Colostrum management practices that improve the transfer of passive immunity in neonatal dairy calves: A scoping review.

The objective of this scoping review was to describe the literature on the characteristics and management practices of colostrum feeding and their associations with the level of transfer of passive immunity (TPI) in dairy calves. Observational and experimental studies were searched in 5 electronic databases and 3 conference proceedings. Two reviewers independently screened primary studies, either analytic observational or experimental studies written in English. Studies on dairy or dual-purpose calves with passive immunity analyzed by blood sampling between 1 to 9 days of age were included. All studies had to compare at least one colostrum intervention or risk factor and their association with passive immunity. Of the 3,675 initially identified studies, 256 were included in this synthesis. One hundred and ninety-five were controlled trials, 57 were cohort studies, and 4 were cross-sectional studies. The effect of colostral quantity at first feeding was investigated in 30 controlled studies including studies that were comparable to each other. The effect of colostral quality was explored in 24 controlled studies with inconsistent criteria used to define the quality. The effect of the timing of first feeding of colostrum was investigated in 21 controlled studies, where the timing of feeding ranged widely from immediately after birth to 60 h of age. Only 4 controlled studies evaluated the relationship between bacterial load in the colostrum and TPI in dairy calves. Of the 256 total studies, 222 assessed blood IgG concentration while 107 measured blood total protein concentration. We identified a gap in knowledge on the association between passive immunity in dairy calves and the bacterial load in colostrum, or the timing of harvesting colostrum from the dam. A possible quantitative synthesis could be conducted among the studies that evaluated colostral quantity at the first feeding in relation to TPI in dairy calves.

Characteristics of global naturopathic education, regulation, and practice frameworks: results from an international survey.

BACKGROUND: This descriptive study provides the first examination of global naturopathic education, regulation and practice frameworks that have potential to constrain or assist professional formation and integration in global health systems. Despite increasing public use, a significant workforce, and World Health Organization calls for national policy development to support integration of services, existent frameworks as potential barriers to integration have not been examined. METHODS: This cross-sectional survey utilized purposive sampling of 65 naturopathic organisations (educational institutions, professional associations, and regulatory bodies) from 29 countries. Organizational representatives completed an on-line survey, conducted between Nov 2016 - Aug 2019. Frequencies and cross-tabulation statistics were analyzed using SPSSv.25. Qualitative responses were hand-coded and thematically analysed where appropriate. RESULTS: Sixty-five of 228 naturopathic organizations completed the survey (29% response rate) from 29 of 46 countries (63% country response rate). Most education programs (68%) were delivered via a national framework. Higher education qualifications (60%) predominated. Organizations influential in education were professional associations (75.4%), particularly where naturopathy was unregulated, and accreditation bodies (41.5%) and regulatory boards (33.8%) where regulated. Full access to controlled acts, and to health insurance rebates were more commonly reported where regulated. Attitude of decision-makers, opinions of other health professions and existing legislation were perceived to most impact regulation, which was globally heterogeneous. CONCLUSION: Education and regulation of the naturopathic profession has significant heterogeneity, even in the face of global calls for consistent regulation that recognizes naturopathy as a medical system. Standards are highest and consistency more apparent in countries with regulatory frameworks.

Primary screen for potential sheep scab control agents.

The efficacy of potential acaricidal agents were assessed against the sheep scab mite Psoroptes ovis using a series of in vitro assays in modified test arenas designed initially to maintain P. ovis off-host. The mortality effects of 45 control agents, including essential oils, detergents, desiccants, growth regulators, lipid synthesis inhibitors, nerve action/energy metabolism disruptors and ecdysteroids were assessed against adults and nymphs. The most effective candidates were the desiccants (diatomaceous earth, nanoclay and sorex), the growth regulators (buprofezin, hexythiazox and teflubenzuron), the lipid synthesis inhibitors (spirodiclofen, spirotetramat and spiromesifen) and the nerve action and energy metabolism inhibitors (fenpyroximate, spinosad, tolfenpyrad, and chlorantraniliprole).

