METHYL-BIS (BETA-CHLOROETHYL) AMINE IN LARGE DOSES IN THE TREATMENT OF NEOPLASTIC DISEASES

Sixty-seven patients with neoplastic diseases were treated with 151 courses of methylbis (beta-chloroethyl)amine hydrochloride (HN₂). Seventy-seven of the courses consisted of single injections of 0.2 to 0.4 mg. per kilogram of body weight, and 35 courses were given as single injections of 0.6 mg. per kilogram of body weight.Twenty-three patients with Hodgkin''s disease were treated. Remissions averaged approximately three months in 13 patients who were in good or fair general physical condition, and 1.5 months in 11 patients who were in poor or moribund condition; one of the 11 did not respond to the therapy.Fifteen patients with lymphosarcoma were treated. Remissions averaged between one and two months in four patients who were in good or fair general physical condition. Of the remaining 11 patients, two showed no response, and the longest remission among the remaining nine was approximately 40 days.Satisfactory remissions of one to three months were obtained in four patients with mycosis fungoides treated with single courses of 0.3 mg. per kilogram of body weight.Serious toxic reactions were observed in six patients, four of whom died. In five of the six instances the reactions consisted of pancytopenia and hemorrhagic diathesis. All these patients were in poor general or hematologic status before therapy.In general, large single doses of HN₂ were neither more nor less effective than the four-to six-day course usually employed with this agent. Combination of the administration of HN₂ with artificial hyperpyrexia, or with concurrent courses of pteroylglutamic conjugates, did not enhance the therapeutic effects of the agent.     

Psychiatric Aspects of Ageing

Psychotic conditions due to structural brain disease of the senile and arteriosclerotic type are numerically less important than was formerly assumed. They account for about 25-30% of the psychiatric illnesses of the aged. Functional psychoses, particularly endogenous depressions, form an important part of these disorders. Their symptomatology and treatment are not essentially different from those of functional psychoses in the younger age groups. Among non-hospitalized old people, neurotic conditions represent the most frequently encountered type of mental disorders. Psychodynamic factors, operative in the older as well as the younger generations, and their interplay are responsible for the neurotic conditions of the elderly. These respond favourably to psychotherapy. Severe acute and subacute confusional states are caused in some aged people by physical and psychological stresses. These conditions have a serious prognosis but are amenable to proper treatment when diagnosed in time. They are the responsibility of the general practitioner and the general hospitals.     

Towards a more rapid diagnosis of rapidly progressive glomerulonephritis.

An attempt was made to provide simple practical guidelines to alert general practitioners to the diagnosis of rapidly progressive glomerulonephritis and lead to early referral to hospital. The duration of illness before referral to this hospital and its effect on outcome in patients with crescentic nephritis were assessed retrospectively from the case notes of 24 patients referred over two years. Four patients had Goodpasture''s syndrome, 11 Wegener''s granulomatosis, seven microscopic polyarteritis, and two idiopathic progressive glomerulonephritis. The duration of symptoms before referral to the local hospital was similar in the four groups of patients and varied from one week to 28 months (mean 10 months). The duration of stay in the local hospital was two, nine, 11, and 180 days in the patients with Goodpasture''s syndrome and a mean of four days (range one to eight) in those with Wegener''s granulomatosis and 10 days (one to 18 days) in those with microscopic polyarteritis. In the local hospital the diagnosis was based on the results of renal biopsy and detection of antibodies to glomerular basement membrane in two patients with Goodpasture''s syndrome and on the results of renal biopsy in seven of the other patients aided by the detection of antibodies to the cytoplasm of neutrophils (ANCA) in 10. Three of the 24 patients died and four required maintenance haemodialysis. Patients who present to their general practitioners with persistent non-specific symptoms should have a urine dipstick test and then blood tests and emergency referral to hospital if necessary. Hospital physicians should be aware of the speed and accuracy with which current assays can confirm a diagnosis of rapidly progressive glomerulonephritis.     

