Early experience in using and 18 Me V linear accelerator for mycosis fungoides at Howard University Hospital.

This paper describes the problems and solutions in using 18 MeV linear accelerator, with minimum 6 MeV electron capability, for total skin irradiation for mycosis fungoides. The 6 MeV electron energy can be degraded to acceptable electron energy of 3.2 MeV by interposing a plexiglass sheet of 9.6 mm in the beam. To minimize the bremsstrahlung, the degrading plexiglass should be kept away from the machine head. A wide area with uniform dose distribution over single plane can be achieved by using dual fields but homogenous dose distribution over irregular body surface cannot be achieved mainly because of self-shielding. The nails and the ocular lens can be easily shielded from the low energy electrons with 1.5 mm lead shield.     

Lymphocyte transformation responses to phytohaemagglutinin and pokeweed mitogen in patients at differing stages of HIV infection: are they worth measuring?

AIMS--To determine whether the routine measurement of lymphocyte transformation responses to mitogenic stimuli provide any information additional to that available from routine T cell CD4 and CD8 analysis in patients with HIV infection. METHODS--The case records of 197 immunologically investigated HIV seropositive patients were reviewed. The influence of disease stage on T lymphocyte subsets and lymphocyte transformation responses (LyTR) to phytohaemagglutinin (PHA) and Pokeweed mitogen was assessed. RESULTS--The median CD3 and CD4 counts and LyTR to PHA and Pokeweed mitogen were highest in patients with persistent generalised lymphadenopathy (PGL) and decreased progressively in the order: asymptomatic patients, those with ARC, those with AIDS. LyTR to PHA was preserved in over 70% of all patients, but the response to Pokeweed mitogen was depressed in 8% of patients with PGL, 34% of asymptomatic patients, 68% of those with ARC and 78% of those with AIDS. Subnormal values of both CD4 + T cells and LyTR to Pokeweed mitogen were more common in patients with ARC and AIDS (68%) than in those who were asymptomatic or had PGL (20%). CONCLUSIONS--CD4 T cell analysis and LyTR to Pokeweed mitogen, but not to PHA, both correlate with disease states in patients with HIV infection.     

Response of the ENPP1-Deficient Skeletal Phenotype to Oral Phosphate Supplementation and/or Enzyme Replacement Therapy: Comparative Studies in Humans and Mice

Inactivating mutations in human ecto-nucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1) may result in early-onset osteoporosis (EOOP) in haploinsufficiency and autosomal recessive hypophosphatemic rickets (ARHR2) in homozygous deficiency. ARHR2 patients are frequently treated with phosphate supplementation to ameliorate the rachitic phenotype, but elevating plasma phosphorus concentrations in ARHR2 patients may increase the risk of ectopic calcification without increasing bone mass. To assess the risks and efficacy of conventional ARHR2 therapy, we performed comprehensive evaluations of ARHR2 patients at two academic medical centers and compared their skeletal and renal phenotypes with ENPP1-deficient Enpp1^asj/asj mice on an acceleration diet containing high phosphate treated with recombinant murine Enpp1-Fc. ARHR2 patients treated with conventional therapy demonstrated improvements in rickets, but all adults and one adolescent analyzed continued to exhibit low bone mineral density (BMD). In addition, conventional therapy was associated with the development of medullary nephrocalcinosis in half of the treated patients. Similar to Enpp1^asj/asj mice on normal chow and to patients with mono- and biallelic ENPP1 mutations, 5-week-old Enpp1^asj/asj mice on the high-phosphate diet exhibited lower trabecular bone mass, reduced cortical bone mass, and greater bone fragility. Treating the Enpp1^asj/asj mice with recombinant Enpp1-Fc protein between weeks 2 and 5 normalized trabecular bone mass, normalized or improved bone biomechanical properties, and prevented the development of nephrocalcinosis and renal failure. The data suggest that conventional ARHR2 therapy does not address low BMD inherent in ENPP1 deficiency, and that ENPP1 enzyme replacement may be effective for correcting low bone mass in ARHR2 patients without increasing the risk of nephrocalcinosis. © 2021 American Society for Bone and Mineral Research (ASBMR).     

