Mortality and cancer incidence among a population previously exposed to environmental cadmium.

OBJECTIVES: This paper evaluates the associations of previous exposure to environmental cadmium (Cd) and renal function with total mortality and cancer incidence. METHODS: The study population comprised 275 residents (aged 40-92 years at baseline) in a Cd-polluted area located on Tsushima Island, Nagasaki, Japan. In the study area, the dietary intake of Cd decreased because the soil of the Cd-polluted rice fields was replaced with new soil between 1980 and 1983. The mortality rate from 1982 to 1997 and cancer incidence from 1985 to 1996 were investigated. Standardized mortality and incidence ratios (SMR and SIR) were calculated by using regional reference rates. The associations of renal function and urinary Cd levels with total mortality and cancer incidence were evaluated with Cox regression models. RESULTS: The SMR for all subjects, and those with a urinary beta2-microglobulin (U-beta2M) concentration > or = 1,000 microg/g creatinine (Cr) and < 1,000 microg/g Cr was estimated at 90 [95% confidence interval (CI) 73-109], 138 (95% CI 101-183) and 66 (95% CI 49-87), respectively. After adjustment for age and other potential confounders, in men, serum beta2M (S-beta2M) (> or = 2.3 mg/l) and in women, serum Cr (> or = 21.2 mg/ 100 ml), relative clearance of beta2M (> or = 21%) and U-beta2M (> or = 1,000 microg/g Cr), were associated with a significantly increased risk of mortality, with hazard ratios exceeding 2.0. After further adjustment for log(U-beta2M), the rate ratio of deaths associated with, in men, increased S-beta2M was 2.53 (95% CI 0.97-6.65) and, in women, increased serum Cr (S-Cr) concentrations was 2.75 (95% CI 1.24-6.14). Urinary Cd concentrations (> or = 10 microg/g Cr) were not significantly associated with mortality. The overall SIR of all malignant neoplasms was 71 (95% CI 44-107). CONCLUSIONS: These findings suggest that renal tubule dysfunction and a reduced glomerular filtration rate are predictors of mortality among persons previously exposed to environmental Cd. However, the results also suggest that overall mortality rates in Cd-polluted areas are not necessarily increased, because of the low mortality among those with no, or only slight, signs of low-molecular weight proteinuria. Overall cancer incidence may not be increased among residents in Cd-polluted areas.

Evaluation of adult T-cell leukemia/lymphoma incidence and its impact on non-Hodgkin lymphoma incidence in southwestern Japan.

The incidence of adult T-cell leukemia/lymphoma (ATL) and its impact on that of total non-Hodgkin lymphoma (NHL) were evaluated in Nagasaki, an area in southwestern Japan where human T-cell lymphotropic virus type I (HTLV-I) is endemic. The first study area comprised 4 towns located on the K Islands, which had a population of 26,870 in 1990. The overall HTLV-I seroprevalence estimated from the serologic survey of 18,485 subjects was 16.2%. By using the data from the Nagasaki Prefectural Cancer Registry (NPCR) and reviewing clinical and laboratory information, we identified 40 cases of ATL and 35 cases of other NHL diagnosed between 1985 and 1995. The crude annual incidence of ATL among 100,000 HTLV-I carriers aged 30 or older was estimated at 137.7 for men and 57.4 for women, with a significant sex difference after adjustment for age (rate ratio = 2.50, 95% confidence interval 1.32-4.73). The cumulative risk from 30 to 79 years of age was estimated at approximately 6.6% for men and 2.1% for women. Among the entire population, ATL accounted for 51 to 59% of the total NHL incidence, showing the strong impact of HTLV-I infection. The second study area comprised the whole of Nagasaki Prefecture (total population in 1990 = 1.56 million). Between 1985 and 1995, 989 cases of ATL and 1,745 cases of other NHL were registered in the NPCR. The world age-standardized annual incidence rate of ATL per 100,000 persons aged 30 or older was estimated at 10.5 for men and 6.0 for women, which accounted for approximately 37 to 41% of the total NHL incidence.