Adjuvant epirubicin followed by cyclophosphamide, methotrexate and fluorouracil (CMF) vs CMF in early breast cancer: results with over 7 years median follow-up from the randomised phase III NEAT/BR9601 trials.

BACKGROUND: The National Epirubicin Adjuvant Trial (NEAT) and BR9601 trials tested the benefit of epirubicin when added to cyclophosphamide, methotrexate and 5-fluorouracil (E-CMF) compared with standard CMF in adjuvant chemotherapy for women with early breast cancer. This report details longer follow-up with interesting additional time-dependent analyses. METHODS: National Epirubicin Adjuvant Trial used epirubicin (E) 3-weekly for four cycles followed by classical (c) CMF for four cycles (E-CMF) compared with cCMF for six cycles. BR9601 used E 3-weekly for four cycles followed by CMF 3-weekly for four cycles, compared with CMF 3-weekly for eight cycles. RESULTS: In all, 2391 eligible patients were randomised and with a median 7.4-year follow-up, E-CMF confirmed a significant benefit over CMF in both relapse-free survival (RFS) (78% vs 71% 5 years RFS, respectively, hazard ratio (HR)=0.75 (95% CI: 0.65-0.86), P<0.0001) and overall survival (OS) (84% vs 78% 5 years OS, respectively, HR=0.76 (95% CI: 0.65-0.89), P=0.0007). Interaction of treatment effect and prognostic factors was demonstrated for duplication of chromosome 17 centromeric enumeration (Ch17CEP) as previously reported. Poor prognostic factors at diagnosis (ER and PR negative and HER2 positive) showed time-dependent annual hazard rates for RFS and OS. In univariate analysis, these factors demonstrated more favourable HRs for RFS after 5 years. Treatment effects also suggested a differential benefit for E-CMF within the first 5 years for poor prognosis tumours. CONCLUSION: Longer follow-up has confirmed E-CMF as significantly superior to CMF for all patients. Ch17CEP duplication was the only biomarker that demonstrated significant treatment interaction. Standard poor prognostic factors at diagnosis were time-dependent, and after 5 years disease-free, poor prognosis patients demonstrated favourable HRs for survival.

The cost-effectiveness of adjuvant chemotherapy for early breast cancer: A comparison of no chemotherapy and first, second, and third generation regimens for patients with differing prognoses.

BACKGROUND: The risk of recurrence following surgery in women with early breast cancer varies, depending upon prognostic factors. Adjuvant chemotherapy reduces this risk; however, increasingly effective regimens are associated with higher costs and toxicity profiles, making it likely that different regimens may be cost-effective for women with differing prognoses. To investigate this we performed a cost-effectiveness analysis of four treatment strategies: (1) no chemotherapy, (2) chemotherapy using cyclophosphamide, methotrexate, and fluorouracil (CMF) (a first generation regimen), (3) chemotherapy using Epirubicin-CMF (E-CMF) or fluorouracil, epirubicin, and cyclophosphamide (FEC60) (a second generation regimens), and (4) chemotherapy with FEC60 followed by docetaxel (FEC-D) (a third generation regimen). These adjuvant chemotherapy regimens were used in three large UK-led randomised controlled trials (RCTs). METHODS: A Markov model was used to simulate the natural progression of early breast cancer and the impact of chemotherapy on modifying this process. The probability of a first recurrent event within the model was estimated for women with different prognostic risk profiles using a parametric regression-based survival model incorporating established prognostic factors. Other probabilities, treatment effects, costs and quality of life weights were estimated primarily using data from the three UK-led RCTs, a meta-analysis of all relevant RCTs, and other published literature. The model predicted the lifetime costs, quality adjusted life years (QALYs) and cost-effectiveness of the four strategies for women with differing prognoses. Sensitivity analyses investigated the impact of uncertain parameters and model assumptions. FINDINGS: For women with an average to high risk of recurrence (based upon prognostic factors and any other adjuvant therapies received), FEC-D appeared most cost-effective assuming a threshold of £20,000 per QALY for the National Health Service (NHS). For younger low risk women, E-CMF/FEC60 tended to be the optimal strategy and, for some older low risk women, the model suggested a policy of no chemotherapy was cost-effective. For no patient group was CMF chemotherapy the preferred option. Sensitivity analyses demonstrated cost-effectiveness results to be particularly sensitive to the treatment effect estimate for FEC-D and the future price of docetaxel. INTERPRETATION: To our knowledge, this analysis is the first cost-effectiveness comparison of no chemotherapy, and first, second, and third generation adjuvant chemotherapy regimens for early breast cancer patients with differing prognoses. The results demonstrate the potential for different treatment strategies to be cost-effective for different types of patients. These findings may prove useful for policy makers attempting to formulate cost-effective treatment guidelines in the field of early breast cancer.

