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reported patency and pregnancy rates of 80-7%and 44-6%, respectively, with a macroscopicstented technique in 208 cases, compared with88.7% and 62-0% with a non-stented microscopictechnique in 142 cases.

Several other factors influence the likelihood ofsuccess. Sperms in the fluid from the testicular endof the vas indicate a favourable outlook; and whensuch sperms are absent the outlook is increasinglypoor _ time since vasectomy. Over-

all, a normal spermall, tL of regaining a normal spermcount fell from 91% within ten years of vasectomycount fell from 91% within ten years of vasectomyto 35% after more than ten years .6 This declinemay have en due to secondary changes in the epi-didymis.19 Vasectomy increases the pressure in thetesticular end of the vas which is transmitted to the

epididymis. Rupture of tubules in the epididymismay produce granulomas and epididymal obstruc-tion ; the epididymis should therefore be examinedin cases with no fluid in the vas to see whether epi-didymovasostomy is indicated. Granuloma forma-tion at the cut testicular end means less dilatationof the vas; better quality vas fluid was observed inthe absence of such dilatation, possibly as a resultof protection against back pressure.6 Vasectomycan also damage the nerves lying adjacent to thevas20 and degenerative changes have been reportedin the alpha-adrenergic nerve supply to the testicu-lar end of the vas and the cauda epididymis; thesenerves regenerated slowly after vasovasostomy andthis may account for the slow recovery of normal

ejaculate content after vasectomy reversal. 21Agglutinating and immobilising antibodies can

be detected in 50—70%22 of vasectomised men andare more common in those with sperm granu-10ma.23 Recovery of fertility is more likely in menwho do not have such antibodies: for example, inone series they were detected in 48% of 29 fertilemen and 94% of 16 infertile men with sperms inthe ejaculate after vasovasostomy.24 Antispermantibodies interfere with fertility less often in vasec-tomy-reversal patients than in naturally infertilemen-apparently because vasectomised men sel-dom have antibodies in the seminal plasma.25

With good surgical technique, vasectomy rever-sal should restore fertility in over 50% of cases. If

19. Silber SJ. Epididymal extravasation following vasectomy as a cause for fail-ure of vasectomy reversal. Fertil Steril 1979; 31: 309-15

20 Pabst R, Martin O, Lippert H. Is the low fertility rate after vasovasostomycaused by nerve resection during vasectomy? Fertil Steril 1979; 31:316-20.

21. Alexander NJ, Fulgham DL, Toyooka DL, Uno H, Wicklund R. Innervationof the rabbit ductus deferens after vasectomy and vasovasostomy. Biol

Reprod 1979, 21: 161-71.22. Ansbacher R. Vasectomy: sperm antibodies Fertil Steril 1975; 24: 788-92.23. Alexander NJ, Schmidt SS. Incidence of antisperm antibody levels and

granulomas in men. Fertil Steril 1977; 28: 655-57.24. Sullivan MJ, Howe GE. Correlation of circulating antisperm antibodies to

functional success in vasovasostomy. J Urol 1977; 117: 189-91.25. Rumke PH, Hellema HWJ. Immunologic studies in long-term follow-up of

vasectomised men. In: Lepow IH, Crozier R, eds. Vasectomy: immunolo-gic and pathophysiologic effects in animals and man. New York AcademicPress, 1979.

the operation is unsuccessful-if sperms appear inthe ejaculate only transiently or not at all-thescrotum should be re-explored: either the anasto-moses need to be redone, with excision of fibroustissue at the site of union,6 or epididymovasostomyis required for secondary epididymal obstruction;very occasionally no sperms can be found, in whichcase testicular biopsy should be done to excludespermatogenic failure.

Lithium in Hæmatology

LITHIUM salts have been used for more than seventyyears in the treatment of patients with psychiatric dis-orders. Since 1950 peripheral blood leucocytosis inpatients on lithium has been reported several times,1but the therapeutic possibilities of lithium for hxmato-logical disorders were only considered when TISMANand his colleagues2 confirmed, in 1973, that almost allpatients taking lithium carbonate for manic-depressivepsychoses had a neutrophil leucocytosis. In addition,the patients had a raised serum level of unsaturatedvitamin-B 12-binding protein. These observations,coupled with the finding that lithium added to normalbone marrow cells cultured in vitro stimulated the

growth of increased numbers of granulocytic colonies,suggested that lithium caused a true increase in thebody’s granulocyte pool and not merely a redistri-bution of granulocyte numbers between marrow andblood. This conclusion was later confirmed in kineticstudies with isotope labelled granulocytes.3More is now known of the way in which lithium in-

