H.H. de Boer

COGNITIVE CHANGES DURING GROWTH HORMONE REPLACEMENT IN ADULT MEN

The present study evaluates the effects of 2 years of growth hormone (GH) replacement therapy on psychological well-being and cognitive performance in adults with childhood-onset growth hormone deficiency (CO-GHD). A total of 48 GHD adult men (mean age: 27 years) were randomly assigned to one of four treatment groups: placebo treatment, or GH replacement in a dose of 1, 2, or 3 IU/m2, respectively. Placebo treatment was given for 6 months. Psychological assessments were made every 6 months. Assessments included somatic and psychological complaints, depression, fatigue, vigor, tension, state/trait anxiety, iconic memory, short-term memory, long-term memory and perceptual-motor skill. GH treatment was considered physiological if the observed insulin-like growth factor-I (IGF-I) levels were within the normal range. It was considered supraphysiological if serum IGF-I rose to a value exceeding the upper normal limit. During the placebo-controlled phase of the study the changes in memory performance were positively correlated to the GH induced changes in serum IGF-I concentration and, more weakly, to the daily GH substitution dose. At 6 months memory only had improved in the group receiving supraphysiological GH treatment, but not in the group of patients who had a normalization of serum IGF-I. However, after 1 year of treatment a normalization of memory functioning was found in both groups of patients and this was preserved during the 2nd year of treatment. No changes were observed in psychological well-being and perceptual-motor skill. We conclude that GH replacement improves memory function in adults with CO-GHD. It has no effect on psychological well-being or perceptual-motor skill. Supraphysiological treatment accelerates the recovery of memory performance. However, the long-term effects are not different from those achieved with physiological GH replacement.

Effects of recombinant human growth hormone in patients with severe sepsis

The objective of this study was to evaluate the safety and the effect of recombinant exogenous growth hormone (GII) on nitrogen production in patients with severe sepsis. It was designed as a prospective, randomized, placebo-controlled trial, and performed in the medical intensive care unit of a university hospital. Twenty patients admitted with septic shock and receiving standard parenteral nutrition served as subjects. Treatment consisted of GH 0.1 mg/kg/day or placebo administered as continuous intravenous infusion on the second, third, and fourth days after admission. The study period was eight days. During GH administration, nitrogen production decreased significantly in the GH group and increased in controls (p < 0.01). Nitrogen balance became slightly positive in the GH group during treatment: 1.2 ± 6.4 versus controls −3.7 ± 3.8 g/day (day 3) (p < 0.05). Within 24 hours after cessation of treatment, differences between GH and controls disappeared. 3-Methylhistidine excretion as a measure of absolute muscle breakdown declined during the study period, but did not differ between groups. The levels of insulin, insulinlikc growth factor 1, glycerol, free fatty acids, and β-hy-droxybutyrate increased during treatment. Despite continuous intravenous administration, GH levels gradually declined during the 3 treatment days, indicating increased metabolic clearance. Side effects other than insulin resistance were not observed. Growth hormone administration reduces nitrogen production and improves nitrogen balance in patients with severe sepsis. These effects are not sustained after cessation of treatment.

Effects of human growth hormone in critically ill nonseptic patients: Results from a prospective, randomized, placebo-controlled trial

OBJECTIVESnTo study the effects of growth hormone administration on insulin-like growth factor I concentration, nitrogen balance, and fuel utilization, and to study its safety in critically ill nonseptic patients.nnnDESIGNnProspective, randomized, placebo-controlled trial.nnnSETTINGnMedical intensive care unit of a university hospital.nnnPATIENTSnEighteen critically ill nonseptic patients were studied for 8 days after admission.nnnINTERVENTIONSnGrowth hormone (0.1 mg/kg/day) or placebo was administered as a continuous intravenous infusion on the second, third, and fourth days after admission. The study period was 8 days.nnnMEASUREMENTS AND MAIN RESULTSnPlasma hormone concentrations were measured every 6 hrs and average daily values were calculated. The 24-hr urinary nitrogen and 3-methylhistidine excretion were measured. Indirect calorimetry was used to calculate fuel utilization. Insulin-like growth factor I concentrations increased in the treatment group from subnormal to normal values and remained increased despite discontinuation of growth hormone treatment (p = .02). Nitrogen balance differed between the groups upon admission: growth hormone group (3.9 +/- 4.1 g/day) vs. controls (13.8 +/- 5.4 g/day), but improved with growth hormone. This finding appeared independent of the imbalance between the groups. The 3-methylhistidine excretion was not different between the groups and did not change during growth hormone administration. Free fatty acids and glycerol concentrations increased during growth hormone treatment, but calculated fuel utilization did not change. During growth hormone treatment, insulin concentrations increased, due to the increased administration of insulin necessary for glycemic control. Side effects other than hyperglycemia were not observed.nnnCONCLUSIONSnGrowth hormone administration in a heterogeneous group of critically ill nonseptic patients resulted in normalization of insulin-like growth factor I levels, even after cessation of growth hormone treatment. Nitrogen balance improved, but this change was transient. Hence, growth hormone affects nitrogen balance, probably partly independent of insulin-like growth factor I.

