Biomedical subjects
S Matsubayashi
Publications and source records attributed to S Matsubayashi.
Clinical evaluation of human granulocyte colony-stimulating factor in chemotherapy for ovarian cancer.
The clinical evaluation of human granulocyte colony-stimulating factor (G-CSF) in 38 patients treated with chemotherapy for ovarian cancer stage III was investigated among 3 groups. G-CSF was not given in group A (19 courses), was administered from day 5 of chemotherapy in group B (53 courses), and was given when the WBC count decreased to below 2,000/mm3 in group C (29 courses). The time to nadir was significantly shorter in group B compared with groups A and C and revealed 10 days for the WBC count and 11 days for the neutrophil count (p <0.01), with mean nadir values of 2,896/mm3 and 982/mm3 respectively, and so the count of WBC and neutrophil have been kept during the course. The effect of G-CSF was not modified by age, body weight or the number of chemotherapy courses in groups B and C. These results demonstrate that early treatment with G-CSF may allow increased intensity of chemotherapy by using greater doses or by shortening of the interval between cycles.
Immunological findings and thyroid function of untreated Graves' disease patients with undetectable TSH-binding inhibitor immunoglobulin.
OBJECTIVE: TSH-binding inhibitory immunoglobulin (TBII) is undetectable in about 10% of untreated Graves' disease patients, but the clinical characteristics and immunological significance of this finding are unknown. In this study we evaluated the clinical characteristics of TBII negative Graves' disease. PATIENTS: We examined TBII in 1048 untreated patients at Kuma hospital from 1986 to 1990 and found 69 TBII undetectable patients (12 men and 57 women, mean age +/- SEM 35 +/- 2 years, group A). MEASUREMENTS: We compared the clinical characteristics and immunological findings of group A with 57 untreated TBII detectable Graves' patients who were selected randomly (11 men and 46 women, mean age +/- SEM 40 +/- 2 years, group B). T4, TSH, FT4, FT3, 123I thyroid uptake, TBII, thyroid stimulating antibodies (TSAb) and the volume of the thyroid using ultrasonography were measured at the first visit. RESULTS: Serum T4, FT4 and FT3 levels in group A were significantly lower than those in group B (P < 0.001). The values of TSAb in group A were significantly lower than those in group B (593 +/- 67 (mean +/- SE) vs 2143 +/- 280%, respectively, P < 0.001). The 123I thyroid uptake in group A was significantly lower than that in group B (53.1 +/- 1.1 vs 61.4 +/- 1.4%, respectively, P < 0.01). The thyroid volume in group A was significantly smaller than that in group B (39.1 +/- 3.0 vs 51.3 +/- 3.3 ml, respectively, P < 0.01). TSAb was undetectable in about 10% (6) of the TBII negative untreated Graves' patients at their first visit. CONCLUSION: In the present study, untreated TBII negative patients with Graves' disease were characterized by mild elevation of thyroid hormones, mildly elevated 123I uptake, weak TSAb activities and small goitres. The finding of both TBII and TSAb negative titres in untreated Graves' disease patients was also confirmed.
Resistance to autoimmune thyroid disease is associated with HLA-DQ.
Genotypes of DQA1 and DQB1 genes were determined by polymerase chain reaction followed by dot blot hybridization with sequence-specific oligonucleotide probes in 105 patients with goitrous autoimmune thyroiditis (Hashimoto's thyroiditis) and in 67 patients with Graves' disease to investigate whether specific DQ alleles were associated with susceptibility or resistance to autoimmune thyroid diseases. Hashimoto's thyroiditis was found to be negatively associated with DQA1*0102 and DQB1*0602 whereas Graves' disease showed a negative association with DQB1*0501. No strongly positive association with a specific DQ allele was found in either disease. These results suggest that the HLA-DQ gene may be a genetic marker for resistance to autoimmune thyroid diseases.
