Symptoms and management of cow's milk allergy: perception and evidence.

Introduction: The diagnosis and management of cow's milk allergy (CMA) is a topic of debate and controversy. Our aim was to compare the opinions of expert groups from the Middle East (n = 14) and the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) (n = 13). Methods: These Expert groups voted on statements that were developed by the ESPGHAN group and published in a recent position paper. The voting outcome was compared. Results: Overall, there was consensus amongst both groups of experts. Experts agreed that symptoms of crying, irritability and colic, as single manifestation, are not suggestive of CMA. They agreed that amino-acid based formula (AAF) should be reserved for severe cases (e.g., malnutrition and anaphylaxis) and that there is insufficient evidence to recommend a step-down approach. There was no unanimous consensus on the statement that a cow's milk based extensively hydrolysed formula (eHF) should be the first choice as a diagnostic elimination diet in mild/moderate cases. Although the statements regarding the role for hydrolysed rice formula as a diagnostic and therapeutic elimination diet were accepted, 3/27 disagreed. The votes regarding soy formula highlight the differences in opinion in the role of soy protein in CMA dietary treatment. Generally, soy-based formula is seldom available in the Middle-East region. All ESPGHAN experts agreed that there is insufficient evidence that the addition of probiotics, prebiotics and synbiotics increase the efficacy of elimination diets regarding CMA symptoms (despite other benefits such as decrease of infections and antibiotic intake), whereas 3/14 of the Middle East group thought there was sufficient evidence. Discussion: Differences in voting are related to geographical, cultural and other conditions, such as cost and availability. This emphasizes the need to develop region-specific guidelines considering social and cultural conditions, and to perform further research in this area.

An ESPGHAN Position Paper on the Use of Low-FODMAP Diet in Pediatric Gastroenterology.

Excluding oligo-, di-, monosaccharides and polyols (FODMAPs) from the diet is increasingly being used to treat children with gastrointestinal complaints. The aim of this position paper is to review the available evidence on the safety and efficacy of its use in children and provide expert guidance regarding practical aspects in case its use is considered . Members of the Gastroenterology Committee, the Nutrition Committee and the Allied Health Professionals Committee of the European Society for Pediatric Gastroenterology Hepatology and Nutrition contributed to this position paper. Clinical questions regarding initiation, introduction, duration, weaning, monitoring, professional guidance, safety and risks of the diet are addressed. A systematic literature search was performed from 2005 to May 2021 using PubMed, MEDLINE and Cochrane Database of Systematic Reviews. In the absence of evidence, recommendations reflect the expert opinion of the authors. The systematic literature search revealed that the low-FODMAP diet has not been comprehensively studied in children. Indications and contraindications of the use of the diet in different pediatric gastroenterological conditions are discussed and practical recommendations are formulated. There is scarce evidence to support the use of a low-FODMAP diet in children with Irritable Bowel Syndrome and no evidence to recommend its use in other gastrointestinal diseases and complaints in children. Awareness of how and when to use the diet is crucial, as a restrictive diet may impact nutritional adequacy and/or promote distorted eating in vulnerable subjects. The present article provides practical safety tips to be applied when the low-FODMAP diet is considered in children.

Artificial insemination in canids: a useful tool in breeding and conservation.

Artificial insemination (AI) and semen freezing have become services available to dog owners worldwide, and the demand for services to freeze semen is increasing. In other canids such as the fox, the fur industry utilizes fresh or frozen semen to artificially inseminate vixens to produce pelts. Clearly, AI facilitates the use of a male to sire several females by diluting the ejaculate, increases breeding hygiene, and allows crossing between species with slightly different breeding seasons. The African wild dog (Lycaon pictus) is currently considered by the World Conservation Union (IUCN) as one of most endangered canids. In captive populations of African wild dogs, semen has been frozen with encouraging results, using a standard cryopreservation protocol for domestic dogs, but successful AI has not been reported. In wolves, there is one report regarding the live birth of an offspring after intravaginal AI of a deslorelin-induced estrous female. In 2005, three Mexican gray wolf females were artificially bred by intrauterine insemination with freshly collected semen from unrelated males, and all females whelped. Artificial insemination may be vaginal, intrauterine or intratubal, and the semen may be fresh, fresh and chilled (diluted), or frozen-thawed, and the source of semen may be epididymal or ejaculated. In the domestic dog, the results are good to excellent for AI with all three types of processed semen when the source is ejaculated semen, whereas epididymal sperm still yields poorer results. Species differences in female physiology, as well as differences in the cryotolerance of the sperm from various canid species, warrant further research and development.

