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J Lima

Publications and source records attributed to J Lima.

At least 37 records · Page 2Linked to original sources
PubMed2000

Sequential group trial to determine gastrointestinal site of absorption and systemic exposure of azathioprine.

Azathioprine (AZA) is used in the treatment of patients with refractory inflammatory bowel disease; however, its use is limited because of systemic toxicity associated with long-term use. Ileocecal delivery of AZA might be advantageous if local intestinal therapeutic effects could be provided with decreased systemic side effects. Decreased cecal systemic absorption would allow higher dosages of AZA to be administered. A two-phase study was performed to compare the systemic exposure of AZA and 6-mercaptopurine (6-MP) following administration of AZA into the stomach, jejunum, and cecum and to compare the systemic exposure to AZA and 6-MP following administration of three different dosages of AZA into the cecum. In phase I, six healthy male volunteers received three 50 mg sequential doses of AZA via an oral tube directly placed into the stomach, jejunum, and cecum, respectively. In phase II, six healthy male volunteers received three different dosages (50, 300, 600 mg of AZA) into the cecum. Plasma concentrations of AZA and 6-MP at various times were quantified and area under the plasma concentration-time curve (AUC) and mean residence time (MRT) were determined. No significant differences in the AUC of AZA were seen at the different sites. The AUC of 6-MP following administration of AZA into the jejunum (67.0 +/- 30.1 ng x hr/ml) was higher compared to the stomach (39.9 +/- 38.1 ng/hr/ml) and cecum (29.2 +/- 10.9 ng x hr/ml). Jejunal absorption was 68% higher than absorption from the stomach and 129% higher than that of the cecum. Gastric absorption was 27% higher than that of the cecum. Increased dosages given into the cecum resulted in increased AUCs of AZA and 6-MP. The AUCs of AZA following 50, 300, and 600 mg dosages were 16.9 +/- 7.4, 52.3 +/- 67.2, and 132 +/- 151 ng x hr/ml, respectively, and the AUCs of 6-MP were 22.2 +/- 14.9, 63.4 +/- 50.6, and 104 +/- 115 ng x hr/ml, respectively. Systemic exposure to 6-MP is reduced following administration of AZA into the cecum, most likely secondary to reduced absorption of 6-MP from the colon. Higher dosages of AZA presented to the cecum do result in increased systemic absorption, but may still allow more drug to be administered with less toxicity than the same dose received orally.

Adolescent↗
PubMed2000

The Charcot foot.

AIMS: To review the clinical manifestations of the Charcot foot in diabetes mellitus, with particular reference to theories concerning aetiology. METHODS: Systematic review of the published literature, searching for the keywords 'Charcot', 'foot and diabetes' and 'neuropathy' on Medline, as well as by examination of the references in recent published reviews. CONCLUSIONS: The Charcot foot of diabetes mellitus is a common problem, and yet is not widely recognized by non-specialists. The failure of professionals to identify the condition in its early phases is probably largely responsible for the gross deformity which follows continued weight-bearing. The condition is confined to those with severe peripheral neuropathy. It is thought to result from three factors: motor neuropathy leading to the development of abnormal forces within the foot, subsequent disorganization of the foot as a result of associated osteopenia and progressive destruction from continued weight-bearing, enabled by reduced pain sensation. The cause of the osteopenia is not known, but it is associated with increased bone blood flow, which may be mainly the result of loss of sympathetic innervation. The importance of increased limb blood flow in the pathogenesis of the Charcot foot has been recognized for over a century. Paradoxically, the increased flow is associated with evidence of macrovascular disease, in that the prevalence of vascular calcification of pedal vessels approaches 90%. After an interval of many months, the condition tends to evolve: the increased blood flow lessens, the osteopenia is reduced and the disorganized bones become sclerotic. This tendency for the condition to evolve remains unexplained, since it would not be expected if the condition was caused solely by progressive denervation. As a result, it is suggested that another factor may be involved in the pathogenesis of the Charcot foot: an abnormal vasomotor reflex, analogous to reflex sympathetic dystrophy, occurring against a background of severe peripheral neuropathy. The resolution of the condition occurs because it is the reflex component of the hyperaemia which proves self-limiting.

Diabetic Foot↗
PubMed1999

[Scleroderma and pregnancy: obstetrical complications and the impact of pregnancy on the course of the disease].