Insulin response to intravenous glucose in patients with anorexia nervosa showing low insulin response to oral glucose.
To investigate the cause of a low insulin secretory response to an oral glucose tolerance test (OGTT) in patients with anorexia nervosa (AN), we performed iv glucose tolerance tests (IVGTT) before and after treatment in 36 anorectic patients who showed low insulin secretion in response to the OGTT. These patients were subdivided into 3 groups by glucose tolerance curves during the OGTT: normal type, blood glucose level peaking 60 min or earlier after oral glucose ingestion; delayed type, blood glucose level peaking 90 min or later after oral glucose; and flat type, peak blood glucose level of 5.56 mmol/L or less after oral glucose. The results showed that the normal and flat type groups had normal glucose and insulin responses to iv glucose. In the delayed type group, in which the longest duration of AN before therapy was found, initial insulin secretion was decreased in response to both oral and iv glucose, indicating diminished pancreatic beta-cell function. After weight gain, this parameter improved significantly in both tests. The rate of glucose disappearance for the IVGTT was lower both before and after weight gain in this subgroup compared to that in normal controls, suggesting insulin resistance. In conclusion, the low insulin response to oral glucose seen in the flat type group may be due to the disturbance of gastrointestinal factors, such as motility. In contrast, the observations suggest that the delayed type group has beta-cell failure corrected by weight gain and has insulin resistance requiring a longer recovery time; these abnormalities are related to the duration of AN.
Severe depression associated with ACTH, PRL, and GH deficiency: a case report.
A 68-year-old man was hospitalized in August, 1990 with general malaise, loss of energy, poor appetite and severe depression. He had experienced depressed moods, markedly diminished interest, feelings of worthlessness, diminished ability to think, general malaise and muscle weakness beginning in November, 1989. He was treated for depression at another hospital until his emergent admission to our hospital because of difficulty in walking. Laboratory studies disclosed hyponatremia, low plasma ACTH level (4.2 pmol/L), and a low cortisol level (27.6 nmol/L). Rapid ACTH test elicited an increase in serum cortisol from 75.6 nmol/L to 361.2 nmol/L at 30 min. Ovine corticotropin releasing hormone (CRH) did not stimulate secretion of either ACTH or cortisol. Human growth hormone releasing hormone (GRH) together with thyrotropin releasing hormone (TRH) elicited a normal response of TSH and low responses of GH and PRL. The patient's serum autoantibodies to anterior pituitary cell membranes using GH3 rat pituitary cells and AtT-20 mouse pituitary cells were positive. On the basis of these data, the diagnosis of selective ACTH, GH and PRL deficiency was made and thought to have been caused by lymphocytic adenohypophysitis. Following cortisol replacement therapy, he quickly regained his appetite and was restored to a normal mental state of being.
[A 85-year-old right-handed woman with aphasia and left hemiparesis].
We report a 85-year-old woman who developed speech disturbance and left hemiparesis. She had a gradual onset of gait disturbance 3 years prior to the present admission. Five days before admission, she started to pace up and down in her house; she did not want to take food on the following day, and she developed fever of 39 degrees C; it was also noted that she became mute. On the next day, she developed left hemiparesis; she was still mute but was able to communicate by hand writing to some extent. She was admitted to our service on February 24, 1992. On admission, she was alert but mute; her body temperature was 37.1 degrees C, and her BP 110/70 mmHg. The lungs were clear and general physical examination was unremarkable. Neurologic examination revealed that she did not utter even a word. She was unable to understand examiner's simple questions; communication by hand writing was also difficult, but she could draw her name and a circle; repetition was also impaired. Examination of other higher cerebral functions such as praxis and gnosis was impossible. Her optic fundi were unremarkable; no anisocoria was noted; extraocular muscles appeared intact, and the vestibulo-ocular reflex was normally elicited. The nasolabial fold was shallower on the left; the tongue showed a slight deviation to the left. She had near complete spastic left hemiplegia; deep tendon reflexes were increased bilaterally.(ABSTRACT TRUNCATED AT 250 WORDS)
[A 55-year-old man with prostate cancer, papilledema, and multiple cranial nerve palsies].
