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1.
S Afr J Surg ; 60(1): 4-9, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35451262

ABSTRACT

BACKGROUND: The negative appendicectomy rate (NAR) is defined as the proportion of surgically removed appendices that are pathologically normal. The acceptable NAR has been a debated issue. Previously, a higher rate was accepted, whilst newer thinking favours a lower rate. Diagnosing appendicitis is often a clinical challenge and may require crosssectional imaging to assist in the diagnosis. METHODS: A retrospective review was conducted at the Charlotte Maxeke Johannesburg Academic Hospital. Appendix histopathological reports were retrieved for patients older than 18 years over a 10-year period. Reports of ultrasound (US) and/or computed tomography (CT) scans were analysed in the last 18 months. RESULTS: One thousand two hundred and seventeen appendicectomy specimens were included. The overall NAR was 19%. This demonstrated a significant downward trend over the period (p < 0.003). Per gender, the female NAR showed a significant decline (p = 0.002) while the male decline was not significant (p = 0.517). Reproductive-age females were found to have significantly higher NAR as compared to other age groups. The overall perforation rate was 17% which demonstrated a significant increase over the study period (p = 0.012). In the last 18 months, 240 appendicectomies were performed. One hundred and eleven patients underwent imaging (46%), of which 78 underwent ultrasound (70%), 14 CT (13%) and 19 US and CT (17%). CONCLUSION: The overall NAR declined significantly over the period. Females under the age of 45 were found to have significantly higher NARs. Further prospective studies are needed to determine the benefit and feasibility of preoperative CT in resource-limited settings, particularly in reproductive-age females to reduce the NAR.


Subject(s)
Appendicitis , Appendix , Appendectomy/methods , Appendicitis/diagnostic imaging , Appendicitis/surgery , Female , Hospitals , Humans , Male , Retrospective Studies , South Africa/epidemiology
2.
S Afr J Surg ; 58(2): 86-90, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32644312

ABSTRACT

BACKGROUND: The heterogeneity of receptor profiles in breast cancer is well known. The differing receptor profiles of primary breast cancer and nodal metastases have been investigated and found to range between 10-50% depending on the hormone receptor tested. A study comparing the hormone status of primary breast cancers and the synchronous ipsilateral involved sentinel lymph node has not been performed in a South African population. METHOD: This is a prospective study where two specialist radiologists performed the simultaneous core needle biopsies of the primary breast cancer and the clinically positive axillary nodes. All receptor status analysis was conducted by one specialist histopathologist. RESULTS: Of 141 patients who gave written informed consent for this study, 29 were excluded; 112 patients met the inclusion criteria. Anonymised demographics of age, clinical stage, HIV status and metastatic screening were recorded. The simultaneous biopsies and receptor measurements identified 10 patients with discordant receptor status in the positive axillary lymph nodes. In each case, the receptor profile of the axillary lymphatic metastases was more aggressive than that of the primary tumour. The luminal A subtype had a significantly greater risk of discordance than other subtypes (p = 0.02). CONCLUSION: Core needle biopsy and receptor analysis should be considered on the positive axillary nodes in breast cancer patients. Adjuvant treatment should be targeted to the receptor profile of the lymph node metastases.


Subject(s)
Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Lymph Nodes , Axilla/pathology , Axilla/physiology , Biopsy, Needle , Female , Humans , Lymph Node Excision , Lymph Nodes/metabolism , Lymph Nodes/pathology , Lymphatic Metastasis/pathology , Lymphatic Metastasis/physiopathology , Prospective Studies , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism , South Africa
3.
Mol Biol Rep ; 47(3): 2361-2369, 2020 Mar.
Article in English | MEDLINE | ID: mdl-32020429

ABSTRACT

Gallbladder cancer (GBC) has a poor prognosis with a 5-year survival rate suggesting the need for more effective treatment strategies. Studying the cross-talk of several pathways involved in crucial cellular and biological processes such as cell growth, proliferation, migration and apoptosis would prove beneficial in identifying key players of GBC progression and targeting them. This review highlights several pathways known to be dysregulated in GBC onset and progression and describes known and potential targets. Within these pathways, there are proteins involved in the signalling cascade, which may be targeted as potential biomarkers and drug targets. Furthermore, the cross-talk of these pathways is investigated in the context of GBC and the implications thereof. A better understanding of the pathways involved in GBC pathogenesis will aid clinicians in the prognosis, diagnosis and treatment of patients. There are significant clinical implications of GBC pathway-based studies as they permit the understanding of onset and progression of the disease.