GERIATRIC PATIENTS IN A MENTAL HOSPITAL

An intensive study was made of men 55 years of age and over admitted to Napa State Hospital with either senile or arteriosclerotic brain disease. A ward treatment program, combining both the medical and psychiatric approaches, was applied to one-half of such patients admitted to a state hospital, with the aim of determining what, if any, effect this program would have on the course of the illnesses.Special laboratory studies showed: (a) Serial electroencephalograms and hospital adjustment ratings appeared to be positively correlated with the patients'' clinical course; (b) In 35 per cent of cases the electrocardiographic tracings at the time of admittance were within normal limits; (c) A “pathological level” of blood bromides was found in only one of 340 consecutive admissions in this age group.Sociopsychiatric study of 100 consecutively admitted patients revealed that: (a) 35 per cent of the patients were from the middle, and 65 per cent from the lower classes of society; (b) Only 59 per cent were admitted because of activities specifically psychotic. (c) 63 per cent needed admittance to this state hospital for observation and diagnosis, but only 44 per cent needed to stay for care and treatment; (d) In 88 per cent, specific emotional stresses were present just preceding and coincident with the clinical appearance of the organic brain syndrome.     

Effect of a training programme to reduce stress in carers of patients with dementia.

OBJECTIVE--To reduce the psychological stress and improve the skills in coping of people who care for relatives with dementia. DESIGN--Assessment and suitability of carers by questionnaire; assessment of patients and carers in a hospital outpatient clinic; allocation to groups according to date of application to study. Linkage of groups of four carers and programme coordinator by telephone conference calls over 12 months after programmes. Reassessment at three, six, 12, and, for those in the "wait list" group, 18 months. SETTING--The programmes were conducted in the psychiatry unit of a Sydney teaching hospital. SUBJECTS--Eligible patients were less than 80 years old, had mild to moderate dementia, and lived at home with their carer. Of the 96 patient-carer pairs in the study, 33 were in the dementia carers'' programme group, 31 were in the memory retraining group, and 32 were in the wait list group. INTERVENTIONS--Carers in the dementia carers'' programme received training in coping with the difficulties of looking after patients with dementia while the patients had sessions in subjects such as memory retraining. In the memory retraining programme patients were admitted and received the patient component of the carers'' programme while their carers had 10 days'' respite. In the wait list group carers waited six months before undertaking the carers'' programme. MAIN OUTCOME MEASURES--Effect of the programmes on carers'' general health questionnaire scores and the rate of placement of patients in institutions. RESULTS--At 12 months'' follow up the carers'' programme had resulted in significantly lower psychological stress among carers than the memory retraining programme (mean (SD) general health questionnaire scores at 0 months were 6.31 (6.23) and 3.60 (6.25) respectively, and at 12 months were 4.69 (5.58) and 7.40 (9.39); p less than 0.05.) In the wait list group distress scores remained stable, even after the carers and patients had undertaken the carers'' programme. Patients deteriorated over 12 months regardless of group allocation, but at 30 months, allowing for patients who died and could not be included in the analysis, 65% of patients in the carers'' programme group were still living at home compared with 26% in the memory retraining programme group. CONCLUSION--The intensive intervention programme described for carers of patients with dementia can reduce the psychological morbidity of the carer and delay the placement of the patient in an institution without increasing the use of health services by either patient or carer.     

Amebic abscess of the liver

In a review of the records in 50 cases of amebic abscess of the liver observed in the Canal Zone between 1920 and 1945 the following features were noted:Incidence was preponderantly in males and highest in persons between the ages of 20 and 40. None of the patients was under 21 years of age. There was a great variety of complaints at the time of admission to hospital. The most common was pain in the right upper quadrant of the abdomen. Demonstration of either elevated or fixed diaphragm by x-ray film and fluoroscopic examination was useful in diagnosis in a number of cases, but absence of such findings did not rule out abscess of the liver. In some cases there was history of previous dysentery with blood in the stools.One or another of three operative procedures was used for drainage of abscesses in 39 patients. Of the 39, six died; in five of the six, multiple abscesses were present. Emetine hydrochloride was given to all patients.     

AMEBIC ABSCESS OF THE LIVER

In a review of the records in 50 cases of amebic abscess of the liver observed in the Canal Zone between 1920 and 1945 the following features were noted:Incidence was preponderantly in males and highest in persons between the ages of 20 and 40. None of the patients was under 21 years of age.There was a great variety of complaints at the time of admission to hospital. The most common was pain in the right upper quadrant of the abdomen.Demonstration of either elevated or fixed diaphragm by x-ray film and fluoroscopic examination was useful in diagnosis in a number of cases, but absence of such findings did not rule out abscess of the liver.In some cases there was history of previous dysentery with blood in the stools.One or another of three operative procedures was used for drainage of abscesses in 39 patients. Of the 39, six died; in five of the six, multiple abscesses were present.Emetine hydrochloride was given to all patients.     

