The Canadian Home Total Parenteral Nutrition (HTPN) Registry: vitamin K supplementation and bone mineral density.

BACKGROUND: Vitamin K supplementation improves bone health, and its absence might be associated with low bone mineral density (BMD). The authors aim to assess vitamin K supplementation practices in Canadian home parenteral nutrition (HPN) programs and their relationship with BMD. METHODS: This is a cross-sectional study of 189 patients from the Canadian HPN registry. RESULTS: All 189 patients studied received M.V.I.-12, which does not contain vitamin K. Of those, 41.3% were supplemented with 10 mg of intravenous vitamin K (VK+) weekly, whereas the others did not receive vitamin K except via lipid emulsion (VK-). Short bowel syndrome accounted for 69% of VK+ and 46% of VK- patients. On univariate analysis, VK+ patients had substantially lower body mass index (BMI) and received lower bisphosphonate infusion than did VK-patients. There were no statistically significant differences in HPN calcium or lipid content, liver function test results, age, sex, or reason for HPN between the 2 groups. Patients who were VK+ had higher lumbar spine T scores and hip T scores than did VK-patients. General linear modeling analysis, adjusted for BMI, age, PN magnesium, PN phosphate, PN calcium, and bisphosphonate as possible predictors of BMD, showed a trend toward better hip T scores (P = .063) for VK+ patients compared with VK- patients. CONCLUSION: In HPN patients supplemented with vitamin K, the trend toward a better hip BMD compared with no supplementation suggests a role for vitamin K in preserving BMD. This requires further study.

Esophageal foreign body causing direct aortic injury.

Foreign bodies in the esophagus are uncommon causes of esophageal perforation. Many nonperforating cases are successfully managed by flexible gastroscopy. However, complicated foreign bodies such as those that result in esophageal perforation and vascular injury are best managed surgically. Gastroscopy remains the primary method of diagnosis. A case of a 59-year-old woman who developed retrosternal and intrascapular pain, odynophagia and hematemesis after eating fish is reported. Flexible gastroscopy showed arterial bleeding from the midthoracic esophagus. Computed tomography scan localized a 3 cm fish bone perforating the esophagus with surrounding hematoma. An aortogram did not reveal an actively bleeding aortoesophageal fistula. The fish bone was surgically removed and the patient recovered with no postoperative complications. This case illustrates the importance of early consideration for surgical intervention when confronted with a brisk arterial bleed from the esophagus with suggestive history of foreign body ingestion.

Clinical and histological predictors of response to medical therapy in collagenous colitis.

OBJECTIVES: Collagenous colitis (CC) is an uncommon form of inflammatory bowel disease. The response to typical medical therapies (antimotility agents, 5-aminosalicylic acid [5-ASA], and corticosteroids) is variable. We aimed to determine if there are clinical or histological variables that can predict response to medical therapy. METHODS: All cases of CC were identified in three tertiary care medical centers. All charts of included patients were reviewed and clinical variables (age, gender, duration of symptoms, frequency of bowel movements, and the use of nonsteroidal anti-inflammatory drugs [NSAIDs]) were recorded. Available histology slides were reviewed by one GI pathologist. Intraepithelial inflammation, epithelial loss or detachment, inflammation in the lamina propria, presence of eosinophilia, crypt inflammation, Paneth's cell metaplasia, and collagen layer thickness were recorded. Depending on their response to therapy, patients were divided into three groups: 1) spontaneous recovery or response to antidiarrheal agents alone, 2) response to 5-ASA agents, and 3) response to corticosteroids after failure of antidiarrheal agents and 5-ASA. RESULTS: Ninety-four patients with CC were identified. Of these, 62 patients were included. The median age was 58 (range = 20-85), and 88% were female. Among the histological parameters only the degree of inflammation in the lamina propria significantly differed between the three response groups (p = 0.007). Patients who required corticosteroids had greater inflammation. Among the clinical parameters age at presentation and use of NSAIDs significantly differed between groups. In the antidiarrheal group, patients tended to be more elderly, and in the corticosteroid group, more patients were on NSAIDs. CONCLUSIONS: 1) The degree of lamina propria inflammation can be used as a histological predictor to guide treatment in patients with CC. 2) Patients who responded to antidiarrheal agents or had spontaneous remissions were significantly older than those patients requiring 5-ASA compounds or corticosteroids. 3) Patients who were taking NSAIDs were more likely to require corticosteroid therapy, presumably reflecting more severe disease.

