South Africa's health. Ethnic differences in health are seen in other countries.
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Biomedical subjects
Publications and source records attributed to I Segal.
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Biochemical assessments of micronutrient antioxidant status were done in 14 consecutive black patients with calcific chronic pancreatitis and 15 controls at Soweto, near Johannesburg in southern Africa. The patients showed subnormal levels of vitamin C in plasma; selenium, beta-carotene and alpha-tocopherol in serum; and inorganic sulphate (as an index of long-term sulphur amino acid intake) in urine (P < 0.001 for each): furthermore, among the patients ascorbate constituted a lower fraction of vitamin C (P < 0.002), indicating heightened oxidation of the bioactive form. By comparing the results in Sowetan controls with reference ranges from Manchester, UK, the markedly lower vitamin C and, hence, ascorbate levels in the Sowetans was underlined (P < 0.001) and their selenium levels were also lower (P < 0.001), but beta-carotene, alpha-tocopherol and inorganic sulphate levels were comparable. The very low bioavailability of ascorbate among Sowetan controls is reminiscent of our previous finding in outwardly healthy people at Madras in southern India: in both these areas chronic pancreatitis is currently endemic, has a propensity to pancreatic calculi and runs a virulent course towards premature death from diabetes, malnutrition or pancreatic cancer. Considering that low ascorbate levels are a feature in patients with chronic pancreatitis who develop pancreatic calculi at Manchester and that antioxidant supplements ameliorate painful symptoms, we suggest that poor antioxidant intake may predispose underprivileged tropical communities to the disease. If so, there could be an opportunity for prophylaxis through a daily tablet containing vitamin C, perhaps along with selenium at Soweto and beta-carotene at Madras.
We report the results of a further study to test our hypothesis that toxic metabolite stress is germane to heightened free radical activity and hence to the genesis of chronic pancreatitis. Consecutive black South African patients with clinically quiescent chronic pancreatitis were studied, provided that the diagnosis had been made within the previous 2 years and that they did not have overt liver disease. All of them had been advised to stop drinking alcohol. Analysis of an early morning sample of urine showed a lower ratio of inorganic to ester sulphate (P < 0.001) and a higher ratio of D-glucaric acid to creatinine (P < 0.02) in the group of 14 patients than in 15 local controls, while plasma analysis showed a lower concentration of glutathione (GSH) in the patients (P < 0.001). This evidence of increased utilisation of phase II conjugative pathways of xenobiotic disposal was in keeping with on-going toxic metabolite stress from heightened phase I oxidative metabolism in the group of patients. Parallel studies of theophylline pharmacokinetics showed heightened drug clearance compatible with induced cytochrome P-4501A2 in two patients, whereas increased activity of gamma-glutamyl transferase in serum suggested persisting induction of P-4502E1, as by ethanol, in several others. The contemporaneous increases in free radical activity and utilisation of xenobiotic disposal pathways in Sowetan Africans with chronic pancreatitis is in line with the toxic metabolite concept of disease pathogenesis.
The steady increase in chronic pancreatitis among black Africans at Soweto, RSA, in the past 40 years necessitates an objective and non-invasive test to detect the disease at an early stage. Given the biphasic nature of the disease--secretory hyperfunction with periodic active inflammatory episodes followed by steady exocrine impairment--we assessed three potential aids. Urinary BT-PABA/PAS excretion index (PEI), serum pancreatic isoamylase (PIA) and faecal chymotrypsin activity (FCA) were measured in the following groups: 16 outwardly healthy hospital workers, 16 consecutive patients with calcifying chronic pancreatitis and 19 with abdominal pain ascribed to other conditions (disease controls). (1) Healthy controls had lower PEI than those at Manchester, UK, or Madras, India, from subclinical acinar loss--as shown by lower PABA recovery whereas intestinal absorptive capacity was maintained, as shown by recovery of PAS. (2) Using the popular cut-off for PEI (0.75) only 9 of 14 patients with chronic pancreatitis were identified (sensitivity 64%, 2 tests unsatisfactory), while a value of less than 0.54, the mean -2 S.D. in local controls, yielded sensitivity of 50%. (3) If PEI of less than 0.75 or PIA outside the reference range was taken to indicate the disease, 5 of 9 disease controls would have been classed as chronic pancreatitis (among those with both tests satisfactory): retrospective ultrasound scans did not identify these. (4) Although FCA was less than the preselected cut-off, 5 units/g, in every patient with chronic pancreatitis (100% sensitivity) its poor predictive value was indicated by low specificity: subnormal levels in 4 of 14 and 6 of 16 healthy controls or disease controls, respectively, most of whom had near-normal values of PEI, PIA or both. (5) Collectively, these results suggest a high frequency of subclinical chronic pancreatitis at Soweto, but also that the combination of tests required to identify it may prove impractical--whether in field surveys or hospital practice.
