Medicine and Health Sciences Commons^™

Effects Of Magnesium-Aluminum Hydroxide And Calcium Carbonate Antacids On Bioavailability Of Ofloxacin, Soledad Flor, David R. P. Guay, John A. Opsahl, Kenneth Tack, Gary R. Matzke

Pharmacotherapy and Outcomes Science Publications

The effects of 15- and 5-ml doses of magnesium-aluminum hydroxide (MAH) and calcium carbonate (CC) antacids, respectively, on the bioavailability of ofloxacin after single oral 400-mg doses of ofloxacin were investigated in a 32-subject, randomized, crossover, open-label study. On four separate occasions, subjects received ofloxacin alone or antacid 24 h before, 2 h before, or 2 h after ofloxacin administration (n = 16 for each antacid). CC administration had no significant effect on the rate and extent of ofloxacin absorption regardless of the timing of antacid administration. A small but significant negative effect of MAH administration 2 h before ofloxacin …

Assessment Of Cefazolin And Cefuroxime Tissue Penetration By Using A Continuous Intravenous Infusion., John E. Connors, Joseph T. Dipiro, Ronald G. Hayter, K. Dale Hooker, Johnny A. Stanfield, Timothy R. Young

Publications from the Office of the Dean

A continuous intravenous infusion was used to assess the tissue penetration of cefazolin (14 subjects) and cefuroxime (15 subjects) in orthopedic surgery patients. Subjects were randomly assigned to receive a continuous intravenous infusion of cefazolin (mean, 178.6 mg/h) orcefuroxime (mean, 330.0 mg/h) at a rate estimated to achieve a target steady-state total concentration of 50 micrograms/ml in serum. The infusion was initiated 12 to 14 h before surgery, and blood and muscle tissue samples were collected intraoperatively at the times of incision and wound closure. Although there was a significant difference between the free concentrations ofcefazolin (at incision, 9.3 micrograms/ml; …

Direct Measurement Of Translingual Epithelial Nacl And Kcl Currents During The Chorda Tympani Taste Response, G. L. Heck, K. C. Persaud, J. A. Desimone

Physiology and Biophysics Publications

ABSTRACT

We have measured the NaCI or KCI currents under voltage clamp across the dorsal lingual epithelium of the rat and simultaneously the response of the taste nerves. Under short-circuit conditions a NaCI stimulus evoked an inward current (first current) that coincided with excitation of the chorda tympani. This was followed by a slower inward current (second current) that matched the kinetics of taste nerve adaptation. The peak first current and the coincident neural response satisfied the same saturating NaCI concentration dependence. Both first and second currents were partially blocked by amiloride as were the phasic and tonic components of …

Cytomegalovirus And Child Day Care, Stuart P. Adler , M.D.

Internal Medicine Publications

Abstract

To determine whether day-care workers acquire cytomegalovirus infection from the children they care for, we studied 610 women employed at 34 day-care centers over two years.

Forty-one percent of the caretakers were seropositive for cytomegalovirus. After adjustment for the effects of race, marital status, and age on seropositivity, the women who cared for children younger than two years of age had a significantly higher seropositivity rate (46 percent) than the women who cared for children older than two years of age (35 percent) (relative risk, 1.29; 95 percent confidence interval, 1.05 to 1.57; P<0.02).

Of 202 initially seronegative caretakers …

Pharmacokinetics Of Gentamicin In Neonates On Extracorporeal Membrane Oxygenation., W. Michael Southgate, Joseph T. Dipiro, Alex F. Robertson

Publications from the Office of the Dean

Extracorporeal membrane oxygenation (ECMO) has been used in more than 1,000 infants in 50 centers in the United States. The extracorporeal circuit contains approximately 400 ml of blood, an amount exceeding the blood volume of most full-term neonates. The effect of this additional blood volume on drug disposition is unknown. In this study, we determined the pharmacokinetic parameters of gentamicin in 10 infants on ECMO. Gentamicin concentrations were determined by a fluorescence polarization immunoassay. Pharmacokinetic parameters were determined from these concentrations by using a two-compartment model. Our study demonstrated a mean steady-state volume of distribution of 0.51 +/- 0.11 liters/kg, …

