Biomedical subjects

A Hjalmarson

Publications and source records attributed to A Hjalmarson.

At least 91 records · Page 5Linked to original sources

PubMed1995

Smoking habits in consecutive patients with acute myocardial infarction: prognosis in relation to other risk indicators and to whether or not they quit smoking.

In all patients hospitalized in one single hospital due to acute myocardial infarction (AMI) during a period of 21 months, we describe the prognosis in relation to smoking habits and other risk indicators with death. Of 862 AMI patients, 37% reported smoking at the onset of AMI. Of the patients who smoked at the onset of AMI and who survived the first year, 53% reported having quit smoking. Patients who had quit smoking reported fewer symptoms of chest pain (p < 0.01), headache (p < 0.01) and dizziness (p < 0.001) as compared with patients who continued to smoke after one year. Of the patients who had quit smoking, the mortality during the subsequent 4 years was 17% as compared with 31% for patients who continued to smoke (p < 0.05). However, patients who quit smoking less frequently had a previous history of myocardial infarction and congestive heart failure. When correcting for such dissimilarities, quitting smoking did not remain significantly associated with prognosis.

Aged↗

PubMed1995

Dilated cardiomyopathy defines serum autoantibodies against G-protein-coupled cardiovascular receptors.

In order further to identify the prevalence of anti-receptor autoantibodies in the sera of patients with dilated cardiomyopathy (DCM), we attempted to detect autoantibodies against a series of G-protein-coupled cardiovascular receptors in a well-defined population of DCM patients from Japan. Peptides corresponding to the sequences of the second extracellular loops of the human beta 1 and beta 2 adrenoceptors, alpha 1 adrenoceptors, M2 muscarinic acetylcholine receptors and angiotensin II-1 (AT1) receptors were used as antigens in an enzyme immunoassay to screen the sera from patients with DCM (n = 28). Nine sera from patients with DCM (32%) and 2 sera from healthy subjects (9%) recognized the beta 1 adrenoceptor peptide. Ten sera from patients (36%) and 3 sera from healthy subjects (13%) recognized the M2 receptor peptide. Thirty-six per cent of the patients with autoantibody against the beta 1 adrenoceptor peptide. Ten sera from patients (36%) and 3 sera from healthy subjects (13%) recognized the M2 receptor peptide. Thirty-six per cent of the patients with autoantibody against the beta 1 adrenoceptor had autoantibody against the M2 receptor. However, no significantly high frequencies of autoantibodies against the beta 2 adrenoceptor, alpha 1 adrenoceptor and AT1 receptor were found in DCM patients. Our results demonstrate that a subgroup of patients with DCM have a specific spectrum of autoantibodies which are specifically directed against the second extracellular loops of the beta 1 adrenoceptors and M2 muscarinic receptors rather than other cardiovascular receptors.

Adult↗

PubMed1994

Functional autoimmune epitope on alpha 1-adrenergic receptors in patients with malignant hypertension.

Because of the growing evidence that hypertensive disease is accompanied by immunological dysfunction, we have investigated autoimmunity in patients with malignant hypertension. Peptides corresponding to the sequence of the second extracellular loops of the human alpha 1-adrenergic receptor and the M2-muscarinic receptor were used as antigens in an ELISA. Serum from 4 (12%) of 33 healthy controls, 3 (20%) of 15 patients with malignant essential hypertension, and 7 (64%) of 11 with secondary hypertension showed positive responses in the ELISA for the alpha 1-adrenergic receptor peptide. Positive responses were significantly more common among the patients with secondary hypertension than in the other two groups (p < 0.01). By contrast, no autoantibodies against the M2-muscarinic receptor peptide were detected in either hypertensive group. Autoantibodies against the alpha 1-adrenergic receptor, affinity-purified from patients with positive responses, specifically recognised bands with molecular masses of 68, 40, and 37 kDa on immunoblotted membrane proteins of rat ventricles. The patients' autoantibodies caused a decrease in tritiated prazosin binding sites and an increase in heart beating frequency of neonatal cultured rat cardiomyocytes; antibodies purified from the controls had no effect. Circulating autoantibodies against the alpha 1-adrenergic receptor are present in a subgroup of patients with malignant hypertension. These autoantibodies have pharmacological activity in vitro, which suggests that they may be involved in the pathogenesis of malignant hypertension.

