Differences in mucosal appearances and in relapse rates in duodenal ulceration treated with sucralfate or cimetidine.

A total of 46 patients with duodenal ulcer were randomly assigned, without the knowledge of the investigators, to treatment with cimetidine 200 mg three times daily and 400 mg at night or sucralfate 1 g four times daily followed by one year of maintenance treatment with cimetidine 400 mg at night or sucralfate 1 g twice daily, respectively, in those patients with healed ulcers. The endoscopic healing rates and relapse rates during the maintenance period were similar, four relapses occurring in each group. All four relapses in the sucralfate group occurred at 12 months and only two were symptomatic. All the cimetidine relapses were symptomatic, two occurring at six months, one at nine months, and one at 12 months. Following the one year maintenance period, 13 cimetidine patients and 11 sucralfate patients were followed up for 36 months. During the first two years, nine of 13 (69 percent) cimetidine-treated and two of 11 (18 percent) sucralfate-treated patients had relapses. During the third year, three more sucralfate-treated patients and one more cimetidine-treated patient had relapses, making a total of 10 of 13 (77 percent) and five of 11 (45 percent) in the cimetidine and sucralfate groups, respectively. Duodenal biopsy specimens obtained before and after healing and after one year of maintenance were examined by light and electron microscopy. The sucralfate group showed greater improvement after one year of maintenance therapy than did the cimetidine group, although the appearances in either group were not predictive of subsequent relapse. The results show that relapses are less frequent and occur later after sucralfate therapy and also that the morphologic appearances are more normal after treatment with sucralfate than after treatment with cimetidine.

Albendazole chemotherapy for AIDS-related diarrhoea in Zambia--clinical, parasitological and mucosal responses.

BACKGROUND: Albendazole reduces diarrhoea in African AIDS patients, but it is unclear if the clinical response to treatment reflects pathogen eradication and/or mucosal recovery. METHODS: Adults with HIV-related persistent diarrhoea were treated with albendazole 800 mg twice daily for 14 days. Clearance of parasites was evaluated at 3 and 6 weeks by stool microscopy. At baseline and at 6 weeks duodenal biopsies were taken for electron microscopy (EM) and morphometry. RESULTS: Ten (7%) of 153 patients had cryptosporidiosis, 54 (37%) had isosporiasis and 23 (16%) had microsporidiosis. By 3 weeks, these protozoa were cleared in 27 (46%) of 59 patients initially positive. By 6 weeks, 34 (39%) of 87 patients experienced complete clinical response, 18 (21%) partial response and 35 (40%) no response. Crypt depth increased by 15% over 6 weeks (P < 0.001), but villous height increased only in patients with complete response (median + 50 microm, interquartile range (IQR) 2-90, compared to patients with partial (+ 4 microm, IQR -15,41) or no response (-13 microm, IQR -2,12; P=0.008)). Fifteen patients died: body mass index < 17.5 kg/m(2) and crypt depth < 180 microm independently predicted death. CONCLUSIONS: Albendazole therapy reduced the burden of protozoal infection and promoted mucosal recovery in patients with a complete clinical response.

Muscle morphology and metabolism in hypothyroid myopathy: effects of treatment.

Needle biopsies from vastus lateralis in untreated hypothyroid patients with muscle weakness confirmed by quadriceps force measurements (n = 11) were repeated when the patients had taken L-thyroxine for a mean period of 9.2 months (range 5.3-13.3 months, n = 8) and had been continuously biochemically euthyroid for a mean period of 4.9 months (range 2-11 months). Biopsies were analysed biochemically for mitochondrial function. On light microscopy, histochemical examination, mean fibre areas and fibre percentages of type I and type II fibres were determined. Electronmicroscopy was also performed. Abnormalities on light microscopy occurred in eight patients of which type II fibre atrophy was the commonest and of the remainder two patients showed a myopathic electromyogram (EMG) and a raised plasma creatine kinase activity and one ultrastructural change on biopsy. After treatment resolution of pathological changes was often slow and half the patients had persistent abnormalities when rebiopsied. The type I mean fibre area was significantly increased in the eight hypothyroid females (p less than 0.05) and type II mean fibre areas tended to be low and in females this was significant (p less than 0.05). After treatment the type I mean fibre area was significantly reduced (p = 0.05). The type II mean fibre area also tended to fall but this was not significant (p greater than 0.05). No change in the fibre percentages occurred. A myopathic EMG, a raised plasma creatine kinase activity, ultrastructural changes and low mitochondrial enzyme activities on needle biopsy were other common findings and their significance is discussed.

