Jorma Kokkonen

Macronutrient and energy contents of human milk fractions during the first six months of lactation.

AIMnTo study the macronutrient and energy contents of human milk fractions during the first 6 mo of lactation.nnnSTUDY DESIGNnA total of 483 milk samples, including 52 pairs of fore- and hindmilk samples from 20 mothers, 253 samples from 53 donor mothers and 126 samples from 36 mothers of preterm infants, were collected longitudinally, starting at 1 wk postpartum and continuing monthly up to 6 mo. Protein, lactose and fat contents were measured and energy density estimated.nnnRESULTSnThe protein content was significantly lower in fore- and hindmilk than in donor or preterm milk during the first months of lactation. In donor and preterm milk, the protein content declined consistently from 2.0 g/100 ml at 1 wk to half of that at 6 mo, and a similar trend was observed in fore- and hindmilk. Lactose content showed no significant changes between the groups or in the course of lactation. The fat content was highest in hindmilk, being approximately two- to threefold that of foremilk. Accordingly, hindmilk included 25-35 kcal/100 ml more energy on average than foremilk.nnnCONCLUSIONSnThe fat content of human milk increases in relation to breast emptying, while the other macronutritients of milk show only slight changes. When enteral feeding with high-energy human milk is preferred, as in the case of very preterm infants, hind milk, with its higher fat content, would be a natural choice.

A 10-year prognosis for childhood allergic rhinitis

The prognosis of allergic rhinitis was studied in 154 children aged 3‐17 years at diagnosis by means of a detailed questionnaire administered 8‐11 years later. The symptoms had completely disappeared in only 15 (10%) patients. The conjunctival symptoms, however, had disappeared or were controlled successfully by topical drug therapy in almost all, and 77 (50%) were managing without medication for allergic rhinitis. Twenty‐five (23%) of the 110 children with seasonal allergic rhinitis had a perennial disease at follow‐up, in contrast to seven (16%) of 44 with perennial allergic rhinitis originally who had only seasonal symptoms at follow‐up. Asthma or wheezing had developed in 29 cases (19%) and was more common (p < 0.01) among those with perennial allergic rhinitis (15 of 44) than among those with seasonal allergic rhinitis (14 of 110). No significant association was found between age at onset of symptoms, family history of atopic disease or type of treatment for allergic rhinitis and allergic rhinitis still present at follow‐up or development of asthma during the observation period.

Social adaptation of young adults with congenital heart disease

The social status of 71 young adults (30 females, 41 males, aged 22.9 +/- 1.9 yr) with congenital heart disease was compared with that of 211 (106 females, 105 males, mean age 23.2 +/- 1.4 yr) randomly selected controls. The clinical examinations included clinical study with ultrasonic visualization, electrocardiography, X-ray and measurement of exercise capacity. In the study group 87% had completed school at the secondary level and another 21% at high school level, while the corresponding figures in the control group were 98% and 51%. About half of both groups continued to vocational training and a fifth to a higher level. Those without any vocational education made up 32% of the study group (95% confidence interval 21-43%) and 11% of the controls (95% confidence interval 7-15%). State benefits were the main source of income for 13% of the study group as compared to 2% among the controls. The employment status of the actual labour force showed no significant difference between the groups. Among patients with congenital heart disease there were significantly more of those who had developed a dependent life style, living with their parents without a marital or quasi-marital relationship. A cyanotic type of severe heart defect is one of the factors predisposing to poor success at school and a dependent lifestyle. Congenital heart disease, even when treated, is a significant factor which influences adult life. The results call for more practical support to assist psychosocial maturation, especially in patients with residual defects.

Children with untreated food allergy express a relative increment in the density of duodenal γδ+ T cells.

(2000). Children with Untreated Food Allergy Express a Relative Increment in the Density of Duodenal ?d+ T Cells. Scandinavian Journal of Gastroenterology: Vol. 35, No. 11, pp. 1137-1142.Background: We investigated whether children with food allergy (FA) express increased densities of intraepithelialg x87 T cells similarly to subjects with celiac disease. Methods: The duodenal specimens taken by gastroduodenoscopy from 20 children with untreated FA, 17 with treated FA, 12 with celiac disease (CD) and 12 controls were studied with monoclonal antibodies and a three-layer peroxidase staining method. Results:The subjects with untreated FA expressed equal densities of total intraepithelial CD3x87 anda/b x87 T cells, but significantly higher densities of g x87 cells than the subjects currently on an elimination diet for FA or the controls. Accordingly, their g x87/CD3x87 ratio was higher. On the other hand, the results differed clearly from CD, where all the three cell populations showed high densities. Another finding that discriminated the subjects with FA from the CD patients was endoscopic examination. Lymphonodular hyperplasia (LNH) of the duodenal bulb with a normal villous pattern was demonstrated in 14 (70%) of the 20 subjects with untreated FA and in 8 (47%) of the 17 with treated FA, but in none of the celiac patients or controls. Surprisingly, the biopsy samples from the subjects with FA showed quite normal histological findings. Conclusions:According to this preliminary observation, high densities of intraepithelialg x87 T cells and a significantly elevated g x87/CD3x87 ratio are associated with untreated FA. If seen LNH in a gastroduodenoscopy and/or increased densities of g x87 T cells in the biopsy specimen, the possibility of gastrointestinal FA should be reliably assessed by a food challenge.

