Antithyroid drugs inhibit radioiodine-induced increases in thyroid autoantibodies in hyperthyroid Graves' disease.

Methimazole (MMI) has been reported to affect prognosis in hyperthyroid Graves' disease patients treated with radioiodine (131I). In the present study, serum concentrations of thyroxine (T4), triiodothyronine (T3), thyroglobulin (Tg), thyrotropin-binding inhibitory immunoglobulin (TBII), thyroglobulin antibody (TgAb), and thyroid-peroxidase antibody (TPOAb) were measured serially for 1 year in patients with Graves' disease after 131I treatment either given alone (group 1, 41 patients) or followed by an antithyroid drug (group 2, 19 patients). The effect of antithyroid drugs on these parameters was analyzed retrospectively. Mean serum concentrations of T4 and T3 both decreased to normal within 3 months after 131I treatment in both groups. Serum Tg concentrations in group 1 showed significant transient increases (about four times the basal value) 1 month after 131I administration. Titers of TBII, TgAb, and TPOAb in group 1 also increased transiently after 131I treatment, with the maximum increase at 3 months. Antithyroid drugs significantly lessened 131I-induced increases in serum concentrations of Tg and all thyroid autoantibodies tested. One year after 131I treatment, 33 of 41 patients (80%) were euthyroid or hypothyroid in group 1; this was true for only 4 of 19 group II patients (22%). The results indicate that administering antithyroid drugs after 131I treatment reduced 131I-induced damage to the thyroid and reduced therapeutic efficacy of 131I in hyperthyroidism. Drug treatment also inhibited release of Tg and blunted 131I-induced increases in titers of thyroid autoantibodies.

Stromal keratitis and anterior uveitis due to herpes simplex virus-2 in a young child.

BACKGROUND: An uncommon case of stromal keratitis and anterior uveitis due to herpes simplex virus type 2 (HSV-2) is reported. CASE: The patient was a 3-year-old boy admitted for conjunctival injection of the right eye of unknown cause, accompanied by corneal opacity and anterior uveitis. OBSERVATIONS: High titers of antibodies against HSV and Epstein-Barr virus (EBV) were found in blood samples. Polymerase chain reaction (PCR) for the detection of HSV-1, -2, and EBV genome fragments was carried out using an anterior chamber sample as a template. An HSV-2 genome fragment was amplified by PCR. Administration of acyclovir and betamethasone was started, with the consequent elimination of corneal opacity, inflammatory cells, and keratic precipitates. CONCLUSION: PCR clearly showed that HSV-2 was the causative pathogen of the stromal keratitis and anterior uveitis in this young patient. Systemic EVB infection may induce systemic immunocompromised conditions that can lead to reactivation of HSV-2 followed by ocular disorders.

Evaluation of end of life care in cancer patients at a teaching hospital in Japan.

OBJECTIVES: To analyse the decision making for end of life care for patients with cancer at a teaching hospital in Japan at two periods 10 years apart. DESIGN AND SETTING: Retrospective study conducted in a 550 bed community teaching hospital in Okinawa, Japan. PATIENTS: There were 124 terminally ill cancer patients (45 women; 79 men; median age, 69 years) admitted either in 1989 and 1999 for end of life care with sufficient data to permit analysis. MAIN MEASUREMENTS: Basic demographic data, notification to the patient that he or she had cancer, patient involvement in do not resuscitate (DNR) orders, and various medical interventions which were performed in the month prior to the patient's death were evaluated. RESULTS: In 1989 none of the patients were notified of their diagnosis; in 1999 five patients were informed (p = 0.026). Of the 113 (91%) patients with a written DNR order, none were involved in consenting to the DNR order. In the month before death, patients in both groups received non-palliative treatments such as feeding tube placements (five in 1989; five in 1999), total parenteral nutrition (six in 1989; eight in 1999), and intravenous albumin infusion (four in 1989; five in 1999). Morphine use increased (30%) significantly in 1999 compared with the 1989 group. CONCLUSIONS: The majority of patients dying of cancer were still not informed of their diagnosis and were seldom involved in DNR decision making at a teaching hospital in Japan. There was no change in the number of potentially futile interventions that were performed (6-13%) but morphine use increased. Modern ethical education is urgently needed in Japanese medical practice to improve decision making process in the end of life care.

Poly(uridylic acid) sequences in messenger ribonucleic acid of HeLa cells.

The poly(uridylic acid [poly(U)] sequences of 30 to 40 nucleotides found in the heterogeneous nuclear ribonucleic acid (RNA) Of HeLa cells are also present in the poly(adenylic acid) [poly(A)] containing messenger RNA (mRNA) of these cells. Twenty-five percent of the total poly(U) sequences in the cell are found in the cytoplasm after HeLa cells have been labeled for 2.5 h with 32P. This value is close to 40% if only poly(A) containing RNA molecules of the cell are considered. The distribution of poly(U) sequences parallels that of poly(A) sequences in different size classes of cytoplasmic messenger RNA. From the concentrations and lengths of the two sequences it can be estimated that about 20% of the poly(A) containing mRNA molecules could contain one poly(U) sequence. Several lines of evidence have been developed to rule out poly(U) containing heterogeneous nuclear RNA (HnRNA) as the source of the poly(U) sequences in cytoplasm. Poly(U) sequences are also found in RNA molecules of the nucleus and cytoplasm which do not contain poly(A). Although poly(U) sequences are most abundant in nuclear RNA species lacking poly(A), they are well represented in a class of RNA molecules in cytoplasm which lack poly(A), but which otherwise resemble the polysomal mRNA of HeLa cells.

