SELECTED SUMMARIES

formulations) as well as drug-prescribing by unqualifiedpersons and patient non-compliance due to financial con-straints.

This paper should serve as an important guide for resear-chers interested in investigating these factors.

REFERENCESWorld Health Organization. The rational use of drugs. Report of the Conferenceof Experts, Nairobi, 1985. Geneva:Worid Health Organization, 1987.

2 How to investigate drug use in health facilities: Selected drug use indicators.Geneva:World Health Organization, 1993, WHOIDAP/93;1:1-87.

3 Srishyla MY, Krishnamurthy M, Naga Rani MA, Clare M Sr, Andrade C,Yenkataraman BY. Prescription audit in an Indian hospital setting using theDDD (defined daily dose) concept. Indian J Pharmacol 1994;26:23-8.

DRD2 Ser3111Cys311 polymorphismin schizophrenia

Arinami T, Itokawa M, Enguchi H, Tagaya H, Yano S,Shimizu H, Hamaguchi H, Toru M. (Department of MedicalGenetics, Institute of Basic Medical Sciences, University ofTsukuba, Ibaraki; Department of Neuropsychiatry, TokyoMedical and Dental University; Department of Psychiatry,Hokushin General Hospital, Nakano, Nagano, Japan.)Association of dopamine D2 receptor molecular variant withschizophrenia. Lancet 1994;343:703-4.

SUMMARYThe authors examined the evidence for an association betweena dopamine D2 receptor variant and schizophrenia. Ser3111Cys311is a missense variant resulting from substitution of serine forcysteine at codon 311 in the third cytoplasmic loop of the receptor. I

This case-control study consisted of 156 schizophrenics (99 menand 57 women in the age range 17-75 years) and 300 controlsubjects. All patients met the American Psychiatric Associa-tion's Diagnostic and Statistical Manual of Mental Disorders(DSM-III-R) criteria for schizophrenia. The control subjects(age range 31-{;0 years; who were unrelated to the patients)consisted of 200 parents of hypercholesterolaemic children and100 individuals requesting annual physical check-ups. Genotypeassessment was done using the polymerase chain reaction(PCR). The products of PCR were digested and subjected togel electrophoresis.

The results indicated that Cys311 allele frequency wassignificantly greater in schizophrenics than in the controls.VThree of the 156 patients with schizophrenia were homozygousfor Cys311 compared to none of the controls. The tentativeodds ratio was 61 for Cys311, suggesting that the homozygousstate for Cys311 may substantially increase susceptibility toschizophrenia, the genetic transmission being in an autosomalrecessive manner with incomplete penetrance. Schizophrenicsin whom the disease onset was longer than 25 years, and thosewho had a positive family history, had a higher allele frequency .In those with a lower frequency of Cys311 there was incoherenceand irrelevance of speech, flattened incongruous affect andpsychomotor retardation. The patients with Cys311 schizophreniahad spent less time in hospital previously as well as during theircurrent admission.

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4 Bimo. Field testing of drug indicators: Report of a field trip to Indonesia,Bangladesh and Nepal, June-July, 1991. Boston: International Network forthe Rational Use of Drugs (INRUD), 1991.

5 A baseline su,vey on drugs use at primary health care level in Bangladesh.Dhaka:UNICEF, 1993.

S. K. BHATTACHARYAA. CHAKRABARTY

Department of PharmacologyInstitute of Medical Sciences

Banaras Hindu UniversityVaranasi

Uttar Pradesh

The authors suggest that the homozygous state may sub-stantially increase susceptibility to schizophrenia. They alsodifferentiated schizophrenia into sub-types based on symptoms.Thought disorder, flattened affect and psychomotor retardationwere less frequent in Cys311 patients. This and the shorterperiod of hospital stay (suggesting a better response to anti-psychotic drugs) indicate that Cys311 schizophrenia may beanalogous to the type I syndrome of schizophrenia. The authorsconclude that if the Ser311/Cys311 variant is confirmed andlinked to the functional change in the receptor this may helpin the elucidation of the pathogenesis of the disease and thedevelopment of methods to prevent it.

