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Biomedical subjects

D Garver

Publications and source records attributed to D Garver.

At least 19 recordsLinked to original sources
PubMed2001

When symptoms persist: clozapine augmentation strategies.

Recent data and clinical experience confirm that, in spite of superior efficacy for treatment-refractory schizophrenia, a substantial proportion of patients receiving clozapine will continue to experience disabling symptoms. Optimizing clozapine monotherapy is the first step in the management of "clozapine nonresponders." Described here is a synthesis of the available literature on the range and efficacy of clozapine augmentation strategies that may be used when monotherapy fails. Treatment options include adjunctive antipsychotic medications, mood stabilizers, selective serotonin reuptake inhibitors, glycinergic agents, and electroconvulsive therapy. The evidence favoring one augmentation strategy over another is lacking; overall, adjunctive therapy is associated with only modest clinical improvement. Moreover, case series and open-labeled clinical trials dominate the extant literature, and there is a dearth of double-blind trials comparing these augmentation agents. Current systematic efforts to enhance the treatment of these patients with adjunctive therapies are worthy of being studied in carefully conducted clinical trials.

Antipsychotic Agents↗
PubMed2000

An assessment of clinical practice of clozapine therapy for veterans.

Clozapine therapy for 2,996 patients with treatment-refractory schizophrenia was examined over a five-year period in the Veterans Affairs health care system. Patients were assessed with the Brief Psychiatric Rating Scale (BPRS) and the Abnormal Involuntary Movement Scale (AIMS). BPRS scores, which were available for 522 patients, indicated a significant improvement, as did AIMS scores, which were available for 252 patients. Compared with individuals who showed a modest improvement, those with a more robust response to clozapine had higher initial BPRS scores and were three times more likely to have been suicidal in the month before starting clozapine therapy.

Adult↗
PubMed1998

Nicotinic receptor desensitization and sensory gating deficits in schizophrenia.

BACKGROUND: Nicotinic receptor dysfunction is a possible mechanism of the abnormal sensory gating observed in schizophrenia with the P50 auditory event-related potential. Although nicotinic receptors normally desensitize after activation by acetylcholine or nicotine, pathologically increased desensitization might cause receptor dysfunction in schizophrenia. To examine this possibility, central cholinergic neuronal activity was diminished by allowing schizophrenic patients to sleep briefly, after which they experienced a transient period of normal P50 gating, consistent with receptor resensitization during the absence of cholinergic stimulation. A critical test of the mechanism is whether this resensitization is blocked by concurrent administration of nicotine, which would provide continuous receptor stimulation. METHODS: Six schizophrenic patients repeated the sleep experiment during nicotine exposure from a dermal patch, in a double-blind, placebo-controlled design. RESULTS: The normalization of P50 gating immediately postsleep was replicated in the placebo arm, but this effect was decreased in all six patients during exposure to nicotine. CONCLUSIONS: The results suggest that nicotinic receptor desensitization is responsible for the loss of P50 gating in schizophrenia.

Acoustic Stimulation↗
PubMed1998

Clozapine therapy for older veterans.

OBJECTIVE: The effectiveness of clozapine treatment in a treatment-refractory sample of older adult veterans with primary psychosis was examined. METHODS: Data were collected over a five-year period for patients age 55 and older who were given clozapine because of a history of treatment-refractory or treatment-intolerant psychosis. At initiation of clozapine therapy, baseline demographic, clinical, and psychopathology data were collected. At baseline and quarterly, patients' psychopathology was rated with the Brief Psychiatric Rating Scale (BPRS), and involuntary movements were rated with the Abnormal Involuntary Movement Scale (AIMS). RESULTS: The 329 patients age 55 or older who received clozapine during the study period represented 10 percent of all patients on clozapine therapy in the VA system. Of the 312 patients for whom demographic information was available, 294 were men and 18 were women. Overall, patients improved on clozapine therapy, although wide variation in drug response was observed. Complete BPRS and AIMS data were available for 97 patients. The 55- to 64-year-old group had a mean improvement in total BPRS score of 19.8 percent, with 42.6 percent showing more than a 20 percent improvement; those age 65 and older had a mean improvement of 5.7 percent, with 17.2 percent showing an improvement greater than 20 percent. The 97 patients with complete AIMS data showed a mean improvement of 16.6 percent in total score. CONCLUSIONS: Clozapine is an important therapeutic agent for older adults with treatment-refractory psychosis. Patients between the ages of 55 and 64 may have a better response than those age 65 and older.

