Standard Therapeutic Regimen Research Articles

Expression of 17-1A antigen and complement resistance factors CD55 and CD59 on liver metastasis in colorectal cancer

Despite radical surgery, the prognosis for colorectal cancer patients with liver metastases has not changed markedly. Furthermore, no standard adjuvant therapeutic regimen has been developed. Adjuvant therapy with monoclonal antibodies (e.g., against 17-1A), which has been shown to be effective in preventing metastatic relapse in patients with Dukes' C colorectal cancer, might be a promising approach for these patients. However, the cytotoxic effects of monoclonal antibodies can be blocked by coexpression of complement resistance factors that inhibit antibody-dependent complement-mediated cytotoxicity. We therefore analyzed immunohistochemically the expression of 17-1A and the membrane-bound complement resistance factors CD55 and CD59 on metastatic tumor cells in the livers of 71 patients with colorectal carcinoma who had undergone resection of their metastases with curative intent. In 67 (94%) of 71 patients, liver metastases with homogeneous expression of 17-1A was seen. Heterogeneous expression of 17-1A was seen in four patients (6%). Heterogeneous expression of CD55 or CD59 was observed in 8 (11%) of 71 patients and 4 (6%) of 71 patients, respectively. None of the patients showed homogeneous expression of either CD55 or CD59. All patients with CD55 or CD59 expression showed homogeneous 17-1A expression, whereas none of the four patients with heterogeneous 17-1A expression was positive for CD55 or CD59. Our data indicate that 17-1A is widely expressed on liver metastases of patients with colorectal carcinoma. Therefore patients with completely resected liver metastases might be suitable candidates for adjuvant therapy with and-17-1A antibody since only a few of these lesions showed coexpression of complement resistance factors.

Childhood cutaneous tuberculosis: a study over 25 years from northern India.

We undertook this study to analyse the pattern of childhood cutaneous tuberculosis prevailing in northern India over the past 25 years and to highlight differences from and similarities to adult tuberculosis. Clinical records of children with cutaneous tuberculosis who attended the Nehru Hospital attached to the Postgraduate Institute of Medical Education and Research, Chandigarh, India, between January 1975 to December 1999 were analysed. Four hundred and two patients with cutaneous tuberculosis were examined during the 25-year period of observation. These patients formed 0.1% of the total dermatology outpatients. Seventy-five (18.7%) of these 402 cases were children (</= 16 years). There were 32 (42.7%) boys and 43 (57.3%) girls with a boy : girl ratio of 0.74 : 1. The majority of the children, 41 (54.7%) were in the 10-14 years age group. There was no significant boy or girl preponderance in any group other than in scrofuloderma (SFD), where girls significantly outnumbered boys at all ages. Of the various patterns of cutaneous tuberculosis seen, 40 (53.3%) had SFD, 30 (40.0%) had lupus vulgaris (LV), 3 (4.0%) had tuberculosis verrucosa cutis (TVC), 1 (1.3%) child each had tuberculids and tubercular gumma. No child had a tubercular chancre or acute miliary cutaneous tuberculosis. The neck was the commonest site afflicted with SFD and the face was the commonest site affected with LV. No child had generalized lymphadenopathy. Eighteen (60.0%) of the 30 children with LV had regional lymphadenopathy of which 15 (83.3%) had localized disease and 3 (16.7%) had disseminated disease. Of the 16 children with systemic organ involvement, 12 (75.0%) had regional lymphadenopathy. Of the 62 children in whom the data regarding vaccination status was available, 31 (50.0%) had been vaccinated and 31 (50.0%) had not. Among the vaccinated group no child had disseminated disease. Three (9.7%) children in the nonvaccinated group had disseminated disease. Information regarding Mantoux reactivity was available in 71 (94.7%) children, 61 (86.0%) with localized disease and 10 (14.1%) with disseminated disease. Of the 61 children with localized disease, 56 (91.8%) were Mantoux positive and of the 10 children with disseminated disease, only 5 (50.0%) were Mantoux positive (> 10 mm). Histopathologic reports were available for evaluation in all 75 children. Out of 30 cases of LV, 24 (80%) showed classical tuberculous histology. In contrast, out of 40 cases with SFD, only 19 (47.5%) showed classical histology. Classical tuberculous histology was noted in all 3 (100%) cases of TVC and 1 (100%) case each with tuberculids and gumma. Tubercle bacilli could be demonstrated in 4/30 (13.3%) cases with LV and 9/40 (22.5%) cases with SFD. Systemic involvement was seen in 16 (21.3%) children, of whom 3 (18.8%) had LV and 13 (81.3%) SFD. The lungs were the most common organs involved in 8 (50.0%) children followed by bone(s) in 4 (25.0%), abdomen in 2 (12.5%), and both lung and bone in 1 (6.3%) child. In contrast to adults, girls outnumbered boys in the childhood series; SFD was a common form of presentation in contrast to LV and TVC, tuberculous gumma and tuberculids were noted less often. In both children and adults, Mantoux reactivity did not correlate with the extent of the disease; patients with disseminated disease were found to be less often vaccinated with BCG and regional lymphadenopathy was noted more often in patients with disseminated disease. In the whole spectrum of cutaneous tuberculosis, there is a proportion of patients with dissemination (systemic involvement) who are of great epidemiological significance as they require a change in the standard therapeutic regimens recommended for cutaneous tuberculosis.