Valproate affects reproductive endocrine function, testis diameter and some semen variables in non-epileptic adolescent goat bucks.

Valproate (VPA) is a major antiepileptic drug with a broad spectrum of antiepileptic activity. There is, however, increasing concern about the possible effects of VPA on reproductive endocrine function. This study investigated the effects of valproate, on the endocrine and reproductive system of adolescent, non-epileptic, goat bucks. Nine goat bucks were orally treated with 62.5mg/kg valproate twice daily from 2 to 10 months of age in order to sustain therapeutic plasma concentrations of between 300 and 600 micromol/l. Seven bucks served as controls. Body weights and testicular diameters were recorded. Blood samples were collected for measurement of luteinising hormone (LH), follicle stimulating hormone (FSH) and testosterone three times weekly until sacrifice at approximately 40 weeks of age. Conventional reproductive endpoints were recorded and flow cytometric (FCM) analyses of spermatogenesis, including the sperm chromatin structure were conducted. Valproate-treated bucks had on average a higher body weight, but a lower testis diameter than controls. No significant differences were found for plasma FSH in comparison to controls. Valproate-treated bucks differed significantly from the control group by showing lower plasma concentrations of LH and testosterone and a later onset of puberty. A significantly higher proportion of sperm from valproate-treated bucks showed abnormal chromatin, demonstrating a harmful effect on DNA from valproate treatment. These results demonstrate that valproate was able to induce reproductive effects in goat bucks related to the hypothalamic-pituitary-axis, as well as to the testes.

Artificial insemination with frozen semen in dogs: a retrospective study of 10 years using a non-surgical approach.

From 1994 to 2003, a total of 526 bitches of 99 different breeds were artificially inseminated in 685 estrus cycles with domestic (n = 353) or imported (n = 332) frozen-thawed semen from 368 males. The overall whelping rate was 73.1% and mean (+/- S.E.M.) litter size 5.7 +/- 0.1 pups. The whelping rate was higher after intrauterine insemination (75.0%; n = 665) than after intravaginal insemination (10.0%, n = 20; P < 0.05). Insemination at the optimal time resulted in a higher whelping rate (78%, n = 559; P < 0.01) and larger litter size (5.8 +/- 0.2; P < 0.05) than inseminations performed late or too late (55.7% and 4.5 +/- 0.5, n = 61). Two inseminations (n = 384) yielded a higher whelping rate (P < 0.05) and mean litter size (P < 0.01) than one insemination (n = 241), 78.1% and 6.0 +/- 0.2 and 70.5% and 5.1 +/- 0.2, respectively. For inseminations performed at the optimal time, however, the whelping rate was not significantly different for bitches inseminated twice (79.3%, n = 358) versus once (76.8%, n = 168), but the litter size was larger (6.0 +/- 0.2 and 5.3 +/- 0.3). Semen classified as of poor quality (progressive motility < 50% or percentage abnormal sperm > 20%) resulted in a lower whelping rate (P < 0.01) than semen classified as of good quality (progressive motility > or = 50% and percentage abnormal sperm < or = 20%), 61 and 77%, respectively. Small breeds (n = 50) had a smaller litter size (3.9 +/- 0.3; P < 0.01) than larger breeds (medium [5.7 +/- 0.3, n = 94], large [5.9 +/- 0.2, n = 295] or giant breeds [6.1 +/- 0.5, n = 62] [P < 0.01]). Bitches older than 6 years had a lower whelping rate (68.2%) than younger ones (77.0%; P < 0.05). The duration of pregnancy was longer (P < 0.01) for bitches with a litter size of < 3 pups (61.7 +/- 0. 4 days, n = 30) than for bitches with larger litters (60.5 +/- 0.1 days, n = 177). These results show the potential of transcervical intrauterine insemination for routine artificial insemination in dogs. The results with frozen semen inseminations were optimised by inseminating bitches < or = 6 years old 2 and 3 days after ovulation with semen of good quality from males < or = 8 years old.

