Fasting hyperinsulinemia and increased waist-to-hip ratios in non-wasting individuals with AIDS.

OBJECTIVE: To identify metabolic and body composition changes associated with HIV-1 infection in a cross-sectional study of individuals stratified by immunologic status and body mass. DESIGN: Metabolic abnormalities including glucose intolerance and changes in body morphology have recently been described in HIV-1-infected individuals following therapy with protease inhibitor-containing highly active anti-retroviral therapy. Although this is suggestive of a direct drug effect, the possibility that HIV infection may induce a tendency towards such underlying derangements should be considered. HIV-infected patients are heterogeneous with respect to immunologic status and body mass. In examining the underlying effect of HIV-1 on metabolic and body composition parameters, stratification by various immunologic and body mass categories may give divergent results that would not be detected otherwise. METHODS: Thirty male participants were categorized into four cohorts: non-wasting HIV-seronegative controls, non-wasting HIV-infected patients with relatively intact immune function (CD4 cell count > 500 x 10(6)/l); non-wasting individuals with AIDS (CD4 cell count < 200 x 10(6)/l); and individuals with AIDS wasting. RESULTS: Increased fasting plasma insulin and waist-to-hip ratios were found specifically in non-wasting individuals with AIDS compared with HIV-negative controls. CONCLUSIONS: Our study emphasises the importance of both body mass and immune function in studying metabolic and body composition abnormalities associated with HIV-1 infection. The association of increased waist-to-hip ratios and hyperinsulinemia suggestive of insulin resistance in non-wasting individuals with AIDS suggest that the tendency towards these metabolic abnormalities may be related to the HIV infectious process or to factors associated with immunologic dysfunction.

Mortality and survival for Minamata disease.

Analysis of mortality of 439 deaths that occurred among 1483 patients with Minamata disease (MD) in Kumamoto Prefecture, Japan was performed from the end of 1981. Causes of death and survival rates were studied by means of the standardized mortality ratio (SMR) and life-table technique. Of the 439 deaths (29.6%) in MD cases, the first death occurred in 1954. There was a first peak incidence in 1956 when MD was initially reported, however, the majority of deaths occurred after 1972 when a second and much larger peak was evident. In 1970 an important milestone occurred when the Public Nuisance Relief Law (an anti-pollution law) was enacted. Among its provisions, this law required and enabled verification of MD among people suspected of having been exposed. In contrast to the early cases, later cases of MD were older and their mean age-at-death was not different from that of the general population. The mortality rate for all causes of death was significantly higher in both sexes compared to the general population. Significantly lower survival rates were noted for older patients. The cause-specific mortality rates also showed significantly increased SMRs for liver diseases and nephritis-nephrosis-nephrotic syndrome in male patients, and for nephritis-nephrosis-nephrotic syndrome and other diseases in females. On the other hand, the SMR for senility without mention of psychosis was significantly lower than expected in both sexes.

Methylmercury exposure and mortality in southern Japan: a close look at causes of death.

This study examines mortality patterns by cause of death to investigate the effect of exposure to methylmercury in a small area of Minamata City (Kumamoto Prefecture, Japan), which has the highest concentration of patients with Minamata disease. Standardised mortality ratios (SMRs) are computed by cause of death for the study area, using the age specific rates of the entire city as a standard. The SMRs for liver cancer and chronic liver disease in the study area are significantly higher than unity and are consistent with the mortality patterns of registered Minamata disease patients. While an excess mortality is observed for cerebral haemorrhage, mortality from cerebral infarction and other cerebrovascular diseases is considerably lower in the study area. The multiple risk factors of liver related diseases and a possible explanation for the cerebrovascular mortality patterns are discussed to suggest further investigation.

A true osteomyocutaneous free-flap model in rats: the saphenous artery osteomyocutaneous flap.