Treatment Of Cryptococcal Meningitis With Combination Amphotericin B And Flucytosine For Four As Compared With Six Weeks, William E. Dismukes , M.D., Gretchen Cloud , M.S., Harry A. Gallis , M.D., Thomas M. Kerkering , M.D., Gerald Medoff , M.D., Philip C. Craven , M.D., Lisa G. Kaplowitz , M.D., John F. Fisher , M.D., Clark R. Gregg , M.D., Cynthia A. Bowles , R.N., Smith Shadomy , Ph.D., Alan M. Stamm , M.D., Robert B. Diasio , M.D., Leo Kaufman , Ph.D., Seng-Jaw Soong , Ph.D., William C. Blackwelder , Ph.D.

Internal Medicine Publications

Abstract

One hundred ninety-four patients with cryptococcal meningitis were enrolled in a multicenter, prospective, randomized clinical trial to compare the efficacy and toxicity of four as compared with six weeks of combination amphotericin B and flucytosine therapy. Among 91 patients who met preestablished criteria for randomization, cure or improvement was noted in 75 percent of those treated for four weeks and in 85 percent of those treated for six weeks. The estimated relapse rate for the four-week regimen was higher — 27 as compared with 16 percent — whereas the incidence of toxic effects for the two regimens was similar …

Tryptase Levels As An Indicator Of Mast-Cell Activation In Systemic Anaphylaxis And Mastocytosis, Lawrence B. Schwartz , M.D., Ph.D., Dean D. Metcalfe , M.D., Jeffrey S. Miller , M.D., Harry Earl , M.D., Timothy Sullivan , M.D.

Internal Medicine Publications

Abstract

Better methods are needed to assess mastcell activation In vivo and to distinguish the activation of mast cells from that of basophils. Tryptase, a neutral protease selectively concentrated in the secretory granules of human mast cells (but not basophils), is released by mast cells together with histamine and serves as a marker of mast-cell activation.

In 17 patients with systemic mastocytosis, concentrations of tryptase in plasma were linearly related to those of histamine (P<0.01). Eleven of the 17 patients had tryptase levels of 4 to 88 ng per milliliter, indicating ongoing mast-cell activation. In each of six patients who experienced corresponding anaphylactic reactions after penicillin, aspirin, or melon ingestion, a wasp sting, exercise, or antilymphocyte globulin injection, tryptase levels in serum ranged from 9 to 75 ng per milliliter, indicating mast-cell activation during each of these events. In contrast, serum tryptase levels were less than 5 ng per milliliter in all patients presenting with myocardial disease (n = 8, 6 with hypotension) or sepsis (n = 6, 3 with hypotension) and in the controls (n = 20). One patient had a myocardial infarction after anaphylaxis in response to a wasp sting and an elevated tryptase level of 25 ng per milliliter. Thus, the plasma or serum tryptase level is a diagnostic correlate of mast-cell-related events. (N Engl J Med 1987; 316: 1622–6.)

Effect Of Hemorrhagic Shock On Cefazolin And Gentamicin Pharmacokinetics In Dogs., Paul L. Dickson, Joseph T. Dipiro, Katherine A. Michael, Richard P. F. Cheung, Edward M. Hall

Publications from the Office of the Dean

The physiologic response to traumatic injury may alter the disposition of drugs and thereby affect their therapeutic or toxic potential. A study was conducted in 10 mongrel dogs to determine theeffect of experimental hemorrhagic shock with resuscitation on the pharmacokinetics of gentamicinand cefazolin. Single simultaneous intravenous doses of gentamicin (3 mg/kg) and cefazolin (25 mg/kg) were administered to each animal on an initial study day, after which serial blood and urine collections were performed. After 1 week, a standard hemorrhagic shock model was applied to each animal. Shock was continued for 1 h, after which the animal was resuscitated with …

Pathophysiology Of Male Hypogonadism Associated With Endogenous Hyperestrogenism — Evidence For Dual Defects In The Gonadal Axis, Johannes D. Veldhuis, James R. Sower, Alan D. Rogol, Frederick A. Klein, Norman Miller, Maria L. Dufau