BACKGROUND: To describe the outcome of the pregnancy in patients with scleroderma. PATIENTS AND METHODS: Patients with scleroderma and control group were included in this retrospective study. Two groups were different in pregnant patients with scleroderma: pregnancy before scleroderma (A1) and pregnancy after scleroderma (A2). The presence of clinical problems during pregnancy and the outcome of scleroderma were collected in a questionnaire. Differences in the frequencies of complications were analyzed using the U Mann-Whitney, the chi-square or Fisher's exact test when necessary. RESULTS: The frequency of global fetal complications was increased in patients group, but there was no significantly increased frequency when variables were analyzed independently: number of births, miscarriages, fetal deaths, preterm births and low weight full term babies. There was no increased frequency of renal crisis, hypertension or eclampsia. Differences between diffuse and limited subsets were no observed. Improvement of scleroderma was seen in only 3 patients and worsening of skin thickening was experienced by 2 patients. CONCLUSIONS: The pregnant scleroderma patients are a group with high risk pregnancies and therefore well-supervised pregnancies are necessary.

Adult↗
PubMed1999

Appraisal of growth hormone (GH) secretion: evaluation of a composite pharmacokinetic model that discriminates multiple components of GH input.

Criteria for a diagnosis of GH deficiency include inadequate GH secretion as assessed by provocative testing. The changes in serum GH concentration in such tests, however, do not uniformly predict treatment responses. We questioned whether the changes in serum GH have a uniform dependence among subjects on the mass of secreted GH. We simulated spontaneous GH secretory events with bolus infusions of recombinant human GH (rhGH) in 15 somatostatin-infused adult subjects. Maximum serum GH responses, the GH areas under the curve, and GH mass calculated from deconvolution techniques are all indexes of GH secretion influenced by GH clearance and distribution volume. In this group, these indexes showed a nonuniform dependence on the known GH dose. Despite somatostatin infusion, we found evidence for low level basal GH secretion with oscillatory characteristics that may have influenced the GH concentration dependence on GH dose. We then developed and evaluated a new pharmacokinetic model to account for pulsatile, basal, and oscillatory inputs to the serum GH concentration profile. The new model is comprised of three terms. The first describes plasma GH concentrations from exogenous administration of rhGH according to a one- or a two-compartment model. The second term accounts for basal GH secretion. The third is a cosinor function that describes the oscillatory pattern of basal GH. The composite pharmacokinetic model predicted plasma GH concentrations well (r2 = 0.88-0.97); pharmacokinetic and cosinor parameters had high precision and narrow 95% confidence intervals. The pharmacokinetic parameters were stable and independent. The mean values and coefficients of variance (SD/mean) of GH pharmacokinetic parameters in our 15 subjects were: clearance, 0.236 L/min (24%); volume of distribution, 3.46 L (30%); and terminal half-life, 12.3 min (37%). The values for the cosinor parameters were: basal concentration, 0.22 ng/mL (85%); amplitude, 0.758 (50%); cycle, 121 min (27%); and time shift (acrophase), 60.3 min (53.6%). During the 9-h study, clearance decreased from 0.259 +/- 0.09 to 0.214 +/- 0.06 L/min (P < 0.03), and basal concentration increased from 0.20 +/- 0.22 to 0.33 +/- 0.33 ng/mL (P < 0.5). We conclude that our model can provide useful estimates of GH pharmacokinetics in the presence of basal, oscillating, endogenous concentrations without administering a dose of radiolabeled GH. The substantial inter- and intrasubject variance in pharmacokinetic parameters between subjects negates the assumption of a uniform relationship between GH secretion and serum GH concentration and detracts from the utility of a GH concentration cut-off point in GH testing. These findings have implications to the valid appraisal of GH deficiency states, selection of rhGH treatment candidates, and physiological regulation of the GH axis.

Adult↗
PubMed1999

Growth hormone stimulation test results as predictors of recombinant human growth hormone treatment outcomes: preliminary analysis of the national cooperative growth study database.

