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Biomedical subjects

N Schneider

Publications and source records attributed to N Schneider.

At least 19 recordsLinked to original sources

Implementing a tuberculosis control program.

Between January 1989 and December 1990, 26 patients acquired multidrug-resistant tuberculosis at our institution. Their exposures occurred when they were admitted to a ward where a patient with acid fast bacillus smear-positive pulmonary tuberculosis was also admitted. In 20 cases, the infectious patients were not isolated until the sputum smears were positive. When the outbreak was recognized in the spring of 1990, the infection control department undertook a risk assessment and instituted measures that would become the tuberculosis control program. Since then, administrative and environmental controls have been implemented, education programs are ongoing, personal protective equipment is in use, and a more aggressive employee health testing program is underway. The steps we took and the barriers we had to overcome to implement our plan are included in this article.

Acquired Immunodeficiency Syndrome

Evaluation of infection control measures in preventing the nosocomial transmission of multidrug-resistant Mycobacterium tuberculosis in a New York City hospital.

OBJECTIVE: To evaluate the efficacy of Centers for Disease Control and Prevention (CDC)-recommended infection control measures implemented in response to an outbreak of multidrug-resistant (MDR) tuberculosis (TB). DESIGN: Retrospective cohort studies of acquired immunodeficiency syndrome (AIDS) patients and healthcare workers. The study period (January 1989 through September 1992) was divided into period I, before changes in infection control; period II, after aggressive use of administrative controls (eg, rapid placement of TB patients or suspected TB patients in single-patient rooms); and period III, while engineering changes were made (eg, improving ventilation in TB isolation rooms). SETTING: A New York City hospital that was the site of one of the first reported outbreaks of MDR-TB among AIDS patients in the United States. PARTICIPANTS: All AIDS patients admitted during periods I and II. Healthcare workers on nine inpatient units with TB patients and six without TB patients. RESULTS: The epidemic (38 patients) waned during period II and only one MDR-TB patient presented during period III. The MDR-TB attack rate among AIDS patients hospitalized on the same ward on the same days as an infectious MDR-TB patient was 8.8% (19 of 216) during period I, decreasing to 2.6% (5 of 193; P = 0.01) during period II. In a small group of healthcare workers with tuberculin skin test data, conversions during periods II through III were higher on wards with than without TB patients (5 of 29 versus 0 of 15; P = 0.15), although the difference was not statistically significant. CONCLUSIONS: Transmission of MDR-TB among AIDS patients decreased markedly after enforcement of readily implementable administrative measures, ending the outbreak. However, tuberculin skin-test conversions among healthcare workers may not have been prevented by these measures. CDC guidelines for prevention of nosocomial transmission of TB should be implemented fully at all US hospitals.

AIDS-Related Opportunistic Infections

Clinical and epidemiologic characteristics of Mycobacterium haemophilum, an emerging pathogen in immunocompromised patients.

OBJECTIVE: To describe 13 infections caused by Mycobacterium haemophilum. DESIGN: Identification of patients by microbiologic record review, followed by medical record review and a case-control study. SETTING: Seven metropolitan hospitals in New York. PATIENTS: All patients with M. haemophilum infections diagnosed between January 1989 and September 1991 and followed through September 1992. Surviving patients were enrolled in the case-control study. RESULTS: Infection with M. haemophilum causes disseminated cutaneous lesions, bacteremia, and diseases of the bones, joints, lymphatics, and the lungs. Improper culture techniques may delay laboratory diagnosis, and isolates may be identified incorrectly as other mycobacterial species. Persons with profound deficits in cell-mediated immunity have an increased risk for infection. These include persons with human immunodeficiency virus infection or lymphoma and those receiving medication to treat immunosuppression after organ transplant. Various antimycobacterial regimens have been used with apparent success to treat M. haemophilum infection. However, standards for defining antimicrobial susceptibility to the organism do not exist. CONCLUSIONS: Clinicians should consider this pathogen when evaluating an immunocompromised patient with cutaneous ulcerating lesions, joint effusions, or osteomyelitis. Microbiologists must be familiar with the fastidious growth requirements of this organism and screen appropriate specimens for mycobacteria using an acid-fast stain. If acid-fast bacilli are seen, M. haemophilum should be considered as the infecting organism as well as other mycobacteria, and appropriate media and incubation conditions should be used.