Surgery Publications

FEMINIZING tumors of the adrenal cortex are associated with symptoms that presumably reflect the combined effects of estrogen excess and androgen deficiency — gynecomastia, diminished libido, attenuated potency, and testicular and prostatic atrophy.1 2 3 4 5 Although such tumors are extremely rare, they provide a unique opportunity to appraise the nature of endogenous estrogen action on the gonadal axis in men. In principle, the pathophysiologic effects of estrogen hypersecretion could be expressed at the level of either the Leydig cell or the hypothalamic–pituitary axis (or both), with consequent suppression of androgen production. In the present studies, we investigated …

Clinical Findings In Four Children With Biotinidase Deficiency Detected Through A Statewide Neonatal Screening Program, Barry Wolf, Gregory S. Heard, Linda G. Jefferson, Virginia K. Proud, Walter E. Nance, Karen A. Weissbecker

Human and Molecular Genetics Publications

Four children with biotinidase deficiency were identified during the first year of a neonatal screening program for this disease in the Commonwealth of Virginia. Two unrelated probands were identified among the 81,243 newborn infants who were screened. In addition, two siblings of one of these infants were found to be affected. Both probands had mild neurologic symptoms at two and four months, respectively, and the two older children had more severe neurologic abnormalities, cutaneous findings, and developmental delay at two and three years of age. However, none of the affected children had acute metabolic decompensation. Previous studies have shown that …

Intraoperative Ceforanide Pharmacokinetics And Protein Binding., Joseph T. Dipiro, Samir M. Bayoumi, Joseph J. Vallner, Robert R. Nesbit, Rajeev Gokhale, J. Peter Rissing

Publications from the Office of the Dean

The pharmacokinetics and protein binding of ceforanide were studied in 15 patients undergoing cholecystectomies. Each patient received ceforanide (20 mg/kg) intravenously on arrival in the operating room, after which serial blood samples were collected during the elimination phase for determination of total and free ceforanide concentrations in the serum. A high-pressure liquid chromatography assay was used, with a centrifugal filtration system for free-drug determinations. Serum concentration data for each individual were subjected to linear regression to determine the elimination rate constants (total and free drug), volumes of distribution, and systemic clearances. The mean elimination rate constants were 0.41 and 0.50 …

Fluorescence Probes For The Study Of Acetylcholine Receptor Function, M. Martinez-Carrion, J.M. Gonzalez-Ros, J.R. Mattingly, J.A. Ferragut, M.C. Farach, D. Donnelly

Biochemistry and Molecular Biology Publications

Our group initiated the use of pyrene derivatives for functional and structural studies of the membrane-bound Acetylcholine Receptor (AcChR) system. Our studies have taken two approaches. We have recently used a hydrophobic derivative (pyrene-l-sulfonyl azide) that is able to bind covalently to regions of the AcChR molecule accessible from the membrane lipid (1) to monitor ligandinduced effects at those hydrophobic regions of the AcChR protein exposed to the membrane matrix (2). The structural effects induced by ligand binding are interpreted in relation to the AcChR "desensitization" process. We have also used a hydrophilic pyrene derivative (1,3,6,8-pyrene tetra sulfonate [PTSA]) to …

Potential And K+ Activity In Skinned Muscle Fibers. Evidence Against A Simple Donnan Equilibrium, R.E. Godt, C.M. Baumgarten

Physiology and Biophysics Publications

ABSTRACT

It has been suggested that potentials measured with conventional microelectrodes in chemically or mechanically skinned muscle fibers arise from a Donnan equilibrium due to myofilament fixed charges. This hypothesis was tested in mechanically skinned frog (Rana pipiens) semitendinosus fibers by measuring the distribution potential (Ed) between fiber and bath with 3 M KCI-filled microelectrodes and the K+ activity gradient (a'K/a) with K+ ion-selective microelectrodes (KISE). If skinned fibers are a Donnan system, Ed should become more positive as pH is decreased, altering the fixed charge on the myofilaments. Consistent with this expectation, Ed was -4.4, -0.6, and +4.8 mV …

Inability To Predict Relapse In Acute Asthma, Robert M. Centor , M.D., Barry Yarbrough , M.D., Judy P. Wood , P.A.