Mesalamine-induced chest pain: a case report.

Cardiac side effects of mesalamine are uncommon. A young man with ulcerative colitis who developed recurrent chest pain and electrocardiographic changes while on mesalamine is presented. Various causes of mesalamine-induced chest pain are discussed.

The crystal structure of plasminogen activator inhibitor 2 at 2.0 A resolution: implications for serpin function.

BACKGROUND: Plasminogen activator inhibitor 2 (PAI-2) is a member of the serpin family of protease inhibitors that function via a dramatic structural change from a native, stressed state to a relaxed form. This transition is mediated by a segment of the serpin termed the reactive centre loop (RCL); the RCL is cleaved on interaction with the protease and becomes inserted into betasheet A of the serpin. Major questions remain as to what factors facilitate this transition and how they relate to protease inhibition. RESULTS: The crystal structure of a mutant form of human PAI-2 in the stressed state has been determined at 2.0 A resolution. The RCL is completely disordered in the structure. An examination of polar residues that are highly conserved across all serpins identifies functionally important regions. A buried polar cluster beneath betasheet A (the so-called 'shutter' region) is found to stabilise both the stressed and relaxed forms via a rearrangement of hydrogen bonds. CONCLUSIONS: A statistical analysis of interstrand interactions indicated that the shutter region can be used to discriminate between inhibitory and non-inhibitory serpins. This analysis implied that insertion of the RCL into betasheet A up to residue P8 is important for protease inhibition and hence the structure of the complex formed between the serpin and the target protease.

Platelet-activating factor receptor activation. An initiator step in HIV-1 neuropathogenesis.

Human immunodeficiency virus type 1 (HIV-1) infection of the central nervous system results in neuronal apoptosis. Activated HIV-1-infected monocytes secrete high levels of the proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) and the phospholipid mediator platelet-activating factor (PAF). TNF-alpha and PAF are elevated in the central nervous system of patients with HIV-1-associated dementia. We now demonstrate that conditioned media from activated HIV-1-infected monocytes induces neuronal apoptosis, which can be prevented by co-incubation with PAF acetylhydrolase, the enzyme that catabolizes PAF in the central nervous system. Preceding apoptosis is a TNF-alpha-induced increase in neuronal ceramide levels. TNF-alpha-mediated neuronal apoptosis can also be blocked by co-incubation with PAF acetylhydrolase, or a PAF receptor antagonist. Blocking pathologic activation of PAF receptors may therefore be a pivotal step in the treatment of HIV-1-associated dementia.

AIDS-related extrapulmonary Pneumocystis carinii infection presenting as a solitary rectal ulcer.

Extrapulmonary infection with Pneumocystis carinii, although uncommon, is increasingly recognized. Use of aerosolized pentamidine versus a systemic medication is thought to be a contributing factor due to the low concentrations of drug that are incapable of suppressing systemic infection. Infection with P carinii has been reported in every organ system including the gastrointestinal system. A 28-year-old acquired immunodeficiency syndrome patient receiving prophylaxis with aerosolized pentamidine who presented with a solitary rectal ulcer is reported. Initial biopsy was characteristic of extrapulmonary P carinii infection, with numerous organisms present. Occasional cytomegalovirus inclusion bodies were noted which may have been a copathogen but which were not treated. Treatment with intravenous pentamidine resulted in documented eradication of P carinii and complete resolution of the ulcer. Although lower gastrointestinal pneumocystosis has been described without ulceration, this is the first description of rectal ulceration presenting as the initial manifestation of extrapulmonary pneumocystosis.

Human immunodeficiency virus infection, the acquired immunodeficiency syndrome, and inflammatory bowel disease.

