Evolution After Anti-TNF Discontinuation in Patients With Inflammatory Bowel Disease: A Multicenter Long-Term Follow-Up Study.

OBJECTIVES: The aims of this study were to assess the risk of relapse after discontinuation of anti-tumor necrosis factor (anti-TNF) drugs in patients with inflammatory bowel disease (IBD), to identify the factors associated with relapse, and to evaluate the overcome after retreatment with the same anti-TNF in those who relapsed. METHODS: This was a retrospective, observational, multicenter study. IBD patients who had been treated with anti-TNFs and in whom these drugs were discontinued after clinical remission was achieved were included. RESULTS: A total of 1,055 patients were included. The incidence rate of relapse was 19% and 17% per patient-year in Crohn's disease and ulcerative colitis patients, respectively. In both Crohn's disease and ulcerative colitis patients in deep remission, the incidence rate of relapse was 19% per patient-year. The treatment with adalimumab vs. infliximab (hazard ratio (HR)=1.29; 95% confidence interval (CI)=1.01-1.66), elective discontinuation of anti-TNFs (HR=1.90; 95% CI=1.07-3.37) or discontinuation because of adverse events (HR=2.33; 95% CI=1.27-2.02) vs. a top-down strategy, colonic localization (HR=1.51; 95% CI=1.13-2.02) vs. ileal, and stricturing behavior (HR=1.5; 95% CI=1.09-2.05) vs. inflammatory were associated with a higher risk of relapse in Crohn's disease patients, whereas treatment with immunomodulators after discontinuation (HR=0.67; 95% CI=0.51-0.87) and age (HR=0.98; 95% CI=0.97-0.99) were protective factors. None of the factors were predictive in ulcerative colitis patients. Retreatment of relapse with the same anti-TNF was effective (80% responded) and safe. CONCLUSIONS: The incidence rate of inflammatory bowel disease relapse after anti-TNF discontinuation is relevant. Some predictive factors of relapse after anti-TNF withdrawal have been identified. Retreatment with the same anti-TNF drug was effective and safe.

Endogenous progesterone is associated to amyotrophic lateral sclerosis prognostic factors.

UNLABELLED: Negative prognostic factors in amyotrophic lateral sclerosis include advanced age, shorter time from disease onset to diagnosis, bulbar onset and rapid progression rate. OBJECTIVE: To compare progesterone (PROG) and cortisol serum levels in patients and controls and ascertain its relationship to prognostic factors and survival. METHODS: We assessed serum hormonal levels in 27 patients and 21 controls. RESULTS: Both hormones were 1.4-fold higher in patients. PROG showed a negative correlation with age, positive correlation with survival and positive trend with time to diagnosis. Increased PROG was observed in spinal onset and slow progression patients. No correlation was demonstrated with cortisol. CONCLUSION: Increased hormonal levels in patients are probably due to hypothalamic-pituitary-adrenal axis activation. Nevertheless, in this preliminary report only PROG correlated positively with factors predicting better prognosis and survival. We hypothesize endogenous PROG and cortisol may be engaged in differential roles, the former possibly involved in a neuroprotective response.

Logistics and safety of edaravone treatment for amyotrophic lateral sclerosis: experience in Argentina.

Since 2015, edaravone is the second drug available for the treatment of Amyotrophic lateral sclerosis (ALS). In this study we analyzed the characteristics and experience of ALS patients treated with this new medication in our country. Sixteen ALS patients were treated with edaravone infusions in three ALS clinics. Most of them were male, had a spinal onset of the disease and a definite diagnosis of ALS. Mean age at first infusion was 53.5 years. Since the diagnosis of ALS, delay in starting treatment with edaravone was five times greater than that of riluzole. Edaravone therapy was usually initiated at a health care facility and was followed by domiciliary cycles. Adverse effects and the need of a special catheter for infusion were rare. Access to edaravone through health insurance was possible in only 43.8% of patients. Altogether, treatment access was limited but feasible and edaravone was well tolerated.

Behçet's syndrome associated with pregnancy.

A case of Behçet's syndrome diagnosed during pregnancy is reported. It is believed that this condition is more common in the United States than previously thought. It should be considered in the differential diagnosis of genital ulceration.