Cycling status of primitive malignant progenitors from patients with acute myelogenous leukemia (Aml)

Hematopoietic progenitors in normal steady state peripheral blood (PB) are quiescent. In contrast, using an overnight 3H-Thymidine (3H-Tdr) assay, we previously found that many AML colony forming cells (AML-CFCs) and long term culture-initiating cells (AML LTC-ICs) were actively cycling. The same 3H-Tdr suicide assay is now used to compare the proliferative status of AML progenitors detected in NOD/SCID mice (NOD/SCID leukemia-IC or NOD/SL-IC) to that of AML-CFC and LTC-IC detected in 6 newly-diagnosed AML patient samples. Culture of AML cells for 16 h without 3H-Tdr in serum-free medium with 50 ng/ml Steel Factor, 20 ng/ml IL-3 and 20 ng/ml G-CSF maintained AML-CFC and LTC-IC numbers at near input levels (mean % input ± SD, 123 ± 72 and 117 ± 47, respectively) but reduced the % CD45+ AML cells detected in NOD/SCID mouse bone marrow 8 wks after i.v. injection as compared to uncultured cells (mean % input ± SD, 58 ± 41). The addition of 20 μCi/ml high specific activity 3H-Tdr to such cultures reduced the numbers of both AML CFC and LTC-IC significantly (mean % kill ± SD 57 ± 42 and 68 ± 30, respectively). However, <50% kill of AML-CFC and/or LTC-IC was seen for 3 of 6 samples. NOD/SL-ICs from these 3 samples were also largely quiescent (% kill 16-43% at 8 wks). In one sample, AML CFC, LTC-IC and NOD/SL-IC were all actively cycling (>80% kill). In the remaining 2 cases, although >90% kill of AML LTC-IC and 61 and 99% kill of AML-CFC were detected, NOD/SL-IC showed 26 and 0% kill at 8 wks. Thus, although a larger proportion actively cycling CFC and LTC-IC are detected in AML blood than in normal steady state PB, a significant proportion of primitive leukemic progenitors from most patient samples are quiescent. These cells may be relatively resistant to standard therapeutic regimens for AML.

Clinical and immunologic parameters during thalidomide treatment of lupus erythematosus.