NEAT: National Epirubicin Adjuvant Trial--toxicity, delivered dose intensity and quality of life.

The NEAT trial reported considerable benefit for ECMF (epirubicin followed by cyclophosphamide, methotrexate and 5-fluorouracil) of 28% for relapse-free survival (RFS) and 30% for overall survival (OS), when compared with classical CMF in early breast cancer. To assess tolerability, toxicity, dose intensity and quality of life (QoL) analyses were undertaken. All 2021 eligible patients had common toxicity criteria (CTC), delivered chemotherapy and supportive treatments details and long-term morbidities recorded. The QoL substudy used multiple validated measures. ECMF produced low CTC scores, although higher than CMF for nausea, vomiting, alopecia, constipation, stomatitis (P<0.001), infection (P=0.001) and fatigue (P=0.03). Supportive treatments required, however, were similar across randomised treatments. On-treatment deaths were more common with CMF (13) than ECMF(5). Optimal course-delivered dose intensity (CDDI > or =85%) was received more often by ECMF patients (83 vs 76%: P=0.0002), and was associated with better RFS (P=0.0006). QoL over 2 years was equivalent across treatments, despite minimally worse side effects for ECMF during treatment. ECMF benefit spanned all levels of toxicity, CDDI and QoL. There are no reported acute myeloid leukaemias or cardiac dysfunctions. ECMF is tolerable, deliverable, and significantly more effective than CMF, with no serious long-term toxicity or QoL detriment.

Influence of surgical resection and post-operative complications on survival following adjuvant treatment for pancreatic cancer in the ESPAC-1 randomized controlled trial.

BACKGROUND/AIMS: The influence of type of surgery and occurrence of post-operative complications on survival following adjuvant therapy for pancreatic cancer are uncertain. METHODS: Cox proportional hazard modelling was used to investigate the influence of type of surgery and the presence of complications on survival in conjunction with clinico-pathological variables in the 550 patients of the ESPAC-1 adjuvant randomized controlled trial. RESULTS: Standard Kausch-Whipple (KW) was performed in 282 (54%) patients, 186 (35%) had a pylorus-preserving (PP) KW, 39 (7%) had a distal pancreatectomy and 21 (4%) had a total pancreatectomy. Post-operative complications were reported in 140 (27%) patients. PP-KW patients survived longer with a median (95% CI) survival of 19.9 (17.3, 23.1) months compared to 14.8 (13.0, 16.7) for KW patients (chi(2)(LR) = 15.1, p < 0.001). KW patients were more likely however to have R1 margins (67 (24%) vs. 29 (16%), chi(2) = 4.59, p = 0.032), poorly differentiated tumours (70 (26%) vs. 19 (10%), chi(2) = 18.65, p < 0.001) and positive lymph nodes (165 (60%) vs. 81 (44%), chi(2) = 11.32, p < 0.001). Post-operative complications did not significantly affect survival. Independent prognostic factors were tumour grade, nodal status and tumour size but not type of surgery or post-operative complications. There was a survival benefit for chemotherapy irrespective of the type of surgery or post-operative complications. CONCLUSIONS: The KW and PP-KW procedures did not significantly influence the hazard of death in the presence of tumour staging, demonstrating that ESPAC-1 surgeons showed good judgement in their choice of operation. Post-operative complications did not adversely affect the survival benefit from adjuvant chemotherapy.

