Search PubMed⌕ Search

Biomedical subjects

S C Mann

Publications and source records attributed to S C Mann.

At least 19 recordsLinked to original sources
PubMed2000

Residual catatonic state following neuroleptic malignant syndrome.

Neuroleptic malignant syndrome (NMS) is usually a self-limited disorder, with most cases resolving within 2 weeks after antipsychotic drug discontinuation. However, the course of NMS may not always be short-lived. In this report, the authors describe five patients who developed a residual catatonic state that persisted after acute hyperthermic symptoms of NMS had subsided and compare them with 27 similar cases in the literature. Two of our patients recovered gradually with supportive treatment. Three patients were treated with electroconvulsive therapy (ECT). Of these, two showed a positive response, although one died later of intercurrent pneumonia. A third patient did not respond to ECT, but recovered gradually thereafter. Although dopamine agonists or benzodiazepines have been advocated for the treatment of residual symptoms in previous case reports, ECT was the treatment most often associated with a rapid response and no mortality, even in patients refractory to pharmacotherapy. In conclusion, catatonic and parkinsonian symptoms of NMS may persist as a residual state lasting for weeks to months after more fulminant acute symptoms abate. These residual symptoms may be more likely to develop in patients with pre-existing structural brain disorders. Although patients may improve gradually with supportive care or pharmacotherapy, ECT can often be highly effective in treating the residual catatonic state that follows NMS.

Adult↗
PubMed1995

Fatal pulmonary embolism in the catatonic syndrome: two case reports and a literature review.

BACKGROUND: Catatonia is associated with excess early mortality when it is unrecognized or inadequately treated. The characteristics of the lethal catatonia subtype are now well described, but the excess mortality of the remaining patients with catatonic syndrome, particularly from pulmonary embolism, appears to be inadequately recognized. The fatal risk of the catatonic syndrome is reviewed. METHOD: Two new case reports of sudden death from pulmonary embolism in catatonic syndrome are presented. The world literature on morbidity, mortality, and pulmonary embolism in catatonia was reviewed by a search of MEDLINE and PsychInfo from 1966 to the present. Additional older references were discovered by screening bibliographies from articles produced by the searches. RESULTS: Twenty cases of autopsy-confirmed pulmonary embolism were found in patients with catatonic syndrome. Catatonic patients were more likely to die of pulmonary embolism and die earlier than patients with other types of schizophrenia. Death from pulmonary embolism did not occur until after the second week of catatonic symptoms and often occurred without warning. CONCLUSION: Risk of a fatal pulmonary embolism is inherent in persistent catatonic symptoms and may explain the observed excess early mortality. Prompt resolution of the catatonic syndrome with benzodiazepines, barbiturates, or electroconvulsive therapy is the best way to reduce risk of pulmonary embolism. The prophylactic value of physical therapy or anticoagulation merits further investigation. Despite the absence of controlled trials of treatment effectiveness, the catastrophic outcome of acute pulmonary embolism warrants early and vigorous intervention in catatonic patients.

Adult↗
PubMed1994

Progression of symptoms in neuroleptic malignant syndrome.

The neuroleptic malignant syndrome (NMS) is a rare but potentially fatal disorder characterized by mental-status changes, muscle rigidity, hyperthermia, and autonomic dysfunction. Systematic examination of early signs and the progression of symptoms in NMS may be worthwhile to facilitate prompt recognition and interventions to abort the syndrome in its incipient stage. The authors present the results of a preliminary review of the temporal sequence of the four predominant signs of NMS as described in 340 clinical reports of NMS in the literature. Of all order implications, 70.5% were consistent with the sequence of mental-status changes, rigidity, hyperthermia, and autonomic dysfunction. Changes in either mental status or rigidity were the initial manifestations of NMS in 82.3% of cases with a single presenting sign and were significantly more likely to be observed before hyperthermia and autonomic dysfunction. Methodological limitations of these data and clinical implications are discussed.

Adolescent↗
PubMed1993

Neuroleptic malignant syndrome.

