Anesthetic management of cleft lip and cleft palate.
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Biomedical subjects
Publications and source records attributed to P K Mukherjee.
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Fine needle aspiration biopsy cytology of salivary gland tumours was performed in 97 patients. Histological confirmation was available in all cases except 9 cases of sialo-adenitis which responded to antibiotics. Accuracy of cytological diagnosis in exact categorisation of benign and malignant tumours was 93.7% and 91.1% respectively. False negative was 4.1%. The overall accuracy was 95.8%. There was no false positive report. Exact classification of tumour was made in 94.1% cases, ie, 80 out of 85 tumours. No complication was encountered in this procedure.
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Indomethacin blocks the biosynthesis of vesicular stomatitis virus (VSV) at the level of primary transcription, RNA replication, and protein synthesis (P. K. Mukherjee and R. W. Simpson (1985), Virology 140, 188-191). Nucleocapsids of infecting virus particles recovered from indomethacin-treated cells were analyzed for in vitro transcriptase activity. Incorporation of [3H]UTP in mixtures containing nucleocapsids from HEp-2 cells pretreated with 10(-3) M indomethacin was inhibited approximately 80% compared to control reactions containing nucleocapsids from untreated infected cells. The level of inhibition of in vitro transcriptase activity of viral nucleocapsids from drug-treated cultures varied according to the cell line used for infection. After indomethacin removal, cells regained their ability to produce enzymatically competent viral-transcribing complexes unless they were subsequently exposed to metabolic inhibitors such as actinomycin D or alpha-amanitin. Enzymatically defective nucleocapsids from indomethacin-treated cells showed enhanced in vitro transcriptase activity in the presence of modulators of prostaglandins and cyclic nucleotides. Electrophoretic analysis of product from in vitro transcriptase reactions revealed that these defective nucleocapsids are unable to synthesize VSV messenger RNA or normal size leader RNA species but only smaller transcripts of undetermined identity.
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An assessment of the efficacy and tolerability of zuclopenthixol dihydrochloride tablets in the treatment of acute psychotic episodes was undertaken in 63 patients in an open multi-centre study. Most patients prior to entering the study had received other neuroleptic drugs, but with inadequate effect. During the 10-week study, the dosage of zuclopenthixol dihydrochloride tablets could be adjusted to obtain optimum clinical benefit. The majority of patients received 20 to 75 mg daily (range 10 to 150 mg daily) at the start of the study and later, for most of those patients successfully treated, the dosage was 20 to 55 mg daily. Assessments before and during treatment utilized the BPRS and CGI rating scales and a check-list of side-effects. A successful response to treatment was achieved in 70% of 50 patients with schizophrenia or schizophreniform psychoses and in 69% of 13 patients with mania or hypomania. Almost half (30) of the patients studied had a successful response within 4 weeks of starting treatment and some after only 1 week of treatment. All patients but 1 had either no side-effects or side-effects not overtly affecting performance.
We investigated the comparative efficacy and tolerance of two initial starting doses of trazodone in 20 elderly inpatients suffering from depressive illness. The first 2-week phase was double-blind. Patients received either 25 mg trazodone tds or 50 mg tds. After this time the study was open, the dose of trazodone being titrated from the initial starting dose to maximise efficacy and tolerance. Patients received study medication for a total of 6 weeks. Assessments for efficacy included the Hamilton Depression rating scale, Zung anxiety scale, visual analogue scales for depression, euphoria and tension, and global assessments of severity and improvement of condition. Tolerance was assessed by means of a checklist of symptoms and adverse effects. Assessments were performed at base line and at weekly or bi-weekly intervals thereafter. A total of 18 patients were included in the analysis. The Zung and visual analogue scales indicated significant superiority for the high-dose group at Week 2. The Hamilton ratings indicated significant superiority for the high-dose group at Week 6 with a strong trend in favour of the high dose group at Week 2. Measures of severity of illness and improvement indicated more rapid improvement over time in the high-dose group. The treatment was generally well tolerated and at no time did adverse events outweigh therapeutic benefit. The incidence of headache and nausea was more frequent in the high-dose group in the first 2 weeks. The group of elderly patients studied benefited from trazodone therapy initiated at a higher therapeutic dose. This dose (150 mg total daily) was well tolerated and proved effective over the course of 6 weeks' treatment.