Diagnosis of allergic disease.

The diagnosis of allergic disease has to be individualized to each patient. In general, it consists of a good clinical history, a physical examination, and identification of specific relevant allergies by both in vitro and in vivo tests. These will contribute to an assessment of the patient's clinical status and severity of disease. One must always be aware that nonallergic mechanisms can also trigger an attack in atopic individuals. These are clinically indistinguishable from those provoked by an allergen-IgE immune response. We predict that the computer and accurate in vitro tests will join us in our offices. Before the end of this century, this high technology will make the clinical allergist a very precise diagnostician.

[Amyotrophic lateral sclerosis: its relationship with thyroid function and phosphate calcium metabolism]. / Esclerosis lateral amiotrófica. Evaluacion de la función tiroidea y del metabolismo fosfocálcico.

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a progressive degenerative disease involving motor neurons of the spinal cord, brain stem, and motor cortex. Previous studies reported the coexistence of motor neuron disease with thyroid dysfunction and primary hyperparathyroidism. These findings suggested an eventual role of the previously mentioned endocrine disorders and the development of ALS. OBJECTIVE: Identify thyroid dysfunction and changes in mineral metabolism in patients affected by sporadic ALS. PATIENTS AND METHODS: We retrospectively analyzed data from 41 in ward patients from June 1998, to June 2001. All of them were diagnosed with sporadic ALS. The following laboratory test were performed: thyrotropin (TSH), thyroxine (T4), serum calcium, serum phosphate, parathyroid hormone (PTH) and ionic calcium concentrations. RESULTS: None of the studied patients was found to be hyperthyroid. Two patients had elevated TSH and normal T4, these findings suggested subclinical hypothyroidism. Elevated PTH was found in one patient; another had primary hyperparathyroidism. Low serum calcium was found in three patients and elevated phosphate was found in another four. CONCLUSIONS: All these findings do not allow us to assert a pathogenic association between thyroid dysfunction or alteration of phosphate calcium metabolism and ALS.

Immunoglobulin G subclass responses to cytomegalovirus in seropositive patients after transfusion.

The immunoglobulin G subclass responses to cytomegalovirus (CMV) after red cell (RBC) transfusion were studied in 26 seropositive surgery patients and 34 transfused seropositive oncology patients. Also included as controls were 18 surgical patients who received no RBCs during surgery. None of the 78 patients studied had IgG2 to CMV before or after transfusion. The absence of a total IgG response to CMV after transfusion could not be attributed to preexisting deficiencies in one or more subclasses, because all 78 patients had similar levels of IgG1, IgG3, and IgG4 to CMV before transfusion. Discriminant analysis was used for statistical evaluation of the combined CMV subclass responses in each patient and the individual subclass responses. Individual patients responded to CMV antigens with an increase in concentration in any of the three subclasses or any combination of the subclasses, excluding IgG2. IgG subclass analysis showed that 10 of 27 patients who did not respond with at least a fourfold total IgG titer rise had a significant increase in IgG subclass antibodies to CMV. Three of 33 patients with at least a fourfold total IgG titer rise lacked a subclass response. These results suggest that the measurement of IgG subclasses may be a sensitive indicator of immune response to CMV.

The art and science of allergy skin testing.

Demographic information, symptoms, and allergy skin test data from 809 patients from four allergy practices (A, B, C, and D) were statistically evaluated. A panel of 42 allergens were used for a total of 24,293 tests. Allergen positivity ranged from 51% for house dust to 9% for cat/dog. The patient population had primarily respiratory tract spring symptoms. Significant differences between the practices were found for (1) the number of skin tests done per patient, (2) the number of positive tests per patient, and (3) the grading of a positive test. A patient had a 3-fold to 6-fold greater chance of being found atopic by practice C or D than by practice A with practice B being intermediate. These differences highlight the need for less variation and better diagnostic standardization in the practice of allergy.

Rapidly progressive glomerulonephritis in Behçet's syndrome.

Rapidly progressive glomerulonephritis developed in a patient with Behçet's syndrome while he was being treated with transfer factor. The therapy did not prevent development of this disease and thus cannot be recommended in patients who have Behçet's syndrome with renal involvement.

Listeria cell wall fraction: a B cell adjuvant.