A new composite free-flap model, namely, the saphenous artery osteomyocutaneous flap, is described in the rat. This is a true osteomyocutaneous flap composed of a skin island from the medial aspect of the lower leg, the gracilis and semitendinosus muscles, and a bone segment from the tibia based on the saphenous vascular pedicle. After anatomic studies in 10 rats, 20 flaps were transplanted microsurgically to the abdominal region in the recipient rats with a 90 percent success rate. In selected animals, arteriography was carried out. The results from gross observation of the flap survival and histologic and fluorochrome bone-labeling studies revealed a complete survival for each component of the flap in all animals with a patent vascular pedicle at 2 weeks after transfer. The model seems to be suitable for use in metabolic, vascular, and immunologic experimental studies on composite free flaps.

Hemifacial degloving approach to tumours in the infratemporal and pterygopalatine fossae: a preliminary report.

A new approach to tumours in the infratemporal or pterygopalatine fossa is presented. Through a midline skin incision, one side of the face from the forehead to the neck is completely degloved. Zygomatic and mandibular osteotomies improve access. All mimic muscles and the facial nerve are included in the elevated flap. This approach provides a widely exposed field from the temporal fossa to the neck without damage to major vessels or nerves other than the supra- and infraorbital nerves. Direct access to tumours in the infratemporal or pterygopalatine fossa is facilitated, thus making tumour resection easier, safer and more reliable. Details of this approach are described.

Migration of hydroxyapatite onlays into the mandible and nasal bone and local bone turnover in growing rabbits.

To determine the effects of local bone turnover on the migration of macroporous hydroxyapatite onlays in the nasal bone and mandibular ramus, we performed histomorphometric analyses of the underlying bone area in 41 New Zealand White rabbits from the age of 4 weeks. The hydroxyapatite implants were placed under the periosteum of the right nasal bone (a depository bone onto its periosteal surface and endosteal resorptive) and the mandibular ramus (resorptive onto its outer surface). The corresponding left sides were sham operated. Following fluorescence bone labeling, composite specimens of the hydroxyapatite block including both sides of the nasal bone and mandible were removed at 0 (n = 1), 3, 6, 9, 12, and 16 weeks postoperatively (n = 8, respectively) and processed to yield undecalcified sections. Bone-bone marrow interfaces in the entire area within 200 microns beneath the base of the hydroxyapatite and in the counter-area on the sham-operated side were measured under a light microscope. In all grafted specimens, the hydroxyapatite matrix was directly united with the underlying tissue by bone ingrowth. However, the sinking of the hydroxyapatite graft in the nasal bone was significant at 3 weeks postoperatively and gradually increased thereafter. In the mandible, the sinking became significant at 6 weeks. In the nasal bone, the bone area density beneath the graft showed a time-dependent decrease during the experimental period, but in the mandibular bone, the value was initially decreased at 3 weeks and then recovered to baseline level. In both bones, parameters of bone resorption, such as osteoclast number and osteoclast surface, were significantly increased from 3 weeks. While the parameters of bone formation, such as osteoblast surface and mineralizing surface, were significantly decreased from 3 weeks in the nasal bone, they were significantly increased in the mandible. Mineral apposition rate showed a significant decrease in both bones. Our data indicate that while the bone area density beneath the hydroxyapatite seemed to depend on bone formation, increased bone resorption would be more critical for the remodeling of underlying bony architecture in the migration of the hydroxyapatite graft.

Does acculturation influence psychosocial adaptation and well-being in Native Hawaiians?

Native Hawaiians have suffered higher disease rates and achieved lower educational and economic levels than other ethnic groups living in Hawaii. This study tests the hypothesis that cultural affiliation protects against psychosocial pathology in Hawaiians. Subjects included 172 Hawaiians of varying blood quantum and 92 non-Hawaiians. The Na Mea Hawai'i, a rationally derived, empirically validated measure of Hawaiian acculturation was administered to all subjects in addition to psychological tests which included 19 visual analogue scales that measure both state and trait variables. The Na Mea Hawai'i proved excellent at differentiating Hawaiians from non-Hawaiians (p = .0001), and it correlated well with blood quantum (r = 0.31, p = .0001). Low acculturation scores among Hawaiians did not correlate with any measure of discontent or psychosocial pathology irrespective of blood quantum. We conclude that Na Mea Hawai'i is a valid measure of Hawaiian acculturation, and that adaptation of the Hawaiians in our sample has been unaffected by level of acculturation.

