinsk sekundärprevention innebär att med hjälp av läkemedel reducera riskfaktorer såsom högt LDL-kolesterol eller hypertoni. Inom sekundärpreventionen har sjuksköterskor en viktig roll i att utbilda och handleda patienter och närstående på ett personcentrerat sätt. Syftet var att undersöka patienters upplevelser av information om läkemedel som ordinerats efter hjärtinfarkt, såväl gällande informationens innehåll som hur den förmedlats. Studiens ansats var induktiv kvalitativ med en deskriptiv design, och baserades på sju intervjuer utifrån en semistrukturerad intervjuguide. Informanterna hade drabbats av hjärtinfarkt och ordinerats sekundärpreventiva läkemedel. Informanterna hade varit på återbesök hos sjuksköterska på sekundärpreventiv öppenvårdsmottagning (kranskärlsmottagning). Intervjuerna analyserades enligt en kvalitativ innehållsanalys på manifest nivå. I resultatet framträdde meningsenheter som sorterades in i tre kategorier; Information under vårdförloppet, Individanpassad information och Struktur vid informationsgivning. Flertalet informanter upplevde bristande läkemedelsinformation under tiden i slutenvården, vilket ledde till osäkerhet kring behandlingen tills återbesök skett. Informanter som erhållit information upplevde en känsla av trygghet och att känna sig införstådda med behandlingen. Majoriteten önskade läkemedelsinformation, som skulle vara tydlig, individanpassad, och påbörjas i slutenvården. Önskemål uttrycktes om att informationen skulle inkludera skälen till vald behandling, effekter och bieffekter, samt förmedlas såväl skriftligt som muntligt och repeteras vid återbesök. Studien visar att personer som drabbats av hjärtinfarkt önskar, men ofta upplever att de saknar, information och dialog kring sekundärpreventiv läkemedelsbehandling. Informationen bör förmedlas och utföras på ett personcentrerat sätt samt vara samstämmig och tydlig, och vid behov fördjupas vid återbesök. / In 2018, circa 24 800 individuals in Sweden suffered a myocardial infarction, circa 5800 fatally so. Secondary prevention can reduce the risk of recurring myocardial infarction. Medical secondary prevention entails reducing risk factors like high LDL-cholesterol or hypertension by means of medication. In secondary prevention, nurses play an important part in educating and counselling patients and relations in a patient-centered manner. The aim was to examine patients' experiences of information about medication prescribed after myocardial infarction, both regarding information content and how it had been conveyed. The study approach was inductive qualitative with a descriptive design and based on seven interviews following a semi-structured interview guide. All informants had suffered myocardial infarction and had been prescribed secondary preventive medication. All informants had met with nurses at hospital-based outpatient clinics (Coronary Artery Clinic). The interviews were analyzed according to a qualitative content analysis on a manifest level. In the results, meaning units appeared and were sorted into three categories; Information during course of medical care, Personalized information and Structure during information. Most informants experienced deficiencies in medication information during inpatient care, generating uncertainty surrounding treatment until revisits had occurred. Informants who had received information experienced a sense of security and understanding of the drug treatment. Most informants wanted information about their drugs, and that the information should be clear, personalized, and start during inpatient care. Requests were expressed that information should include reasons for selected treatment, effects and side effects, be conveyed both in writing and orally, and repeated during revisits. The study shows that people who have suffered myocardial infarction want, but often lack, information and dialogue concerning secondary prevention medication. The information should be conveyed and carried out in a patient-centered manner and be consistent and clear. The information should be repeated and, if needed, deepened during revisits.

No description available.

No description available.

No description available.