A crude cell wall-rich fraction of Listeria monocytogenes (LCWF) has previously been shown to induce resistance to Listeria infection in mice, to be a murine B cell mitogen, and to be an immunologic adjuvant. Data reported here show that LCWF stimulates immune responses by three different murine B cell populations that respond poorly or not at all to thymus-dependent antigens when T cells are severely depleted or absent. These B cell populations include nude mouse spleen cells, anti-theta serum-treated spleen cells and bone marrow-derived spleen cells. In addition, sheep erythrocytes coated with LCWF are converted to thymus-independent antigens. The adjuvant effect of LCWF on B cell populations is not enhanced by the presence of T cells, nor does LCWF increase in vivo education of T cells to sheep erythrocyte antigens. Thus, a direct effect of LCWF on T cells could not be demonstrated, suggesting that LCWF does not act on T cells. Because of these LCWF effects on B cells, the possible role of B cells in resistance to infection by Liseria monocytogenes is discussed.

Induction of Resistance by Listeria monocytogenes Cell Wall Fraction.

A crude cell wall fraction of Listeria monocytogenes was prepared by sonic disruption and differential centrifugation of viable, washed cultures. When injected into mice, this sterile, crude cell wall fraction protected mice against an intraperitoneal challenge with 18 to 85 50% mean lethal dose of L. monocytogenes. Resistance was greatly enhanced when bacterial endotoxin (lipopolysaccharide) was injected along with the cell wall fraction. Resistance was measured both by enumerating the bacteria in the livers and spleens of vaccinated and control mice and by survival studies. Two major lines of evidence suggest that the resistance induced by cell wall fraction is at least in part specific. Unlike non-specific resistance, the cell wall fraction-induced resistance was relatively long-lived, (i.e., it was demonstrable 6 weeks after the last injection of cell wall fraction and lipopolysaccharide). In addition, cell wall fraction protected against challenge with L. monocytogenes, but not against challenge with S. typhimurium.

The use of humidity in asthmatic children.

Controversy exists as to the advisability of mist therapy in pulmonary disease. We studied the effects of several forms of humidity on asthmatic airways. Thirty-four children were tested over a period of 8 months as follows: (1) mist with a mean particle size of 3 mu was delivered for 30 min by an ultrasonic nebulizer to 11 children individually in a plastic tent; (2) to another 11 subjects in a tent, mist with a mean particle size of 10 mu was delivered by a jet nebulizer for 30 min;3) 15 patients in a croup room recieved for 30 min water droplets ranging from a microscopic fog to large rain particles (mean 16 mu) generated by a Melco natural fog generator; (4) 10 children were challenged with 3 solutions used commonly for the production of mist: distilled water, half-normal saline, and normal saline. Pulmonary functions were studied on each patient pre- and post-mist exposure. Approximately two thirds of the patients had a significant response, either improvement or deterioration, when challenged with the various forms of mist. No particular group trends were produced either by increasing the mean particle size of humidity, or by using solutions of increasing salinity.

[Fulminant hepatitis in children. Treatment by exchange transfusion]. / Hepatitis fulminante en niños. Tratamiento con exsanguinotransfusión.

Fulminant hepatitis is a potentially fatal clinical form of viral hepatitis. The experience at the Infectious Disease Hospital of the I.M.S.S. in Mexico City is presented. Twenty-two children with encephalopathy, grade III or IV managed with exchange transfusion were included. Results between these patients and a similar control group treated conservatively were compared. The mortality rates for the exchange transfusion and the control group were 91 and 100% respectively. A review of the literature revaled great differences in results obtained by several other authors. We conclude that well controled, prospective studies should be done, before the true efficiency of exchange transfusion can be properly evaluated.

Listeria cell wall fraction: a B cell mitogen.

A crude cell wall-rich fraction of Listeria monocytogenes contains a substance or substances which cause blast transformation and thymidine incorporation by mouse spleen cells. The substance, Listeria cell wall fraction (LCWF), is a B cell mitogen in the mouse. It is not endotoxin, in that it stimulates B cells in C3H/HeJ mice. It is weakly mitogenic for rat spleen cells and not at all mitogenic for human peripheral blood or tonsil lymphocytes. Thus, it is dissimilar to both endotoxin and purified protein derivative (PPD) in its spectrum of activity. A cell wall-associated mitogen may play an early role in Listeria resistance.

