A pas de deux of osteoporosis and sarcopenia: osteosarcopenia.

The musculoskeletal conditions osteoporosis and sarcopenia are highly prevalent in older adults. Osteoporosis is characterized by low bone mass and microarchitectural deterioration of bone, whereas sarcopenia is identified by the loss of muscle strength, function and mass. Osteoporosis represents a major health problem contributing to millions of fractures worldwide on an annual basis, whereas sarcopenia is associated with a range of adverse physical and metabolic outcomes. They both affect physical and social function, confidence and quality of life as well as contributing to high health-care costs worldwide. Osteosarcopenia is the term given when both conditions occur concomitantly and it has been suggested that interactions between these two conditions may accelerate individual disease progression as co-existence of osteoporosis and sarcopenia is associated with higher morbidity from falls, fracture, disability as well as mortality. In this review, we will outline the epidemiology, pathogenesis and clinical consequences of osteosarcopenia and discuss available management strategies.

Approaches to the diagnosis and prevention of frailty.

An individual who is living with frailty has impairments in homeostasis across several body systems and is more vulnerable to stressors that may ultimately predispose them to negative health-related outcomes, disability and increased healthcare use. Approximately a quarter of individuals aged > 85 years are living with frailty and as such the identification of those who are frail is a public health priority. Given that the syndrome of frailty is defined by progressive and gradual loss of physiological reserves there is much scope to attempt to modify the trajectory of the frailty syndrome via physical activity and nutritional interventions. In this review we give an up to date account on the identification of frailty in clinical practice and offer insights into physical activity and nutritional strategies that may be beneficial to modify or reverse the frailty syndrome.

A systematic review of the provision and efficacy of patient and carer information and support (PCIS) interventions for patients with dementia and their informal carers.

BACKGROUND: The NHS dementia strategy identifies patient and carer information and support (PCIS) as a core component of gold-standard dementia care. This is the first systematic review of PCIS, performed to analyse the literature and evidence for these interventions. AIMS: To systematically review literature evaluating the effectiveness of the provision of PCIS for people with dementia and their informal carers, in inpatient and outpatient settings. METHODS: Searches of four online biomedical databases, accessed in September 2018. Studies were selected if they were: relating to people with dementia or their informal carers, based in inpatient or outpatient settings, published in English-language peer-reviewed journals no earlier than the year 2000 and assessed dementia-related information or social support interventions, by measuring qualitative or quantitative carer or patient-reported outcomes. Standardised data extraction and quality appraisal forms were used. RESULTS: 7 of 43 full-text papers analysed were eligible for analysis. 3 papers were different arms of one original study. Trends were present in the quantitative results towards reduced patient and carer depression and anxiety and the themes in the qualitative analysis were in favour of the intervention. CONCLUSIONS: The studies analysed were too heterogeneous in design, population and outcomes measured to make a conclusive opinion about the efficacy of these interventions. It is surprising that for such a common condition, a gold-standard evidence-based intervention and standardised delivery for provision of PCIS for people living with dementia in the UK does not exist. Further research is therefore vital.

COVID-19 and associations with frailty and multimorbidity: a prospective analysis of UK Biobank participants.

BACKGROUND: Frailty and multimorbidity have been suggested as risk factors for severe COVID-19 disease. AIMS: We investigated, in the UK Biobank, whether frailty and multimorbidity were associated with risk of hospitalisation with COVID-19. METHODS: 502,640 participants aged 40-69 years at baseline (54-79 years at COVID-19 testing) were recruited across UK during 2006-10. A modified assessment of frailty using Fried's classification was generated from baseline data. COVID-19 test results (England) were available for 16/03/2020-01/06/2020, mostly taken in hospital settings. Logistic regression was used to discern associations between frailty, multimorbidity and COVID-19 diagnoses, after adjusting for sex, age, BMI, ethnicity, education, smoking and number of comorbidity groupings, comparing COVID-19 positive, COVID-19 negative and non-tested groups. RESULTS: 4510 participants were tested for COVID-19 (positive = 1326, negative = 3184). 497,996 participants were not tested. Compared to the non-tested group, after adjustment, COVID-19 positive participants were more likely to be frail (OR = 1.4 [95%CI = 1.1, 1.8]), report slow walking speed (OR = 1.3 [1.1, 1.6]), report two or more falls in the past year (OR = 1.3 [1.0, 1.5]) and be multimorbid (≥ 4 comorbidity groupings vs 0-1: OR = 1.9 [1.5, 2.3]). However, similar strength of associations were apparent when comparing COVID-19 negative and non-tested groups. However, frailty and multimorbidity were not associated with COVID-19 diagnoses, when comparing COVID-19 positive and COVID-19 negative participants. DISCUSSION AND CONCLUSIONS: Frailty and multimorbidity do not appear to aid risk stratification, in terms of positive versus negative results of COVID-19 testing. Investigation of the prognostic value of these markers for adverse clinical sequelae following COVID-19 disease is urgently needed.

