Biomedical subjects
Publications and source records attributed to M Shah.
Pyoderma gangrenosum (PG) of the scrotum is extremely rare. We report a case of scrotal PG associated with dermatomyositis. Initial healing was slow despite the use of oral prednisolone and azathioprine. Healing was accelerated by the local use of a potent topical corticosteroid. PG should be considered in the differential diagnosis of ulcerating lesions of the genitalia.
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The overall prevalence of vulval involvement in women with lichen planus is unknown. In a series of 37 women with lichen planus, we found vulval lesions in 19 (51%). Vulval lesions are often chronic and may undergo malignant change. All patients presenting with cutaneous or oral lesions of lichen planus should be questioned about, and examined specifically for, signs of genital involvement. Long-term follow-up of these patients is necessary.
BACKGROUND: Patients may present with a range of unexplained oral symptoms, and there has been debate about the role of contact sensitivity in these patients. OBJECTIVE: The aim of this study was to review patch test results in patients presenting with oral and perioral symptoms and to determine the relevance of positive reactions. METHODS: Forty-seven patients with oral symptoms were studied. Patients were tested to the European Standard Series and a range of other allergens, including bakery products, dental materials, medicaments, and metals. RESULTS: Sixty-four percent of the patients had one or more positive allergic reactions. In 14 patients (30%), the results were believed to be relevant to their clinical problem. Relevant allergens included metals, rubber chemicals, food additives, and dental products. Symptoms resolved rapidly in all of the 13 patients in whom the source of the offending allergen was removed. CONCLUSION: Patch testing is a useful investigation in patients with unexplained oral and perioral symptoms. Avoidance of the relevant allergen can result in complete resolution of symptoms.
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Intestinal endometriosis mimics a wide variety of inflammatory, infectious, or neoplastic digestive diseases. To alert clinicians to its diverse manifestations, we describe nine patients who required laparotomy. The underlying diagnosis was elusive initially. In no case were symptoms clearly cyclic or temporally related to phases of the menstrual cycle. Presenting complaints included acute or subacute lower abdominal pain (three patients), hematochezia (two patients), signs or symptoms of small-bowel obstruction (two patients), peritonitis (one patient), and a partially obstructing sigmoid lesion (one patient). The findings of barium enema were nondiagnostic in the five cases in which it was performed. Surgery was needed in each case; indications included inability to exclude carcinoma (two patients), small-bowel obstruction (two patients), diffuse peritonitis (one patient), persistent colonic obstruction (one patient), pericolonic abscess (one patient), and intractable pain (one patient). Intestinal endometriosis has a diverse clinical spectrum, with nonspecific features in many patients. This disease should be considered during the evaluation of unexplained digestive complaints in women of childbearing years.
In a previous study [Coon et al., Am J Hum Genet 52:1234-1249, 1993], we found suggestive evidence of linkage between manic-depressive illness (MDI) in eight multiplex pedigrees and D5S62, a DNA marker mapping to the telomeric region of 5q. As the D1 dopamine receptor gene (DRD1) maps to this region and as alterations in dopaminergic neurotransmission have been indirectly implicated in the pathogenesis of MDI, we directly searched for mutations in the coding region of the DRD1 gene in 22 unrelated cases of bipolar I (BPI) disorder derived from multiplex families. Using single strand conformation polymorphism (SSCP) analysis, we did not observe any abnormal SSCP variants in the BPI cases that differed from controls.
