Slow responder against methotrexate 50 mg intramuscular in severe psoriatic patients: A case series

Methotrexate is the drug of choice used on moderate to severe psoriasis. The limited availability of oral tablet methotrexate stimulates the initiation of the protocol therapy 50 mg intramuscular methotrexate weekly in six consecutive weeks for severe psoriasis cases. There were 30 cases treated using this treatment modality. Twenty-six cases (86%) showed a good response and achieved PASI-90(Psoriasis Area Severity Index-90), four cases (13%) showed a slow response and did not achieve PASI-90. This case report collected slow response cases and identified their risk factor of slow responsiveness with this treatment modality. The comorbidity condition like metabolic syndrome, drugs induced psoriasis, continuous trauma, the side effect of methotrexate administration (ulceration), or the possibility of allergic or irritant contact dermatitis from occupation are suspected to be the risk factor for slow responders in this treatment modality.

Overview of Perimetry

Like a painter, the practitioner of perimetry must learn his or her profession from experience. Just as a painting does not spring from the paint and brushes alone, the perimetrist does get his or her diagnosis from just a printout of the field test. Rather, the perimetrist’s experience in interpreting field test results, his clinical skill in examining the validity of the patient’s performance, and his selection of the needed field technique chosen under the appropriate clinical circumstances combine to produce a suitable test and interpretation of results. In this age of computerization, we tend to accept the infallibility of perimetry. It is true that new developments have corrected some of the errors in technique that have been troubling in earlier methods such as the tangent screen and Goldmann perimeter. However, in our rush to embrace these new techniques, we might forget that there is still a place for these older techniques in selected cases. Among other things, these older techniques may allow for a human element to be introduced when the patient is overwhelmed by technology—that is, a well-performed tangent screen is more valuable on a given occasion than a poorly performed computerized field examination. Such circumstances occur almost always with neuro-ophthalmology patients, who are usually ill in other ways than just visually and need more help in performing the test. Most other patients, particularly those with glaucoma, are much more reliable in their responses in using the newer techniques. They frequently start testing at a younger age and do their testing frequently so they become skilled at performing the test. Many neuro-ophthalmologic patients do not have that experience. Interpreting the blind spot remains a standard part of any field examination. Interpreting the blind spot size requires experience. The blind spot may be enlarged because the patient is a slow responder or because a large myopic crescent is present. An important use of measuring the blind spot is to show the patient what a scotoma is and to test his validity of fixation by putting the target in the blind spot from time to time.

Immunological relationships during primary infection with Heligmosomoides polygyrus: Th2 cytokines and primary response phenotype

SUMMARYThe primary immune response to infection with Heligmosomoides polygyrus was studied in mice differing in response phenotype (fast-SWR, intermediate-NIH, slow-CBA). Marked IgGl and IgE but not IgG2a antibody responses were detected in infected mice and the former were more intense in fast compared with slow responder strains. Mastocytosis, MMCP-1, and the secretion of cytokines by mesenteric lymph node cells, following stimulation in vitro by Con A, were also more intense initially in SWR mice. Secretion of IL-4 declined in all strains by the 4th week of infection, irrespective of response phenotype. IL-10 was only produced briefly by SWR mice. However, the temporal patterns of secretion of IL-3 and IL-9 clearly distinguished fast from slow responder phenotypes. Following initial intense secretion of IL-3, production declined in all strains but in the 5–6th weeks enhanced secretion was evident in SWR and NIH mice and was sustained until week 10 p.i. In contrast, CBA mice never recovered from the initial down-regulation in weeks 3–4 and secretion declined to background levels by week 6 p.i. despite the continued presence of adult worms. Temporal changes in the secretion of IL-9 were very similar: secretion declined in CBA mice by week 6 p.i., whilst SWR and NIH mice continued to secrete high amounts. We suggest that fast and slow responder mice differ not only in their initial responsiveness to parasite antigens but also in their ability to sustain a Th2 response to the parasite and we propose that the latter is in part determined by their different susceptibilities to parasite-mediated immunomodulation. Only the fast responder strains can sustain a Th2 response of sufficient intensity to facilitate expulsion of adult worms.

Immunological relationships during primary infection with Heligmosomoides polygyrus. Regulation of fast response phenotype by H-2 and non-H-2 genes

SummaryThe inheritance of response phenotype to Heligmosomoides polygyrus was investigated in Fl hybrid progeny of fast and slow responder mouse strains. The fast responses of SJL(H-2s) and SWR(H-2q) mice were mediated by dominant genes complementing each other in Fl hybrids which lost worms earlier and produced faster parasite-specific IgG1 antibody responses than either parent. However, the response of Fl hybrids from crosses of C57BL/10 (B10, H-2b) mice with either SJL or SWR differed from that of the parental strains and from each other: (B10 × SWR)F1 lost worms earlier than SWR whilst (B10 × SJL)F1 lost worms later than SJL mice. The Fl progeny of SJL mice with congenic strains B10.G (H-2q) and B10.S (H-2s) lost worms as quickly as SJL. Therefore, the response phenotype mediated by the genome of SJL mice was unaffected by H-2 heterozygosity (with H-2q) or homozygosity (H-2s) despite heterozygosity with B10 background genes, but was slowed significantly by heterozygosity with H-2b. All hybrids involving heterozygosity with B10, irrespective of MHC haplotype or background, failed to clear worms completely, in each case a proportion of mice harbouring residual worm burdens after loss of worms from parental strains.

Involvement of α2-Adrenoreceptors and G Proteins in the Modulation of Platelet Secretion in Response to Streptococcus sanguis

In the presence of plasma, human platelets secrete the contents of their dense granules and then aggregate in response to certain strains of Streptococcus sanguis. After 2 to 5 min of incubation with streptococci, platelets from fast-responding donors will begin to aggregate. Slow responders aggregate after a longer delay. Platelets may secrete after a short (fast responder) or long (slow responder) delay because of differences in the basal levels or responses to potentiating catecholamines. To test this hypothesis in vitro, endogenous basal catecholamine levels in platelets and plasma from fast and slow responders were analyzed by HPLC with electrochemical detection. The total basal concentration of epinephrine in platelets plus plasma was fourfold higher in fast responders, with the platelet compartment showing the greatest difference. The basal affinity of α2-adrenoreceptors in platelets from both groups was similar when estimated using a specific antagonist, [3H]-yohimbine. Platelets from all donors showed decreased α 2-adrenoreceptor affinity in the presence of low (2 n M), but not higher (10 n M), concentrations of added epinephrine. Platelets in the two groups were then compared for secretion of ATP. More ATP was secreted after a shorter delay from fast responding platelets, which was mimicked in slow responders by adding physiologically attainable levels (40 n M) of epinephrine. Addition of the α2-antagonist, phentolamine (10 μ M), to the platelets of slow and fast responders completely inhibited or reduced secretion by one third, respectively. Therefore, α 2-adrenoreceptors modulate the secretory response of platelets to cells of S. sanguis. Modulation of secretion may involve coupling of the α2-adrenoreceptor and S. sanguis receptor via G proteins because secretion in response to S. sanguis was inhibitable by pertussis or cholera toxins, or GTPyS.