Notes: The primary classes of drugs used for pain control in horses include the non-steroidal anti-inflammatory drugs (NSAIDS), the alpha-2 agonists, and the opiates, but each of these drug classes has significant adverse effects. Ketamine hydrochloride is a non-competitive antagonist at N-methyl D-aspartate (NMDA) receptors in the spinal cord and has been used in both dogs and humans to provide analgesia. The purpose of this study was to identify a safe administration rate for a continuous infusion of ketamine to awake horses and describe the clinical effects of this infusion. Six horses were administered a continuous infusion of ketamine hydrochloride at a low dose (0.4 mg/kg/hr) and high dose (0.8 mg/kg/hr). Each infusion took place over 6 hours and the horses were monitored during infusion as well as for the 6 hours post-infusion. The following parameters were evaluated: heart rate, blood pressure, respiratory rate, activity level, and analgesic thresholds. Both the low dose and high dose rates were tolerated well by all horses with no signs of excitation or discomfort. Post-infusion heart rate and mean arterial blood pressure were significantly decreased as compared to pre-infusion values (p=0.02 and p=0.02, respectively) A significant increase in analgesic threshold was not identified.Subanesthetic infusions of ketamine to awake horses appear to be well tolerated and cause only mild changes in clinical parameters. Further research is needed to evaluate the analgesic potential of these infusions.

Notes: Objective Guidelines in some European countries and the United States suggest that pregnant women should avoid prolonged standing and heavy lifting in the workplace during the second and third trimester of pregnancy. However, results from epidemiological studies on this topic are ambiguous. The aim of this study was to evaluate the influence of standing and walking at work in the second trimester on preterm delivery in a population with a low frequency of other workplace hazards.Subjects and design A prospective cohort of 8711 women with singleton pregnancies was established during 1989 through 1991. Information was collected during the 16th week of pregnancy about medical and obstetrical history, general lifestyle factors and exposures at work. The analyses were restricted to 4259 respondents who worked at the 16th week. Potential confounders and effect modifiers were evaluated by stratification and multivariate analyses.Results After adjustment for confounders, women standing more than five hours per work day had an odds ratio (OR) for preterm delivery of 1.2 (95% CI 0.6 to 2.4) compared with women standing two hours or less. For walking, the OR was 1.4 (95% CI 0.7 to 2.5). Many women were unable to separate periods of standing from periods of walking; a combined measure of these two exposures was created to reflect exposure intensity. Women who reported more than five hours of both standing and walking had an adjusted OR of 3.3 (95% CI 1.4 to 8.0) compared with women who reported two hours or less on either of the exposures. No adverse effects were seen for lifting or other types of physical exertion.Conclusions Our findings suggest that standing and walking at work during the second trimester may present a particular risk for preterm delivery, and workplace guidelines are justified. Further research is needed to address the specific mechanisms by which physical exertion, including standing and walking, might cause preterm delivery.

Notes: The surface ultrastructure of normal and abnormal endometrial cells from patients receiving oestrogen therapy for the climacteric syndrome was studied by scanning electron microscopy. Patients with endometrial pathology were treated with oral progestogens. Excessive oestrogen stimulation caused proliferation of cilia and microvilli. Cystic hyperplasia was characterised by a proliferation of cilia until they covered more than one-third of the surface area of the endometrium; further proliferation occurred in cases of adenomatous hyperplasia when the surface was almost completely covered with cilia. Cell morphology remained apparently normal until atypical hyperplasia, when occasional cells appeared large and irregular, or adenocarcinoma occurred, when the surface cells appeared large, pleomorphic and sometimes wrinkled, being mostly devoid of cilia. Although cystic hyperplasia was converted to a normal histological picture of atrophic or pseudo-decidual endometrium by courses of progestogen, the deciliated endometrial cells showed persisting abnormal ultrastructural characteristics.