An epidemiologic analysis of parathyroidectomy in chronic dialysis patients. The Okinawa Dialysis Study Group.

Parathyroidectomy (PTX) is one of the treatments of choice for secondary hyperparathyroidism in chronic dialysis patients. Due to the large increase in long-term dialysis patients, hyperparathyroidism is becoming a common clinical problem. Several studies on PTX have reported various surgical procedures, but limited information is available on the incidence and risk factors of the surgery. The Okinawa Dialysis Study (OKIDS) registry is a community-based dialysis registry. It covers the entire area of Okinawa from when the use of chronic dialysis began in 1971. By the end of 1990, a total of 1,986 chronic dialysis patients were registered and 128 of these had undergone PTX by the end of 1993. The cumulative incidence of PTX was 4.3 in DM and 15.2 in non-DM per 1,000 patient-years. About half of the PTX patients underwent the surgery within 10 years of dialysis. By logistic analysis, the risk of PTX was seen to increase significantly with the duration of dialysis, P < 0.0001. Other clinical variables such as sex, age at the start of dialysis and the presence of diabetes mellitus were not significant predictors of PTX. The probability of PTX increased linearly with the duration of dialysis (r = 0.83, p < 0.0001). After the introduction of active vitamin D in 1981, the probability of PTX was significantly decreased (p < 0.05) compared to the pre-vitamin D period ('71-'80). With prolongation of the duration of dialysis, the risk of PTX increased steadily and was estimated to be 10 percent in 10 years and 20 percent in 20 years. Other uremic factors determining a pathological transformation of parathyroid tissue from reactive to autonomous growth remained to be investigated.

[Studies on the biological effects of disulufiram--effect of an active metabolite of disulfiram on the activity of delta-aminolevulinic acid synthetase].

The effect of diethyldithiocarbamic acid methyl eater (Me-DDC), a metabolite of disulfiram, on hepatic delta-aminolevulinic acid (ALA) synthetase activity was investigated in male rats. The results obtained were as follows: 1) When rats were given intraperitoneally Me-DDC at the dose levels of 0.0625, 0.125, 0.25 and 0.50 mmol/kg, the activity of ALA synthetase showed a maximum level at a dose of 0.125 mmol/kg. 2) ALA synthetase activity increased rapidly and reached a maximum level in about 2 hr after the intraperitoneal administration of Me-DDC (0.125 mmol/kg). 3) Pretreatment with phenobarbital (an inducer of drug metabolizing enzymes) tended to depress the increase of ALA synthetase caused by Me-DDC, whereas pretreatment with SKF 525-A (an inhibitor of drug metabolizing enzymes) stimulated slightly the Me-DDC-induced increased of the enzyme. 4) The apparent Km value of the enzyme for glycine did not change but the Vmax value increased in Me-DDC-treated rats. 5) Actinomycin D (a potent inhibitor of DNA-dependent synthesis of RNA), when administered to rats before Me-DDC, completely prevented the induction of ALA synthetase caused by the latter compound. 6) Pretreatment with phorone (a glutathion depletor) 4 hr prior to the administration of Me-DDC completely inhibited the Me-DDC-induced increase of ALA synthetase.

An induction of heme oxygenase and its possible relation to the decrease of cytochrome P-450 content during liver regeneration.