Insulin-like growth factors-I and -II and insulin-like growth factor-binding protein-2 in dominant equine follicles during spring transition and the ovulatory season.

The period between seasonal anoestrus and cyclicity is characterized in many mares by cyclical growth and regression of large dominant follicles. The insulin-like growth factor (IGF) system plays a key role in follicular growth and regression; therefore, we hypothesized that changes in the IGF system and its binding proteins would modulate onset of cyclicity in mares. Ovaries were obtained from pony mares on the day after detection of an actively growing 30 mm transitional anovulatory follicle, and also at the second or third oestrus of the breeding season on the day after the preovulatory follicle reached 30 mm in diameter. Size of dominant follicles at the time of removal was similar in transition (32 +/- 0.8 mm) and at oestrus (34 +/- 0.6 mm). IGF-I mRNA was present in granulosa cells, with low thecal expression, whereas IGF-II mRNA was confined to the theca layer. Expression of IGF-I and -II mRNAs, and intrafollicular concentrations of oestradiol, were lower (P < 0.01; paired t test) in transitional anovulatory follicles than in preovulatory follicles. Messenger RNA encoding IGFBP-2 was present in both theca and granulosa layers. Steady-state concentrations of mRNA encoding IGFBP-2 mRNA increased (P < 0.001) in theca in preovulatory follicles. Intrafollicular concentrations of IGFBP-2 were higher (P < 0.001) in transitional than in preovulatory follicles. The similarity in circulating concentrations of IGF-I in transitional and cyclic mares, suggested that the somatotrophic axis is not involved in transition from anovulatory to ovulatory cycles. The results suggest that the increased expression of IGF-I and -II mRNAs in preovulatory follicles, along with the decrease in IGFBP-2 concentrations, could increase the bioavailability of intrafollicular IGF in large follicles during the breeding season, and support our hypothesis that intrafollicular IGF bioavailability must exceed a threshold level before ovulation can occur.

Somatoform disorders in consultation-liaison psychiatry: a comparison with other mental disorders.

Consultation-liaison (C-L) psychiatry has an important role in the management of somatoform disorders (SD). Characteristics of SD patients in C-L psychiatry are largely unknown and are presented in this paper. We analyzed 13,314 Dutch psychiatric consultations from 1984 to 1991 and compared patients diagnosed with SD to patients with other mental disorders and to those without a mental disorder. The comparison included socio-demographic variables, consult characteristics, medical history, current somatic morbidity, information about additional diagnostic tests, hospital admission time and aftercare management. Of the 544 SD patients 39.5% (n = 215) were diagnosed with a conversion disorder that illustrates the highly selected nature of SD patients in C-L psychiatry. Employment among SD patients decreased significantly from 58% in the group aged 20-29 years to 6% in the group aged 50-59 years. This decrease was significantly larger as compared to other mental disorders and no mental disorders and was virtually unaffected by correction for potential confounding by gender. Contrary to our expectation no difference between the three groups was observed in claims for disability benefits. Of the SD patients 74.5% were referred for aftercare management, significantly more than the other two groups which is considered a promising development in C-L psychiatry.

Association of uterine edema with follicle waves around the onset of the breeding season in pony mares.