AIDS-Related Opportunistic Infections

Prompt diagnosis of 'acute groin' conditions in infants.

Urgent sonographic examination of the groin was performed in 58 patients under the age of two years. Accurate diagnosis was done in conditions such as: incarcerated inguinal hernia, twisted undescended testis, incarcerated ovary in inguinal hernia and others. Ultrasonography facilitated decision-making and differentiation between surgical and non-surgical conditions.

Abdomen, Acute

The t(1;22) (p13;q13) is nonrandom and restricted to infants with acute megakaryoblastic leukemia: a Pediatric Oncology Group Study.

We report the nonrandom occurrence and frequency of the t(1;22)(p13;q13) in acute myeloid leukemia (AML) and its close association with the French-American-British M7 subtype of AML in infants (less than 1 year). This chromosomal abnormality occurred in 6 of 252 (2.4%) children and adolescents with AML (6 of 28 infants, 22%; 6 of 18 M7 AML cases overall, 33%; and 6 of 6 M7 cases in infants). Infants with AML of M7 subtype and the t(1;22) often presented with prominent abdominal masses. Two of these infants were not treated and died early. Three of four treated infants entered complete remission with therapy for AML; the remaining infant died of hemorrhage on day 8. Of the three infants who entered remission, only one remains alive and disease free at 5+ months. The other two infants relapsed in the bone marrow at 5 and 2 months from the start of therapy, respectively. We conclude that M7 AML with the t(1;22) usually presents in infants with extensive infiltration of abdominal organs by leukemic cells and may confer a poor prognosis despite intensive AML-directed treatment. Identification of this nonrandom translocation exclusively in infants with acute megakaryoblastic leukemia (AMkL) implies that it may serve as an additional diagnostic marker for this disease and links it to the pathogenesis of AMkL in infants.

Antigens, CD

The tal gene undergoes chromosome translocation in T cell leukemia and potentially encodes a helix-loop-helix protein.

We have analyzed t(1;14)(p32;q11) chromosome translocations from two patients with T cell acute lymphocytic leukemia. The chromosome 1 breakpoints of these patients lie within a kilobasepair of each other, and thus define a genetic locus (designated tal) involved in T cell oncogenesis. Moreover, we have identified sequences within tal that potentially encode an amphipathic helix-loop-helix motif, a DNA-binding domain found in a variety of proteins that control cell growth and differentiation. The homology domain of tal is especially related to that of lyl-1, a gene on chromosome 19 that has also been implicated in T cell oncogenesis. Hence, tal and lyl-1 encode a distinct family of helix-loop-helix proteins involved in the malignant development of lymphocytes.

Amino Acid Sequence

[Air transportation of patients: a danger of hypoxic organ lesions?].

As illustrated by two cases, a fall in alveolar oxygen pressure at high altitude, such as during transportation by plane, can cause hypoxic pulmonary failure, especially in patients with already impaired pulmonary or circulatory functions. Arterial oxygen saturation was recorded by pulse oximetry in 14 healthy volunteers and eight patients during air transportation. Oxygen saturation decreased with reduced cabin pressure. Decreased saturation for each 100 mm Hg reduction in cabin pressure was markedly greater in the patients than the healthy volunteers. Pulmonary and circulatory status should be assessed before air transport of patients and if necessary departure delayed. Oxygen ought to be added to inspired air with appropriate supervision in all acutely ill patients. Indications for endotracheal intubation before flight should be generously defined. Continuous pulse oximetry is noninvasive and highly informative. It is urgently recommended that air ambulances be equipped with them.

Adult

The chromosome translocation (11;14)(p13;q11) associated with T-cell acute lymphocytic leukemia: an 11p13 breakpoint cluster region.