Treatment of HEp-2 cells with 10(-3) M indomethacin prior to infection with vesicular stomatitis virus (VSV) blocked synthesis of viral RNA species and proteins. Host cell macromolecular synthesis was also inhibited by this antagonist of prostaglandin metabolism. The reversibility of this drug-mediated inhibition was a time-dependent process that could be prevented after removal of indomethacin if cells were exposed to low concentrations of cycloheximide which do not normally interfere with VSV replication. That indomethacin exerts its inhibitory effect at an early stage of infection is suggested by the finding that this drug can compromise viral transcription either in vitro or in vivo.
Papaverine, an inhibitor of cAMP phosphodiesterase, reduced yields of infectious vesicular stomatitis virus in HEp-2 cells approximately 100-fold if added to cultures at a concentration of 30 microM before and after virus infection. The extent of papaverine-induced suppression of viral growth was dependent on drug dose and treatment regimen. Cells progressively recovered their viral permissive state after removal of drug. The cyclic nucleotide, cGMP, nullified the inhibitory effect of papaverine if added to cells during drug treatment. Pulse labeling experiments with [35S]methionine showed that papaverine compromises production of all virus-specific proteins in infected cells without adversely affecting host cell protein synthesis. Treatment of cells with papaverine strongly inhibited the production of viral RNA and both cellular RNA and DNA. It was found that VSV causes an immediate but transient stimulation of DNA synthesis in HEp-2 cells which is prevented by papaverine treatment. This drug also selectively blocked primary transcription of VSV in vivo and to a lesser extent in vitro RNA polymerase activity of the virion-bound transcriptase. The finding that papaverine has a strong inhibitory effect on viral biosynthesis including early transcription suggests that VSV replication may depend on host factors that regulate intracellular levels of cyclic nucleotides such as cAMP.
Indomethacin, a potent nonsteroidal inhibitor of prostaglandin synthetase (cyclooxygenase) reduced yields of infectious vesicular stomatitis virus in HEp-2 cells more than 99% if added to cultures at levels of 10(-3)M either before or after infection. Other permissive cell lines differed according to the treatment period and drug level required for restricting productive infections. The inhibitory effect of indomethacin was progressively reduced if infection of cells was delayed for increasing times after drug removal. Strong inhibition of viral replication also occurred in cells treated with the cyclooxygenase antagonists naproxen, phenylbutazone, and oxyphenylbutazone whereas phenacetin, which does not block cyclooxygenase function, was inactive. Enhanced viral replication occurred in indomethacin-treated HEp-2 cultures when these cells were subsequently exposed to such substances as prostaglandin E1, cyclic AMP, or insulin. Conversely, indomethacin-treated cells remained restrictive for VSV if they were subsequently exposed to metabolic inhibitors of functional DNA (actinomycin D or mitomycin C), messenger RNA synthesis (alpha-amanitin), or protein synthesis (cycloheximide) at concentrations that normally do not compromise viral replication. Pretreatment of HEp-2 cells with mitomycin C markedly shifted the dose response for indomethacin-mediated inhibition of VSV from a 90% inhibitory dose of about 10(-4)M to one of 10(-9)M or lower. These findings suggest that preexisting host factors essential for replication of VSV, although rendered nonfunctional by the drug indomethacin, can be replenished unless their synthesis is blocked by various classes of metabolic inhibitors.
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Forty patients with primary chronic alcoholism took part in a randomized, double-blind, comparative group study of clobazam and chlordiazepoxide in the treatment of acute alcohol withdrawal. Assessments were carried out during an initial in-patient week followed by a week of out-patient assessments. Both benzodiazepines were shown to be highly effective when compared with baseline measurements. However, the Hamilton Anxiety Rating Scale showed clobazam to be more effective than chlordiazepoxide at both 7 days (p = 0.03) and 14 days (p less than 0.05). The clobazam group showed significant improvements compared with baseline for all four factors of the Leeds Sleep Evaluation Questionnaire, whereas the chlordiazepoxide group showed a significant improvement in only one factor. At the end of the in-patient week, clobazam showed a significant improvement (p less than 0.01) compared to chlordiazepoxide for the Linear Analogue Rating Scale of anxiety/tension. The 1,5 benzodiazepine clobazam has been shown to be a valuable addition to currently available regimens when used alone in the treatment of acute alcohol withdrawal, especially during the initial period where anxiety and insomnia related symptoms are at their peak.
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