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Biomedical subjects

J S Markowitz

Publications and source records attributed to J S Markowitz.

At least 91 records · Page 5Linked to original sources
PubMed1995

Delirium associated with clozapine and benzodiazepine combinations.

Delirium has many organic causes, one of which is the combination of medications. This is sometimes difficult to differentiate in the psychotic individual. To our knowledge there are no published cases of delirium definitively established by "rechallenge" with a combination of clozapine and benzodiazepines. Lorazepam was given for agitation in two individuals on clozapine. Because of either the short half-life, or the lack of knowledge about this interaction, multiple doses were given. Clonazepam was given to a third individual. Two of the reported individuals developed a delirium associated with the administration and onset of lorazepam. These patients had received both lorazepam and clozapine singularly in the past without the adverse effects seen with the combination. Both patients were rechallenged with second doses of lorazepam, when they again developed a delirium. In one case the patient was admitted on clonazepam and then started on clozapine. A delirium developed at a clozapine dose of 150 mg/day; she was not rechallenged. In all three cases the patients' sensorium cleared when benzodiazepines were discontinued. The combination of benzodiazepines and clozapine should be avoided if possible, and if they are used in combination, it should be with great caution.

Adult↗
PubMed1994

Activation of T cells by superantigen in class II-negative mice.

The ability of the staphylococcal enterotoxins to stimulate T cells has been thought to depend on their association with class II MHC products. Here, we demonstrate that a subgroup of staphylococcal enterotoxins, which includes staphylococcal enterotoxin C and staphylococcal enterotoxin E, stimulates strong MHC-independent responses, thereby resulting in T cell expansion and generation of CTL. The immunologic consequences of MHC-independent activation of T cells by superantigens differ from those of class II-dependent activation, inasmuch as this pathway does not result in detectable T cell deletion. These findings delineate a novel MHC-independent T cell activation pathway that leads to both clonal expansion and expression of CTL effector function in response to a subgroup of bacterial superantigens.

Animals↗
PubMed1994

Failure of symptomatic relief after pancreaticojejunal decompression for chronic pancreatitis. Strategies for salvage.

OBJECTIVE: To evaluate causes of intractable recurrent pain following pancreaticojejunostomy for chronic pancreatitis and to evaluate treatment strategies aimed at lasting pain relief. DESIGN: Case series. SETTING: Tertiary care referral center. PATIENTS: Fifteen selected patients having severe pain associated with chronic pancreatitis with onset 0 to 60 months (median, 5 months) following pancreaticojejunostomy. Each patient underwent computed tomography and endoscopic retrograde cholangiopancreatography. Two patients (13%) were found to have pancreatic cancer, two (13%) had inadequate pancreatic duct decompression, two (13%) had biliary stenosis, and 10 (67%) had presumed neuropathy in the pancreatic head. INTERVENTIONS: Fourteen (93%) of the 15 patients underwent the following reoperations: distal pancreatectomy and splenectomy (one patient), extension of the pancreaticojejunostomy and choledochojejunostomy (one patient), biliary stenting followed by choledochojejunostomy (one patient), and Whipple-type resection of the pancreatic head (14 patients). Two patients subsequently underwent a completion pancreatectomy. MAIN OUTCOME MEASURES: Pain relief, functional capacity, and pancreatic exocrine and endocrine status were determined. The median follow-up after reoperation was 39 months. RESULTS: Of the 14 patients who underwent reoperation, 13 were long-term survivors. One died of pancreatic cancer. Ten of the other 13 have had satisfactory-to-excellent relief of pain, with resumption of a normal level of function. Of the 10 previously euglycemic patients who underwent pancreatic head resection, eight remain free of diabetes mellitus to date. CONCLUSIONS: The causes of recurrent or persistent pain following pancreaticojejunal decompression for chronic pancreatitis are complex and include neuropathic changes, residual or evolving pancreatic and biliary duct obstruction, and unrecognized pancreatic cancer. Acceptable outcomes can usually be achieved by following a treatment strategy aimed at addressing identified residual disease while maximally preserving pancreatic tissue.

Adult↗
PubMed1994

A multinational study of the effects of low-dose pravastatin in patients with non-insulin-dependent diabetes mellitus and hypercholesterolemia. Pravastatin Multinational Study Group for Diabetes.