Subject(s)
Biomarkers, Tumor , Gallbladder Neoplasms/etiology , Gallbladder Neoplasms/metabolism , Signal Transduction , Animals , Disease Management , Disease Susceptibility , Gallbladder Neoplasms/drug therapy , Gallbladder Neoplasms/pathology , Gene Expression Regulation, Neoplastic , Humans , Molecular Targeted Therapy
4.
S. Afr. j. surg. (Online) ; 57(1): 30-36, 2019. ilus
Article in English | AIM (Africa) | ID: biblio-1271045

ABSTRACT

Background: Present on arrival infection is a common indication for admission of surgical patients initially managed at primary care level. We aimed to describe the demographic and disease profile of patients presenting with infection requiring surgical management, describe determinants of patients' health-seeking behaviour, and identify barriers to care.Methods: A prospective descriptive questionnaire-based study was conducted at Edenvale General Hospital between February 2014 and October 2016. Minors were excluded. Results: Eighty-nine patients participated. Abscesses (26%), diabetic foot (22%), and cellulitis (16%) were the commonest categories of infection necessitating admission. The majority of patients were South African (88%), Black African (82%), males (58%), without medical aid (99%), who were not formally employed (58%), were from poor households (74%), inhabited some form of formal housing (90%), were in charge of decisions regarding personal health (80%), and first sought help at the primary care level (71%). Delay to presentation was noted in 69% of patients, and delay to referral in 46%. Age, race, history of diabetes, and main source of monthly income were significant variables in delayed presentation (p<0.05), and age and level of care on first contact in delayed referral (p<0.05) in the study sample. The most common reason for delay to presentation (84%) and referral (61%) was patients' belief that their problem would resolve spontaneously. Conclusions: Patients' socio-economic status, past medical history, demographics, level of first contact with the health care system, and perceptions of their own health contributed to delays in seeking and receiving care in the study sample. These delays may be addressed by interventions that target the availability, accessibility, acceptability and affordability of health care services


Subject(s)
Patients , South Africa , Surgical Wound Infection/pathology
5.
S Afr J Surg ; 55(2): 18-22, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28876619

ABSTRACT

BACKGROUND: Surgical dogma dictates that serosal injuries should be repaired during laparotomy as these injuries may result in localised areas of bowel ischaemia and may perforate. No study has investigated whether there is a correlation between the extent of serosal injuries and the risk for perforation under normal physiological conditions. We hypothesized that small bowel serosal injuries do not result in early or late perforation at physiological intraluminal pressures regardless of their size. METHOD: An in-vivo rabbit small bowel serosal injury model was developed and two experiments were conducted. The first - to determine whether and at which pressures various lengths and circumferences of serosal injuries in small bowel result in immediate bowel perforation - was performed infusing saline into isolated bowel segments with or without a variety of serosal injuries. In the second study - to determine whether or not serosal injuries result in delayed perforation - a range of injuries was created in rabbits and the effect assessed at re-laparotomy 5 days after the creation of the injury. RESULTS: No perforations were observed at the site of serosal injuries at physiological intraluminal pressures. Perforations occurred at 43.7+ 18.6 cmH2O, 23.3+ 14.4 cmH2O, and 24.4+ 23.9 cmH2O for controls, 4 cm long and 100% circumference serosal injuries respectively (p-value = 0.18 for various lengths and 0.71 for various circumferences). No serosal injuries perforated within 72 or 120 hours after creation. CONCLUSION: Small bowel serosal injuries do not perforate or leak at physiological intraluminal pressures, either at the time of creation or up to 120 hours thereafter.