During spring transition, when estrus may be exhibited for prolonged periods, it is important for veterinarians and stud farm personnel to be able to predict whether a large follicle will ovulate or regress. It is thought that the presence of ultrasonically detectable uterine edema indicates that a follicle will ovulate, however, there is little evidence to support this. In the present study, 16 mares were regularly examined by transrectal ultrasonography to follow growth and regression of follicles from seasonal anestrus in February until second ovulation. Blood samples were collected daily for measurement of estradiol concentrations when a large ovarian follicle was present. Estrous-like uterine edema was detected during 7 of 11 (64%) anovulatory follicle waves, in 12 of 14 (86%) mares before their first ovulation, and in 100% of mares before their second ovulation. Uterine edema was first detected 43+/-6.7 days before first ovulation. Large anovulatory follicles tended to be present for longer periods of time than ovulatory follicles. Uterine edema was present for a significantly greater proportion of time in the presence of a large follicle at second ovulation than at first ovulation (P<0.05) or for anovulatory follicles (P<0.01). Peak plasma estradiol concentrations and mean plasma estradiol concentrations were significantly higher (P<0.001) when a dominant preovulatory follicle was present compared with a dominant anovulatory follicle, but there was no difference in estradiol concentrations between first and second ovulations. It was apparent, therefore, that uterine edema was not a reliable indicator of follicular steroidogenic competence, or of whether the follicle would ovulate.

Concentrations of inhibin, progesterone and oestradiol in fluid from dominant and subordinate follicles from mares during spring transition and the breeding season.

Dominant and subordinate follicles were collected from mares on the day after the dominant follicle reached 30 mm in diameter, to investigate regulation of folliculogenesis during spring transition and the breeding season. Concentrations of oestradiol-17beta, progesterone and inhibin A, but not inhibin isoforms with pro- and alpha C-immunoreactivity, were significantly higher in preovulatory follicles than in dominant anovulatory transitional follicles. Steroidogenic activity was regained gradually in the dominant follicles of successive anovulatory waves through spring transition. The dominant follicles, during both spring transition and cyclicity, contained higher concentrations of oestradiol, progesterone and inhibin A, but not inhibin pro- and alpha C-isoforms, than subordinate follicles. The results indicate that high follicular levels of oestradiol, progesterone and inhibin A are associated with continued follicle growth and ovulation. The low concentrations of oestradiol and progesterone in transitional follicles indicate that the deficiency in steroidogenesis exists early in the steroidogenic pathway. The similarity in patterns of follicular hormones in spring transition and during cyclicity strongly suggests that the mechanism of dominance is the same in both types of follicle.

Antipsychotic medication and venous thrombosis.

BACKGROUND: In an autopsy series, 10 out of 27 deaths in which 'idiopathic' pulmonary emboli were discerned as the sole cause of death had occurred in psychiatric patients. AIMS: To investigate whether antipsychotic medication is a risk factor for venous thrombosis. METHOD: A description of the 10 psychiatric patients was obtained from the pulmonary emboli autopsy reports. We carried out a brief historic overview of the literature. We re-analysed data from the Leiden Thrombophilia Study (LETS), a case-control study on patients with venous thrombosis. RESULTS: In the autopsy reports, five out of 10 psychiatric patients with fatal pulmonary embolism had confirmed use of antipsychotic drugs. After the application of chlorpromazine and its analogues a higher incidence of venous thrombosis in psychiatric patients was described in the German literature between 1953 and 1977. In the re-analysis of the LETS case-control study, four patients used antipsychotic drugs versus none in the control group. Recent epidemiological studies of good methodological quality have confirmed these findings. CONCLUSIONS: Venous thrombosis appears to be associated with the use of antipsychotic drugs in psychiatric patients.

Artificial insemination with frozen semen in dogs: a retrospective study.