Ultrastructural changes after concentric and eccentric contractions of human muscle.

Four normal subjects performed a 20 min step test using a step of the same relative height. During the test the quadriceps muscle of one leg contracted concentrically throughout by stepping up, while the contralateral muscle contracted eccentrically by controlling the step down. Thus both muscles performed the same amount of work. Three subjects had bilateral needle biopsies just prior to exercise. All four had bilateral biopsies immediately after exercise, and 24-48 hours later when the muscles which had contracted eccentrically were painful. The samples were examined by light and electron microscopy. No abnormalities were seen in pre-exercise samples nor after exercise in muscles which had contracted concentrically. The muscles which had contracted eccentrically showed some damage immediately after exercise. In the samples taken 24-48 hours after exercise the damage was more marked and involved a greater percentage of fibres. In view of the known differences between these types of contractions it is suggested that the initial damage is mechanically induced. The exacerbation of damage with time could be due to mechanical or chemical factors.

Menopause as an issue for women with breast cancer.

Menopause is beginning to be recognized as a survivorship issue for women with a diagnosis of breast cancer. This article presents an outline of the literature relating to natural menopause and its symptoms, moves on to discuss general management of menopausal symptoms, then reflects on the particular implications of breast cancer diagnosis and treatment. Finally, the role of nursing in restoring a holistic perspective to the subject of menopause generally, and to women with breast cancer specifically, is considered.

Acute menopause symptoms during adjuvant systemic treatment for breast cancer: a case-control study.

The purpose of this study was to ascertain whether acute menopause symptoms experienced by women with breast cancer differed from those of women experiencing a natural menopause. For the study, 200 women younger than 65 years of age receiving adjuvant systemic treatment for breast cancer were invited to complete a self-report questionnaire incorporating a previously validated tool: the Greene Climacteric Scale. The control group consisted of 200 women 50 to 64 years of age who did not have a breast cancer diagnosis. An overall response rate of 59.5% was obtained. The majority of the respondents were peri- or postmenopause at the time of the study, reporting either "irregular periods" or "no periods." Findings demonstrated that women receiving adjuvant systemic breast cancer treatment were more likely than the control group to report a current experience of menopause symptoms. Women with breast cancer also reported a higher incidence and severity of specific menopause symptoms (tiredness, hot flushes, night sweats) than control subjects. These differences remained statistically significant when controls were used for potential confounding variables such as age, menopause status, and time since last period. Hot flushes ranked second only to tiredness as side effects attributed to cancer treatments. Because of the intimate and supportive nature of their role, nurses are in a key position to conduct future research relating to women's experiences of menopause symptoms and potential therapeutic interventions. Within the specific context of breast cancer care, oncology nurses are recognized as having a central role in informing and supporting women throughout the breast cancer trajectory. Thus they are ideally placed to address menopause as a particular survivorship issue.

Herceptin: implications for breast cancer management.

It appears that no further significant improvements in the survival of women with metastatic breast cancer are likely to result from the use of traditional chemotherapeutic agents. Research attempting to identify novel agents has focused on biological therapies, which can be used to target specific abnormalities in cancer cells. Human epidermal growth factor receptor-2 (HER2) is a cell membrane receptor with growth-regulating activity. Studies indicate that the 25-30% of women with breast cancer who overexpress HER2 have aggressive disease and a worse prognosis than those who do not overexpress HER2. Herceptin targets HER2 and is the first humanized monoclonal antibody approved for therapeutic use. Clinical trials have demonstrated that Herceptin is well tolerated, produces durable objective responses and improves survival in women with metastatic breast cancer. Its side-effects are generally mild to moderate and differ from those of traditional cytotoxic agents. Cardiotoxicity, the most significant adverse effect of Herceptin, is manageable in most patients using standard therapy. The likely positioning of Herceptin in the treatment of HER2-overexpressing metastatic breast cancer is in combination with paclitaxel as first-line therapy and as second- or third-line therapy when administered alone. It is likely that the exploitation of HER2 as a target for therapy and the development of Herceptin will serve as a model for the development of future biological therapies.

Ivacaftor: the first therapy acting on the primary cause of cystic fibrosis.