Internal Medicine Publications

No abstract provided.

Cellular Dna Content As A Predictor Of Response To Chemotherapy In Infants With Unresectable Neuroblastoma, A. Thomas Look, F. Ann Hayes, Ruprecht Nitschke, Nancy B. Mcwilliams, Alexander A. Green

VCU Health Publications

We studied the relation between the DNA content of neuroblastoma cells and the response to therapy in 35 infants under one year of age with a diagnosis of neuroblastoma. Using flow cytometric techniques, we found that in 27 cases the primary malignant stem line consisted of neuroblasts with hyperdiploid DNA content, ranging from 1.07 to 2.42 times the finding in normal diploid cells. All remaining cases had diploid stem lines. Diploidy was more common in infants with clinical Stage D neuroblastoma (metastases beyond regional lymph nodes) than in those with other, less advanced stages: 6 of 10 as compared with …

Ventriculostomy-Related Infections, C. Glen Mayhall, Nancy H. Archer, V. Archer Lamb, Alice C. Spadora, Jane W. Baggett, John D. Ward, Raj K. Narayan

VCU Health Publications

We conducted a prospective epidemiologic study of ventriculostomy-related infections (ventriculitis or meningitis) in 172 consecutive neurosurgical patients over a two-year period to determine the incidence, risk factors, and clinical characteristics of the infections. Ventriculitis or meningitis developed in 19 of 172 patients (11 per cent) undergoing a total of 213 ventriculostomies. When data from all these cases plus five cases of nonventriculostomy-related infection were combined, cerebrospinal-fluid pleocytosis was more significantly associated with the diagnosis of ventriculitis or meningitis (P<0.0001) than were fever and leukocytosis (P = 0.07). Risk factors for ventriculostomy-related infections included intracerebral hemorrhage with intraventricular hemorrhage (P = 0.027), neurosurgical operations (P = 0.016), intracranial pressure of 20 mm Hg or more (P = 0.019), ventricular catheterization for more than five days (P = 0.017), and irrigation of the system (P = 0.021). Previous ventriculostomy did not increase the risk of infection with subsequent procedures. We conclude that ventriculostomy-related infections may be prevented by maintenance of a closed drainage system and by early removal of the ventricular catheter. If monitoring is required for more than five days, the catheter should be removed and inserted at a different site. (N Engl J Med 1984; 310:553–9.)

Unidirectional Calcium And Nucleotide Fluxes In Sarcoplasmic Reticulum. I. Interpretation Of Flux Ratios For Different Reaction Schemes, J. J. Feher

Physiology and Biophysics Publications

The relation between unidirectional calcium and nucleotide fluxes was examined for different ATPase reaction schemes of the sarcoplasmic reticulum. The schemes considered differed in the order of sorption and desorption of calcium, ATP, and ADP. The results suggest that the theoretical relation between calcium and nucleotide fluxes depends on the reaction scheme and that experimental measurements can distinguish among them. The results obtained are generally valid and do not depend on assumptions of equilibrium or pseudoequilibrium between intermediate states of the pump.

Undirectional Calcium And Nucleotide Fluxes In Cardiac Sarcoplasmic Reticulum. Ii. Experimental Results, J. J. Feher, F. N. Briggs

Physiology and Biophysics Publications

Unidirectional calcium influx and efflux were evaluated in cardiac sarcoplasmic reticulum (SR) by 45Ca-"0Ca exchange at steady state calcium uptake in the absence of calcium precipitating anions. Calcium efflux was partitioned into a pump-mediated efflux and a parallel passive efflux by separately measuring passive efflux referable to the steady state. Unidirectional and net ATP-ADP fluxes were measured using [3H]-ATP -- ADP and [3H]- ADP -- ATP exchanges. Methods are presented that take into account changing specific activities and sizes of the nucleotide pools during the measurement of nucleotide fluxes. The contribution of competent and incompetent vesicles to the unidirectional and …