Dual regulatory effects of interferon-alpha, -beta, and -gamma on interleukin-8 gene expression by human gingival fibroblasts in culture upon stimulation with lipopolysaccharide from Prevotella intermedia, interleukin-1alpha, or tumor necrosis factor-alpha.

In a previous study, we demonstrated that the amount of interleukin (IL)-8 mRNA expressed by human gingival fibroblasts stimulated with lipopolysaccharide (LPS) from Prevotella intermedia ATCC 25611 is increased by pre-treatment with beta or gamma interferon (IFN-beta or -gamma). In the present study, we identified the regulatory effects of these IFNs on IL-8 mRNA expression and IL-8 production by human gingival fibroblasts. Priming with IFN-alpha (alpha), -beta, or -gamma upregulated the IL-8 mRNA expression in response to P. intermedia LPS, whereas co-stimulation with these IFNs reduced the amount of mRNA expressed by the cells. The regulation of IL-8 mRNA expression induced by recombinant human tumor necrosis factor-alpha (rHuTNF-alpha) or rHuIL-1alpha was similar to that induced by LPS. The IL-8 mRNA expression in response to P. intermedia LPS was enhanced by IFN-gamma independently of de novo protein synthesis, and was regulated, at least in part, at the transcriptional level. The IL-8 mRNA accumulation in response to P. intermedia LPS was inhibited by tosylphenyl-alanyl chloromethyl-ketone, an inhibitor of NF-kappaB activation, although the NF-kappaB activation itself was not altered by IFN-gamma. These findings suggest that IFNs might be capable of both enhancing and inhibiting inflammatory responses in periodontal tissues through the dual regulation of IL-8 production by gingival fibroblasts in response to bacterial components and cytokines.

Possible association between adult T-cell leukemia/lymphoma and acute myeloid leukemia.

BACKGROUND: To the authors' knowledge, an association between adult T-cell leukemia/lymphoma (ATL) and acute myeloid leukemia (AML) has been reported only in four patients. The authors identified five additional patients with both neoplasms. METHODS: A review of the clinical records of patients with AML, ATL, or lymphoid neoplasms other than ATL diagnosed between 1986 and 1995 was performed. Cytokine levels were assayed in selected patients. The authors searched for reports from other institutions using MEDLINE and the proceedings of two Japanese hematology societies. RESULTS: ATL was diagnosed in 134 patients, whereas 180 had AML. Five patients with both neoplasms were identified (3.7% of ATL patients and 2.8% of AML patients). In seven of the nine patients (including four patients in the literature) with ATL and AML, the ATL was diagnosed prior to the AML, whereas in the remaining two patients both neoplasms were diagnosed simultaneously. Six of the nine cases were therapy-related (t)-AML, which developed after chemotherapy for ATL. Monoclonal integration of proviral human T-lymphotropic virus type 1 was detected in ATL cells but not in AML cells in the six patients examined. The plasma levels of macrophage colony-stimulating factor (M-CSF), granulocyte-colony stimulating factor, and granulocyte-macrophage-colony stimulating factor (GM-CSF) were elevated in 3, 1, and 1, respectively, of the 4 patients examined at AML onset who had active ATL. In one case, the levels of several cytokines, including GM-CSF and M-CSF, in the supernatant fluid of short term cultured ATL cells were elevated. Three patients with de novo ATL and AML received remission induction therapy, and two achieved a complete remission (CR) of both diseases. Among the four patients who received chemotherapy for t-AML, two achieved CR. CONCLUSIONS: ATL patients also can develop AML, irrespective of treatment with chemotherapy for ATL. This association does not indicate exclusive chemoresistance of both neoplasms. Cytokines produced by ATL cells may support the growth of AML cells.

[Immunogenetic studies of spina bifida--sibling cases in three families].