Neuroleptic malignant syndrome is a rare but potentially fatal reaction associated with neuroleptic drugs. It occurs in about 0.2% of patients treated with neuroleptics. Risk factors include previous episodes, dehydration, agitation, and the rate and route of neuroleptic administration. Although NMS has been reported in patients with diverse psychiatric diagnoses, as well as in normal subjects, patients with organic brain disorders or mood disorders, particularly when receiving lithium, may be at increased risk. Standardized criteria for the diagnosis of NMS have been developed and emphasize the classic findings of hyperthermia, muscle rigidity, mental status changes, and autonomic dysfunction. The syndrome lasts 7 to 10 days in uncomplicated cases receiving oral neuroleptics. Treatment consists primarily of early recognition, discontinuation of triggering drugs, management of fluid balance, temperature reduction, and monitoring for complications. Use of dopamine agonists or dantrolene or both should be considered and may be indicated in more severe, prolonged, or refractory cases. Electroconvulsive therapy has been used successfully in some cases and is particularly useful in the post-NMS patient. As a result of these measures, mortality from NMS has declined in recent years although fatalities still occur. Neuroleptics may be safely reintroduced in the management of the majority of patients recovered from an NMS episode, although a significant risk of recurrence does exist, dependent in part on time elapsed since recovery and dose or potency of neuroleptics used. Data drawn from clinical observations and basic studies support the primary role of an acute reduction in brain dopamine activity in the development of NMS. Additional studies of facilitating cofactors may lead to innovative risk-reduction strategies and the development of safer neuroleptic drugs.

Age Factors↗
PubMed1991

Expression of the c-Ha-ras oncogene in mouse NIH 3T3 cells induces resistance to cisplatin.

The effect of expression of the c-Ha-ras oncogene on cisplatin (DDP) sensitivity was examined in murine NIH 3T3 cells transfected with the dexamethasone (DEX)-inducible mouse mammary tumor virus promoter linked to an activated c-Ha-ras gene [LTR H-ras(A) cells]. Treatment of these cells with 5 microM DEX for 24 h induced c-Ha-ras expression and produced an 8.2 +/- 1.3-fold (SD) increase in DDP resistance as quantitated by clonogenic assay. Induction of the c-Ha-ras oncogene reduced DDP accumulation by 40% and intrastrand adduct formation by 17%. In nontransfected wild-type NIH 3T3 cells, DEX did not induce DDP resistance nor did it decrease DDP accumulation. Induction of c-Ha-ras expression did not alter cellular glutathione content or the activity of glutathione-S-transferase in the LTR H-ras(A) cells. DEX increased cellular metallothionein content by 1.6-fold in NIH 3T3 cells and 3.3-fold in LTR H-ras(A) cells. We conclude that DEX-induced overexpression of a mutant c-Ha-ras gene confers DDP resistance and that this resistance is associated with an impairment of cellular drug accumulation and an increase in metallothionein content.

3T3 Cells↗
PubMed1991

Modulation of cis-diamminedichloroplatinum(II) accumulation and sensitivity by forskolin and 3-isobutyl-1-methylxanthine in sensitive and resistant human ovarian carcinoma cells.

We have determined the effect of forskolin, an adenyl cyclase agonist, and 3-isobutyl-1-methylxanthine (IBMX), a phosphodiesterase inhibitor, on the accumulation and cytotoxicity of cisplatin (DDP) in 2008 human ovarian carcinoma cells. In DDP-sensitive 2008 cells, forskolin and IBMX caused 2.1-fold and 2.3-fold increases, respectively, in the short-term accumulation of DDP relative to untreated cells. The inactive analogue, 1,9-dideoxyforskolin, decreased DDP accumulation. Forskolin and IBMX also increased accumulation in A2780 cells. Neither forskolin nor IBMX had any effect on DDP accumulation in DDP-resistant 2008 cells. The effects were detectable as early as 1 min and persisted at 60 min. The concentrations for half-maximal stimulation of DDP accumulation were approximately 0.2 microM for forskolin and 0.2 mM for IBMX. Forskolin caused marked increases in cAMP levels in both sensitive and resistant 2008 cells within 1 min, although there were differences in the subsequent time-courses of the response. Both 2008 cell types had identical cAMP-dependent protein kinase (PKA) activity. These results suggest that there is a target downstream of PKA that is an important participant in DDP accumulation, and that this target is defective or missing in DDP-resistant cells. Following a 1-hr exposure to drugs, forskolin and IBMX at concentrations that were by themselves completely non-toxic increased the slopes of the clonogenic survival vs. DDP concentration curves in 2008 cells 1.9-fold and 3.3-fold, respectively. In DDP-resistant 2008 cells, however, forskolin and IBMX increased the slopes only 1.2 and 2.6-fold, respectively. These effects of forskolin and IBMX on DDP cytotoxicity did not directly correlate with the effects on the 1-hr DDP accumulation which suggested that, in addition to modulating DDP accumulation, these agents increase the cytotoxicity of the intracellular platinum. The results indicate that modulation of cAMP levels can have important effects on DDP accumulation and cytotoxicity in 2008 cells and that these effects are significantly diminished in DDP-resistant cells.

