Dysgénésies gonadiques et métabolisme osseux

Gonadal dysgenesis is defined as congenital hypogonadism related to abnormalities of the sex chromosomes. Because sex steroids play a central role in the acquisition and maintenance of bone mass, studies have been done to investigate bone status in patients with gonadal dysgenesis, particularly Turner's syndrome and Klinefelter's syndrome, which are the two most common types. The severe estrogen deficiency characteristic of Turner's syndrome (44, X0) is associated with a significant bone mass decrease ascribable to increased bone turnover, as shown by histological studies and assays of bone turnover markers. Estrogen therapy is followed by a significant bone mass gain and a return to normal of bone turnover markers, suggesting that it is the estrogen deficiency rather than the chromosomal abnormality that causes the bone mass deficiency, although abnormalities in the renal metabolism of vitamin D have been reported. Combined therapy with estrogens and growth hormone seems beneficial during the prepubertal period. In Klinefelter's syndrome (47XXY),  serum testosterone levels are at the lower end of the normal range and dihydrotestosterone levels are low. Histological studies show depressed osteoblast function and a decrease in 5-alpha-reductase activity responsible for partial tissue resistance to androgens. Assays of bone turnover markers show evidence of increased bone turnover. The bone deficiency is most marked at the femoral neck and seems correlated with serum testosterone and estradiol levels. Androgen therapy has favorable effects on the bone only if it is started before puberty. Recent data suggest that estrogens may contribute to the development of demineralization in KS and that bisphosphonate therapy may be beneficial.     

Myélolipome présacré

Presacral myelolipoma is a rare benign tumour of unknown aetiology, composed of mature adipose tissue with intermixed normal haematopoietic cells. Computed tomography is of help in the diagnosis but biopsy is mandatory in order to avoid unnecessary surgery. A case is reported.     

Les cystadénocarcinomes pancréatiques sont-ils des cystadénomes mucineux dégénérés?

Objectives of the studyTo define arguments in agreement or disagreement with the generally accepted theory of transformation from benign mucinous cystadenoma (MC) to malignant cystadenocarcinoma (CC) of the pancreas.MethodsA review of the literature since 1978 was conducted together with a comparative analysis of a multicentre retrospective study of the different mucinous cystic tumours of the pancreas: 150 MC, 79 CC and 55 intraductal papillary mucinous tumours of the pancreas (TIPMP). Multiple epidemiological and clinicopathological data were compared between MC and CC: mean age at diagnosis, sex distribution, association with diabetes or concurrent cancer, tumour location and size, type of pancreatic main duct communication, pancreatic fibrosis and serum CA 19-9 levels. The analysis concerned also histopathological features of resected cystadenocarcinomas (n = 58).ResultsTwo features suggested malignant transformation of mucinous cystadenomas: older mean age at diagnosis of CC and histological characteristics revealing areas of benign-appearing epithelium associated with areas of invasive carcinoma in 55% of cases. Conversely, two statistically significant discordant features were observed: a higher proportion of men (40% for CC vs 13% for MC) and a more frequent location in the head of the pancreas (49% vs 27%). The other differences were not in contradiction with the malignant transformation of MC: associated diabetes mellitus, increasing serum CA 19-9 levels and chromosomal aberrations were more frequent in CC. TIPMP were predominant in men (67%), and more common in the head of the pancreas (67%).ConclusionThe risk of malignant transformation of MC should not be questioned, despite sex distribution and location differences between MC and CC. These differences may be due to inaccurate designation of intraductal mucinous carcinomas as communicating CC or of CC as pancreatic mucinous adenocarcinomas.     

Médicalisation préhospitalière héliportée et agressions cérébrales secondaires d'origine systémique chez les traumatisés craniocérébraux graves

Advanced supportive therapy at the site of the accident, associated with direct transfer to a trauma centre increases survival and reduces morbidity rates. Patients with severe head injury, especially those with multiple injuries, often arrive in the emergency department with potentially causes of serious secondary systemic insults to the already injured brain, such as acute anemia (Hematocrit ≤ 30 %), hypotension (systolic arterial pressure (Pa_sys) ≤ 95 mmHg, 12,7 kPa), hypercapnia (PaCO₂ ≥ 45 mmHg, 6 kPa) and/or hypoxemia (Pao₂ ≤ 65 mmHg, 8,7 kPa). The incidence of such insults and their impact on mortality were studied in a group of 51 consecutive adults suffering from non penetrating severe head injury (Glasgow score ≤ 8, mean age 31 ± 17 yrs) rescued by a medicalised helicopter. Each patient received medical care on the site of the accident by an anaesthesiologist of a university hospital (UH) complying with an advanced trauma life support protocol including intubation, hyperventilation with FIO₂ = 1, restoration of an adequate Pa_sys and direct transportation to the UH. Mean delay from call to arrival of the rescue team on the site was 15 ± 5 min. Mean scene time was 32 ± 10 min in cases not requiring extrication. Nineteen patients (Group I) were admitted without secondary systemic insults to the brain, 13 with isolated head injury, and 6 with multiple injuries, with a low Glasgow Outcome Score (GOS 1–3) of 42 % at 3 months. In 32 patients (Group II), despite advanced supportive measures at the scene of the accident and during transportation, one or more secondary systemic insults to the brain were detected upon arrival at the emergency room, one with isolated head injury, 31 with multiple injuries, with a bad GOS of 72 % at 3 months. We conclude that : 1) advanced trauma life support prevents from secondary systemic insults in the great majority of isolated severe head injured patients, 2) secondary systemic insults to the already injured brain are frequent in patients with multiple injuries and are difficult to avoid despite rapid aeromedical trauma care, 3) secondary systemic insults to the brain have a catastrophic impact on the outcome of severely head injured patients.     