We report a 55-year-old man with papilledema and multiple cranial nerve palsies. He was well until 52 years of age when there was an onset of progressive difficulty in initiating urination; he visited the urology service of our hospital where a diagnosis of prostate cancer was made; the cancer was invading the bladder and was metastasizing to lymph nodes and bones. He was treated with oochiectomy and estrogen preparations with some improvement in his symptoms. Two years later, he developed difficulty in urination again, and transurethral resection of the tumor was performed in 1991. In December 1991, he noted tingling and numb sensation in his left face, which had become progressive worse within the next one month, and he developed blepharoptosis and deafness all on the left side. He was admitted to the urology service on February 4, 1992, and a neurological consultation was asked. On physical examination, general findings were unremarkable, except for lymph node enlargements of about 0.5 to 1.0 mm in size in cervical and inguinal regions. On neurologic examination, he was alert with normal mental activities; higher cerebral functions were intact. He had normal vision and visual fields, however, papilledema was present bilaterally; pupils and light reactions were normal. Extraocular muscles were intact on the right side, however, moderate restriction was noted in the left eye in that all the extraocular muscles except for the medial rectus were weak; blepharoptosis was noted on the left; no nystagmus was present. The sensation was diminished in the left face, and left facial paresis of the peripheral type was also noted; the taste sensation was also diminished in the left anterior two thirds of the tongue. He had sensorineural deafness on the left side. The other cranial nerves appeared intact. He walked normally; no weakness or muscle atrophy was noted; muscle tone was normal and no ataxia was observed. Deep reflexes were normally elicited and symmetric; the plantar response was flexor. No meningeal signs were present. Laboratory examination revealed following abnormalities: Hb 7.1 g/dl, platelet 47,000/cmm, WBC3,800/cmm, LDH 950IU/l, PAP232ng/ml (normal less than 1.6), PA2.631ng/ml (normal less than 7.4); a small amount of effusion was noted in the left pleural cavity; cytological examination of the fluid was class V. A cranial CT scan as well as MRI were entirely normal, as was the spinal tap. He was treated with glycerol, however, there was progressive increase in the pleural effusion, and he developed dyspnea; moist rale had become audible in the end of February.(ABSTRACT TRUNCATED AT 400 WORDS)
[A 52-year-old man with sensory aphasia and multiple intracranial masses].
We report a 52-year-old-man who developed aphasia, apraxia and agnosia. He was well until December of 1991 when he noted an onset of skin scaling in the extensor sides of his elbow joints; he was admitted to the dermatology service of our hospital and was diagnosed as having pemphigoid. Treatment with PDN 30 to 60 mg/day and azathioprine 50-100 mg was started. While in the hospital there was a insidious onset of right tinnitus and tingling sensation in his right leg in the middle of March, 1991. During next one week, his family noted that the patient responded incoherently in his speech once in a while. Neurological consult was requested on April 2, 1991. On neurologic examination, he was alert but incoherent in his speech. His spontaneous speech was reduced but it was fluent. However, he had a difficulty in understanding spoken as well as written language. Naming and repetition were also impaired, and he appeared to have Wernicke's aphasia. Ideational apraxia, ideomotor apraxia, constructional apraxia, left-right disorientation, finger agnosia, and body agnosia were noted as well, but he did not have dressing apraxia or spatial disorientation. Right homonymous hemianopsia was present, but any other cranial nerves were not disturbed. He had no weakness or ataxia; gait was normal. Deep reflexes were normal and symmetric. Sensations were intact. Complete blood counts and routine blood chemistries were normal. The lung was clear. Opening pressure at spinal tap of CSF was under a normal pressure; CSF contained 6 lymphocytes/microliters and 78mg/dl of protein; a cytological study showed no malignant cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Vascular responses to angiotensin II in anorexia nervosa.