Effect of solvent on the characteristics of pentamidine loaded microcapsule

Biodegradable microcapsules of pentamidine/poly(L-lactide-co-D,L-lactide) were prepared by solvent evaporation technique using a mixture of organic solvents. The control batch of microcapsules was prepared using dichloromethane. The effect of solvent on the characteristics of pentamidine loaded microcapsules was examined by substituting up to 30% of dichloromethane with acetone, methanol, DMSO, ethyl acetate, and ethanol, respectively. No significant change in the surface morphology was observed when dichloromethane was substituted with 20% or less amount of other solvents. These microcapsules were all porous and spherical. However, the use of 30% DMSO or ethanol, along with dichloromethane, resulted in a mixture of elongated and spherical microcapsules. The efficiency of encapsulation of these two batches was also significantly higher than the other batches of microcapsules. The average particle size of the microcapsules prepared with 30% DMSO (165 microm) was significantly higher than the other batches (< 80 microm). A substitution of 10-30% dichloromethane with other listed organic solvents also showed a significant difference in the initial drug release. The drug release within the first twenty-four hours varied from 4 to 16%. The use of a second organic solvent, except ethanol, resulted in a significantly higher drug release during the second half of the dissolution study. The drug release continued more than 60 days.     

Regulation of rat mesangial cell migration by platelet-derived growth factor, angiotensin II, and adrenomedullin

This study sought to determine whether platelet-derived growth factor (PDGF) and angiotensin II (AngII) stimulate migration of cultured rat glomerular mesangial cells. After finding that this was so, the effects of adrenomedullin (ADM) and cAMP-elevating agents on basal and stimulated mesangial cell migration were examined. Two isoforms of PDGF, AB and BB, stimulated migration in a concentration-dependent manner between 1 and 50 ng/ml, while the AA isoform lacked significant effect. AngII modestly but significantly stimulated migration in a concentration-dependent manner between 10(-7) and 10(-6) mol/L. Rat ADM significantly inhibited the PDGF BB- and AngII-stimulated migration in a concentration-dependent manner between 10(-8) and 10(-7) mol/L. Inhibition by rat ADM was accompanied by an increase in cellular cAMP. cAMP agonists or inducers such as 8-bromo cAMP, forskolin, and prostaglandin I2 also significantly reduced the stimulated migration. H 89, a protein kinase A (PKA) inhibitor, attenuated the inhibitory effect of ADM, and a calcitonin gene-related peptide (CGRP) receptor antagonist, human CGRP (8-37), abolished the inhibitory effects of rat ADM. These results suggest that PDGF AB and BB as well as AngII stimulate rat mesangial cell migration and that ADM can inhibit PDGF BB- and AngII-stimulated migration, at least in part through cAMP-dependent mechanisms likely to involve specific ADM receptors with which CGRP interacts. The adenylate cyclase/cAMP/PKA system may be involved in the migration-inhibitory effect of ADM in these cells.     

Environmental covariates: effects on the power of sib-pair linkage methods

The effect of inclusion of environmental risk factors on the power of sib-pair linkage methods was tested for a qualitative trait. It was found that inclusion of an environmental variable did not increase the power of the Haseman-Elston (H-E) sib-pair nonparametric linkage analysis test. However, a significant increase in power was observed for both the H-E and affected-sib-pair tests, even in small samples, when persons unexposed to the environmental risk factor were coded as unknown.     

Sturge-Weber syndrome with bilateral congenital syndactyly: a previously undescribed association

The Sturge-Weber syndrome consists of unilateral port-wine haemangioma of the face which may be associated with an ipsilateral intracranial haemangioma and choroidal angioma. The common derivation of the meningeal, choroidal and facial vessels may explain a congenital malformation of all three areas. I report the case of a child with typical Sturge-Weber syndrome who had a previously undescribed association with bilateral congenital syndactyly.