Thalidomide is used as an experimental drug for the treatment of chronic inflammatory diseases with an autoimmune or infectious background. The pharmacologic action involves the downregulation of the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) and inhibition of basic fibroblast growth factor (bFGF)-induced angiogenesis; however, not much is known about thalidomide's effect on immunologic parameters in lupus erythematosus (LE). Method This is an open study of a group of five consecutive systemic lupus erythematosus (SLE) patients treated with thalidomide (100 mg/day) and five consecutive cutaneous LE patients not responsive to conventional therapy. The clinical and immunologic parameters (C-reactive protein, immunoglobulin, and complement serum levels, lymphocyte counts) were investigated during thalidomide treatment for up to 2 years in both patient groups. An increase in the absolute peripheral lymphocyte count was observed beginning after 2 weeks of systemic thalidomide treatment in nine out of 10 LE patients, and remained stable throughout thalidomide treatment. Elevated serum levels of C-reactive protein and titers of autoantibodies to double-stranded (ds) DNA decreased in SLE patients. No significant changes were detected in the serum levels of the complement components C3 and C4 and immunoglobulins in all LE patients. Regression of inflammatory skin lesions and regrowth of hair were recorded. As a side-effect, polyneuropathy was observed in four out of 10 patients, with the earliest onset at 3 weeks of thalidomide treatment. Thalidomide is a potent anti-inflammatory drug in patients with SLE and cutaneous LE, possibly interacting with the recruitment of lymphocytes. It leads to the regrowth of hair in LE-related alopecia and effluvium. Early symptoms of polyneuropathy should be registered and the drug should be withdrawn. Thalidomide should be restricted to patients who show no response to standard therapeutic regimens and should only be used under strict precautions with regard to its known teratogenic risk.

Best hope or last hope: access to phase III clinical trials of HER-2/neu for advanced stage breast cancer patients.

Breast cancer is a major public health problem, with a 12% incidence among women. The over-expression of the proto-oncogene HER-2/neu is associated with 30% of breast and ovarian cancers that are very aggressive and do not respond to standard therapeutic regimens. Entrance into clinical trials can represent the best hope and even the last hope for these patients. Entrance, however, is based on satisfying eligibility criteria. In examining advanced stage breast cancer patients' access to phase III clinical trials for HER-2/neu, two specific arguments regarding eligibility will be addressed. First, if research is to provide the utilitarian goal of the 'greatest good to the greatest number', delineation of the population receiving the 'good', rather than a homogeneous sub-set of this population, must be addressed, along with patients' values and goals, very relevant to determining a 'good life', how to achieve it, and whether a treatment is a part of that process. Second, the 'good' being generated should involve realistic, practical values of quality ways of living with advanced breast cancer and not just increased survival, or cure. Arguments for relaxing criteria are based on an accurate versus over-simplified interpretation of utilitarian principles and concepts of human flourishing. Only through addressing these issues can the true 'good' of clinical trials and research be given to the greatest number of people.

Metabolism of polyunsaturated fatty acids by skin epidermal enzymes: generation of antiinflammatory and antiproliferative metabolites

In the skin epidermis, the metabolism of polyunsaturated fatty acids (PUFAs) is highly active. Dietary deficiency of linoleic acid (LA), the major 18-carbon n-6 PUFA in normal epidermis, results in a characteristic scaly skin disorder and excessive epidermal water loss. Because of the inability of normal skin epidermis to desaturate LA to gamma-linolenic acid, it is transformed by epidermal 15-lipoxygenase to mainly 13-hydroxyoctadecadienoic acid, which functionally exerts antiproliferative properties in the tissue. In contrast, compared with LA, arachidonic acid (AA) is a relatively minor 20-carbon n-6 PUFA in the skin and is metabolized via the cyclooxygenase pathway, predominantly to the prostaglandins E(2), F(2)(alpha), and D(2). AA is also metabolized via the 15-lipoxygenase pathway, predominantly to 15-hydroxyeicosatetraenoic acid. At low concentrations, the prostaglandins function to modulate normal skin physiologic processes, whereas at high concentrations they induce inflammatory processes. PUFAs derived from other dietary oils are also transformed mainly into monohydroxy fatty acids. For instance, epidermal 15-lipoxygenase transforms dihomo-gamma-linolenic acid (20:3n-6) to 15-hydroxyeicosatrienoic acid, eicosapentaenoic acid (20:5n-3) to 15-hydroxyeicosapentaenoic acid, and docosahexaenoic acid (22:6n-3) to 17-hydroxydocosahexaenoic acid, respectively. These monohydroxy acids exhibit antiinflammatory properties in vitro. Thus, supplementation of diets with appropriate purified vegetable oils, fish oil, or both may generate local cutaneous antiinflammatory and antiproliferative metabolites which could serve as less toxic in vivo monotherapies or as adjuncts to standard therapeutic regimens for the management of inflammatory skin disorders.