Pupillary evaluation for differential diagnosis of coma.

OBJECTIVES: To determine the usefulness of bedside evaluation of pupils in determining the aetiology of coma by adopting a probabilistic approach. PATIENTS AND METHODS: One hundred and fifteen consecutive patients presenting with coma were enrolled in this prospective cohort during the 12 month study period in the emergency room of a community teaching hospital. Patients underwent structured clinical examinations and laboratory and imaging tests. Assignment of aetiology of coma was based on strict adherence to predetermined criteria and achieved by consensus of the two physician investigators. One year follow up was obtained in all patients. RESULTS: Aetiology of coma was determined in 98% of the patients. It was metabolic in 69 patients (60%) and structural in 46 patients (40%). Metabolic causes included drug overdose, acute alcohol intoxication, hypoglycaemia, sepsis, and pneumonia. Structural causes included intracerebral haemorrhage, subarachnoid haemorrhage, cerebral infarction, subdural haematoma, and epidural haematoma. Multivariate logistic regression analysis showed light reflex loss (likelihood ratio for positive test result 3.59) and anisocoria (likelihood ratio for positive test result 9.0) as independent predictors of structural origin. CONCLUSIONS: In this prospective study of patients presenting to the emergency room of a community based teaching hospital with coma, in about 60% the coma is of metabolic origins and in about 40% of structural origins. Light reflex loss and anisocoria suggest a structural aetiology.

CT-guided stereotactic aspiration of intracerebral hematoma--result of a hematoma-lysis method using urokinase.

CT-guided stereotactic aspiration was performed in the CT room on 97 patients with hypertensive intracerebral hematomas, using a standard ventricular cannula. Residual hematomas were liquefied by urokinase and aspirated through the drainage tube. Major and minor rebleeding were seen in 7 cases. Two out of the 4 major rebleeding cases were followed by craniotomy, while the other cases were treated conservatively. More than 80% of the hematomas were aspirated in 68 cases, 50-70% in 19 cases and 30-40% in 6 cases. Operation in the CT room and hematoma lysis with urokinase is very useful for the aspiration of intracerebral hematomas.

Measurement of red blood cell zinc concentration with Zn-test kit: discrimination between hyperthyroid Graves' disease and transient thyrotoxicosis.

We have previously reported in patients with hyperthyroidism that the red blood cell (RBC) zinc (Zn) concentration reflects the mean thyroid hormone concentration over the preceding months. In the present study, the concentration of RBC Zn was measured by a simple and easy method with a Zn-test Wako kit. Within-run and between-run precision were 1.4% and 1.3%, respectively. The relationship between RBC concentration and dilution was linear. The average recovery was 103%. A good correlation (r=0.97) was obtained between this method and atomic absorption spectrophotometry. The mean concentration of RBC Zn in 39 euthyroid controls was 12.6 +/- 1.3 mg/l, ranging from 10.4 to 15.1 mg/l. The RBC Zn concentrations in 38 patients with Graves' disease, in 10 patients with silent thyroiditis and in 3 patients with gestational thyrotoxicosis were 7.3 +/- 1.6 (3.2-9.8), 12.0 +/- 1.6 (9.5-14.2) and 11.8 +/- 1.7 (10.5-13.7) mg/l, respectively. The concentration of RBC Zn was able to differentiate hyperthyroid Graves' disease from transient thyrotoxicosis except in 1 case and was a better index than TSH-binding inhibitory immunoglobulin. These results indicate that measuring RBC Zn with the Zinc-test Wako kit is very useful in differentiating hyperthyroid Graves' disease from transient thyrotoxicosis.

Role of thyroid-stimulating blocking antibody in patients who developed hypothyroidism within one year after 131I treatment for Graves' disease.

OBJECTIVE: We recently reported that thyroid-stimulating blocking antibody (TSBAb) may not contribute to the development of hypothyroidism more than six years after 131I treatment. In the present study, we attempted to determine whether hypothyroidism that develops within a shorter period of time following 131I therapy is associated with TSBAb. DESIGN: Retrospective study. PATIENTS: Sera were obtained from 8 patients who developed hypothyroidism within 6 months after 131I therapy (Group 1), 8 patients who became euthyroid one year after 131I therapy (Group 2), and 7 patients who developed transient hypothyroidism (Group 3). MEASUREMENTS: Thyroid stimulating antibody (TSAb) activity was measured as the amount of cyclic adenosine monophosphate (cAMP) produced by cultured FRTL-5 cells, and TSBAb activity as the inhibition of cAMP produced in response to 100 mU/l bovine TSH. RESULTS: At about 3 months after 131I treatment, TSAb activity increased significantly in Groups 2 and 3, but did not change in Group 1. In contrast, TSBAb activity in Group 1 increased significantly and was positive in 6 patients at that time. At 12-18 months after 131I treatment, TSBAb activity tended to decrease and remained positive in 3 patients but became negative in 3 patients. It did not change in the patients in Groups 2 and 3. The patients in Group 1 were treated with levothyroxine, 75-125 micrograms/day. Levothyroxine was discontinued in the 3 patients whose TSBAb activity disappeared. Two of them remained euthyroid, and 1 became hypothyroid. CONCLUSION: Results indicate that the hypothyroidism that develops within a short time after 131I treatment may be caused by TSBAb activity. Thyroid function may be recovered when TSBAb activity disappears.