The objective of this study was to determine the effect of human immunodeficiency virus (HIV) infection/acquired immunodeficiency syndrome (AIDS) on inflammatory bowel disease (IBD). A retrospective survey of the medical records of St. Paul's Hospital and its AIDS-care physicians/gastroenterologists searching for patients with both HIV/AIDS and IBD was conducted. Of 1,839 hospitalized patients (4,459 hospital admissions) from 1989 to 1993, two patients with AIDS/HIV and IBD were found. The physician survey revealed four patients for a total of six patients. Four patients developed de novo IBD--two ulcerative colitis (UC), one Crohn's disease (CrD), and one indeterminate colitis (IC)--after HIV infection. Two patients had UC predating HIV seroconversion. The absolute CD4 count of patients with de novo IBD was 210-700 cells/ml at the time of IBD. The patient with IC maintained quiescent IBD from a CD4 count of 190-30 cells/ml. The other had many relapses before HIV seropositivity. With CD4 count depletion, disease activity improved. IBD medications were discontinued at a CD4 count of 130 cells/ml. Diarrhea returned at a CD4 count of 20 cells/ml; however, sigmoidoscopy was unremarkable, and mucosal biopsy revealed cryptosporidiosis without active UC. No patient had an AIDS-related illness during active IBD. Two patients followed to CD4 counts of < 30 cells/ml suffered AIDS-related infections with quiescent IBD. With a progressive decline in CD4 count, IBD disease activity may improve and remit. The CD4 count at which remission occurs may reflect severe immunodeficiency such that risk for AIDS-related infection is high. Active IBD may occur with lesser degrees of immunodeficiency.

Immune thrombocytopenic purpura in three patients with preexisting ulcerative colitis.

Ulcerative colitis (UC) is associated with extraintestinal diseases in numerous target tissues. Associated immune-mediated hematological diseases, however, are rarely described. We report three Caucasian adult patients with UC and immune thrombocytopenic purpura (ITP). Platelet-associated antibodies (IgG) were positive in two patients, and bone marrow examinations in two patients revealed normal to increased megakaryocyte numbers. ITP was treated with corticosteroids in all patients. Two patients eventually received intravenous immune gamma-globulin, and one patient required surgical splenectomy. Of particular interest, UC preceded the onset of ITP in all patients (by from 1 to 19 yr). This suggests that ITP in these patients is causally associated with UC, possibly secondary to immunostimulation from lumenal antigens and altered immunoregulation.

Energy balance in stable malnourished patients with chronic obstructive pulmonary disease.

We have measured caloric intake, energy expenditure, and the thermogenic effect of food in ten patients with stable COPD who had a history of involuntary weight loss over several years and were malnourished (< 85 percent ideal body weight). Each patient completed a 7-day food record. Indirect calorimetry was performed in the resting postabsorptive state. After placement of a nasoenteric tube, patients were randomly assigned to be refed or sham-fed (mean +/- SD, 16 +/- 3 days), following which, metabolic measurements were repeated. Indirect calorimetry was also performed before and after a large meal in each patient. Home caloric intake was 135 +/- 23 percent of resting energy expenditure. Resting energy expenditure was 94 +/- 16 percent of that predicted by the Harris-Benedict equation and did not change significantly during inpatient refeeding. Refeeding resulted in weight gain (2.4 +/- 1.9 kg, p < 0.02). A large meal caused substantial increases in energy expenditure (24 +/- 18 percent), carbon dioxide production (39 +/- 18 percent), and oxygen consumption (23 +/- 16 percent). We conclude that stable malnourished COPD patients consume adequate calories to meet average energy requirements and are not hypermetabolic. Inpatient refeeding by nocturnal nasoenteric infusion is well tolerated and results in weight gain, but the thermogenic effect of a large meal poses a considerable metabolic and ventilatory load that could precipitate acute respiratory failure.

Histological examination of peroperative frozen sections in suspected lung cancer.

BACKGROUND: Despite extensive investigations some patients with suspected lung cancer may undergo thoracotomy without preoperative histological proof of malignancy. A questionnaire on the use of histological examination of peroperative frozen sections in such patients was sent to 50 thoracic surgeons. Replies were received from 41 surgeons and indicated an absence of consensus on the usefulness of histological examination of frozen sections in this context, confirming the need for this study. METHODS: During one year 60 consecutive patients undergoing thoracotomy for suspected lung cancer without a prior histological diagnosis were studied prospectively. At thoracotomy the surgeon assessed the lesion macroscopically and a verdict on whether it was malignant was recorded. A biopsy specimen was then taken for examination of a frozen section and the result recorded. The appropriate operation was performed and the surgeon's verdict and the report on the frozen section were compared with the definitive histological diagnosis based on a paraffin section. RESULTS: Of 50 malignant lesions, 43 were identified by the surgeon and 47 by examination of the frozen section (sensitivity 86% and 94% respectively). Of 10 benign lesions, four were identified by the surgeon and nine by examination of the frozen section (specificity 40% and 90% respectively). CONCLUSIONS: Clinical and macroscopic assessment at thoracotomy are inferior to examination of frozen sections in suspected lung cancer, particularly where the lesion is benign. Lung resection should not be performed without examination of peroperative frozen sections when thoracotomy is performed for suspected but unproved lung cancer.