Analgésie postopératoire. Spécificités du sujet âgé

The necessity of an adapted, optimal postoperative analgesia in the elderly is widely recognised. Reduced physiological capacities must be taken into consideration during the perioperative period. Class I analgesics, such as paracetamol, are both safe and efficient, and can be used for basic analgesia. Non steroid anti-inflammatory drugs carry an increased iatrogenic risk in the elderly. Their benefits should always be considered with regard to their risk. Their dosage should be decreased by 40–60% in comparison to the standard adult doses. Opioids, though highly efficient, carry a higher risk of respiratory depression due to the increased sensitivity to this class of molecules in the elderly. Doses must be reduced by 50% of the standard adult dose in order to limit adverse events while maintaining an equivalent level of analgesia. Patient-controlled and spinal opioid analgesia can be used in elderly patients. However surveillance of both the state of consciousness and respiratory rate must be carried out hourly over a period ranging from 12 to 24 hours. Pulse oximetry can be of value. After orthopaedic surgery, perineural or peripheral analgesia should be favoured considering the excellent benefit-risk ratio. Close clinical monitoring is essential for providing safe and efficient analgesia in the elderly using the techniques currently at our disposal.     

Hypothermie modérée et protection cérébrale

To define the part played by mild-to-moderate hypothermia in neuroprotection, it is necessary to take into account the thermoregulatory responses that occur in the normal human as the change in central temperature exceeds 0.2 °C. The mechanisms induced by cold are cutaneous vasoconstriction and shivering. They must be suppressed before starting controlled hypothermia. In these conditions, controlled moderate hypothermia between 32 and 35 °C dœs not seem to have deleterious side-effects, especially on coagulation. Caution is needed with the analysis of the numerous papers reporting experiments concerning the effects of moderate hypothermia in animals with induced cerebral ischaemia because of significant differences in the study designs. These differences concern mainly the time of onset of hypothermia, viz before or after ischaemia, the fact that the ischaemia is either global or focal, that it is caused by vascular occlusion posttraumatic or initiated by hypo or hyperglycemia. Some differences are also existing in the criteria used to appreciate the neuronal damage, as well as in the level of temperature and the site where it is measured. The mechanism of neuroprotectionfrom moderate hypothermia seems to be not only a decrease in cerebral metabolism, but also involves a specific action on some intra-cellular events such as the blocking of the release of glutamate and of lipid peroxydation in brain tissue. An indirect proof of the neuroprotective effect of moderate hypothermia is the increase in the neuronal damage induced by moderate hyperthermia. It is conceivable that moderate hypothermia could exert a better neuroprotective effect than the drugs having this reputation, such as barbiturates, isoflurane and propofol. The possible induction of hypothermia into experiments concerning barbiturate or isoflurane protection could even explain the protection observed, as this has been proven for anti NMDA, MK-801. The few clinical studies already published do not show obvious differences allowing to recommend moderate hypothermia as a standard technique among the therapeutic modalities used for cerebral protection for intracerebral vascular surgery or cerebral resuscitation after severe head trauma. However, the experimental results are strong enough to justify futur controlled clinical studies. The prevention of brain hyperthermia may also emerge as a major objective of resuscitative intervention.     

Hypercalcémie sévère et lupus érythémateux disséminé

A rare case of severe hypercalcemia strongly associated with systemic lupus erythematosus (SLE) is reported. On admission, a young woman showed severe hypercalcemia and photosensitivity. Criteria for diagnosis of SLE were not sufficient. All causes of hypercalcemia were excluded. Radiographs of the skeleton were normal. One year later diagnosis of SLE was evident. In addition, diffuse and severe osteopenia and chest deformities had occurred. The treatment of SLE normalized persistently calcemia. Mild elevation of calcium levels occurred during flares of SLE. It has been hypothesized that hypercalcemia in patients with SLE could be caused by the presence of stimulatory anti-PTH receptor antibodies. This case report suggests that in patients with severe hypercalcemia associated with SLE early diagnosis and treatment of SLE may prevent bone loss. In these patients the prevention of severe bone damage is very important. Indeed severe osteopenia may favour skeletal deformities and fractures; in addition it may represent a serious obstacle in using adequate doses of glucocorticoids for treatment of SLE.     

Kyste du cholédoque ≪dégénéré≫. Une observation

Choledochal cysts have an increased risk of biliary tract malignancy, induced by reflux of pancreatic juice and anomalous pancreatobiliary ductal junction. We report one case of congenital choledochal cyst in a 68-year-old female whose malignancy was revealed by history of pain and jaundice. Pancreatico-duodenectomy was performed and the patient was alive 6 months later.     

Protection cérébrale médicamenteuse : agents spécifiques

Dysfunctional sodium influx is the first step in the ischaemic cascade. It has been recently demonstrated that reducing ionic flux through voltage-gated Na channels shortens the NMDA receptor activity of cultured hippocampal slices in which oxidative phosphorylation and glycolysis have been blocked. The implication of this finding is that blocking initial events in the ischaemic cascade, events which do not directly cause neuronal damage, will reduce the damage done by downstream events. It also seems intuitively reasonable to suppose that truncating initial steps of the ischaemic cascade, as distinct from blocking glutamate receptors and scavening free radicals, will reduce the probability of interferring with endogenous mechanisms of repair. Clinically useful, substantive, prophylactic, pharmacological cerebral protection will come from drugs that work upstream. And for pharmacological protection that can only be initiated subsequent to an ischaemic event, the more we learn about endogenous repair, or genetic pharmacology, the closer we will come to maximizing the benefits and minimizing the costs of downstream intervention.