Effects of therapeutic hypothermia on intracranial pressure and outcome in patients with severe head injury

OBJECTIVE: Therapeutic hypothermia may improve outcome in patients with severe head injury, but clinical studies have produced conflicting results. We hypothesised that the severe side effects of artificial cooling might have masked the positive effects in earlier studies, and we treated a large group of patients with severe head injury with hypothermia using a strict protocol to prevent the occurrence of cooling-induced side effects. DESIGN: Prospective clinical trial. SETTING: University teaching hospital. PATIENTS: Hundred thirty-six consecutive patients admitted to our hospital with severe head injury (Glasgow Coma Scale (GCS) < or =8). MEASUREMENTS AND RESULTS: Patients included are the 136 patients with a GCS of 8 or less on admission in whom intracranial pressure (ICP) remained above 20 mmHg in spite of therapy according to a step-up protocol. Those who responded to the last step of our protocol (barbiturate coma) constituted the control group (n=72). Those who did not respond to barbiturate coma (n=64) were treated with moderate hypothermia (32-34 degrees C). Average APACHE II scores were higher (28.9+/-14.4 vs 25.2+/-12.1, p<0.01) and average GCS at admission slightly lower (5.37+/-1.8 vs 5.9+/-2.1, p<0.05) in the hypothermia group, indicating greater severity of illness and more severe neurological injury. Predicted mortality was 86% for the hypothermia group versus 80% in controls (p<0.01). Actual mortality rates were significantly lower: 62% versus 72%; the difference in mortality between hypothermic patients and controls was significant (p<0.05). The number of patients with good neurological outcome was also higher in the hypothermia group: 15.7% versus 9.7% for hypothermic patients versus controls, respectively (p<0.02). These differences were explained almost entirely by the subgroup of patients with GCS of 5 or 6 at admission (mortality 52% vs 76%, p<0.01; good neurological outcome 29% vs 8%, p<0.01). CONCLUSIONS: Artificial cooling can significantly improve survival and neurological outcome in patients with severe head injury when used in a protocol with great attention to the prevention of side effects. Because there is likely to have been bias against the hypothermia group in this study, the positive effects of hypothermia might even have been underestimated. In addition, our results confirm the value of therapeutic hypothermia in treating refractory intracranial hypertension.     

Quantitative tumor apoptosis imaging using technetium-99m-HYNIC annexin V single photon emission computed tomography.

PURPOSE: Radiolabeled annexin V may allow for repetitive and selective in vivo identification of apoptotic cell death without the need for invasive biopsy. This study reports on the relationship between quantitative technetium-99m- (99mTc-) 6-hydrazinonicotinic (HYNIC) radiolabeled annexin V tumor uptake, and the number of tumor apoptotic cells derived from histologic analysis. PATIENTS AND METHODS: Twenty patients (18 men, two women) suspected of primary (n = 19) or recurrent (n = 1) head and neck carcinoma were included. All patients underwent a spiral computed tomography (CT) scan, 99mTc-HYNIC annexin V tomography, and subsequent surgical resection of the suspected primary or recurrent tumor. Quantitative 99mTc-HYNIC annexin V uptake in tumor lesions divided by the tumor volume, derived from CT, was related to the number of apoptotic cells per tumor high-power field derived from terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling (TUNEL) assays performed on sectioned tumor slices. RESULTS: Diagnosis was primary head and neck tumor in 18 patients, lymph node involvement of a cancer of unknown primary origin in one patient, and the absence of recurrence in one patient. Mean percentage absolute tumor uptake of the injected dose per cubic centimeter tumor volume derived from tomographic images was 0.0003% (standard deviation [SD], 0.0004%) at 1 hour postinjection (PI) and 0.0001% (SD, 0.0000%) at 5 to 6 hours PI (P =.012). Quantitative 99mTc-HYNIC annexin V tumor uptake correlated well with the number of apoptotic cells if only tumor samples with no or minimal amounts of necrosis were considered. CONCLUSION: In the absence of necrosis, absolute 99mTc-HYNIC annexin V tumor uptake values correlate well with the number of apoptotic cells derived from TUNEL assays.     