Subject(s)
Digestive System Surgical Procedures/adverse effects , Intestinal Mucosa/injuries , Intestinal Perforation/etiology , Intestine, Small/injuries , Intraoperative Complications/etiology , Laparotomy/adverse effects , Postoperative Complications/etiology , Animals , Intestinal Mucosa/surgery , Intestinal Perforation/diagnosis , Intestinal Perforation/prevention & control , Intestine, Small/surgery , Intraoperative Complications/diagnosis , Intraoperative Complications/prevention & control , Postoperative Complications/diagnosis , Postoperative Complications/prevention & control , Rabbits
6.
S Afr Med J ; 106(11): 1129-1133, 2016 Nov 02.
Article in English | MEDLINE | ID: mdl-27842637

ABSTRACT

BACKGROUND: Intimate partner violence (IPV) is actual or threatened physical, sexual, psychological, emotional or stalking abuse by an intimate partner. Despite the high prevalence of IPV in South Africa (SA), there is a paucity of data on university students training in fields where they are likely to have to manage the after-effects of such events in their personal capacity in the future. OBJECTIVES: To ascertain the prevalence of IPV in an SA tertiary institution population with a diverse demographic profile. METHODS: Students from the faculty of health sciences and the faculty of humanities, social work department, completed an anonymous questionnaire. Students were made aware of psychological counselling available to them. RESULTS: Responses were obtained from 1 354 of 1 593 students (85.0%) (67.8% female, 45.9% black, 32.7% white, 16.6% Indian, 4.8% coloured). Of the respondents, 53.0% indicated that they were in a relationship. The prevalence of any type of IPV (sexual, physical or emotional abuse) among all respondents was 42.6%. Emotional abuse was reported by 54.9% of respondents, physical abuse by 20.0% and sexual abuse by 8.9%. Thirty-five females (6.5% of respondents who had suffered IPV) indicated that they had been emotionally, physically and sexually abused. Fourteen percent identified themselves as perpetrators of abuse, but only three perpetrators of sexual abuse reported having also been victims of sexual abuse. Most respondents (58.7%) knew where to get help. CONCLUSION: The extent of IPV among the medical and social work students sampled was found to be unacceptably high, both as victims and as perpetrators. As a result of their exposure to IPV, these individuals may have difficulty in managing patients who have been subjected to abuse.

7.
S. Afr. med. j. (Online) ; 106(11): 1129-1133, 2016.
Article in English | AIM (Africa) | ID: biblio-1271080

ABSTRACT

Background. Intimate partner violence (IPV) is actual or threatened physical; sexual; psychological; emotional or stalking abuse by an intimate partner. Despite the high prevalence of IPV in South Africa (SA); there is a paucity of data on university students training in fields where they are likely to have to manage the after-effects of such events in their personal capacity in the future. Objectives. To ascertain the prevalence of IPV in an SA tertiary institution population with a diverse demographic profile.Methods. Students from the faculty of health sciences and the faculty of humanities; social work department; completed an anonymous questionnaire. Students were made aware of psychological counselling available to them.Results. Responses were obtained from 1 354 of 1 593 students (85.0%) (67.8% female; 45.9% black; 32.7% white; 16.6% Indian; 4.8% coloured). Of the respondents; 53.0% indicated that they were in a relationship. The prevalence of any type of IPV (sexual; physical or emotional abuse) among all respondents was 42.6%. Emotional abuse was reported by 54.9% of respondents; physical abuse by 20.0% and sexual abuse by 8.9%. Thirty-five females (6.5% of respondents who had suffered IPV) indicated that they had been emotionally; physically and sexually abused. Fourteen percent identified themselves as perpetrators of abuse; but only three perpetrators of sexual abuse reported having also been victims of sexual abuse. Most respondents (58.7%) knew where to get help.Conclusion. The extent of IPV among the medical and social work students sampled was found to be unacceptably high; both as victims and as perpetrators. As a result of their exposure to IPV; these individuals may have difficulty in managing patients who have been subjected to abuse


Subject(s)
Intimate Partner Violence , Prevalence , Sex Offenses , Students
8.
Acta Physiol (Oxf) ; 214(4): 497-510, 2015 Aug.
Article in English | MEDLINE | ID: mdl-26010805