The translocation (11;14)(p13;q11) was observed in karyotypes of leukemic cells from a 3-year-old boy with T-cell acute lymphocytic leukemia (T-ALL). Since this translocation is a recurrent marker of T-ALL, we undertook to investigate its mode of formation and role in leukemogenesis. The cytogenetic breakpoint on chromosome 14 occurs in 14q11, the same band wherein lies the T-cell receptor alpha/delta chain gene; and Southern hybridization analysis of peripheral blood and bone marrow DNA uncovered a tumor-specific rearrangement in the D delta-J delta region of this locus. DNA encompassing the rearrangement was isolated by molecular cloning, and further analysis revealed it to be the t(11;14)(p13;q11) junction. Nucleotide sequence determination of the junction indicates that the 14q11 breakpoint occurs immediately adjacent to the D delta 2 gene segment. Hence, the translocation arose as an aberrant rearrangement between the downstream recombination signal of D delta 2 and a pseudo recombination signal adjacent to the chromosome 11 breakpoint. Finally, comparison of the breakpoint in band 11p13 with those of other translocations (11;14)(p13;q11) identified a breakpoint cluster region of approximately 1.2 kilobase-pairs (kb), alterations of which may promote the development of T-ALL.

Base Sequence

Hospitalized schizophrenic patient views about seclusion.

Twenty-six of 100 consecutively admitted schizophrenic or schizoaffective patients required seclusion during their hospital stays. Seclusion episodes usually involved involuntarily committed, severely ill patients and occurred early in their hospitalizations. The recollections of the personal seclusion experiences of 17 patients were generally factually accurate, except for a tendency to play down disruptive aggressive behavior on their part. Patients described seclusion as a painful experience associated with feelings of helplessness, fear, sadness, and anger. However, patients also stated that seclusion rooms were necessary on inpatient psychiatric units and that the rooms were used for the control of disruptive aggressive patient behaviors. This study highlights not only the need for staff to clarify for patients what behavior has led to seclusion and what behavior will lead to release, but also the need for staff to acknowledge patients' distress at the experience.

Adult

Drop in heart rate following smoking cessation may be permanent.

Data are reported on the heart rates of nine smokers who underwent 5 weeks of abstinence. There was an initial fall of 9.1 beats per min from 79 to 69.9 beats per min on the 1st day, with no significant change thereafter. The average heart rates after 2, 3, 4 and 5 weeks were 69.1, 69.1, 71.7 and 69.9 beats per min, respectively. Heart rate after 5 weeks was still significantly below baseline. The results indicate that the drop in heart rate which occurs open smoking abstinence is either a permanent change, or if it is a temporary withdrawal effect lasts longer than 5 weeks. If it is a permanent change then it may not make sense to consider drop in heart rate as part of a withdrawal syndrome; it could merely reflect absence of nicotine's stimulant action.

Adult

Thyrotropic activity of acidic isoelectric variants of human chorionic gonadotropin from trophoblastic tumors.

Previous studies have indicated that hCG has a weak intrinsic thyroid-stimulating activity. Differences in the molecular composition and biological activity of hCG in patients with trophoblastic diseases and pregnant women occur, but are not well defined. Therefore, we have studied the effect of serum samples and purified hCG preparations from patients with trophoblastic diseases on T3 release from human and porcine thyroid slices in vitro. We examined 30 serum samples from 13 patients with nonseminomatous testicular germ cell tumors, 3 from women with choriocarcinoma, and 5 from patients with hydatidiform moles. In all but 1 serum sample from the tumor patients, but in none of 11 serum samples of pregnant women, T3-releasing activity was found. Two patients with testicular cancer and 1 patient with molar pregnancy experienced episodes of frank hyperthyroidism. Isoelectric focusing on polyacrylamide gels of tumor sera (n = 15) revealed substantial amounts of acidic isoelectric variants, pI 3.3-3.9, which were only barely detectable in pregnancy sera. The percentage of acidic hCG variants with pI 3.3-4.0 to total hCG with pI 3.3-5.2, as determined by hCG (+hCG beta) RIA of the eluted fractions of polyacrylamide gel isoelectric focussing, varied from 12-45% in sera of tumor patients and from 0-4% in pregnant sera. We purified the acidic variants of hCG with pI 3.6-3.8 (hCGav) from the urine of our patients. The beta-subunit of purified hCGav had a slightly higher mol wt (35,750) than that of hCG CR 119 (34,190) on polyacrylamide gel electrophoresis. The hCGav showed a dose-dependant stimulation of T3 release and cAMP generation from human thyroid slices, whereas the other hCG fractions on isoelectric focussing had no thyrotropic effect in similar dose levels. The TSH-like activity of hCGav could be roughly estimated as 10 mIU TSH/IU hCGav. Anti-hCG (+hCG beta) antiserum, but not anti-hTSH antiserum, neutralized the biological activity of hCGav. These findings strongly suggest that acidic hCG variants act as functional stimulators of the human thyroid in vitro. Since these molecular variants of hCG can exist in patients with trophoblastic diseases in significant amounts, they could be responsible for some cases of hyperthyroidism in trophoblastic diseases.