This multinational, 16-week, randomized, double-blind, placebo-controlled study evaluated the efficacy and safety of low-dose pravastatin in 325 patients with non-insulin-dependent diabetes mellitus (NIDDM) and hypercholesterolemia [serum total cholesterol concentrations of 5.2-7.8 mmol/l (200 to 300 mg/dl)]. Patients were randomized to receive pravastatin 10 mg or matching placebo with doubling of the dose after 8 weeks if predefined target levels for total cholesterol [(i.e., < 5.2 mmol/l (200 mg/dl) or > 15% decrease from baseline] had not been achieved. At Week 16, pravastatin-treated patients showed a 21.4% decrease in serum low-density lipoprotein cholesterol (LDL-C) and a 13.5% reduction in serum total cholesterol (TC) concentrations (p < 0.001 compared with placebo). Levels of triglycerides (TG) were reduced 9.6% during pravastatin treatment (p < 0.05 compared with placebo) while high-density lipoprotein cholesterol (HDL-C) levels were increased 4.4% (p = NS). Adverse events and laboratory test abnormalities were similar among patients treated with pravastatin or placebo. Glycosylated hemoglobin (HbA1C) levels remained unchanged. The results of this study demonstrate that low-dose pravastatin is effective and well tolerated for lowering elevated cholesterol concentrations during short-term treatment of patients with NIDDM and hypercholesterolemia.

Adult↗
PubMed1993

Most gamma delta T cells develop normally in the absence of MHC class II molecules.

MHC class I and class II molecules are essential for intrathymic maturation of a normal repertoire of alpha beta T cells. The development of gamma delta T cells may similarly require exposure to conventional MHC or MHC-like molecules for appropriate negative and positive selection. The availability of mice that are devoid of cell surface expression of MHC class II molecules allowed us to test directly the hypothesis that conventional class II molecules play a role in the development of gamma delta T cells. The proportions of gamma delta cells in thymus, lymph nodes, and spleens were indistinguishable between class II-deficient mice and littermate controls by FACS analysis. gamma delta T cells from class II-deficient mice proliferated normally in response to anti-TCR mAb. Examination of epidermal sheets from ear, torso, and tail skin demonstrated that class II-deficient mice had the same population density and distribution of gamma delta+ dendritic epidermal T cells as that of control littermates. gamma delta Cells in the epidermis of class II-deficient mice expressed Thy-1 and CD3 and were predominantly V gamma 3+. There were no significant differences in the immunophenotype of class II-deficient mice and their normal littermates in two-color immunofluorescence analysis of intestinal intraepithelial lymphocytes. Class II-deficient mice and control mice had 29 to 39% gamma delta bearing intestinal intraepithelial lymphocytes, of which 16 to 21% expressed V delta 4. Dendritic cells that stained positively for Thy-1, CD3, and gamma delta were identified in the vaginal epithelium of class II-deficient mice and their normal littermates. Our results indicate that MHC class II expression is not essential for the development of most gamma delta T cells.

Animals↗
PubMed1993

The role of "indirect" recognition in initiating rejection of skin grafts from major histocompatibility complex class II-deficient mice.

In vitro studies have revealed several pathways by which T cells can respond to alloantigens, including CD4+ direct responses to allogeneic class II antigens, CD8+ direct responses to allogeneic class I antigens, and CD4+ "indirect" responses to peptides of alloantigens presented in association with responder class II molecules. In vivo studies of skin graft rejection, however, have so far provided clear evidence for the contribution of only the two direct pathways and not for indirect recognition. We have used major histocompatibility complex class II-deficient mice as donors to test the role of indirect recognition in rejection of skin grafts. Class II-deficient skin was always rejected without delay by normal recipients. Removal of recipient CD8+ cells (to leave the animals dependent on CD4+ function) or depletion of recipient CD4+ cells revealed that CD4+ cells were usually involved and sometimes absolutely required in this rapid rejection. Since the donor grafts lacked class II antigens, the CD4+ cells must have recognized donor antigens presented in association with recipient class II molecules. These results therefore indicate that indirect recognition can initiate rapid skin graft rejection.

Animals↗
PubMed1993

Class II-positive hematopoietic cells cannot mediate positive selection of CD4+ T lymphocytes in class II-deficient mice.

