Hay Fever. 2. Clinical Features, Diagnosis, Investigation and Treatment

This is the second of two reviews of hay fever. The first articledealt with prevalence and natural history, historical backgroundand mechanisms. This article outlines the clinical featuresof hay fever, examines the correlation of symptoms with pollencount and describes current views of diagnosis and investigation.History and examination, skin testing, the radio-immunosorbenttest (RIST) and radio allergosorbent test (RAST) and the correlationbetween RAST and skin testing are described. Some considerationis given to the part played by nasal challenge tests and measurementsof nasal airways resistance. The section on treatment includessome general considerations, avoidance measures, anti-histamines,nasal steroids, sodium cromoglycate, systemic steroids, nasalvasoconstrictors, hyposensitisation and eye preparations. Thefinal section is centred on future developments.     

Inhibition of binding of phospholipase Cγ1 SH2 domains to phosphorylated epidermal growth factor receptor by phosphorylated peptides

A series of tyrosine-containing peptides 1–12: Asp-Ala-Asp-Glu-Tyr⁹⁹²(PO₃H₂)-Leu-Ile-Pro-Gln-Gln-Gly-OH (1) Asp-Ala-Asp-Glu-Tyr⁹⁹² -Leu-Ile-Pro-Gln-Gln-Gly-OH (2) Phe-Leu-Pro-Val-Pro-Glu-Tyr¹⁰⁶⁸(PO₃H₂)-Ile-Asn-Gln-Ser-Val-OH (3) Phe-Leu-Pro-Val-Pro-Glu-Tyr¹⁰⁶⁸ -Ile-Asn-Gln-Ser-Val-OH (4) Asp-Asn-Pro-Asp-Tyr¹¹⁴⁸JR(PO₃H₂)-Gln-Gln-Asp-Phe-Phe-OH (5) Asp-Asn-Pro-Asp-Tyr¹¹⁴⁸ -Gln-Gln-Asp-Phe-Phe-OH (6) Ala-Glu-Tyr¹¹⁷³(PO₃H₂)-Leu-Arg-Val-Ala-Pro-Gln-Ser-OH (7) Ala-Glu-Tyr¹¹⁷³ -Leu-Arg-Val-Ala-Pro-Gln-Ser-OH (8) Ala-Glu-Tyr¹¹⁷³(PO₃H₂)-Leu-Arg-Val-Ala-OH (9) Ala-Glu-Tyr¹¹⁷³ -Leu-Arg-Val-Ala-OH (10) Tyrl¹¹⁷³(PO₃H₂)-Leu-Arg-Val-Ala-Pro-Gln-Ser-OH (11) Tyr¹¹⁷³ -Leu-Arg-Val-Ala-Pro-Gln-Ser-OH (12) (six pairs with and without the tyrosine phosphorylated) has been synthesized. The peptides were derived from tyrosine autophosphorylation sites in the epidermal growth factor receptor (EGFR): Tyr 992, 1068, 1148 and 1173. Peptide 1, derived from the Tyr 992 site, inhibited binding of a ³⁵S-labelled fusion protein containing both of the SH2 domains from PLCγ1 to the phosphorylated EGFR with an IC₅₀ of 8 μM. All of the phosphorylated peptides except 11 (1, 3, 5, 7 and 9) inhibited this binding to some degree (20–55%) at 10 p μM. The nonphosphorylated peptides were inactive in this assay. The nonphosphorylated peptides 2, 4, 6, 8, 10 and 12 were obtained by standard solid-phase synthetic methodologies using both Boc/benzyl and Fmoc/tert-butyl strategies. The phosphorylated peptides 1, 3, 5, 7, 9 and 11 were similarly obtained using a Fmoc/tert-butyl strategy incorporating unprotected N^x-Fmoc-Tyr, followed by phosphitylation and oxidation of the tyrosine in the resin-bound peptide. In addition, Asp-Ala-Asp-Glu-Phe⁹⁹²(4-CH₂PO₃H₂)-Leu-Ile-Pro-Gln-Gln-Gly-OH (15), an analog of 1 incorporating an enzymatically stable phosphotyrosine mimic, 4-phosphonomethyl-l -phenylalanine, was synthesized and found to be inactive.     

