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Biomedical subjects

G R Brown

Publications and source records attributed to G R Brown.

At least 19 recordsLinked to original sources

The opening of the inositol 1,4,5-trisphosphate-sensitive Ca2+ channel in rat cerebellum is inhibited by caffeine.

Ins(1,4,5)P3(InsP3)-induced Ca2+ release and [3H]InsP3 binding were measured in rat cerebellar microsomes in the presence or absence of caffeine. The quantal Ca2+ release was shown to occur in an apparently co-operative fashion with a Hill coefficient (h) of 2.2. Half-maximal Ca2+ release was observed at 900 nM-InsP3. Addition of caffeine caused changes both to the concentration of InsP3 required to cause half-maximal Ca2+ release (3.9 microM at 50 mM-caffeine) and to the apparent co-operativity (h = 1.0 at 50 mM-caffeine). Under standard conditions for [3H]InsP3 binding, caffeine had no effect, and it had no effect on InsP3 metabolism. Cyclic AMP also had no effect on the quantal release induced by InsP3. These results are consistent with the view that caffeine affects the opening (Ca2+ release) events rather than the ligand-binding events in the operation of the InsP3-sensitive Ca2+ channel.

Adenosine Triphosphate

Polymeric sorbents for bile acids. I: Comparison between cholestyramine and colestipol.

Isotherms for the sorption of bile acids at 20 degrees C, in tris(hydroxymethyl)aminomethane.HCl(tris) and KH2PO4-NaOH (phosphate) buffers (pH 7.4), indicate that the binding by cholestyramine and colestipol is mainly through ionic linkages, although hydrophobic interactions are also of importance. Cholestyramine has a higher sorption capacity for bile acids, in both buffers, than colestipol. The chloride form of cholestyramine has a higher capacity for cholate in tris buffer than the iodide form. Increased ionic strength of the medium leads to decreased amounts of sorption.

Absorption

Therapeutic interchange of cefazolin with metronidazole for cefoxitin.

The effects on patient outcome and drug therapy costs of a therapeutic interchange program using a cefazolin and metronidazole combination in place of cefoxitin were studied. A therapeutic interchange program was initiated in which the pharmacy department automatically replaced orders for cefoxitin with orders for a cefazolin and metronidazole combination. Data were compared for 100 consecutive patients who received cefoxitin before initiation of the program and the first 100 patients who received cefazolin and metronidazole as part of the program. The impact of the program on therapeutic efficacy, adverse effects associated with therapy, and drug therapy costs was assessed. The two patient groups were similar in age, gender, and white blood cell count. The failure rates for treatment or prophylaxis of infection did not significantly differ between the groups. Duration of therapy and incidence of adverse effects did not significantly differ between the groups. The average cost saving was +72 per patient for treatment with cefazolin and metronidazole instead of cefoxitin. A program for therapeutic interchange of cefazolin and metronidazole in place of cefoxitin demonstrated equivalent efficacy and adverse effects, as well as considerable cost savings.

British Columbia

Experience with a partnership program for cardiac surgery at a regional military medical center.

A Partnership Program between USAF Medical Center, Wright-Patterson (WPAFB) and Miami Valley Hospital (MVH), Dayton, Ohio, was created through CHAMPUS to provide cardiac surgical services for eligible patients. During the first year of this program, 82 patients underwent 89 percutaneous transluminal coronary angioplasty (PTCA) procedures. Sixty-one patients underwent cardiac surgery at WPAFB, 50 were referred to MVH due to ineligibility or other reasons, and five were referred to other military or civilian hospitals. The program has been successful with low morbidity and mortality (3%). Cost savings for PTCAs was $241,853 and for cardiac surgery was $462,046.

Cardiac Surgical Procedures

DSM-III-R brief reactive psychosis among Air Force recruits.

BACKGROUND: Clinical characteristics of patients diagnosed with brief reactive psychosis based on DSM-III-R criteria and the incidence of this disorder in a defined population have not been sufficiently studied. Some military recruits who are subjected to relatively uniform levels of stress in a monitored environment over a specified time period develop transient, severe psychotic symptoms consistent with a diagnosis of brief reactive psychosis. METHOD: We retrospectively reviewed all cases of brief reactive psychosis that occurred among 139,360 Air Force recruits during 6-week basic training experiences over a 3-year period. Brief case descriptions, including clinical courses, are provided. RESULTS: Six cases were found among 557 consecutive psychiatric admissions between January 1, 1988, and January 1, 1991 (annual incidence = 1.43 cases per 100,000 recruits). An apparent temporal relationship was found between the onset of the stressor (basic military training) and the development of psychosis. Paranoid symptomatology, including persecutory delusions, was present in all cases. Adjustment disorders were the most common diagnoses in patients admitted from the training environment (N = 464). CONCLUSION: Brief reactive psychosis is a rare discharge diagnosis in this large population of young Air Force recruits. Prospective studies are warranted to evaluate the usefulness of DSM-III-R criteria for this disorder and to determine the longitudinal course of patients who have received this diagnosis.