Generation of immunocompetent alpha/beta T-cell receptor-positive T cells from CD4+CD8+ thymocytes depends upon their interaction with thymic major histocompatibility complex (MHC) molecules. This process of positive selection provides mature T cells that can recognize antigens in the context of self-MHC proteins. Previous studies investigating haplotype restriction in thymic and bone-marrow chimeras concluded that radioresistant thymic cortical epithelium directs the positive selection of thymocytes. There is controversy, however, as to whether intra- or extrathymic radiosensitive bone marrow-derived macrophage and dendritic cells also can mediate positive selection. To determine whether CD4+ T cells can be positively selected by hematopoietic cells, we generated chimeric animals expressing MHC class II molecules on either bone marrow-derived or thymic stromal cells by using a recently produced strain of MHC class II-deficient mice. CD4+ T cells developed only when class II MHC molecules were expressed on radioresistant thymic cells. In contrast to what recently has been observed for the selection of CD8+ T lymphocytes, MHC class II-positive bone marrow-derived cells were unable to mediate the selection of CD4+ T cells when the thymic epithelium lacked MHC class II expression. These data suggest that CD4+ and CD8+ T cells may be generated by overlapping, but not identical, mechanisms.

Animals↗
PubMed1993

B lymphocyte development and activation independent of MHC class II expression.

A murine model of MHC class II deficiency created by targeted gene disruption was used to investigate whether class II expression influences B cell maturation and function. There appeared to be fewer total B cell precursors, a higher proportion of which were in a very early stage of maturation, in class II-deficient vs control bone marrow; however, the differences did not reach statistical significance. Mature B cells were unaffected; IgM, IgD, B220, and CD5 surface expression were similar in class II-deficient and control animals. Serum Ig determinations revealed that the class II-deficient animals had elevated IgM but decreased IgG1 (and, variably, IgE) compared to control. The antibody response against thymic-independent Ag was intact in class II-animals, as was the in vitro response of small resting B cells from class II deficient animals to stimulation with polyclonal B cell activators. Preactivated T cells were able to induce differentiation and proliferation of class II-deficient, small resting B cells. Together, these data indicate that B cell development, T cell-independent, and T cell-dependent B-cell activation, can occur independently of class II MHC expression.

Animals↗
PubMed1993

Determinants for hospitalization from an emergency mental health service.

There has been limited systematic study of determinants of acute psychiatric hospitalization of children and adolescents. This study reviewed the records of children and adolescents who received emergency mental health services in one New Jersey county during 6 months of 1990 (N = 226). Using a structured form to abstract data, information was obtained on demographics, precipitating problems, past mental health services, substance use, family problems, and disposition. While suicidal behavior was not a predictor of acute hospitalization, the interaction of assaultive and suicidal behavior was predictive. Other contributory factors identified in the multivariate analysis included: child's substance use, family member's substance use, and initial emergency screening site. Recognition of present utilization patterns will facilitate the development of intensive community-based options for those with acute mental health problems.

Adolescent↗
PubMed1993

Immunoregulatory effects of superantigens: interactions of staphylococcal enterotoxins with host MHC and non-MHC products.

Staphylococcus aureus carries a highly conserved set of genes which encode a set of secreted enterotoxins. Although it is likely that these enterotoxins affect the host/parasite in favor of the bacterium, we do not understand the molecular basis of this interaction. We summarize recent evidence that defines two types of interaction between the bacterial toxin and host cellular receptors that may subvert the host immune response to S. aureus. An interaction between the toxin and class II products on APC can result in inhibition of costimulatory activity and thus impair clonal expansion of T cells specific for bacterial antigens. Studies using anti-class II antibodies suggest that this may reflect transmission of a negative signal to APC after ligation of class II products. A second interaction between a subset of toxins, including SEC, with non-MHC products stimulates both T-cell proliferation as well as toxin-specific cytotoxic T cells (CTL). We put forward the hypothesis that this interaction reflects binding of a VCAM-1-like subsequence of SEC to VLA-4 expressed by activated target cells. We suggest that this interaction may serve to inhibit the host response by subversion of lymphocyte homing to sites of infection by SEC-producing staphylococci and by local elimination of (VLA-4+) memory T cells.

Amino Acid Sequence↗
PubMed1992

General versus systematic inquiry about emergent clinical events with SAFTEE: implications for clinical research.