A systematic review of specialist inpatient dementia care services versus standard inpatient dementia care in acute hospitals.

BACKGROUND: Specialist inpatient dementia units (SIDU) have been developed to address adverse outcomes often experienced by people living with dementia admitted to acute hospitals. However, the evidence base of their effectiveness remains limited. AIM: To review the current literature to establish the comparative effectiveness of acute hospital SIDU vs. standard ward care (SWC). METHODS: We did an online search of 12 biomedical databases from inception to 31st October 2017. Studies of inpatients with any form of dementia in acute hospitals, published in English language peer-reviewed journals, using experimental, observational or qualitative study designs, comparing SIDU with SWC and which measured any qualitative or quantitative outcome of the patient or carer experience were included in the search criteria. We used a standardised data extraction and appraisal form. RESULTS: Three of 46 full-text studies evaluated were suitable for analysis. Due to study heterogeneity, pooled odds ratios were only possible for mortality [OR 1.06 (CI 1.0-1.4)]. Otherwise, a narrative synthesis was performed. Although quantitative measures of length of stay, mortality and behavioural and psychiatric symptoms of dementia are not significantly lower, SIDU are associated with greater patient and carer satisfaction, reduced readmission rates, more accurate and comprehensive assessment processes, documentation of resuscitation decisions, and increased rates of discharge to the patient's own home. CONCLUSIONS: Although SIDU may be associated with improved care outcomes, the current evidence of their effectiveness is markedly limited. Further research and service evaluation of SIDU as a method for providing high-quality dementia care in acute NHS Trusts is needed. PROSPERO: CRD42017078364.

Muscle Mass, Muscle Morphology and Bone Health Among Community-Dwelling Older Men: Findings from the Hertfordshire Sarcopenia Study (HSS).

Sarcopenia and osteoporosis are associated with poor health outcomes in older people. Relationships between muscle and bone have typically been reported at a functional or macroscopic level. The aims of this study were to describe the relationships between muscle morphology and bone health among participants of the Hertfordshire Sarcopenia Study (HSS). 105 older men, mean age 72.5 (SD 2.5) years, were recruited into the HSS. Whole body lean mass as well as appendicular lean mass, lumbar spine and femoral neck bone mineral content (BMC) and bone mineral density (BMD) were obtained through dual-energy X-ray absorptiometry scanning. Percutaneous biopsy of the vastus lateralis was performed successfully in 99 participants. Image analysis was used to determine the muscle morphology variables of slow-twitch (type I) and fast-twitch (type II) myofibre area, myofibre density, capillary and satellite cell (SC) density. There were strong relationships between whole and appendicular lean body mass in relation to femoral neck BMC and BMD (r ≥ 0.43, p < 0.001). Type II fibre area was associated with both femoral neck BMC (r = 0.27, p = 0.01) and BMD (r = 0.26, p = 0.01) with relationships robust to adjustment for age and height. In unadjusted analysis, SC density was associated with whole body area (r = 0.30, p = 0.011) and both BMC (r = 0.26, p = 0.031) and area (r = 0.29, p = 0.017) of the femoral neck. We have demonstrated associations between BMC and changes in muscle at a cellular level predominantly involving type II myofibres. Interventions targeted at improving muscle mass, function and quality may improve overall musculoskeletal health. Larger studies that include women are needed to explore these relationships further.

Skeletal muscle morphology in sarcopenia defined using the EWGSOP criteria: findings from the Hertfordshire Sarcopenia Study (HSS).

