The possibility of vertical transmission of human papillomavirus through maternal milk.

Human papillomavirus (HPV) DNA has been detected in the oral cavity of infants and breast cancer tissue, suggesting its vertical transmission through maternal milk. We determined whether HPV is detected in maternal milk and is vertically transmitted by breast-feeding. Informed consent was obtained, and maternal milk samples (n=80) were analysed for high-risk HPV DNA. In 43 women, this DNA was measured in the uterine cervix. In women with positive samples, this DNA was measured in the oral cavities of their children. The domain including HPV E6 and E7 was amplified by polymerase chain reaction using consensus primers, and HPV serotype determined by electrophoresis after restriction enzyme digestion. High-risk HPV-16 was detected in two of 80 samples (2.5%), and in these two cases, high-risk HPV was not detected in the uterine cervix or oral cavity of the child. It was concluded that the infection of HPV in maternal milk is rare (2/80); vertical transmission through maternal milk was not detected in this study (0/80). HPV infection through maternal milk may occur, but its likelihood is low.

A case of ovarian endometrioid adenocarcinoma with a yolk sac tumor component.

Endometrioid adenocarcinoma of the ovary coexists very rarely with yolk sac tumor (YST). This unusual mixed tumor is thought to be a rare variant of endometrioid ovarian carcinoma because of its aggressive behavior, lack of response to chemotherapy, and unfavorable prognosis. We report a case of ovarian endometrioid adenocarcinoma with a YST component in a postmenopausal woman. The patient was treated by surgery and a combination of bleomycin, etoposide, and cisplatin and taxol and carboplatin. She has been clinically free of tumor for 20 months. Immunohistochemically, the YST component reacted for alpha-fetoprotein. YST areas were negative for both CA125 and sex-hormone receptors. Cytokeratin7 and epithelial membrane antigen were negative in YST, but positive in endometrioid adenocarcinoma. The occurrence of this unusual case suggests that even somatic carcinomas may acquire an extraembryonal germ cell differentiation.

Expression of Tn and sialyl-Tn antigens in the neoplastic transformation of uterine cervical epithelial cells.

The expression of simple mucin-type carbohydrate antigens, Tn and sialyl-Tn antigens, was evaluated by immunohistochemical staining with monoclonal antibodies in normal squamous epithelium, dysplasia, carcinoma in situ, and invasive squamous cell carcinoma of the uterine cervix. The expression of the Tn antigen detected by HB-Tn1 and B1.1 was found in 17 (20%) and 19 (23%) of the 83 invasive carcinomas, respectively, but was not found in the 36 normal squamous epithelia, 22 severe dysplasias, or 24 carcinomas in situ. The sialyl-Tn antigen was detected by HB-STn1 and TKH-2 in 14 (64%) and 11 (50%) of the 22 severe dysplasias, 13 (54%) and 10 (42%) of the 24 carcinomas in situ and 48 (58%) and 42 (51%) of the 83 invasive carcinomas, respectively, but was completely absent in 36 normal squamous epithelia. Coexpression of the sialyl-Tn antigen was observed in 89% of the cases expressing the Tn antigen. No significant difference was observed between the immunoreactivities of the antigens in the metastatic lymph nodes and primary tumors. No correlation was found between the expression of each antigen and clinical state, histologic type, depth of invasion, parametrial spread, lymphatic and vessel permeation, lymph node metastasis, or 5-year survival rate. The expression of Tn and sialyl-Tn demonstrates a specific change in the neoplastic progression from carcinoma in situ to invasive carcinoma and from normal to dysplasia, respectively, in squamous cell neoplastic lesions of the cervix. Tn and sialyl-Tn antigens may be useful markers for biologic investigation of neoplastic transformation in cervical squamous cell carcinoma.

Apolipoprotein E is present in primary localized cutaneous amyloidosis.

