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Biomedical subjects

C Siegel

Publications and source records attributed to C Siegel.

At least 19 recordsLinked to original sources

Synthesis and pharmacological evaluation of ether and related analogues of delta 8-, delta 9-, and delta 9,11-tetrahydrocannabinol.

The primary goal of this research was to synthesize a series of ether analogues of the cannabinoid drug class and to evaluate their agonist and antagonist pharmacological properties in either the mouse or the rat. Agonist and antagonist activity was evaluated in mice using a multiple-evaluation procedure (locomotor activity, tail-flick latency, hypothermia, ring immobility) and activity in rats determined in a discriminative stimulus paradigm. Additionally, novel analogues were evaluated for their ability to bind to the THC receptor site labeled by 3H-CP-55,940. None of the cannabinoid analogues were capable of attenuating the effects of delta 9-THC (3 mg/kg) in either the rat (doses up to 10 mg/kg) or in the mouse (doses up to 30 mg/kg). It also appears that the compounds with minimal in vivo activity are not mixed agonist/antagonists. These data would suggest that the phenolic hydroxyl is important for receptor recognition (binding) and in vivo potency. Additionally, cannabinoid methyl ethers previously considered inactive have been found to produce limited activity. Lastly, data suggest that delta 9,11-THC is more potent than previous reports indicated, and does possess pharmacological activity.

Animals

A survey of hospitals in New York State treating psychiatric patients with chemical abuse disorders.

Eighty-eight of 143 hospitals in New York State providing psychiatric inpatient treatment responded to a mailed questionnaire designed to determine the size of three subgroups of chemical abusers--alcohol abusers, drug abusers, and polychemical abusers--among inpatients with psychiatric diagnoses, as well as the availability of services for these patients. Data for New York City and its metropolitan area were analyzed separately. In 1987 almost one-third of psychiatric admissions both in and outside the metropolitan area had comorbid chemical abuse disorders. Seventy-five percent of patients in the metropolitan area with comorbid chemical abuse had a drug abuse disorder; in rural areas 88 percent of patients with chemical abuse disorders abused alcohol. Both hospital- and community-based aftercare services, especially in the metropolitan area, were less available to psychiatric patients with chemical abuse than to patients without these disorders.

Aftercare

[Automated measurement of retinal vascular diameter].

We describe a new unit of the Jena retinal camera for automatic measurement of retinal vessel diameter. The brightness profile perpendicular to the vessel is registered by CCD line sensor and the signal is transmitted to the computer. An adaptive computer program recognizes the edges of vessels and estimates the vessel diameters automatically. Applying several measurements per vessel, the intraindividual standard deviation may be smaller than 3%. By using the same objective measuring edge criterion, the measuring results are comparable between different observers and methods. Error sources are discussed. Measured vessel reactions to oxygen breathing and reduced perfusion pressure are presented to demonstrate the efficiency of this new method.

Adult

Isolation of measles virus in primary rhesus monkey cells from a child with acute interstitial pneumonia who cytologically had giant-cell pneumonia without a rash.

The isolation of measles virus in primary Rhesus monkey kidney cells (PRMK) in patients with documented giant-cell pneumonia who have presented without a rash is limited. The diagnosis usually is made by cytologic examination of nasal or bronchial secretions in which characteristic multinucleated giant cells with intranuclear and intracytoplasmic inclusion bodies are observed. The diagnosis of giant-cell pneumonia has been associated with measles virus but not exclusively. Canine distemper, herpes group viruses, and parainfluenza infections have been associated with these cells. In addition, vitamin A deficiency also has been cytologically associated with multinucleated giant cells. The authors describe the isolation of measles virus from bronchial washing and sputum in PRMK cells at 4 days from an 11-year-old child with acute interstitial pneumonia who was in remission for acute lymphocytic leukemia. Classic cytopathologic effect (CPE) consisting of syncytial and hole formation on the PRMK monolayer was apparent. In addition, a foamy appearance of the monolayer was noted in an otherwise clean lot of monkey cells. Confirmatory testing with measles antibody of the infected areas of the monolayer by indirect immunofluorescence (IFA) was positive for measles antigen and negative for mumps, parainfluenza (types I, II, and III) and influenza A and B virus. Serologic studies for measles antibody revealed an IFA IgG titer of greater than 1:10,240, and an IgM titer of 1:128. Cytologic examination of the same bronchial fluid revealed the typical giant cells with characteristic inclusions associated with measles virus. Because this disease usually is severe, and often fatal, prompt recognition of this virus is essential, not only to the patient, who can be treated with immunoglobulin and/or antiviral therapy, but also to prevent the spread of the virus to other patients and medical personnel. These findings also support direct evidence for the etiologic role of measles virus in giant-cell pneumonia that has been detected either histologically or cytologically and in tissue culture at autopsy.