BACKGROUND: Sarcopenia is defined as the loss of muscle mass and function with age and is associated with decline in mobility, frailty, falls and mortality. There is considerable interest in understanding the underlying mechanisms. Our aim was to characterise muscle morphology changes associated with sarcopenia among community dwelling older men. METHODS: One hundred and five men aged 68-76 years were recruited to the Hertfordshire Sarcopenia Study (HSS) for detailed characterisation of muscle including measures of muscle mass, strength and function. Muscle tissue was obtained from a biopsy of the vastus lateralis for 99 men and was processed for immunohistochemical studies to determine myofibre distribution and area, capillarisation and satellite cell (SC) density. RESULTS: Six (6 %) men had sarcopenia as defined by the European Working Group on Sarcopenia in Older People (EWGSOP) criteria. These men had lower SC density (1.7 cells/mm(2) vs 3.8 cells/mm(2), p = 0.06) and lower SC/fibre ratio (0.02 vs 0.06, p = 0.06) than men without sarcopenia. Although men with sarcopenia tended to have smaller myofibres and lower capillary to fibre ratio, these relationships were not statistically significant. CONCLUSION: We have shown that there may be altered muscle morphology parameters in older men with sarcopenia. These results have the potential to help identify cell and molecular targets for therapeutic intervention. This work now requires extension to larger studies which also include women.

Primary hyperparathyroidism: an analysis of failure of parathyroidectomy.

BACKGROUND: Preoperative imaging in patients undergoing surgery for primary hyperparathyroidism (PHPT) is used primarily to facilitate targeted parathyroidectomy. Failure of preoperative localisation mandates a bilateral exploration. It is thought that the results of imaging may also predict the success of surgery. The aims of this study were to assess whether the findings on preoperative localisation influenced outcomes following parathyroidectomy for PHPT and to explore factors underlying failure to cure at surgery. METHODS: We analysed outcomes of all patients who underwent first-time surgery for PHPT in two centres over a 5-year period to determine an association with demographic characteristics and findings on preoperative imaging. Records of patients not cured by initial surgery were reviewed to explore factors underlying failure to cure. RESULTS: The failure rate (persistent disease) in the entire cohort was 5 % (25/541) (bilateral neck explorations, 5 %; unilateral exploration, 7 %; targeted approach, 4 %), while two patients developed recurrent disease. In patients who had undergone dual imaging with an ultrasound scan and (99m)Tc-sestamibi scintigraphy, failure rates with "lateralised and concordant" imaging, "nonconcordant" imaging, and "dual-negative" imaging were 2, 9, and 11 %, respectively (p = 0.01). Of the 25 patients with persistent disease, multigland disease (MGD) was present in 52 % (13/25) and ectopic adenoma in 24 % (6/12). CONCLUSIONS: Patients with PHPT who do not have lateralised and concordant dual imaging are at higher risk of persistent disease. A significant proportion of failures are due to the inability to recognise the presence and/or extent of MGD.

Systematic review of intravenous methylene blue in parathyroid surgery.

BACKGROUND: Methylene blue is an intraoperative adjunct for localization of enlarged parathyroid glands. The availability of preoperative and other intraoperative localization methods, and the reported adverse effects of methylene blue make its routine use debatable. The aim of this study was to perform a systematic review of the use of methylene blue in parathyroidectomy. METHODS: A systematic review of English-language literature in MEDLINE and Scopus databases on the use of intravenous methylene blue in parathyroid surgery was carried out. RESULTS: There were no randomized clinical trials. Thirty-nine observational studies were identified, of which 33 did not have a control arm. The overall median staining rate for abnormal parathyroid glands was 100 per cent. The median cure rates in the methylene blue and no-methylene blue arms were 100 and 98 per cent respectively. Neurotoxicity was reported in 25 patients, all of whom were taking serotonergic medication. CONCLUSION: Observational evidence suggests that methylene blue is efficacious in identifying enlarged parathyroid glands. Toxicity appears to be mild in the absence of concomitant use of serotonin reuptake inhibitors. The effectiveness of methylene blue in the context of currently used preoperative and intraoperative localization techniques has yet to be shown.

Making sense of postoperative CT imaging following laparoscopic partial nephrectomy.

The increasing popularity of laparoscopic partial nephrectomy (LPN) necessitates radiologists to become familiar with the operative techniques as well as normal and abnormal postoperative findings. Due to the varying presentation of abnormal changes following LPN and their similarities with other disease entities, radiologists should be cognizant of common pitfalls to avoid inadvertent misdiagnosis. A few common pitfalls discussed in this paper are the identification of laparoscopic port placement issues, recognizing a myriad of post-surgical materials, differentiating haemostatic materials from postoperative abscess and infection, non-absorbable suture material mimicking rim calcifications, as well as hints for differentiating exuberant granulation tissue from tumour recurrence.

Demonstration of pemphigus antibodies on the cell surface of murine epidermal cell monolayers and their internalization.

