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.     

The Effect of Phenothiazines on the Electrocardiogram

Thioridazine, chlorpromazine and trifluoperazine were administered to six psychiatric patients. Each was used in four dosage levels (thioridazine and chlorpromazine: 200, 400, 800 and 1200 mg. daily; trifluoperazine: 8, 16, 32, 64 mg. daily); and each increase in dosage was effected after four days of drug administration.Before the trial, twice during each drug period and before commencement of the next dose regimen, an electrocardiogram (ECG) was recorded. The findings indicated that thioridazine modifies the terminal portion (S-T segment, T and U waves) of the human ECG. A similar change occurred in three of six subjects while taking chlorpromazine and in one of six while taking trifluoperazine. Thioridazine induced changes in all six subjects studied, viz., blunting and notching of T waves with or without prolongation of QT interval. In some the notching produced a doublehump appearance in which a T wave of reduced voltage formed the proximal hump and a positive U wave of increased voltage formed the distal hump.Thioridazine-induced alterations in the ECG have been described as resembling those caused by quinidine; they also resemble changes associated with hypokalemia.     

Pigment Deposition in Viscera Associated with Prolonged Chlorpromazine Therapy

Twelve physically healthy young adult mental hospital patients died unexpectedly while on prolonged chlorpromazine therapy. Five of them had clinically obvious pigmentation of the exposed skin. Two of these had impairment of vision as well. Autopsies were performed on all 12 patients. Extensive deposits of pigment (exhibiting the physical and histochemical properties of melanin) were present in macrophages in the dermis and throughout the reticuloendothelial system, and in the parenchymal cells of internal organs. The dopa tyrosinase reaction indicated increased melanocyte activity in the epidermis.The possible mechanism of production of this pigment is discussed, and the belief is expressed that the increased melanin production is due, at least partly, to the effect of chlorpromazine on the autonomic nervous system, blocking the production of pigment-lightening factors, of which melatonin is the most important. A short outline of contemplated further investigation is given.     

Reversible hepatic black pigmentation and enzyme alteration induced by prolonged feeding of high dose of crocin dyes in rats

Crocin dyes, isolated from Gardenia jasminodes, did not affect hepatic function when they were orally administered to rats in a daily dose of 50 mg/kg for 8 days, but could induce acute hepatic discoloration. A high dosage of 100 mg/kg for 2 weeks could induce both hepatic damage and black pigmentation, but a lower dose of 100 mg/kg for 40 days did not. Rats fed on diet containing 1% of crocin dyes for four months were shown to have mild hepatic functional disorders and pigmentation. The black pigmentation of the liver and the acute hepatic damage associated with the discoloration were completely reversible. During the period of hepatic pigmentation caused by high dose of crocin dyes, the urine had abnormally increased porphyrin excretion and tended to display a blackish green color. The skin also appeared purplish black. The mechanism of black pigmentation seemed to correlate with the gradual accumulation of crocin dyes. In summary, the crocin dyes have a very low toxicity in rats even in high experimental dosage which would hardly happen in human practice. It is therefore suggested that the crocin dyes are safe for coloring foods.     

Skin Pigmentation and Corneal and Lens Opacities with Prolonged Chlorpromazine Therapy

Previously undescribed ocular and dermatologic complications of prolonged chlorpromazine therapy have been noted in 70 patients of a series of many thousands receiving similar therapy. All affected patients were women who had been receiving high doses of chlorpromazine, averaging 500 to 1500 mg. daily, for at least three to five years before the complications became apparent. Skin manifestations consisted of a peculiar purplish pigmentation of the skin of exposed areas of the face, neck and hands, characterized histologically by deposition of material with the staining properties of melanin in the superficial layers of the dermis, particularly in a perivascular distribution. Ocular complications consisted of granular opacity of the cornea and often of the lens as well, the latter producing a central stellate type of cataract.     

Trimethoprim-sulphamethoxazole in Acute Brucellosis

Eight patients with proved brucella infection were treated with trimethoprim-sulphamethoxazole. The dose varied from two to four tablets given twice daily for three weeks. Clinical response was rapid and all patients were asymptomatic and afebrile within two to seven days of starting therapy. Three patients relapsed clinically and bacteriologically within three weeks of ending treatment. There were no side effects of the treatment. It is suggested that the treatment be continued for at least six weeks to prevent relapses.     