Animals

Comparison of a serum replacement (Omni Serum) and fetal bovine serum in cell cultures used to isolate herpes simplex virus from clinical specimens.

Traditionally, fetal bovine serum (FBS) has been the principal component in media used in the growth and maintenance of cell cultures. Recent shortages have affected the cost and availability of FBS to clinical laboratories. Furthermore, lot-to-lot variability can affect cell culture performance and growth. We evaluated a commercially available serum replacement (Omni Serum; Advanced Biotechnologies Inc., Columbia, Md.) for use in the growth of cell cultures and for use in maintenance media used for the isolation of herpes simplex virus from clinical specimens. Cells (rhabdomyosarcoma and mink lung) raised on 5% Omni Serum grew as well as those grown on 10% FBS. The sensitivity of the Omni-raised cells to herpes simplex virus that had been isolated from 111 clinical specimens was equal to that of the cells raised and maintained with FBS. Cells grown with 10% FBS and maintained with 2% Omni Serum displayed the same sensitivity and integrity in tubes (rhabdomyosarcoma and mink lung) and vials (MRC-5 cells) as cells grown with 10% FBS and maintained with 5% FBS. This study indicates that Omni Serum is an acceptable substitute for FBS in maintenance media for cell culture tubes and vials used for viral isolation from clinical specimens.

Animals

Neutrophil adherence to isolated adult canine myocytes. Evidence for a CD18-dependent mechanism.

Cardiac myocytes were isolated from adult dogs and incubated with isolated canine neutrophils (PMN). Intercellular adhesion was low and unchanged by stimulation of the PMN with zymosan activated serum or platelet activating factor (PAF) at concentrations that significantly enhance PMN adhesion to protein-coated glass and canine endothelial cell monolayers. Intercellular adhesion was significantly increased only when both myocytes and PMN were stimulated (e.g., myocytes incubated with IL-1, tumor necrosis factor, or phorbol myristate acetate, and PMN were chemotactically stimulated). Inhibitors of protein synthesis diminished the IL-1 beta-induced effect by greater than 80%. The IL-1 beta, PAF-stimulated PMN-myocyte adhesion was associated with substantial H2O2 production. Under conditions with low PMN-myocyte adhesion (i.e., IL-1 beta alone, PAF alone, or no stimulus) H2O2 production was generally less than 5% of that occurring with high adhesion. An anti-CD18 monoclonal antibody (R15.7) inhibited stimulated PMN-myocyte adhesion by greater than 95% and reduced H2O2 production by greater than 90%. Control isotype-matched, binding, and nonbinding antibodies were without effect on adherence or H2O2 production. The results indicate that cytokine stimulation of adult myocytes induces expression of a ligand involved in CD18-dependent adherence of canine neutrophils.

Animals

Meptazinol and morphine in postoperative pain assessed with a new method for onset and duration.