Anorexia nervosa (AN) patients have a tendency to develop renin-angiotensin-aldosterone (RAA) abnormalities caused by abnormal behaviors expressed over long periods of time. Short-term dietary sodium intake is a known modulator of blood pressure response to infused angiotensin II (A II) in normal subjects. Therefore AN patients and normal gender-matched and age-matched controls were studied for vascular responses to exogenous A II. Untreated AN patients needed significantly greater quantities of exogenous A II to raise diastolic blood pressure (DBP) to over 20 mmHg for 30 min compared with controls (12.1 +/- 0.47 versus 7.6 +/- 0.69 ng/kg/min, p < 0.01). The amount of A II required to raise DBP to over 20 mmHg in AN patients in tests before and after completion of treatment (4.2 +/- 0.33 months later) was significantly different (12.1 +/- 0.47 versus 8.1 +/- 0.25 ng/kg/min, p < 0.01). There was no significant difference between AN patients following treatment and controls. Our results indicate that it requires long time before decreased A II responsiveness caused by chronic sodium depletion normalizes in AN patients.
Carbohydrate oxidation rates in patients with anorexia nervosa.
Twenty-one hospitalized anorexia nervosa (AN) patients underwent a 50-g glucose challenge. All patients were then fed for 10 days and divided into two groups based on weight gain. Group AN-a (n = 10) gained little or no body weight over the 10-day period, whereas the second group, AN-b (n = 11), did gain weight during the same period. A third group of normal women (n = 10) served as control subjects (NC). Following ingestion of 50 g of glucose, group AN-a showed virtually the same nonprotein respiratory quotient (NPRQ) response as group NC. Group AN-b showed significant increases in basal and glucose-stimulated NPRQ and carbohydrate oxidation rate responses compared with group NC. Serum insulin responses in both AN groups were lower than those of group NC. These results indicate that insulin sensitivity in both liver and muscle may be increased in AN patients, and that refeeding tends to increase body weight rapidly in some patients due to this mechanism.
Changes in plasma cholecystokinin concentrations after oral glucose tolerance test in anorexia nervosa before and after therapy.
There is considerable evidence that the gastrointestinal hormone cholecystokinin (CCK) induces satiety and reduces food intake in both animals and humans. Impaired CCK secretion was recently reported in patients with bulimia nervosa (BN) in whom plasma CCK responses to a standardized mixed-liquid meal were significantly lower than in controls. The present study was undertaken to determine whether CCK levels were abnormal in another relatively common eating disorder, anorexia nervosa (AN), before and after therapy and to investigate the relationship to the abnormal eating behavior. Plasma CCK, serum glucose, and immunoreactive insulin (IRI) responses to a 50-g oral glucose load were measured in 13 women with AN and in nine normal sex- and age-matched controls. The AN patients were all hospitalized during treatment; following partial restoration of body weight, the tests were repeated. Initial body weights were 70.8% +/- 1.8% (mean +/- SEM) of ideal body weight (IBW), and following partial restoration were 84.3% +/- 1.4%. Body weights in normal controls were 96.3% +/- 2.1% of IBW. Initial basal CCK concentrations in the AN patients before nutritional and cognitive behavioral therapy were significantly greater than those in controls (P < .01). After partial restoration of body weight, basal CCK concentration in AN patients approached that of control subjects. When AN patients were given a glucose load before therapy, the change in CCK response was diminished when compared with that of controls. However, CCK responses to the glucose load in AN patients following therapy were similar to those of controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Thyroid histology of hyperthyroid Graves' disease with undetectable thyrotropin receptor antibodies.