This study compares two methods for elicitation of treatment-emergent side effects. One is the open-ended general inquiry and the other is a specific inquiry that asks about a wide range of events thought to be treatment-related. The study goal was to determine the extent to which the specific inquiry method elicits clinically useful information over and above that elicited by the general inquiry method. The assessment instrument we used is SAFTEE, a structured interview schedule developed by the National Institute of Mental Health. We looked for differences between general and specific inquiry formats in terms of number of events elicited, type of event, severity, functional impairment, and clinician action taken. We found that both methods contributed to elicitation of events that, in the clinician's opinion, required some change in management. However, events reported on the General Inquiry form were significantly more distressing, more often interfered with daily functioning, and elicited more extensive changes in clinical management. No medically serious events were elicited on the specific inquiry form alone. Based on these findings, and in view of the amount of time and effort required to administer and score it, we do not recommend the specific inquiry form of SAFTEE as a standard assessment tool for routine use in all clinical trials. We do consider it to be a useful method for comprehensive elicitation about treatment-emergent effects in targeted and specific research contexts. We see the schedule as a comprehensive document or library of queries to be tailored to the needs of individual protocols.

Adolescent↗
PubMed1991

Prognosis after initial recurrence of cutaneous melanoma.

We reviewed 231 patients who developed recurrent disease 1 to 218 months after surgical therapy for clinical stage I cutaneous melanoma. Metastatic lesions amenable to surgery, including visceral recurrences, were resected. Adjuvant systemic chemotherapy/immunotherapy or regional hyperthermic perfusion was added in patients with unresected disease. Local irradiation was employed for nonresectable brain or other isolated symptomatic metastases. The overall 5-year survival rate after initial recurrence was 36%. In patients with soft tissue or nodal recurrence, the 5-year survival rates were 49% and 38%, respectively; six (11%) of 53 patients whose initial recurrence was in a visceral organ achieved prolonged remission. Primary lesion anatomic site, thickness, pathologic type, and interval from initial therapy to recurrence were unrelated to survival. Significant prognostic factors included the site of initial metastasis, stage of primary disease, and the successful complete eradication of gross disease by surgical excision or intensive chemotherapy.

Adult↗
PubMed1990

Panic disorder and cardiovascular/cerebrovascular problems: results from a community survey.

Follow-up studies of psychiatric patients with panic disorder have shown an abnormally high mortality rate in men due to cardiovascular and cerebrovascular events. The authors report that in the New Haven portion of the Epidemiologic Catchment Area program the risk for stroke in persons with lifetime diagnoses of panic disorder was over twice that in persons with other psychiatric disorders or no psychiatric disorder. After adjustments for demographic differences between groups, the risk was even higher. While the results should be interpreted cautiously because of the small sample and absence of medical examinations, these findings are consistent with clinical studies showing an association between panic disorder and cardiovascular/cerebrovascular events.

Adolescent↗
PubMed1989

Suicidal ideation and suicide attempts in panic disorder and attacks.

Panic disorder, which is found in about 1.5 percent of the population at some time in their lives, includes recurrent episodes of sudden, unpredictable, intense fear accompanied by symptoms such as palpitations, chest pain, and faintness. Panic attacks, which do not meet these diagnostic criteria fully, are two to three times more prevalent. Since panic symptoms can mimic those of other medical disorders, patients with these symptoms use medical services frequently. To determine the risk of suicidal ideation and suicide attempts in panic disorder and attacks, we studied a random sample of 18,011 adults drawn from five U.S. communities. Subjects who had panic disorder, as compared with other psychiatric disorders, had more suicidal ideation and suicide attempts, with an adjusted odds ratio for suicide attempts of 2.62 (95 percent confidence interval, 1.83 to 3.74). The odds ratio was 17.99 (95 percent confidence interval, 12.18 to 26.58) when the group with panic disorder was compared with subjects who had no psychiatric disorder. Twenty percent of the subjects with panic disorder and 12 percent of those with panic attacks had made suicide attempts. These results could not be explained by the coexistence of major depression or of alcohol or drug abuse. We conclude that panic disorder and attacks are associated with an increased risk of suicidal ideation and suicide attempts. Physicians working in general medical settings and emergency departments should be alert to this problem.

Adolescent↗