The pathogenic effects of pemphigus vulgaris (PV) antibodies on epidermal cells can be demonstrated both in vitro using skin organ culture or primary epidermal cell cultures (PECC) and in vivo by passive transfer of PV antibodies into neonatal BALB/c mice. Although PV antibodies have been localized on the epidermal cell surface by several techniques, little is known about the fate of these autoantibodies subsequent to their surface binding. We have examined this, using murine PECC which express pemphigus antigen on their surface, and followed the fate of the bound antibody molecules. Forty-eight-hour PECC were incubated at 37 degrees C with PV antibodies for 20 min and then with horseradish peroxidase-labelled antihuman IgG. This was considered time 0. The monolayers were fixed with glutaraldehyde after 0, 0.5, 1, 3, 6, 18, and 24 h incubation at 37 degrees C and then processed for electron microscopy. At time 0 hour, PV antibodies is detected bound evenly along the surface of keratinocytes. Within 30 min, the bound PV antibodies becomes clustered, internalized into submembranous vesicles via surface pits, and eventually fused with lysosomes. Widening of the intercellular spaces was also seen in PECC treated with PV antibodies within the first 24 h. PECC treated with normal human IgG in parallel cultures showed no such surface binding, internalization, or cell-cell detachment. Treatment with cytochalasin-D and/or colchicine did not affect the internalization of the PV antibodies, but fusion with lysosomes was not seen in treated cultures. These findings suggest that PV antibodies binds a surface antigen and the complex is internalized and fused with lysosomes in a process that may have pathophysiologic relevance.

Experimentally induced pemphigus vulgaris in neonatal BALB/c mice: a time-course study of clinical, immunologic, ultrastructural, and cytochemical changes.

Pemphigus vulgaris autoantibodies (PV IgG) promote cell detachment in epidermal cell cultures and acantholysis in the epidermis of neonatal BALB/c mice in vivo. We have studied the evolution of the immunologic and ultrastructural changes in the epidermis of BALB/c mice that receive parenteral injections of PV IgG. Neonatal BALB/c mice received a single i.p. injection of PV IgG (10 mg/g body weight) or control IgG from normal humans. The skin and serum of these animals was obtained at 0, 1, 3, 6, 12, 18, and 24 h post injection, and examined by immunofluorescence (IF), electron microscopy (EM), and immunoelectron microscopy (IEM). PV IgG was detected in the mouse serum and bound to the epidermal cells as soon as 1 h after injection by IF and IEM. The intensity of the binding in the skin (by IF) increased sharply between 3 and 6 h, and remained positive at 24 h. Early epidermal cell detachment was demonstrable by EM at 1 h as widening of the epidermal intercellular spaces (ICS), and by 6 h the ICS between desmosomes had detached completely. Desmosomal junctions are the last to separate, occurring at 12-18 h. At this point, complete cell detachment occurred in the suprabasilar layers of the epidermis. Basal cells remain attached to the underlying dermis (tombstone row). Coincident with cell detachment, intracellular tonofilaments retracted from the cell periphery and clustered in a perinuclear position. IEM confirmed the binding of PV antibodies to the surface of epidermal cells in early and established lesions. This study demonstrates that the early immunologic and ultrastructural changes that occur in human pemphigus vulgaris are reproduced in this mouse model of the disease.

Pemphigus and pemphigoid antigens are expressed in human amnion epithelium.

The sera of patients with pemphigus vulgaris (PV) and bullous pemphigoid (BP) contain autoantibodies which react with antigens present in a variety of mammalian squamous epithelia. The biologic role of these epithelial antigens is unknown; however, they do appear to be markers of epithelial differentiation. We have examined many human tissues that may be used as sources of large amounts of BP and PV antigens, including the human amnion, which is composed of the amnion reflectum and placentum (epithelial monolayers) and amnion cord (stratified epithelium). Human amnion was obtained from normal term deliveries and specimens of each area of the amnion were processed for light and electron microscopy. Samples of amnion were snap-frozen in liquid nitrogen and 4-micron sections were used as a substrate for BP and PV antibodies by indirect immunofluorescence (IF) techniques. Well-characterized BP serum (indirect IF titer 1:2560), PV serum (indirect IF titer 1:160), and normal human serum (negative indirect IF) were utilized as sources of BP and PV autoantibodies and a negative control, respectively. Linear staining of the BMZ was produced by BP antibodies in 8/8 specimens of amnion reflectum, 8/8 specimens of amnion placentum, and 3/3 specimens of amnion cord. Staining of the epithelial intercellular spaces was produced by PV antibodies of 2/3 specimens of amnion cord and none of the amnion reflectum (0/8) or amnion placentum (0/8) tested. Normal human serum produced no specific staining of the amnion. The light and the ultrastructural features of human amnion basement membrane zone and intercellular spaces resembles closely their epidermal counterparts. The restricted distribution of BP antigen in amnion epithelial basal cells (amnion reflectum, placentum, and cord) and PV antigen in stratified amnion epithelium (amnion cord) reinforces their relationship with epithelial differentiation. The abundance and availability of these tissues facilitate extraction and characterization of BP and PV antigens.