Cystic fibrosis (CF) is a life-shortening disorder that affects over 30,000 people in the U.S. and 70,000 worldwide. CF is caused by mutations in the CFTR gene, which codes for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. CFTR is a chloride and bicarbonate channel and regulates several ion transporters at the epithelial cell membrane, controlling hydration or ionic composition of epithelial secretions. Management of CF is currently supportive, but recent advances in drug development have focused on therapies that assist mutant CFTR function. In the current review, we summarize the development and clinical experience with VX-770 (ivacaftor), a small molecule that increases CFTR chloride conductance in vitro and in vivo, including wild-type and G551D CFTR. The G551D CFTR mutation is the third most common CF disease-causing mutation, in which the CFTR protein localizes to the epithelial cell membrane but has defective gating. With restoration of adequate CFTR function through pharmacotherapy, it is possible that the clinical course of patients with CF could be markedly improved, including longevity, quality of life and treatment burden.

There's no such thing as a healthy glow: cutaneous malignant melanoma--the case against suntanning.

One of the objectives of the 1992 United Kingdom Government White Paper 'Health of the Nation', is to reduce ill health and death caused by skin cancers by the year 2005. The Europe Against Cancer Programme shares those aims for the entire European population. Skin cancer was the first cancer demonstrated to have a chemical cause, with Percival Pott's 1775 description of squamous cell carcinoma of the scrotum induced by chimney soot, and skin cancers were also the first to be linked with ionising radiation. Currently there is a general consensus amongst researchers which acknowledges solar ultraviolet radiation as the major carcinogenic agent for the development of skin cancers. Changing attitudes and lifestyles affecting sun exposure is deemed responsible for the upward trends in incidence and mortality from skin cancers. The recognition of skin cancer as a preventable malignancy has implications for the health promotion role of nurses and of their multidisciplinary colleagues throughout Europe. This paper reviews the literature relating to sunlight as a risk factor for cutaneous malignant melanoma, and considers the behavioural issues which need to be addressed by healthcare professionals generally, and by nurses specifically, when establishing or participating in health promotion initiatives.

Management of change: an essential skill for nursing in the 1990s.

Change is nothing new and indeed has been our only constant, but change today is faster and more complex than it has ever been before (Manion 1994). Bushy (1992) agrees that the past decade has been a time for rapid global changes, with Muller (1992) citing the rapid increase in technology as the root cause. Muller (1992) believes that nurses need to develop a new mindset which is more in tune with the realities of the 1990s, acknowledging that we are and will be living in a constantly changing world, and Zukowski (1995) suggests that regardless of whether or not we accept change, we must learn to manage it. Although change creates uncertainty and discomfort, Poggenpoel (1992) emphasizes that it often leads to real innovation, providing abundant opportunities for creating a better way forward. This paper explores the subject of change management, looking first at the reasons behind the current climate of change in the healthcare system, then outlining change theory in relation to nursing, before discussing the role of the nurse as a change agent.

Women's experience of breast conserving treatment for breast cancer.

The implementation of the National Breast Screening Programme in the UK, and subsequent increase in early detection of small cancers, has facilitated breast conserving treatment for more women with a breast cancer diagnosis than ever before. While a substantial body of literature has evolved regarding psychosocial morbidity and support needs of women at diagnosis and during treatment, there are specific gaps in the current knowledge base. The purpose of this study was to describe the experiences of women who had breast conserving treatment for early breast cancer, focusing on issues related to diagnosis, surgery, and radiotherapy. The study was designed within the context of clinical audit, with a view to informing service development. Seventy-six women who had undergone breast conserving surgery within the last 3-12 months, completed a self-report questionnaire. Findings indicated that although the majority of women expressed satisfaction with their treatment overall, a number of specific areas require attention from healthcare professionals. Further research is required to validate these findings and to explore: potential implications of different referral routes; information and support needs preceding definitive diagnosis; particular needs of those women with ductal carcinoma in situ (DCIS) vs. invasive disease; 'end of treatment' and ongoing information and support needs.

A useful low temperature method for post-embedding electron immunocytochemistry in routine histopathology.

Using a low temperature resin, we have developed a reliable technique for post-embedding electron immunocytochemistry which is rapid enough to be used in a routine histopathology laboratory. Glutaraldehyde fixed human tissues were dehydrated and embedded at -25 degrees C in a new acrylic resin called LR-Gold. Using the immunogold technique, ultra-thin sections of the tissues were labelled with monoclonal antibodies to cytokeratin, human milk fat globule and HLA-D region antigen; and with polyclonal antisera to lysozyme, kappa and lambda light chains and immunoglobulin M. The resin was easy to section and the preservation of fine structure was excellent. Immunolabelling procedures gave clean and consistent results, and electron micrographs of examples of this are included. It was felt that the preservation of ultrastructure and antigenicity compared well with the results of other workers using low temperature resins such as Lowicryl K4M, but LR-Gold was superior to Lowicryl K4M because sectioning was considerably easier and the sections were more stable in the electron beam.