ABSTRACT

BACKGROUND: The tallest animal on earth, the giraffe (Giraffa camelopardalis) is endowed with a mean arterial blood pressure (MAP) twice that of other mammals. The kidneys reside at heart level and show no sign of hypertension-related damage. We hypothesized that a species-specific evolutionary adaption in the giraffe kidney allows normal for size renal haemodynamics and glomerular filtration rate (GFR) despite a MAP double that of other mammals. METHODS: Fourteen anaesthetized giraffes were instrumented with vascular and bladder catheters to measure glomerular filtration rate (GFR) and effective renal plasma flow (ERPF). Renal interstitial hydrostatic pressure (RIHP) was assessed by inserting a needle into the medullary parenchyma. Doppler ultrasound measurements provided renal artery resistive index (RI). Hormone concentrations as well as biomechanical, structural and histological characteristics of vascular and renal tissues were determined. RESULTS: GFR averaged 342 ± 99 mL min(-1) and ERPF 1252 ± 305 mL min(-1) . RIHP varied between 45 and 140 mmHg. Renal pelvic pressure was 39 ± 2 mmHg and renal venous pressure 32 ± 4 mmHg. A valve-like structure at the junction of the renal and vena cava generated a pressure drop of 12 ± 2 mmHg. RI was 0.27. The renal capsule was durable with a calculated burst pressure of 600 mmHg. Plasma renin and AngII were 2.6 ± 0.5 mIU L(-1) and 9.1 ± 1.5 pg mL(-1) respectively. CONCLUSION: In giraffes, GFR, ERPF and RI appear much lower than expected based on body mass. A strong renal capsule supports a RIHP, which is >10-fold that of other mammals effectively reducing the net filtration pressure and protecting against the high MAP.


Subject(s)
Arterial Pressure/physiology , Giraffes/physiology , Hemodynamics/physiology , Kidney/physiology , Animals , Female , Glomerular Filtration Rate , Kidney/blood supply , Male
10.
Eur J Vasc Endovasc Surg ; 35(3): 301-5, 2008 Mar.
Article in English | MEDLINE | ID: mdl-17988906

ABSTRACT

OBJECTIVES: The aim of this study was to determine whether the collar graft (standard dacron graft with a customized flexible collar attached to the proximal rim) decreased anastomotic bleeding and the overall clamp time. DESIGN: Prospective randomised single center study. METHODS: Between November 2003 and January 2006, 21 patients were treated with a collar graft and 19 with a standard dacron graft. Routine endoaneurysmorraphy was used. Only infra-renal aneurysms between 5.5cm and 6.5cm were included. Aneurysms were diagnosed by CT scans. The total number of bleeding points, the total clamp time, and the number of teflon felt pledgets, was determined. RESULTS: The total number of bleeding points; the number of aortic re-clamps and total clamp time (minutes) per patient were all significantly lower in the collar graft group (1.2 versus 2, p<0.04; 0.5 versus 2.0, p<0.001; 13.6 versus 20.1, p<0.003 respectively). The number of teflon felt pledgets and new sutures used was significantly lower in the collar graft group (p<0.001 and p<0.003 respectively). CONCLUSION: The collar graft resulted in fewer anastomotic bleeding points and a shorter clamp time.


Subject(s)
Aortic Aneurysm, Abdominal/surgery , Blood Vessel Prosthesis , Suture Techniques , Aged , Aged, 80 and over , Anastomosis, Surgical , Blood Vessel Prosthesis Implantation , Constriction , Female , Humans , Male , Middle Aged , Prospective Studies , Prosthesis Design
11.
S. Afr. j. surg. (Online) ; 46(1): 14-16, 2008.
Article in English | AIM (Africa) | ID: biblio-1270997

ABSTRACT

BACKGROUND. A new device made by ThebeMedicare allows efficient local anaesthetic washout of wound areas; by utilising an attachment to an existing drain. The aim of this trial was to explore 'proof of concept' in patients undergoing abdominoplasty procedures. PATIENTS AND METHODS. Thirty-one patients who had undergone abdominoplasty procedures were selected for instillation of a local anaesthetic preparation; ropivacaine (Naropin; AstraZeneca) into the wound site on day 1 and 2 after surgery; followed by early mobilisation. Efficacy of the system; patient comfort and mobilisation were documented. RESULTS. The abdominoplasty patients experienced no discomfort from the procedure and claimed effective relief of pain for an average of 12 hours following instillation of local anaesthetic. All mobilised effectively. The device worked well; with no technical problems. CONCLUSION. The lavage drain extension has proved to be a cost-effective and efficient way of providing postoperative pain control and promoting early mobilisation in this patient group


Subject(s)
Abdominal Injuries/surgery , Abdominal Injuries/therapy , Anesthetics , Plastics , Surgical Procedures, Operative
12.
Int J Tuberc Lung Dis ; 11(5): 528-33, 2007 May.
Article in English | MEDLINE | ID: mdl-17439676

