Monitoring the state of the occlusion – gnathosonics can be reliable

Monitoring the state of the occlusion should include records that can be compared. Gnathosonics has not become generally accepted as an everyday method of assessing the quality of the occlusion. It is suggested that this may be due to inconsistencies in the results obtained by various workers in the field. It is further suggested that such inconsistencies could be due to the manner of data gathering in the areas of equipment, transfer of data from the patient and interpretation of the records. A reliable method of data gathering using accelerometers is suggested and, taking account of the complexities of sound transmission through the skull, concludes that the overall envelope of the sounds produced by the occlusion of the teeth is more informative that the actual frequencies generated. Ways in which gnathosonics could be placed on a scientific footing and areas where further investigation might be useful are suggested. Gnathosonics, properly controlled, can provide a simple, quick and reliable method of making permanent records of occlusal sounds for comparison and assessment of stability or change in the state of the occlusion.     

Inpatient treatment of children with multiple personality/dissociative disorders and their families

A number of children who are admitted for inpatient psychiatric treatment have experienced significant trauma and abuse. It is important to evaluate them for the presence of a DD. The variety, complexity, and subtlety of the symptomatic presentation of childhood MPD makes differential diagnosis difficult, and it is probable that many cases have been missed in the past. Detailed historical information and extensive behavioral observations in a variety of settings can assist in establishing the diagnosis and in delineating areas for therapeutic intervention. Hospitalization may be necessary to conduct an adequate evaluation, develop a therapeutic alliance, safely manage behaviors that are injurious to the child or others, and/or to diffuse potentially volatile family situations. All members of a multidisciplinary inpatient team play important roles in the achievement of successful therapeutic intervention with dissociating children and their families. Skilled family therapy is often an important adjunct to therapeutic interventions focused on the child, particularly when the parent also has MPD. Knowledge of the psychodynamic issues involved in dissociation can be used to develop behavioral interventions that are successful in decreasing the child's need to dissociate, improving his or her overall functioning, and help him or her gain mastery over problematic behaviors.     

Practical management of patients with non-small-cell lung cancer treated with gefitinib.

PURPOSE: The use of gefitinib, the first drug approved to inhibit the epidermal growth factor receptor tyrosine kinase, is indicated in patients with non-small-cell lung cancer with tumors progressive after chemotherapy. The unique mechanism of action of this agent leads to distinctive patterns of response and toxicity in persons with lung cancer. Many of the principles of management relevant to gefitinib are distinct from those with conventional cytotoxic drugs. To meet this need, we present practical guidelines on the use of gefitinib in patients with non-small-cell lung cancer. METHODS: This article reviews gefitinib's indications, dosing, response phenomena, and patterns of relapse in individuals with radiographic response. RESULTS: We present our recommendations for the management of rash and diarrhea caused by this agent. CONCLUSION: This information can guide practitioners and help them inform their patients about what to expect when they receive gefitinib.     

A glutamatergic mechanism for aluminum toxicity in astrocytes

The effect of aluminum on the metabolism of glutamate and glutamine in astrocytes was studied to provide information about a possible biochemical mechanism for aluminum neurotoxicity and its potential contribution to neurodegenerative disease. Exposure of cultured rat brain astrocytes for 3–4 d to 5–7.5 mM aluminum lactate increased glutamine synthetase activity by 100–300% and diminished glutaminase activity by 50–85%. Increased glutamine synthetase enzyme activity was accompanied by an elevated level of glutamine synthetase mRNA. Alterations in glutaminase and glutamine synthetase following aluminum exposure caused increased intracellular glutamine levels, decreased intracellular glutamate levels, and increased conversion of glutamate to glutamine and the release of the latter into the extracellular space. The results of these changes may alter the availability of neurotransmitter glutamate in vivo and may be a mechanism for the aluminum neurotoxicity observed in individuals exposed to the metal during dialysis procedures and other situations.     

Prostate development in prune belly syndrome (PBS) and posterior urethral valves (PUV): etiology of PBS--lower urinary tract obstruction or primary mesenchymal defect?

Prune belly syndrome (PBS) has been recognized since 1950 as the triad of absent abdominal wall musculature, undescended testes, and urinary tract anomalies. The etiology, however, remains uncertain. Theories of mesenchymal maldevelopment, obstruction, and genetic origin have been proposed. To evaluate the role of lower urinary tract obstruction as it relates to prostatic development and PBS, we studied the lower urinary tract of 15 cases of PBS, 8 cases of posterior urethral valves (PUV), and 34 age-matched controls. It is generally accepted that prostatic growth and development are dependent on mesenchymal-epithelial interactions. We evaluated the mesenchymal and epithelial differentiation and relationships, and found distinctly different and consistent abnormalities between PBS and PUV as compared with one another and controls. The findings suggest that in PBS, prostatic growth and development are hindered because of destruction or absence of the appropriate primitive mesenchyme. Our studies could not definitely exclude very early obstruction as a cause of the findings because of lack of appropriate fetal material.     

Prostate Development in Prune Belly Syndrome (PBS) and Posterior Urethral Valves (PUV): Etiology of PBS-Lower Urinary Tract Obstruction or Primary Mesenchymal Defect?