Effect of flax supplementation and growth promotants on lipoprotein lipase and glycogenin messenger RNA concentrations in finishing cattle.

Lipoprotein lipase (LPL) hydrolyzes triacylglycerols into monoacylglycerol and fatty acids, which are taken up by tissues and used for energy. Glycogenin is the core protein on which glycogen molecules are synthesized. There is one molecule of glycogenin per molecule of glycogen in skeletal muscle; therefore, glycogen storage is limited by the amount of glycogenin present in muscle. The objective of this study was to investigate the effect of feeding flaxseed, a source of PUFA, and administering a growth promoter on steady-state LPL and glycogenin mRNA content of muscle in finishing cattle. Sixteen crossbred steers (initial BW = 397 kg), given ad libitum access to a 92% concentrate diet for 28 d, were used in a four-treatment, 2 x 2 factorial experiment, with flaxseed supplementation (0 or 5% of dietary DM) and implanting (not implanted or implanted with Revalor-S) as the main effects. Muscle biopsies were obtained from the LM at 0, 14, and 28 d, and used to quantify LPL and glycogenin mRNA concentrations using real-time quantitative PCR. Implanting with Revalor-S did not affect LPL (P = 0.13) or glycogenin (P = 0.98) mRNA concentrations. A day x flaxseed interaction (P < 0.001) was observed for both LPL and glycogenin mRNA concentrations. No differences (P > 0.10) were observed between 0 and 5% flaxseed supplemented steers; however, at 28 d, nonflaxseed-fed steers had 4.1- and 5.7-fold increases (P < 0.001) over flaxseed steers for LPL and glycogenin mRNA concentrations, respectively. To further evaluate the effects of alpha-linolenic acid (alpha-LA) on LPL and glycogenin mRNA concentrations, muscle satellite cells were isolated from five finishing steers, and different alpha-LA concentrations were applied in culture. The RNA was isolated from the bovine satellite cells. Addition of alpha-LA numerically increased (P = 0.16) the LPL mRNA concentration 48% at 1 microM alpha-LA compared with the control. The expression of glycogenin was increased (P < 0.05) 50% at 1 microM alpha-LA compared with the control. These results suggest that flaxseed supplementation to finishing steers for 28 d decreased gene expression of both LPL and glycogenin compared with not feeding flaxseed. Alterations in local concentrations of these two proteins could affect the ability of muscle to use fatty acids and glucose for energy, and, ultimately, affect carcass quality.

Effects of flax supplementation and a combined trenbolone acetate and estradiol implant on circulating insulin-like growth factor-I and muscle insulin-like growth factor-I messenger RNA levels in beef cattle.

