Practical guidelines for the assessment and treatment of selective mutism

OBJECTIVE: To provide practical guidelines for the assessment and treatment of children with selective mutism, in light of the recent hypothesis that selective mutism might be best conceptualized as a childhood anxiety disorder. METHOD: An extensive literature review was completed on the phenomenology, evaluation, and treatment of children with selective mutism. Additional recommendations were based on clinical experience from the authors' selective mutism clinic. RESULTS: No systematic studies of the phenomenology of children with selective mutism were found. Reports described diverse and primarily noncontrolled treatment approaches with minimal follow-up information. Assessment and treatment options for selective mutism are presented, based on new hypotheses that focus on the anxiety component of this disorder. Ongoing research suggests a role for behavior modification and pharmacotherapy similar to the approaches used for adults with social phobia. CONCLUSION: Selectively mute children deserve a comprehensive evaluation to identify primary and comorbid problems that might require treatment. A school-based multidisciplinary individualized treatment plan is recommended, involving the combined effort of teachers, clinicians, and parents with home- and clinic-based interventions (individual and family psychotherapy, pharmacotherapy) as required.     

Revision of the medical malpractice law--legal aspects

Since the beginning of this century, modifications of the criminal law regarding medicine have been outlined frequently. The focus of these modifications was to eliminate the circumstance that each medical procedure is a criminal offense even if it was performed correctly and was successful. Treatment without consent was supposed to be punished. The draft recently submitted to the ministry of justice seems to be a failure. The prerequisites of an effective consent remain unclear. An incorrect information of the patient would be classified as intent and, thus, be punishable. By application of uncertain criteria, medical experiments and treatment procedures might be followed by excessive punishment.     

Reflex sympathetic dystrophy in hemiplegia--two case reports and review of the literature

Reflex sympathetic dystrophy (RSD) can be precipitated by a variety of events. We report two cases of RSD in hemiplegic patients detected within three months of the cerebrovascular accidents. Diagnosis of RSD was based upon clinical and scintigraphic findings. Management included elevation, range of movement of the affected joints and analgesics. With treatment, the pain and swelling subsided, range of motion of joints improved and the patients were able to participate in the rehabilitation programme. A high index of suspicion, early diagnosis and aggressive treatment were found to be essential for the successful treatment of RSD.     

Mu and kappa opioid receptors in periaqueductal gray and rostral ventromedial medulla

The periaqueductal gray (PAG) and rostral ventromedial medulla (RVM) are important brain stem pain modulating regions. Recent evidence suggests that kappa opioids antagonize the effects of mu opioids in the RVM. However, the anatomical relationship between mu and kappa opioid receptors in PAG and RVM is not well characterized. This study examined relationships between mu and kappa opioid receptor immunoreactivity (IR) and mRNA in PAG and RVM. Brain slices were processed for either immunocytochemistry or in situ hybridization. We found considerable anatomical overlap of mu and kappa opioid IR and mRNA in the RVM and PAG. These results provide an anatomical basis for recent behavioral and electrophysiological findings in RVM, and suggest modulatory interactions between mu and kappa opioids in PAG.     

DNA-based immunization against hepatitis B surface antigen (HBsAg) in normal and HBsAg-transgenic mice

Hepatitis B virus (HBV) remains a serious worldwide health problem and the possibility to control it will depend on the availability of safe, effective and affordable vaccines. Recombinant protein or plasma-derived vaccines containing HBV surface antigen (HBsAg) are safe and generally efficacious, however, they are too expensive for widespread use in areas of HBV endemicity and are only partially effective for treatment of HBV chronic carriers. Immunization of mice by injection of HBsAg-expressing plasmid DNA results in rapid induction of strong and long-lasting humoral and cell-mediated immune responses. Here we report optimization of the humoral response with the use of necrotizing agents, co-expression of cytokines or co-stimulatory molecules and formulation of the DNA with cationic liposomes. DNA-based immunization of HBsAg-transgenic mice can also overcome non-response to HBsAg. Thus, DNA vaccines against HBV may be useful for both prophylactic and therapeutic purposes.     