Experimental mouse muscle damage: the importance of external calcium.

The involvement of extracellular calcium in experimental muscle damage has been studied in an isolated mouse soleus muscle preparation. The enzyme efflux and ultrastructural damage seen after excessive contractile activity were markedly reduced when the extracellular calcium was withdrawn. Low extracellular calcium also protected against the large enzyme efflux seen after treatment with low concentrations of detergent. Treatment of the muscle with the calcium ionophore A 23187 caused significant release of enzyme from the muscle. Nifedipine did not prevent the enzyme release after stimulation and although in some circumstances verapamil appeared to have some protective effect this was probably due to a local anaesthetic action on the muscle and not to any specific effect on calcium movement. It is concluded that extracellular calcium is important in mediating at least the two forms of muscle damage studied here.

Corticosteroid myopathy: a clinical and pathological study.

In six patients with Cushing's syndrome and three with steroid myopathy, the clinical, functional, biochemical and structural characteristics of myopathy are described. Proximal muscle weakness occurred in all the patients, preferentially affected the lower limbs and was accompanied by muscle wasting in all but one patient. Force measurements confirmed quadriceps weakness in every patient. Vastus lateralis muscle biopsies showed light microscopic abnormalities in two of three patients with steroid myopathy and one of five patients with Cushing's syndrome. Type II fibre atrophy was the commonest abnormality. Reduced type II mean fibre areas occurred in all the patients with steroid myopathy and were common in Cushing's syndrome patients. Type I mean fibre areas were also reduced in two of the former group and one of the latter group and two further patients in this group had areas at the lower end of the normal range. Abnormalities in electron microscopy, mitochondrial function tests and chemical content of skeletal muscle were frequent and are described and discussed. A plasma creatine kinase activity (CK) at the lower end of the normal range, a myopathic electromyogram (EMG) and a raised 24-h urinary 3-methylhistidine/creatinine ratio on a creatine free diet were other characteristic findings in both groups of patients.

Paneth cell granule depletion in the human small intestine under infective and nutritional stress.

Paneth cells are important contributors to the intestinal antimicrobial barrier through synthesis and release of antimicrobial peptides and proteins. Animal studies indicate that Paneth cell numbers, location and granule morphology are altered by infection and zinc status. We examined human tissue to determine whether Paneth cell numbers, distribution or granule morphology are altered in infective, inflammatory and nutritional disorders. Archival sections from infective disorders (giardiasis, cryptosporidiosis, HIV, helminth infection) were compared with active inflammatory conditions (coeliac, Crohn's and graft-versus-host diseases) and histologically normal tissues. A subset of tissues was studied by electron microscopy and TUNEL staining for apoptosis. Human defensin-5 (HD5) peptide and mRNA was analysed by immunohistochemistry, in situ hybridization and quantitative reverse transcription polymerase chain reaction. Sections from a tropical population cohort study were then analysed to determine the relationship of granule depletion to infection, nutritional status and plasma zinc concentration. In HIV-related cryptosporidiosis, but not other disorders, Paneth cells were reduced in number and markedly depleted of granules. Paneth cell granule depletion was associated with reduced HD5 immunoreactivity, but this was not due to apoptosis and there was no reduction in mRNA transcripts. In the tropical population studied, depletion of granules was associated with reduced body mass index, reduced plasma zinc levels and HIV infection. Paneth cell granules in human small intestine may be depleted in response to infective and nutritional stress. We postulate that this is one mechanism through which zinc status influences host susceptibility to intestinal infection.

The neuromuscular features of acromegaly: a clinical and pathological study.