Mutations of human immunodeficiency virus type 1 (HIV-1) protease at four positions, Val82, Asp30, Gly48, and Lys45 were analyzed for the resulting effects on kinetics and inhibition. In these mutants, Val82 was substituted separately by Asn, Glu, Ala, Ser, Asp, and Gln; Asp30 was individually substituted by Phe or Trp; Gly48 by His, Asp, and Tyr, respectively; and Lys45 by Glu. By examination of the inhibition of a single inhibitor, the differences in Ki values between the native and mutant enzymes can range from very large to insignificant even for the mutants with substitutions at the same position. By examination of a single mutant enzyme, the same broad range of Ki changes was observed for a group of inhibitors: Thus, how much the inhibition changes from the wild-type enzyme to a mutant is dependent on both the mutation and the inhibitor. The examination of Ki changes of inhibitors with closely related structures binding to Val82 mutants also reveals that the change of inhibition involves subsites in which Val82 is not in direct contact, indicating a considerable flexibility of the conformation of HIV protease. For the catalytic activities of the mutants, the kcat and Km values of many Val82 mutants and a Lys45 mutant are comparable to the native enzyme. Surprisingly, Gly48 mutations produce enzymes with catalytic efficiency superior to that of the wild-type enzyme by as much as 10-fold. Modeling of the structure of the mutants suggests that the high catalytic efficiency of some substrates is related to an increase of rigidity of the flap region of the mutants. The examination of the relative changes of inhibition and catalysis of mutants suggests that some of the Val82 and Gly48 mutants are potential resistance mutants. However, the resistance is specific with respect to individual inhibitors.
OBJECTIVE: To determine whether women with chorioamnionitis developed elevated serum granulocyte colony-stimulating factor (G-CSF) concentrations and, if so, whether the G-CSF crossed to the fetus. METHODS: We quantified G-CSF before, during, and after delivery and in the cord blood of 12 women with clinical chorioamnionitis and 12 matched controls. We also measured G-CSF messenger RNA (mRNA) transcripts in mononuclear cells isolated from maternal and cord blood at delivery. RESULTS: At study entry, G-CSF concentrations were much higher in women with chorioamnionitis (1397 +/- 950 pg/mL, mean +/- standard error of mean) than in controls (17 +/- 5 pg/mL, P < .05). At delivery, concentrations had increased in both groups (2752 +/- 1100 pg/mL in the chorioamnionitis group, 165 +/- 61 pg/mL in controls; P < .05). After delivery, G-CSF concentrations had diminished to 839 +/- 594 pg/mL in women with chorioamnionitis and to 83 +/- 16 pg/mL in controls (P < .05). Concentrations in the cord blood were 2729 +/- 974 pg/mL for the chorioamnionitis group and 51 +/- 17 pg/mL for controls (P < .05). Granulocyte colony-stimulating factor mRNA transcripts were more abundant in women with chorioamnionitis than in controls but were scarce in all matched cord blood samples tested. CONCLUSION: Serum G-CSF concentrations were elevated during clinical chorioamnionitis, and similar levels were found in maternal and cord serum. Because G-CSF mRNA levels were very low in cord mononuclear cells, the G-CSF in cord serum might be maternal in origin.
Pyogenic granuloma, also known as lobular capillary haemangioma, is a solitary, benign vascular skin tumour. Although a single pyogenic granuloma is common, multiple eruptive pyogenic granulomas are extremely rare. We report the occurrence of multiple, eruptive pyogenic granulomas in a previously healthy 17-year-old girl. Over 200 lesions appeared spontaneously over an 8-month period. Lesions were initially treated with cryotherapy, and then with the pulsed dye laser, resulting in their complete clearance.
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Papuloerythroderma has been described as a distinct clinical entity. It is characterized by pruritus, red flat-topped papules with skin crease sparing, blood eosinophilia and lymphopenia. It has been described almost exclusively in elderly men. We report a case of cutaneous T-cell lymphoma which, at presentation, was indistinguishable from papuloerythroderma, in a 79-year-old male. An excellent clinical response to low dose oral corticosteroids and photochemotherapy was observed. There have only been two previous reports linking papuloerythroderma with T-cell lymphoma. This patient is in keeping with the two previously reported cases and would support the view that papuloerythroderma may predispose to, or in fact represent, an early form of cutaneous T-cell lymphoma.
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Animal studies have shown that maternal protein deficiency during pregnancy affects fetal birth weight. This study has examined whether or not the fetal birth weight of full-term newborns has any relationship with the acute protein nutrition status of the mother. Protein nutrition status was assessed by measuring the plasma transthyretin (prealbumin) concentrations. Plasma transthyretin concentrations (mean +/- SE) from the cord blood of 20 newborns (10.9 +/- 0.5 mg/dl) were significantly lower (p < 0.000000001) compared with respective maternal concentrations (17.8 +/- 0.8). There was a significant correlation of transthyretin concentrations between mother and newborns (r = 0.61, p < 0.005), and of newborn birth weight with plasma transthyretin concentrations of newborns (r = 0.57, p < 0.01) and mothers (r = 0.51, p < 0.03). This study documents a relationship of fetal birth weight with maternal and newborn plasma transthyretin concentrations.