Auswirkungen der Kneipp-Kur, einer standardisierten Komplextherapie, auf Schmerz, Lebensqualität und Medikamentenverbrauch: Kohortenstudie mit 1-Jahres-Follow-up

Background: Inpatient as well as outpatient cure in a spa environment with commonly 3- to 4-week duration features a combination of different treatments customized according to the needs of the individual patient. The physiological rationale and the mode of action are widely accepted. However, firm quantitative evidence of the clinical effectiveness is incomplete. Objective:To document the effects of a well standardized complex therapeutic regimen (Kneippism) on pain, quality of life, and drug consumption during therapy and with 1-year follow up. Study Design:Prospective cohort study with assessments at the beginning, during, and at the end of treatment and with follow-up investigations 3, 6, and 12 months thereafter. Setting:Four spa clinics in Bad Wörishofen, Southern Bavaria. Patients:363 patients (248 outpatients, mean duration of therapy 23.3 days, and 115 inpatients, mean duration of therapy 27.4 days), one half between 40 and 60 years old above 60 years of age, predominantly suffering from musculoskeletal and/or cardiovascular diseases. Intervention: Custom-tailored combination of therapies comprising of hydro-, kinesi-, and phytotherapy, dietetics, `ordnungstherapie', and continued disease-specific standard treatment, if necessary. Main Outcome Measure:Pain, patients' self-rating, (IRES questionnaire), medication. Results:The monitored dimensions of pain improved significantly during treatment and remained at that level essentially for the complete follow up interval. The same was true for various dimensions of reported subjective complaints as well as for drug consumption. Conclusion:When estimating the clinical relevance of a complex therapeutic regimen such as a cure of 3- to 4-week duration, the question of the impact of the specific effect of single components is secondary to the question of the overall relevance of that therapeutic concept. The findings of this study point at potential long-term effects of at least 1-year duration.

