Neonatal diabetes, with hypoplastic pancreas, intestinal atresia and gall bladder hypoplasia: search for the aetiology of a new autosomal recessive syndrome.

AIMS/HYPOTHESIS: Neonatal diabetes is a rare disease with several identified molecular aetiologies. Despite associations with other malformations, neonatal diabetes with intestinal and biliary anomalies has not been described. The current study aims to describe a new syndrome, and to examine a possible link with one of three genes known to cause neonatal diabetes. METHODS: Five clinical cases are described. Immunohistochemical staining for pancreatic islet hormones was performed on three of the infants. DNA from one infant was analysed for abnormalities of the PLAGL-1 (ZAC), glucokinase and PDX-1 (IPF-1) genes. RESULTS: Five infants (two sibling pairs from two families, and an isolated case) presented with neonatal diabetes, hypoplastic or annular pancreas, jejunal atresia, duodenal atresia and gall bladder aplasia or hypoaplasia. One sibling pair was born to consanguineous parents. One patient with a milder form is surviving free of insulin. Four children died in the first year of life despite aggressive medical management. Pancreatic immunohistochemistry revealed few scattered chromogranin-A-positive cell clusters but complete absence of insulin, glucagon and somatostatin. Exocrine histology was variable. In one case from the consanguineous family, molecular analysis showed no duplication or uniparental isodisomy of PLAGL-1 at 6q24, no contiguous gene deletion involving the glucokinase gene, and no mutation in the coding sequences or splice sites of PDX-1. CONCLUSIONS/INTERPRETATION: This combination of multiple congenital abnormalities has not been previously described and probably represents a new autosomal recessive syndrome involving a genetic abnormality that interferes with normal islet development and whose aetiology is as yet unknown.

[Physical activity--what minimal level is sufficient seen from health perspective?]. / Fysisk aktivitet--hvilket minimum er tilstraekkeligt i et sundhedsmaessigt perspektiv?

Physical inactivity represents an important risk factor for development of cardiovascular and metabolic disease and is tightly coupled to a reduced energy expenditure both at work and during leisure activities. Although comprehensive physical training is known to influence oxygen uptake capacity, muscle strength and metabolic factors, also increased weekly energy expenditure achieved through activities with moderate intensity will influence risk factors such as hypertension, insulin resistance, oxidative metabolism in skeletal muscle and a low HDL/total cholesterol ratio beneficially and improve metabolic fitness. To achieve this, all adults should aim at a total of 30 min of moderate physical activity daily, preferentially through activities that can be a natural part of daily living (walking, cycling or gardening). This recommendation can also be achieved through accumulation of several minor activity periods of 5-10 min each. Further increase in amount or intensity of physical activity above the minimal recommendations improves the morbidity preventive effect further, although several risk factors show a curvelinear and levelling-off pattern of their dosis-response curve between training and risk factors.

Effects on the foetus of exercise in pregnancy.

Maternal training during pregnancy has been the subject for numerous investigations lately, which are presented in this survey. No studies in human beings have shown any negative effect of training on the embryogenesis. During physical training a small rise in foetal heart rate of 5-25 bpm is a common finding. This could be due to a reduction in oxygen delivery or more likely stimulation from maternal vasoactive hormones or training-induced uterine contractions. Foetal growth seems to be influenced by maternal activity, as some investigations have found significantly bigger babies born by moderately trained females compared to non-trained or heavily trained women. In the latter group the reduction could be explained by a reduced neonatal fat mass. Increased maternal temperature during training has not been found to lead to any foetal abnormalities. The results indicate that moderate training during pregnancy can be recommended with observance of simple directives.

[Positron-emission tomography with gamma camera in patients with colorectal and anal cancer. Preliminary results]. / Positron-emissionstomografi med gammakamera hos patienter med kolorektal cancer og analcancer. Praeliminaere resultater.

Metastasectomy after the primary surgical treatment of colorectal cancer may prolong survival in patients with resectable recurrences. Dedicated 18F-FDG-PET is of growing interest as a diagnostic tool in the staging and diagnosis of recurrent disease. We wanted in our departments to investigate whether a dual-head gamma camera with coincidence detection could serve as a substitute for the dedicated PET scanner. Twenty consecutive PET scans of 18F-FDG were performed by means of an Adac VertexPLUS gamma camera in 14 patients with colorectal cancer and four patients with anal cancer with known or suspected recurrences. Evaluation of the patients were, however, according to the routine in the department. In fourteen patients one or more abnormal foci were detected by PET, nine of these were verified by biopsy and one by renewed CT scan. In the four patients with negative PET the findings were in agreement with later biopsies. In one patient PET was "falsely" negative with regards to other processes than a solitary metastasis to be removed, as he six months later revealed dissemination confirmed by biopsy. Four patients with positive PET findings and elevated CEA remain to be evaluated. We conclude that PET with a coincidence detection gamma camera in this preliminary study seems to have the same possibilities to stage and diagnose recurrent anal- and colorectal cancer as the dedicated PET scanner.