Meptazinol, m-(3-ethyl-1-methyl-hexahydro-1-H-azepin-3-yl) phenol hydrochloride is a centrally active opioid analgesic with a specificity for the mu-1 receptor. It has been reported to lack many of the side effects commonly observed with morphine and morphinelike drugs in man. The objective of this study was to assess the analgesic efficacy and safety of meptazinol (50 mg and 100 mg) relative to morphine (5 mg and 10 mg) when administered intramuscularly for the treatment of postoperative pain. In addition, a new clinical method for measuring onset and duration and a statistical technique for evaluating the study data are presented. One hundred and seventeen patients were evaluated for 6 hours in a randomized double blind, single dose, parallel-groups trial. Estimates of relative potency for hourly pain and relief parameters, and the summary variables sum of pain intensity differences (SPID) and total pain relief (TOTPAR) were performed. The estimate of relative potency of meptazinol to morphine for pain relief was 0.19 at 1/2 hour (i.e. 100 mg of meptazinol was approximately equivalent to 20 mg of morphine). Thereafter, there was a rapid decline of efficacy for meptazinol, with a relative potency estimate of 0.12 at 1 hour and 0.06 at 2 hours. The distribution functions for several time related events were estimated including time to onset, duration and time to remedication. The two drugs had approximately equal onset, but meptazinol had significantly shorter duration. More patients on meptazinol required remedication with a rescue analgesic and at an earlier time than patients on morphine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Inpatients of Taipei City Psychiatric Center, Zhenjiang Psychiatric Hospital and New York State Mental Hospital, Rockland Psychiatric Center: comparison of the diagnostic distribution and sex ratios.

Description among Zhenjiang Psychiatric Hospital (ZPH) Taipei City Psychiatric Center (TCPC), and New York State Psychiatric Hospital, Rockland Psychiatric Center (RPC) admission cohorts during the identical year indicates that the RPC cohort demonstrates different frequencies of major psychiatric illness than the ZPH and TCPC cohorts which are remarkably similar. Schizophrenia is more prevalent among RPC public admissions than ZPH and TCPC. Mania exceeds depression in ZPH and TCPC samples while depression exceeds mania in RPC. Females predominate among ZPH and TCPC admissions, in contrast to male predominance in RPC. Wherease alcoholism is almost non-existant among ZPH and TCPC admissions, over half the RPC sample had a diagnosis of substance abuse.

Alcoholism

Analgesic efficacy of piroxicam in the treatment of postoperative pain.

Two randomized, double-blind, single-dose studies were conducted to assess the analgesic efficacy and safety of piroxicam for the treatment of moderate or severe postoperative pain. Study 1 evaluated the analgesic efficacy of piroxicam 20 mg compared with that of codeine sulfate 60 mg and placebo. A final patient population of 149 subjects rated pain intensity and pain relief at one half hour and one hour following treatment and then hourly for six hours, with a global assessment made at the completion of 24 hours. Piroxicam 20 mg was significantly more efficacious than placebo for all analgesic variables, including the sum of the pain intensity differences (SPID), total pain relief (TOTAL), percent SPID, duration of effect, and time to remedication. Codeine 60 mg was significantly superior to placebo for percent SPID and some hourly measures. Piroxicam 20 mg was significantly more effective than codeine 60 mg for percent SPID and a few hourly measures including time to remedication. Study 2 assessed the efficacy of piroxicam 20 mg or 40 mg compared with aspirin 648 mg and placebo. Sixty patients rated their pain intensity and relief hourly for 12 hours and at 24 hours after administration of study medication. Both doses of piroxicam were significantly more effective than placebo from Hours 2 to 12 for pain intensity difference (PID) and relief scores, as well as for SPID and TOTAL. Aspirin was significantly more effective than placebo from Hours 2 to 8 for relief and Hours 2 to 10 for PID as well as SPID and TOTAL. Piroxicam 40 mg was significantly more effective than aspirin 648 mg for SPID, TOTAL, and hourly measures beginning with Hour 6 through Hour 12. Piroxicam 20 mg was significantly better than aspirin for a few hourly measures: Hours 7 to 9 for relief and Hour 7 for PID. In addition, effects of piroxicam 20 mg had a significantly longer duration than aspirin. Similarly, piroxicam 20 mg had a significantly longer time to remedication compared with aspirin and placebo. The results of these studies provide evidence in support of the longer duration of analgesic efficacy of piroxicam compared with codeine or aspirin in patients with postoperative pain.