Management of unresectable pancreatic ductal cancer

1 The median duration of survival for patients with unresectable pancreatic ductal cancer is 6 to 10 months. 2 Given this modest duration of survival, quality of life is an important clinical end point in the management of patients with unresectable pancreatic ductal cancer. Relief or palliation of biliary tract and gastroduodenal obstruction and pain are the major clinical issues affecting quality of life. 3 Multiple therapeutic approaches have been evaluated for the management of biliary tract and gastroduodenal obstruction. Choice of therapeutic approach is dictated by the temporal recognition of unresectability. Two broad groups of patients with unresectable pancreatic cancer are (1) the majority of patients with unresectable pancreatic ductal cancer recognized nonoperatively (by imaging) and (2) the minority of patients with unresectable pancreatic ductal cancer recognized intraoperatively. 4 The preponderance of controlled and uncontrolled studies strongly support the consensus that endoscopic biliary stenting provides optimal relief of jaundice in patients with unresectable pancreatic ductal cancer recognized nonoperatively. Percutaneous transhepatic stenting is reserved for patients in whom endoscopic stenting has failed or is precluded technically. When sectable pancreatic ductal cancer is recognized intraoperatively, controlled and uncontrolled data support operative bilioenteric bypass, regardless of prior biliary stenting. 5 Accumulated data support open gastroenterostomy for palliation of gastroduodenal obstruction. Data are insufficient for consensus on prophylactic gastroenterostomy during operative bilioenteric bypass. 6 Pain adversely affects quality of life in a majority of patients with unresectable pancreatic ductal cancer; pain control improves quality of life. Both controlled and uncontrolled data support the consensus that both operative and percutaneous neurolytic celiac plexus block are more effective than oral analgesia for relief of pain. 7 Antineoplastic therapy—irradiation, chemotherapy, and immunotherapy—currently have limited impact on overall duration of survival. Controlled data for combined irradiation and systemic chemotherapy and chemotherapy alone show overall survival is improved by a few months. Sparse data on immunotherapy do not support a survival benefit. There are insufficient controlled or uncontrolled data to support a consensus on a standard antineoplastic therapeutic regimen for patients with unresectable pancreatic ductal cancer. 8 Future studies of patients with unresectable pancreatic ductal cancer should address objective measures of quality of life and survival. Stage of disease and specific symptoms should be carefully defined for patients in studies.

Management of cutaneous lupus erythematosus with low-dose methotrexate: indication for modulation of inflammatory mechanisms.

There is no consensus about an effective and safe treatment for patients with cutaneous lupus erythematosus (LE) who are refractory to antimalarials and/or low-dose oral glucocorticosteroids. Therefore, we retrospectively analyzed the clinical data and laboratory findings of 12 patients who received weekly administrations of 10-25 mg methotrexate (MTX). Previous treatment with antimalarials and/or glucocorticosteroids was not effective or had to be withdrawn because of side effects. Of 12 patients, ten showed improvement of their skin lesions; two patients did not respond to low-dose MTX; two patients cleared rapidly, and five other patients had long-lasting remissions of 5-24 months after stopping MTX treatment. A reduction of circulating autoantibodies was detected in five patients. In all patients, MTX was well tolerated subjectively and objectively. Weekly low-dose MTX is useful for the treatment of cutaneous LE, particularly in those cases which need long-term treatment and/or do not respond to standard therapeutic regimens.

Biologic and clinical significance of CD7 expression in acute myeloid leukemia.

CD7 antigen, a T-cell lineage associated antigen, is expressed in a minority of patients with acute myeloid leukemia (AML). The biologic and clinical significance of this finding is not clearly established. In this retrospective study of patients with de novo acute myeloid leukemia, we have identified CD7 expression and analyzed its association with markers expressed early in hemopoietic ontogeny and clinical parameters. Among 60 consecutive AML patients, we found six (10%) expressing CD7 on leukemic cells. There were five males and one female and the mean age was 59.6 years (age range: 32-76 years) with no demographic peculiarities. The FAB subtypes were: M0 (2), M1 (1), M2 (1), and M4 (2). CD7 expression was associated with immature antigens CD34, HLA-DR, and terminal deoxynucleotidyl transferase (TdT) and antigen receptor gene rearrangements (rearrangements of T-cell receptor gamma chain in 6/6 and immunoglobulin heavy chain in 2/6). Hepatomegaly was present in three and this was associated with splenomegaly with lymphadenopathy in one patient. Mediastinal or central nervous system involvement was absent. Complete remission was achieved in two patients with standard chemotherapy; one of these is in remission and alive (5 years later), while one died following relapse 9 months later. Three patients had significantly lower response to standard therapeutic regimen (two died during induction and one died 7 months later without ever achieving complete remission). One patient has been excluded in determining the prognostic significance of CD7 due to early death. Our results suggest origin of CD7+ AML from early hemopoietic precursors and indicate biologic aggressiveness in a significant proportion of patients. We suggest evaluation of CD7 in all patients with AML at the time of diagnosis in view of poor clinical outcome.

