Acute coronary syndromes following abrupt cessation of oral propranolol therapy.

Abrupt cessation of oral propranolol therapy was followed by 15 acute coronary events in 14 patients with severe angina who had been receiving propranolol in daily doses of 80 to 400 mg for periods of 7 days to 6 years. Propranolol had been stopped 1 to 14 days before each acute event because of angiographic study (seven patients), increasing symptoms (three), acute coronary insufficiency (one), asymptomatic bradycardia (one), elective surgery (one) and unknown reasons (two). Before abrupt cessation of propranolol treatment anginal symptoms had been stable in six instances but had increased in the other nine. Cessation was followed by rapid progression of symptoms prior to 11 of the 15 acute events. There were six acute transmural myocardial infarctions with three deaths, three intramural myocardial infarctions, one with ventricular fibrillation, and six episodes of acute coronary insufficiency, Unstable angina followed nine of the events and responded to propranolol therapy (160 to 320 mg/d) in eight instances. Three other patients underwent aortocoronary bypass surgery; perioperative acute myocardial infarction occurred in two. These data suggest that in a minority of patients abrupt cessation of propranolol may be hazardous, particularly in severe or unstable disease. Cessation or propranolol therapy in such patients should be gradual and closely observed. Recurrent symptoms respond to reinstitution of propranolol therapy.     

Dermatitis herpetiformis: effect of gluten-free diet on skin IgA and jejunal structure and function.

To clarify the controversy about the effectiveness of a gluten-free diet in dermatitis herpetiformis, 10 highly motivated patients were investigated. The indices used to assess improvement included deposition of sub-epidermal IgA in unaffected skin, counts of intraepithelial lymphocytes, deposition of IgA in jejunal villi, and electrical tests of glucose absorption. In every patient subepidermal IgA concentrations fell after gluten withdrawal. In all but one patient the dose of dapsone necessary to control symptoms was reduced. Indeed, six patients stopped taking the drug completely within a year. In nine patients biopsy specimens were taken from the jejunum; seven showed abnormalities in jejunal morphology, eight had increased numbers of intraepithelial lymphocytes, and five had increased numbers of IgA-reactive cells in the lamina propria. Two of these three indices improved after gluten withdrawal, which confirmed that all nine patients were adhering to their diet. Routine screening for malabsorption proved to be unsatisfactory for showing the mild jejunal disease found in patients with dermatitis herpetiformis. The electrical test of glucose absorption showed subnormal results in all eight patients tested, however, and in six the results improved after gluten withdrawal.     

Cyclophosphamide Therapy in the Nephrotic Syndrome in Childhood

Forty-six children with the nephrotic syndrome whose renal biopsy specimens showed minimal changes and whose response to corticosteroid therapy was unsatisfactory were treated with cyclophosphamide. Three patients were completely steroid-resistant from the outset and the remainder were steroid-dependent. In several patients steroids controlled the condition less effectively with time. Most patients showed signs of steroid toxicity, and growth retardation was striking.A moderate leucopenia was induced with cyclophosphamide, and treatment was maintained for three to four months in the majority of cases. Thirty-eight children (83%) have remained in complete remission off all treatment for periods of 3 to 23 months, 33 after one course of cyclophosphamide and five after a second course. Two other patients who remitted but relapsed later are still on treatment. In only six patients was full remission not obtained, and three of these were steroid-resistant from the start. Two died from pneumonia and adrenal failure and four continued to have proteinuria, though in one an impressive reduction occurred.The results indicate that cyclophosphamide therapy is an effective alternative for nephrotic children with normal glomeruli on light microscopy who develop steroid dependence or resistance, and who exhibit toxic effects of steroid therapy.     

Biphasic pattern of hypersensitivity following acute propranolol withdrawal in normal subjects

The effect of abrupt propranolol withdrawal on exercise-induced changes in heart rate and blood pressure was studied in six normal volunteers. Response to exercise was measured on two occassions during propranolol treatment and 1, 2, 3, 4, 5 and 7 days after the last dose of propranolol. Exercise-induced changes in heart rate were significantly lower than control during propranolol treatment (p less than 0.005). Following propranolol cessation, all subjects showed a biphasic pattern of hypersensitivity. Heart rate response was significantly greater than control 2, 3 and 7 days after the last propranolol dose (p less than 0.05) and not significantly different from control 1, 4 and 5 days after the last dose of propranolol. Exercise-induced changes in pulse pressure showed a biphasic pattern similar to the changes in heart rate.     