Adjustment Disorders

Medication refusal by psychiatric inpatients in the military.

Military psychiatrists must occasionally treat mentally ill active duty patients who refuse medications. Unlike their civilian counterparts, military psychiatrists have no established procedure to allow for involuntary treatment under non-emergency conditions. The following case and discussion is presented to illustrate how existing guidelines do not allow for optimal care of some of these patients.

Adult

Intravenous haloperidol treatment of severely regressed, nonviolent psychiatric inpatients.

The use of intravenous haloperidol in five severely regressed, nonviolent, psychiatric inpatients with psychotic disorders is described. Unlike previous reports in the consultation psychiatry literature, this treatment was not instituted to control combative behavior in the medically ill. All patients had intravenous access in place for hydration. Four of five patients were discharged in complete remission of psychotic symptoms after brief hospitalizations. The indications for use, dosages, and general absence of side effects are described. Intravenous haloperidol is a viable option for treating severely ill psychiatric inpatients with psychotic disorders.

Adult

Proliferating cell nuclear antigen immunolocalization in gastro-intestinal epithelia.

Proliferating cell nuclear antigen (PCNA), also called DNA polymerase delta-associated protein, is found in the cells of the proliferative compartment of normal tissues and is essential for DNA replication. It can be recognized by many monoclonal antibodies to various epitopes on the molecule. In this investigation one of these, PC10, has been used on formalin-fixed, paraffin-embedded, human and rodent gastro-intestinal epithelial tissues to assess numerically the labelling index of PC10 and to compare it, in the rat liver and gastrointestinal tract, with the S-phase fraction as determined by bromodeoxyuridine (BrdUrd) labelling. The distribution of PC10-labelled cells was recorded with respect to cell position in the intestinal crypts of man. In tissues where both modes of assessment were used, PC10 staining in the well-established proliferative compartments was found to be more extensive than that of BrdUrd. The higher labelling index with PC10 can be explained by its identification of PCNA outside the S phase of the cell cycle and also by the long half-life of PCNA protein in post-proliferative intestinal epithelial cells as they migrate towards the villus. Nevertheless the data suggest PC10 immunostaining in gastro-intestinal epithelia is an operational marker of cell proliferation which is reproducible, quantifiable and can be performed on routinely processed tissues.

Animals

Psychiatric morbidity in adult inpatients with childhood histories of sexual and physical abuse.

OBJECTIVE: To extend the knowledge on long-term effects of childhood abuse in psychiatric patients to a large sample, the authors explored childhood sexual and physical abuse in adult inpatients over 1,040 consecutive admissions. METHOD: The 947 patients were admitted to a tertiary-care military medical center. Each patient was interviewed, and abuse history, DSM-III-R diagnosis, and other characteristics were recorded. RESULTS: The prevalence of reported childhood abuse was 18% overall: 9% for sexual abuse (with or without physical abuse), 10% for physical abuse (with or without sexual abuse), and 3% for combined abuse. More female than male patients reported abuse. Alcohol use disorders were more common in victims of physical or combined abuse than in sexually abused or nonabused patients. Axis II diagnoses, particularly borderline personality disorder, were more frequent in abuse victims than in nonabused patients. Histories of drug and alcohol abuse were more common in patients reporting physical or combined abuse than in nonabused patients. Suicidality was also more frequent in abused than nonabused inpatients and was noted in 79% of the patients with histories of combined abuse. Combined abuse in women and physical abuse in men were associated with a family history of psychiatric illness, most commonly alcoholism in male relatives. CONCLUSIONS: These findings emphasize the need for greater attention to family dynamics, aggressive diagnosis and treatment of alcoholism within the family, and, especially, determination of patients' abuse histories, even if repeated questioning is necessary.

Adult

Direct mechanical ventricular actuation for cardiac arrest in humans. A clinical feasibility trial.

Direct mechanical ventricular actuation (DMVA) is a non-blood-contacting method of biventricular cardiac massage which may be applied expediently for total circulatory support. The purpose of this study was to assess the feasibility of DMVA application for patients suffering refractory cardiac arrest. Following informed consent, DMVA was applied in 22 patients. Vascular access for hemodynamic monitoring was possible in only 12 patients, whose outcomes serve as the basis for this report. The mean age of the patients was 48.2 +/- 4.2 years (seven men; five women). The average time from witnessed cardiac arrest to DMVA application was 81 +/- 9 minutes. Application took less than two minutes from the time of skin incision and resulted in immediate hemodynamic improvement. Systolic and diastolic blood pressures averaged 78 +/- 4 and 41 +/- 4 mm Hg, respectively, with a mean cardiac output of 3.14 +/- 0.18 L/min during a mean of 228 +/- 84 minutes of circulatory support (range, 25 minutes to 18 hours). In selected cases the device was temporarily removed for 2 to 3 minutes and open-chest cardiac massage (OCCM) performed at similar compression rates. DMVA increased arterial pressures 65 percent and cardiac output 190 percent compared to OCCM. Initial arterial pH (7.12 +/- 0.04) improved by the time the device was removed (7.24 +/- 0.05). Serum lactate levels decreased from 18.0 +/- 2.3 mumol/L to 14.9 +/- 2.9 mumol/L. Four patients were successfully defibrillated: two had inadequate cardiac function and died within 1 h, and two were successfully resuscitated, but later died from cardiac failure and respiratory insufficiency. Another patient regained normal neurologic function during DMVA and was successfully bridged to cardiopulmonary bypass for emergent coronary artery bypass grafting, but died later from myocardial infarction. There were only two complications: (1) a cardiac laceration during pericardiotomy (1/22 patients); and (2) a ventricular rupture during OCCM (1/22). No complication resulted from the device. We found DMVA to be a feasible method for acute cardiovascular stabilization in victims suffering refractory cardiac arrest. Human clinical trials employing earlier DMVA application are required to determine its resuscitative potential.