To determine the histological characteristics of hyperthyroid Graves' disease with undetectable TSH receptor antibodies (TRAb), we examined the thyroid histological findings of patients with hyperthyroidism who were referred for subtotal thyroidectomy and who lacked circulatory TRAb. Four patients had undetectable TRAb (6.4 +/- 4.2%) before treatment (group A). Their pathological and clinical findings were compared with those of four patients who had hyperthyroid Graves' disease with detectable TRAb (83.8 +/- 8.3%) before treatment (group B). The groups were matched for sex, age, duration of antithyroidal drug therapy, anti-Tg antibody, and antimicrosomal antibody levels. All patients were in a euthyroid state just before operation. Papillate hyperplastic epithelia in group A were significantly less severe than in group B. Enlarged colloids were not observed in two of the four patients in group A but were observed in all four patients in group B. Moderate or marked lymphocytic infiltrations were observed in all patients in group A but were virtually absent in group B. Based on these results, it is probable that hyperthyroid Graves' disease with undetectable TRAb titers represents an early stage or subtype of usual hyperthyroid Graves' disease in which there is marked or moderate lymphocytic infiltration.
Treatment of methimazole-induced agranulocytosis using recombinant human granulocyte colony-stimulating factor (rhG-CSF).
Agranulocytosis, although extremely infrequent, is a serious complication of antithyroidal drug therapy in patients with hyperthyroidism. Presently, there is no specific therapy for this life-threatening complication, and recovery time is highly variable. Recently, recombinant human granulocyte colony-stimulating factor (rhG-CSF) was reported to be effective in shortening the recovery time of the neutropenia in patients undergoing chemotherapy. The present study was undertaken to determine the efficacy of rhG-CSF administration in patients with methimazole-induced (MMI) agranulocytosis. Thirty-four patients (7 males and 27 females, ages 16-68 yr) with MMI agranulocytosis were divided into 3 groups: group A (n = 11) was treated with antibiotics only; group B (n = 11) received antibiotics and dexamethasone, 8 mg/day; and group C (n = 12) was treated with antibiotics and im injections of rhG-CSF, 75 micrograms/day. Patients in groups A and B were studied retrospectively. When rhG-CSF became available, patients in group C were studied prospectively. Bone marrow sternal punctures were performed in all group C patients who were then divided into 2 subgroups according to the granulocyte to erythrocyte count ratio (G:E). Group C1 (n = 6) had a G:E ratio of less than 0.5, and group C2 (n = 6) had a ratio of more than or equal to 0.5. Recovery time in all groups was defined as the number of days required for the peripheral granulocyte count to be greater than 1.0 x 10(9)/L. There was no significant difference in recovery time between groups A and B: 10.1 +/- 2.2 and 12.3 +/- 1.9 days (mean +/- SE), respectively. P was not significant; the administration of dexamethasone proved to be ineffective in shortening the time for recovery from peripheral granulocytes. On the other hand, recovery time was significantly shorter in group C (6.8 +/- 1.2 days mean +/- SE) compared with groups A and B (P < 0.05). Group C2 recovered in 2.2 +/- 0.6 days whereas group C1 took much longer, 9.8 +/- 1.3 days (P < 0.001). There was a direct correlation between the G:E ratio and the peripheral leucocyte count, r = 0.806, P < 0.01. Furthermore, rhG-CSF significantly shortened recovery time when the peripheral granulocyte count was greater than 0.1 x 10(9)/L (group C2) compared with patients whose counts were less than 0.1 x 10(9)/L (group C1), 2.2 +/- 0.4 vs. 8.6 +/- 1.3 days, respectively (P < 0.001). These data indicate that administration of steroids is ineffective in shortening the duration of recovery in patients with MMI agranulocytosis.(ABSTRACT TRUNCATED AT 400 WORDS)
Immunoelectronmicroscopic differentiation of linear IgA bullous dermatosis of adults with coexistence of IgA and IgG deposition from bullous pemphigoid.