Additive antianginal effect of verapamil in patients receiving propranolol

Ten men with stable angina pectoris not fully relieved by optimal doses of propranolol (mean 218 mg daily) were given a single oral dose of 120 mg verapamil or a placebo on alternate mornings; the order of treatment was double blind. Patients had trained in a protocol that precipitated angina after three to six minutes of exercise on a bicycle ergometer. On test days, and with continued propranolol treatment, bicycle exercise was performed just before the administration of verapamil or placebo and hourly thereafter for eight hours. Mean exercise tolerance was 118 seconds greater one hour after verapamil than one hour after placebo (p <0·001), and a significant though somewhat diminished difference of 66 seconds was still present at six hours (p <0·01). Verapamil lowered resting systolic blood pressure by 12 mm Hg (p <0·01) without changing heart rate. None of the 10 patients showed adverse effects from the verapamil-propranolol combination.The results of this study suggest that verapamil is a highly effective antianginal supplement to propranolol.     

Cholestyramine in uraemic pruritus.

In a patient with longstanding severe uraemic pruritus who was undergoing chronic haemodialysis cholestyramine caused the pruritus to disappear completely within a few days. A four-week randomised controlled double-blind study was therefore performed in 10 other patients with uraemic pruritus who were on chronic haemodialysis. The pruritus improved considerably in four of the five treated patients, whereas only one of those treated with placebo experienced relief. The patient who had no relief while on cholestyramine showed a considerable improvement when the dose subsequently doubled. One of the five patients receiving cholestyramine experienced mild and easily reversible constipation, and another suffered nausea. Neither of these complications prevented the patients from continuing treatment. Cholestyramine seems to be useful in treating uraemic pruritus, although it is not known how it acts.     

Response to Propranolol and Diazepam in Somatic and Psychic Anxiety

A total of 12 chronically anxious psychiatric outpatients were treated with racemic propranolol (Inderal), diazepam (Valium), and placebo for one week each, using a balanced cross-over experimental design. Six patients had predominantly somatic anxiety, complaining mostly of bodily symptoms, and six had mainly psychic anxiety, complaining primarily of psychological symptoms. Clinical ratings of anxiety were made by patient and psychiatrist after each treatment. Though diazepam was in general more effective than propranolol or placebo in relieving anxiety, propranolol was more effective than placebo in patients with somatic anxiety but not in those with psychic anxiety. We suggest that propranolol should be reserved for patients whose anxiety symptoms are mainly somatic.     

Effect of herbal therapy on herpes labialis and herpes genitalis

Administration of hot water extracts of six herbs to four patients with recurrent herpes labialis led to prompt crusting over and complete recovery within a few days. Similar treatment for one female patient who had been suffering from recurrent genital herpes resolved the associated pain dramatically. In all cases mentioned, symptoms disappeared much more quickly than with previous outbreaks when herb extracts were not administered.     

Use of beta-adrenolytics in treatment of hyperthyroidism in pregnant women]

Use of propranolol in the treatment of hyperthyreosis in pregnant women is discussed. It was noted, that propranolol given for 24-28 days in low doses, starting from the 34th-35th week of pregnancy, and in higher doses during 5 or 2 days preceding labour diminishes clinical symptoms of hyperthyreosis. It influences thyreotropic hormone levels. No side effects were seen in neonates of mothers treated with propranolol; thyreotrophic hormone levels were within normal values.     

Effect of propranolol and metoprolol on parathyroid hormone and calcitonin secretions in uraemic patients.

Nine uraemic patients not being treated by dialysis received intravenous propranolol 1 microgram/kg/min for 85 minutes after a priming dose of 1 mg. Fifteen days later, six of them received intravenous metoprolol 1.2 microgram/kg/min after a priming dose of 1.2 mg. Plasma concentrations of parathyroid hormone (PTH) and calcitonin fell significantly after propranolol but not after metoprolol, whereas no change in plasma concentrations of ionised calcium and phosphate occurred with either drug. Heart rate fell similarly with both drugs. The fact that propranolol acutely suppressed PTH and calcitonin secretion in uraemic patients indicates that further studies are warranted to assess the long-term effects of the drug on the secretion of these hormones and on renal osteodystrophy. The contrast between the responses to propranolol and metoprolol supports the concept that PTH and calcitonin secretion is modulated through specific beta 2-receptors.     

Remission of Thyrotoxicosis during Treatment with Propranolol

Twenty-eight thyrotoxic patients were treated with propranolol. In seven patients the drug had to be discontinued after one or two months, but in the remaining 21 clinical improvement was observed. Serial clinical studies and tests of thyroid function performed at monthly intervals showed that in four patients thyrotoxicosis remitted and all indices of thyroid function returned to normal. A fifth patient shows distinct evidence of remission with the 20-minute ¹³²I uptake falling to normal, although the free-thyroxine index remains slightly raised. It is likely that these remissions reflect the natural tendency of the disease to remit since propranolol is not considered to have any direct in-vivo effect on thyroid function.However, because of failure to gain adequate control of symptoms in all patients treated, and the fact that circulating thyroid hormone levels were often not restored to normal, propranolol is considered an unsatisfactory alternative to conventional antithyroid drugs for routine treatment.     

