Immunological and C-peptide studies of patients with diabetes in northern Ethiopia: existence of an unusual subgroup possibly related to malnutrition.

AIMS/HYPOTHESIS: Surveys in northern Ethiopia have demonstrated that apparent type 1 diabetes occurs more frequently than elsewhere in Africa and, indeed, in other parts of the world. We therefore investigated in detail a cohort of diabetic patients from this region to clarify the nature of this type of diabetes. METHODS: All patients attending the diabetic clinic at Mekelle Hospital in the Tigray region of northern Ethiopia were investigated over a 6 week period. Clinical, demographic and anthropometric data were collected, as well as measurements of HbA(1c), fasting lipid profile, fasting serum C-peptide and serum markers of beta cell autoimmunity, i.e. islet antigen-2 and GAD antibodies (GADA). RESULTS: Of 105 patients seen, 69 (66%) were on insulin treatment and had been from or close to diagnosis. Their median age and diabetes duration were 30 and 5 years, respectively, with a male excess of 2:1. Median BMI was 20.6 kg/m². Despite these clinical characteristics suggestive of type 1 diabetes, only 42 of 69 (61%) patients were C-peptide-negative and 35% GADA-positive. Overall, 38 (36%) of the total group (n = 105) had immunological or C-peptide characteristics inconsistent with typical type 1 or type 2 diabetes. The clinical characteristics, local prevalence of undernutrition, and GADA and C-peptide heterogeneity suggest a malnutrition-related form of diabetes. CONCLUSIONS/INTERPRETATION: Not all patients in northern Ethiopia with apparent type 1 diabetes appear to have the form of disease seen in Europids; their disease may, in fact, be related to malnutrition.

Ghrelin restores 'lean-type' hunger and energy expenditure profiles in morbidly obese subjects but has no effect on postgastrectomy subjects.

OBJECTIVE: To examine the effects of ghrelin on appetite and energy expenditure in lean, obese and postgastrectomy subjects. DESIGN: A randomized, double-blind, placebo-controlled study. PATIENTS: Nine lean subjects (mean body mass index (BMI) 23.5+/-3 kg/m(2)) and nine morbidly obese subjects (mean BMI 51.4+/-10 kg/m(2)) and eight postgastrectomy subjects (mean BMI 22.4+/-1.0 kg/m(2)). INTERVENTIONS: Subjects were infused with either intravenous ghrelin (5 pmol kg(-1) min(-1)) or saline over 270 min. They were given a fixed energy breakfast followed by a free buffet lunch towards the end of the infusion. MAIN OUTCOME MEASURES: Visual analogue scales were used to record hunger and energy expenditure was measured by indirect calorimetry. RESULTS: Ghrelin increased energy intake at the buffet lunch in lean subjects (a 41% increase, P<0.01) and obese subjects (35% increase, P=0.04) but not in postgastrectomy subjects. Lean subjects showed a characteristic preprandial rise and postprandial fall in hunger scores, which was exaggerated by ghrelin infusion. Obese subjects showed little variation in hunger scores, but a 'lean-type' pattern was restored when given exogenous ghrelin. Ghrelin had no effect on resting metabolic rate but did increase respiratory quotient (RQ) in obese subjects. Ghrelin also increased RQ variability over time in all three groups (ANOVA, P<0.001). CONCLUSIONS: Hunger scores are abnormal in the obese, perhaps because of impaired ghrelin secretion. The effect of ghrelin in restoring normal hunger profiles in the obese suggests causality, confirming an important role in eating behaviour. Ghrelin also increases RQ in obese humans and increased RQ variability in all groups. This suggests that ghrelin regulates substrate utilization and may promote metabolic flexibility.

Increased 1-Aminocyclopropane-1-Carboxylic Acid Oxidase Activity in Shoots of Flooded Tomato Plants Raises Ethylene Production to Physiologically Active Levels.