1-Methyl-3-isobutylxanthine↗
PubMed1991

Role of the Na+, K(+)-adenosine triphosphatase in the accumulation of cis-diamminedichloroplatinum(II) in human ovarian carcinoma cells.

We examined the importance of the Na+, K(+)-ATPase in cisplatin (DDP) accumulation in 2008 human ovarian carcinoma cells and describe changes in the Na+, K(+)-ATPase in DDP-resistant cells with DDP accumulation defects. Approximately 50% of DDP accumulation was inhibitable by ouabain. DDP accumulation into 2008 cells could be maximally inhibited when cells were preincubated with ouabain for 1 h prior to DDP exposure. The half-maximal inhibition was obtained with 0.13 microM ouabain. Similar inhibition of DDP accumulation was obtained when the Na+, K(+)-ATPase was blocked by ATP depletion or by incubating cells in K(+)-free medium. This same percentage of DDP accumulation was Na+ dependent and varied directly with Na+ concentration. These effects on DDP accumulation could be detected as early as 1 min after the imposition of 0-trans conditions, strongly suggesting that the inhibition was due to modulation of a drug influx step. The Na+, K(+)-ATPase in 2008/DDP cells had a similar KD for ouabain binding and 36% less Na+, K(+)-ATPase molecules/mg of protein than 2008 cells. 2008/DDP cells 2.3 +/- 0.2 (SE, n = 3) fold cross-resistant to ouabain in a continuous exposure clonogenic assay. Despite these changes in the Na+, K(+)-ATPase, the net basal Na+, K(+)-ATPase activity was the same in sensitive and DDP-resistant cells as determined by ouabain-inhibitable 86Rb+ influx. The basal Na+ levels were also similar in the sensitive and resistant cells. These data suggest that DDP accumulation is partially Na+ dependent and that, therefore, the Na+, K(+)-ATPase which maintains the Na+ gradient may play an important role in determining how much DDP enters cells. Whether there is a causal link between the changes in the Na+, K+-ATPase in DDP-resistant cells and their DDP accumulation defect is not yet known.

Cisplatin↗
PubMed1990

Short-term cis-diamminedichloroplatinum(II) accumulation in sensitive and resistant human ovarian carcinoma cells.

We examined the short-term accumulation of cisplatin (DDP) in sensitive 2008 human ovarian carcinoma cells and in a 2- to 3-fold DDP-resistant and accumulation-deficient variant. During the 1st min of exposure to 500 microM DDP, sensitive cells accumulated platinum at a rate of 187 +/- 63 pmol/mg protein per min, whereas resistant cells accumulated platinum at 123 +/- 85 pmol/mg protein per min, a rate that was 66% that of sensitive cells. From 2-10 min of exposure, sensitive and resistant cells accumulated the drug at rates of 51.4 +/- 21.5 and 34.0 +/- 9.70 pmol/mg protein per min, respectively. In resistant cells, this rate again represented 66% that of sensitive cells. For each cell line, the DDP accumulation was 3.6 times faster during the 1st min than it was over 2-10 min. Initial DDP accumulation was linear with drug concentration in each cell line. Efflux measurements were made over a 50-min period after a 10-min load in 500 microM DDP. The loss of platinum was biphasic in each cell line, with an initial, rapidly effluxing component being lost within 10 min in each cell line. The rate constant for loss of platinum from this rapidly effluxing pool, measured after a 10-min loading period in 500 microM DDP, was 0.67 +/- 0.09 s-1 in sensitive cells and 1.03 +/- 0.15 s-1 (a 53% increase) in resistant cells. Between 5 and 50 min of an accumulation time course in 500 microM DDP, the size of the rapidly effluxing platinum pool remained relatively constant in each cell line, with the major contribution to the increase in total platinum over time coming from growth of the slowly effluxing platinum pool. We conclude that diminished retention of platinum in the rapidly effluxing pool of resistant cells is a major determinant of decreased DDP accumulation in these cells.