COMMENTGenetic factors in the aetiology of schizophrenia have longbeen explored with the help of family pedigree.? twin? andadoption studies." These have consistently suggested thatthe disease may have a genetic basis." Further research focusedon linkage studies has demonstrated an association betweenattributes with a known fixed genotype and schizophrenia.However, the initial results of these studies have not beencorroborated by later work. 5 With advancements in the fieldof molecular biology, the focus has now shifted to directstudies of the human genome.

The authors studied the association of a variant in thedopamine D2 receptor sequence with schizophrenia. Thechoice of the D2 receptor was appropriate as the dopaminetheory" is widely accepted as an explanation for this disorderand supported by a large volume of biochemical, pharma-cological and histochemical research. The D2 receptor islocated on the llq chromosome and at least one linkagestudy has found an association between porphobilinogendeaminase (PBGD) located distal to the D2 receptor geneon this chromosome and schizophrenia." The present studyis based on the fact that a missense variation in the D2receptor gene at position 311 was detected by the sameworkers earlier in a Japanese population. I The finding ofan association between the Cys311 allele frequency andschizophrenia suggests a functional change in the variantreceptor protein which may be aetiologically related to thisdisorder, Since schizophrenia is believed to be a heterogene-ous disease, the association of Cys311 with type I syndromeis even more meaningful than the overall association.

Four other studies on the same topic have been publishedin 1994. Nanko et al.8 from Japan studied 100 patients with

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schizophrenia and an equal number of controls and foundno association between schizophrenia and DRD2 Ser3111Cys311 polymorphism. Asherson et al. 9 also did not find anyassociation between the Cys variant and schizophrenia in awestern European population. Gejman et al.1Oused denaturinggel electrophoresis and found no association betweenSer3111Cys311, Pr031O/Ser31O and Ala961V al 96 poly-morphism and schizophrenia. However, Shaikh et at. 11 havereported an association between Cys311 and schizophrenia,although homozygotes were absent in their study.

Thus the association between D RD2 Ser3111Cys311 andschizophrenia has not yet been firmly established, but hasopened up exciting possibilities of further investigation intothe genetic basis for the disorder.

REFERENCESItokawa M, Arinami T, Futamara N, Hamaguchi H, Toru M. A structuralpolymorphism of human dopamine D2 receptor, D2 (Ser311-Cys). BiochemBiophys Res Commun 1993;196:1369-75.

2 Kendler KS, Gruenberg AM, Tsuang MT. Psychiatric illness in first-degreerelatives of schizophrenic and surgical control patients: A family study usingDSM-III criteria. Arch Gen Psychiatry 1985;42:77~9.Gottesman II, McGuffin P, Farmer AE. Clinical genetics as clues to the 'real'genetics of schizophrenia (a decade of modest gains while playing for time).Schizophr Bull 1987;13:23-47.

Living related liver transplantation

Rogiers X, Burdelski M, Broelsch CEo (Departments ofGeneral Surgery and Paediatrics, University HospitalEppendorf, Hamburg, Germany.) Liver transplantationfrom living donors. Br J Surg 1994;81:1251-4.

SUMMARYThe authors present an overview of living related liver trans-plantation (LRLT) along with recent results from major centres.The use of living donors is justified on the basis that the mortalityon the waiting list due to lack of size-matched cadaveric donorsfor paediatric patients can be reduced and patients can be trans-planted electively with improved results at a less advanced stageof their liver disease. Another factor promoting this newapproach to the problem of donor supply in countries like Japan.is the lack of a cadaveric donor programme. The feasibility ofseparating the right and left lobes of the liver as viable unitswith their own independent vascular supply has been demon-strated successfully in split liver transplantation and providesthe anatomical basis for using partial livers from donors. Donor.selection is based on informed consent using a double consentsystem, extensive medical and psychological evaluation toexclude unknown diseases and risk factors, computerizedtomography with volumetry of the donor liver segment andangiography to exclude hepatic vascular abnormalities. Thesecriteria led to the exclusion of 55% of potential donors in thepresent series. The left lateral segment is usually harvested asit involves the removal of the least amount of transplantableliver from the donor. It has a standard portal and hepatic venousanatomy and the raw area resulting from the resection is small.The technique of resection involves isolation of the vascularinflow and outflow and division of the liver without vascular