Gastrointestinal Disturbances Associated with Withdrawal of Ataractic Drugs

The psychological effects of abrupt withdrawal of ataractic drugs have been studied by others. Physical symptoms also occur under such circumstances and include abdominal pain, nausea and vomiting. Forty patients were divided into four groups of 10, each group receiving one of the following drugs: chlorpromazine, thioridazine, perphenazine or chlorprothixene. This medication was then suddenly withdrawn. In each of the chlorpromazine and thioridazine groups, three patients had gastrointestinal symptoms within 48 hours, lasting one to eight days. One patient on chlorprothixene, 450 mg. daily, experienced symptoms for six days. Perphenazine withdrawal produced no such symptoms. Thioridazine has little antiemetic action but perphenazine is prescribed for vomiting; hence it seems unlikely that the reported symptoms are due to a rebound action on the vomiting centre.These findings are relevant to the situation of withdrawal of ataractics prior to administration of anesthetics and to drug studies involving cross-over from an active compound to a placebo. The increasing use of ataractics suggests that this additional diagnostic possibility should be considered in the presence of obscure gastrointestinal symptoms.     

Thiopropazate Hydrochloride in Persistent Dyskinesia

Thiopropazate (Dartalan) was found to be significantly more effective than a placebo in relieving dyskinesia in 23 patients with functional psychosis and persistent dyskinesia associated with prolonged phenothiazine therapy. Each patient whose dyskinesia had persisted unchanged for at least one month after phenothiazine withdrawal received thiopropazate by mouth for three weeks and the placebo for a similar period. Patients were evaluated before the trial, at three weeks, and at six weeks.The drug also improved psychotic behaviour. Possible side effects, which were generally mild, were noted in eight patients, of whom six had Parkinsonism and four drowsiness. None had side effects while on the placebo.The findings indicate that thiopropazate is of value in persistent dyskinesia associated with prolonged phenothiazine intake—a condition hitherto unresponsive to other treatment. Further research is required to determine the long-term effectiveness of the drug.     

Propranolol in the Control of Schizophrenic Symptoms

All schizophrenic symptoms remitted completely in six out of 14 adults who had not responded to phenothiazine drugs and who were then given propranolol. Another patient improved markedly and four improved moderately. Two had minimal or transient improvement, and one left hospital unchanged after a short, severe, toxic reaction. The six with complete remissions all began to improve within a few days of starting propranolol and the florid symptoms remitted completely after three to 26 days. They were stabilized on a daily dose of 500-3,500 mg of propranolol and at the time of writing had remained well for up to six months. Two patients who stopped propranolol after their symptoms remitted relapsed severely within a few days. Toxic effects (ataxia, visual hallucinations, and confusional states) were related to the rate of increase rather than to the absolute dose of propranolol. After the procedure was modified unwanted effects were usually mild or absent.     

An open-label, multicentre study of levocetirizine for the treatment of allergic rhinitis and urticaria in Taiwanese patients

Levocetirizine has been shown in observational studies in the west as an effective and satisfactory therapy for patients with allergic respiratory and skin disease. An open-label, multicentre observational study was conducted to investigate the patients' perception of levocetirizine in the treatment of allergic rhinitis (AR) and urticaria in Taiwanese patients. Three hundred and thirty-three patients (236 AR and 97 urticaria patients) attending out-patient clinics of medical centres across Taiwan were included in the study. Patients were treated with levocetirizine 5 mg once daily (AR patients for 2-4 weeks and urticaria patients for 2-6 weeks) and at the end of treatment, they evaluated for symptoms of disease, perception of change in symptoms, global efficacy and tolerability, global preference over previous antiallergic treatment, change in quality of sleep/daily activities, and safety and adverse events (AEs). Levocetirizine markedly improved the symptoms of AR and urticaria; with 70-75% of AR patients and 60-80% of urticaria patients reporting complete or marked improvements in individual symptoms. Asthma symptoms were completely or markedly improved in 44% of patients with AR and concomitant asthma. A majority of the patients was satisfied with levocetirizine therapy and 50-70% indicated preference for levocetirizine over previous therapy. Overall, 50-74% of all patients perceived improvements in quality of sleep/daily activities and 50-65% of the patients rated the onset of action for levocetirizine as very rapid or rapid. Somnolence was the most common AE, reported by 7.4% of AR and 7.0% of urticaria patients. The results of this study indicated that levocetirizine is an effective and satisfactory therapy for the management of allergic respiratory and skin disease in Taiwanese subjects.     