TREATMENT OF CONDYLOMATA ACUMINATA WITH ORAL ISOTRETINOIN

Purpose The aim of our study was to evaluate the efficacy and safety of oral isotretinoin in the treatment of condylomata acuminata. Materials and Methods A total of 56 male patients with a history of condylomata acuminata refractory to at least 1 standard therapeutic regimen was treated orally with isotretinoin (1 mg./kg. daily) during a 3-month period. Results At the end of treatment 21 of the 53 evaluated patients (39.6%) had complete response, 7 (13.2%) had partial response and 25 (47.1%) had no response. A statistically significant inverse relationship was found between age and area of treated lesions and response to medication. Two complete responders (9.5%) revealed recurrence during the 1-year followup. Conclusions Oral isotretinoin may be regarded as an effective, fairly well tolerated and noninvasive alternative form of therapy for immature and small condylomata acuminata.

4 Drug disposition and action in the burned patient

Thermal injury causes a prolonged, complex pathophysiological response which involves major changes in cardiovascular, renal and hepatic function. These changes, in addition to alterations in plasma protein concentrations, are responsible for significant changes in the disposition and action of many drugs in patients. Changes in drug absorption, plasma protein binding, hepatic blood flow and drug biotransformation, and renal blood flow, drug filtration and secretion have been demonstrated for many classes of drugs in burned patients. These pharmacokinetic factors often mean that standard therapeutic regimens may be inappropriate for such patients. In addition, burn injury may also cause a disruption of the functioning of drug receptors, causing altered pharmacological responses to plasma drug concentrations that are usually effective in non-burned patients. Such pharmacokinetic and pharmacodynamic changes have been observed in several classes of drugs used commonly in anaesthetic practice, these classes including the muscle relaxants, opioid analgesics, aminoglycoside antibiotics, benzodiazepines, exogenous catecholamines and H 2 -receptor antagonists. Careful attention to the use of these agents in burned patients is required, with close monitoring of drug effect being particularly important.

Atypical pathogen pneumonia.

The term atypical pathogens has been applied in recent years to Chlamydia pneumoniae, Mycoplasma pneumoniae, and the various species of Legionella. The incidence of pneumonia caused by these pathogens has increased with the development of specific diagnostic techniques. Atypical pathogen community-acquired pneumonia demonstrates a broad spectrum of severity from a mild disease not requiring hospitalization to adult respiratory distress syndrome necessitating mechanical ventilation. The clinical, radiological, and laboratory manifestations of the disease are similar to those of community-acquired pneumonia caused by other pathogens, and reliable etiological differentiation cannot be based on these factors alone. The possibility of shortening treatment time, at least in some patients, by antibiotic therapy with the new macrolides has been added to standard therapeutic regimens with erythromycin, tetracyclines, or quinolones.

Pelvic Inflammatory Disease and Human Immunodeficiency Virus Infection

To identify the effect of human immunodeficiency virus (HIV) infection on the clinical course of pelvic inflammatory disease (PID). Women hospitalized with PID at an urban hospital serving a population at high risk for HIV were studied cross-sectionally. Data abstracted from medical records of 349 women, admitted between July 1992 and April 1994 were linked anonymously to HIV serology. Main outcome measures were length of hospital stay, prolonged fever, tubo-ovarian abscess, surgery, and change in antibiotics. Among the 349 women with PID, 27 were HIV-positive. These HIV-positive women had lower mean white blood cell counts at admission (7411 versus 11,266, P < .01), lower mean lymphocyte counts (1411 versus 1928, P < .01), greater febrile morbidity (54 versus 28.3%, P < .01), and longer hospital stays (10.5 versus 6.4 days, P < .01) than HIV-negative women. Women who were HIV-positive required more time for defervescence and needed to change their antibiotic regimen more frequently (41 versus 12.7%, P < .01); differences in tubo-ovarian abscesses (19 versus 14%, P = .52) or surgery (15 versus 6.2%, P = .10) were not significant. The differences in hospital course between HIV-positive and HIV-negative women were modest, and they were resolved largely by the fourth or fifth hospital day. All HIV-positive women were treated successfully with first- or second-line antibiotic regimens. Despite more severe initial presentation and a prolonged hospital course, HIV-positive women with PID, but without other acute illnesses, were treated successfully with standard therapeutic regimens. These observations support current recommendations for hospitalization of HIV-positive women with PID and treatment according to current standards.