Cisplatin↗
PubMed1988

cis-Diamminedichloroplatinum(II) accumulation in sensitive and resistant human ovarian carcinoma cells.

We have characterized the accumulation of cisplatin (DDP) into parent and cisplatin-resistant 2008 human ovarian carcinoma cells. Accumulation of DDP at 1 h was a linear function of concentration from 0.25 to 100 microM DDP in both cell types. DDP-resistant cells that were only 3.3-fold resistant had approximately 50% less accumulated platinum at all concentrations examined. Accumulation of 1.0 microM DDP was linear for approximately 3 h and then slowed but did not reach equilibrium at up to 24 h in either cell type. The decreased DDP accumulation in resistant cells did not appear to be due to increased efflux; similar percentages of platinum were available for exodus in parent and resistant cells. Intracellular metabolites of DDP appeared to be decreased by similar amounts in the resistant cells. Native DDP was not driven uphill into cells against a concentration gradient, suggesting that DDP uptake does not involve primary active transport. The metabolic inhibitors, dinitrophenol and NaF, did not decrease DDP accumulation; iodoacetate had a stimulatory effect. Dinitrophenol, however, in combination with NaF or iodoacetate decreased DDP accumulation. A 30-min exposure to 0.2 mM ouabain also decreased DDP accumulation in both parent and resistant cells. A component of DDP accumulation thus appears to be energy dependent. These studies have identified decreased DDP accumulation as an important mechanism of resistance that is expressed early in the acquisition of DDP resistance in human ovarian carcinoma cells.

Carcinoma↗
PubMed1987

Malignant hyperthermia susceptibility in neuroleptic malignant syndrome.

The relationship between neuroleptic malignant syndrome (NMS) and malignant hyperthermia (MH) was investigated using the in vitro skeletal muscle contracture test to screen for MH-susceptibility in NMS patients. The maximum contracture tension which developed following exposure to halothane (1-3%), and incremental doses of fluphenazine (0.2-25.6 mM) was measured in muscle obtained from seven NMS, six MH, and six control patients. Comparison of the cumulative responses to fluphenazine revealed no significant differences among the groups. However, the response (mean +/- SEM) to halothane in the NMS group (1.7 +/- 0.7 g), which was similar to the response in the MH group (1.5 +/- 0.2 g), was significantly greater than the response found in controls (0.2 +/- 0.1 g). In addition, five of seven NMS patients could be diagnosed as MH-susceptible, based on the development of muscle contractures greater than 0.7 g in response to 1-3% halothane. In contrast, none of the controls were MH-susceptible. These findings appear to correlate with clinical evidence suggesting an association between NMS and MH.

Adult↗
PubMed1986

Lethal catatonia.

Lethal catatonia, a life-threatening febrile neuropsychiatric disorder, was widely reported in this country and abroad before the introduction of modern psychopharmacologic treatments. A comprehensive review of the world literature indicates that although the prevalence of lethal catatonia may have declined, it continues to occur, now reported primarily in the foreign literature. Lack of recognition probably accounts for the scarcity of recent American reports. Furthermore, lethal catatonia is a syndrome rather than a specific disease and may develop in association with both functional and organic illnesses. Familiarity with the clinical features and varied etiologies is essential for effective management of this catastrophic reaction.

Adolescent↗