Distal urethral electrical conductance (DUEC)—a preliminary assessment of its role as a quick screening test for incontinent women

Summary. Measurement of distal urethral electrical conductance (DUEC) has been used to detect the movement of urine along the distal urethra. DUEC was used as a screening test in 100 women attending the urodynamic clinic with incontinence and in the 33 women who voided over 250 ml, the findings correlated well with subsequent urodynamic diagnosis of urethral sphincter incompetence and detrusor instability.     

Intracranial aspergillosis in a non-immunocompromised patient treated for muscle-invasive bladder cancer

We report a case of intracerebral Aspergillosis in a patient undergoing radical cystectomy for the treatment of muscle-invasive bladder cancer who did not reveal any deterioration of the immune system. Aspergillus fumigatus is an ubiquitously present, airborne fungus that tends to infect the upper respiratory tract. However, the latter was not observed in the patient presented. Complications in the form of an involvement of the central nervous system are very rarely recognized as a result of an Aspergillus infection and primarily occur in patients who are not immunologically competent. To our knowledge, we present the first case of intracerebral invasive Aspergillosis in an otherwise healthy patient diagnosed with an urological malignancy.     

Immunohistochemical Localization of Acetaminophen in Target Tissues of the CD-i Mouse: Correspondence of Covalent Binding with Toxicity

Administration of hepatotoxic doses of acetaminophen (APAP)to mice results in necrosis, not only of liver cells but ofrenal proximal tubules and bronchiolar and olfactory epithehum.In the liver, covalent binding is localized to the centrilobularhepatocytes which later undergo necrosis. This study was undertakento compare the cellular distribution of bound APAP in all fourmajor target tissues with that of cytochrome P4502E1 (a P450isoenzyme commonly associated with APAP bioactivation), withemphasis on the cell types which later undergo necrosis. Tissueswere collected from mice at selected times after APAP administration(600 mg/kg, po) and fixed by microwave irradiation for immunohistochemistry,or in formalin for histopathological study. Immunohistochemicallocalization of bound APAP was performed on 5-µm paraffinsections using an affinity-purified anti-APAP antibody. Similartissues from naive mice were used for immunohistochemical localizationof cytochrome P4502E1 (using a polyclonal sheep anti-P4502E1antibody). Positive staining with both the anti-APAP and theanti-P4502E1 antibodies was similar in distribution, being presentin the cell types which become damaged by APAP in all four targettissues. These results demonstrate that covalent binding andsubsequent necrosis are localized in common with cytochromeP4502E1, suggesting that, as in the liver, toxicity in extrahepatictargets is also related to the ability of these tissues to activateAPAP in situ.     

Cutaneous Effects of Cryogen Spray Cooling on In Vivo Human Skin

BACKGROUND: Despite widespread clinical use of cryogen spray cooling (CSC) in conjunction with laser dermatologic surgery, in vivo cutaneous effects have not been systematically evaluated. OBJECTIVE: The authors characterize the in vivo cutaneous effects for Fitzpatrick skin types I through VI after CSC exposures of varying spurt durations and spurt delivery patterns (single vs. multiple spurts). MATERIALS AND METHODS: Twenty-seven normal human subjects were exposed to single cryogen spurts from 10 to 80 milliseconds, and multiple spurt patterns consisting of two 20-millisecond spurts, four 10-millisecond spurts, and eight 5-millisecond spurts. Subjects were evaluated by clinical observation and photography at 1 hour, 1 day, and 1, 4, 8, and 12 weeks after CSC exposure. RESULTS: Acute erythema and urticaria (1-24 hours) were noted in 14 of 27 and 3 of 27 subjects, respectively. Transient hyperpigmentation occurred in 4 of 27 subjects (skin types III-VI) but resolved spontaneously without medical intervention in all subjects by 8 weeks. No permanent skin changes were noted in any subjects. Skin reactions were more common with longer single-spurt durations (50 milliseconds or greater) and multiple spurt patterns. CONCLUSION: Acute erythema, urticaria, and, less commonly, transient hyperpigmentation were observed after CSC exposure. Permanent skin injury was not observed and is unlikely.