Comparison Of Intermediate-Dose Methotrexate With Cranial Irradiation For The Post-Induction Treatment Of Acute Lymphocytic Leukemia In Children, Arnold I. Freeman , M.D., Vivian Weinberg, Martin L. Brecher , M.D., Barbara Jones , M.D., Arvin S. Glicksman , M.D., Lucius F. Sinks , M.D., Marise Weil , M.D., Hansjuerg Pleuss , M.D., Juliet Hananian , M.D., E. Omer Burgert , Jr., M.D., Gerald S. Gilchrist , M.D., Thomas Necheles , M.D., Michael Harris , M.D., Faith Kung , M.D., Richard B. Patterson , M.D., Harold Maurer , M.D., Brigid Leventhal , M.D., Louise Chevalier , M.D., Edwin Forman , M.D., James F. Holland , M.D.

Pediatrics Publications

Abstract

We compared two regimens with respect to their ability to prolong disease-free survival in 506 children and adolescents with acute lymphocytic leukemia. All responders to induction therapy were randomized to treatment with 2400 rad of cranial irradiation plus intrathecal methotrexate or to treatment with intermediate-dose methotrexate plus intrathecal methotrexate, as prophylaxis for involvement of the central nervous system and other "sanctuary" areas. Patients were then treated with a standard maintenance regimen. Complete responders were stratified into either standard-risk or increased-risk groups on the basis of age and white-cell count at presentation.

Among patients with standard risk, hematologic relapses occurred …

Lack Of Influence Of Commonly Used Drugs On Bioassay Indicator Organisms., Joseph T. Dipiro, A. Thomas Taylor, John C. H. Steele Jr.

Publications from the Office of the Dean

Many commonly used pharmaceutical agents have been found to inhibit bacterial growth in vitro. Determinations of antimicrobial concentrations in sera of patients taking nonrecognized antibacterial agents could possibly be altered if bioassay systems are utilized for the determinations. We therefore attempted to determine the in vitro effect of commonly used drugs on bioassay indicator organisms. Fifty-one different agents (antihistamines, anticholinergics, central nervous system agents, cardiovascular agents, analgesics, steroids, muscle blockers, and other miscellaneous agents) were tested for inhibition or enhancement of the growth of Bacillus subtilis, Staphylococcus aureus, Micrococcus luteus, and Klebsiella pneumoniae. None of the agents tested exhibited any …

Treatment Of Inborn Errors Of Urea Synthesis — Activation Of Alternative Pathways Of Waste Nitrogen Synthesis And Excretion, Mark L. Batshaw , M.D., Saul Brusilow , M.D., Lewis Waber , Ph.D., M.D., Wim Blom , Ph.D., Ann Mari Brubakk , M.D., Barbara K. Burton , M.D., Howard M. Cann , M.D., Douglas Kerr , M.D., Peter Mamunes , M.D., Reuben Matalon , M.D., David Myerberg , M.D., Irwin A. Schafer , M.D.

Pediatrics Publications

Abstract

Children with inborn errors of urea synthesis accumulate ammonium and other nitrogenous precursors of urea, leading to episodic coma and a high mortality rate. We used alternative pathways for the excretion of waste nitrogen as substitutes for the defective ureagenic pathways in 26 infants. These pathways involve synthesis and excretion of hippurate after sodium benzoate administration, and of citrulline and argininosuccinate after arginine supplementation.

The children were treated for seven to 62 months; 22 survived. The mean plasma level of ammonium (±S.E.) was 36±2 μmol per liter, and that of benzoate was 1.5±1.0 mg per deciliter. Alternative pathways accounted …

Discordant Expression Of Fetal Hydantoin Syndrome In Heteropaternal Dizygotic Twins, Mary C. Phelan , B.S., John M. Pellock , M.D., Walter E. Nance , M.D., Ph.D.

Human and Molecular Genetics Publications

No abstract provided.

A Cyproheptadine-Reversible Defect In Acth Control Persisting After Removal Of The Pituitary Tumor In Cushing's Disease, Harvey V. Lankford , M.D., H. St. George Tucker , M.D., William G. Blackard , M.D.