Prune belly syndrome (PBS) has been recognized since 1950 as the triad of absent abdominal wall musculature, undescended testes, and urinary tract anomalies. The etiology, however, remains uncertain. Theories of mesenchymal maldevelopment, obstruction, and genetic origin have been proposed. To evaluate the role of lower urinary tract obstruction as it relates to prostatic development and PBS, we studied the lower urinary tract of 15 cases of PBS, 8 cases of posterior urethral values (PUV), and 34 age-matched controls. It is generally accepted that prostatic growth and development are dependent on mesenchymal-epithelial interactions. We evaluated the mesenchymal and epithelial differentiation and relationships, and found distinctly different and consistent abnormalities between PBS and PUV as compared with one another and controls. The findings suggest that in PBS, prostatic growth and development are hindered because of destruction or absence of the appropriate primitive mesenchyme. Our studies could not definitely exclude very early obstruction as a cause of the findings because of lack of appropriate fetal material.     

Repair of left ventricular aneurysm. Changes in ventricular mechanics, hemodynamics, and oxygen consumption.

Anteroapical left ventricular aneurysms were produced in 23 sheep by coronary arterial ligation. Plication of the aneurysm does not change stroke volume or cardiac output and does not significantly change left ventricular oxygen consumption from the preoperative value of 5.1 +/- 2.6 ml/100 gm per minute. Plication, however, does increase left ventricular end-systolic elastance from 3.2 +/- 0.9 to 4.4 +/- 1.5 mm Hg/mm (p = 0.005). In nine of these sheep the midsagittal plane of the left ventricle was imaged by means of an array of sonomicrometry crystals before and after plication of the aneurysm. Regional wall stresses at end-systole and end-diastole and changes in diastolic function were calculated for anterior and posterior ventricular walls in the border zone adjacent to the aneurysm and in more basilar myocardium remote from the infarct. Plication significantly reduced end-systolic wall stresses and systolic stress integrals in the posterior border zone and remote myocardium, but it did not significantly change anterior wall systolic stresses or stress integrals. Plication also decreased diastolic stretching of border zone myocardium. Plication of anteroapical left ventricular aneurysm produced a shorter, more spherical ventricle and removed the dyskinetic segments but altered deformation (strain) in both circumferential and longitudinal directions. The changes in ventricular wall geometry and deformation provide an explanation for the increased ventricular end-systolic elastance and unchanged stroke volume observed after aneurysm plication.     

Relative sensitivity of four noninvasive methods in assessing systolic cardiovascular effects of isoproterenol in healthy volunteers.

STUDY OBJECTIVE: The study was performed to evaluate the relative sensitivity of various noninvasive methods to detect and describe the systolic cardiovascular effects of stepwise increasing doses of isoproterenol: two-dimensional left ventricular echocardiography (main variable, ejection fraction), ACVF (attenuation compensated volume flow)--dual-beam Doppler echoaortography (time-averaged mean velocity), electrical impedance cardiography [(dZ/dtmax)/RZ index], and systolic time intervals from mechanocardiography (PEP and QS2c). METHODS: Isoproterenol was administered by constant rate intravenous infusion in consecutive steps of 0.1, 0.2, 0.4, 0.75, and 1.5 micrograms/min (each for 15 minutes). Saline control infusions were given in analog fashion. The treatments (isoproterenol and saline solution) were administered in a period-balanced two-way crossover design with randomly allocated sequences. The subjects, observers, and analysts were blinded to the treatment protocol. Study subjects were 10 healthy male volunteers (age range, 23 to 31 years; mean age, 26.6 years). RESULTS: Compared with saline solution, isoproterenol caused a dose-related increase in ejection fraction, (dz/dt)/RZ index, and time-averaged mean velocity and a dose-related shortening of PEP and QS2c. The responses are congruent with an enhancement of cardiac systolic performance caused by a positive inotropic stimulation and an afterload reduction ("inodilatory" response). The effects on systolic time intervals reached statistical significance (alpha = 0.05) at the first isoproterenol dose step, the effects on the impedance cardiography and the Doppler echoaortography variables reached statistical significance at the second dose step, and the effects on the two-dimensional echocardiography reached statistical significance at the third dose step. CONCLUSIONS: All methods allowed to detect isoproterenol-related changes. Systolic time intervals were the most sensitive, followed by impedance cardiography, ACVF--dual-beam Doppler echoaortography, and two-dimensional echocardiography. The practical convenience and high sensitivity of the systolic time intervals makes them suitable to evaluate investigational systolic inodilatory changes in humans.     

Clinical and molecular study in congenital muscular dystrophy with partial laminin alpha 2 (LAMA2) deficiency

Complete laminin alpha2 (LAMA2) deficiency causes approximately half of congenital muscular dystrophy (CMD) cases. Many loss-of-function mutations have been reported in these severe, neonatal-onset patients, but only single missense mutations have been found in milder CMD with partial laminin alpha2 deficiency. Here, we studied nine patients diagnosed with CMD who showed abnormal white-matter signal at brain MRI and partial deficiency of laminin alpha2 on immunofluorescence of muscle biopsy. We screened the entire 9.5 kb laminin alpha2 mRNA from patient muscle biopsy by direct capillary automated sequencing, single strand conformational polymorphism (SSCP), or denaturing high performance liquid chromatography (DHPLC) of overlapping RT-PCR products followed by direct sequencing of heteroduplexes. We identified laminin alpha2 sequence changes in six of nine CMD patients. Each of the gene changes identified, except one, was novel, including three missense changes and two splice-site mutations. The finding of partial laminin alpha2 deficiency by immunostaining is not specific for laminin alpha2 gene mutation carriers, with only two patients (22%) showing clear causative mutations, and an additional three patients (33%) showing possible mutations. The clinical presentation and disease progression was homogeneous in the laminin alpha2-mutation positive and negative CMD patients.