We evaluated effects of a 5% (dry matter basis) ground flaxseed supplement (flax) and a trenbolone acetate and estradiol-17beta implant, Revalor-S, on circulating IGF-I and muscle IGF-I messenger RNA (mRNA). Sixteen crossbred yearling steers (initial BW = 397 kg) were assigned randomly to one of four treatments: 1) flax/implant; 2) nonflax/implant; 3) flax/nonimplant; and 4) nonflax/nonimplant. Serum was harvested from blood collected on d 0 (before implant or flax addition), 14, and 28, and used in subsequent analyses of circulating IGF-I. Biopsy samples (0.5 g) were obtained from the longissimus muscle on d 0, 14, and 28. Total RNA was isolated from the muscle samples, and real-time quantitative-PCR was used to assess relative differences in IGF-I mRNA. Flax supplementation had no effect (P > 0.10) on circulating IGF-I concentrations. Following implantation, sera from implanted steers had 52 and 84% greater (P < 0.05) IGF-I concentrations than sera from nonimplanted steers on d 14 and 28, respectively. On d 28, local muscle IGF-I mRNA levels increased 2.4-fold (P < 0.01) in biopsy samples obtained from implanted compared with nonimplanted steers. Muscle biopsy samples from nonflax cattle had 4.4-fold higher (P < 0.01) levels of IGF-I mRNA than those from flax cattle on d 28. To determine whether a component of flax, alpha-linolenic acid (alphaLA), was directly responsible for IGF-I mRNA down-regulation, we incubated primary cultures of bovine satellite cells, from implanted and nonimplanted steers, in two concentrations of alphaLA (10 nM and 1 microM). An implant x dose interaction (P < 0.05) was observed for IGF-I mRNA concentrations in bovine satellite cells cultured for 72 h with alphaLA. Satellite cells from nonimplanted steers had similar (P > 0.10) IGF-I mRNA concentration regardless of the level of alphaLA exposure; however, satellite cells from implanted steers exposed to 10 nM and 1 microM alphaLA had 2.5- and 2.0-fold greater IGF-I mRNA levels, respectively, than cells from implanted steers that were not exposed to alphaLA (P < 0.05). Administration of a Revalor-S implant increased circulating IGF-I and local muscle IGF-I mRNA concentrations in finishing cattle. However, muscle IGF-I mRNA levels were decreased by flax supplementation. Muscle cell culture experiments suggested that alphaLA was not responsible for the IGF-I mRNA down-regulation.

[Adjuvant and additive therapy for cancer of the pancreas]. / Adjuvante und additive Therapie beim Pankreaskarzinom.

Recent advances have been made in the treatment of pancreas cancer. Specialized pancreas centres have reported an increasing rate of resections with reduced postoperative mortality. On account of the highly aggressive nature of pancreas cancer, there is a great challenge in identifying effective therapy concepts for advanced stages of the cancer as well as for the development of resection-associated measures. As large-scale, randomised, controlled studies are lacking, the additive therapy concepts after resection do not have a sufficiently scientific basis. The ESPAC-1 study, which included 600 patients, surpassed all previous studies on adjuvant therapy for pancreas cancer. This study has shown,for example, that the most promising adjuvant chemotherapy with 5-fluorouracil and folic acid leads to an equal if not better result than the multimodal regimen. This regimen can be superseded with the use of Gemcitabine, which will be evaluated in the ESPAC-3 study that includes 990 patients from various European countries including Germany, as well as from Canada and Australia. Participation in the large, phase-3 study therefore plays a key role in the continued development of the management of pancreas cancer.

Adjuvant chemoradiotherapy and chemotherapy in resectable pancreatic cancer: a randomised controlled trial.