Internal Medicine Publications

Abstract

We studied two phases of cortisol feedback suppression of ACTH in nine patients who had had adrenalectomy for Cushing's disease. Four had been treated by adrenalectomy alone and presumably had ACTH-secreting pituitary tumors. Five others were studied two or more years after transsphenoidal removal of an ACTH-secreting microadenoma. In both groups, cortisol-ACTH feedback during the first 30 minutes of cortisol infusion was abnormal; plasma ACTH fell only 2.7±2.6 per cent (mean ±S.E.), as compared with 28.0±10.1 per cent in five hypoadrenal controls (P<0.01). The fall in ACTH during the second phase of cortisol infusion was similar in the patients and the controls. Cyproheptadine corrected the feedback abnormality occurring during the first phase in both groups of patients with Cushing's disease; ACTH fell by 24.4±4.8 per cent (P<0.005). Persistence of a cortisol-ACTH feedback abnormality after removal of the pituitary tumor in Cushing's disease, as well as the correction by cyproheptadine, suggests that higher centers have a role in the pathophysiology of Cushing's disease. (N Engl J Med. 1981; 305:1244–8.)

Traumatic Acute Subdural Hematoma — Major Mortality Reduction In Comatose Patients Treated Within Four Hours, John M. Seelig , M.D., Donald P. Becker , M.D., J. Douglas Miller , M.D., Ph.D., F.R.C.S., F.A.C.S., Richard P. Greenberg , M.D., Ph.D., John D. Ward , M.D., Sung C. Choi , Ph.D

Biostatistics Publications

To discover which factors contributed to recovery after surgical intracranial decompression, we reviewed the records of 82 consecutive comatose patients with traumatic acute subdural hematoma (ASDH) who were treated in a single center under a uniform protocol. The delay from injury to operation was the factor of greatest therapeutic importance. Patients who underwent surgery within the first four hours had a 30 per cent mortality rate, as compared with 90 per cent in those who had surgery after four hours (P

The Location Of Olfactory Receptor Sites. Inferences From Latency Measurements, T. V. Getchell, G. L. Heck, J. A. Desimone, S. Price

Physiology and Biophysics Publications

Excitatory responses recorded from vertebrate olfactory sensory neurons are characterized by long latencies compared with those from other sensory receptors. Explanations which assume free access of the stimuli to receptor molecules presumably located on the olfactory cilia necessarily imply an intrinsic delay in the transduction mechanism. In contrast, the possibility of restricted or delayed access due to diffusion of the stimulus to molecular receptors located on the dendritic knob or proximal portions of the cilia suggests transduction processes having time courses similar to those in other sensory systems. We show that the threshold stimulus concentration and the latency of the …

A Network Thermodynamic Approach To Compartmental Analysis: Na+ Transients In Frog Skin, D. C. Mikulecky, E. G. Huf, S. R. Thomas

Physiology and Biophysics Publications

We introduce a general network thermodynamic method for compartmental analysis which uses a compartmental model of sodium flows through frog skin as an illustrative example (Huf and Howell, 1974a). We use network thermodynamics (Mikulecky et al., 1977b) to formulate the problem, and a circuit simulation program (ASTEC 2, SPICE2, or PCAP) for computation. In this way, the compartment concentrations and net fluxes between compartments are readily obtained for a set of experimental conditions involving a square-wave pulse of labeled sodium at the outer surface of the skin. Qualitative features of the influx at the outer surface correlate very well with …

Early Diagnosis Of Relapse In Acute Myeloblastic Leukemia — Serologic Detection Of Leukemia-Associated Antigens In Human Marrow, Michael A. Baker , M.D., Judith A. Falk , B.Sc., Walter H. Carter , Ph.D., Robert N. Taub , M.D., Ph.D.

Internal Medicine Publications

Abstract

We tested serial bone-marrow samples from 47 adults with acute myeloblastic leukemia in remission for reactivity with heteroantiserums to leukemia-associated antigens, to determine whether imminent relapse could be detected in patients with acute leukemia. Of 26 patients who relapsed by standard morphologic criteria, 21 had increased immunoreactivity of bone marrow for one to six months (mean, 3.7 months) before relapse. High concordance was observed between a positive test and relapse during the period of study (chi-square = 27.53, P

Human Infection From An Unidentified Erythrocyte-Associated Bacterium, Gordon L. Archer , M.D., Philip H. Coleman , D.V.M., Ph.D., Roger M. Cole , M.D., Ph.D., Richard J. Duma , M.D., Ph.D., Charles L. Johnston , Jr., M.D.