Adult↗

PubMed1994

Effect of nicotine nasal spray on smoking cessation. A randomized, placebo-controlled, double-blind study.

BACKGROUND: Nicotine replacement therapies have proved to be of value in smoking cessation. However, not all smokers can use the nicotine gum or nicotine patch owing to side effects. In addition, the absorption of nicotine from these formulas is slow compared with smoking. A nicotine nasal spray delivers nicotine more rapidly. The objective of this study was to evaluate the efficacy and safety of the nicotine nasal spray for smoking cessation. METHODS: Subjects were recruited through advertisements in newspapers and among patients referred to the smoking cessation clinic at Sahlgren's Hospital, Göteborg, Sweden. Two hundred forty-eight smokers were treated in small groups with eight counseling sessions over 6 weeks. At their first group session, subjects were randomized to a group receiving nicotine spray (n = 125), 0.5 mg of nicotine per single spray, or to a placebo group (n = 123). The procedure was double blind. Success rates were measured up to 12 months. The nonsmoking status was verified by expired carbon monoxide less than 10 ppm. RESULTS: Significantly more subjects in the nicotine group were continuously abstinent for 12 months than in the placebo group (27% vs 15%; odds ratio, 2.16; 95% confidence interval, 1.15 to 4.12). Ten of the 34 abstinent subjects in the nicotine group used the spray for 1 year. Mild or moderate side effects were rather frequent for both sprays, but they were significantly more for the nicotine spray. Subjects with high scores (> 7) on Fagerström's tolerance questionnaire had a significantly lower success rate with placebo than with the nicotine spray. For subjects with low scores, there was no difference. CONCLUSION: Nicotine nasal spray in combination with group treatment is an effective aid to smoking cessation.

Adult↗

PubMed1994

The appropriateness of performing coronary angiography and coronary artery revascularization in a Swedish population.

OBJECTIVE: To evaluate the appropriateness of performing coronary angiography and revascularization in a Swedish population. DESIGN: Prospective population study of questionnaires and medical records. SETTING: All the hospitals in southwestern Sweden that perform coronary angiography and revascularization. PATIENTS: Random sample of 831 patients (with chronic stable angina) on the waiting list for coronary angiography or revascularization in southwestern Sweden in September 1990. MAIN OUTCOME MEASURE: Percentage of patients referred for coronary angiography or revascularization for appropriate, uncertain, or inappropriate indications. RESULTS: Of the patients referred for angiography, 89% were classified as appropriate, 9% as uncertain, and 2% as inappropriate. The percentages are similar for patients referred for coronary artery bypass graft surgery and for angioplasty (91% and 86%, respectively, classified as appropriate). The majority of patients had chest pain rated as Canadian Cardiovascular Society classes II through IV (93%), despite maximum anti-ischemic therapy in 90% of these patients. CONCLUSIONS: Few patients were referred for coronary angiography or revascularization for inappropriate or uncertain indications. The percentage of these patients who are from southwestern Sweden is similar to the percentage recently reported from New York State.

Adult↗

PubMed1994

Properties of G-protein modulated receptor-adenylyl cyclase system in myocardium of spontaneously hypertensive rats treated with adriamycin.

Properties of the receptor--G protein--adenylyl cyclase system were studied in spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar-Kyoto rats (WKY) treated with adriamycin (ADR, 1 mg/kg per week) for 12 weeks. An identical dosing schedule caused a significantly greater decline in body weight gain and a marked elevation of plasma norepinephrine level in SHR than in WKY. A significant increase in the messenger RNA encoding Gi-alpha 2 was found in SHR+ADR group. The activity of the adenylyl cyclase stimulated by guanyliminodiphosphate [Gpp(NH)p] was decreased by 49% in SHR and 73% in SHR+ADR. However, stimulated activities of adenylyl cyclase by both sodium fluoride and forskolin remained unchanged. Functional level of stimulatory G-protein (Gs) as measured by reconstitution assay in sarcolemmal membrane was unaltered among different groups. Furthermore, the density of beta-adrenoceptor was significantly decreased without change of its affinity. Muscarinic receptors exhibited a three-site affinity distribution in SHR+ADR whereas other groups displayed only two-site affinity distribution. These results suggest that SHR exhibited a depressed myocardial adenylyl cyclase signaling system which may not be due to the functional uncoupling of beta-adrenoceptors from Gs but to the increased inhibitory G-protein (Gi) activity as demonstrated by the increased mRNA of Gi-alpha 2, increased inhibition of Gpp(NH)p-mediated adenylyl cyclase and the super high affinity for carbachol of the muscarinic receptors. Decreased beta-adrenoceptor density and functional alteration of Gi might be regarded as the predisposing factors for the increased susceptibility of myocardium of SHR to ADR.