Apolipoprotein E (apoE) is one of the amyloid associated proteins that is found in the amyloid plaque of Alzheimer's disease and systemic amyloidosis. ApoE might play an important part in the etiology of Alzheimer's disease by functioning as a "pathologic chaperone" to promote the formation of amyloid filaments. In this study, we investigated whether apoE is associated with amyloid deposits of primary localized cutaneous amyloidosis using immunohistochemistry, immunogold electron microscopy, and immunoblotting. The subjects consisted of 12 patients with lichen amyloidosus and one patient with macular amyloidosis. Light microscopically, amyloid deposits in the dermal papillae were round in shape and stained with Congo red. Immunohistochemically, apoE was detected in amyloid deposits in all the cases examined. Immunogold electron microscopy showed apoE immunoreactivity on the amyloid deposition. Immunoblots of amyloid-positive skin showed 35K and 14K proteins, which were taken to be apoE and its fragment, respectively. In normal skin extract, only the 35K protein was detected by the anti-human apoE. Moreover, the intensity of the amyloid-positive skin sample was stronger than that of the normal skin sample. Monoclonal anti-cytokeratin antibody reacted with the 45K protein of the amyloid-positive skin extract. These results indicate that apoE is a component of primary localized cutaneous amyloidosis, and that it might play an important role in primary localized cutaneous amyloidosis.

Effect of dye laser pulse duration on selective cutaneous vascular injury.

The pulsed dye laser at 577 nm, a wavelength well absorbed by oxyhemoglobin, causes highly selective thermal injury to cutaneous blood vessels. Confinement of thermal damage to microvessels is, in theory, related to the laser exposure time (pulsewidth) on selective vascular injury. This study investigates the effect of 577 nm dye laser pulsewidth on selective vascular injury. Nine Caucasian, normal volunteers received 577 nm dye laser exposures at pulsewidths of 1.5-350 microseconds to their skin. Clinical purpura threshold exposure doses were determined in each volunteer, and biopsies of threshold and suprathreshold doses were examined in each volunteer. The laser exposure dose required to produce purpura increased as pulsewidth increased in all 9 subjects (p less than 0.001). This finding corresponds to laser pulsewidths equal to or exceeding the thermal relaxation times for dermal blood vessels. Histologically, vessel damage was selectively, but qualitatively, different for short vs long pulsewidths. Pulsewidths shorter than 20 microseconds caused vessel wall fragmentation and hemorrhage, whereas longer pulsewidths caused no significant hemorrhage. The purpura noted clinically appears to be due to a coagulum of intralumenal denatured erythrocytes. At 24 h, there was marked vessel wall necrosis at all pulsewidths. The short pulsewidths may cause erythrocyte vaporization, rapid thermal expansion, and mechanical vessel rupture with hemorrhage. Long pulsewidths appear to cause thermal denaturation with less mechanical vessel damage. The selective, nonhemorrhagic, vascular necrosis caused by the long-pulsewidth dye laser may lead to a more desirable clinical outcome in the therapy of blood vessel disease processes.

5S rRNA binding proteins from the hyperthermophilic archaeon, Pyrococcus furiosus.

A determination was made of the nucleotide sequence of the 2719 bp region of a ribosomal protein gene cluster (PfeL32-PfeL19-PfL18-PfS5-PfL30) containing a 5S rRNA binding protein L18 homolog of hyperthermophilic archaea Pyrococcus furiosus. The organization of the archaeal ribosomal protein gene cluster is similar to that in the spc-operon of Escherichia coli (L6-L18-S5-L30-L15) but has two additional genes, namely those encoding PfeL32 and PfeL19, which were identified as extra proteins that are apparently not present in bacterial E. coli. Using an inducible expression system, P. furiosus mature PfL18 protein and a mutant PfL18 with the basic N-terminal amino acid region deleted were produced in large amounts in E. coli and Northwestern analysis showed the N-terminal region of PfL18, including the conserved arginine-rich region, to have a significant role in 5S rRNA-PfL18 interaction.