UNLABELLED: Diminished levels for fecal short chain fatty acids (SCFAs) have been linked to occurrence of ulcerative colitis, colorectal polyps, and colon cancer, diseases that are rare or uncommon in African populations. PURPOSE: The aim of this study was to determine fecal SCFA concentrations and fecal pH values in groups of black South Africans (African) and white South Africans (white) subjects. METHODS: Twenty healthy Africans (all women; mean age, 35 years) and 17 healthy whites (7 women; 10 men; mean age, 32 years) were tested. RESULTS: Mean total concentrations of SCFAs in the two groups were 142.1 (+/- 53.9) and 69.2 (+/- 26.0) mmol/kg wet feces, respectively (P = 0.0001). Mean values for Africans were significantly higher in all subfractions except butyrate. There was a significant inverse correlation between fecal pH value and total fecal SCFA concentration (r = 0.704; P = 0.001). CONCLUSION: High concentrations of fecal SCFAs in the African group could protect against chronic bowel diseases.
Most studies on colorectal carcinogenesis suggest a field defect, preceding overt development of cancer. The low incidence of adenomatous polyps in the African population, however, suggests that there may be an alternative route for cancer development. The aim of the study was to discover if the difference in incidence of colorectal cancer in Africans compared with the white population is reflected in a different pattern of cell proliferation. Histological normal mucosa from 30 patients (15 white South African (W), 15 South African Africans (A)) with confirmed colon cancer were examined. Proliferating cells were detected using the Ki-67 antigen. In addition, cell proliferation data were obtained, from 30 age matched controls (15 Africans, 15 white South Africans), without colorectal disease. The African controls were significantly younger (mean (SD) (A: 42 (20), W: 66 (13), p < 0.05)) than the white controls. The second control group had a significantly higher mean (SD) total labelling index (W: 11 (3), A: 6 (4), p < 0.05). In addition the proliferative pattern of the white group without evidence of colorectal cancer showed a comparatively large amount of dividing cells in compartment 2, compared with African controls (mean (SD) (W: 21 (8), A: 9 (8), p < 0.05)). Mucosa from Africans with cancer showed a proliferative pattern with the same increased total labelling index (A: 15 (5), W: 16 (6), p = NS, phase II proliferative lesion) and an even more pronounced upward expansion (phase I proliferative lesion) compared with white cancer patients. This suggests that the mechanism of colorectal carcinogenesis is similar in Africans and the white population. The lack of clinical evidence of the adenoma-carcinoma sequence, and the incidence of cancer at a comparatively young age in Africans may be explained by the fact that colorectal cancer in this ethnic group behaves more aggressively and that adenomatous polyps are rapidly converted into overt cancer before detection.
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Four indices of free radical activity were measured in fasting serum/plasma samples from 14 consecutive blacks with clinically quiescent chronic pancreatitis and 15 outwardly healthy hospital personnel at Soweto, the township near Johannesburg in South Africa. The patients had higher serum levels than did controls of lipid isomerisation (P < 0.002) and peroxidation (P < 0.05) markers, with lower plasma levels of glutathione (P < 0.0001) and bioactive fraction of vitamin C (P < 0.002). Lipid peroxide and non-bioavailable vitamin C concentrations in Sowetan patients were significantly higher than in their counterparts from Manchester, UK (P < 0.0001, P < 0.0005, respectively). These differences mirrored those in controls in that outwardly healthy Sowetans had much higher serum lipid peroxide levels than Manchester controls (P < 0.001) and much lower plasma concentration of vitamin C (P < 0.001) and hence of the bioavailable fraction ascorbate (P < 0.0002). Heightened free radical activity is thus a common denominator in chronic pancreatitis irrespective of geography, or putative aetiological factors whether alcoholism or idiopathic, since that ratio was approximately 95:5 at Johannesburg and 50:50 at Manchester. The further finding of subclinical oxidative stress in Sowetan controls and the endemic nature of chronic pancreatitis in that area supports the hypothesis that oxidative stress may be involved in its pathogenesis.
Distal splenorenal shunt (DSRS) is a once-only form of treatment. It is suitable for many black South Africans with non-cirrhotic variceal bleeding who cannot attend repeated follow-up sclerotherapy sessions. However, persistent hyperbilirubinaemia and encephalopathy may occur following DSRS in schistosomiasis. Forty-one consecutive patients with DSRS have been treated over a 7-year period. The causes of portal hypertension were schistosomiasis (32), portal vein thrombosis (8) and diffuse nodular hyperplasia (1). Operative mortality was 6%. Encephalopathy was observed in 1 patient. Galactose elimination capacity (GEC) and technetium-diethylenetriamine penta-acetic acid hepatic perfusion index (HPI) were used to assess liver function and hepatic perfusion pre- and postoperatively, respectively, in schistosomiasis. GEC was 348 +/- 37 (M +/- SD) before, compared with 343 +/- 67 postoperatively (P = 0.78). HPI showed long-term preservation of hepatopetal portal venous flow following DSRS. Morbidity and mortality were observed only in patients with schistosomiasis associated with hepatitis B chronic active hepatitis. DSRS is ideal treatment in selected patients with non-cirrhotic variceal bleeding.