Adenylyl Cyclases↗

PubMed1994

Prognosis during one year of follow-up after acute myocardial infarction with emphasis on morbidity.

Previous descriptions of the prognosis after acute myocardial infarction (AMI) have mainly included patients admitted to coronary care units, often with an upper age limit. This study describes the prognosis, with emphasis on morbidity, during 1 year in 921 patients admitted to one single hospital with AMI regardless of age and regardless of whether or not they were admitted to the coronary care unit. During the first year, 29% of the patients died and 16% developed a reinfarction. Fifty-four percent required rehospitalization for various reasons, mainly for AMI, chest pain of other origins, and congestive heart failure. After 1 year, 52% of the surviving patients had symptoms of angina pectoris. Among patients younger than 65 years, only 37% were back to work full time after 1 year. Of patients alive after 1 year, 25% fulfilled the following criteria: no reinfarction, no rehospitalization, and no angina pectoris. Of patients aged less than 65 years at follow-up, 12% fulfilled the same criteria and were back to work full time after 1 year. In this unselected, consecutive series of patients with AMI, mortality and morbidity were high during the first year. Only a small percentage of patients were free of events or symptoms of angina pectoris.

Adolescent↗

PubMed1994

Impact of clinical trials on the use of beta blockers after acute myocardial infarction and its relation to other risk indicators for death and 1-year mortality rate.

Based on selected patient populations, several randomized trials have shown beta blockers to decrease mortality after acute myocardial infarction (AMI). The purpose of this study was to describe the use of beta blockers in various subsets of patients admitted to Sahlgren's Hospital between February 15, 1986, and November 9, 1987, with AMI, and the relation of AMI to other risk indicators for death and to a 1-year mortality rate. Beta blockers, mainly metoprolol, were prescribed for 66% of all survivors at discharge. They were more frequently prescribed for younger patients and for those with a previous history of AMI and hypertension, but less frequently for those with a history of congestive heart failure and diabetes mellitus. Patients for whom beta blockers were not prescribed haa a 1-year mortality of 27% versus 11% for the rest (p < 0.001). Independent predictors of 1-year mortality after discharge were age (p < 0.001), history of hypertension (p < 0.001), prescription of beta blockers at discharge (p < 0.001), congestive heart failure during hospitalization (p < 0.001), and a history of AMI (p < 0.01). P values were corrected for baseline differences. Beta blockers were not prescribed at discharge for one-third of survivors after AMI. This group had a very high mortality during the first year. When simultaneously considering various risk indicators for death, prescription of beta blockers at discharge was associated with an increased rate of survival.

Adrenergic beta-Antagonists↗

PubMed1994

Autoantibodies against cardiac G-protein-coupled receptors define different populations with cardiomyopathies but not with hypertension.

It was previously shown that the second extracellular loop of cardiovascular G-protein-coupled receptors is an antigenic target for pharmacologically active autoantibodies in patients with idiopathic dilated cardiomyopathy. To extend these observations to cover patients with the same disease from different geographical origins or to patients with other cardiac diseases, peptides corresponding to the sequences of the second extracellular loops of the human M2 muscarinic receptors and beta adrenoceptors were used as antigens in an enzyme immunoassay. Sera from patients from Sweden and Japan with idiopathic dilated cardiomyopathy (DCM, n = 32), hypertrophic cardiomyopathy (HCM, n = 23), malignant essential hypertension (MEH, n = 11), malignant secondary hypertension (MSH, n = 10), and sera from healthy blood donors (HBD, n = 49) were tested. Sera from patients with DCM recognized the muscarinic receptor peptide in 38% of cases and the beta 1 adrenoceptor peptide in 31% of cases. In 50% of the positive patients, autoantibodies against both peptides coexisted as shown by competition experiments using both peptides as inhibitors. In HCM patients, there was a lower frequency of autoantibodies but with a higher but not significant predominance against the M2 peptide. No autoantibodies were detected in sera from patients with MEH or MSH. Autoantibodies against the M2 muscarinic receptors, affinity-purified from positive patients, displayed pharmacological activity as demonstrated by changes in the affinity and number of radioligand binding sites. In contrast, antibodies purified from positive HBD had no effect. These results confirm that autoantibodies displaying pharmacological activity against G-protein-coupled cardiovascular receptors are mainly restricted to patients with idiopathic dilated cardiomyopathy and that different autoantibody populations are responsible for the recognition of the different receptors.

