The child guidance clinic: Catalyst and coordinator in community treatment of the psychotic child

Over a period of four years a child guidance clinic has maintained a program for the treatment of psychotic children in the community. A total of 27 community agencies has assisted with the care of 25 children. The primary role assumed by the clinic was that of catalyst and coordinator of the other agencies' work rather than the usual role of treatment of children in relative isolation. Clinic workers actively solicited the aid of family members and community agencies. In this program it was essential to maintain open communication at frequent intervals between the clinic and other agencies.     

Arthrogryposis multiplex congenita. Search for prenatal factors in 66 sporadic cases

In a family and epidemiological survey of 66 cases of arthrogryposis multiplex congenita all cases were found to be sporadic and no family association with clubfoot, congenital dislocation of the hip, or hereditary neuromuscular disease was found. The mothers were significantly older than average. Oligohydramnios was noted in only one-third of cases but many other complications of pregnancy, including probable attempts at abortion, had occurred. It is likely that most cases of arthrogryposis are nongenetic and result from a defective intrauterine environment, whether hormonal, vascular, mechanical, or possibly infective.     

Lymphedema after complete axillary node dissection for melanoma: assessment using a new, objective definition

OBJECTIVES: The objectives of this study were to define appropriate criteria for assessing the presence of lymphedema, and to report the prevalence and risk factors for development of upper limb lymphedema after level I-III axillary dissection for melanoma. SUMMARY BACKGROUND DATA: The lack of a consistent and reliable objective definition for lymphedema remains a significant barrier to appreciating its prevalence after axillary dissection for melanoma (or breast carcinoma). METHODS: Lymphedema was assessed in 107 patients (82 male, 25 female) who had previously undergone complete level I-III axillary dissection. Of the 107 patients, 17 had also received postoperative axillary radiotherapy. Arm volume was measured using a water displacement technique. Change in volume of the arm on the side of the dissection was referenced to the volume of the other (control) arm. Volume measurements were corrected for the effect of handedness using corrections derived from a control group. Classification and regression tree (CART) analysis was used to determine a threshold fractional arm volume increase above which volume changes were considered to indicate lymphedema. RESULTS: Based on the CART analysis results, lymphedema was defined as an increase in arm volume greater than 16% of the volume of the control arm. Using this definition, lymphedema prevalence for patients in the present study was 10% after complete level I-III axillary dissection for melanoma and 53% after additional axillary radiotherapy. Radiotherapy and wound complications were independent risk factors for the development of lymphedema. CONCLUSIONS: A suggested objective definition for arm lymphedema after axillary dissection is an arm volume increase of greater than 16% of the volume of the control arm.     

Prenatal protein restriction does not affect the proliferation and differentiation of rat preadipocytes

Poor development in utero may favor the development of obesity in adulthood. Animal studies showed that embryo manipulation in vitro or nutritional insults during the embryonic and fetal stages of development may lead to obesity in adult life. We studied the in vitro proliferation and differentiation of adipocytes to investigate whether early protein restriction may program cell growth and development. In a series of experiments, 2 different low-protein diet protocols were compared. In both cases, pregnant rats were fed a diet with a high (18-20%) or low (8-9%) protein content during gestation and/or lactation. Preadipocytes were isolated from the fetuses, neonates, and weanling offspring. Moderate protein restriction, imposed during either gestation and/or lactation, did not affect the capacity of preadipose cells to divide or store fat. Because previous studies showed that early protein restriction alters the metabolism of sulfur amino acids, we also investigated the effects of methionine, taurine, and homocysteine on proliferation and differentiation of preadipocytes. The supplementation of the diet with methionine or the addition of homocysteine and taurine to the culture media did not influence the development of preadipocytes. We obtained no evidence for the direct reprogramming of the precursor or stem cells and suggest that the subsequent alteration in fat accretion may therefore reflect a change in the neuroendocrine environment.     

Alpha-fodrin is cleaved by caspase-3 in a chronic ocular hypertensive (COH) rat model of glaucoma

Purpose: α-Fodrin is a neuronal cytoskeletal protein and a known caspase-3 target. We sought to determine whether caspase-3 cleaves α-fodrin in COH rat retinas and whether this process is reduced by adeno-associated virus (AAV)-induced retinal ganglion cell expression of baculovirus inhibitory repeat-containing 4 (BIRC4), a potent caspase-3 inhibitor.Methods: Ocular hypertension was induced unilaterally in five rat eyes by limbal injection of hypertonic saline. In a similar experiment, ocular hypertension was induced in four eyes pre-treated with an intravitreal injection of AAV-BIRC4 to assess α-fodrin cleavage. Western immunoblotting was performed on all retinas.Results: Caspase-3 cleavage of α-fodrin yields a specific 120 kDa protein fragment. COH retina immunoblots indicated significantly more caspase-3 cleavage of α-fodrin than controls (P<0.01, paired t-test). Inhibition of retinal caspase-3 activity with BIRC4 reduced caspase-3-mediated α-fodrin cleavage compared to controls.Conclusion: This confirms our previous finding of caspase-3 cleavage of α-fodrin in COH retinas and parallels pathology seen in Alzheimer’s disease, in which neurons undergo chronic caspase activation, slow build-up of cleavage products, and delayed apoptosis. If caspase activation in glaucoma leads to protracted rather than rapid retinal ganglion cell apoptosis, a much longer therapeutic window exists for apoptosis inhibition with caspase inhibitors such as BIRC4.     