A pool of bullous pemphigoid antigen(s) is intracellular and associated with the basal cell cytoskeleton-hemidesmosome complex.

Bullous pemphigoid (BP) antibodies are known to react with an antigen of the basement membrane zone (BMZ) of squamous epithelia and produce, by the indirect immunofluorescence technique, linear fluorescence at the BMZ. Direct and indirect immunoelectron microscopy (IEM) have demonstrated BP antigen to be within the lamina lucida, in close association with the basal cell membrane. Trypsin-dissociated epidermal basal cells bind BP antibodies in a polar distribution, presumably because the BP antigen is restricted to the dermal pole of the basal cell membrane. In this study we have utilized newborn BALB/c mouse skin to obtain both dissociated basal cells (by trypsinization) and epidermal sheets (by dithiothreitol treatment). We show that viable basal cells, which are impermeable to IgG molecules, do not react with BP antibodies. When the basal cell plasma membrane is disrupted by cytospin centrifugation, air drying, freezing and thawing, or hypotonic lysis, or permeated by nonionic detergents (saponin), cells become reactive with BP antibodies. Basal cell cytoskeletons, prepared by sequential treatment with Triton X-100, deoxyribonuclease, and 2 M NaCl continue to react with BP antibodies. Similarly, viable epidermal sheets fail to bind BP antibodies. When epidermal sheets are treated with nonionic detergents, water, or freezing and thawing prior to incubation with BP antibodies, linear BMZ fluorescence is observed. IEM study of saponin-treated basal cells shows the immunoreactants to be localized on intracytoplasmic vacuoles which represent internalized hemidesmosomes. IEM of permeated epidermal sheets shows the immunoreactants as aggregates on the inner surface of the dermal pole of the basal cell membrane. These observations suggest that the BP antigen is intracellular and is in close association with the basal cell cytoskeleton and hemidesmosomes.

The use of human pemphigoid autoantibodies to study the fate of epidermal basal cell hemidesmosomes after trypsin dissociation.

It is known that during trypsinization of the skin, the epidermis is first separated from the dermis and individual keratinocytes are dissociated by disruption of the epidermal intercellular spaces. The desmosomal unit is separated at the level of the intercellular space and the split desmosomes are internalized in plasma membrane-limited vesicles; however the fate of the hemidesmosome under such conditions has not been studied. We have recently shown (Mutasim et al: J Invest Dermatol 84:47-53, 1985) that autoantibodies from the sera of patients with bullous pemphigoid bind in vitro to hemidesmosomes but not to desmosomes providing a highly specific marker for these organelles. Utilizing these autoantibodies, we studied the fate of the hemidesmosome during trypsin dissociation of epidermal basal cells derived from the skin of neonatal BALB/c mice. During trypsinization, portions of the dermal face of the plasma membrane which include hemidesmosomes formed pits which pinched off to produce vesicles that moved toward the nucleus. This was accompanied by retraction of the tonofilaments away from the cell periphery. The mechanism of this internalization process is not yet known, but may involve contractile elements of the cytoskeleton. The highly specific binding of bullous pemphigoid autoantibodies to the hemidesmosome may prove helpful in future biochemical and immunocytochemical studies of this organelle.

An autoantibody in pemphigus serum, specific for the 59 kD keratin, selectively binds the surface of keratinocytes: evidence for an extracellular keratin domain.