High expression rate of Tn antigen in metastatic lesions of uterine cervical cancers.

The significance of altered expression of MN blood group antigens was examined by studies on the expressions of Thomsen-Friedenreich antigen (T antigen) and Tn antigen in primary and metastatic lesions of 29 human uterine cervical cancers. These antigens were measured by the avidin-biotin-peroxidase (ABC) method with peanut agglutinin (PNA) lectin for T antigen and Vicia villosa agglutinin (VVA) lectin for Tn antigen. Proportion of cancer cells expressing Tn antigen was higher in the metastatic lesions than in the primary tumors in 10 of the 29 cases, less in the metastasis than in the primary tumor in one case, and similar in the primary and metastatic lesions in the other 18 cases. Reaction for Tn antigen was positive in 24 (82.8%) of the 29 metastases, and in 17 (58.5%) of the 29 primary lesions. Thus, the rate of Tn antigen expression was significantly higher in the metastases than in the primary lesions (P < 0.05). On the other hand, there was no significant difference between the immunoreactivities of T antigen in metastases and primary tumors. These findings support our previous suggestion that expression of Tn antigen is closely related to the metastasis to regional lymph nodes and may reflect an important role of this carbohydrate in the process of metastasis of cervical cancer.

Serum osteoprotegerin/osteoclastogenesis-inhibitory factor during pregnancy and lactation and the relationship with calcium-regulating hormones and bone turnover markers.

Pregnancy and lactation induce dynamic changes in maternal bone and calcium metabolism. A novel cytokine termed osteoprotegerin (OPG)/osteoclastogenesis-inhibitory factor (OCIF) was recently isolated; this cytokine inhibits osteoclast maturation. To define the effects of pregnancy and lactation on circulating OPG/OCIF in mothers, we studied the changes in the levels of OPG/ OCIF as well as those of calcium-regulating hormones and biochemical markers of bone turnover in the maternal circulation during pregnancy (at 8-11 weeks, at 22-30 weeks, at 35-36 weeks and immediately before delivery) and lactation (at 4 days and at 1 month postpartum). Serum intact parathyroid hormone levels did not change and were almost within the normal range in this period. In contrast, serum 1,25-dihydroxyvitamin D levels increased with gestational age and were above the normal range during pregnancy. After delivery, they fell rapidly and significantly (P<0.01) to the normal range. The levels of serum bone-specific alkaline phosphatase, one of the markers of bone formation, increased with gestational age. After delivery, these levels were further increased at 1 month postpartum. The levels at 1 month postpartum were significantly higher than those at 8-11 and 22-30 weeks of pregnancy (P<0.01 and P<0.05 respectively). The levels of serum C-terminal telopeptides of type I collagen, one of the markers of bone resorption, did not change during pregnancy. After delivery, they rapidly and significantly (P<0.01) rose at 4 days postpartum, and had then fallen by 1 month postpartum. Circulating OPG/OCIF levels gradually increased with gestational age and significantly (P<0.01) increased immediately before delivery to 1.40+/-0.53 ng/ml (means+/-S.D.) compared with those in the non-pregnant, non-lactating controls (0.58+/-0.11 ng/ml). After delivery, they fell rapidly to 0.87+/-0.27 ng/ml at 4 days postpartum and had fallen further by 1 month postpartum. These results suggest that the fall in OPG/OCIF levels may be partially connected with the marked acceleration of bone resorption after delivery.

Immunological functions of adult T cell leukemia cells of a patient complicated with synchronous double primary gynecologic cancer.