Direct medical costs associated with using vancomycin in methicillin-resistant Staphylococcus aureus infections: an economic model

OBJECTIVES: To quantify the direct medical costs associated with using vancomycin, as inpatient treatment, in methicillin-resistant Staphylococcus aureus infections, in four clinical indications: complicated skin and soft tissue infections (SSTI), bacteremia, infective endocarditis (IE), and hospital-acquired pneumonia (HAP). Research design and methods: A decision-analytic model was constructed to evaluate the cost of administering intravenous vancomycin. Cost inputs included hospitalization, drug procurement, materials, preparation and administration, renal function and drug monitoring, treating adverse events, and treatment failure. Probabilities and lengths of stay and treatment were obtained from the literature, an antimicrobial therapy database and clinical expert opinion. Univariate and multivariate sensitivity analyses were conducted to confirm the robustness of the baseline scenario. MAIN OUTCOME MEASURES: The cost of using vancomycin in the four indications, including and excluding hospital cost. RESULTS: Whereas the drug acquisition price of vancomycin 1g is US dollars 9.01 per dose, when all costs associated with using vancomycin were included, the cost per dose rose to US dollars 29-US dollars 43 per patient. Total costs per patient receiving multiple doses in a single course of treatment, excluding hospital room costs, were for SSTI, bacteremia, IE, and HAP,US dollars 779, US dollars 749, US dollars 2261, and US dollars 768, respectively. Total costs, including hospital length of stay, were for SSTI US dollars 23616, bacteremia US dollars 26446, IE US dollars 48925, and HAP US dollars 22493. In univariate analyses varying per diem hospital costs and length of stay had the greatest impact. Results of the multivariate analysis were comparable to the costs in the baseline scenario for all indications. CONCLUSIONS: This analysis highlights the importance of capturing all costs associated with using a drug and not simply focusing on drug acquisition cost. Future economic analyses should identify and account for the key cost burdens of a particular treatment to calculate its true cost.     

Tonopen measurement of intraocular pressure in mice

PURPOSE: To standardize a method of non-invasive measurement of intraocular pressure (IOP) in mice. METHODS: Cannulated-eye study: IOP was measured simultaneously with a Tonopen and by direct cannulation of the vitreous compartment while pressure was manipulated in steps between 10 and 45 mmHg by a saline reservoir via a second vitreal cannula (five mice, one rat). Non-cannulated-eye study: Tonopen and servo-null measurements were performed in independent groups (48 mice) to verify Tonopen measurements in non-cannulated-eyes. Topical brimonidine (0.15%) was used to decrease IOP. RESULTS: In the rat, there was a similar relationship between Tonopen readings and direct measurements via cannulation of the eye as previously reported. Although readings from mice eyes were higher in variability than those obtained from the rat, the measurements were reproducible and the correlation between the invasive and the non-invasive methods was good (r = 0.97). The IOP lowering effect of brimonidine was detected with Tonopen as well as servo-null measurements (p < 0.001) and the results with both techniques were similar. CONCLUSION: The Tonopen can be used for rapid and reproducible measurements of IOP in mice. The method is easy to apply and can provide a useful means for IOP measurement in mouse models of induced ocular hypertension, in knock-out and transgenic mice, or in pharmacological studies.     

Importance of vitreous liquefaction in age-related cataract

PURPOSE: Vitrectomy is associated with the rapid progression of nuclear cataracts. This study was conducted to test the hypothesis that age-related liquefaction of the vitreous gel may also be associated with lens opacification. METHODS: Lenses from eye bank eyes were graded for nuclear, cortical, and posterior subcapsular opacities, and the amount of liquid vitreous was measured. RESULTS: Nuclear sclerosis (NS) grade, percent liquefaction, and age all correlated highly (P < 0.0001). After adjustment was made for age, the correlation between NS and percent liquefaction was 0.37 (P < 0.0001), and the correlation between age and NS after adjustment for liquefaction was 0.57 (P < 0.0001). After the eyes were stratified into age groups, the correlation between NS and percent liquefaction was found to be highest in eyes from donors aged 51 to 70. Cortical and posterior subcapsular opacities increased with age, but scores for these cataract types did not significantly correlate with vitreous liquefaction. CONCLUSIONS: Loss of vitreous gel during aging increases the risk of nuclear cataracts. Preservation or replacement of the vitreous gel may protect patients from nuclear cataract.