fluences hasmopoiesis. Lithium is a univalent cation re-sembling sodium and potassium and so can interferewith many sodium and potassium dependent enzymes.Its capacity to inhibit the action ofadenyl cyclase and soreduce intracellular levels of cyclic AMP is the

probable basis of its hasmatological effects. Furtherattempts to define its site of action with a murine sys-tem showed no direct stimulatory effect on granulocyteprogenitor cells but suggested instead that lithiumenhances the production of the colony-stimulatingactivity (CSA) that is necessary for granulopoiesis invitro and is considered a possible modulator of granu-lopoiesis in vivo.4 In man oral lithium carbonate raisesurinary levels of CSA 5and augments the production ofCSA by peripheral blood mononuclear cells.6 Thismight suggest that the principal action of lithium in

1. Radomski JL, Fuyat HN, Nelson AA, Smith PK The toxic effects, excretion anddistribution of lithium chloride. J Pharmacol Exp Ther 1950, 100: 429-44.

2. Tisman G, Herbert V, Rosenblatt S. Evidence that lithium induces human

granulocyte proliferation: elevated serum vitamin B12 binding capacity in vivo andgranulocyte colony proliferation in vitro. Br J Hœmatol 1973; 24: 767-76.

3 Rothstein G, Clarkson DR, Larsen W, Grosser BI, Athens JW. Effect of lithium onneutrophil mass and production. N Engl J Med 1978, 298: 178-80.

4 Harker WG, Rothstein G, Clarkson DR, Athens JW, Macfarlane JL. Enhancement ofcolony-stimulating activity production by lithium Blood 1977; 49: 263-67

5 Malloy ML, Zauber NP, Chervenick PA. The effect of lithium on blood and marrowneutrophils. Blood 1978; 52: suppl 1, 228 (abstr).

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vivo is to enhance the production of a humoral stimu-lator of granulopoiesis, but newer work suggeststhat this is not the whole answer. If lithium is given togrey collie dogs with cyclical neutropenia, a conditionin which the defect is believed to lie in the pluripoten-tial stem cell and not in aberrant control mechanisms,the "cycling" of neutrophil, platelet, and reticulocytenumbers is eliminated.’ Moreover, when I EVITT andQUESENBERRY studied the effects of adding lithium toa murine bone marrow liquid culture system, lithiumsubstantially increased the number both ofgranulocyte-committed progenitor cells and of pluri-potential stem cells.8 Lithium therefore seems to haveat least two distinct actions in hæmopoiesis—it en-hances the production of CSA and it directly stimulatesthe proliferation of pluripotential stem cells.What possible clinical benefits can be derived from

this knowledge? Patients with aplastic anxmla have,with some exceptions, gained little from treatmentwith lithium;-" one patient with congenitalneutropenia, however, showed a rise in neutrophilnumbers and clearing of infection after lithium treat-ment.12 Lithium is very effective in raising the level ofgranulocytes in the blood of patients with Felty’s syn-drome.’ In practice lithium may be most valuablewhen used in conjunction with cytotoxic drugs fortreating malignant disease. For example, lithium treat-ment can shorten the median duration of granulocy-topenia in patients undergoing remission induction foracute myeloid leukæmia14 and reduces the degree ofleucopenia in patients treated with chemotherapy forsolid tumours. 15 LYMAN and his colleagues’ haverecently reported that in patients treated with cytotoxicdrugs for small-cell carcinoma of lung the hxma-tological benefits of lithium are associated with a

significant reduction in the frequency of fever andinfection. In most of the reports of lithium therapy, thetoxicity has been remarkably mild. Nausea and

vomiting occurred in some studies but could not

definitely be separated from the effects of the cytotoxicdrugs. Lithium-related diabetes insipidus was notseen. For any patient who may benefit, at least in theshort term, from pharmacological stimulation of gran-ulopoiesis, lithium is worth a thought.

6. Turner AR, Allalunis MJ. Mononuclear cell production of colony stimulating activityin humans taking oral lithium carbonate. Blood 1978, 52: suppl 1, 234 (abstr)

7. Hammond WP, Dale DC. Lithium therapy of canine cyclic hematopoiesis. Blood 1980,55: 26-28

8 Levitt LJ, Quesenberry PJ. The effect of lithium on murine hematopoiesis in a liquidculture system. N Engl J Med 1980, 302: 713-19

9 Barrett AJ Hæmatological effects of lithium and its use in treatment of neutropenia.Blut 1980, 40: 1-6.

10 Blum SP. Lithium therapy of aplastic anemia N Engl J Med 1979, 300: 67711 Pi EH, Dempsey GM Lithium carbonate in aplastic anemia Arch Gen Psychiat 1980;