Childhood deaths from intussusception in England and Wales, 1984-9.

OBJECTIVE--To assess the incidence of potentially avoidable factors contributing to death of children with intussusception. DESIGN--Review of children who died with intussusception in England and Wales between 1984 and 1989 from data of the Office of Population Censuses and Surveys, case notes, coroners'' records, and necropsy reports. MAIN OUTCOME MEASURES--Unambiguous objective criteria such as failure to diagnose intussusception within 24 hours of admission. RESULTS--33 children died of acute intussusception in England and Wales between 1984 and 1989 compared with 67 in the previous six years. Their median age was 7 months (range 2 months to 12 years), and two thirds were boys. Half of the deaths occurred at home or soon after arrival at hospital but 15 patients had surgery. Potentially avoidable factors contributing to death were identified in 20 (61%) children, all but three of whom had ileocolic intussusception. These factors were excessive delay in diagnosis, inadequate intravenous fluid and antibiotic therapy, delay in recognising recurrent or residual intussusception after hydrostatic reduction, and surgical complications. Of the 13 patients in whom no avoidable factors were identified, there were nine of 11 children with isolated small bowel intussusception, who tended to have atypical presentations. CONCLUSION--Although the mortality from intussusception has declined, there remains ample opportunity for improved management.     

Prognosis of new and worsening angina pectoris.

The natural history of new and worsening angina pectoris was studied in 251 men aged under 70 years. Most were ambulant and all were referred by selected general practitioners to a special hospital clinic over two and a half years. Heart attacks developed in 39 patients, nine of whom died. Seventy-two per cent of the attacks occurred within six weeks of the onset or worsening of angina. Of the 212 patients who did not suffer myocardial infarction and who were clinically reviewed six months after their first attendance 66 had been pain free for the previous three months and 14 had experienced only infrequent attacks of angina. Of the 128 men aged under 65 years who were previously in employment 81% had returned to full-time work six months after their first attendance. A discriminant function analysis using many variables was made to develop a predictive index that would allow patients with new or worsening angina who were likely to develop serious cardiac complications to be identified. This did not prove possible, and the only predictive factor of significance was an increased cardiothoracic ratio. The syndrome of new and worsening angina has a low risk of early death, and many patients are symptom free six months later. In general, emergency coronary arteriography and surgery is not indicated.     

Clinical significance of a high mean corpuscular volume in nonanemic patients.

A prospective study of the clinical significance of macrocytosis (mean corpuscular volume 100 fL or more) was carried out for 9 months in a teaching hospital in 1975. Of the 140 patients with macrocytosis at the time of admission (0l7% of all hospital admissions) 46 (33%) had low activity of serum or erythrocyte folate, or both, and 16 (11%) had low serum vitamin B12 concentrations. Among the 78 patients with normal B12 and folate values the most commonly associated significant clinical conditions were alcoholism or hepatic disease (36 patients), malignant disease or the effects of chemotherapy (25 patients) and chronic obstructive lung disease (10 patients).     

Cardiac transplantation in severely ill patients requiring intensive support in hospital

Sixty four patients were referred for cardiac transplantation from a single cardiac team at this hospital between October 1984 and December 1986. Of these patients, 33 were referred for urgent transplantation, all of whom required intensive treatment in hospital with intravenous infusions of cardiac drugs, intra-aortic balloon counterpulsation, peritoneal dialysis, ventilation, or any combination of these to sustain life. Of these 33 patients, six died while awaiting transplantation, one was removed from the waiting list for a transplant, and 26 received cardiac transplants. There were five deaths within 24 hours of operation and one death 10 days after the operation. Twenty of those who had surgery had a successful outcome of transplantation, but there was one late death 10 weeks postoperatively and a further death 31 months after surgery. Eighteen patients were alive and well 10 to 33 months (mean 19·4 months) after transplantation, with an overall survival rate after surgery of 69%.Provided that surgery can be performed before renal failure has progressed such that renal transplantation is necessary, the results are excellent (surgical survival 85·5%) and, we believe, justify the expenditure and staffing requirements necessary to treat these terminally ill patients.     

Neurological complications of coronary artery bypass graft surgery: six month follow-up study.

