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Biomedical subjects

I Segal

Publications and source records attributed to I Segal.

At least 37 records · Page 2Linked to original sources

Iron overload in Sub-Saharan Africa: to what extent is it a public health problem?

Excessive deposition of Fe in the organs and tissues of Sub-Saharan Africans was first described in South Africa in 1929. Fe overload, or siderosis, was initially attributed to infections and to metallic poisoning (Cu, Sn, Zn), and then to malnutrition. In 1953 it was hypothesized that it was due primarily to excessive Fe intake derived from foods and drinks prepared in Fe vessels. Recently, in 1992 it was advanced that a gene distinct from any HLA-linked locus may also play a role. As to sequelae, in early research on series of hospital patients, the condition was linked to scurvy, osteoporosis, diabetes, cirrhosis, and latterly, to hepatocellular cancer and tuberculosis. Accordingly, many have concluded that Fe overload is responsible for considerable morbidity and mortality, that adventitious Fe intake should be reduced, and that phlebotomy be recommended for those severely affected. However, there are numerous limitations in the evidence. There are also problems in interpretation, since levels of Fe in the serum are affected additionally by a variety of factors: infection, inflammation, certain cancers and alcohol intake. These considerations complicate attempts to assess to what extent the associations described denote causation, and whether Fe overload has significant ramifications for ill in the general African population. While the adverse sequelae of overload may be less of significance than many believe, the precise pathogenicity of the phenomenon will remain uncertain until further investigations, including prospective studies, are undertaken.

Adult↗

Is hydrosalpinx fluid cytotoxic?

Accumulation of oviductal fluid in the ampullar lumen as a result of occlusion of the infundibulum is referred to as hydrosalpinx. A low pregnancy rate (10%) after in-vitro fertilization (IVF) in hydrosalpinx patients and a relatively high incidence (50%) of abortions during the first trimester suggested that leakage of this fluid into the uterine cavity may exert a cytotoxic effect on the developing embryo. To examine this possibility, we analysed the composition of the hydrosalpinx fluid and tested its effect on human granulosa cells and embryos. Hydrosalpinx fluids and granulosa cells were collected from IVF patients at ovum pick-up. IVF eggs containing three pronuclei (3PN) were employed for this study. Analysis of hydrosalpinx fluids revealed electrolyte concentrations similar to those in serum with lower amounts of total protein and albumin. No blood cells were detected and bacterial cultures were negative. Granulosa cells incubated in hydrosalpinx fluid-containing medium (diluted 1:1) were not morphologically different and showed a steroidogenic capacity that was higher than that of cells incubated in its absence. Fertilized 3PN eggs incubated in IVF culture medium successfully developed into 6- to 8- and 8- to 16-cell embryos within 48 and 72 h, respectively. This rate of embryonal development was not impaired by hydrosalpinx fluid (at either 50 or 100% concentration). In the absence of a demonstrable detrimental effect we suggest that the low implantation rate in hydrosalpinx IVF patients may not be due to an embryotoxic effect. We further suggest that constant passage of fluid into the uterine cavity in these patients could possibly introduce some mechanical interference that may result in implantation failure.

Animals↗

Rarity of colorectal adenomas in the African black population.

In South African blacks colorectal cancers are uncommon and adenomatous polyps are rare, despite major changes in diet and lifestyle in the large urbanized community of Soweto (population over 3 million). Factors favouring adenomas formation are changes in bowel function. Thus, stool weights, defaecation frequencies, oro-caecal transit times and whole-gut transit times in Sowetans approximate those of western populations. Moreover a measure of westernization of diet has occurred, the salient feature being a greatly reduced fibre intake (14 g daily). Factors thought to inhibit adenoma formation are physiological malabsorption of maize, lactose and fructose. Sucrose activity is significantly lowered compared with whites. With regard to diet, fat consumption is well below that of western societies. There are differences in colon cell proliferation, faecal short chain fatty acids, faecal pH and colonic microflora compared with white groups. Equivocal factors that may be involved in adenoma formation are time trends and genetic background. In the context of the above it is apparent that in South African blacks inhibiting factors outweigh promotive factors in adenoma formation.

Adenoma↗

Pancreatitis in Soweto, South Africa. Focus on alcohol-related disease.