We reported sibling cases of spina bifida in three families. In the first family, three boys were the products of one mother and different two fathers. They all suffered from spina bifida cystica with various degrees of hydrocephalus. Cyst closure and ventriculo-peritoneal shunt were performed. Elder boys had more severe neurological deficits. In the second family, two boys and one girl were affected. The elder boy had minimum neurological deficit but the younger boy had a severe neurological deficit and hydrocephalus. Cyst closure was performed on both of them but the shunting procedure was not. The girl was normal. In the third family, three girls were affected. The second girl suffered from spina bifida cystica with hydrocephalus and cyst closure was performed. After that ventriculo-peritoneal shunt was done. Other two girls were spina bifida occulta without any neurological deficit. HLA typing, red blood cell antigen typing and chromosome test were studied in three families. There was no evidence of linkage between spina bifida and HLA antigens. Also no relationship between spina bifida and red blood cell antigens. They all had normal chromosomes. We could not make as one material for genetic counseling from above studied three methods.

[Clinical assessment of meningeal carcinomatosis; from the viewpoint of the analysis of intracranial pressure].

Meningeal carcinomatoses (MC) have been mainly studied from the viewpoint of the analysis of intracranial pressure (ICP). From the CT findings, ten patients were divided into two groups: group I, six patients showed characteristics of MC; group II, four showed normal characteristics. Ventricular fluid pressure (VFP) was continuously measured by a controlled ventricular drainage tube using a Spectramed P-10EZ at 3.1 +/- 2.1 months after the onset of the neurological symptoms. At the same time as VFP monitoring, the CBF by 133Xe method was measured in 5 cases and RI cisternography was performed in 9 cases. "A" wave was observed in 5 cases of group I and in 3 cases of group II. "B" wave was observed in all cases of both groups. In all 10 cases, the occurrence rate of both A and B waves (ORA, ORB) were high, averaging 2.34 +/- 0.54 times/hour, 74.0 +/- 16.6% time, respectively. Mean resting pressure(R) and mean peak pressure(P) tended to be high, averaging 28.8 +/- 12.2mmHg, 58.9 +/- 13.7mmHg, respectively. Mean cerebral perfusion pressure corresponding with R and P (CPPR, CPPP) was markedly reduced, averaging 79.1 +/- 15.9mmHg, 50.9 +/- 12.7mmHg, respectively. Both ORA and ORB in group I were higher, and both CPPR and CPPP in group 1 were lower, than in group II. Statistically, this is significant. Both R and P in Group I tended to be higher than in group II. This has no statistical significance. CBF in all 5 cases averaged 34.8 +/- 8.4ml/100g/min. No significant difference in the impairment of CBF was found between both groups. RI cisternography showed delayed clearance in all 9 cases.(ABSTRACT TRUNCATED AT 250 WORDS)

[A case of cortical deafness with bilateral putaminal hemorrhage].

A 56 years old right-handed female, a housewife, had suffered from right putaminal hemorrhage which had been treated surgically in July, 1985. Since it was difficult to approach the trans-sylvian fissure, evacuation of the hematoma was performed transcortically through the superior temporal gyrus. She was neurologically free and lived normally until she suddenly became completely deaf in April, 1991. On admission, she was alert, well oriented and spontaneously stated that she was deaf. She showed no response to verbal commands or loud noises but followed complex written commands. No other neurological deficit was observed. In addition to an irregular low-density area in the right temporal lobe, CT scan revealed a left putaminal hemorrhage. Audiological testing disclosed pure tone thresholds to be below 90db on both sides. Auditory brain stem response (ABR) showed waves I to VI in normal latency ranges, but wave VII was not observed. She was treated conservatively. Although her hearing loss had been gradually improving for 1 month, she suffered from word deafness, an inability to comprehend speech, for the following 2 months. Clinical features, CT findings as well as results of ABR suggest that hearing loss observed in this case, cortical deafness, was presumably due to bilateral damage of acoustic radiation of the temporal lobe. It was also suggested that, although she was asymptomatic, cortical and subcortical damage to the right temporal lobe following evacuation of the putaminal hematoma may have been extensive. During surgical procedures for evacuation of the putaminal hematoma, it has to be always kept in mind not to damage the auditory cortex and its radiations.

Non-invasive automatic determination of anaerobic threshold using double gas exchange parameters.