As part of a major prospective study of the neurological complications of coronary artery bypass graft surgery patients were reviewed over six months to determine the clinical course and functional impact of early postoperative complications. One hundred and ninety one out of 312 (61%) patients had developed early postoperative disorders. At six months 165 of the 191 patients with early neurological complications were reviewed. Of the 165, 85 still had detectable neurological signs, but these were often minor and of little functional importance. Only 10 patients had neurological disability at six months, and this was major in only four patients, all of whom had suffered major perioperative stroke. No patient with non-disabling neurological complications in hospital became functionally impaired on returning home. Neurological disorders are not a major cause of failure to return to work by six months after coronary artery bypass surgery. Of 139 patients who were of working age and had not returned to work by six months, only four were prevented by neurological injury related to surgery. The long term prognosis for early neurological disorders after coronary artery bypass surgery is usually favourable, except in those patients who have sustained major perioperative stroke.     

Facilitating care of patients with HIV infection by hospital and primary care teams.

To complement the role of primary care teams working with patients with HIV disease and AIDS within greater London and to ease the load on the special hospital units a home support team was developed. It comprises six specialist nurses, a general practitioner trained medical officer, and a receptionist and is funded from regional and district sources and charities. A nurse is available for out of hours and emergency weekend calls, with support from the patient''s general practitioner or the attached medical officer. During the first 18 months 249 patients were seen; the mean duration of care was five months. Nearly a third (18/50, 30%) of patients who were terminally ill died at home. The team''s activities included practical nursing care, emotional support for carers and patients, and advice and guidance to primary care teams. Problems in providing care in patients'' homes included issues relating to confidentiality and 24 hour cover. With the increasing incidence of HIV infection the home support team may be a useful model for care of large numbers of patients with symptomatic HIV disease, especially in large urban areas.     

Successful treatment of Cushing's disease using yttrium-90 rods.

Interstitial irradiation using yttrium-90 (90Y) rods implanted by needle into the pituitary gland was used as primary treatment in 16 patients with pituitary dependent Cushing''s disease. Clinical and biochemical remission was observed within three or six months in 13 and in the remaining three after a supplementary implant. There was no perioperative morbidity. Follow-up from the time of definitive operation ranged from six to 123 months (mean 39). No recurrence has been observed. The return of a normal diurnal cortisol rhythm has been observed in 10/12 patients studied after remission. Some form of long-term pituitary hormone replacement therapy was required in only the six patients who had received the largest irradiation dose. Implantation of 90Y is safe and effective treatment for patients with Cushing''s disease, comparing favourably with selective trans-sphenoidal pituitary surgery.     

Effect of Psychiatric Intervention in Attempted Suicide: A Controlled Study

All patients presenting at the casualty department of King''s College Hospital during the first six months of 1968 with deliberate self-poisoning or self-injury were followed up. Of 211 patients 204 (97%) were traced after a mean interval of 18 months (range one to two years). Despite official hospital policy, 22% had not been seen by a psychiatrist before discharge; these 44 untreated patients were compared with the remaining 160 who had received either brief (one or two interviews) or more prolonged psychiatric and social help.Subsequent suicidal attempts occurred significantly more often among untreated than among treated patients, prolonged treatment being associated with the best prognosis. The same trend was observed in respect of actual suicide, though the numbers were small and differences did not reach statistical significance. These findings held good when the untreated and treated groups were controlled for other variables which were found to be correlated with outcome. These results indicate that psychiatric intervention is associated with a significant reduction in subsequent suicidal behaviour.     

Broken Heart: A Statistical Study of Increased Mortality among Widowers

A total of 4,486 widowers of 55 years of age and older have been followed up for nine years since the death of their wives in 1957. Of these 213 died during the first six months of bereavement, 40% above the expected rate for married men of the same age. Thereafter the mortality rate fell gradually to that of married men and remained at about the same leveLThe greatest increase in mortality during the first six months was found in the widowers dying from coronary thrombosis and other arteriosclerotic and degenerative heart disease. There was also evidence of a true increase in mortality from other diseases, though the numbers in individual categories were too small for statistical analysis.In the first six months 22·5% of the deaths were from the same diagnostic group as the wife''s death. Some evidence suggests that this may be a larger proportion than would be expected by chance association, but there is no evidence suggesting that the proportion is any different among widows and widowers who have been bereaved for more than six months.     

Lithium treatment: prescribing and monitoring habits in hospital and general practice.