THE LONG-TERM EFFECTS OF CHILDREN'S EARLY-ONSET DISABILITY ON MARITAL RELATIONSHIPS

To investigate the long‐term effects of a childs chronic illness or severe physical or intellectual disability on parents and their marital relationship, the parents of 89 children, aged 14–17, years were interviewed. The parents returned a questionnaire and a social worker interviewed them. One‐fifth of the respondents had experienced the childs disability as contributing positively to the marital relationship, 25% reported impairment in some areas of the marital relatonship, while only 7% felt that they had drawn apart from each other. A higher level of occupational education, insecurity at onset, heavy daily demands for care of the child, unequal distribution of tasks between the spouses and a lack of time for leisure activities were found to be risk factors for impaired marital satisfaction. Adequate information, a realistic notion of the illness or disability and practical advice for everyday life seemed to be the protective factors for the marital relationship.

Long-term Clinical Outcome in Patients With Congenital Chloride Diarrhea

Objectives: Congenital chloride diarrhea (CLD) is a rare, autosomal recessive disorder of intestinal Cl−/HCO3− exchange caused by mutations in the SLC26A3 gene and characterized by persistent Cl− rich diarrhea from birth. Treatment is symptomatic and replacement therapy with NaCl and KCl has been shown to be effective in children, but the long-term prognosis remains unclear. We studied the largest known cohort of patients to evaluate the long-term outcome of CLD and to search for extraintestinal manifestations. Methods: This is a cross-sectional clinical evaluation and retrospective analysis of medical history of 36 Finnish patients with CLD, born in the 1960s (n = 8), 1970s (n = 7) and 1980s (n = 21). Results: Early diagnosis and aggressive salt replacement therapy were associated with normal growth and development, in addition to significantly reduced mortality rates among the groups of patients born in the different decades, respectively (P = 0.001). No deaths due to CLD were observed after 1972. Enuresis, slight soiling and hospitalizations for gastroenteritis were common, especially in childhood, but 92% of the patients found their health excellent or good. Complications documented were end-stage renal disease (n = 1) and hyperuricemia (n = 4), novel findings possibly associated with CLD being male subfertility (n = 3), spermatoceles (n = 3), intestinal inflammation (n = 2), inguinal hernias (n = 4) and increased concentrations of sweat Cl− in 12% of the patients. Conclusions: When early diagnosed and adequately treated, the long-term prognosis of CLD is favorable. A putative role of a primary anion exchange defect of SLC26A3 in male subfertility and the decline of renal function due to chronic dehydration deserve further characterization.

Gastrointestinal complaints and diagnosis in children: a population-based study.

Aim: To find out the extent to which children at 10–11 y of age suffer from various gastrointestinal complaints and how often a food‐induced or other diagnostic disorder might be assessed behind them, we carried out a population‐based survey of 404 children in a rural Finnish town. Methods: A questionnaire filled in retrospectively by their parents was used to describe the frequency of various abdominal symptoms during the previous 2 y and to select the symptomatic subjects for closer clinical examination. In the clinical investigation of the children, an elimination challenge with milk protein and lactose intolerance tests, as well as endoscopic examinations in selected cases and blood tests, were performed. Results: In all, 110 (27%) subjects reported some gastrointestinal (GI) complaints during the last 2 y; 64 (16%) meeting the Apley criteria for recurrent abdominal pain. A specific organic or functional disorder was found in 26 subjects (6%), two having no GI symptoms. Milk protein intolerance was the most common specific disorder diagnosed in nine subjects (2.2%), followed by lactose intolerance in eight (2%), coeliac disease in five (1.2%) and Helicobacter pylori infection in three (0.7%). An endoscopic examination performed on 17 subjects (4.2%) and a colonoscopy on three revealed significant findings in 11; lymphonodular changes being most common, occurring in five subjects. Subjects with milk protein‐induced disorders showed significantly lower IgA‐class antibodies to milk and its fractions than the non‐symptomatic controls. Chronic diseases, short breastfeeding, GI problems and food intolerance during the first year of life were observed as significant risk factors in determining whether a subject belonged to the group experiencing any GI complaints.

