Treatment of the exposed knee prosthesis

Ten knees with early tissue breakdown after knee arthroplasty resulting in exposed prostheses were treated with different plastic surgical techniques. Six knees were successfully covered: four using a gastrocnemius musculocutaneous flap, one using a fasciocutaneous flap, and one using split-skin grafts. Four knees failed: two using local skin flaps and two using split-skin grafts. A gastrocnemius musculocutaneous flap seems to provide a reliable coverage of the exposed knee joint.     

Quality of life and standard of living in a randomly selected group of psychiatrically disabled people in Sweden 2 years after a psychiatry reform.

In Sweden, a psychiatry reform, aimed at improving the living conditions of the psychiatrically disabled, came into force in 1995. The aim of the present study was to evaluate the impact of the reform by investigating quality of life and standard of living 2 years later in a randomly selected group of people with longstanding psychiatric disability. Self-ratings and interviews were conducted in a study group and a control group. The study group consisted of 19 women and 18 men (mean age 46.1 years) diagnosed with neurosis, schizophrenia or affective disorder. The control group consisted of 19 women and 17 men (mean age 48.7 years). Self-rated quality of life was significantly poorer in the study group (P < 0.0001, unpaired t-test), and so was housing (P < 0.001, test of similar proportions in independent samples). We found no significant positive correlation between subjective quality of life and standard of living in either group but a significant negative correlation in the control group (P < 0.05; r = 0.40, Pearson correlation coefficient). The results suggest that, in 1997, people with longstanding psychiatric disability still had poorer quality of life than the general population. This may be due to factors other than outward standard of living.     

Effects of MPP+ on catecholamine levels in adrenal glands and heart of rats

The effects of MPP⁺ (2.5–20 mg/kg) on the adrenal glands and heart were investigated in rats. At various periods after s.c. drug administration the rats were decapitated and tissue catecholamine levels were determined by means of HPLC with electrochemical detection. Adrenal dopamine (DA) levels were reduced at 2–8 h after MPP⁺ administration, but this decrease was followed by an elevation after 16 h and return to the control values after one week. Three successive injections of MPP⁺ caused a statistically significant elevation in adrenal DA, one day, with a tendency to elevation four and seven days after the last injection, whereas a severe (up to 96%) decrease in heart noradrenaline (NA) was found one day after the last injection. Seven days after the last injection a 50% depletion of NA in the heart was still observed. Pretreatment with GBR 12909 (30 mg/kg, 4 h) blocked the MPP⁺ (10 mg/kg, 2 h) induced reduction of adrenal DA levels, but at the same time GBR 12909 failed to block the effects of MPP⁺ in the heart. One day after three successive daily injections of MPP⁺ (10 mg/kg each), the DA-uptake inhibitor GBR 12909 (30 mg/kg, 6 h) could still induce an increase in adrenal DA.MPP⁺ appears to lack persistent cytotoxic action in the adrenal medulla but rather to cause a transient inhibition of DA synthesis followed by a compensatory stimulation. The inhibition can be blocked by specific inhibitor of the DA-uptake mechanism, suggesting a direct effect of MPP⁺ taken up by adrenomedullary cells. The data obtained so far do not suggest any involvement of peripheral dopaminergic nerves in the action of MPP⁺ on the adrenal medulla. The long-lasting depletion of the heart NA, however, suggests a lesion of peripheral noradrenergic nerves.Part of this work was presented at 6th International Symposium on Chromaffin Cell Biology, Marburg, Germany, 18–23 August 1991 Correspondence to: M. Kujacic at the above address     

Pneumonia: a deadly disease despite intensive care treatment

In a retrospective study of 30 patients with pneumonia treated in the intensive care unit, it was found that cultures from sputum and bronchial secretions did poorly correspond with blood cultures or serological tests. In only 15 of the patients a reliable etiological diagnosis was ever established. Mechanical ventilation was used in 22 patients, usually with a high oxygen need. At the start of this ventilation a significant blood pressure fall and a further pulmonary deterioration was observed. In fatal cases this pulmonary dysfunction was progressive. The overall mortality was 47%. When an FI02 above 0.6 was needed in the ventilator the mortality was 13/14 (93%).     

Comparative in vivo evaluation of technetium and iodine labels on an anti-HER2 affibody for single-photon imaging of HER2 expression in tumors.