[Effect of specific training on menstruation and bone strength]. / Specifik traenings indvirkning på menstruation og knoglestyrke.

Secondary amenorrhoea is found with increased incidence in female athletes performing hard endurance training, especially when combined with demands for a low body weight. The etiology is multifactorial, but the energy balance (energy intake) in relation to the amount and intensity of training probably plays a crucial role. Long-lasting amenorrhoea may reduce the bone mineral content, perhaps partly irreversibly, especially in the lumbar vertebrae in long-distance runners. In gymnasts and light-weight rowers with a similarly high incidence of amenorrhoea, a much less pronounced effect on the lumbar bone mineral content has been reported in a few, small studies, pointing to a possible positive influence of specific training. The finding of stress fractures in an amenorrhoeic athlete should lead to further evaluation of the bone mineral status.

[Effects of maternal physical training on the fetus]. / Føtale effekter af maternel traening.

The latest results of influences of physical training during pregnancy on the foetus are presented. In humane, no pathological effects on the embryogenesis have been demonstrated. During exercise, a modest increase (5-25 bpm) in foetal heart rate is a common finding. This might be caused by reduced oxygen supply to the foetus, but could more likely be due to stimuli from vasoactive hormones or training-induced uterine contractions. Foetal growth seems to be influenced by maternal training, as moderate training has resulted in significantly bigger babies compared to both inactivity and hard training. In one study it was shown that low body weight in babies from hard-training mothers was due to reduced neonatal fat mass. Pathological sequelae due to increased maternal temperature during training have not been found in humans. The results strongly suggest that moderate training during pregnancy can be recommended if simple precautions are taken.

Does the decrease in heart rate prevent a detrimental decrease of the end-systolic volume during central hypovolemia in man?

Central hypovolemia occurring with epidural anesthesia was investigated by measurement of hemodynamic and endocrine variables in 10 patients. Responses fell into two categories. Four patients experienced a hypotensive bradycardic episode after seventeen +/- four minutes. In this group epidural anesthesia initially induced a tendency toward an increase in heart rate from 65 +/- 4 to 73 +/- 5 beats/min concomitantly with decreases in end-diastolic (172 +/- 22 to 138 +/- 16 mL), end-systolic (67 +/- 12 to 51 +/- 9 mL), and stroke (105 +/- 10 to 85 +/- 7 mL) volumes (radionuclide cardiography). A subsequent decrease in mean arterial pressure from 76 +/- 3 to 67 +/- 4 mmHg was associated with a decrease in venous return as reflected by the decrease in cardiac output from 6.1 +/- 0.4 to 4.7 +/- 0.7 L/min. In this situation when the venous return was critically reduced, the heart rate was 49 +/- 4 beats/min and no further reduction in end-diastolic and end-systolic volumes was observed. The observed endocrine changes were compatible with a response to central hypovolemia. In the other 6 patients the reaction to epidural anesthesia did not induce statistically significant changes in hemodynamic and endocrine variables. It is concluded (1) that the decrease in heart rate associated with central hypovolemia during epidural anesthesia seems to be elicited when the left ventricular end-systolic volume is decreased by about 25% and (2) that a further decrease in end-systolic volume during progressive central hypovolemia is avoided possibly as a direct consequence of the slowing of the heart.

Comparison of insulin-mediated and glucose-mediated glucose disposal in patients with insulin-dependent diabetes mellitus and in nondiabetic subjects.