Both acute pancreatitis and chronic pancreatitis now appear to be endemic at Soweto, South Africa, and they carry a substantial toll in terms of morbidity and mortality. Case-control studies identified the same three environmental factors in each disease, namely, heavy alcohol consumption, marked exposure to occupational chemicals and low intake of fruit (a major source of vitamin C). This congruity, and parallel trends on blood biochemical analysis indicating heightened free radical activity coupled with poor antioxidant status, suggest that the two diseases may be part of a pathobiological spectrum that is linked by pancreatic oxidant stress. Further, asymptomatic chronic alcoholics had plasma glutathione concentrations that were midway between the values in non-alcoholic controls and patients with chronic pancreatitis, being significantly different from each. And, finally, apparently healthy Sowetans were actually in a state of oxidant stress that was tied in with their very poor vitamin C status, and lower serum selenium concentrations than in the UK. These data, and evidence that both antioxidants mitigate against alcoholic toxicity in experimental studies, may offer scope for disease prophylaxis in this unprivileged community.

Acute Disease↗

Effects of transition on bowel diseases in sub-Saharan Africans.

In populations in sub-Saharan Africa, transitional changes in patterns of morbidity and mortality are taking place, with decreases in the diseases of poverty and infection, but rises in chronic diseases of prosperity, associated, however, with greater longevity. Remarkably, bowel diseases - appendicitis, diverticular disease, colon cancer - while nearly absent in rural areas, have very low incidences in urban dwellers, despite rises in risk factors, including a decreasing intake of fibre-containing foods. Currently, there is no explanation for the phenomenon, which stands in marked contrast to the considerable rises which have occurred in dental caries, obesity in women and diabetes.

Africa South of the Sahara↗

Acute pancreatitis in Sowetan Africans. A disease with high mortality and morbidity.

CONCLUSION: In African blacks, acute pancreatitis requiring hospital admission is a severe disease associated with a high mortality and significant long-term morbidity in surviving patients. BACKGROUND: It has been suggested that acute pancreatitis has a benign course in Africans in contrast to Western populations. The aim of the present study was to ascertain the incidence of acute pancreatitis at Baragwanath Hospital for a 1-yr period and to test the validity of the above hypothesis. METHODS: One hundred thirty-six patients with acute pancreatitis were retrospectively assessed. Fifty patients were available for a prospective follow-up examination and underwent sonographic and biochemical investigations. Acute pancreatitis was diagnosed if the patient presented with the typical clinical picture and a raised serum amylase level > 800 U/L. RESULTS: The study consisted of 108 male and 28 female patients. Alcohol was identified as the predominant etiologic factor in 83.1%, biliary disease in 7.4%, and idiopathic causes in 6.6%. Substantial morbidity was encountered in 32.3% and was caused mainly by pancreatic complications, metabolic derangements, alcohol-related symptoms, and respiratory impairment. A portion (10.3%) of the patients developed further pancreatic pathology, such as pseudocysts, necroses, or an abscess. The overall mortality rate was 8.1%. Patients who died had a higher mean serum amylase, and most deaths occurred within 2 d of admission. Prospective follow-up after an average of 9.3 mo revealed serious morbidity in two-thirds of patients. Fifty-two percent suffered from severe abdominal pain, 36% complained of weight loss, and 18% were shown to have a sonographically abnormal pancreas. Fecal chymotrypsin levels indicated exocrine pancreatic impairment in 30.6%.

Acute Disease↗

Expression of Ad4-BP/cytochrome P450 side chain cleavage enzyme and induction of cell death in long-term cultures of human granulosa cells.