A phase 1/2 clinical trial of enzyme replacement in fabry disease: pharmacokinetic, substrate clearance, and safety studies

Fabry disease results from deficient alpha-galactosidase A (alpha-Gal A) activity and the pathologic accumulation of the globotriaosylceramide (GL-3) and related glycosphingolipids, primarily in vascular endothelial lysosomes. Treatment is currently palliative, and affected patients generally die in their 40s or 50s. Preclinical studies of recombinant human alpha-Gal A (r-halphaGalA) infusions in knockout mice demonstrated reduction of GL-3 in tissues and plasma, providing rationale for a phase 1/2 clinical trial. Here, we report a single-center, open-label, dose-ranging study of r-halphaGalA treatment in 15 patients, each of whom received five infusions at one of five dose regimens. Intravenously administered r-halphaGalA was cleared from the circulation in a dose-dependent manner, via both saturable and non-saturable pathways. Rapid and marked reductions in plasma and tissue GL-3 were observed biochemically, histologically, and/or ultrastructurally. Clearance of plasma GL-3 was dose-dependent. In patients with pre- and posttreatment biopsies, mean GL-3 content decreased 84% in liver (n=13), was markedly reduced in kidney in four of five patients, and after five doses was modestly lowered in the endomyocardium of four of seven patients. GL-3 deposits were cleared to near normal or were markedly reduced in the vascular endothelium of liver, skin, heart, and kidney, on the basis of light- and electron-microscopic evaluation. In addition, patients reported less pain, increased ability to sweat, and improved quality-of-life measures. Infusions were well tolerated; four patients experienced mild-to-moderate reactions, suggestive of hypersensitivity, that were managed conservatively. Of 15 patients, 8 (53%) developed IgG antibodies to r-halphaGalA; however, the antibodies were not neutralizing, as indicated by unchanged pharmacokinetic values for infusions 1 and 5. This study provides the basis for a phase 3 trial of enzyme-replacement therapy for Fabry disease.     

Treatment of Nelson's syndrome by pituitary implantation of yttrium-90 or gold-198.

Eight patients with Nelson''s syndrome were treated with a pituitary implant of yttrium-90 or gold-198 four to 16 years after adrenal surgery. All had considerable pigmentation. One already had cranial nerve abnormalities and visual field defects and had had both a craniotomy and deep x-ray treatment. Radiographs showed that the pituitary fossa was abnormal in seven patients. A biopsy performed in six cases showed mucoid (or basophil) adenoma in all. In the four specimens examined ACTH was identified by electron microscopy or immunofluorescence, or both. Patients were followed up after pituitary implantation for three months to 12 years. All showed decreased pigmentation, and six became normal. Four patients regained normal ACTH levels and the other two studied had decreased levels. In no case did new cranial nerve disease or further sellar expansion develop since operation, and two patients showed remodelling of the sella. Complications were temporary leakage of cerebrospinal fluid and diabetes insipidus in one patient and gonadotrophin deficiency in another.     

A marked effect of electroconvulsive stimulation on behavioral aberration of mice with neuron-specific mitochondrial DNA defects

We developed transgenic (Tg) mice modeling an autosomally inherited mitochondrial disease, chronic progressive external ophthalmoplegia, patients with which sometimes have comorbid mood disorders. The mutant animals exhibited bipolar disorder-like phenotypes, such as a distorted day-night rhythm and a robust activity change with a period of 4-5 days, and the behavioral abnormalities were improved by lithium. In this study, we tested the effect of electroconvulsive stimulation (ECS) on the behavioral abnormalities of the model. Electroconvulsive therapy, which has long been used in clinical practice, provides fast-acting relief to depressive patients and drug-resistant patients. We performed long-term recordings of wheel-running activity of Tg and non-Tg mice. While recording, we administrated a train of ECS to mice, six times over two weeks or three times over a week. The treatment ameliorated the distorted day-night rhythm within three times of ECS, but it had no effect on the activity change with a period of 4-5 days in the female mice. To study the mechanism of the action, we investigated whether ECS could alter the circadian phase but found no influence on the circadian clock system. The potent and fast-acting efficacy of ECS in the mutant mice supports the predictive validity of the mice as a model of bipolar disorder. This model will be useful in developing a safe and effective alternative to lithium or electroconvulsive therapy.     