A patient with triple malignancies is reported, who presented cervical cancer, vulvar cancer and adult T cell leukemia (ATL). ATL was diagnosed as a smouldering type, because antibody to human T cell leukemia virus associated antigen (ATLA) was positive with a titer of 1:160. Although her malignant cells had an OKT 4+8-3+Tac+ phenotype, the cells did not display helper T cell functions. Namely they showed no response to Phytohemagglutinin (PHA) and Interleukin 2 (IL-2) and suppressed the PWM driven IgG synthesis of B cells obtained from healthy donor. They did not produce IL-2 by stimulation with PHA and phorbol myristate acetate (PMA). Furthermore, these ATL cells were producing IL-2 inhibitor like factors. As synchronous triple malignancies are extremely rare, two gynecologic cancers seem to ascribe to the suppressing state of the immunosurveillance mechanism by viral infection.

Establishment and characterization of a novel human promonocytic cell line from peripheral blood of a patient with psoriasis.

Human monocyte/macrophage lineages have unique phagocytic and immune-regulatory functions. We established a promonocytic cell line from the peripheral blood of a patient with psoriasis vulgaris. The newly established cells, termed YAP cells, grew in a suspension culture. In Wright-Giemsa-stained preparations, YAP cells were round or polygonal in shape. Transmission electron microscopy showed that the cells had clear nuclei with well-defined nucleoli. There were frequent mitochondria, a relatively abundant endoplasmic reticulum profile, free ribosomes and an occasional Golgi apparatus. Cytochemical studies showed a positive reaction for alpha-naphthyl butyrate esterase, which was completely inhibited by sodium fluoride, a diffuse positive reaction for periodic acid-Schiff, and a negative result for alkaline phosphatase and peroxidase. A large population of YAP cells reacted with the CD4, CD11b, CD25 and CD33 surface markers, but not with CD2, CD3, CD8 or CD19. We also found that YAP cells produced considerable amounts of TNF alpha, which was detected in the culture supernatant when the cells were treated with 1 ng/ml 12-O-tetradecanoylphorbol-13-acetate (TPA). Chromosome analyses showed that YAP cells contained a variety of marker chromosomes. It should be stressed that YAP cells were derived from a patient with a non-neoplastic disorder, whereas most monocytic cell lines previously reported are of malignant origin. This newly established cell line might be valuable for studying the pathogenesis of psoriasis, especially the role of monocytes/macrophages in the aetiology of the disease.

Association of apolipoprotein allele epsilon 2 with psoriasis vulgaris in Japanese population.

We studied phenotypic variations of apolipoprotein E (apoE) and the corresponding allele frequencies in 100 Japanese patients with psoriasis vulgaris (PV). The phenotypes of apoE were examined using analytical isoelectric focusing followed by immunoblotting with goat anti-apoE antibody and alkaline phosphatase-conjugated rabbit antigoat IgG. The phenotypic frequency of apoE3/2 in PV was significantly higher than in healthy controls, and this elevation was associated with an increased frequency of the epsilon 2 allele. Therefore, it is suggested that the apoE molecule plays an important role in the development of PV.

Successful treatment of vitiligo with a sex steroid-thyroid hormone mixture.

Four patients with generalized vitiligo were successfully treated by oral administration of a sex steroid-thyroid hormone (Metharmon-F, 2 tablets daily). Histopathologically, the repigmented skin showed increased numbers of melanocytes and melanin granules in the keratinocytes.

Group practice--trend for the future.