The Influence of Parasympatholytics on the Resolution of Acute Attacks of Asthma

PURPOSE: To evaluate the role of parasympatholytics in the resolution of acute attacks of asthma.METHODS: This study employed a prospective sequential design in which the influence of 0.5 and 1.0 mg of ipratropium bromide on peak expiratory flow rates (PEFR), hospital admissions, and length of stay (LOS) in the emergency department (ED) was evaluated. The parasympatholytic was added to a well-investigated standard therapeutic regimen that was anchored by the use of repetitive doses of albuterol, and employed pretested decision algorithms.RESULTS: One hundred and thirty-one patients received ipratropium (I) and 123 who did not (NI) served as controls. There were no significant pretreatment between group differences in gender, racial composition, clinical signs and symptoms, or PEFR. The presence of ipratropium in the regimen did not influence discharge/admission patterns, LOS, the rate of improvement of the patients, or the level of PEFR achieved.CONCLUSION: Anticholinergic agents such as ipratropium are not first-line treatments for acute asthma. They do not add any therapeutic benefit to the effects of albuterol given in divided doses over 1 hour, nor do they facilitate recovery in patients whose immediate response to sympathomimetics is impaired.

Subglottic stenosis complicating Wegener's granulomatosis: Surgical repair as a viable treatment option

Wegener's granulomatosis frequently involves the subglottis and trachea, often leading to compromise of the upper airway. Moreover, the stenotic segments may persist or progress despite control of the disease elsewhere in the body. In this report, we describe the cases of five patients with Wegener's granulomatosis who, in addition to nasal, sinus, pulmonary and renal involvement, had symptomatic subglottic or tracheal stenosis. Biopsy specimens from involved sites in the subglottis and trachea were often not diagnostic, and the diagnosis was later confirmed by a positive antineutrophil cytoplasm antibody titer. All patients had clinical remission on standard therapeutic regimens with prednisone and cyclophosphamide but continued to have symptoms of extrathoracic airway obstruction. Three of the five patients underwent primary thyrotracheal anastomosis while their disease was in clinical remission, without postoperative compromise of anastomotic integrity or wound healing despite concurrent use of prednisone and cyclophosphamide. There has been no evidence of local disease recurrence during follow-up periods ranging from 3 months to 14 years. We conclude that surgical intervention is a viable treatment option for patients who have symptomatic stenotic segments of the subglottis and trachea as a result of Wegener's granulomatosis in clinical remission. (J T HORAC C ARDIOVASC S URG 1996;111:961-6)

The significance of polyunsaturated fatty acids in cutaneous biology.