An accessory skull suture mimicking a skull fracture

This paper describes an investigation of the sudden and unexpected death of a five-and-a-half-month-old boy. As in every Dutch case of sudden unexpected death in infancy (SUDI), a multidisciplinary diagnostic approach was used. This included post-mortem radiography, showing a linear discontinuity of the parietal bone. Originally this was interpreted as a skull fracture, but autopsy indicated no signs of mechanical trauma. Instead the defect was defined as a unilateral accessory suture of the parietal bone. The initial erroneous diagnosis had severe adverse consequences and thus every health care professional or forensic specialist dealing with paediatric mechanical traumas should be cautious of this rare anomaly.

Cranial trauma and the assessment of posttraumatic survival time

Assessment of trauma on skeletal remains can be very difficult, especially when it comes to the estimation of posttraumatic survival time in partially healed lesions. The ability to reliably estimate the time an individual has survived after sustaining an injury is especially important in cases of child abuse and torture, but can also aid in determining the association between an injury and eventual death. Here a case from South Africa is reported, where the skeletal remains of an unknown individual were found with cranial and scapular fractures. These fractures all presented with macroscopic features indicative of healing. Using recently published data on the timing of fractures by De Boer et al., the two sets of cranial trauma and the scapular fracture were assessed by means of radiology, histology and microCT scanning. This was primarily done in order to obtain more information on the events surrounding the death of this individual, but also to assess the usability of the published methods on cranial fractures. It was found that the initial trauma was most likely sustained at least two weeks before death, whilst a neurosurgical procedure was performed at least one week before death. It seems that cranial fractures, especially if stable, may show some different healing features than postcranial fractures. The individual has since been identified, but unfortunately as is often the case in South Africa, limited information is available and the medical records could not be found.

Dutch population specific sex estimation formulae using the proximal femur

Sex estimation techniques are frequently applied in forensic anthropological analyses of unidentified human skeletal remains. While morphological sex estimation methods are able to endure population differences, the classification accuracy of metric sex estimation methods are population-specific. No metric sex estimation method currently exists for the Dutch population. The purpose of this study is to create Dutch population specific sex estimation formulae by means of osteometric analyses of the proximal femur. Since the Netherlands lacks a representative contemporary skeletal reference population, 2D plane reconstructions, derived from clinical computed tomography (CT) data, were used as an alternative source for a representative reference sample. The first part of this study assesses the intra- and inter-observer error, or reliability, of twelve measurements of the proximal femur. The technical error of measurement (TEM) and relative TEM (%TEM) were calculated using 26 dry adult femora. In addition, the agreement, or accuracy, between the dry bone and CT-based measurements was determined by percent agreement. Only reliable and accurate measurements were retained for the logistic regression sex estimation formulae; a training set (n=86) was used to create the models while an independent testing set (n=28) was used to validate the models. Due to high levels of multicollinearity, only single variable models were created. Cross-validated classification accuracies ranged from 86% to 92%. The high cross-validated classification accuracies indicate that the developed formulae can contribute to the biological profile and specifically in sex estimation of unidentified human skeletal remains in the Netherlands. Furthermore, the results indicate that clinical CT data can be a valuable alternative source of data when representative skeletal collections are unavailable.

Four possible cases of osteomalacia: The value of a multidisciplinary diagnostic approach

Rickets and residual rickets are often encountered in Dutch archeological skeletal samples. However, no archeological Dutch paleopathological case of adult osteomalacia has been described in literature to date. This paper describes the first four archeological Dutch paleopathological cases of osteomalacia and assesses the value of the various modalities (macroscopic assessment, radiology and histology) that may be used for diagnosis. The skeletal remains investigated originate from the Meerenberg psychiatric hospital cemetery in Bloemendaal, the Netherlands, and date from 1891 - 1936. The remains of 69 adult individuals were inspected for macroscopic lesions which may be associated with osteomalacia. In cases suspect for osteomalacia, complimentary radiological and histological investigations (BSE-SEM and light microscopy) were performed. Macroscopically, four individuals presented with lesions (highly) suggestive of osteomalacia. Histological examination (both BSE-SEM and light microscopy) provided valuable information to come to an eventual diagnosis of osteomalacia in all four cases. Light microscopy proved to be an feasible alternative for BSE-SEM. The added value of radiological analyses was limited. The individuals identified were most likely patients in the psychiatric hospital, and the reason for their institutionalization and/or the regime in the institution may have played a role in the development of the osteomalacia observed.