In a retrospective study, from 1994 to 1998, of inseminations with frozen semen in dogs, a total of 312 bitches of 70 different breeds were inseminated with imported (n = 183) or domestic (n = 129) semen. The overall whelping rate was 70% and mean (+/- SEM) litter size was 5.3 +/- 0.2 pups. The whelping rate was higher after intrauterine insemination (71%; n = 305) than after intravaginal insemination (29%; n = 7; P < 0.05). Timing of insemination was crucial; timing classified as optimal resulted in a higher whelping rate and larger litter size (P < 0.05) than did timing classified as early, late or too late. In the too late category, none of the bitches (n = 5) whelped. For optimal timing, whelping rate and mean (+/- SEM) litter size were 76% (n = 252) and 5.6 +/- 0.2, for early 33% (n = 6) and 1.5 +/- 0.5, and for late 47% (n = 19) and 2.8 +/- 0.7. Two inseminations yielded a higher whelping rate (P < 0.05) and greater mean litter size (P < 0.05) than that of one insemination, 77% and 5.6 +/- 0.3, and 60% and 4.6 +/- 0.3, respectively. However, the results obtained after one insemination were poorer partly because of an over-representation of late insemination in this group. Semen classified as of poor quality (progressive motility < 50% or percentage of abnormal spermatozoa > 20%) gave a lower whelping rate (53%) than did semen of medium (progressive motility = 50%) or good quality (progressive motility > 50% and percentage of abnormal spermatozoa < 20%), which gave whelping rates of 76 and 74%, respectively (P < 0.05). The mean litter sizes were not significantly different. Eighty-two per cent of bitches (120 of 147) inseminated twice into the uterus at a time classified as optimal with frozen semen of good or medium quality whelped. The mean (+/- SEM) litter size was 5.6 +/- 0.3 pups in this group. These results show the potential of transcervical intrauterine insemination for routine artificial insemination in dogs.

Prevalence of dementia in centenarians.

Above age 65, the prevalence of dementia rises exponentially from 1 to 15% at age 85. Despite many studies concerning dementia, little is known about the prevalence of dementia in the 'oldest old'. Whether the prevalence levels off around age 95 is yet unanswered. This question is important because it addresses whether dementia is an inevitable consequence of ageing or a disorder occurring within a specific age range. All 17 persons aged 100 or more in three Dutch towns with 250 000 inhabitants were examined by means of cognitive tests, informant questionnaires, clinical interviews and anamneses. Fifteen out of 17 Dutch centenarians in a complete population sample of 250 000 were found to be demented. Two could not be examined.

Prevalence of dementia over age 100.

All nine persons aged 100 or older in a Dutch town with some 100,000 inhabitants were examined by means of cognitive tests, informant questionnaires, and clinical interviews. Formal testing was difficult in most subjects because of visual, auditory, and motor handicaps. By combining the results of cognitive tests and clinical examinations, a diagnosis of moderate to severe dementia could be made in eight subjects. One subject was not examined but by informant questionnaire was found to be mildly demented.

In vitro maturation and fertilization of oocytes from Norwegian semi-domestic reindeer (Rangifer tarandus ).

Reindeer oocytes were submitted to in vitro maturation, fertilization and culture (IVM,IVF,IVC) using the established procedures for bovine in vitro embryo production. The study was conducted outside the main breeding season. Semen was collected from epididymides immediately after slaughter, and was diluted in Tris-fructose-citric acid extender containing 6% glycerol and 20% egg-yolk and then frozen in liquid nitrogen. Following 24 h of maturation, cumulus expansion was complete, and 71% of the oocytes reached Metaphase II (MII), with extrusion of the first polar body. Of the remaining oocytes, 22% were at the germinal vesicle stage (GV), 2% at diakinesis and 5% at Metaphase I (MI). The percentages of fertilization and cleavage were 36.0 and 31.8%, respectively. Two of the fertilized oocytes developed to the morula stage after 7 d of culture.

Attitudes of Dutch general practitioners towards presymptomatic DNA-testing for Huntington disease.

The attitudes of 1020 Dutch GP's towards presymptomatic and prenatal testing for Huntington disease (HD) were studied by means of a postal questionnaire. The questionnaire contained questions about: approval of presymptomatic DNA-testing, informing individuals at-risk who do not request predictive testing, referral to a clinical genetics center, and opinions about different strategies of informing and supporting individuals at-risk. The response rate was 62%. More than two-thirds of the GP's considered post-test counselling and support as their responsibility. Twenty-six per cent were of the opinion that the test results should be disclosed by the GP. Fifty-nine per cent of GP's who had an individual at-risk in their practice were familiar with the test. The attitudes of GP's towards giving support and giving test results were independent of familiarity with the test and the incidence of HD-patients or at-risk individuals in the practice. Although GP's were willing to play an important role in presymptomatic DNA-testing procedures, there is a risk that they might underestimate the difficulties in communicating genetic information and the psychosocial effects of DNA-testing. Hence, we favor the premise that extensive pretest counselling and test disclosure should remain the prime responsibility of the clinical geneticist. Increasing involvement of GP's should, however, be encouraged and combined with appropriate postgraduate education about predictive DNA-testing in general.