Adult↗

PubMed1994

Ten-year mortality rate among patients in whom acute myocardial infarction was not confirmed in relation to clinical history and observations during hospital stay: experiences from the Göteborg Metoprolol Trial.

BACKGROUND: The majority of patients hospitalized due to suspected acute myocardial infarction (AMI) will eventually not develop infarction. Information about the long-term prognosis in this patient population is limited. AIM: To describe the mortality during 10 years of follow-up in patients hospitalized due to an initially strong suspicion of AMI, but in whom the diagnosis of AMI could not be confirmed. PATIENTS: All patients participating in an early intervention trial with metoprolol in suspected AMI, but in whom the diagnosis was not confirmed. Patients were included during 1976-1981. RESULTS: In all 1395 patients were included in the study, of whom 586 did not fulfil the criteria for confirmed AMI. The overall mortality during 10 years of follow-up in this population was 26%. In a multivariate analysis considering age, sex, history of cardiovascular diseases, initial heart rate and various complications during the hospital stay, including congestive heart failure, severe ventricular arrhythmias, tachycardia, hypotension, high degree AV-block and severe chest pain, the following appeared as independent predictors of death: previous infarction (P < 0.001), age (P < 0.001), history of diabetes mellitus (P < 0.001) history of smoking (P < 0.05), history of hypertension (P < 0.05), male sex (P < 0.05), and the initial heart rate (P < 0.05). CONCLUSION: Among patients in whom AMI was not confirmed the major risk indicators for death during 10 years of follow-up were: a history of cardiovascular diseases and smoking, age, male sex and high heart rate on admission to hospital.

Double-Blind Method↗

PubMed1994

Epitope analysis of T- and B-cell response against the human beta 1-adrenoceptor.

Several reports have recently raised the possible significance of the presence of autoantibodies against the beta 1-adrenoceptor in patients with idiopathic dilated cardiomyopathy. An investigation was thus initiated to study the immune response against this receptor at the T-cell and the B-cell level. Using membranes of E coli transfected with the human beta 1-adrenoceptor gene as immunogen, T-helper cells of the immunized mice were stimulated with synthetic peptides derived from the receptor and predicted to be immunogenic to assess the T-cell immunodominant regions of the receptor. Three peptides derived from the second transmembrane region, from the second extracellular loop and from the C-terminal domain were shown to be stimulatory. Synthetic peptides, derived from two domains of the receptor which could be potential targets for autoantibodies, yielded an antibody response after immunization with the free peptides. The peptide derived from the N-terminal region yielded antibodies which recognized the receptor in immunoblot and by immunoprecipitation but they had no functional effect on the receptor. The peptide derived from the second extracellular loop yielded antibodies which recognized the receptor in immunoblot and by immunoprecipitation of the free receptor and which had a pharmacological effect on the receptor. The second extracellular loop thus contains T- and B-cell epitopes which could be involved in the autoimmune process.

Animals↗

PubMed1994

Improved exercise hemodynamic status in dilated cardiomyopathy after beta-adrenergic blockade treatment.