Ventilatory dysfunction in severe anorexia nervosa.

A 25-year-old woman suffering from chronic anorexia nervosa lost more than 50 percent of her body weight and presented with generalized muscle weakness. Pulmonary function tests showed a severe restrictive defect, and she had marked impairment of respiratory muscle strength and endurance, peripheral muscle function, and hypercapnic ventilatory responses, all of which improved following refeeding. The interaction and response to treatment of these effects on respiratory function are discussed.

Middle ear adenoma: tumour of mixed mucinous and neuroendocrine differentiation.

Two cases of progressive hearing loss due to middle ear tumours are described. The histological characteristics numbered intraluminal mucin production and neuroendocrine features, as shown by argyrophilia and ultrastructural demonstration of dense core granules. These tumours have been known by many different names, reflecting the controversies relating to their presumed histogenesis and differentiation. The currently preferred designation is middle ear adenoma, and these two cases provide further evidence for dual lines of differentiation.

The effects of refeeding on peripheral and respiratory muscle function in malnourished chronic obstructive pulmonary disease patients.

We carried out a prospective randomized controlled trial to investigate the effects of short-term refeeding (16 days) in 10 malnourished inpatients with chronic obstructive pulmonary disease (COPD). Six patients were randomized to receive sufficient nasoenterically administered calories to provide a total caloric intake equal to 1,000 kcal above their usual intake. The other four patients were sham fed, receiving only 100 kcal more. Measurements of nutritional status, respiratory muscle strength and endurance, adductor pollicis function, and pulmonary function were performed initially and at study end. The refed group gained significantly more weight and showed significant increases in maximal expiratory pressure and mean sustained inspiratory pressure. There were no significant changes in the maximal inspiratory pressure or in adductor pollicis function. In malnourished inpatients with COPD, short-term refeeding leads to improvement in respiratory muscle endurance and in some parameters of respiratory muscle strength in the absence of demonstrable changes in peripheral muscle function.

Intracardiac ectopic thyroid: a case report and review of published cases.

A woman with ectopic intracardiac thyroid tissue showing features of a colloid storage goitre presented with ventricular tachycardias and signs of right ventricular outflow obstruction. As the tumour was benign and removed at necropsy, the results of surgery are likely to have been good, but she died from a cardiac arrest before operation.

Nutritional therapy of hospitalized patients with inflammatory bowel disease.

The use of total parenteral nutrition and enteral nutrition in inflammatory bowel disease has become commonplace. Except for well-documented improvements in nutritional parameters, the efficacy of these treatments for primary therapy or for complications remains largely unproven.

Concordance of histological classification of lung cancer with special reference to adenocarcinoma in Osaka, Japan, and the North-West Region of England.

In routinely collected data adenocarcinoma of the lung appeared to be 3 times more frequent in Osaka, Japan, than in the North-Western (NW) Region of England (Manchester). Before embarking on comparative epidemiological studies, it was decided to investigate the comparability of histological diagnosis. Specimens from 60 NW Region lung cancer patients and 52 Osaka patients were exchanged and reviewed. The entire material was then independently assessed by the WHO Collaborating Centre for Histological Classification of Tumours. The interpretation of the WHO Classification (WHO, 1981) by the NW Region and by Osaka was upheld by the WHO Collaborating Centre in 89% and 93% of all cases and in 97% and 100% of adenocarcinoma cases respectively. Agreement between the 2 centres was 88% for the main cell types. Differences in the frequency of adenocarcinoma of lung between the NW Region and Osaka are thus not due to diagnostic artefact and require further exploration. The aetiological implications of the finding that many Chinese and Japanese women with lung adenocarcinoma do not smoke (77% in Osaka) are discussed.