A study of the neuromuscular features of acromegaly was performed in six patients. Clinical assessment was supplemented by quadriceps force measurements, plasma creatine kinase (CK) activities, electromyography (EMG) and nerve conduction studies. Muscle mass was measured by urinary creatinine/height indices (CHI) and cross sectional area (CSA) of thighs and calves on computed tomography. Quadriceps force/unit cross sectional area was derived. Needle biopsies of vastus lateralis were studied by histochemical and ultrastructural methods. Mean fibre area (MFA) and fibre type proportions were measured. Most of the subjects studied had muscle pain and proximal muscle weakness confirmed by quadriceps force measurements. This occurred in the absence of muscle wasting, as shown by cross sectional area measurements and normal or raised creatinine/height indices. "Myopathic" features were demonstrated by needle biopsy in half the patients and occasionally by electromyography and raised plasma creatine kinase activity. Abnormalities on needle biopsy included variation in fibre size, type 2 fibre atrophy and large type 1 MFA relative to type 2 MFA. Electronmicroscopy showed the non-specific findings of increased glycogen accumulation, excess lipofuscin pigment and myofilament loss.

Comparison of relapse rates and of mucosal abnormalities after healing of duodenal ulceration and after one year's maintenance with cimetidine or sucralfate: a light and electron microscopy study.

Forty six patients with endoscopically diagnosed duodenal ulceration were randomly allocated to treatment with either sucralfate 1 g qds (n = 24) or cimetidine 200 mg tds and 400 mg nocte (n = 22). When the ulcers healed, a maintenance dose of sucralfate 1 g bd or cimetidine 400 mg nocte was given for one year (or until relapse if earlier). Biopsies of duodenal mucosa adjacent to ulcer sites for light and electron microscopy were obtained before and after healing and again after one year's maintenance if the ulcer remained healed. Duodenal biopsies were also taken from 20 age and sex matched controls. Rates of healing and relapse during maintenance did not differ between the two treatments, although relapses occurred earlier with cimetidine. In the three year post-maintenance follow up period 10/13 cimetidine patients relapsed compared with four of 11 sucralfate patients (p less than 0.05), the relapses occurring significantly earlier in the cimetidine treated patients (p less than 0.05). Mucosal biopsies from both treatment groups still showed considerable abnormalities after healing. During maintenance, however, the sucralfate scores fell significantly (p less than 0.02) to near control levels unlike the cimetidine scores which remained raised at pretreatment values. The histological and ultrastructural changes were not predictive of later relapse. These findings favour the use of sucralfate in preference to cimetidine for maintenance treatment in the prevention of relapse of healed duodenal ulcers.

Enteropathy in Zambians with HIV related diarrhoea: regression modelling of potential determinants of mucosal damage.

BACKGROUND: AIDS is characterised by small intestinal mucosal damage, but its aetiopathogenesis is poorly understood. Enteric infections in Africa differ from those in northern countries, where protozoan infections have been associated with severe enteropathy in AIDS patients. AIMS: To characterise enteropathy in Zambian AIDS patients compared with local controls, and to assess relative contributions of enteric infection, nutritional impairment, and immune dysfunction. METHODS: Computer aided mucosal morphometry of small intestinal biopsy specimens from 56 HIV infected Zambians with persistent diarrhoea and 26 diarrhoea free controls, followed by regression modelling. RESULTS: Patients with HIV related diarrhoea had reduced villous height and increased crypt depth compared with controls. There was no difference between HIV positive and negative controls. In regression models applied to AIDS mucosal measurements, villous height and crypt depth were related to nutritional parameters and to serum soluble tumour necrosis factor receptor p55 concentration. Crypt depth was also related to lamina propria plasma cell count. Intestinal infection was found in 79%, which consisted predominantly of microsporidia in 34%, Isospora belli in 24%, and Cryptosporidium parvum in 21%, but detection of these enteropathogens was not related to severity of enteropathy. CONCLUSIONS: Nutritional and immune disturbances were associated with enteropathy, accounting for over one third of the variation in mucosal morphometric parameters.

PIP: The relative contributions of enteric infection, nutritional impairment, and immune dysfunction to AIDS-related enteropathy were investigated in a comparative study of small intestinal biopsy specimens from 56 HIV-positive patients from Lusaka, Zambia, with persistent diarrhea and 26 diarrhea-free controls. Compared with both HIV-positive and HIV-negative controls, patients with HIV-related diarrhea had a 40% reduction in mean villous height and a 19% increase in mean crypt depth. In regression models applied to AIDS mucosal measurements, villous height and crypt depth were related to nutritional parameters and to the serum soluble tumor necrosis factor receptor p55 concentration. Crypt depth also was related to lamina propria plasma cell count. Intestinal infection, primarily microsporidia, was detected in 79% of cases; however, the presence of enteropathogens was not related to the severity of enteropathy. These findings suggest that nutritional and immune disturbances account for more than 33% of the variation in mucosal morphometric parameters in AIDS-related enteropathy.