OBJECTIVES: This study was performed to investigate exercise hemodynamic status in a double-blind, placebo-controlled trial and was a substudy in the Metoprolol in Dilated Cardiomyopathy Trial. BACKGROUND: Previous open studies have shown beneficial effects on exercise hemodynamic status after beta-adrenergic blocking agent therapy in patients with congestive heart failure. METHODS: The study included 41 patients with idiopathic dilated cardiomyopathy with ejection fraction < 0.40 (metoprolol, 20 patients; placebo, 21 patients) whose hemodynamic status was investigated at rest and during supine submaximal exercise, at baseline and after 6 and 12 months of treatment. Myocardial metabolism was evaluated in a subset of 19 patients. RESULTS: Metoprolol-treated patients responded favorably, as expressed by improved exercise cardiac index ([mean +/- SD] placebo 4.8 +/- 1.6 to 4.7 +/- 1.8 liters/min per m2, metoprolol 4.3 +/- 1.1 to 5.4 +/- 1.9 liters/min per m2, p = 0.0001) and stroke work index (placebo 44 +/- 20 to 41 +/- 27 g.m/m2, metoprolol 35 +/- 16 to 58 +/- 28 g.m/m2, p < 0.0001). Exercise systolic arterial pressure increased (placebo 161 +/- 25 to 151 +/- 23 mm Hg, metoprolol 155 +/- 29 to 165 +/- 37 mm Hg, p = 0.0003) as well as exercise oxygen consumption index (placebo 463 +/- 194 to 474 +/- 232 ml/min per m2, metoprolol 406 +/- 272 to 507 +/- 298 ml/min per m2, p = 0.045). There was a significant increase in exercise duration in the metoprolol group (63 +/- 38 s) compared with the placebo group (-24 +/- 42 s) (p = 0.01). Net myocardial lactate extraction increased in the metoprolol group, suggesting less myocardial ischemia (placebo 17 +/- 22 to 9.5 +/- 6.4 mmol/min, metoprolol -32 +/- 100 to 42 +/- 45 mmol/min, p = 0.03). Peripheral levels of norepinephrine tended to decrease at rest and during exercise, whereas myocardial net spillover was unchanged. CONCLUSIONS: Metoprolol improved hemodynamic status in patients with dilated cardiomyopathy at rest and had a more pronounced effect during exercise. These positive effects were achieved along with improved or stable myocardial metabolic data.

Analysis of Variance↗

PubMed1994

Reoxygenation-induced cell damage of isolated neonatal rat ventricular myocytes can be reduced by chain-breaking antioxidants.

To study the role of chain-breaking antioxidants on reperfusion injury in the ischemic heart, cultured ventricular heart cells (myocytes) were subjected to hypoxia and reoxygenation. The myocytes were prepared from neonatal rats and cultured in F10 medium that was supplemented with serum. As a marker for cell damage, lactate dehydrogenase was analyzed in the medium. Cells subjected to hypoxia for 5 h showed a 1.9 fold increase in lactate dehydrogenase (LD) leakage, while cells subjected to 1 h hypoxia followed by 4 h reoxygenation showed a 5-fold increase in LD intake. Alpha-tocopherol, beta-carotene, nordihydroguairetic acid (NDGA), butylated hydroxyltoluene (BHT), and ICI211965 were added to the cell medium every 24 h for 6 d prior to reoxygenation. All compounds protected against reoxygenation-induced cell damage. In the presence of the 5-lipoxygenase inhibitor ICI211965, protection against LD leakage was found only at high concentrations, which corresponded to the antioxidative effect of ICI211965, and not to inhibition of 5-lipoxygenase. We conclude that cultured ventricular myocytes can be used to evaluate the protective effect of antioxidants on reoxygenation-induced cell damage, and that chain-breaking antioxidants protected well against reoxygenation-induced cell damage.

Animals↗

PubMed1994

Does a history of hypertension influence the prognosis among diabetics with acute chest pain?

The purpose of this study was to relate the 1-year risk of death and development of acute myocardial infarction among diabetics with acute chest pain to whether they had a history of hypertension or not. All patients with a history of diabetes mellitus who, during 21 months, were admitted to the Emergency Room in Sahlgrenska Hospital, Göteborg, due to chest pain or other symptoms suggestive of acute myocardial infarction, were included. Among the 427 patients with a history of diabetes mellitus 44% also had a history of hypertension. These hypertensives had a 1-year mortality rate of 22% as compared with 26% in diabetics without such a history (p > 0.2). The corresponding values for development of myocardial infarction during 1 year were 33 and 30%, respectively (p > 0.2). We did not find a history of hypertension to adversely affect the prognosis among diabetics with acute chest pain.

Acute Disease↗

PubMed1994

Emergency room prediction of mortality and severe complications in patients with suspected acute myocardial infarction.