Adult

Activity of amikacin against Mycobacteria in vitro and in murine tuberculosis.

Amikacin was found to be a potent inhibitor of clinical isolates of Mycobacterium tuberculosis in vitro. The drug was also active against some, but not all, strains of M. intracellulare, M. kansasii and rapidly growing mycobacteria in concentrations that may be attained clinically. Activity was independent of susceptibility or resistance of the isolates to commonly used antituberculosis agents. Groups of mice were infected intravenously with M. tuberculosis H37Rv and then treated daily with amikacin, streptomycin, isoniazid or kanamycin. One third of the mice in each group were killed 30, 60 and 90 days after infection. Extent of pulmonary disease was recorded and tubercle bacilli were enumerated in lungs. Isoniazid eradicated tubercle bacilli from the lungs within 90 days. The remaining drugs were suppressive. Amikacin was more efficacious than streptomycin or kanamycin given in equivalent or greater dosages. Because of its potent activity in vitro, efficacy in experimental tuberculosis and activity against drug resistant mycobacteria, amikacin merits further study as a potential therapeutic agent for tuberculosis and other mycobacterial infections.

Amikacin

Tissue deposition and metabolism of 125I-labeled synthetic amino-terminal parathyroid hormone bPTH(1-34).

The tissue deposition and metabolism of 125I-labeled synthetic amino-terminal parathyroid hormone, bPTH(1-34), were studied in rats. In comparison with the intact hormone molecule bPTH(1-84), the synthetic fragment was (a) cleared more rapidly from serum; (b) degraded more rapidly in peripheral tissues; (c) deposited to a greater extent in kidney; (d) deposited to a much smaller extent in liver. In bone, the accumulation of total radioactivity was approximately the same with both labeled hormones. The possible physiological significance of these patterns of distribution and metabolism is discussed.

Animals

The parathyroid hormone-sensitive adenylate cyclase system in plasma membranes of rat liver.

Purified plasma membranes were prepared from normal rat livers. These membranes were unable to degrade parathyroid hormone (PTH), bovine PTH-(1-84) [bPTH-(1-84)], or bPTH-(1-34). The entire molecule bPTH-(1-84) caused a marked activation of adenylate cyclase (cAMP production increased over 5-fold), with half-maximal stimulation at 6.9 X 10(-8) M. The amino-terminal fragment bPTH-(1-34) was equipotent but gave a smaller maximal cAMP production. The human (h) amino acid sequence, hPTH-(1-34) was only weakly effective at a concentration of 10(-5) M. A similar species specificity was shown with crude rat renal cortical membranes. Of a variety of ligands, only glucagon and 10(-3) M F- were cyclase activators in these liver plasma membranes. Binding of [125I]iodo-bPTH by these membranes was fairly extensive but showed a saturation of binding only at high hormone concentrations (> 10(-6) M). Clearly, cleavage of the intact molecule PTH-(1-84) is not required for activation of the adenylate cyclase system of liver membranes. It appears that two rat tissues, liver and kidney, exhibit some species specificity in cyclase activation, i.e. the hPTH-(1-34) (Niall sequence) is inactive.

Adenylyl Cyclases