Support after perinatal death: a study of support and counselling after perinatal bereavement.

After an earlier study into the practical aspects of the management of perinatal death, a counselling service was introduced for parents whose baby had died in the perinatal period. The service was monitored, and the parents who received the service were compared with a group that did not. Fifty families were allocated randomly either to the counselling (supported) group or to the contrast group, who received routine hospital care. Assessment was carried out at six and 14 months after the death, using a semi-structured interview and two self-rating scales (the general health questionnaire and the Leeds scales). Two of 16 mothers in the supported group showed psychiatric disorder at six months, compared with 10 of 19 in the contrast group (p less than 0.01, Fisher''s exact test). There was no significant difference between the two groups at 14 months, when 80% of all the women studied had recovered psychiatric symptoms. Socially isolated women and those who marital relations lacked intimacy had a higher incidence of psychiatric symptoms at six months. Early pregnancy (within six months) was associated with a higher incidence of psychiatric symptoms in the unsupported group. The duration of bereavement reaction after perinatal death was appreciably shortened by support and counselling.     

Evaluation of adverse events after influenza vaccination in hospital personnel.

Reactogenicity of trivalent influenza vaccine prepared for the 1988-89 season was assessed as part of a first-time voluntary influenza prevention program among hospital staff. Of approximately 500 full-time workers in areas with the highest concentrations of patients at high risk for influenza complications offered the vaccine 288 accepted. Of these, 266 (92%) returned a questionnaire regarding any symptoms experienced within 48 hours after vaccination; 238 (90%) of the respondents reported adverse effects. Soreness at the injection site was described by 229 subjects, 58 (25%) of whom had constant aching and 123 (54%) soreness with arm movement. Symptoms resolved in 1 to 2 days, and only 21 (9%) of those who reported symptoms said they took analgesic medication. Systemic adverse effects were described by 130 subjects (49%). Intercurrent illness accounted for some of these complaints, but 65 people (24%) described at least two of the following symptoms: generalized aching, tiredness, nausea, chills or onset of fever within 12 hours after vaccination (a symptom complex previously attributed to influenza vaccine). Systemic symptoms resolved within 0.5 to 2 days. Thirteen subjects (5%) reported missing work because of arm soreness (1 subject) or systemic symptoms (12). Adverse effects were encountered more often than expected, probably because most of the workers were young and lacked immunity to influenza. Acceptability of the program could likely be improved by using a split-virus vaccine.     

Eustachian Tube Obstruction and Radiation Therapy

One hundred and ninety-four patients with eustachian tube obstruction due to lymphoid tissue were treated with radiation therapy administered once a week for four weeks. Total dose to the skin for each lateral port was 600 r, and midline dose for a skull of 12 cm. width was approximately 42 rad for every 100 r on the skin. Of 121 patients under 15 years of age, 70% were completely better or markedly improved at six months; 8% showed no change. Long-term follow-up, averaging four and a half years after therapy, indicated that 82% were completely better or markedly improved and 8% were unchanged. Of 73 patients over 15 years of age, 58% were completely better or markedly improved at six months and 20% showed no change. After long-term follow-up (four years and four months after treatment) 68% were completely better or markedly improved and 17% showed no change.     

Controlled trial of azathioprine in chronic ulcerative colitis.

A double-blind controlled trial of azathioprine in a dose of 2-2.5 mg/kg body weight over six months was conducted among 44 patients with active chronic ulcerative colitis. Three patients treated with placebo did not complete the trial because their disease became so severe that colectomy was performed. Among patients who completed the trial the mean dose of prednisolone necessary to control the disease decreased in those treated with azathioprine and those treated with placebo; the reduction was greater among those who took azathioprine (p less than 0.001). Activity of the disease apparently improved in both treatment groups but a significant (p less than 0.001) trend was observed only in those patients treated with azathioprine. No serious side effects from azathioprine occurred during the trial but seven of 24 patients had to stop the drug because of nausea. Azathioprine may have a role in the treatment of a few patients wih troublesome chronic colitis for whom conventional drug treatment is ineffectual, or for whom continuous systemic corticosteroid treatment is needed to control symptoms, and for whom surgical treatment is inappropriate.     

One year's treatment with propranolol after myocardial infarction: preliminary report of Norwegian multicentre trial.