The alterations of various enzymes responsible for drug metabolism and heme metabolism were examined in regenerating livers of male rats. Microsomal cytochrome P-450 content and aminopyrine demethylase activity were significantly decreased during liver regeneration. In contrast, microsomal heme oxygenase activity was markedly increased under the identical conditions. The increased heme oxygenase activity which appeared within 4 h and reached maximum at 1 d after partial hepatectomy was sustained for 5 d. In sham-operated rats, the changed patterns of these parameters were similar, but to a lesser extent as compared to partially hepatectomized rats. The increase of heme oxygenase activity following partial hepatectomy was blocked by the administration of cycloheximide or actinomycin D. Other enzymes involved in heme synthesis did not change appreciably during liver regeneration. The inverse relationship between the decrease of cytochrome P-450 content and the increase of heme oxygenase activity was also observed in female rats and male mice. These findings suggest that the increase of heme oxygenase activity in regenerating rodent liver would be correlated to the decrease of cytochrome P-450 content. Adrenalectomy enhanced the increase of heme oxygenase activity following partial hepatectomy, though the decrease of cytochrome P-450 content was less extensive under the experimental conditions. The results also suggest that the inverse relationship between the increase of heme oxygenase activity and the decrease of cytochrome P-450 content would be a biochemical phenomenon seen in regenerating liver and that the phenomenon would not be simply due to the surgical stress to the animals.

Effects of ethanol on methyl mercury toxicity in rats.

This study was designed to investigate the effect of different doses of ethanol on the morbidity, mortality, and distribution of mercury in the tissues of groups of rats treated orally once daily with methyl mercury chloride (MMC: 5 mg/kg . d) for 10 consecutive days. Ethanol potentiated the toxicity of methyl mercury in terms of neurological manifestations (hindleg crossings and abnormal gait) and mortality. The magnitude of effect depended on the concentration of ethanol administered. The concentration of mercury in the kidney and brain also increased with the dose of ethanol given. These findings indicate that epidemiologic studies designed to evaluate methyl mercury toxicity must take into account the multiple environmental burdens that can affect the population cumulatively and simultaneously.

Onlay silicone and hydroxyapatite-tricalciumphosphate composite (HAP-TCP) blocks interfere with nasal bone growth in rabbits.

We investigated how a new type of synthetic porous hydroxyapatite ceramic (HAP-TCP) acts when it is implanted in growing membranous bone. Seventy-six New Zealand White infant male rabbits (4-week-olds) were used. Rabbits received HAP-TCP block or silicone block implantation in their right nasal bone. The left nasal bone was used for a sham. Serial or cross-sectional examinations by morphometry, radiology, blood biochemistry, and histology were carried out. Both the HAP-TCP and silicone groups exhibited no systemic growth disturbance in terms of morphometry and blood biochemistry. Dual energy x-ray absorptiometry (DEXA) revealed, however, a decrease in the bone mineral content (BMC) of the right nasal bone in the silicone group. Histology revealed a superior affinity of HAP-TCP to bone tissue than that of silicone. When a HAP-TCP block was implanted under the periosteum it bonded directly to bone tissue. However, sinking of the implants into the bone tissue were noted both in the HAP-TCP and the silicone groups in longitudinal observation. These results suggest that although HAP-TCP has superior affinity to bone tissue, this by itself is not enough sufficient reason to believe that HAP-TCP can be effectively applied during the growth period.

The effects of tissue expansion on the hemodynamic and survival characteristics of reverse-flow island flaps: an experimental study in rabbits.