BACKGROUND: The differentiation between linear IgA bullous dermatosis (LABD) and bullous pemphigoid (BP) is sometimes difficult in patients who have both IgA and IgG deposition in a linear pattern at the basement membrane zone. OBJECTIVE: We address whether two cases of acquired subepidermal blistering disease with coexistence of IgA and IgG deposition in a linear pattern at the basement membrane zone are LABD or BP. METHODS: The two cases were investigated by immunoelectron microscopy and compared with two typical cases of LABD. RESULTS: In both cases, the deposition of IgA and IgG was ultrastructurally localized below the lamina densa in close association with anchoring fibrils, as was seen in two cases of typical LABD. CONCLUSION: These findings indicate that our two cases of acquired blistering disease with co-existence of IgA and IgG deposition are LABD, rather than BP.
Pancreatic B-cell functioning after intravenous glucagon administration in anorexia nervosa.
Abnormal glucose tolerance is often found in patients with anorexia nervosa (AN). We attempted to evaluate pancreatic B-cell functioning after intravenous glucagon administration. Fourteen patients with the restricting type of AN (percentage of ideal body weight 71.5 +/- 1.6%, mean +/- SE) and 6 patients with the bulimic type of AN (77.0 +/- 3.0%) were studied. After an overnight fast, glucagon (0.02 mg/kg) was injected i.v. into all subjects and 6 normal controls. Blood samples were obtained at 0, 5, 30, 60, 90 and 120 min to measure blood glucose (BS), serum insulin (IRI) and C-peptide (CPR). The same tests were repeated in 8 patients with restricting AN after therapy and restoration of body weight (85.9 +/- 1.0% of ideal body weight). BS responses did not differ among the groups. Peak serum levels (5 min) of both IRI and CPR in restricting AN patients were significantly lower than those in bulimic AN patients and in normal controls. BS, IRI and CPR concentrations did not change significantly following restoration of body weight. Pancreatic B-cell dysfunction after glucagon administration was observed in restricting AN patients and the abnormality persisted after short-term weight restoration.
Aldosterone responses to angiotensin II in anorexia nervosa.
Patients with anorexia nervosa (AN) tend to have renin-angiotensin-aldosterone (RAA) abnormalities caused by abnormal behaviors such as strict dieting, fasting, vigorous exercise, self-induced vomiting and abuse of laxatives and/or diuretics. Adrenal responsiveness to angiotensin II (A II) was studied in 13 AN patients before and after therapy and in 6 normal sex- and age-matched controls: adrenal responses to postural change (1 h of walking following 1 h in a supine position) and to exogenous A II injection (A II: 10 ng/kg/min intravenous infusion for 30 min). The 24-h urine sodium concentration was significantly lower in AN patients before therapy than after therapy. Plasma aldosterone secretory response to A II was significantly higher in AN patients before therapy in both postural change and exogenous A II injection tests compared with after therapy response and that of controls. On the other hand, there was no significant difference in adrenal response to postural change or to exogenous A II between AN patients after therapy and controls. In conclusion, increased A II sensitivity caused by chronic sodium deficiency in AN patients normalized over time as the patients recovered.
[A case of small epidermoid cyst in cauda equina with manifest regional hypesthesia].
This report concerns the 22-year-old female who has been suffering the paresthesia in the left buttock and thigh for three months. Neurological examination revealed nothing other than hypesthesia and hypalgesia which distributed in the third, fourth and fifth segments of left sacral region with the loss of anal reflex. Pain had not been noticed until when she came to our clinic. Myelography and MRI showed small irregular round mass occupying a third of the spinal canal behind the body of fourth lumbar spine. In the axial view of MRI, the mass was enhanced by the gadolinium (Gd) except for the small portion of its center. She underwent the surgical treatment which revealed the tumor entangling four nerves of cauda equina in its center as imaged in MRI. The tumor was epidermoid cyst which presumably caused the chemical meningitis and involved those nerves. That resulted in the sensory disturbance in the left sacral region, although the tumor was not large enough to compress the nerves.