Adult↗
PubMed1995

The epidemiology of prosthetic heart valves in the United States.

The Center for Devices and Radiological Health of the Food and Drug Administration, in collaboration with the National Center for Health Statistics, conducted the Medical Device Implant Supplement to the 1988 National Health Interview Survey, generating the 1st available population-based estimates of the use of prosthetic heart valves in the United States. The 1988 National Health Interview Survey was a massive, nationally representative cross-sectional survey that encompassed 47,485 households and 122,310 individuals. Data from the Medical Device Implant Supplement indicate that an estimated 253,283 persons with 279,175 heart valves were present in the civilian, non-institutionalized US population (population prevalence of 1.1/1,000, 95% CI 0.8-1.3). Prevalence of valve prostheses ranged from 0.2 per 1,000 in those age 44 and under to 5.3 per 1,000 in those 75 years of age and older. Age-adjusted prevalence of valve prostheses did not differ significantly according to sex, race, region of residence, education, or income of recipients. Two thirds of aortic valve recipients identified by the survey were male, compared with only one third of mitral valve recipients. Approximately two thirds of both aortic and mitral valve implants were reported as mechanical. Reported use of anticoagulative agents was significantly more common in recipients of mechanical than of bioprosthetic valves. The single most common reported reason for prosthetic valve implantation was rheumatic heart disease. These data provide useful epidemiologic and public health planning information on prosthetic heart valve use.

Adult↗
PubMed1993

Familial differences between rapid neuroleptic response psychosis and delayed neuroleptic response psychosis.

Recent data suggest that latency of neuroleptic response may be used to separate distinct subtypes of psychotic disorders. In this preliminary study we contrast family patterns of illness of rapid neuroleptic response psychotics and delayed neuroleptic response psychotics. The data show that first-degree relatives of delayed neuroleptic response psychotics evidence higher levels of psychiatric disorder than rapid responders: relatives of delayed neuroleptic response psychotics evidenced a morbid risk for schizophrenic-spectrum disorder that was more than twice as high as the morbid risk for such disorders among relatives of rapid neuroleptic response psychotics. Relatives of delayed neuroleptic responders that received a diagnosis of schizophrenia, schizoaffective, or schizophreniform disorder evidenced significantly more residual impairment than schizophrenic-spectrum relatives of rapid neuroleptic responders. These preliminary data indicate the possibility that latency of therapeutic response to neuroleptic medication may be used to discriminate two familially distinct psychotic disorders and they suggest that delayed neuroleptic response may characterize a familially transmitted poor-outcome disease.

Adult↗
PubMed1993

The course of DSM-III-R schizophreniform disorder.

This study compared the course of illness of 36 patients who received a diagnosis of either DSM-III-R schizophreniform disorder or schizophrenia. Approximately 3.5 and 4.0 years after their index hospitalization, the two groups were compared for differences in positive and negative symptoms of psychosis, interpersonal and occupational role functioning, and other aspects of the deficit state. Multivariate data analyses indicate that the course of illness of the two groups is significantly different (p < .007), and the data also indicate that patient symptoms and functioning changed significantly over time (p < .008). The schizophreniform patients showed a low level of negative symptoms at both follow-ups; schizophrenics initially showed a higher level of negative symptoms, but these symptoms decreased significantly over time (p < .04). These data indicate that the course of DSM-III-R schizophreniform disorder is distinct from the course of schizophrenia.

Activities of Daily Living↗
PubMed1990

Histamine receptors in human fibroblasts: inositol phosphates, Ca2+, and cell growth.

Histamine stimulated inositol phosphate formation by human skin fibroblasts. The effect of histamine was reduced but still readily apparent in the absence of extracellular Ca2+. Histamine caused a transient increase in intracellular free Ca2+ as detected by indo-1 and fura-2 fluorescence studies on cell populations and on individual cells. Similar increases were observed in the absence of extracellular Ca2+, indicating that the effect was primarily due to mobilization of Ca2+ from intracellular stores, presumably by inositol trisphosphate (IP3). The effects of histamine on phosphoinositide metabolism and intracellular Ca2+ were inhibited by pretreatment of the cells with phorbol esters, suggesting that the histamine receptor in fibroblasts is subject to feedback regulation by protein kinase C. Histamine inhibited the incorporation of [3H]-thymidine into DNA. The effects of histamine on inositol phosphate formation, intracellular Ca2+, and thymidine incorporation were blocked by the H1 receptor antagonist mepyramine. Our results indicate that human skin fibroblasts have H1 receptors coupled to the formation of inositol phosphates and mobilization of intracellular Ca2+. We suggest that this H1 receptor also mediates a block of the cell cycle and that histamine may play a physiological role in the regulation of fibroblast proliferation.