To determine whether glucose-mediated as well as insulin-mediated regulation of glucose utilization and glucose production is impaired in patients with insulin-dependent diabetes mellitus (IDDM), six nonobese, diabetic patients and seven age-, sex-, and weight-matched nondiabetic subjects were studied. Despite slightly higher free insulin concentrations in the diabetic patients than in the nondiabetic subjects during 0.2 mU/kg X min (22 +/- 3 versus 15 +/- 2 microU/ml) and 1.0 mU/kg X min (98 +/- 10 versus 75 microU/ml) insulin infusions, glucose utilization at plasma glucose concentrations of 95, 135, and 175 mg/dl was lower in the diabetic patients than in the nondiabetic subjects. The increment in glucose utilization per increment in plasma glucose (i.e., slope) in the diabetic and nondiabetic subjects, respectively, did not differ significantly during either the 0.2 (1.7 +/- 1.3 versus 1.4 +/- 0.5 dl/kg X min) or 1.0 (4.4 +/- 1.1 versus 6.2 +/- 1.0 dl/kg X min) mU/kg X min insulin infusions, although they tended to be higher in the nondiabetic subjects during the latter infusion. Thus, although stimulation of glucose utilization by insulin is impaired in patients with IDDM, the ability of an increase in glucose concentration to increase glucose utilization does not appear to differ from that present in nondiabetic subjects, at insulin concentrations in the low physiologic range. Whether differences exist in the high physiologic range remains to be determined.

The 2-deoxyglucose test as a supplement to fasting for detection of childhood hypoglycemia.

The acute response to simulated hypoglycemia induced by 2-deoxyglucose (2DG) was compared with the prolonged fasting test as a possible screening test for detection of childhood hypoglycemia. Ten children, ages 2-9 yr, without a documented history of hypoglycemia were classified retrospectively as reference subjects. While fasting, their plasma glucose decreased to an average of 50 mg/dl (range, 30-74) between 28-36 h. After infusion of 2DG, 50 mg/kg IV over 30 min, their plasma glucose increased by an average of 35 mg/dl (range, 19-56) between 60-120 min. The half-life of plasma 2DG was 48 min. Twenty-three other children in the same age range had an abnormal response to one or both of these tests. Thirteen of these children became definitely hypoglycemic while fasting (glucose less than 30 mg/dl) and also failed to increase their plasma glucose by more than 10 mg/dl after 2DG. Five children had plasma glucose values between 30-40 mg/dl during the first 24 h of fasting that were associated with a change in mental status but responded to 2DG with an increase in plasma glucose. The remaining five subjects had an apparently normal response to fasting but did not respond to 2DG; two of these had documented spontaneous hypoglycemia. No cases of documented hypoglycemia were undetected by either test. It is concluded that the 2DG test is a short safe supplement to fasting which is equally effective as the prolonged fasting test in detecting hypoglycemia. Neither test alone is completely reliable, but the combination is complementary.

The 2-deoxyglucose test as a supplement to fasting for detection of childhood hypoglycemia.

The acute response to simulated hypoglycemia induced by 2-deoxyglucose (2DG) was compared with the prolonged fasting test as a possible screening test for detection of childhood hypoglycemia. Ten children, ages 2-9 yr, without a documented history of hypoglycemia were classified retrospectively as reference subjects. While fasting, their plasma glucose decreased to an average of 50 mg/dl (range, 30-74) between 28-36 h. After infusion of 2DG, 50 mg/kg IV over 30 min, their plasma glucose increased by an average of 35 mg/dl (range, 19-56) between 60-120 min. The half-life of plasma 2DG was 48 min. Twenty-three other children in the same age range had an abnormal response to one or both of these tests. Thirteen of these children became definitely hypoglycemic while fasting (glucose less than 30 mg/dl) and also failed to increase their plasma glucose by more than 10 mg/dl after 2DG. Five children had plasma glucose values between 30-40 mg/dl during the first 24 h of fasting that were associated with a change in mental status but responded to 2DG with an increase in plasma glucose. The remaining five subjects had an apparently normal response to fasting but did not respond to 2DG; two of these had documented spontaneous hypoglycemia. No cases of documented hypoglycemia were undetected by either test. It is concluded that the 2DG test is a short safe supplement to fasting which is equally effective as the prolonged fasting test in detecting hypoglycemia. Neither test alone is completely reliable, but the combination is complementary.

Identification of human connective tissue in transplant of human oral mucosa in nude mice.

The present study describes a method for identification of connective tissue of human oral mucosal transplants in nude mice. The method was based on the development of a murine antiserum to human fibroblasts. After absorption with murine fibroblasts the antiserum in an immunofluorescence method appeared to react specifically with human connective tissue of frozen sections, whereas the antiserum did not react with murine connective tissue. The antiserum, applied to frozen sections of human oral mucosal transplants in nude mice, could distinguish between human and murine connective tissue in the sections. The ability to distinguish between the two types of tissue was utilized to elucidate a possible relation between epithelial morphology and underlying type of connective tissue. It was found that the formation of rete ridges of transplanted human oral epithelium was dependent on the presence of subepithelial human connective tissue. The method described may be useful for the recognition of human tissue in experimental studies of human transplants to other species.