The effects of tissue expansion on the hemodynamic and survival characteristics of reverse-flow island skin flaps were investigated in New Zealand White rabbits. The animals were divided into 3 groups of 15: group I (control) had no surgery prior to flap elevation, group II (nonexpansion) had a noninflated expander, and group III (expansion) had an inflated expander of 80 ml. After 3 weeks of expansion, a reverse-flow island flap based on the distal saphenous pedicle was elevated. A series of hemodynamic studies was performed to test reverse venous flow--in particular, valve competence. Besides observing the reverse flow under an operating microscope, the changes in the intravenous pressure were measured at 0, 5, 15, 30, 60, and 120 minutes after flap elevation. Moreover, reverse-flow resistance (RFR) was measured in each group to test the competence of venous valves. At each time interval, the values of intravenous pressure were significantly lower (p < 0.01) in group III than in the groups I and II. However there was no statistically significant difference between group I and group II. The RFR was measured as 126.7 +/- 33.52 mmHg in group I, 59.3 +/- 29.86 mmHg in group II (p < 0.01), and 25.1 +/- 7.68 mmHg in group III (p < 0.01). Ten days after flap elevation the mean survival of group III (100%) was statistically higher than that of group I (57.4 +/- 18.3%; p < 0.01) and group II (81.6 +/- 12.8%; p < 0.05). These findings simply suggest that controlled tissue expansion improves retrograde venous drainage and increases the survival of reverse-flow island flaps in rabbits. Abnormal dilatation of the venous tree and incompetence of the venous valves seem to be the main factors in explaining the decrease in the values of RFR and intravenous pressure in the expanded flaps. The potential mechanisms to explain the effects of tissue expansion, and the clinical implications are discussed.

Studies on the metabolism of d-Limonene (p-Mentha-1,8-diene). III. Effects of d-Limonene on the lipids and drug-metabolizing enzymes in rat livers.

1. After a single oral dose of d-limonene (200-1200 mg/kg) no effects were observed on liver triglyceride, microsomal protein, cytochrome b5, and the drug-metabolizing enzymes. Glycogen content was slightly decreased at doses higher than 800 mg/kg, and cytochrome P-450 and delta-aminolaevulinic acid synthetase activity was slightly increased at 1200 mg/kg. 2. After repeated treatment (400 mg/kg/day) for 30 days, the relative liver weight and hepatic phospholipid content were only slightly increased, and liver and serum cholesterol were decreased 49 and 8%, respectively. Of the phospholipid fatty acids, palmitic, linoleic and arachidonic acids were increased, and stearic acid was decreased. Aminopyrine demethylase and aniline hydroxylase were increased 26 and 22%, respectively, and cytochrome P-450 and b5 were likewise increased 31 and 30%.

Causes of death in Minamata disease: analysis of death certificates.

The causes of death in Minamata disease were analyzed and compared with those of control subjects. Of the 1422 Minamata disease patients in the Kumamoto Prefecture, 378 had died by the end of 1980. Of these 378, the first death occurred in 1954 with a peak incidence in 1956 when Minamata disease was officially reported for the first time. The number of deaths increased rapidly after 1972 with a second peak in 1976. The male:female ratio was 1.8:1 and the mean age-at-death was 67.2 years (SD = +/- 18.65). The mean age-at-death was younger in the cases of the initial outbreak than in those recently. There were, on the average, 2.8 causes of death per person. Of these cases, 157 (41.5%) had Minamata disease indicated on the death certificate, though 64 (16.9%) had Minamata disease coded as the underlying cause. Minamata disease and the noninflammatory diseases of the central nervous system (CNS) were the main underlying causes of death between 1954 and 1969, while, in the multiple cause data, pneumonia and non-ischemic heart disease were the most prevalent. Cerebrovascular diseases (18.0%) were the main underlying causes of death followed by malignant neoplasms (14.7%), cardiovascular diseases (14.1%) and Minamata disease (14.1%) in 1970 or later, while cardiovascular diseases (18.6%), Minamata disease (14.5%), cerebrovascular diseases (10.4%) and malignant neoplasms (7.1%) were the major multiple causes of death. As compared with the control, the proportions of deaths due to noninflammatory diseases of CNS and pneumonia were higher in the initial outbreak. Although the difference in the causes of death was less apparent recently, malignant neoplasms and hypertensive diseases tended to be lower. These results suggest that there is a need for a long-term follow-up of Minamata disease patients. The data also show the potential value of multiple causes of death coding in analyses of mortality.