BACKGROUND: The role of adjuvant treatment in pancreatic cancer remains uncertain. The European Study Group for Pancreatic Cancer (ESPAC) assessed the roles of chemoradiotherapy and chemotherapy in a randomised study. METHODS: After resection, patients were randomly assigned to adjuvant chemoradiotherapy (20 Gy in ten daily fractions over 2 weeks with 500 mg/m(2) fluorouracil intravenously on days 1-3, repeated after 2 weeks) or chemotherapy (intravenous fluorouracil 425 mg/m(2) and folinic acid 20 mg/m(2) daily for 5 days, monthly for 6 months). Clinicians could randomise patients into a two-by-two factorial design (observation, chemoradiotherapy alone, chemotherapy alone, or both) or into one of the main treatment comparisons (chemoradiotherapy versus no chemoradiotherapy or chemotherapy versus no chemotherapy). The primary endpoint was death, and all analyses were by intention to treat. Findings 541 eligible patients with pancreatic ductal adenocarcinoma were randomised: 285 in the two-by-two factorial design (70 chemoradiotherapy, 74 chemotherapy, 72 both, 69 observation); a further 68 patients were randomly assigned chemoradiotherapy or no chemoradiotherapy and 188 chemotherapy or no chemotherapy. Median follow-up of the 227 (42%) patients still alive was 10 months (range 0-62). Overall results showed no benefit for adjuvant chemoradiotherapy (median survival 15.5 months in 175 patients with chemoradiotherapy vs 16.1 months in 178 patients without; hazard ratio 1.18 [95% CI 0.90-1.55], p=0.24). There was evidence of a survival benefit for adjuvant chemotherapy (median survival 19.7 months in 238 patients with chemotherapy vs 14.0 months in 235 patients without; hazard ratio 0.66 [0.52-0.83], p=0.0005). Interpretation This study showed no survival benefit for adjuvant chemoradiotherapy but revealed a potential benefit for adjuvant chemotherapy, justifying further randomised controlled trials of adjuvant chemotherapy in pancreatic cancer.

The supportive care needs of men with prostate cancer (2000).

The diagnosis and subsequent treatment of prostate cancer is followed by a range of significant disease specific and iatrogenic sequelae. However, the supportive care needs of men with prostate cancer are not well described in the literature. The present study assesses the supportive care needs of men with prostate cancer who are members of prostate cancer self-help groups in Queensland, Australia. In all, 206 men aged between 48 and 85 years (mean=68) completed the Supportive Care Needs Survey (SCNS) (62% response). The SCNS is a validated measure assessing perceived need in the domains of psychological needs, health system and information needs, physical and daily living needs, patient care and support, and sexuality. Items assessing need for access to services and resources were also included. One third of the sample reported a moderate to high need for help for multiple items in the sexuality, psychological and health system and information domains. Younger men reported greater need in the sexuality domain; living in major urban centres was predictive of greater psychological need; being closer to the time of diagnosis was related to greater need for help in the physical and daily living domain; having prostate cancer that is not in remission, having received radiation therapy, and lower levels of education were predictive of greater need for help in patient care and support. Of the total sample, 55% of men had used alternative cancer treatments in the past 12 months, with younger and more educated men more likely to use alternative therapies. Interventions in sexuality, psychological concerns and informational support are priorities for men with prostate cancer.

Nonsurgical septal reduction therapy for hypertrophic obstructive cardiomyopathy: one-year follow-up.

OBJECTIVE: The objective of this study is to evaluate the one-year outcome of the first 50 patients who underwent nonsurgical septal reduction for symptomatic hypertrophic obstructive cardiomyopathy at our institution. BACKGROUND: Left ventricular outflow tract obstruction is an important determinant of clinical symptoms in patients with hypertrophic obstructive cardiomyopathy. Nonsurgical septal reduction is a new therapy that has been shown to result in left ventricular outflow tract gradient reduction and resolution of symptoms immediately after the procedure and on midterm follow-up. METHODS: Fifty patients with hypertrophic obstructive cardiomyopathy who underwent nonsurgical septal reduction at our institution and completed 1-year follow-up are described. Complete history, physical examination, two-dimensional echocardiography with Doppler and exercise treadmill testing have been analyzed. RESULTS: The mean age of the study group was 53 +/- 17 years. All patients had refractory symptoms before enrollment. Ninety-four percent had class III or IV New York Heart Association class symptoms at baseline compared to none at 1 year (p < 0.001). The exercise duration increased by 136 s at 1 year (p < 0.021). Only 20% of patients were either receiving beta-blockers or calcium-channel blockers on follow-up. The resting left ventricular outflow tract gradient decreased from 74 +/- 23 mm Hg to 6 +/- 18 mm Hg (p < 0.01) and from 84 +/- 28 mm Hg to 30 +/- 33 mm Hg (p < 0.01) in patients with dobutamine-provoked gradient at one year. These changes are associated with decreased septal thickness and preserved systolic function. CONCLUSION: Nonsurgical septal reduction therapy is an effective therapy for symptomatic patients with hypertrophic obstructive cardiomyopathy with persistence of the favorable outcome up to one year after the procedure.