Group practices in various forms and combinations appear to set the trend for small animal practice management. By pooling their financial resources, energies, and talents, veterinarians can share the burden of increasing overhead costs and enjoy the benefits of specialization, new technologies, continuing education, consultations and referrals, peer review, applied research and publication, and fringe benefits such as paid vacation and sick leave, profit sharing, and pension. Group practices preserve ownership continuity at fair market value and afford opportunities for the utilization of expert business consultants. There are prerequisites to establishing a successful group practice: An adequate personal income base, a sufficient pet population, and business associates with compatible practice philosophy. Special considerations must be given to the social, economic, and psychological forces at work in a group practice environment. Professional and personal interactions can make or break a group practice. The group concept, MIP treatment of clients and their pets, and personalized appointments are important features which must be emphasized. The law of supply and demand and the law of diminishing returns must be kept in focus at all times. In tandem, they dictate the fortunes of all business enterprises and group practices can be particularly vulnerable to them. Long-term business commitment is a condition of group practice ownership and may pose a conflict with other interests. A predetermined buy-sell agreement and deferred compensation plan may provide the answer in case of dissolution, termination, or early retirement. A system of animal and material transport and transfer of business transactions and medical records must be set up between satellite clinics and the base hospital. A hospital-owned-and-operated shuttle service appears to offer the greatest flexibility and convenience. Cost-effectiveness of a shuttle service depends on the volume of referral cases generated for the base hospital. Computers may provide the answer to rapid and reliable transfer of data between satellite clinics and central or base hospitals in the near future. New approaches to small animal medicine and practice management must be explored and adopted. Prepaid pet medical insurance seems to be the answer to rapidly growing sophistication and escalating cost of small animal patient care. Human and companion animal interactions have been given a fresh impetus by veterinary educators, clinical psychologists, psychiatrists, humane societies, organizations for the mentally and physically handicapped, gerontologic centers, and others.(ABSTRACT TRUNCATED AT 400 WORDS)

[Magnetic resonance imaging in chronic toluene abuse, and volitional hyperkinesia].

We described the central nervous system impairments and findings of magnetic resonance imaging (MRI) of the brain in three chronic toluene abusers. Patient 1 and 2 had a history of chronic toluene inhalation for 1 or 2 years and patient 3 has a history of it for 16 years. The patients were evaluated after an abstinence period of at least 4 weeks, to avoid neurologic effects of acute intoxication. Neurologic signs included cerebellar, cognitive and pyramidal dysfunctions in all 3 patients and hyperkinésie volitionnelle (HV; volitional hyperkinesia) in patient 3 who had a long history of toluene inhalation. This HV was found to be tremulous by surface electromyography. Appearance of HV in chronic toluene abuse seems to be related to a period or quantity of inhalation of toluene. T2-weighted MRI in the 3 patients revealed the following abnormalities: (1) increased signal intensity of middle cerebellar peduncle and cerebellar white matter, deep cerebral white matter, and posterior limb of internal capsule; and (2) decreased signal intensity of thalamus and basal ganglia. Proton-weighted MRI in patient 3 with HV showed decreased signal intensity of lateral portion of the thalamus and tegmentum of the brainstem. These MRI findings correlate remarkably well with the neurologic signs seen in the 3 patients. Cerebellar, cognitive, and pyramidal dysfunctions appear to be related to involvement of middle cerebellar peduncle (cerebellar white matter), deep cerebral white matter, and internal capsule, respectively, and HV seems to correlate with involvement of the thalamus or tegmentum of the brainstem, especially the latter.

[Frontal type adrenoleukodystrophy: the progress of the white matter lesion--a neuroradiological and pathological study].