THE NATIONAL MEDICAL JOURNAL OF INDIA VOL. 8, NO.3, 1995

4 Kety SS. The significance of genetic factors in the etiology of schizophrenia:Results from the national study of adoptees in Denmark. 1 Psychiatr Res1987;21:423-9.

5 Kendler KS, Diehl SR. The genetics of schizophrenia: A current geneticepidemiologic perspective. Schizophr Bull 1993;19:26H!5.

6 Snyder SH, Banerjee SP, Yamamura HI, Greenberg D. Drugs, neuro-transmitters, and schizophrenia: Phenothiazines, amphetamines and enzymessynthesizing psychotomimetic drugs aid schizophrenia research. Science1974;184:1243-53.

7 Sanders AR, Hamilton ill, Fann WE, Patel PF. Association of genetic variationat the porphobilinogen deaminase gene with schizophrenia. Am 1Hum Genet1991;49:358.

8 Nanko S, Hattori M, Dai XY, Fukuda R, Kazamatsuri H. DRD2 Ser3111Cys311polymorphism in schizophrenia. Lancet 1994;343:1044.

9 Asherson P, Williams N, Roberts E, MeGuffin M, Owen M. DRD2 Ser311!Cys311 polymorphism in schizophrenia. Lancet 1994;343:1045.

10 Gejman PV, Ram A, Gelernter J, Friedman E, Cao Q, Pickar D, et al.No structural mutation in the dopamine D2 receptor gene in alcoholism orschizophrenia: Analysis using denaturing gradient gel electrophoresis. lAMA1994;271:204-8.

11 Shaikh S, Collier D, Arranz M, Ball D, Gill M, Kerwin R. DRD2 Ser311 ,Cys311 polymorphism in schizophrenia: Lancet 1994;343:1045-6.

HEMRAJPALSHEKHAR SAXENA

Department of PsychiatryAll India Institute of Medical Sciences

New Delhi

exclusion. Once the left lateral segment is fully mobilized, thevessels are divided, the graft is removed, immediately perfusedon the bench and preserved in ice. The recipient inferior venacava is preserved and the graft is implanted anastomosingthe donor hepatic vein' to one of the recipient hepatic veinorifices on the cava. All four major centres with living relatedliver transplant programmes have achieved excellent I-yearactuarial survival rates ranging from 85% to 91%. No majordonor complications have been reported, excepting one deathfrom pulmonary embolism, out of 300 cases worldwide. Theauthors conclude that LRLTs function uniformly well, can reducewaiting list mortality and allow elective transplantation inrecipients at an optimal time.

COMMENTEver since the first successful liver transplant from a livingrelated donor was carried out by Strong in 1989,1 it has beenperformed in a number of major centres=' with excellentresults. This does not mean that LRL T has become a standardpractice. Several issues need to be addressed before LRL Tcan be a universally applicable and successful procedure.

The current protocols of donor assessment invariably resultin the rejection of the majority of potential donors. The highrate of donor exclusion and the inevitable delay that ensuesin investigating a potential donor rule out the use of LRL Tin emergency situations. A hasty decision to accept a livingdonor may place him or her at an unacceptably high riskand preclude the possibility of obtaining fully informedconsent. In the present era, when cadaveric donor liver trans-plantation is an established procedure of proven efficacy,the risk to a living donor, however small, is unjustified fortransplanting adults if size-matched cadaveric organs areavailable. Therefore, only a select group of the paediatricpatients needing elective liver transplantation can be trans-planted using this option if cadaveric organ supply is satisfac-