Growth hormone (GH) stimulation tests are considered a prerequisite to clinical trials of recombinant human GH (rhGH) therapy, but the test results may not be predictive of the treatment outcomes with rhGH. We examined the GH stimulation test results as a predictor of the treatment outcome in a cohort of prepubertal subjects in the National Cooperative Growth Study. A standard is proposed in which a diagnosis of GH deficiency is considered appropriate when a patient has significant first-year catch-up growth and that a positive stimulation test result predicts this outcome. With this construct, a traditional interpretation of GH stimulation test results correctly identifies 64% of the rhGH treatment outcomes. The analysis shows an upper limit of diagnostic sensitivity of 82% and a lower limit of specificity of 25% in our study population. The results of our recent studies suggest that the sensitivity and specificity of the current GH stimulation tests are attributable in part to broad intersubject variation in GH clearance, rates of GH elimination, and GH volume of distribution. The combined studies suggest that the use of subject-specific pharmacokinetic parameters will improve the diagnostic interpretation of GH stimulation test results and improve rhGH treatment outcomes.growth hormone stimulation tests, recombinant human growth hormone, pharmacokinetic parameters, maximal stimulated growth hormone concentration.

Child↗
PubMed1998

Antigen-specific antibody responses in lupus patients following immunization.

OBJECTIVE: To determine the safety and efficacy of 3 clinically relevant vaccines in patients with systemic lupus erythematosus (SLE). METHODS: We studied 73 consecutive SLE patients immunized with pneumococcal, tetanus toxoid (TT), and Haemophilus influenzae type B (HIB) vaccines. Patients were evaluated preimmunization and 12 weeks postimmunization for disease activity and immunization side effects. RESULTS: Eighty-four percent of the SLE patients developed a 4-fold titer increase in response to at least 1 vaccine, with 51% developing a 2-fold titer increase with all 3 vaccines. The majority of SLE patients developed protective levels of antibody to TT (90%) and HIB (88%). Although protective antibody levels could not be determined for pneumococcus, almost half of the patients (47%) developed a 4-fold antibody response. There was a trend toward a lower antibody response in patients with active disease treated with immunosuppressive therapy. Overall lupus disease activity was unaffected by immunization. CONCLUSION: Immunization is safe in SLE patients, with the overwhelming majority developing protective antibody levels. Therefore, SLE patients should receive immunizations according to the recommendations of the Centers for Disease Control and Prevention and the Immunization Practices Advisory Committee.

Adolescent↗
PubMed1997

Apatite deposition on titanium surfaces--the role of albumin adsorption.

Titanium implant surfaces are known to spontaneously nucleate apatite layers when in contact with simulated body fluids. However, adsorption of proteins may influence the process of apatite layer formation. In this study the role of bovine serum albumin (BSA) adsorption in the process of apatite deposition on titanium substrates is investigated. Deposition of calcium phosphate was induced by immersing titanium substrates in a Hank's balanced salt solution (HBSS) for times ranging from 1 to 23 days. The resulting substrates were studied by scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), X-ray photoelectron spectroscopy (XPS), wettability measurements and electrochemical impedance determinations. All these methods indicate the presence of a calcium phosphate layer. The same procedure was repeated substituting HBSS with a solution of BSA in HBSS. Although SEM, EDS and electrochemical impedance spectra do not reveal the presence of an apatite layer, XPS analysis strongly indicates that the inhibition of apatite formation by BSA is only partial. The competition between BSA adsorption and apatite deposition seems to lead to a mixed film where the protein co-exists with calcium phosphate. Wettability studies suggest that this surface film is heterogeneous and porous, similar to the thicker films formed in albumin-free HBSS.

Adsorption↗
PubMed1997

Survival prognostic factors and markers of morbidity in Spanish patients with systemic sclerosis.