Effect of hyperventilation on brain tissue oxygenation and cerebrovenous PO2 in rats.

Previous studies have shown that cortical tissue oxygenation is impaired during hyperventilation. However, it is important to quantify the effect of hyperventilation on brain tissue PO(2) and cerebrovenous PO(2) simultaneously especially since cerebral venous oxygenation is often used to assess brain tissue oxygenation. The present study was designed to measure the sagittal sinus PO(2) (PvO(2)), brain tissue PO(2) in the thalamus (PtO(2)), and brain temperature (Bt) simultaneously during acute hyperventilation. Isoflurane-anesthetized rats were hyperventilated for 10 min during which time the arterial carbon dioxide tension (PaCO(2)) dropped from 40.3+4.9 mmHg to 23.5+2.8 mmHg. PtO(2) declined from 26.0+/-4.2 mmHg to 14.8+/-5.2 mmHg (P=0.004) while brain temperature decreased from 36.5+0.3 degrees C to 36.2+0.3 degrees C (P=0.02). However, PvO(2) and arterial blood pressure (BP) did not change during hyperventilation. The maintenance of PvO(2) when perfusion is thought to decline and PtO(2) decreases suggests that there may be a diffusion limitation, possibly due to selective perfusion. Therefore, cerebrovenous PO(2) may not give a good assessment of brain tissue oxygenation especially in conditions of acute hyperventilation, and deeper brain regions other than the cortex also show impaired tissue oxygenation following hyperventilation.

Persistence of iodine deficiency 25 years after initial correction efforts in the Khumbu region of Nepal.

AIMS: To assess the current status of, and understanding about iodine deficiency disorders among Sherpa residents of the Khumbu region of Nepal, 25 years after the introduction of iodised oil injections. METHODS: Several groups of Khumbu Sherpas were studied and goitre rate, urinary iodine level and cretinism prevalence were measured as indicators of iodine deficiency. Subjects were also questioned in detail about their food consumption, with particular reference to salt use, and about their understanding of the causes and treatment of iodine deficiency disorders. RESULTS: The prevalences of goitre, deaf-mutism and cretinism were 21%, 1.3% and 0.5% respectively (compared to 92%, 4.7% and 5.9% in 1966). No cretins had been born since 1966. The median urine iodine concentration was 35 microg/L. Most people preferred uniodised Tibetan rock salt, although 44% regularly consumed iodised salt. All granulated salt tested from the local market contained adequate amounts of iodine. Only 11% of those surveyed knew that goitre was caused by iodine deficiency CONCLUSIONS: Although prevalences of iodine deficiency disorders are much less than 30 years ago, iodine deficiency continues to be a major problem in Khumbu and demands a clear control strategy, combining ongoing iodine supplementation and education. Iodised salt is usually the best approach to control of iodine deficiency disorders for most regions of the world but the Khumbu experience shows that local cultural and commercial factors can severely limit its impact. To be successful, control programme for iodine deficiency disorders also needs assessment of the salt trade, monitoring, education and occasional targeted interventions with iodised oil or other supplements.

Short-term vitamin E supplementation before marathon running: a placebo-controlled trial.