ABSTRACT

SETTING: Deceased miners from South Africa whose cardiorespiratory organs were submitted for autopsy for compensation for occupational lung diseases from 1996 to 2000. OBJECTIVES: To 1) calculate the prevalence of cryptococcal pneumonia in 8421 autopsied miners, a population with a high prevalence of human immunodeficiency virus (HIV) infection; 2) document the association of cryptococcal pneumonia with other pulmonary infection; 3) document the association of cryptococcal pneumonia with a clinical diagnosis of cryptococcal meningitis; and 4) determine the accuracy of the clinical diagnosis of cryptococcal pneumonia. DESIGN: Case series of 589 black miners with histological evidence of cryptococcal pneumonia at autopsy, defined as the presence of cryptococcal organisms in the lung parenchyma, identified by staining of the mucinous capsule. RESULTS: The incidence of cryptococcal pneumonia at autopsy was 7%. Ninety-seven of the 589 cases (16.5%) had a concomitant respiratory infection, most commonly Pneumocystis jirovecii pneumonia (51.5%), followed by mycobacterial infection (42.3%). In life, cryptococcal meningitis was diagnosed in 46.9% and cryptococcal pneumonia in only 2.7%. CONCLUSION: Although tuberculosis remains the most common HIV-associated respiratory disease in Africa, it is important to consider the diagnosis of cryptococcal pneumonia in acquired immune-deficiency syndrome (AIDS) patients, and to bear in mind the possibility of dual pathology.


Subject(s)
Black People/statistics & numerical data , Cryptococcosis/ethnology , Lung Diseases, Fungal/ethnology , Mining , Pneumonia/ethnology , Adult , Aged , Aged, 80 and over , Autopsy , Cryptococcosis/complications , HIV Infections/complications , Humans , Lung Diseases, Fungal/complications , Meningitis, Cryptococcal/complications , Middle Aged , Pneumonia/microbiology , Prevalence , South Africa/epidemiology
13.
Int J Tuberc Lung Dis ; 10(7): 756-60, 2006 Jul.
Article in English | MEDLINE | ID: mdl-16848337

ABSTRACT

SETTING: Deceased miners from South Africa whose cardio-respiratory organs were submitted for autopsy for compensation for occupational lung diseases from 1996 to 2000. OBJECTIVES: 1) To document the incidence of Pneumocystis jirovecii pneumonia (PJP) in autopsied miners; 2) to compare the incidence of PJP over a 5-year period; 3) to record the incidence of concomitant lower respiratory tract infection in a group of PJP-infected deceased miners coming to autopsy from 1996 to 2000; and 4) to describe the accuracy of the in-life diagnosis of PJP in this group. DESIGN: Case series of 328 deceased Black miners with histological evidence of PJP at autopsy. RESULTS: Of the 328 miners with PJP at autopsy, 107 (32.6%) had a concomitant respiratory infection, the most common being cryptococcal pneumonia (46.7%), followed by bacterial pneumonia (34.6%) and pulmonary tuberculosis (13.1%). Overall, Pneumocystis pneumonia was unsuspected prior to death in 89% of cases; however, diagnostic accuracy in life improved from 7% in 1996 to 21% in 2000. CONCLUSION: The high rate of undiagnosed PJP is cause for concern. Clinicians should have a heightened awareness for PJP in Africa, particularly as the disease is treatable at low cost and effective prophylaxis is available.


Subject(s)
Mining , Pneumocystis carinii/isolation & purification , Pneumonia, Pneumocystis/epidemiology , Autopsy , Humans , Pneumonia, Pneumocystis/pathology , South Africa/epidemiology
14.
San Juan, P.R; U.P.R., R.C.M., Escuela Graduada de Salud P£blica; 2006. ix, 118 p gr ficas, tablas.
Thesis | Puerto Rico | ID: por-46018

Subject(s)
Puerto Rico
16.
Cardiovasc J S Afr ; 12(2): 75-80, 2001.
Article in English | MEDLINE | ID: mdl-11447495