Endocrine Response to Substitution of Corticotrophin for Oral Prednisolone in Asthmatic Children

The hypothalamo-pituitary-adrenal axis has been assessed in 17 asthmatic children before and after long-term prednisolone therapy was changed to daily corticotrophin. In 14 of the 17 children the plasma corticosteroid concentration exceeded 15 μg/100 ml within five days of starting corticotrophin. No exacerbation of asthmatic symptoms occurred during conversion. The plasma corticosteroid response to insulin-induced hypoglycaemia was normal in four children about six weeks after conversion to corticotrophin, took up to 36 months to become normal in nine, and remained abnormal in one child throughout the period of the trial.     

Transorbital lobotomy; its use in relapsing psychotic states

Twenty-five private patients were treated by transorbital lobotomy. The period of observation after operation was from six months to three years. In 14 cases of affective disorders in which there was not adequate response to shock therapy, nine patients made social recovery and maintained good health and four were improved. Some follow-up shock therapy was necessary for about one-fifth of the patients. Of eight schizophrenic patients four made excellent social recoveries, two improved and two were not improved. In three cases of obsessive compulsive states, results were not satisfactory. In light of the factors of less disturbance to the total personality, absence of postoperative complications, shortened hospitalization, pecuniary savings and better clinical results, the authors prefer transorbital lobotomy to prefrontal lobotomy in private psychiatric practice and believe that in cases of frequent relapse early use of the procedure should be considered to prevent development of a chronic state.     

TRANSORBITAL LOBOTOMY—Its Use in Relapsing Psychotic States

Twenty-five private patients were treated by transorbital lobotomy. The period of observation after operation was from six months to three years. In 14 cases of affective disorders in which there was not adequate response to shock therapy, nine patients made social recovery and maintained good health and four were improved. Some follow-up shock therapy was necessary for about one-fifth of the patients. Of eight schizophrenic patients four made excellent social recoveries, two improved and two were not improved. In three cases of obsessive compulsive states, results were not satisfactory.In light of the factors of less disturbance to the total personality, absence of postoperative complications, shortened hospitalization, pecuniary savings and better clinical results, the authors prefer transorbital lobotomy to prefrontal lobotomy in private psychiatric practice and believe that in cases of frequent relapse early use of the procedure should be considered to prevent development of a chronic state.     

A prospective, blinded, randomized, controlled clinical trial of topical negative pressure use in skin grafting

Topical negative pressure has been demonstrated to improve graft take in a number of noncomparative studies. This study aimed to assess whether split-thickness skin graft take is improved qualitatively or quantitatively with topical negative pressure therapy compared with standard bolster dressings. A blinded, prospective, randomized trial was conducted of 22 adult inpatients of Liverpool Hospital between July of 2001 and July of 2002 who had wounds requiring skin grafting. After grafting, each wound half was randomized to receive either a standard bolster dressing or a topical negative pressure dressing. Skin graft assessment was performed at 2 weeks by a single observer blinded to the randomization. Two patients were lost to follow-up and were excluded from the study. There were 20 patients (12 men and eightwomen) in the study group. The median patient age was 64 years (range, 27 to 88 years), and the mean wound size was 128 cm2 (range, 35 to 450 cm2). The wound exposed subcutaneous fat in eight patients, muscle in six patients, paratenon in four patients, and deep fascia in two patients. At 2 weeks, wounds that received a topical negative pressure dressing had a greater degree of epithelialization in six cases (30 percent), the same degree of epithelialization in nine cases (45 percent), and less epithelialization in five cases (25 percent) compared with their respective control wounds. Graft quality following topical negative pressure therapy was subjectively determined to be better in 10 cases (50 percent), equivalent in seven cases (35 percent), and worse in three cases (15 percent). Although the quantitative graft take was not significant, the qualitative graft take was found to be significantly better with the use of topical negative pressure therapy (p < 0.05). Topical negative pressure significantly improved the qualitative appearance of split-thickness skin grafts as compared with standard bolster dressings.     