Aminopyridines↗
PubMed1989

RBC lithium transport in the psychoses.

In vitro and in vivo red blood cell (RBC) lithium (Li+) intracellular/extracellular ratios were determined in 93 DSM-III schizophrenics (SCZ) in 47 DSM-III schizophreniform disorder patients (SF), in 22 DSM-III bipolar manics (M), in 15 affective disorders patients with mood-incongruent psychotic features (AD-MIP), and in 40 normal controls. There were no significant differences among groups in the in vitro Li+ ratio. Similarly, there was no significant difference among patient groups in the in vivo Li+ ratio. Furthermore, there was no significant difference in the mean Li+ ratios between the Li+-responsive and nonresponsive schizophrenic-like subjects. However, the distribution of Li+ ratios (both in vitro and in vivo) in the Li+-responsive group was significantly abnormal, showing more ratios in the extremes of the distribution (a platykurtic distribution).

Bipolar Disorder↗
PubMed1988

Lithium transport in human fibroblasts: relationship to RBC lithium transport and psychiatric diagnoses.

Cultured fibroblasts were prepared from six normal controls, five DSM-III manic patients, and six DSM-III schizophrenic patients. Lithium (Li+) uptake, 24-hour Li+ ratios, and steady-state membrane potential were measured in these cell lines. The uptake of 10 mM Li+ reached maximum at 2 hours, with an intracellular concentration of approximately 15 mM. No significant difference in uptake was found among subject groups. Twenty-four hour Li+ (ratio of intracellular/extracellular Li+) ratios were determined by incubating the cell lines for 24 hours in the presence of 2 mM Li+. No significant difference was observed among groups; nor was there any significant correlation between the fibroblast 24-hour ratios and 24-hour in vitro ratios determined in donor red cells. The relationship between membrane potential and the 24 hour Li+ ratio in fibroblasts was determined. The average potential in these cell lines was -56 mV and was not affected by Li+ treatment. No correlation between the Li+ ratio and membrane potential was found.

Adult↗
PubMed1987

Weight loss, cortisol levels, and dexamethasone suppression in major depressive disorder.

Appetite and/or weight loss are integral, albeit not necessary, symptoms of depression. We explored the contribution of diminished appetite and/or weight loss ascertained by history to the hypothalamic-pituitary-adrenocortical (HPA) axis dysregulation in 120 patients with primary major depressive disorder. Significant positive relationship for both appetite and weight loss with cortisol levels in plasma and cerebrospinal fluid (CSF) were observed. Plasma cortisol levels were consistently higher in patients who noted both appetite and weight loss as opposed to patients without appetite or weight loss. Depressed patients with weight loss showed higher rates of dexamethasone-nonsuppression. Age and severity of depression influenced but did not eliminate the significance of the findings, suggesting that weight loss accounts in part for the HPA-axis function changes observed in depression.

Adult↗
PubMed1985

Characteristics of phospholipid methylation in human erythrocyte ghosts: relationship(s) to the psychoses and affective disorders.

Recent studies have shown that patients with a schizophrenic-like illness have a significant deficit in erythrocyte ghost membrane (EGM) phosphatidylcholine (PC); patients with the most severe deficiency showed a marked decrease in Na+-Li+ counterflow activity (Hitzemann et al. 1984a and b). The present study was undertaken to see if the decrement in PC is associated with a decrease in phospholipid methylation activity. Phospholipid methylation in human EGMs is distinctly different from that in rat EGMs (Hirata and Axelrod 1980) in that the human activity is not Mg++-dependent, and apparent methyltransferase I activity is located in the external membrane surface. The patient population consisted of 20 DSM-III schizophrenics (SCZ), 13 DSM-III schizophreniform (SF) disorder patients, and 11 DSM-III manics (M). Twelve age- and sex-matched controls were used for the comparison group. Methylation activity was significantly decreased in all three patient groups, although the M group had significantly higher activity than the SF group. Twenty-four of the SCZ and SF patients entered a Li+ trial. The Li+ responder group (n = 8) showed significantly lower activity than the nonresponder group (n = 16). Overall, we conclude that the decrement in phospholipid methylation activity partially contributes to the decrement in PC levels.