Analgesics

Pharmaco-epidemiology in 136 hospitalized schizophrenic patients.

The authors surveyed pharmacotherapy in a group of 136 newly admitted patients with a DSM-III diagnosis of schizophrenia. They found that nine antipsychotic agents were used; the median daily dose (in chlorpromazine equivalents) was 1088 mg (mean +/- SD = 1428 +/- 1260 mg; range = 75-6186 mg). Women received greater mean daily doses of antipsychotics than men (1688 versus 1284 mg). Using a Cox model survival analysis, the authors found no statistical association between length of stay and the mean daily dose of antipsychotic medication. The mean daily dose of high-potency agents was 2.7 times greater than the dose of low-potency agents. The excess exposure to haloperidol alone resulted in 16.3% of the overall neuroactive drug costs.

Adolescent

The correlation between blood levels of ibuprofen and clinical analgesic response.

A clinical trial comparing ibuprofen, 400, 600, and 800 mg, with aluminum ibuprofen, 400 mg, and placebo was conducted in patients with moderate or severe pain subsequent to third molar extraction. Pain intensity ratings and ibuprofen serum levels were obtained at baseline, 30 minutes, 1 hour, and hourly thereafter for 3 hours. Pain intensity ratings were also obtained at hours 4, 5, and 6. Serum levels at 1, 2, and 3 hours correlated significantly with the log dose of ibuprofen (r = 0.35, 0.49, and 0.48, respectively) and with global analgesic response as measured by the percentage of the sum of the pain intensity scores (r = 0.28, 0.34, and 0.26, respectively). However, possibly because of differences in drug formulation, the percentage of the sum of the pain intensity scores did not correlate significantly with log dose. The highest correlations were found between contemporaneous serum levels and pain intensity difference values, particularly at hour 1 (r = 0.54). Our results support the proposition that increased ibuprofen serum levels lead to increased analgesia.

Adolescent

An alternative to DRGs. A clinically meaningful and cost-reducing approach.

A statistical methodology based on the Cox proportional hazards model (a survival time analysis method), an alternative to the approach underlying DRGs, is presented. The method is used to obtain an estimate of the length-of-stay (LOS) distribution of a patient incorporating either patient-specific or hospital variables. A percentile of the distribution chosen to minimize prediction error serves as the assigned LOS. Absolute deviation is used as the loss function both to determine the choice of a predicted LOS and to examine how well the scheme works. Multiple assignment schemes may also be developed from this approach. The results of the method, tested on a national probability sample of 4,608 psychiatric patients treated in psychiatric units of general hospitals, suggest that with respect to average absolute deviation, the proposed methodology may provide a scheme that is superior to the present DRG scheme. For the sample, the average percent improvement obtained using the median of the estimated LOS distribution as the predicted LOS over the sample mean of the DRG group is 19%. A two assignment strategy results in average improvements over DRGs of 43%.

Cost Control

Elderly schizophrenic inpatients in the wake of deinstitutionalization.

The authors investigated the factors relating to the observation that in a large state hospital, there is an age-related increase in the ratio of patients with a DSM-II diagnosis of paranoid schizophrenia to those with a diagnosis of nonparanoid schizophrenia. Elderly inpatients (N = 1,518) treated over a 5-year period were studied and the hypotheses of proportionately greater numbers with late onset of paranoid conditions, longer lengths of stay for recently admitted paranoid patients, and changing diagnosis over time were tested and rejected. The data suggest that the buildup among the elderly of those diagnosed under DSM-II to have paranoid conditions is due to patients admitted well before age 54. The authors discuss the reasons for the poor prognosis of this group.

Age Factors

Problems in the care of the infant diabetic patient.

The unique problems of three infants who developed diabetes mellitus at 13 months of age or younger are discussed. These problems include: the administration of small doses of insulin; the difficulty in attaining control; and the evaluation of urinary sugar content. Suggestions for care are made.

Diabetes Mellitus, Type 1