Serum angiotensin-converting enzyme activity in normal children and in those with sarcoidosis.

Serum angiotensin-converting enzyme was measured in 185 children of different ages, in 32 normal adults, in 21 children with sarcoidosis, and in 36 children with other diseases. Children had higher serum ACE volumes than did adults; an intermediate level was absorbed in adolescents. Serum ACE values did not vary according to sex. Children with sarcoidosis had significantly elevated serum ACE levels that closely reflected the activity of the disease. Our results indicate that serum ACE is useful in confirming the diagnosis of sarcoidosis in childhood, and is of greater value as a sensitive indicator for following the course of the disease and the effectiveness of steroid therapy.

Rat macrophages in experimental IgA nephropathy.

To test whether the peripheral macrophage functions as early index of oxygen free radical release in association with the development of IgA nephropathy (IgAN), we studied female Lewis rats. IgAN was produced by treatment over 8 weeks with 0.1% bovine gamma globulin (BGG) in drinking water, followed by three daily intravenous injections of BGG, 1 mg/dose. Fifteen rats were divided randomly into three groups: control, IgAN, and IgAN fed vitamin E 100 IU/kg chow. At the end of the treatment period, rats were placed in individual metabolic cages for 24-h urine collections and then anesthetized with Inactin (100 mg/kg BW) for aspiration of peritoneal macrophages. The results (mean +/- SD) extended our previous data in male rats, confirming that the elevated proteinuria of IgAN (3.62 +/- 0.79 mg/day) was significantly reduced with vitamin E treatment (2.59 +/- 0.28 mg/day) in female rats (P < 0.002) More importantly, we indicated for the first time that oxygen free radicals production by peritoneal macrophages in IgAN was significantly reduced by vitamin E: 1.58 +/- 0.91 nmol/10(6) cells/15 min in the untreated group vs 3.28 +/- 0.54 nmol/10(6) cells/15 min in the vitamin E-treated group (P < 0.05).

Foreign body granulomatosis. Clinical and immunologic findings.

We studied the clinical and immunologic features of 10 patients with foreign body granulomatosis associated with injection of pentazocine. Five had typical micronodules on chest radiographs, 9 had abnormal 67Ga lung images, and 9 had elevated serum angiotensin-converting enzyme levels. Pulmonary function tests showed significant decreases in diffusing capacity in 8 subjects, but were otherwise normal. Bronchoalveolar lavage fluid had significantly (p less than 0.02) increased total cell numbers (13.8 +/- 7.5 x 10(7) and significantly lower percentages of lymphocytes (2 +/- 1) and neutrophils (2 +/- 1) (p less than 0.02) when compared with that from control subjects. Peripheral blood lymphocytes were normal when expressed as percentages of total leukocytes or as percent T-lymphocytes. Monoclonal antibody determinations of T-lymphocyte subsets (helper and suppressor) were similar to those in control subjects (p = NS). Lymphocyte transformation responses to a variety of antigens and skin test reactivity were normal. Foreign body granulomatosis contrasts with other interstitial lung diseases in its bronchoalveolar lavage cellular profile and in the absence of altered peripheral immunologic indexes.

[Meningitis caused by Salmonella]. / Meningitis por Salmonella.

The clinical and laboratory characteristics of eleven cases of bacterial meningitis due to Salmonella, are reviewed. Meningitis was more common in children under the age of 13 months. In younger children the symptoms and neurological signs were not evident. Convulsive disorders and neurological coma were the most frequent complications in 4 and 5 cases respectively. The mortality ratio was high, 36% (4 patients) and the neurological sequelae were very important: two patients presented spastic paralytic alterations and other two had hydrocephalia. The main findings in the cerebral spinal fluid were: increased leukocytes and proteins with low glucose determinations; comparing with other purulent meningitis, mononuclear cells were predominant over polymorphonuclear cells in 7 cases (64%). Salmonella was isolated in all cases; Salmonella typhi was recovered in 3 cases; one had group "C" Salmonella and 7 cases Salmonella group "B". These cases were treated with either chloramphenicol or ampicillin.