In vivo diagnosis with cancer-specific targeting agents that have optimal characteristics for imaging is an important development in treatment planning for cancer patients. Overexpression of the HER2 antigen is high in several types of carcinomas and has predictive and prognostic value, especially for breast cancer. A new type of targeting agent, the Affibody molecule, was described recently. An Affibody dimer, His6-(ZHER2:4)2 (15.4 kDa), binds to HER2 with an affinity of 3 nmol/L and might be used for the imaging of HER2 expression. The use of 99mTc might improve the availability of the labeled conjugate, and Tc(I)-carbonyl chemistry enables the site-specific labeling of the histidine tag on the Affibody molecule. The goals of the present study were to prepare 99mTc-labeled His6-(ZHER2:4)2 and to evaluate its targeting properties compared with the targeting properties of 125I-4-iodobenzoate-His6-(ZHER2:4)2 [125I-His6-(ZHER2:4)2]. METHODS: The labeling of His6-(ZHER2:4)2 with 99mTc was performed with an IsoLink kit. The specificity of 99mTc-His6-(ZHER2:4)2 binding to HER2 was evaluated in vitro with SK-OV-3 ovarian carcinoma cells. The comparative biodistributions of 99mTc-His6-(ZHER2:4)2 and 125I-His6-(ZHER2:4)2 in tumor-bearing BALB/c nu/nu mice were determined. RESULTS: The labeling yield for 99mTc-His6-(ZHER2:4)2 was approximately 60% (50 degrees C), and the radiochemical purity was greater than 97%. The conjugate was stable during storage and under histidine and cysteine challenges and demonstrated receptor-specific binding. The biodistribution study demonstrated tumor-specific uptake levels (percentage injected activity per gram of tissue [%IA/g]) of 2.6 %IA/g for 99mTc-His6-(ZHER2:4)2 and 2.3 %IA/g for 125I-His6-(ZHER2:4)2 at 4 h after injection. Both conjugates provided clear imaging of SK-OV-3 xenografts at 6 h after injection. The tumor-to-nontumor ratios were much more favorable for the radioiodinated Affibody. CONCLUSION: The use of Tc(I)-carbonyl chemistry enabled us to prepare a stable, site-specifically labeled 99mTc-His6-(ZHER2:4)2 conjugate that was able to bind to HER2-expressing cells in vitro and in vivo. The indirectly radioiodinated conjugate provided better tumor-to-liver ratios. The labeling of Affibody molecules with 99mTc should be investigated further.     

Regulation of G-PROTEIN mRNA abundancy and cAMP accumulation after long-term opioid incubation in primary cultures of astroglia from the rat cerebral cortex.

Primary astroglial cultures were incubated with delta (10(-6) M DPDPE) or kappa (10(-5) M U-50,488H) receptor agonists for 5 days. Thereafter, the acute inhibitory actions of delta or kappa receptor agonists on forskolin stimulated cAMP accumulation were assayed. The G alpha s, G alpha i-1 and G alpha i-2 mRNA levels were quantified after 5 days of either delta or kappa receptor agonist treatment using a solution hybridization, RNase protection assay. Pronounced effects were observed after 5 days of kappa receptor agonist [10(-5) M U-50,488H] incubation. This treatment resulted in an attenuation in the acute inhibitory action of delta and kappa receptor agonists. Furthermore, a decreased stimulatory action of forskolin was seen. Similar effects were also seen after delta receptor stimulation. We also investigated the effects after 24 h and 3 days of incubation with the kappa receptor agonist (10(-5) M) U-50,488H. The 24 h incubation resulted in a decreased sensitivity to the acute inhibitory action of delta and kappa receptor agonists in the astroglial cultures. This effect was further accentuated after the 3 days of incubation with 10(-5) M U-50,488H. No significant change was seen in the basal accumulation of cAMP after incubation with the kappa agonist U-50,488H. However, after 5 days of incubation with the delta agonist DPDPE, a significantly increased basal accumulation of cAMP was seen in the astroglial cultures. After 5 days of delta or kappa agonist incubation, an increase in G alpha s mRNA level and a decrease in G alpha i-2 mRNA level was seen compared with controls. No statistically significant alterations in the amount of G alpha i-1 mRNA were seen. The data obtained in the present study indicate that the effects of long-term opioid treatment alters the sensitivity of glial cell opioid receptors. Furthermore, long term opioid treatment induces alterations in glial G-protein mRNA levels.     

Anosognosia in mild cognitive impairment: Relationship to activation of cortical midline structures involved in self-appraisal.

Awareness of cognitive dysfunction shown by individuals with Mild Cognitive Impairment (MCI), a condition conferring risk for Alzheimer's disease (AD), is variable. Anosognosia, or unawareness of loss of function, is beginning to be recognized as an important clinical symptom of MCI. However, little is known about the brain substrates underlying this symptom. We hypothesized that MCI participants' activation of cortical midline structures (CMS) during self-appraisal would covary with level of insight into cognitive difficulties (indexed by a discrepancy score between patient and informant ratings of cognitive decline in each MCI participant). To address this hypothesis, we first compared 16 MCI participants and 16 age-matched controls, examining brain regions showing conjoint or differential BOLD response during self-appraisal. Second, we used regression to investigate the relationship between awareness of deficit in MCI and BOLD activity during self-appraisal, controlling for extent of memory impairment. Between-group comparisons indicated that MCI participants show subtly attenuated CMS activity during self-appraisal. Regression analysis revealed a highly significant relationship between BOLD response during self-appraisal and self-awareness of deficit in MCI. This finding highlights the level of anosognosia in MCI as an important predictor of response to self-appraisal in cortical midline structures, brain regions vulnerable to changes in early AD.