Adult↗
PubMed1985

Familial differences in lithium responsive versus lithium nonresponsive psychoses.

Psychiatric life histories of 218 first degree family members of 16 lithium responsive and 33 lithium non-responsive psychotic (mood incongruent) probands were contrasted. While the morbid risk of schizophrenic spectrum disorder was 9.8% in the 142 relatives of lithium nonresponsive probands, no cases of schizophrenic spectrum disorder were found among the 76 first degree relatives of lithium responsive psychotics (p less than 0.03). Lithium responsive psychotic illnesses appear to be familially, and perhaps genetically distinct from the bulk of the schizophrenias.

Bipolar Disorder↗
PubMed1984

Membrane abnormalities in the psychoses and affective disorders.

Erythrocyte ghost phospholipid data were collected on 67 psychotic and/or manic patients and compared to a group of 35 age and sex matched controls. Patients meeting DSM-III criteria for schizophreniform disorder or schizophrenia but not mania showed a small but significant decrease in membrane phosphatidylcholine (PC). In 53 of the patients data were available on lithium transport across red cell membranes. Patients in the upper quartile of the PC distribution showed a significant (-47%) decrease in the 24 h in vitro lithium ratio as compared to patients in the lower PC quartile. This difference was due to an increase in Na-Li+ counterflow activity in the upper PC quartile and not to a change in passive lithium leak. These data illustrate one example of a possible relationship between membrane composition and a membrane function, counterflow activity, which has been associated with the underlying mechanism(s) of lithium action.

Adult↗
PubMed1984

Membranes, methylation and lithium responsive psychoses.

Data are presented showing that the erythrocyte ghost membranes of lithium-responsive and non-responsive schizophrenic-like patients are different from control membranes. In both groups of patients there was a significant decrement of phosphatidylcholine (PC) which was largely compensated for by an increase in sphingomyelin. The decrement in PC may in part be associated with a decrease in phospholipid methylation which converts phosphatidylethanolmine (PE) to PC. Interestingly, in the lithium-responsive but not the non-responsive patients, lithium stimulates methylation activity. This stimulation may affect a variety of membrane functions, e.g. adenyl cyclase activity, which would be involved in lithium's therapeutic actions.

Blood Platelets↗
PubMed1983

Comparative efficacy and safety of bupropion and placebo in the treatment of depression.

This was a 4-week, three-center, double-blind, randomized, parallel, placebo-controlled evaluation of the efficacy and safety of bupropion in hospitalized depressed patients. Results from 27 placebo and 48 bupropion-treated patients were analyzed for efficacy and safety. Assessments of efficacy and safety were made at baseline and weekly during the study. Preliminary and secondary measures of efficacy included the Clinical Global Impressions for severity (CGI-S) and improvement (CGI-I) of illness, Hamilton Depression and Hamilton Anxiety Scales, and the Zung Self-Rating Scales for depression and anxiety. Assessments of safety included vital signs, electrocardiogram, clinical laboratory tests, and adverse experiences. Dosages of bupropion were 300-600 mg/day. Results showed that bupropion was significantly (P less than 0.01) more effective than placebo at termination of study on the CGI-S, CGI-I, Hamilton Depression and Hamilton Anxiety Scales. On the Zung Self-Rating Depression and Anxiety Scales, statistical trends favored bupropion at termination of study over placebo (P less than 0.10). Adverse events in the bupropion and placebo groups were minimal with notable absence of sedation and anticholinergic- and cardiovascular-related side effects. We conclude that bupropion was significantly more effective than placebo in treating depression and accompanying anxiety in depressed inpatients.

Adult↗
PubMed1983

Plasma and erythrocyte electrolytes in affective disorders.

Plasma and erythrocyte sodium (Na+), total and free (ultrafiltrable) plasma magnesium (Mg2+) as well as erythrocyte magnesium were measured in patients with affective disorders and in healthy control subjects. Depressed and manic patients had higher total plasma Mg2+ than did hospitalized healthy control subjects, but concentrations of ultrafiltrable Mg2+ did not differ. Although erythrocyte Mg2+ was significantly elevated in the depressed subjects in comparison with that found in the non-hospitalized healthy controls, this difference was not seen between the depressives and the hospitalized healthy controls. Depressed, manic or healthy control subjects did not differ with respect to either plasma or erythrocyte.

Adult↗