The skin epidermis displays a highly active metabolism of polyunsaturated fatty acids (PUFA). Dietary deficiency of linoleic acid (LA) and 18-carbon (n-6) PUFA results in characteristic scaly skin disorder and excessive epidermal water loss. Arachidonic acid, a 20-carbon (n-6) PUFA is metabolized via the cyclooxygenase pathway into predominantly prostaglandin E2 (PGE2) PGF2 alpha, and PGD2 and via the lipoxygenase pathway into predominantly 15-hydroxyeicosatetraenoic acid (15-HETE). The prostaglandins modulate normal skin physiological processes at low concentrations and inflammatory reactions at high concentrations. Similarly, the very active epidermal 15-lipoxygenase transforms dihomogammalinolenic acid (DGLA) into 15-hydroxy eicosatrienoic acid (15-HETrE), eicosapentaenoic acid (EPA) into 15-hydroxyeicosapentaenoic acid (15-HEPE) and docosahexaenoic acid (DHA) into 17-hydroxydocosahexaenoic acid (17-HDoHE), respectively. These monohydroxy acids exhibit anti-inflammatory properties. In contrast, the 18-carbon (n-6) PUFA is transformed into 13-hydroxy-9,11-octadecadienoic acid (13-HODE), which exerts antiproliferative properties in the tissue. Thus, the supplementation of diets with appropriate purified vegetable oils and/or fish oil may generate local cutaneous anti-inflammatory metabolites which could serve as a less toxic in vivo monotherapy or as adjuncts to standard therapeutic regimens for the management of skin inflammatory disorders.

High Helicobacter pylori numbers are associated with low eradication rate after triple therapy.

This study tested the influence of pretreatment bacterial density on the eradication rate of Helicobacter pylori with triple therapy. One hundred and thirty two patients with endoscopically confirmed H pylori positive, duodenal ulcer or antral gastritis were treated with triple therapy (colloidal bismuth/metronidazole/amoxicillin) for two weeks. Pretreatment urease activity was assessed by the 14C-urea breath test (UBT) in all patients. The mean (SD) pretreatment UBT concentration was similar in patients with duodenal ulcers (318.4 (175.0)) and patients with antral gastritis (288.9 (165.5)). Overall eradication of H pylori was achieved in 85 of 132 patients (64.4%), but was significantly different between patients with high, intermediate, or low pretreatment urease activity (37.5%, 69.5%, and 87.8% respectively). The mean post-treatment UBT value of patients in whom eradication failed was in direct correlation with the pretreatment UBT values. In conclusion, bacterial density, as assessed by urease activity, is an important factor in predicting H pylori eradication. It is suggested that the pretreatment UBT has the potential to identify patients who require modification of the standard therapeutic regimen.

Clinical parameters associated with recalcitrant oral candidosis in HIV infection: a preliminary study.

Clinical resistance in oropharyngeal candidosis is an increasingly significant management problem in HIV-seropositive patients. This study was undertaken to identify predisposing risk factors including the isolation of particular species of Candida which may be associated with the development of clinical resistance. The effect of particular antifungal prescribing regimens was also assessed. Data were compiled by chart review of 2 groups, each of 10 HIV-seropositive CDC stage IV patients with recurrent oropharyngeal candidosis. All patients had swabs taken at intervals during treatment and all candida isolates were species typed. The patients in group 1 exhibited candida infections which did not respond clinically to standard therapeutic regimens. The second patient group did respond to standard oral antifungal therapies. An association was found between the frequent utilization of azoles, particularly fluconazole and the development of clinically resistant oral candidosis. The number of candida isolates grown from the initial swab was also significantly related to the development of resistance.

Primary malignant lymphoma of the central nervous system--report of four long-term survivors.

Four of 47 patients treated between 1977 and 1993 for histologically confirmed primary malignant lymphoma of the central nervous system (non-Hodgkin's type of B-cell origin) achieved long-term survival for more than 5 years with a good quality of life. Three have remained disease-free for 9-12.5 years. The fourth achieved complete remission for more than 5 years before death from tumor recurrence. All four patients were treated with a standard therapeutic regimen, consisting of radiotherapy (50-60 Gy local and 30-40 Gy whole brain irradiation) followed by four to six courses of chemotherapy with cyclophosphamide, vincristine, adriamycin, and prednisolone at 4- to 8-week intervals. No further treatment was performed after remission had been obtained. No specific predictors for long-term survival including sex, age, tumor location, multiplicity of lesions, histology, or treatment modality was identified. All four patients showed an immediate tumor response to radiation. We recommend chemotherapy at increasing intervals as part of the post-therapeutic management of long-term, disease-free patients.