37: 720

12. Barrett AJ, Griscelli C, Buriot D, Faille A. Lithium therapy in congenital neutropenia.Lancet 1977, ii: 1357-58

13 Gupta RC, Robinson WA, Kurnick JE Felty’s syndrome. Effect of lithium ongranulopoiesis. Am J Med 1976, 61: 29-32.

14 Stem RS, Flexner JM, Graber SE Lithium and granulocytopenia during inductiontherapy of acute myelogenous leukemia Blood 1979, 54: 636-41

15 Steinhera PG, Rosen G, Ghavimi F, et al. Effect of lithium carbonate on leukopeniaafter chemotherapy. J Pediat 1980; 36: 923-27.

16 Lyman GH, Williams CC, Preston D. The use of lithium carbonate to reduce infectionand leukopenia during systemic chemotherapy. N Engl J Med 1980; 302: 257-60.

PROPRANOLOL IN SCHIZOPHRENIA—MOREGUESS THAN GAUSS

ENCOURAGED by news from Israel, Yorkston and hiscolleagues2 reported in 1974 that some patients with schizo-phrenia had got much better after administration of quitelarge doses of propranolol. Only fourteen patients wereincluded in the trial. All of them were also taking phenothia-zines, but four of the successfully treated patients were dis-charged taking propranolol alone. As the authors themselvesstated, the series was small, follow-up short, and control nil.Chronic schizophrenia, on the other hand, is long, its coursefluctuating, and its patients notoriously, perhaps pathetic-ally, susceptible to bursts of therapeutic enthusiasm. In otherwords, the stage should have been set for more systematicstudies of larger groups of patients. Nearly six years later,what more can be added to the initial observations?

In 1977, the same group3 could’claim that twenty-eight outof fifty-five patients had shown at least a temporary remissionafter treatment with propranolol, and they then described atrial on fourteen patients, half of whom received the drug fortwelve weeks, while others received placebo-all in additionto their current phenothiazines. There was some improve-ment in both groups, but those receiving the active drug im-proved much more, and continued to do so throughout thetwelve-week period. In some cases, the improvement wasvery striking, considering that they had been chosen aschronic patients who had failed to respond to phenothiazinesalone. Last year, Sheppard4 reported an uncontrolled studyon eight men, in which propranolol was added to currentphenothiazine medication for three weeks. Seven patients im-proved and these maintained their improvement when kepton the drug for six months.Two reports have lately come from Sweden. Hanssen and

his colleagues5 in Stockholm treated six patients, initiallywith propranolol alone and later with the addition of pheno-thiazines. Three improved on propranolol alone and threedid not. Five were discharged on a combination of drugswhich was felt to be more effective than either drug alone.Lindstrom and Persson,6 in Uppsala, treated twelve patients,all of whom were also receiving a phenothiazine by injection.After the open administration of propranolol for a period ofthree to four weeks, a two-week cross-over trial was started,comparing propranolol with placebo, ratings being made by ablind observer. Judged by total symptom scores, six patientsimproved, three remained largely unchanged, and threedeteriorated. Some of the improvements were very striking,with significant reduction of overall scores.The theme of the story so far is the familiar conflict between

inspired guess-work and uninspiring Gauss work. There issome evidence that propranolol may benefit some patientssuffering from chronic schizophrenia, in most cases as an ad- ’

dition to phenothiazine treatment. But the overall evidence isunlikely to convince the sceptics who will be mindful not onlyof the normal variations in schizophrenic symptoms within aparticular distribution, but also of the drug’s many other act-

1. Atsmon A, Blum I, Sterner M, et al Further studies in psychotic patients. Psychophar-macologia 1972; 27: 249-54.

2 Yorkston NJ, Zaki SA, Malik MKU, et al Propranolol in the control of schizophrenicsymptoms. Br Med J 1974; iv: 633-35.

3. Yorkston NJ, Zaki SA, Pitcher DR, et al. Propranolol as an adjunct to the treatment ofschizophrenia. Lancet 1977, ii: 575-78.

4. Sheppard GP High-dose propranolol in schizophrenia. Br J Psychiatry 1979; 134:470-76.

5. Hanssen T, Heyden T, Sundberg I, et al. Propranolol in schizophrenia. Arch Gen Psy-chiatry 1980, 37: 685-90

6. Lindström LH, Persson E. Propranolol in chronic schizophrenia: a controlled study inneuroleptic-treated patients Br J Psychiatry 1980; 137: 126-30.