ABSTRACT

AIM: We evaluated whether any one variant of genes that encode for substances that could modulate renin-angiotensin-aldosterone (RAA) system activity can account for a substantial proportion of the variability of plasma RAA system profiles in black South African hypertensives (HTs). METHODS: Plasma renin activity (PRA) and aldosterone concentrations (ALD) were determined in 59 black subjects with mild-to-moderate HT off therapy on an ad libitum diet. Patients were genotyped for the angiotensin-converting enzyme (ACE) gene insertion/deletion, angiotensinogen (AGT) gene M235T, A-20C and G-6A, aldosterone synthase (CYP11B2) gene C-344T, G protein beta3-subunit (GNB3) gene C825T, G(s) protein gene C131T, atrial natriuretic peptide (ANP) gene exon 3 stop condon and intron 2, alpha-adducin gene Gly460Trp, and epithelial Na(+) channel (eNa(+) (c)) gene T594M polymorphisms. RESULTS: Risk genotype frequencies for the G(s) (7%), ANP intron 2 (0%), and eNa(+)(c)(7%) variants were too low for each to account for a substantial portion of the variability of plasma RAA profiles in the group studied. Moreover, assuming either recessive or dominant inheritance models, neither ACE, AGT, GNB3, CYP11B2, ANP exon 3 nor alpha-adducin polymorphisms were significantly associated with the variance of PRA, ALD or ALD/PRA. CONCLUSIONS: These results do not support a substantial individual role for the gene candidates studied in contributing to plasma RAA system profiles in black South African HTs. However, a potential small role for some loci may exist, and epistasis or genotype-phenotype interactions as well as alternative inheritance models and variants still need to be evaluated.


Subject(s)
Black People/genetics , Hypertension/genetics , Hypertension/physiopathology , Renin-Angiotensin System/genetics , Renin-Angiotensin System/physiology , Aldosterone/blood , Aldosterone/genetics , Female , Genotype , Humans , Hypertension/blood , Male , Middle Aged , Renin/blood , Renin/genetics , South Africa/ethnology
17.
Arch Intern Med ; 161(7): 965-71, 2001 Apr 09.
Article in English | MEDLINE | ID: mdl-11295959

ABSTRACT

BACKGROUND: Thiazides are recommended to initiate antihypertensive drug treatment in black subjects. OBJECTIVE: To test the efficacy of this recommendation in a South African black cohort. METHODS: Men and women (N = 409), aged 18 to 70 years, with a mean ambulatory daytime diastolic blood pressure between 90 and 114 mm Hg, were randomized to 13 months of open-label treatment starting with the nifedipine gastrointestinal therapeutic system (30 mg/d, n = 233), sustained-release verapamil hydrochloride (240 mg/d, n = 58), hydrochlorothiazide (12.5 mg/d, n = 58), or enalapril maleate (10 mg/d, n = 60). If the target of reducing daytime diastolic blood pressure below 90 mm Hg was not attained, the first-line drugs were titrated up and after 2 months other medications were added to the regimen. RESULTS: While receiving monotherapy (2 months, n = 366), the patients' systolic and diastolic decreases in daytime blood pressure averaged 22/14 mm Hg for nifedipine, 17/11 mm Hg for verapamil, 12/8 mm Hg for hydrochlorothiazide, and 5/3 mm Hg for enalapril. At 2 months the blood pressure of more patients treated with nifedipine was controlled: 133 (63.3%, P

Subject(s)
Angiotensin-Converting Enzyme Inhibitors/classification , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Antihypertensive Agents/classification , Antihypertensive Agents/therapeutic use , Black People , Calcium Channel Blockers/classification , Calcium Channel Blockers/therapeutic use , Enalapril/classification , Enalapril/therapeutic use , Hydrochlorothiazide/classification , Hydrochlorothiazide/therapeutic use , Hypertension/drug therapy , Hypertension/genetics , Nifedipine/classification , Nifedipine/therapeutic use , Sodium Chloride Symporter Inhibitors/classification , Sodium Chloride Symporter Inhibitors/therapeutic use , Vasodilator Agents/classification , Vasodilator Agents/therapeutic use , Verapamil/classification , Verapamil/therapeutic use , Adolescent , Adult , Aged , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Antihypertensive Agents/pharmacology , Blood Pressure/drug effects , Calcium Channel Blockers/pharmacology , Diastole/drug effects , Diuretics , Drug Therapy, Combination , Enalapril/pharmacology , Female , Humans , Hydrochlorothiazide/pharmacology , Hypertension/complications , Hypertension/diagnosis , Hypertrophy, Left Ventricular/etiology , Hypertrophy, Left Ventricular/pathology , Hypertrophy, Left Ventricular/prevention & control , Male , Middle Aged , Nifedipine/pharmacology , Practice Guidelines as Topic , Proportional Hazards Models , Sodium Chloride Symporter Inhibitors/pharmacology , South Africa , Time Factors , Treatment Outcome , Vasodilator Agents/pharmacology , Verapamil/pharmacology
18.
Circulation ; 103(8): 1083-8, 2001 Feb 27.
Article in English | MEDLINE | ID: mdl-11222470