Local hyperthermia and SR 4233 enhance the antitumor effects of radioimmunotherapy in nude mice with human colonic adenocarcinoma xenografts

Local hyperthermia and the hypoxic cytotoxin SR 4233 were administered to nude mice with 693 +/- 47 mm3 (mean +/- SE) s.c. HCT-8 human colonic adenocarcinoma xenografts in an attempt to enhance the antitumor effects of radioimmunotherapy. Biodistribution studies revealed preferential binding of NR-Lu-10, a murine monoclonal antibody, to the tumors compared with an isotype-matched control antibody, CCOO16-3.A single injection of 25 microCi 90Y-NR-Lu-10 significantly inhibited tumor growth (control versus 90Y-NR-Lu-10: P = 0.048). The administration of hyperthermia at 41.5 degrees C for 1 h immediately following the injection of 111In-labeled NR-Lu-10 up-regulated tumor-associated antigen expression and increased antibody uptake in the tumors by 73% (P = 0.001) without significantly affecting antibody uptake in normal tissues. However, the heat treatment did not produce a more homogeneous distribution of the antibodies in the tumors and did not significantly enhance the tumor growth delay produced by 90Y-NR-Lu-10 (P = 0.07). The administration of local hyperthermia at 43.0 degrees C for 1 h, on the other hand, had direct cytotoxic effects (P = 0.03) and enhanced the tumor growth delay produced by 90Y-NR-Lu-10 (P = 0.01). SR 4233 also enhanced the tumor growth delay produced by 90Y-NR-Lu-10 (P = 0.03). The greatest antitumor effects were observed when both hyperthermia at 43.0 degrees C and SR 4233 were administered in combination with 90Y-NR-Lu-10 (P = 0.002). No toxicity was produced by the local hyperthermia, and the only toxicities produced by 90Y-NR-Lu-10 and SR 4233 were neutropenia and weight loss.     

Cardiac afferents attenuate the muscle metaboreflex in the rat

The influence of cardiac afferents on the muscle metaboreflex was examined in 16 rats instrumented with a Silastic-tipped catheter in the pericardial space and right atrium, Doppler ultrasonic flow probe and a pneumatic vascular occluder around the terminal aorta, and a Teflon catheter in the thoracic aorta. In protocol I (cardiac efferent and afferent blockade), the muscle metaboreflex was examined under three experimental conditions: 1) control, 2) cardiac autonomic efferent blockade [intrapericardial methylscopolamine (10 micrograms/kg) and propranolol (50 micrograms/kg)], and 3) combined cardiac autonomic efferent and afferent blockade (intrapericardial procainamide, 2%). In protocol II (blood volume expansion), the muscle metaboreflex was examined before and after 15% blood volume expansion. Mild treadmill exercise (9 m/min, 10% grade) increased heart rate (71 +/- 9.4 beats/min), mean arterial pressure (12 +/- 2.0 mmHg), and terminal aortic blood flow velocity (6 +/- 1.0 kHz). During exercise, a reduction of terminal aortic blood flow velocity (10.5 +/- 1.1%) reduced mixed venous PO2 18 +/- 6%. The gain of the muscle metaboreflex in the control condition was 14.6 +/- 2.9 mmHg/kHz. Efferent blockade reduced the gain 51 +/- 7%. However, combined cardiac efferent and afferent blockade increased the gain 207 +/- 64% above the efferent blocked condition and restored the gain to levels above those obtained in the control condition (18.3 +/- 4.6 mmHg/kHz). In addition, 15% blood volume expansion reduced the gain of the muscle metaboreflex regulation of mean arterial pressure and heart rate (44 +/- 9.5% and 41 +/- 12.0%, respectively). Thus cardiac afferents tonically inhibit the pressor response to a reduction in terminal aortic blood flow velocity during exercise.     

ACE (I/D) genotype as a predictor of the magnitude and duration of the response to an ACE inhibitor drug (enalaprilat) in humans

BACKGROUND: We have investigated the possible effects of contrasting ACE (I/D) genotypes on the responses to the ACE inhibitor enalaprilat in normotensive men. METHODS AND RESULTS: Subjects with DD (n=12) and II (n=11) ACE genotypes received an intravenous infusion of enalaprilat or placebo. Pressor responses to stepwise, incremental doses of angiotensin I were measured at 1 and 10 hours after dosing. The dose required to raise mean blood pressure by 20 mm Hg (PD20) was calculated individually, and the ratio of PD20 during enalaprilat to that during placebo (dose ratio, DR) was used for assessment of the extent of ACE inhibition. The pressor response was significantly attenuated at 1 hour after enalaprilat in both groups, but significant attenuation was evident at 10 hours after dose only in the II subjects. The DRs at both 1 hour (median, 5.43 versus 2.82, P=0.0035) and 10 hours (2.06 versus 0.84, P=0.0008) after enalaprilat were significantly higher in II subjects than in DD subjects. CONCLUSIONS: The effect of enalaprilat was significantly greater and lasted longer in normotensive men homozygous for the II ACE genotype. By multivariate analysis, ACE (I/D) genotype and plasma angiotensin II levels were predictive of >50% of the variation in response to ACE inhibition.