OBJECTIVE: To identify survival prognostic factors and markers of morbidity among patients with systemic sclerosis (SSc). PATIENTS AND METHODS: The study included 72 patients diagnosed with SSc. According to the extent of skin involvement, three groups of patients were established: group 1, without sclerosis and with sclerosis of fingers and neck; group 2, with sclerosis of face and distal to elbows and knees; group 3, with generalised sclerosis including the trunk. All patients were included in a study protocol to determine visceral involvement. Cumulative survival after first symptom has been estimated according to the Kaplan-Meier method. The association between a hypothetical prognostic factor and cumulative survival after first symptom was assessed by log rank test. The association between a hypothetical risk factor and the prevalence of severe morbidity was assessed by the odds ratio. Multiple logistic regression models were used to identify the main predictors of severe morbidity. RESULTS: Survival was estimated to be 85% 10 years after first SSc symptom. Survival was higher among SSc patients with skin involvement distal to elbows and knees than among the rest of patients; a forced vital capacity (FVC) on spirometry lower than 70% of expected value was associated with a shorter survival, even after adjustment for diffuse SSc. Skin involvement proximal to elbows or knees was associated with a higher prevalence of severe morbidity (OR = 46.57; p < 0.001). According to a multiple logistic regression, severe morbidity was higher among patients with skin involvement proximal to knees or elbows (OR = 40.92; p < 0.001) or among patients with pulmonary hypertension detected by Doppler echocardiography (OR = 23.66 p < 0.001). CONCLUSIONS: In patients with SSc the extent of skin sclerosis was found to be a determining factor on the prognosis. According to skin sclerosis extent two main subsets of SSc patients with different survival incidence and degree of morbidity could be clearly established: limited SSc, formed by patients with no skin sclerosis or with sclerosis distal to elbows and knees and diffuse SSc, formed by patients with skin sclerosis distal and proximal to elbows and knees. Moreover, lung involvement (FVC < 70% on survival study and pulmonary hypertension on morbidity study) was an important and independent prognostic factor.

Adolescent↗
PubMed1995

The immune response and the eye. TCR alpha-chain related molecules regulate the systemic immunity to antigen presented in the eye.

Injection of antigen into the anterior chamber (AC) of the eye results in the induction of immune deviation in which antibody production is activated and delayed-type hypersensitivity (DTH) is inhibited. This system is termed anterior chamber associated immune deviation (ACAID) and the model is used to examine certain aspects of the immunologic privilege of the eye. Recent studies have established that following antigen presentation in the eye, an 'ACAID-inducing' signal is produced that directly enters the blood. This signal then homes to the spleen where T cells that down-regulate DTH are activated. For many antigens this 'ACAID signal' is a soluble protein released within 2 days of AC injection. Although the presence of this molecule (or molecules) has been described using several antigens, the exact nature of the soluble mediator has escaped characterization. We have further explored the nature of this signal using HSV-1-induced immune deviation. Our results show the soluble 'signal' was released by T cells that encounter antigen in the ocular microenvironment. This mediator was antigen specific, contained TCR alpha-chain (but not the TCR beta-chain) determinants and had an apparent molecular weight of 46 kDa. These results show that the release of soluble TCR alpha-chain from sites of T cell interaction within the microenvironment of the eye can regulate systemic immune responses. These results have implications for the control of immune response that might be damaging to organs such as the eye.

Animals↗
PubMed1994

[Isonitrile (sestamibi) as a valid alternative to thallium 201 for myocardial perfusion studies].

OBJECTIVE: SestaMIBI is a new technetium labeled radiopharmaceutical agent approved for myocardial perfusion studies. In the present work the authors analyzed the accuracy of this agent on the study of ischemic heart disease. CONCEPTION: The present paper was made considering the results of four previous studies around defined goals performed by the same research group. SETTING: Cardiology and Nuclear Medicine departments in a general hospital. RESULTS: Planar studies: global sensitivity for the diagnosis of ischemic heart disease was 100% and specificity of 67%. Tomocintigraphic studies and segmentary analysis of IHD: the accuracy for stenosis involving the left anterior descending artery was of 80%, 91% for the right coronary artery and 67.2% for left circumflex artery. Planar studies versus tomocintigraphy--SPECT (comparative study in the same population): global sensitivity of 86% for planar method and 97% for "SPECT". In patients with single vessel disease the results are also better with "SPECT" (75% vs 94%). In this series the presence of rest perfusion defects is frequent. In 75% was possible to correlate them with a significant lesion over the related coronary artery. The positive predictive value of this finding is of 92% for the lesions on the left coronary artery, 100% for left cincumflex and 59% for the right coronary artery. CONCLUSIONS: 1. The SestaMIBI is an excellent radiopharmaceutical agent for myocardial perfusion studies. 2. The accuracy of this agent for diagnosis of ischemic heart disease is quite good with a high sensitivity and specificity values. This conclusion is also valid for those patients with single vessel disease. 3. Scintigraphic studies performed with planar acquisition provide good quality images. Nevertheless tomoscintigraphy (SPECT) is more accurate namely in patients with single vessel disease. 4. In the present state of the art and regarding our results we can conclude that is too early for considering SestaMIBI like and agent for viability studies.