We have identified a novel IgG antikeratin autoantibody in the serum of a Brazilian pemphigus foliaceus patient (Cascas-42). This antibody is specific for the 59 kD acidic murine keratin and its 56.5 kD human counterpart (Moll's catalogue #10), and is distinct from the pemphigus antibody system. Antikeratin autoantibodies present in the Cascas-42 serum were purified by affinity chromatography with a 59 kD murine keratin-agarose column (IAP-Cascas-42 antibodies). The specificity of the IAP-Cascas-42 antibodies was tested by indirect immunofluorescence and immunoelectron microscopy against epidermal cryosections, trypsin-dissociated keratinocytes, and epidermal cell cultures. The serum was also tested with extracts from unlabeled and surface 125I-labeled keratinocytes (Iodo-Gen method) by immunoblot analysis of one- and two-dimensional polyacrylamide gel electrophoresis. The IAP-Cascas-42 antibodies bind the intercellular spaces of murine epidermis, and the cell surfaces of viable, dissociated murine keratinocytes, as well as murine epidermal cells in culture by immunofluorescence and immunoelectron microscopy. These autoantibodies did not stain cytoplasmic keratins and did not react with parallel human epidermal substrates. The Cascas-42 serum identified the 59 kD murine acidic keratin and its 56.5 kD human counterpart in epidermal extracts by two-dimensional polyacrylamide gel electrophoresis and immunoblot analysis. In addition, surface radioiodination of viable murine keratinocytes selectively labeled the 59 kD keratin suggesting that a domain of this molecule is exposed on the cell surface. The 125I-labeled 59 kD keratin was also recognized by the Cascas-42 serum by immunoblotting and autoradiography. These studies suggest that in murine epidermis, the 59 kD keratin is a transmembrane protein with an extracellular domain recognized by the IAP-Cascas-42 antibodies.

Bullous pemphigoid autoantibodies are markers of corneal epithelial hemidesmosomes.

Sera from patients with bullous pemphigoid (BP) contain autoantibodies that bind to the BP antigen, which is a component of the epithelial-stromal junction of the cornea. Previous studies, employing direct immunoelectron microscopy (IEM) on perilesional skin of patients have localized the BP antigen to the lamina lucida. On this basis, studies of corneal epithelial-stromal adhesion and wound healing have employed BP antigen as a marker of the lamina lucida of the corneal basement membrane zone (BMZ). The authors used indirect IEM with BP autoantibodies on frozen sections of cornea and found that the majority of the BP antigen is intracellular and is closely associated with the corneal epithelial hemidesmosome. Only a small amount of BP antigen appears to be extracellular, limited to the portion of the lamina lucida directly beneath individual hemidesmosomes. When rabbit corneal epithelium is extracted and analyzed by Western immunoblotting, BP autoantibodies recognize two polypeptides of molecular weights of 240 and 180 kilodaltons, which comigrate with BP antigens extracted from epidermis. BP autoantibodies are a specific marker of corneal epithelial hemidesmosomes and can be used as a probe to identify and study the role of hemidesmosomes in epithelial-stromal adhesion.

Human pemphigus autoantibodies are pathogenic to squamous epithelium.

In 1957, Witbesky et al. put forward several criteria that ideally should be fulfilled in order to prove the pathogenic role of an autoantibody in a putative autoimmune disease. There can now be very little doubt of the autoimmune nature of this disease and of the primary role of autoantibodies in its pathogenesis. The evidence that supports the concept that pemphigus autoantibodies are of primary pathogenic importance in the disease is as follows: IgG class autoantibodies can be found both circulating in the serum and bound to the epithelial cell surfaces in and around lesions in patients with pemphigus. These autoantibodies, purified from the serum of pemphigus patients, can induce acantholytic lesions typical of pemphigus both in experimental animals (neonatal mice) and in human and murine epidermal cell cultures. These autoantibodies react with a specific antigen of the epidermal cell. This purified antigen has been used to immunize rabbits and the resulting antibodies are capable of inducing pemphigus-like lesions in neonatal mice.

Malignant lymphoma of the gastrointestinal tract.

AIMS: The gastrointestinal tract (GIT) is the most common site of extra-nodal lymphoma. Most of these lymphomas arise from mucosa associated lymphoid tissue (MALT). We attempt in this study to define the natural history and treatment outcome of this type of lymphoma. METHODS: We carried out a retrospective study of patients presenting at our centre with histopathological diagnosis of primary GIT lymphoma between 1990 and 1994. RESULTS: Equal numbers of cases of stomach and small bowel lymphoma were found. Vomiting and feeling of fullness were the two most common presenting symptoms. Large cell type and high grade tumours were found to be the commonest histological types. All the patients were treated with surgery followed by chemotherapy. A 5-year disease-free survival (DFS) rate of 73%) was observed with a confidence interval of 0.65-1.35. Survival in stomach cancer was 73.5% (95% CI 0.26-1.74) while it was 76.4% in small bowel tumours (95% CI 0.54-1.46). The difference in survival was not statistically significant. CONCLUSIONS: Although there is no consensus regarding treatment of primary GI lymphoma, surgery and adjuvant chemotherapy yield good survival.