Assignment of the Locus for Congenital Lactase Deficiency to 2q21, in the Vicinity of but Separate from the Lactase-Phlorizin Hydrolase Gene

Congenital lactase deficiency (CLD) is an autosomal recessive, gastrointestinal disorder characterized by watery diarrhea starting during the first 1-10 d of life, in infants fed lactose-containing milks. Since 1966, 42 patients have been diagnosed in Finland. CLD is the most severe form of lactase deficiency, with an almost total lack of lactase-phlorizin hydrolase (LPH) activity on jejunal biopsy. In adult-type hypolactasia, the most common genetic enzyme deficiency in humans, this enzyme activity is reduced to 5%-10%. Although the activity of intestinal LPH has been found to be greatly reduced in both forms, the molecular pathogenesis of lactase deficiencies is unknown. On the basis of the initial candidate-gene approach, we assigned the CLD locus to an 8-cM interval on chromosome 2q21 in 19 Finnish families. At the closest marker locus, a specific allele 2 was present in 92% of disease alleles. On the basis of a genealogical study, the CLD mutation was found to be enriched in sparsely populated eastern and northern Finland, because of a founder effect. The results of both the genealogical study and the haplotype analysis indicate that one major mutation in a novel gene causes CLD in the Finnish population. Consequently, the critical region could be restricted further, to an approximately 350-kb interval, by ancient-haplotype and linkage-disequilibrium analyses. Surprisingly, the LPH gene was shown to lie outside the critical CLD region, excluding it as a causative gene for CLD. The LPH locus was found to reside >2 Mb from the critical CLD region.

Lymphonodular hyperplasia on the mucosa of the lower gastrointestinal tract in children: an indication of enhanced immune response?

Background To discover the prevalence and significance of lymphonodular hyperplasia (LNH) of the lower gastrointestinal tract, the authors did a retrospective analysis of a consecutive series of children using colonoscopy to evaluate persistent and severe gastrointestinal symptoms. The authors also sought to discover in more detail how often subjects with LNH of the terminal ileum (TI) or colon show an association with food allergy (FA). Methods The analysis included a consecutive series of 140 children evaluated at the Oulu University Hospital using colonoscopy, which extended to the TI in 74 of these children. A total of 102 patients underwent gastroduodenoscopy. The disease category was assessed using endoscopic, histopathologic, and clinical information. To diagnose FA, a masked or an open food challenge was administered to all patients who aroused any suspicion of food-related exacerbation of symptoms. Results Of 140 patients, LNH of the colon was diagnosed in 46 subjects, 9 of 38 patients had colitis, 1 of 8 patients had Crohn disease, and 36 of the remaining 94 subjects did not have colitis. Twelve patients of the 22 with LNH of the colon (55%) showed concomitant LNH on the bulb of the duodenum. Lymphonodular hyperplasia of the TI was diagnosed in 53 of the 74 subjects in whom TI could be visualized. It was seen in most patients without colitis (80%), in one half the subjects with colitis (48%), and in one quarter of those with Crohn disease (25%). Among the whole study group 37 (26%) could be defined as having FA. It was more prevalent in patients with (52%) than in those without (13%) LNH of the colon (P < 0.001). The presence of LNH in the TI also showed some association with FA (P < 0.05), but less than did LNH of the colon. Conclusion We consider LNH on the mucosa of the colon or TI common but not an innocent bystander. Significantly related to a diagnosis of gastrointestinal FA in this study, it is an expression of mucosal immune response. If detected on the colon, FA should be considered, whereas if present in TI, it may be related to FA but also to a variety of other immunologically active disease states.

Mutations in the Translated Region of the Lactase Gene (LCT) Underlie Congenital Lactase Deficiency

Congenital lactase deficiency (CLD) is a severe gastrointestinal disorder characterized by watery diarrhea in infants fed with breast milk or other lactose-containing formulas. We initially assigned the CLD locus by linkage and linkage disequilibrium on 2q21 in 19 Finnish families. Here we report the molecular background of CLD via characterization of five distinct mutations in the coding region of the lactase (LCT) gene. Twenty-seven patients out of 32 (84%) were homozygous for a nonsense mutation, c.4170T-->A (Y1390X), designated Fin(major). Four rare mutations--two that result in a predicted frameshift and early truncation at S1666fsX1722 and S218fsX224 and two point mutations that result in substitutions Q268H and G1363S of the 1,927-aa polypeptide--confirmed the lactase mutations as causative for CLD. These findings facilitate genetic testing in clinical practice and enable genetic counseling for this severe disease. Further, our data demonstrate that, in contrast to common adult-type hypolactasia (lactose intolerance) caused by a variant of the regulatory element, the severe infancy form represents the outcome of mutations affecting the structure of the protein inactivating the enzyme.