We studied the correlation between neuroradiological findings and pathological observations of white matter lesions in a patient with frontal type adrenoleukodystrophy. A 41-year-old man developed schizophrenic symptoms and generalized convulsions at the age of 40. Examination revealed baldness, loss of the axillary hair, stereotypical behavior, mutism, dysphagia echographia, right hemiparesis, and brisk reflexes in all four limbs with bilateral extensor plantar responses. Blood examination revealed a high concentration of very-long-chain fatty acids in plasma; the patient was diagnosed as having adrenoleukodystrophy. His condition continued to worsen, and gradually he became akinetic. He died of pneumonia at the age of 43. T1- and T2-weighted MR images distinguished three abnormal zones in the cerebral white matter in this case. In the first zone (Z1), the signal intensity was moderately high on T2-weighted images and slightly low on T1-weighted images; this zone was not enhanced with Gd-DTPA. In the second zone (Z2), the signal intensity was slightly high on T2-weighted images, while moderately low on T1-weighted images; Z2 was enhanced with Gd-DTPA. In the third zone (Z3), the signal intensity was markedly high on T2-weighted images and low on T1-weighted images; Z3 was not enhanced with Gd-DTPA. Z3 was located in the frontal pole; Z2 and Z1 were consecutively located in rostro-caudal fashion in the brain. The subsequent pathological study of the brain of this patient revealed the following findings: Z1 showed destruction of myelin with axonal sparing, Z2 showed numerous lipid-laden macrophages, demyelinated axons, and a vigorous perivascular mononuclear cell response, Z3 consisted of a dense mesh of glial fibrils and scattered astrocytes without any evidence of an active process. In this study, the correlation between MR images and pathological findings in adrenoleukodystrophy was clearly established. Single photon emission tomography with 99mTc-hexamethylpropyleneamine oxime, and positron emission tomography with 15O2 continuous inhalation technique showed a reduction in the regional cerebral blood flow (rCBF) and in the regional cerebral metabolic rate of oxygen (rCMRO2) in the cerebral cortex near the Z1 and Z3. A normal or slight increase of rCBF and a reduction of r CMRO2 was found in the cerebral cortex near the Z2. Coronal MR images showed that Z3 was located in the deep white matter, while Z2 and Z1 were consecutively located in an inner-outward fashion, suggesting that the demyelination process started in the cingulum and spread in an inner-outward fashion and progressed in rostro-caudal manner.

[Rhythmic skeletal myoclonus without palatal myoclonus].

We reported a case of 89-year-old woman showing rhythmic skeletal myoclonus mainly on the right upper limb. This myoclonus appeared five days after the cerebral infarction. It was seen constantly both at rest and in posture, and decreased during voluntary movement. When the patient was under emotional stress, it spread to the submandibular, neck and trunks of upper limb. During sleep, this movement completely disappeared. There was no myoclonus in palato-pharyngo-laryngo-oculo-diaphragmatic muscle group. In the examination of the surface electromyography, the movement was not reciprocal between extensor and flexor muscles, and its cycle was about 3.5 Hz. It was different from the intention tremor because it did not increase during the movement phase on the finger nose test. The examination of MRI revealed a small infarction including right dentate nucleus and right superior cerebellar peduncle, and from which an infarction of the superior cerebellar artery territory was considered. Only a few cases of rhythmic skeletal myoclonus without palatal myoclonus have been reported in the literature. All of these cases had small infarction of the same region as the above case. Their myoclonus began 5 to 15 days after the onset of cerebral infarction. These periods were markedly shorter than that of intention tremor and palatal myoclonus. This fact suggest that the rhythmic skeletal myoclonus has a different mechanism from that of the palatal myoclonus.

[Oculogyric crisis as an initial symptom of juvenile parkinsonism-like disease].

A 12-year-old boy developed occasional attacks of oculogyric crisis after physical exercises or when tired. Following the initial symptom, progressive Parkinsonian features such as bradykinesia, muscular rigidity, hand tremors in posture, mild dysarthria and disorder of postural reflexes developed. There was no marked diurnal fluctuation o symptoms. Serum ceruloplasmin, copper levels, cranial X-ray CT scan and MRI were normal. Measurement of the plasma levels of L-dopa after single oral administration (300 mg) were normal. The treatment with L-dopa improved the Parkinsonian features excluding the attacks of oculogyric crisis in a few weeks. This case is not identical with juvenile Parkinsonism proposed by Yokochi et al for lack of both crural or truncal dystonia and remarkable response to L-dopa. Oculogyric crisis is known in several patients with severe generalized dystonia, and seldom in patients with Parkinson disease or juvenile Parkinsonism. Oculogyric crisis may be one of focal dystonias confined to extraocular muscles.

[Punch drunk syndrome due to repeated karate kicks and punches].