ABSTRACT

BACKGROUND: We previously reported beneficial effects of pentoxifylline, a xanthine-derived agent known to inhibit the production of tumor necrosis factor-alpha, in patients with idiopathic dilated cardiomyopathy treated with diuretics, digoxin, and ACE inhibitors. Since then, 3 large clinical trials showed important clinical benefits of beta-blockers in this population. Therefore, we designed the present study to establish whether in patients with heart failure already receiving treatment with ACE inhibitors and beta-blockers, the addition of pentoxifylline would have an additive beneficial effect. METHODS AND RESULTS: In a single-center, prospective, double-blind, randomized, placebo-controlled study, 39 patients with idiopathic dilated cardiomyopathy were randomized to pentoxifylline 400 mg TID (n=20) or placebo (n=19) if they had a left ventricular ejection fraction <40% after 3 months of therapy with digoxin, ACE inhibitors, and carvedilol. Primary end points were New York Heart Association functional class, exercise tolerance, and left ventricular function. Patients were followed up for 6 months. Five patients died (3 in the placebo group). Patients treated with pentoxifylline had a significant improvement in functional class compared with the placebo group (P:=0.01), with an increment in exercise time from 9.5+/-5 to 12.3+/-6 minutes (P:=0.1). Left ventricular ejection fraction improved from 24+/-9% to 31+/-13%, P:=0.03, in the treatment group. CONCLUSIONS: In patients with idiopathic dilated cardiomyopathy, the addition of pentoxifylline to treatment with digoxin, ACE inhibitors, and carvedilol is associated with a significant improvement in symptoms and left ventricular function.


Subject(s)
Carbazoles/therapeutic use , Cardiomyopathy, Dilated/drug therapy , Digoxin/therapeutic use , Pentoxifylline/therapeutic use , Propanolamines/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Cardiomyopathy, Dilated/immunology , Carvedilol , Double-Blind Method , Drug Therapy, Combination , Exercise Tolerance/drug effects , Female , Humans , Male , Middle Aged , Prospective Studies , Treatment Outcome , Tumor Necrosis Factor-alpha/metabolism , Vasodilator Agents/therapeutic use , Ventricular Function, Left/drug effects , fas Receptor/metabolism
20.
Am J Hypertens ; 13(6 Pt 1): 719-23, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10912759

ABSTRACT

The alpha-adducin gene contributes significantly to hypertension in MHS rats (rats of the Milan hypertensive strain) and in some white and Japanese populations, causing a low renin, sodium, and diuretic-sensitive hypertension. No data are available from populations of African ancestry who have a high prevalence of low renin, sodium, and diuretic-sensitive hypertension. We studied the relationship between the 460-Trp variant of alpha-adducin gene with hypertension using a case-control study design in black South Africans. Surprisingly we found that the overall frequency of the 460-Trp allele was low (approximately 6%), but in spite of such relatively low frequency, the 460-Trp allele was 2.5-fold more frequent in hypertensives than normotensives (P = .028), with an odds ratio for hypertension associated to the state of carrier of at least one 460-Trp allele of 2.68. The finding of such low frequency of the 460-Trp allele in individuals of African ancestry points to the substantial ethnic variability of the genes that have been found to be associated with hypertension. On the other hand, it suggests an association of the 460-Trp allele with hypertension also in subjects of African origin.


Subject(s)
Calmodulin-Binding Proteins/genetics , Cytoskeletal Proteins/genetics , DNA/analysis , Hypertension/genetics , Polymorphism, Genetic , Adult , Alleles , Blood Pressure , DNA Primers/chemistry , Female , Gene Frequency , Genetic Predisposition to Disease , Genotype , Humans , Hypertension/epidemiology , Hypertension/metabolism , Male , Middle Aged , Point Mutation , Polymerase Chain Reaction , Prevalence , Retrospective Studies , South Africa/epidemiology , Tryptophan/genetics
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