Blood Pressure

Prospective study of psychiatric morbidity in HIV-seropositive women without AIDS.

Prospective studies of psychiatric morbidity in HIV-seropositive women without AIDS have not been previously reported. As part of a 5-year longitudinal study, psychiatric diagnoses are described in 20 employed, educated women who are not intravenous drug abusers. This population is markedly different from the urban, minority, intravenous drug dependent groups previously studied and may be more representative of women who acquire the virus through heterosexual contact. Heterosexual transmission was the rule; 20% had HIV-seropositive spouses. All women were largely asymptomatic and in the early stages of infection. Mean length of knowledge of seropositivity was 14.4 months. Fifty percent were found to have an Axis I diagnosis (35% if minor diagnoses are excluded). None developed major depression or became dependent on drugs; 5% abused alcohol. Fifteen percent exhibited subtle signs of cognitive decline. Suicidal behavior and psychiatric hospitalization were absent. Sexual functioning was disrupted in a majority, with 20% meeting criteria for new onset hypoactive sexual desire disorder. Consistently "safe sex" practices were adhered to in 40%; in spite of intensive and repeated HIV education, 60% engaged in unprotected intercourse after knowledge of seropositivity. Progression of HIV infection was found to be three times faster than in a comparable male sample.

Adult

Associations between cerebrospinal fluid parameters and high degrees of anxiety or depression in United States Air Force personnel infected with human immunodeficiency virus.

The relationship between anxiety and depression, and serum and cerebrospinal fluid (CSF) immune parameters was studied in 98 patients randomly selected from those undergoing routine medical evaluation for human immunodeficiency virus seropositivity as part of the U.S. Air Force's mandatory screening program. A total of 95% of the sample did not have acquired immunodeficiency syndrome (AIDS). The population was subdivided into high and low anxiety or depression groups for statistical purposes. Significant correlations were obtained between high Hamilton Rating Scale for Depression scores (greater than 10) and CSF nucleated cell count and protein levels. High Hamilton Rating Scale for Anxiety (greater than 10) scores were positively correlated with CSF nucleated cell count and absolute CD4a counts. There were no statistically significant group differences with respect to mean laboratory values between high and low anxiety or depression subgroups. Serum viral titers to Epstein-Barr virus and cytomegalovirus were not correlated with anxiety or depression scores. These results suggest a complex relationship between CSF and systemic immune abnormalities and degree of anxiety and depression.

Adult

Improved synthetic routes to the novel thromboxane receptor antagonist ICI 192605: activity of synthetic 1,3-dioxane intermediates.

A study of the synthetic routes to the thromboxane receptor antagonist ICI 192605 4(Z)-6-(2-o-chlorophenyl-4-o-hydroxyphenyl-1,3-dioxan-cis-5-yl) hexenoic acid is described which led to an improvement in overall synthetic yield from 20 to 55%. Invitro thromboxane receptor antagonist data are reported for the novel 1,3-dioxane synthetic intermediates. These data indicated that shortening of the side chain in an appropriately substituted 2,2-dimethyl-1,3-dioxane (e.g. ICI 180080) from a heptenoic acid, to a hexenoic acid, had little effect on thromboxane receptor antagonist potency (pA2 = 7.5 rabbit thoracic aorta for the heptenoic acid ICI 180080 and pA2 = 6.9 for the corresponding hexenoic acid. Human platelet aggregation pA2 values were 6.7 and 7.0, respectively).

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5

Synthesis and resolution of the novel appetite suppressant 2-benzylmorpholine, a nonstimulant isomer of phenmetrazine.

The synthesis of 2-benzylmorpholine from allylbenzene together with its resolution into its (+)- and (-)-enantiomers is reported. Oral dosing of the racemate to dogs caused appetite suppression with an ED50 of 3 and 5.5 mg kg-1 at 1 and 2 h, respectively, after access to a meat meal. No stimulant activity was observed in dogs given oral doses of 200 mg kg-1 but the appetite suppressant effect in dogs declined during 20 days of chronic oral dosing at 10 mg kg-1. Appetite suppression activity was shown to reside in the (+)-enantiomer.

Administration, Oral