Notes: In high risk pregnancies with severe fetal distress, a reduction of fetal movements may take place before fetal death occurs. This decrease is accompanied by a weakening of the fetal movements. One hundred and twenty pregnant women (310 recordings) between 20 and 41 weeks gestation recorded fetal movements and classified them into weak, strong, and rolling. The movements noted by the woman were correlated to those recorded by a fetal movements recorder. The rate of weak movements gradually decreased until the 36 to 37th week, while the strong and rolling movements increased. From the 36 to 37th week till term weak movements increased again with a decline in strong and rolling movements. Before fetal death, or in severe fetal distress with decreased total movements, the relative rate of weak movements increased. Reduction in daily total movements without a change in the distribution of the type of movement may not indicate fetal distress.

Notes: The objective of this study was to investigate whether circulating basement membrane zone (BMZ) antibodies are present in erosive lichen planus (LP) of the vulva. In total, 56 consecutive women with biopsy-confirmed erosive LP of the vulva were recruited from a vulval clinic in a district general hospital and teaching hospital in Oxfordshire. Indirect immunofluorescence (IgG and IgA) was performed on 56 sera, and 15 were tested to IgG subclasses (1–4). Immunoblotting was carried out on salt-split and urea-extracted epidermal skin extracts on 11. The main outcome measure was the presence or absence of staining at the BMZ. Of the 56 sera, 34 (61%) had weak (neat or 1 : 5) epidermal-binding BMZ antibodies (25 had IgG, 5 had IgA, 4 had both IgG and IgA). All 15 sera tested to IgG showed epidermal binding to one or more IgG subclasses: IgG1 (7 sera), IgG2 (7), IgG3 (7) and IgG4 (0). Immunoblotting identified IgG antibodies to bullous pemphigoid (BP)180 (10/11) and BP230 (2/11). The majority (61%) of patients with vulval erosive LP had circulating serum IgG BMZ antibodies, chiefly reacting with BP180. There was subclass restriction of the IgG response to IgG1, 2 and 3. The significance of these antibodies is uncertain, but they may be a marker for the disease.

Notes: Histopathology demonstrates disruption of the basal layer of the epidermis in lichen planus (LP) and altered expression of basement membrane zone (BMZ) components occurs in cutaneous and oral LP. This is the first study in erosive LP of the vulva to investigate the expression of components of the BMZ and extracellular matrix by indirect immunofluorescence. Six biopsies from lesional vulval erosive LP were compared with two biopsies from normal vulva and five biopsies from normal skin. In erosive vulval LP there was widespread disruption of several BMZ components compared to normal skin. The hemidesmosome antigens were disrupted and attenuated, or absent. Expression of lamina lucida proteins and anchoring filaments also showed some alteration. Lamina densa components were altered and in particular there was very marked thickening, streaking and fragmentation of the anchoring fibrils. Some dermal extracellular matrix proteins were increased. This study has demonstrated widespread damage to the BMZ in erosive LP of the vulva, in particular the hemidesmosomes (α6β4 integrin, BP230, BP180) and anchoring fibrils (collagen VII). This suggests an alteration in antigenic expression in the BMZ that may lead to exposure of epitopes and thus make these proteins vulnerable to attack by autoantibodies.

Notes: Background  In bullous pemphigoid (BP), cicatricial pemphigoid (CP) and linear IgA disease (LAD), autoantibodies to the basement membrane zone (BMZ) are found in skin and mucosa, blood and blister fluid. Objectives  To assess whether BMZ antibodies might also be detected in urine. Methods  Urine and serum samples from 62 patients (32 with BP, 17 with CP and 13 with LAD) were analysed for antibody isotypes and subclasses by indirect immunofluorescence, and urine and serum samples from 40 patients (25 with BP, eight with CP and seven with LAD) were screened for target antigens using immunoblotting. Results  Fourteen of 32 patients with BP had detectable levels of IgG BMZ autoantibodies in their urine, and all 32 had positive sera. Of these 14 BP patients, 13 had epidermal-binding serum autoantibodies at a titre 〉 1 : 160, and one had dermal-binding serum antibodies at a titre of 1 : 40. BMZ autoantibodies were not detected in the urine of the CP or LAD patients, but the corresponding sera were of low titre or negative. IgG subclasses (IgG1–4) were less frequently detected in urine than in serum. IgG4 was the predominant subgroup found (10 urine samples and all 14 sera), followed by IgG1 (two urine samples and 12 sera); IgG2 was detected in a single urine sample and three sera, and IgG3 was not detected. Eight of 25 BP and one of eight CP urine samples were positive on immunoblotting, and bound BP230 and/or BP180 with IgA and/or IgG autoantibodies. IgA autoantibodies were not detected in the urine of the seven LAD patients. The corresponding sera were often more positive, with 21 of 25 BP, five of eight CP and six of seven LAD sera immunoblotting the major BP antigens. Conclusions  The detection of IgG autoantibodies from urine samples using indirect immunofluorescence correlated with a high titre of IgG autoantibodies in the serum. IgG and IgA autoantibodies in the urine were detected by immunoblotting, although less frequently than in serum. The finding of BMZ antibodies in the urine of many BP patients may have clinical relevance, and may have a restricted application in the diagnosis of immunobullous disease.