Exogenous addition of neutralising antibody to transforming growth factor-beta 1,2 to cutaneous wounds in adult rodents reduces scarring. Three isoforms of transforming growth factor-beta (1, 2 and 3) have been identified in mammals. We investigated the isoform/isoforms of TGF-beta responsible for cutaneous scarring by: (i) reducing specific endogenous TGF-beta isoforms by exogenous injection of isoform specific neutralising antibodies; and (ii) increasing the level of specific TGF-beta isoforms by exogenous infiltration into the wound margins. Exogenous addition of neutralising antibody to TGF-beta 1 plus neutralising antibody to TGF-beta 2 reduced the monocyte and macrophage profile, neovascularisation, fibronectin, collagen III and collagen I deposition in the early stages of wound healing compared to control wounds. Treatment with neutralising antibodies to TGF-betas 1 and 2 markedly improved the architecture of the neodermis to resemble that of normal dermis and reduced scarring while the control wounds healed with scar formation. Exogenous addition of neutralising antibody to TGF-beta 1 alone also reduced the monocyte and macrophage profile, fibronectin, collagen III and collagen I deposition compared to control wounds. However, treatment with neutralising antibody to TGF-beta 1 alone only marginally reduced scarring. By contrast, wounds treated with neutralising antibody to TGF-beta 2 alone did not differ from control wounds. Interestingly, exogenous addition of the TGF-beta 3 peptide also reduced the monocyte and macrophage profile, fibronectin, collagen I and collagen III deposition in the early stages of wound healing and markedly improved the architecture of the neodermis and reduced scarring. By contrast, wounds treated with either TGF-beta 1 or with TGF-beta 2 had more extracellular matrix deposition in the early stages of wound healing but did not differ from control wounds in the final quality of scarring. This study clearly demonstrates isoform specific differences in the role of TGF-betas in wound healing and cutaneous scarring. TGF-beta 1 and TGF-beta 2 are implicated in cutaneous scarring. This study also suggests a novel therapeutic use of exogenous recombinant, TGF-beta 3 as an anti-scarring agent.
Scarring, leading to impaired function, growth and appearance, is a major problem following many forms of surgery. Fetal wounds, unlike those in the adult, are characterised by a reduced growth factor profile and the absence of scar tissue (Whitby & Ferguson, 1991 a, b). The antiparasitic drug, suramin (a heparin analogue) inhibits binding of various growth factors (e.g. PDGF, bFGF, TGF-beta, EGF, IGF-I, IGF-II) to their receptors in vitro. These growth factors play key roles in wound healing. We attempted to manipulate experimentally their effectiveness in healing adult rat dermal incisional wounds by injecting suramin into the wound margins and comparing the resultant healing with an unmanipulated control wound in the same animal. Immunohistochemical staining demonstrated that, on d 7 and 14 postwounding, the numbers of monocytes/macrophages and blood vessels are markedly increased in suramin treated wounds compared with controls. Extracellular matrix deposition is lower, although very compact in organisation, lacking the usual honeycombed appearance of normal skin. These effects are widespread, being present not only in the wound area, but also in the surrounding tissue. No difference was detected at 70 d postwounding between the scars of suramin-treated and unmanipulated control wounds in the same animals. All such effects are increased slightly through the concentration range of 0.04-40 mg/kg suramin, with no significant change as concentrations greater than 40 mg/kg are applied. This suggests that suramin has marked effects on the early stages of wound healing, which plateau at 40 mg/kg concentration, but has no effect on scar formation.
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Abductor digiti minimi transfer was used to restore opposition in 20 patients, the majority suffering from congenital anomalies of the hand. The transfer was shown to be effective in restoring abduction, but less effective in restoring the rotational component of opposition in these cases. The donor site was critically reviewed and found to be acceptable. The surgical techniques and benefits of this transfer are reviewed.