Soil flooding increased 1-aminocyclopropane-1-carboxylic (ACC) acid oxidase activity in petioles of wild-type tomato (Lycopersicon esculentum L.) plants within 6 to 12 h in association with faster rates of ethylene production. Petioles of flooded plants transformed with an antisense construct to one isoform of an ACC oxidase gene (ACO1) produced less ethylene and had lower ACC oxidase activity than those of the wild type. Flooding promoted epinastic curvature but did so less strongly in plants transformed with the antisense construct than in the wild type. Exogenous ethylene, supplied to well-drained plants, also promoted epinastic curvature, but transformed and wild-type plants responded similarly. Flooding increased the specific delivery (flux) of ACC to the shoots (picomoles per second per square meter of leaf) in xylem sap flowing from the roots. The amounts were similar in both transformed and wild-type plants. These observations demonstrate that changes in ACC oxidase activity in shoot tissue resulting from either soil flooding or introducing ACC oxidase antisense constructs can influence rates of ethylene production to a physiologically significant extent. They also implicate systemic root to shoot signals in regulating the activity of ACC oxidase in the shoot.

Food fails to suppress ghrelin levels in obese humans.

UNLABELLED: Ghrelin is the first circulating hormone shown to stimulate feeding in humans following systemic administration. Food consumption decreases circulating ghrelin concentrations in lean subjects but the effects of feeding have not been studied in the obese. METHODS: We investigated the effects of a test meal on plasma ghrelin and leptin concentrations in 13 lean and 10 obese subjects. RESULTS: Fasting ghrelin was significantly higher in lean than in obese subjects (857 pmol/1 vs. 325 pmol/l, (p = 0.002) and fell by 39.5% thirty minutes after eating in the lean group before returning rapidly towards baseline values: (p = 0.003). There was no change in circulating ghrelin in the obese group. Circulating leptin concentration also fell acutely 15 minutes following food intake in lean but not obese subjects (p < 0.0001). CONCLUSIONS: Obese subjects do not exhibit the decline in plasma ghrelin and leptin seen after a meal in the lean. The role of the decline in leptin is unclear but given the orexigenic properties of ghrelin, the lack of suppression following a meal in obese subjects could lead to increased food consumption and suggest that ghrelin may be involved in the pathophysiology of obesity.

Myoglobinuric acute renal failure associated with major urological surgery--an avoidable problem?

Recently, the problems associated with crush injury have recently been highlighted [1]. The association between major urological surgery and severe muscle damage is well recognised [2]. We report a case of myoglobinuric acute renal failure following radical cystectomy and suggest possible prevention.

Thrombophlebitis diagnosed on indium-111 labelled white cell scan.

A 64-year-old lady with type 2 diabetes and a non-resolving right foot ulcer, had an indium-111 labelled white cell scan (indium-111 WCS) to investigate the possibility of underlying osteitis. The scan suggested the possibility of infective thrombophlebitis. Unknown to the clinical team who requested the scan and the radiologist who performed it, the lady was admitted to hospital 2 days following the procedure with cellulitis and septic thrombophlebitis in the right leg. There is only one previous report in the literature of septic thrombophlebitis being diagnosed in this way. Perhaps indium-111 WCS has something to offer in the diagnosis of this condition and in determining those who require antibiotic treatment.

Ghrelin does not orchestrate the metabolic changes seen in fasting but has significant effects on lipid mobilisation and substrate utilisation.