Bowel diseases (appendicitis, diverticulitis and colon cancer) in South African whites and populations of prosperous Western countries are similar. Among rural South African blacks with a traditional lifestyle these diseases are very uncommon or almost unknown. A study was undertaken to measure stool weight and faecal pH in South African urban blacks and whites. There was no difference in stool weight, but the faecal pH was significantly higher in whites (P = 0.002).
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Cancer incidence rates and patterns in three African populations in the Gambia, Mali and South Africa, have been compared with corresponding data on the Black population in Connecticut, USA. In the African populations, total rates for cancer are much lower than that of US Blacks, even allowing for under-reporting. Chief cancers are those of the oesophagus, liver and cervix. In Mali, stomach cancer is very common. As to trends, among South African Blacks, a population in transition, rates are rising, albeit slowly, of cancers of prosperity--prostate, lung, breast and colon-rectum. Salient questions are: can the number of cancers of underprivilege be lessened, and can cancers linked with rising socioeconomic states be restrained? Discussions of common risk factors, including diet, reproduction, smoking and drinking practices, indicate that for Africans as a whole, continuing poverty will prevent major changes in cancer pattern and rises in occurrence of the disease. However, should prosperity increase for Africans in big cities, rates are ultimately likely to attain those prevailing in the US Black population. Significant avoiding action seems almost impossible.
Prior to the advent of somatostatin conservative therapy for pancreatic fistulas, treatment included intravenous nutritional therapy with nothing per mouth and therapeutic agents to diminish pancreatic secretions. None of these modalities were uniformly successful. A prospective study to evaluate the efficacy of a long-acting somatostatin analogue (Sandostatin) was carried out. 18 patients-10 with pancreatic ascites and 8 with external pancreatic fistulas-were treated. The ascites resolved in 9 of 10 patients in a mean period of 22 days (+/- 3 days). The external fistulas were all high output fistulas and resolved in 7 of 8 patients. Mean period for closure was 23 days. There were no side effects associated with Sandostatin. Sandostatin has made a major impact on the conservative treatment of pancreatic ascites and is an important adjunct to the management of external pancreatic fistulas. It is emphasised however that surgery may be required for the underlying pancreatic disease. In this regard close surveillance of these patients is necessary.
Surgery has been the cornerstone of treatment for pancreatic pseudocysts. This was based on studies that delineated the natural history and showed high morbidity and mortality rates if surgery was not performed. Recently this view has been challenged. Observations using new imaging techniques indicate that pseudocysts may resolve over time and surgery may not be necessary. An additional advantage of modern imaging and technical expertise is that pseudocysts can be successfully drained percutaneously. Also, the ingenuity of interventional endoscopists has led to another form of therapy--endoscopic cystoenterostomy, which is now part of the therapeutic armamentarium. With regard to drug therapy, octreotide acetate has emerged as an important adjunct to the treatment of fistulas complicating percutaneous catheter drainage. Moreover, it has been used as a primary treatment of pseudocysts. The nonsurgical types of treatment provide alternatives to surgery in some patients with pancreatic pseudocysts. However, these modalities should be viewed as complementary rather than conflicting alternatives and should be used selectively on the basis of clinical and radiological observations. This review discusses the major methods of nonsurgical therapy.
Conflicting data have been reported on the use of total enteral nutrition (TEN) in pancreatic disease. TEN was used in 17 patients who were candidates for nutritional support with total parenteral nutrition (TPN). There were 7 patients with internal pancreatic fistulas, 2 with protracted traumatic pancreatitis, 7 with severe alcoholic pancreatitis and 1 with a traumatic pancreatic pseudocyst. The mean inhospital stay was 30 days. Precision LR was administered orally or nasally for a mean of 16 days. Five patients with internal pancreatic fistulas were healed during the initial admission on TEN, 1 required surgery and 1 defaulted from hospital treatment. Nine patients with pancreatitis improved on TEN with resolution of pseudocysts or phlegmons (8 patients); 1 patient required a cystojejunostomy. Three patients who defaulted on TEN and consumed a ward diet had relapse of the pancreatitis, which responded rapidly to re-institution of hyperalimentation. There was no mortality in this group of patients. This preliminary report suggests that TEN may be considered as an alternative to TPN for nutritional support in pancreatic disease.
Fermentation of dietary fiber and resistant starch is one of the major physiological functions of the human large intestine. The major substrate for fermentation is probably starch. This study assessed the effect of bananas--a carbohydrate with a highly resistant starch content--on breath hydrogen and methane production in methane and nonmethane-producing subjects. The results showed that both groups produced significant quantities of hydrogen after a banana meal, compared with a sucrose control test meal, measured as area under the curve (28 +/- 5.6 vs. 8.1 +/- 1.4 10(3) pm/min, p = 0.008 in methane producers and 39 +/- 15.2 vs. 10.5 +/- 4.1 10(3) ppm/min, p = 0.01 in methane nonproducers). The rise in breath hydrogen started a half hour after the banana meal and peaked at 3 1/2 h in methane nonproducers, whereas in methane producers, the rise began after 2 h and peaked at 5 h. Methane production was not significantly stimulated by the test meals. This study shows that bananas stimulate fermentation mainly through the production of hydrogen, with minimal effect on methane production. The possible mechanisms for this process are discussed.