Internal Medicine Publications

Abstract

A 49-year-old splenectomized man had an infection from an unidentified, gram-positive, rodshaped bacterium that adhered to the majority of his peripheral-blood erythrocytes. On transmission electron microscopy, the bacterium was seen to be extraerythrocytic and was 0.2 μm wide by 1.0 to 1.7 μm long. It possessed a thick, granular cell wall, a trilamellar membrane external to the cell wall and prominent mesosomes. Attempts to cultivate the organism in vitro or to duplicate the patient's disease in splenectomized animals were unsuccessful. The patient's response suggested that the bacterium was susceptible to cell-wall-active antibiotics and to chloramphenicol but not to tetracycline. …

A Comparison Of Amphotericin B Alone And Combined With Flucytosine In The Treatment Of Cryptoccal Meningitis, John E. Bennett , M.D., William E. Dismukes , M.D., Richard J. Duma , M.D., Gerald Medoff , M.D., Merle A. Sande , M.D., Harry Gallis , M.D., John Leonard , M.D., Branch T. Fields , M.D., Major Bradshaw , M.D., Hubert Haywood , M.D., Zell A. Mcgee , M.D., Thomas R. Cate , M.D., C. Glenn Cobbs , M.D., John F. Warner , M.D., David W. Alling , M.D., Ph.D.

Internal Medicine Publications

Abstract

We compared amphotericin B therapy for cryptococcal meningitis with a newer regimen containing both amphotericin B and flucytosine. In 50 patients with 51 courses of therapy adherent to the protocol, 27 courses were with amphotericin B and 24 with the combination. Even though the combination regimen was given for only six weeks and amphotericin B for 10 weeks, the combination cured or improved more patients (16 vs. 11), produced fewer failures or relapses (three vs. 11), more rapid sterilization of the cerebrospinal fluid (P<0.001) and less nephrotoxicity (P<0.05) than did amphotericin B alone. The number of deaths was the same (five) with each regimen. Adverse reactions to flucytosine occurred in 11 of 34 patients but were not life threatening. We conclude that combined flucytosine-amphoericin B therapy is the regimen of choice in cryptococcal meningitis. (N Engl J Med 301:126–131, 1979)

[Beta]-(2-Hydroxyphenyl)Ethanolamine Hydrochloride [2-Amino-1-(2-Hydroxyphenyl)Ethanol Hydrochloride], Alexandros Makriyannis, James B. Anderson, Joseph T. Dipiro, Edward Kostiner, Gilbert Hite

Publications from the Office of the Dean

CsH~2NO2+.C1 -, m.p. 441-449 K (from ethyl acetate), P212~2 l, a = 7.363 (2), b = 21.824 (6), c = 5.790 (2)/~, Z = 4, D x = 1.354, D m = 1.356 Mg m -3 (flotation: CC14-C6H6). The structure was solved by MULTAN. Full-matrix least-squares refinement converged to R = 0.057 for the R configuration and to R = 0.056 for the S configuration (P < 0.05). This is consistent with spontaneous resolution of the title compound, single crystals of which provided optically active aqueous solutions. A partially occupied oxygen site O(1)' is attributed to the oxidation of the alkyl hydroxyl group to a ketone during the data collection. The CI- is hydrogen bonded to H2(N)554, H3(N)555, and 1-t(O2)655 (2.37, 2-19, and 2.10 A). Both O(1) and 0(2) are internally hydrogen bonded [HI(N)...O(1), 2.41 and H(O1)...O(2) = 2.24 A]. Intramolecular hydrogen bonding may account for the unusual pharmacological properties of this compound in which only the N-C(1)-C(2)-O(1) and the O(1)-C(2)- C(3)-C(4) and O(1)-C(2)-C(3)-C(8) torsion angles (-41, -60, +122 ° ) differ significantly from those of other phenylethanolamines.