Freshly isolated granulosa cells obtained from women undergoing in-vitro fertilization (IVF) become refractory to further gonadotrophin stimulation in culture due to their previous hormonal treatment. However, when precultured for 7 days in gonadotrophin-free medium they regain their response to both human chorionic gonadotrophin (HCG) and follicle stimulating hormone (FSH) with a 10-fold and 5-fold increase in progesterone production respectively, within an additional 7 days of culture. Forskolin, a direct activator of adenylate cyclase, increased progesterone levels 12-fold compared with non-stimulated cultures. Oestradiol formation was also significantly elevated (P < 0.005) following 48 h stimulation with luteinizing hormone (LH), FSH or forskolin. Intracellular cAMP levels rose 1.5-fold, 10-fold and 15-fold after 1 h of FSH, HCG or forskolin treatment. Expression of both cytochrome P450 side chain cleavage enzyme (SCC) and the steroidogenic transcription factor SF1/Ad4BP could be demonstrated by Western blotting. However, elevation of P450 SCC alone was evident following FSH and HCG stimulation. In the presence of serum, the ultrastructure of these cultured cells displayed numerous lipid droplets and well-developed mitochondria, characteristic of highly steroidogenic cells. The proportion of apoptotic nuclei in these cultures was < 30%. Removal of the serum increased apoptotic incidence to 40%, whereas addition of FSH prevented cell death significantly (P < 0.01). HCG and forskolin increased apoptosis to approximately 50%, while treatment with 8Br-cAMP led to 80% cell death. Our data suggest that, after prolonged culture, human granulosa cells can regain cAMP and steroidogenic response to gonadotrophin stimulation. Moreover, our experiments indicate that apoptosis and steroidogenesis can coexist in the same cell population while the interrelationship between these processes can be determined by the intracellular levels of cAMP.

Apoptosis↗

Iron, ascorbate and copper status of Sowetan Blacks with calcific chronic pancreatitis.

Vitamin C can be used to overcome oxidative stress and ease pain in chronic pancreatitis. But its use is deprecated in conditions of tissue iron overload, because its bioactive form, ascorbate, can accelerate free-radical reactions that are driven by transition metals. We measured iron, ascorbate and copper in Sowetan Blacks (RSA) with chronic pancreatitis, obtaining serum/plasma from 14 consecutive patients and 15 controls. Compared with data from corresponding groups in Manchester, African samples had less ascorbate (p < 0.0001), but more caeruloplasmin (p < 0.0001). African and British controls had comparable iron and iron-binding capacity. Plasma from African patients had less ascorbate than that from African controls (p < 0.005) and in six samples, ferritin exceeded 300 micrograms/l (677 pmol/l). Low-molecular-mass iron or copper, capable of participating in free radical reactions, was not detected. British patients, had similar caeruloplasmin levels to African patients but higher ascorbate levels. There is no evidence of iron overload in our African samples. Outwardly healthy controls from Soweto have elevated levels of caeruloplasmin, possibly to compensate for dietary deficiency of ascorbate. Persistent oxidative stress is a unifying feature of chronic pancreatitis, but its degree is higher in African than British patients. Supplements of vitamin C should be safe in Blacks of southern Africa.

Adult↗

Efficacy and tolerability of pantoprazole 40 mg versus 80 mg in patients with reflux oesophagitis.

BACKGROUND: Pantoprazole is a substituted benzimidazole which is a potent inhibitor of gastric acid secretion by its action upon H+, K+-ATPase. METHODS: Pantoprazole 40 mg and 80 mg were compared in a randomized double-blind study in 192 out-patients with stage II or III (Savary-Miller classification) reflux oesophagitis. Patients received either pantoprazole 40 mg (n = 97) or pantoprazole 80 mg (n = 95), once daily before breakfast for 4 weeks. Treatment was extended for a further 4 weeks if the oesophagitis had not healed. RESULTS: After 4 weeks complete healing of the reflux oesophagitis was seen in 78% of protocol-correct patients given pantoprazole 40 mg daily (n = 86), and in 72% in the 80 mg (n = 87) group. The cumulative healing rates after 8 weeks were 95 and 94%, respectively (P > 0.05, Cochran-Mantel-Haenszel), and time until healing of oesophagitis comparable in both groups. Differences between doses were also not significant in an intention-to-treat analysis. Both dosing schedules were well tolerated and the patients experienced remarkable symptom relief. No adverse event or changes in laboratory values of clinical significance could definitely be ascribed to the trial medication. CONCLUSION: The 40 mg pantoprazole dosage is comparable to 80 mg in reflux oesophagitis, both in efficacy and tolerability.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Perforation of the gastro-intestinal tract by a foreign body. A case report.

Most ingested foreign bodies pass through the gastro-intestinal tract without giving rise to complications. If they become lodged in a narrow segment of the gastro-intestinal tract, perforation may occur. The resulting morbidity depends on the further route of the penetrating object and whether septic sequelae ensue. This article describes an unusual case of foreign body perforation with a protracted clinical course. It emphasises that there are no insurmountable barriers in the pathway of foreign bodies.

Adult↗