Hormonal treatment for unilateral inguinal testis: comparison of four different treatments.

BACKGROUND: Hormonal treatment of cryptorchidism has been used since the 30s, but controversies persist on its efficacy. It is also unclear whether there are differences with the use of different hormonal trials. Aims: To evaluate the efficacy of four hormonal treatments on testicular descent in a homogeneous group of cryptorchid boys. PATIENTS: 155 patients (age 10-48 months) with unilateral inguinal palpable testis were studied. Methods: The patients were subdivided into four groups according to hormonal treatment: group 1 = hCG [500 IU/week (if the chronological age was <2 years) or 1,000 IU/week (if the chronological age was >2 years) for 6 weeks]; group 2 = hCG + hMG (hCG as in group 1 + hMG 75 IU/week for 6 weeks); group 3 = GnRH (1,200 microg/daily for 28 days); group 4 = GnRH + hCG (1,200 microg/daily for 28 days + 1,500 IU/week for 3 weeks, respectively). The results were evaluated at the end of the treatment period and 6 months later to exclude temporarily positive results. RESULTS: At the end of the hormonal therapy, scrotal testicular descent was present in 30 of 155 boys (success rate 19.3%). Seven testes relapsed during follow-up (23.3%). The long-term success rate was 14.8% (23/155 testes). No significant differences were observed in success rates as well as in relapse rates among the four groups. CONCLUSIONS: Hormonal therapy induced permanent testicular descent in a minority of young cryptorchid boys with inguinal palpable testis. Similar results were obtained with four different trials.     

阿托伐他汀改善冠心病患者血管内皮功能的临床研究

目的：观察短期阿托伐他汀治疗对高胆固醇血症的冠心病患者血管内皮功能的影响。方法：78例高胆固醇血症患者每日口服阿托伐他汀共8周,服药前后测量患者血清的总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白胆固醇（IDIrC）、高密度脂蛋白胆固醇（HDL-C）和氧化低密度脂蛋白（ox-LDL）以及NO值,并用彩色多普勒超声测定反应性充血时肱动脉内径的变化。结果：高胆固醇血症患者经阿托伐他汀8周治疗后,血清的TC、TG、LDL-C和ox-LDL明显下降,血清的HDL-C以及NO值明显增加,反应性充血时肱动脉内径扩张程度明显增加,这些与治疗前相比有明显差异。结论：阿托伐他汀治疗能使高胆固醇血症的冠心病患者血脂改变,NO值增加,血管内皮功能改善。     

Subcutaneous interleukin-2 and interferon-alpha 2b in patients with metastatic renal cell cancer: the German outpatient experience

A phase II clinical trial was conducted using subcutaneous recombinant human interleukin-2 (rIL-2, EuroCetus) and subcutaneous interferon-alpha 2b (rIFN-alpha 2b, Essex) in patients with advanced cancer. Safety and tolerance of this outpatient regimen were assessed in 17 patients with progressive metastatic renal carcinoma, 14 of whom were evaluable for clinical response to combined rIL-2 and rIFN-alpha 2b. In this study, rIL-2 was administered every 12 hours, at 1.5 million (Cetus) U/m2 on days 1 and 2, followed by 0.3 million U/m2 5 days per week for 6 consecutive weeks. Concomitantly, rIFN-alpha 2b was given as 5 million U/m2 three times weekly for 6 consecutive weeks. Patients presenting with stable or regressive disease after 6 weeks of rIL-2 and rIFN-alpha 2b (11 of 14) were scheduled to repeat combination therapy. After one treatment cycle, five of 14 patients presented with partial remission; two of these patients achieved complete regression of metastatic lesions. After therapy, six patients have been in stable disease for up to 8 months. toxicity of this regimen was moderate, with local inflammation of the injection sites, grade I-II (World Health Organization criteria) fevers, chills, malaise, nausea and/or vomiting, and anorexia in 70% to 100% of patients treated. After 6 weeks of rIL-2 and rIFN-alpha 2b, laboratory evidence of treatment-related hypothyroidism and hyperthyroidism was obtained in one and four patients, respectively. Immunogenicity of sc rIL-2 was mostly limited to the development of nonneutralizing antibodies that occurred in approximately 40% of patients. None of the patients exhibited antibodies specific to rIFN-alpha 2b.