OBJECTIVES--To define current clinical practice of lithium prescribing and monitoring and to compare hospital based practice with general practice. DESIGN--Prospective study of doctors'' practice. SETTING--Psychiatric hospital day and outpatient facilities and general practices in Edinburgh and Midlothian district (population 600,000). SUBJECTS--458 patients taking lithium who had been stabilised and who remained as outpatients during the year of study. 219 were treated by their general practitioner and 190 by the hospital; 49 had shared care or care transferred during the study. MAIN OUTCOME MEASURES--Daily dose, duration of treatment, psychiatric diagnosis, mean annual serum lithium concentration, frequency of occurrence of and response to raised serum concentrations. RESULTS--Compared with hospital doctors general practitioners were more likely to prescribe lithium three or more times daily (43/219 (general practice) v 10/190 (hospital); chi 2 = 18.6, p = 0.001) and to estimate serum concentrations less frequently (4.5 v 5.3 measurements/year; t = 3.04, p = 0.003), and their patients were more likely to experience raised lithium concentrations (39/219 v 17/190; chi 2 = 6.8, p = 0.01). One third of doctors made no response to raised lithium concentrations in the next six weeks. CONCLUSIONS--General practitioners and hospital doctors care for similar types of patients and the stringency of lithium surveillance varies greatly among doctors. Certain aspects of practice give cause for concern and could be improved by following more uniform guidelines.     

Interim discharge summaries: how are they best delivered to general practitioners?

All patients discharged from a medical ward during four months were randomly assigned to one of two groups. In one group the patients were given their interim discharge summary for delivery to their general practitioner by hand; in the other group the summary was posted by the hospital. Of the 289 summaries sent by either method, 279 (97%) arrived at the general practitioner''s surgery. A mean (median) time of two (one) days elapsed before arrival when summaries were delivered by hand and a mean (median) of four and a half (four) days when they were posted; at least 55% of summaries delivered by hand arrived within one day of the day of discharge compared with 8% of those posted. If all interim discharge summaries were given to patients to deliver communication between hospitals and general practitioners would be accelerated and considerable savings might be made.     

First year of an inner city general practitioner community hospital.

The first inner city general practitioner community hospital opened on 4 January 1982. This paper describes the operation of the hospital over the first 12 months. There were 316 admissions, with an average length of stay of 13 days. The average age of the patients was 73 and the most common reason for admission was disease of the respiratory system. Thirty five per cent of patients were admitted because of an acute illness and 37% were admitted on the same day as the request for admission. The policies of intermittent or phased care allowed for the admission of patients at regular intervals to relieve carers, and the assessment of the home circumstances of all patients allowed for planning the patient''s return home.     

盐酸多奈哌齐联合综合康复训练对老年痴呆患者认知功能、事件相关电位及血清BDNF、IGF-1的影响

目的:探讨盐酸多奈哌齐联合综合康复训练对老年痴呆患者认知功能、事件相关电位及血清脑源性神经营养因子(BDNF)、胰岛素样生长因子1(IGF-1)的影响。方法:选取2017年3月~2020年3月期间来我院接受治疗的120例老年痴呆患者,根据随机数字表法分为对照组(n=60,盐酸多奈哌齐治疗)和联合组(n=60,盐酸多奈哌齐联合综合康复训练治疗)。对比两组疗效,治疗前、治疗3个月后的认知功能评分、事件相关电位、血清BDNF和IGF-1水平变化,以及治疗期间不良反应发生情况。结果:联合组的临床总有效率为91.67%,高于对照组的70.00%(P<0.05)。两组治疗3个月后日常生活能力评估量表(ADL)、临床痴呆量表(CDR)评分降低,且联合组低于对照组(P<0.05);简易精神状态量表(MMSE)评分升高,且联合组高于对照组(P<0.05)。两组治疗3个月后N1潜伏期、P2潜伏期均缩短,P3波幅均升高,且联合组治疗3个月后P2潜伏期短于对照组,P3波幅高于对照组(P<0.05);两组治疗3个月后N1潜伏期比较未见统计学差异(P>0.05)。联合组治疗3个月后BDNF水平高于对照组(P<0.05);两组治疗3个月后IGF-1水平比较未见统计学差异(P>0.05)。对照组与联合组不良反应发生率对比无统计学差异(P>0.05)。结论:老年痴呆患者在盐酸多奈哌齐基础上联合综合康复训练,认知功能可得到明显改善,同时还可调节患者事件相关电位及血清BDNF、IGF-1水平。