Transtympanic ventilator tubes in the treatment of seromucous otitis. Indications and results.

400 patients with bilateral secretory otitis media (SOM) were treated with ventilating tubes (VT) in a prospectiv study. The ear drums were normal on both sides before VTs treatment thus allowing ear drum changes and complications during VT treatment to be recorded. 618 VT were placed in the ear drum after suction of the fluid. In 182 patients unilateral myringotomy with suction of fluid were done and VT placed in the contralateral ear. Adenoidectomy with myringotomy, with an obstructing adenoid, gave 30% better chance. 10 different VTs were used. The most frequent pathology found in the ear drum after one period of VT treatment was tympanosclerosis. In the ears only treated with myringotomy tympanosclerosis occurred in 1%. 3 factors seemed to give more tympanosclerosis: metal (stainless steel or titanium), polyethylene and prolonged stay-time in the ear drum. Chronic perforations of the ear drum occurred with great variations between the different tubes. The Goode modified T-tube caused perforations in 17%. In the other VTs the perforations occurred in 2.1%. Chronic perforation together with tympanosclerosis will happen more often when the VT is made of polyethylene compared to silicone or fluoroplastic (p < 05). 90% of the perforations were located at the site of the VT. The ideal VT will stay in for 8-18 months at an average and it can be shown to improve middle ear function better than only waiting or myringotomy. Long-term VTs should not be used at the first VT procedures.

Spontaneous cor pulmonale in laboratory beagles.

Right heart failure associated with postmortem evidence of pulmonary hypertension (cor pulmonale) was observed in nearly 1% of the young beagles of a large research colony. During the past 18 years, 176 dogs with cor pulmonale were observed. Most cases occurred between September and April of each year. Nearly equal numbers of males and females were involved, and some siblings were affected. Ninety-six percent of known affected dogs died, and 85% of the deaths occurred by 5 weeks of age. Clinically, most dogs were stunted and exhibited ascites, subcutaneous edema, hypothermia, dyspnea, cyanosis, and systolic murmur. Radiography revealed cardiomegaly, and electrocardiography revealed right axis deviation and an enlarged right atrium. Postmortem evidence of cor pulmonale included subcutaneous edema, ascites, hydrothorax, mediastinal and mesenteric edema, splenomegaly, centrolobular hepatic congestion and necrosis, right ventricular hypertrophy, interstitial pneumonia, and medial hypertrophy of pulmonary arteries and arterioles. The specific cause of the disease was not determined.

Osteopenia with decreased bone formation in beagles with malabsorption syndrome.

Morphometric and bone density studies were performed on bones from 10 healthy adult dogs and 9 dogs that had exhibited signs of intestinal malabsorption for variable periods of time. The dogs with malabsorption syndrome had a marked decrease in the amount of trabecular bone in lumbar vertebrae (P less than 0.001). Evaluation of undecalcified rib cross sections revealed these dogs had a decrease in trabecular thickness (P less than 0.01) and cortical area (P less than 0.01). There was a decrease in the proportion of the trabecular surface covered with osteoblasts (P less than 0.01) and an increase in resting resorption surface (P less than 0.01) and trabecular specific surface (P less than 0.01). Three of the dogs with malabsorption syndrome and all control dogs were labeled with oxytetracycline prior to sacrifice. The dogs with malabsorption syndrome had a decreased number or complete absence of labeled bone formation sites when compared to controls. No difference was found in bone mineral density in the malabsorption cases as a group, although 1 of the dogs that had an increase in percent osteoid volume and percent osteoid-covered surface had lower ash/ml in trabecular bone samples from lumbar vertebrae. Parathyroid gland weights were available for 6 of the 9 dogs, and these were not significantly different from controls. The findings indicate that decreased bone formation, probably due to the poor nutritional status associated with malabsorption, was an important factor in the development of osteopenia.