OBJECTIVE: Short-term fasting is associated with increased GH pulsatility and mobilisation of fats, but underlying mechanisms are unclear. We studied ghrelin's role during fasting and the effects of exogenous ghrelin on lipid mobilisation. DESIGN: Randomised placebo-controlled study. METHODS: In this study, ten controls (body mass index (BMI) 23.3±3.2), ten morbidly obese subjects (BMI 50.1±10.6) and six post-gastrectomy subjects (BMI 25.2±1.0) were fasted for 36  h undergoing regular blood sampling. On a separate occasion, subjects were infused with either i.v. ghrelin (5  pmol/kg per min) or saline over 270  min. RESULTS: Obese and post-gastrectomy subjects had lower ghrelin compared with controls (ANOVA, P=0.02) during the fast. Controls and gastrectomy subjects showed a similar increase in GH pulsatility, circulating non-esterified fatty acids (NEFA) and 3ß-hydroxybutyrate (3 HB). Obese subjects had an impaired GH response (P<0.001), reduced excursions of 3 HB (P=0.01) but no change in NEFA excursions (P=0.09) compared with controls. Ghrelin infusion increased GH, NEFA and ketone bodies (ANOVA, P<0.0001) in all the three groups, but GH response was impaired in the obese subjects (P=0.001). Ghrelin also induced a significant (ANOVA, P=0.004) biphasic NEFA response to meals in all the subjects. CONCLUSIONS: Despite low circulating ghrelin, gastrectomy subjects maintain a normal metabolic response to fasting, implying that ghrelin plays a minimal role. In contrast, infused ghrelin has significant effects on lipid mobilisation and induces a marked biphasic NEFA response to meals. Hence, ghrelin may play a significant role in meal-related substrate utilisation and metabolic flexibility.

Metformin prolongs the postprandial fall in plasma ghrelin concentrations in type 2 diabetes.

BACKGROUND: Weight loss is difficult to achieve in type 2 diabetes and many therapies are associated with weight gain, an effect attenuated by metformin. We studied the effects of metformin on energy expenditure, appetite and the regulation of PYY and ghrelin in type 2 diabetes. METHODS: Plasma peptide YY (PYY), ghrelin, resting metabolic rate (RMR), postprandial thermogenesis (PPTG), and appetite ratings were measured at baseline and following a mixed meal in 11 type 2 diabetic subjects treated with diet alone (T2D) and 10 treated with metformin monotherapy (T2MF). The groups were similar in age, gender and adiposity. RESULTS: There were no differences in baseline anthropometric, or metabolic variables between the groups. Postprandially, plasma ghrelin fell equally in both groups (23% versus 24.5%, p < 0.05 versus baseline, p = NS between groups) but were reduced for longer in T2MF (below baseline 60-240 min T2MF versus 60-180 min T2D) coincidentally with a prolonged sensation of fullness and suppression of hunger in the metformin-treated group. There were no differences in PYY concentrations, RMR or PPTG. CONCLUSIONS: Metformin prolongs the postprandial fall in ghrelin concentrations. These effects may prolong the inter-meal interval, thereby decreasing snack intake and daily energy intake, promoting weight loss.

Videourodynamic assessment of the Stamey procedure for stress incontinence.

Fifty-three patients underwent the Stamey procedure after stress incontinence was demonstrated by videourodynamic assessment. It was possible to repeat this assessment in 45 patients post-operatively; 58% were shown to be continent and in 20% the leakage was less. Failed operations were unrelated to age, weight, parity, degree of bladder neck descent or previous pelvic surgery. Coexisting detrusor instability was not a contraindication to surgery. Delayed voiding was common immediately after surgery but voiding problems were not encountered once micturition had been re-established. Although a significant objective failure rate was demonstrated, the Stamey procedure has many advantages and it can be recommended as first-line treatment in cases of stress incontinence.

Coagulation tests in predicting haemorrhage after prostatic resection.

It is known that disseminated intravascular coagulation (DIC) can contribute towards blood loss after transurethral resection of the prostate because of the absorption of various prostatic substances. The aim of the present study was to establish whether simple coagulation tests (prothrombin time/activated partial thromboplastin time) carried out immediately after surgery would be useful in predicting those patients who bleed excessively after prostatic resection due to DIC. Criteria to determine significant post-operative haemorrhage were defined. Of 110 patients entered into the study, 34.5% had significant post-operative bleeding and 74% of these had an abnormal prothrombin time (> or = 15 s) immediately after surgery. An abnormal prothrombin time was associated with the resection of large prostates but could also predict the risk of bleeding independent of the resected weight; 18% of patients with an abnormal prothrombin time were also found to have an abnormal activated partial thromboplastin time and all of these had significant blood loss. A group of patients with an abnormal prothrombin time and a resected dry weight > or = 35 g was identified as a high risk group.

Survey of services and practices of cleft palate-craniofacial teams.