A prospective, randomised, double-blind study was performed to compare the effects of propranolol and placebo on sudden cardiac death in a high-risk group of patients who survived acute myocardial infarction. Altogether 4929 patients with definite acute myocardial infarction were screened for inclusion: 574 (11.6%) died before randomisation, and 3795 (77%) were excluded. Five hundred and sixty patients aged 35 to 70 years were stratified into two risk groups and randomly assigned treatment with propranolol 40 mg four times a day or placebo. Treatment started four to six days after the infarction. By one year there had been 11 sudden deaths in the propranolol group and 23 in the placebo group (p less than 0.038, two-tailed test analysed according to the "intention-to-treat" principle). Altogether there were 25 deaths in the propranolol group and 37 in the placebo group (P less than 0.12), with 16 and 21 non-fatal reinfarctions respectively. A quarter of the patients were withdrawn from each group. Withdrawal because of heart failure during the first two weeks of treatment was significantly more common among propranolol-treated patients than among the controls, but thereafter the withdrawal rate was the same. The significant reduction in sudden death was comparable with that after alprenolol, practolol, and timolol, which suggests that the mechanism of prevention is beta-blockade rather than any other pharmacological property of the individual drugs.     

High-dose IgG for post-transfusion purpura-revisited

Therapy for post-transfusion purpura (PTP) is controversial. We have evaluated the effect of high-dose IgG (HDIgG) in 11 PTP cases investigated in our institution and summarized the clinical data of 8 additional cases reported in the literature. Two of these 19 cases had to be eliminated from the analysis (1 patient received a total dose of less than 30 g of IgG; 1 patient died 2 days after starting HDIgG therapy from congestive heart failure). Out of a total of 17 cases, 16 had good or excellent response reaching normal platelet values within few days; only one failure was observed. Five patients relapsed, but attained complete remission after a second course (dose) of IgG. Total doses per course ranged between 52 and 180 g of IgG. Five different IgG preparations were used and seemed similarly effective. No adverse reactions were observed. We conclude that HDIgG is the treatment of choice for PTP.     

Outcome of [131I]metaiodobenzylguanidine therapy of neuroblastoma: seven years after.

Beginning in 1984 and based on a total of 40 treatments with [131I]metaiodobenzylguanidine (131I-MIBG) in most cases with a follow-up of 5 years or more, it seems to be worthwhile reevaluating our clinical data and draw some final conclusions: We treated 12 children with a neuroblastoma (NB) IV and 3 with a NB III. In no case 131I-MIBG was the primary therapy. The great majority suffered from recurrence. The mean treatment interval after chemotherapy was 6 months (range 0-54). We calculated a median cumulative tumor dose of 77 Gy (range 0-259) in patients with stage III and 30 Gy (range 4-267) in stage IV NB. The tumor half-life time of 131I-MIBG does not significantly differ between stage III (3 days) and IV (2-5 days). Although the median tumor dose of stage III NB exceeded that of stage IV, we found in NB IV a significant tumor remission in 7 out of 12 cases. On the other hand, a slight reduction of tumor size was seen in only 1 case of stage III NB. This indicates a lower radiation sensitivity of stage III NB. Despite this fact, the two patients with stage III NB who presented a sufficient 131I-MIBG-tumor uptake turned to become operable after 131I-MIBG. Stage IV patients improved, too, even if most of them suffered from recurrence with a very poor prognosis: 3 patients of stage IV lived longer than 48-60 month or are still alive. However, no one of this group remitted completely.(ABSTRACT TRUNCATED AT 250 WORDS)     

Raynaud's phenomenon as side effect of beta-blockers in hypertension.

A series of 102 hypertensive patients were assessed for the frequency of symptoms of Raynaud''s phenomenon and absent peripheral pulses. Out of 21 patients receiving methyldopa alone only one had cold hands and feet whereas among patients on beta-blockers the incidence was 50%. The frequency of both symptoms and absent pulses was highest in patients taking propranolol compared with those taking atenolol or oxprenolol. Patients without a foot pulse were much more likely to have cold hands. A change from propranolol to oxprenolol in some symptomatic patients resulted in improvement. In two patients the skin temperature fell after an 80-mg dose of propranolol. The mechanism by which beta-blockers induce Raynaud''s phenomenon is still not clear.     

Functional reconstruction using a depressor anguli oris musculocutaneous flap for large lower lip defects, especially for elderly patients

Described here is a new technique to reconstruct large lower lip defects using one or two musculocutaneous island flaps, which includes an innervated depressor anguli oris muscle and has a facial artery in its pedicle. Vermilion is simultaneously reconstructed using a mucosal transposition flap. Three patients who had a total lower lip defect and five patients who had a defect larger than one-half of the lower lip were treated by our procedure. All the flaps survived completely without any signs of vascular stasis. In six patients, sphincter function and sensation appeared within 3 months after surgery. In one patient who needed a total lower lip reconstruction, the depressor anguli oris muscle was atrophic and the motor nerve could not be found. This patient could not regain motion. One other patient complained of a sialorrhea accompanied by sensory loss; however, his sensation improved within 6 months after surgery. All of the reconstructed lower lips were large enough to enable the patient to wear dentures and were of a cosmetically acceptable appearance 1 year after surgery.