We reported a 39-year-old man with punch drunk syndrome who had cerebellar ataxia, seizure and dementia. CT scan of the brain revealed remarkable atrophy and enlargement of the ventricular system. MRI of the brain showed severe atrophy which was especially evident in the frontal base. On RI cisternography both early ventricular reflux at 3 hours and delayed ventricular stasis at 52 hours were found, which resembled the findings of the normal pressure hydrocephalus. The MRI and RI cisternographic findings suggested that the remarkable brain atrophy and enlargement of the ventricular system were caused by repeated KARATE traumas including minor brain contusion or subarachnoid hemorrhage in the base of the brain, since traumatic brain contusions affect particularly the orbital surfaces of the frontal lobes and the lateral and inferior surfaces of the temporal lobes. Communicating hydrocephalus may be one of the pathogenesis of punch drunk syndrome.

[Selective impairment of downward gaze; report of two cases of midbrain and bilateral paramedian thalamic infarction].

Selective paralysis of downward gaze, first described by André-Thomas et al. in 1933, is rare to be observed and not many cases have been so far reported in the literature. Two additional cases of selective impairment of downward gaze have been reported. X-ray CT scan revealed the infarcted areas in the midbrain tegmentum and bilateral paramedian thalami in both cases. Angiographic studies have revealed that the arteries occluded might be the paramedian thalamic arteries and their mesencephalic branches. According to the reported clinico-pathological studies and, in addition, to the results of the physiological studies in animal models, the responsible site of lesion for downward gaze failure is thought to be the rostral interstitial nucleus of MLF (riMLF). In one of the cases (28 year-old female, case 1), while vertical slow pursuit eye movements and upward saccade were normal in speed and range, maximum speed of eyes in voluntary downward saccade was markedly reduced and the eyes moved down slowly as if moving in oil (slow eye movement, viscosité). Passively extending the patient's head while she tried to fix her eyes on an unmoving object (doll's eye phenomenon), the speed of her eyes in downward saccade did not increase. In the other case (45 year-old male, case 2), the patient's voluntary and reflex downward eye movements were completely impaired and he could not look down nor follow the object below extending the horizontal meridian level. With regard to the unique features of abnormal eye movements observed in our cases, the possibility of coexistence of saccadic and slow pursuit eye movement systems in the vertical plane was discussed.

[Shy-Drager syndrome and the syndrome of inappropriate secretion of antidiuretic hormone].

We report a 52-year-old male patient with Shy-Drager syndrome (SDS) complicated by an occurrence of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). The patient first developed impotence at the age of 48, accompanied by urinary incontinence, and episodes of dizziness while standing. The following year, the patient had developed a staggering gait and speech became monotonous. At age 52, the patient was admitted to the hospital after experiencing frequent episodes of syncope associated with complete loss of consciousness. Upon examination, blood pressure was 100/70 in a recumbent position, and 80/60 when standing. The pulse rate varied from 60 per minute to 62. The patient was alert. The alternating Horner sign was observed, and a paucity of facial movements was visible. His speech was slow and monotonous. Muscle tone was increased bilaterally. There was incoordination. A laboratory examination revealed reduced serum sodium levels of 127 mEq/L and increased sodium excretion with plasma hypoosmolality (262 mOsm/kg/H), urine hyperosmolality and low serum renin activity (0.2 ng/ml/h). Renal functions were normal and the levels of adrenocortical and thyroid hormones were normal. There were no abnormalities observed in the chest roentgenogram taken. The level of antidiuretic hormone (ADH) was unreasonably high (5.74 pg/ml). A water-load test demonstrated failure of both water diuresis and inhibition of ADH secretion. These data suggested that hyponatremia in this case was caused by SIADH. The correlation between plasma osmolality and the concentration of ADH suggested that osmolality that initiates ADH release appeared to have been reset to around 230 mOsm/kg lower than normal.(ABSTRACT TRUNCATED AT 250 WORDS)