Notes: Many of the techniques used in the diagnosis and characterization of the acquired blistering diseases of the skin and of their target antigens require the use of tissue that has been modified by heat, chemicals, or by proteolytic digestion. The effect these treatments may have on the blistering disease antigens is poorly understood and has seldom been taken into account in the interpretation of the results. Likewise, their effect on the immunodetection and expression of the ubiquitous proteins of the basement membrane zone and extracellular matrix has rarely been investigated. We have addressed this problem by probing tissue split after heat, chemical treatment and proteolytic digestion with an extensive panel of antibodies to the hemidesmosome-plasma membrane-anchoring filament complex, the extracellular matrix and the anchoring fibrils. The results showed that chemical modification by sodium chloride, calcium chloride and ethylenediaminetetraacetic acid, and incubation in 0.15 mol/L NaCl at 56°C for 1 min did not adversely affect the expression of the α6β4 integrin, laminin-5, the LH39 antigen, laminin-1, collagen type IV or collagen type VII. The methods that involved proteolytic digestion had thegreatest detrimental effect on these basement membrane components, with pepsin having a damaging effect on the greatest number of antigens, and the LH39 antigen being the most sensitive to proteolytic degradation. This project has highlighted the susceptibility of the basement membrane zone and extracellular matrix proteins to proteolytic hydrolysis. It has demonstrated a way of differentiating between specific proteins, and has shown its potential for the differential diagnosis of the autoimmumme blistering disease antigens.

Notes: Background Immunobullous diseases are uncommon in childhood. In contrast to adults, the most commonly seen is IgA-mediated chronic bullous disease of childhood (CBDC), while IgG-mediated bullous pemphigoid (BP), cicatricial pemphigoid (CP) and epidermolysis bullosa acquisita (EBA) are rare. We have demonstrated both IgG and IgA autoantibodies to basement membrane zone target antigens in eight children with ‘mixed immunobullous disease of childhood’. Objectives To elucidate whether a dual antibody response makes these patients distinct regarding their presentation, immunopathology, course and prognosis. Methods We compared the eight children showing the double antibody response with 62 children with CBDC, BP, CP and EBA in whom only one antibody isotype was demonstrated. Clinical information at presentation, clinical course and response to treatment were recorded, and immunoblotting and direct and indirect immunofluorescence (IF) were performed. Results Six of the eight patients presented with clinical features of CBDC. In two others, it was uncertain whether they had CBDC or BP. Seven of the eight demonstrated a dual antibody response on indirect IF and three on direct IF. Immunoblotting revealed a variety of epidermal and dermal target antigens (BP230, BP180, 97-kDa protein and laminin 5). Five of the eight responded well to dapsone, two to sulphonamides, and one to systemic erythromycin alone. The clinical course was not protracted. Five are in remission 1–4 years following treatment, and three still have active disease suppressed by treatment after 6 months−2 years. Conclusions Although we do not know why these children have ‘mixed immunobullous disease’ (the dual antibody response), our results indicate that the presence of IgA is associated with a good response to treatment with antimicrobials (dapsone, sulphonamides, erythromycin), and the clinical course is no more protracted than that found in children with a single antibody response.