Coronary Disease↗
PubMed1991

[Study of the capillary microscopy changes in scleroderma and their association with organ disease, clinical manifestations and disease progression].

BACKGROUND: The changes of nailfold capillaries detected by capillary microscopy is a characteristic frequently observed in systemic sclerosis. The relationship between the different capillary microscopic changes and clinical manifestation, organic disease and disease progression were studied. METHODS: Sixty-three patients were studied in whom capillary microscopy was performed and organic disease was determined by analytical and morphological examination. The presence of association between the capillary microscopic signs and clinical manifestation and disease progression were investigated by the chi-square and Fisher tests. RESULTS: Capillary microscopic alterations were found in 95% of the patients. The extense capillary loss was associated as statistically significant to the diffuse form of scleroderma. Statistically significant associations were not found between the different capillary microscopic signs and disease progression and organic disease (global and individual per each organ). CONCLUSIONS: Although capillary microscopic changes are present in most scleroderma patients they are not useful in the evaluation of organ involvement of the disease. The presence of extense capillary loss is linked to worse prognosis in its association to the diffuse form of scleroderma.

Adolescent↗
PubMed1991

Treatment decisions in end-stage bladder cancer. Bilingual liaison rounds.

A bilingual conference was held in order to assist a Spanish-speaking patient and her physicians in planning for her care. The patient spoke only Spanish and her oncologists were primarily English-speaking. Her daughter, who was bilingual, did not attend the conference. One of the authors translated and served as interpreter and liaison between the patient and her other physicians. The patient was severely depressed and terminally ill with end-stage bladder cancer. Her depression and hopelessness complicated her care.

Carcinoma, Squamous Cell↗
PubMed1991

How can we combat excess mortality in Harlem: a one day survey of substance abuse in adult general care.

Our hypothesis was that a one-day survey of all patients hospitalized on Adult General Care would demonstrate a need for expanded addiction services in a municipal teaching hospital in East Harlem. We interviewed 276 patients in Adult General Care on February 16, 1990 to assess whether they abused drugs or alcohol or were hospitalized for reasons related to substance use. Of the 276 patients interviewed, 18 percent used alcohol alone, 14 percent used drugs alone, 17 percent used both drugs and alcohol and 2 percent were hospitalized for reasons related to substance use. One hundred forty or 51 percent of all patients were admitted because of substance use and its sequelae or as a result of violence associated with the buying or selling of drugs. The percentage was highest on one medical floor where 89 percent of the patients were substance users and on medical floors in general where the average was 60 percent. Forty patients or 14 percent were known to be HIV seropositive. Given the high mortality in Harlem, the results of our one-day survey indicate a need for expanded addiction services.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Platelet activation, endothelial cell dysfunction in the absence of anticardiolipin antibodies in systemic sclerosis.

The presence of anticardiolipin antibodies (aCL), von Willebrand factor activity and platelet function was studied in 35 patients with systemic sclerosis (SSc) scleroderma and 22 healthy controls. aCL positivity was observed in no patient with SSc or controls, whereas beta-thromboglobulin and platelet factor 4 levels were significantly higher in patients with SSc (p less than 0.001 and p less than 0.002, respectively). Furthermore, plasma from patients with SSc had a greater degree of aggregation to adenosine diphosphate 1 microM (p less than 0.05) but not to collagen or arachidonic acid. The plasma of patients with scleroderma also had increased von Willebrand factor activity compared with controls (p less than 0.001). We conclude that aCL appears not to play a central role in the pathogenesis of vascular and hemostatic alterations in SSc.

Adult↗
PubMed1991

Genetic aspects of familial multiple myeloma.

To elucidate the role of genetics in familial multiple myeloma, two sisters having plasma cell dyscrasia were studied. The women were 58 and 56 years old, and the diagnoses were made 22 months apart. Specific antisera for patient 1's lambda light chains produced in rabbits had no cross-reactivity with her sister's lambda light chains. Karyotypic analysis by G.T.G. banding revealed abnormalities in both patients, but no common abnormalities. HLA typing disclosed identical tissue types (AW24, A26, B13, BW55). An immunologic epidemiologic study performed on 26 family members, encompassing four generations, disclosed no additional cases of paraproteinemia.

Female↗