A new technique for determining the anaerobic threshold (AT) in real-time during a progressive exercise test was proposed with special consideration to its safety. We applied the discriminant analysis based on the linear logistic regression model to two groups of gas exchange parameters at times just before and after the lactate (LA) threshold (determined by blood LA kinetics; the external criterion of AT) during the incremental exercise test in 21 young males. As a result, the selected variables for estimating AT accurately (the discriminant rate = 100%), were VE/VO2 and the relative change in VE. Our idea of the new technique for determining AT is based on the probability function (p(x)) derived from the discriminant analysis. At each time at which the gas exchange parameters are acquired during the exercise test, p(x) is calculated, and the decision whether the present exercise level is in the pre, just, or post-AT level is made by the p(x). The technique is able to stop the exercise test as quickly as possible after passing through the AT level. To evaluate the new technique, the data set of 66 females (aged 16-57) was applied as a form of simulation. It was shown that the exercise test could be stopped by the technique at a level of only 0.2-0.5 l/min in VO2 higher than AT. This advantage of the technique makes the exercise test safer for middle-aged or old men, and patients during cardiac rehabilitation.

[4 cases of one and a half syndrome' observed following surgery of primary pontine hemmorhage].

In 1967, Fisher named the "one and a half syndrome" for a particular ocular movement which is observed in the lesion of pontine tegmentum, when horizontal movement of one eye is totally disabled and the abducence of another eye is only preserved associating mono-ocular nystagmus in the same eye. Vertical movement and convergence are preserved. We experienced this syndrome in four cases of small localized hematoma of the pontine tegmentum which were all removed under operative microscope. All patients are alive more than 10 months under consciousness and with improved neurological sign. Three of them were probably due to hypertensive hemorrhage and the rest was due to arterio-venous malformation of the pontine tegmentum. Three of them showed this syndrome before operation and observed even after operation. One patient was operated on one and a half hours after the apoplectic attack under semicomatous condition and he improved with this syndrome postoperatively. In most previous reports, this syndrome was noted in severe cases of pontine hematoma or basilar artery thrombosis and they expired soon thereafter. All our cases survived in satisfactory condition and ocular movement could be followed up for a long time. The mechanism of this syndrome was also discussed.

[Two cases showing subarachnoid hemorrhage from angioblastic meningioma and vascular hamartoma (author's transl)].

As a causative factor in spontaneous subarachnoid hemorrhage, vascular anomalies, especially aneurysm or arteriovenous malformation, have been generally recognized. On the other hand, subarachnoid hemorrhage from brain tumor and cryptic vascular malformation are rare. We experienced two cases showing subarachnoid hemorrhage from angioblastic meningioma and vascular hamartoma as an initial symptom. Case 1: A 48-year-old woman, who complained of severe headache and vomiting on Feb. 10th, 1972, gradually became lethargic. Lumbar puncture revealed moderately hemorrhagic C.S.F.. On the fifth day after the onset, she was admitted to our hospital. On admission she showed disorientation and disturbance of resent memory. Aphasia and agnosia were slightly observed. On ophthalmologic examination right homonymous lower quadrant hemianopsia was observed. The carotid angiogram showed slight square shift of the anterior cerebral artery to the right side, elevation of the middle serebral artery and a homogeneous tumor stain in the occipital region in capillary phase. A walnut sized tumor invading the middle portion of the left lateral sinus and showing firm adhesion to the tentrium was found. There was an intracerebral hematoma behined the tumor. The tumor, the tentrium and the lateral sinus were extirpated en bloc and the intracerebral hematoma was aspirated. Histologically, the tumor was angioblastic meningioma. Case 2: A 7-year-old boy, who complained of severe abrupt headache, nuchal pain and vomiting on Sept. 17th, 1972, became gradually lethargic. Lumbar puncture revealed hemorrhagic C.S.F., On the tenth day after the onset, he was admitted to our hospital. He showed confusion and agitation. The carotid angiogram showed an unrolling of the pericallosal artery, but no findings of space taking lesions. An air study indicated a globular filling defect protruding into the anterior horn of the right lateral ventricle. The tumor located in the laterobasal wall of the anterior horn was removed picemiel by transventricular approach. Histologically, the tumor was vascular hamartoma. Furthermore, we discussed various brain tumors showing subarachnoid hemorrhage as an initial symptom, its frequency and bleeding mechanism on the literature.