Gastrointestinal complaints and occult bleeding have been commonly described in marathon runners. We hypothesized that these complaints may arise from intestinal ischemia caused by the shunting of blood away from the splanchnic circulation during endurance racing followed by reperfusion injury. Studies in animal models have suggested prophylactic vitamin E supplementation may prevent this type of injury. We sought to determine if prerace vitamin E supplementation would prevent intestinal ischemia/reperfusion injury in humans. Forty subjects who planned to complete the 1996 Houston-Tennaco Marathon were randomized to receive vitamin E (1000 IU daily) or placebo (soya lecithin) for 2 wk before the race in a double-blinded trial. Inclusion criteria included no use of non-steroidal anti-inflammatory drugs (NSAIDs) within 24 d of the race or vitamin or mineral supplements containing vitamins C or E or selenium within 30 d of the race. Subjects were studied 2 wk before the race and immediately following the race. Blood was obtained for serum vitamin E and total lipid and salicylate concentrations. A solution of lactulose (5 g) and mannitol (2 g) was consumed and urine was collected for 6 h. Aliquots were assayed for lactulose and mannitol concentration. Stool samples were tested for occult blood and following the race subjects rated their nausea, abdominal pain, and cramping on a 1-5 scale. Twenty-six subjects (24 male, 2 female) completed the marathon. Finish times ranged between 2 h 43 min and 5 h 28 min. All subjects had heme-negative stool prerace and four developed heme-positive stool postrace, with no difference between vitamin E and placebo groups (Fisher's exact = 0.63). All had non-detectable salicylate concentrations pre- and postrace. Serum vitamin E concentration increased in botPP = 0.02 in the vitamin E group and 1.45 +/- 0.40 to 1.66 +/- 0.48 mg/dL in the placebo group, P = 0.02). However, the serum vitamin E: total lipid ratio increased significantly in the vitamin E-supplemented group (0.0022 +/- 0.0002 to 0.0051 +/- 0.0015, P = 0.02), but not in the placebo group (P = 0.25). Overall, the urinary lactulose:mannitol ratio increased from 0.03 +/- 0.02 to 0.06 +/- 0.08 postrace (P = 0.06) without difference between vitamin E or placebo groups. Intestinal permeability increased significantly more in those who developed occult bleeding. More subjects in the placebo group developed abdominal cramping (Fisher's exact = 0.04) and abdominal pain (Fisher's exact = 0.06), although there was no difference in severity between groups. There was no difference in the incidence of nausea and no diarrhea was reported by any subject. Intestinal permeability tends to increase and occult gastrointestinal bleeding occurs during endurance running, suggesting the occurrence of intestinal ischemia/reperfusion injury. Prerace supplementation with the antioxidant vitamin E had no effect on performance, intestinal injury, occult bleeding, or the severity of postrace gastrointestinal complaints. Vitamin E supplementation was associated with a decreased incidence of these complaints but had no effect on their severity.

Intermittent oral administration of potassium iodide solution for the correction of iodine deficiency.

Iodized salt and iodized oil are the main methods used to prevent iodine deficiency, but sometimes alternative approaches are needed. We tested the efficacy of various regimens for the intermittent administration of potassium iodide in Hwedza, Zimbabwe, an area of known severe iodine deficiency. We divided 304 schoolchildren aged 7-13 y into five equal groups that received iodine as a 10% solution of potassium iodide as follows: 8.7 mg every 2 wk (group A), 29.7 mg every month (group B), 148.2 mg every 3 mo (group C), 382 mg every 6 mo (group D), or 993 mg once (group E). The follow-up period was 13 mo. No adverse effects were encountered with any of these doses. After 6 mo, the median blood spot thyroglobulin concentration had decreased in all groups and had normalized in groups A and B to values found in iodine-sufficient populations. The number of children with elevated thyroid-stimulating hormone concentrations decreased in groups A-C, but the changes were not significant. Urine iodine concentration generally remained low in all groups but increased in group A. After 13 mo, mean thyroid volume measured by ultrasound had decreased in groups A and B to values comparable with those in iodine-sufficient areas, and was unchanged in the other groups. We conclude that oral potassium iodide is effective for the prophylaxis of iodine deficiency if given as a dose of 30 mg I monthly or 8 mg biweekly.