Questionnaire data about services and practices of cleft palate-craniofacial teams were obtained from 63 teams in 35 states. Findings indicate the following: (1) research was the least frequently conducted activity, although 73 percent of the teams indicated that they conducted research; and (2) the majority of those responding regarded cinefluoroscopy, endoscopy, perceptual assessment, oral examination, and videoendoscopy as important procedures, yet most patients (90%) seen by these teams did not receive instrumental assessment of velopharyngeal function.

The aetiology and management of acute epididymitis.

The aetiology of acute epididymitis presenting to a surgical unit in a District General Hospital is presented. Patients over 45 years old frequently have a coliform urinary tract infection which may be associated with bladder neck obstruction. These patients require treatment with a suitable antibiotic (Co-trimoxazole) and further investigation. This condition occurs more commonly in patients under 45 years old in whom it is not associated with urinary tract infection. We have not demonstrated significant chlamydial infection and in a double blind study the antibiotic Co-trimoxazole did not hasten recovery. In this group the aetiology remains obscure.

Idiopathic hydronephrosis in childhood--a comparison between diuresis renography and upper urinary tract morphology.

Twenty-seven children undergoing surgery for suspected pelviureteric junction obstruction were studied by pre-operative diuresis renography. The results obtained by this test were compared with histological and histochemical studies of the resected specimens of renal pelvis. A significant correlation was found between these methods of assessment. In addition, the morphological appearances of the renal pelvis tended to show more marked changes in the younger children.

Modified method of diuresis renography for the assessment of equivocal pelviureteric junction obstruction.

Thirty-five hydronephrotic kidneys, in which diuresis renography showed either an equivocal (13) or non-obstructive (22) response pattern, were studied by a modified method in which intravenous frusemide was given 15 min before the start of the renogram so as to assess elimination during the period of maximum diuresis. Thirteen kidneys were identified as obstructed, including three in which the standard diuretic renogram appeared to exclude obstruction. These results indicate that the modified method increases the specificity of diuresis renography when used to assess patients with equivocal pelviureteric junction obstruction.

Intravesical chemotherapy: in vitro studies on the relationship between dose and cytotoxicity.

The relative importance of two variables, drug concentration and period of exposure, in relation to the therapeutic potential of intravesical chemotherapy was examined in an experimental system. A human bladder cancer cell line was exposed to a range of concentrations of the four drugs commonly used to treat superficial bladder cancer (adriamycin, epodyl, mitomycin-c, thiotepa) for periods of 30, 60 and 120 min. An exponential relationship was observed between clonogenic cell kill and both drug concentration and period of exposure. Thus, under the experimental conditions employed, cytotoxicity is proportional to dose (i.e. concentration X period of exposure). These two variables are of equal importance in relation to tumor cell kill, indicating that maximum therapeutic benefit may be obtained by using the highest concentration achievable for as long as the patient can retain the instillate, bearing in mind the potential increase in toxicity to the patient and the cost.

Pain relief and quality-of-life assessment following intravenous and oral clodronate in hormone-escaped metastatic prostate cancer.

OBJECTIVE: To establish the efficacy of intravenous clodronate followed by maintenance oral clodronate in patients with painful bone metastases resulting from hormone-resistant prostate cancer. PATIENTS AND METHODS: A multicentre open study of 27 patients assessed the efficacy of clodronate treatment by estimating the reduction in World Health Organization (WHO) Pain Score, the increase in WHO Performance Status and by a novel quality-of-life/activity score. RESULTS: Ten of 27 patients achieved significant pain relief after receiving 300 mg/day of intravenous clodronate for 10 days. This was matched by an improvement in the activity score and WHO Performance Status. Three of 27 patients continued to have relief from pain after 3 months of oral clodronate therapy. CONCLUSION: Intravenous clodronate therapy was effective in relieving the pain resulting from prostate cancer bone metastases in 10 of 27 patients but the benefit was shortlived. The use of a personal quality-of-life/activity questionnaire which assesses aspects of everyday life that are important to the patient may be more appropriate for patients with very advanced prostate cancer than are other quality-of-life questionnaires in current use.