Trade-off Mediated Effects on the Genetics of Human Survival Caused by Increasingly Benign Living Conditions

It is sometimes suggested that modern life, with its planned fertility and medically assisted compensation for genetic disadvantage, has greatly reduced the power of natural selection to produce significant further human evolution. However, this overlooks the very recent and dramatic changes that have occurred in the patterns of human mortality, driven by the development of increasingly benign living conditions. Where the genetics of survival are significantly influenced by life history trade-offs, as is now thought to be the case for ageing and longevity, a change in the environment can shift the optimal balance that was established through natural selection under previous conditions. We examine this possibility in the context of the dramatic recent change in the mortality pressure exerted by infectious disease using a model of a hypothetical immunogenetic trade-off that weighs survival against fecundity. Our results predict that such a change might have a significant effect on population genetics over relatively short-timescales, and they may also resolve the paradox of genes that impair fertility in present-day populations by showing how such genes might be a legacy from a powerful trade-off that has acted until very recently.     

Prognostic implications of atypical histologic features in choroid plexus papilloma

The prognostic significance of atypical histologic features in choroid plexus tumors remains uncertain. Therefore, a series of 164 choroid plexus tumors was evaluated for the presence of atypical histologic features, including mitotic activity, increased cellularity, nuclear pleomorphism, blurring of papillary growth pattern, and necrosis. The impact of histopathologic and clinical features on the probability of recurrence and survival was investigated. Twenty-four tumors displaying frank signs of malignancy were diagnosed as choroid plexus carcinoma according to World Health Organization criteria. Of 124 choroid plexus papillomas that had not received adjuvant treatment, 46 tumors (37%) displayed at least one atypical feature, including increased cellularity (n = 25 [20%]), mitotic activity (> or =2 mitoses per 10 high-power fields; n = 19 [15%]), nuclear pleomorphism (n = 16 [13%]), solid growth (n = 15 [12%]), and necrosis (n = 5 [4%]). Only one tumor-related death, but 10 recurrences, were observed on a mean observation time of 58 months. On univariate analysis, incomplete surgical resection (p = 0.03) and mitotic activity (p < 0.001) were the only clinicopathologic factors associated with recurrence. Using a multivariate model, an independent effect of mitotic activity on the probability of recurrence could be confirmed (p = 0.001). Because mitotic activity is the sole atypical histologic feature independently associated with recurrence, we propose to define atypical choroid plexus papilloma by mitotic activity (> or =2 mitoses per 10 high-power fields) corresponding to World Health Organization grade II, thus adjoining other intermediate tumor entities associated with increased mitotic activity such as atypical meningioma. Close follow up of patients harboring atypical choroid plexus papillomas may be warranted.     

Effect of inner myometrium fibroid on reproductive outcome after IVF

To evaluate the influence of inner myometrium fibroids (myomas) on the outcome of IVF cycles, a retrospective agematched controlled study was performed at SISMeR Reproductive Medicine Unit. The study group included 129 IVF/intracytoplasmic sperm injection cycles in 75 patients with one or more intramural and/or submucosal fibroids, while the control group consisted of 129 cycles in 127 patients without fibroids. The two groups were similar for mean oestradiol concentration at human chorionic gonadotrophin administration (1205.16 +/- 874 versus 1395 +/- 821 pg/ml), mean number of transferred embryos (2.02 +/- 0.4 versus 2.14 +/- 0.6) and clinical pregnancy rate (34.9 versus 41.1%). Conversely, the implantation rate was significantly lower in the study group (18.0%) than in the control group (26.5%; chi(2) = 4.81, P < 0.05), whereas the rate of spontaneous abortion demonstrated an opposite trend (40 versus 18.9%; chi(2) = 4.34, P < 0.05). Further research should be aimed at classifying fibroids on the basis of their location, especially when they are positioned in the junctional zone of the myometrium. Whether this classification will be superior in predicting the impact of fibroids on the reproductive outcome should be elaborated in a large multicentric study.