This study aims at describing the in-hospital prognosis of patients admitted with suspected acute myocardial infarction, focusing on the possibility of emergency room prediction of the risk for death and severe complications. From 7157 consecutive patients with chest pain or other symptoms suggestive of acute myocardial infarction in the emergency room, 4690 were hospitalized. Of these, 246 (5%) died in hospital, with a mortality rate among the 921 patients who developed myocardial infarction of 14%, and among those without infarction of 3%. From the clinical history, examination and electrocardiogram in the emergency room, independent predictors of death and death or any severe complication were determined by logistic regression analysis. These included age, initial degree of suspicion of infarction, electrocardiographic pattern, history of diabetes mellitus, history of congestive heart failure and on admission arrhythmias, loss of consciousness, acute congestive heart failure, or unspecific symptoms. From these analyses the probability of death or death or any severe complication can be calculated. Thus, 18% of patients hospitalized due to suspected acute myocardial infarction suffered a severe complication or died in hospital. From a statistical model it is possible to predict the in-hospital prognosis of every such patient.

Adolescent↗

PubMed1994

Causes of death in patients presenting to hospital with symptoms suggestive of acute myocardial infarction: a one-year follow-up study with autopsy results.

BACKGROUND: About 20% of patients admitted to a medical emergency room have chest pain or other symptoms raising suspicion of acute myocardial infarction. AIM: To describe the place and mode of death in such patients during 1 year of follow-up. PATIENTS: All patients (n = 5362) admitted to a single hospital during 21 months because of such symptoms. RESULTS: In all, 565 patients (11%) died. Death rate was directly related to the initial degree of suspicion of acute myocardial infarction. Of these patients, 196 (35%) died during initial hospitalization and only 89 (16%) died outside the hospital. The overall autopsy rate was 53%. Of the deaths that occurred during initial hospitalization, the majority were judged as cardiac, most being due to acute myocardial infarction, particularly if the patients died in the coronary care unit. Among patients who died after discharge from hospital, non-cardiac factors contributed more substantially to death, particularly in patients who died during rehospitalization. The cause of death was not established in a high proportion of patients who died outside hospital. CONCLUSION: The results suggest that, among patients admitted to the emergency room because of suspected acute myocardial infarction, causes of death other than a documented cardiac event become increasingly important when the interval between admittance to the emergency room and death increases.

Aged↗

PubMed1994

Characterization of anti-peptide antibodies directed against an extracellular immunogenic epitope on the human alpha 1-adrenergic receptor.

A synthetic peptide corresponding to amino acids 192-218 of the second extracellular loop of the human alpha 1A-adrenergic receptor was used to raise antibodies in rabbits. Affinity-purified antibodies specifically recognized main bands with a molecular weight of about 68, 40 and 37 kD on the electrotransferred membrane proteins of rat ventricle membranes. The incubation of these antibodies with rat myocardial membranes resulted in a decrease in the number of binding sites for the specific radiolabelled alpha 1-antagonist prazosin. These antibodies were also able to mimic the effects of agonist stimulation as demonstrated by a positive chronotropic effect on cultured cardiomyocytes. These results constitute the first immunochemical evidence of the presence of both the A and B subtypes of the alpha 1-adrenergic receptor in the heart. They also confirm that the second extracellular loop of the alpha 1-adrenergic receptors is an immunologically and functionally important domain.

Amino Acid Sequence↗

PubMed1994

The epidemiology of a coronary waiting list. A description of all of the patients.

OBJECTIVES: To describe the characteristics and the severity of symptoms amongst patients on the waiting list for possible coronary revascularization. DESIGN: All the patients were sent a postal questionnaire for symptom evaluation. SETTING: All hospitals in western Sweden. SUBJECTS: All patients in western Sweden on the waiting list in September 1990, who had been referred for coronary angiography or revascularization (n = 904) and a sex- and age-matched reference group (n = 809). RESULTS: More than half of the patients had daily attacks of chest pain, whereas 16% reported less than one attack per week or no pain at all. However, other symptoms such as dyspnoea, tachycardia and nervous reactions were also common and 25% of all patients used sedatives. A long waiting time for a given procedure was not associated with more pain but with more nervous symptoms such as restlessness and insomnia (P < 0.0001) and greater use of sedatives and cigarettes (P < 0.05). CONCLUSIONS: We conclude that a long waiting time for possible coronary revascularization is associated with more nervous symptoms but not with more pain.

Adult↗