Early alterations in plasma esterases with associated pathology following oral administration of diethylnitrosamine and butylated hydroxytoluene singly or in combination.

Plasma esterase changes are apparent in BALB/c mice within 3 weeks after feeding them laboratory chow with 0.75% of the antioxidant BHT added. Other esterase changes, different from those in BHT-treated animals, are also apparent in plasma of mice during exposure to the carcinogen DENA. Interference with these DENA esterase alterations is apparent in plasma of mice treated concomitantly with both DENA and BHT. Esterase changes resulting from either the carcinogen or antioxidant exposure precede the overt histologically detected changes induced by these compounds. The early esterase changes and subsequent tumorigenesis resulting from DENA exposure are more severe in female mice. Some of the esterases altered by DENA or BHT exposure are testosterone-related.


Tumor-associated and embryonic antigens in soluble fractions of a chemically-induced rat colon carcinoma.

Soluble intracytoplasmic protein fractions and solubilized tumor membrane preparations produced by 3 M KC1 or papain treatment were isolated from a 1,2 dimethylhydrazine-HC1 (DMH)-induced rat colon carcinoma, DHM-BU 1. Solubilized preparations were fractionated by DEAE cellulose and Sephadex G200 column Chromatography. Crude extracts and fractionated materials were tested for their ability to inhibit the cytotoxicyt of lymph-node cells (LNC) from rats bearing isografts of an N-methyl-N-nitro-N-nirosoguanidine (NG)-induced colon carcinoma, ng-W1...


Microscopical cancer of the stomach--a study on histogenesis of gastric carcinoma.

In order to elucidate the histogenesis of gastric cancer preceded by "chronic gastritis", 67 foci (58 cases) of minute cancer less than 5 mn in largest diameter were examined histologically. The results obtained were as follows: (1) Except in two cases, all minute cancerous foci were found unexpectedly in the mucosa of the antrum or of the angulus having peptic ulcer or gastric cancer. They were more frequent in the lesser curvature than in other parts of the stomach. (2) Histologically, 18 foci were found in an area close to the main lesion, while 40 were far from the lesion. Seven foci were detected in the mucosa adjacent to ulcer scars. (3) In retrospective macroscopical examinations, 41 foci showed minimal erosion or tiny depressions on the affected mucosa, while in the other 26 no recognizable changes were observable. (4) Histologically, the gastric mucosa outside the cancer lesions was more or less atrophic with or without intestinal metaplasia. (5) Regardless of histological types, all the minute cancers were found in the transitional zone between foveolar epithelium and pyloric glands corresponding to "generative cell layer" in autoradiographic studies. (6) Poorly differentiated adenocarcinomas containing signet-ring cells occurred most often in combination with no or slight intestinal metaplasia of the mucosa, while well-differentiated adenocarcinomas were always found in ventricles with severe intestinal metaplasia.


Characterization of the mononuclear cell infiltrate in human malignant melanoma.

In the skin infiltrate of superficial spreading melanoma, non phagocytosing mononuclear cells (NPMC) represent a major cell component. The number of NPMCs decreases as a function of tumour progression. In addition, when an NPMC is in contact with a malignant melanocyte, the latter cell exhibits ultrastructural degenerative changes. In the blood of healthy donors and of melanoma patients, atypical mononuclear cells (AMC) can be identified. AMCs have been shown to participate in antibody-dependent cellular cytotoxicity (ADCC) reactions against melanoma cells in vitro. In this paper, it is reported that NPMCs and AMCs have in common their size, and some ultrastructural features such as indented nuclei, dispersed organelles, rough endoplasmic reticulum profiles and surface microvilli. The two cell types are negative for non-specific esterase. They also fail to react for peroxidase at either the light or the electron microscopic level. They do not adhere to glass. AMCs do not form spontaneous E rosettes, they have no surface IgG and they have no receptors for complement. However, they do form rosettes with EAIgG. On frozen sections firm binding of EAIgG has been seen on the skin infiltrate in three cases out of 10. It is concluded that NPMCs might react with tumour cells in vivo, in the same manner as do AMCs in vitro.


Inactivation of the DNA template in HeLa cells treated with chlorambucil.

The effect of chlorambucil on the colony-forming ability of HeLa cells following either treatment for 1 h or continuous treatment has been measured. Concentrations of chlorambucil which had only minimal effects on cell survival inhibited the rate of DNA but not RNA and protein synthesis within 1 h of treatment. Nevertheless, cells continued to synthesize DNA for many hours after this treatment in the absence of cell division. Synchronous populations of HeLa cells treated prior to DNA synthesis, in the G1 phase of the cell cycle, were not delayed in their progression into the S phase where they exhibited a marked dose-dependent inhibition of the rate of DNA synthesis. Cells in which DNA synthesis had been depressed showed a prolongation of the S phase and this was accompanied by a corresponding dose-dependent mitotic delay. Treatment during the G2 phase of the cell cycle did not induce any delay or block in the next mitosis, but did inhibit the rate of DNA synthesis in the following cell cycle in a dose-dependent manner; this depression of DNA synthesis was followed by a delay in the next mitosis. Cross-linking of either isolated DNA or DNA present in treated HeLa cells was demonstrated, and in the latter case calculated to be of the same order as that which occurred with other difunctional agents at comparable toxic concentrations.


Increased thymidine uptake by methylcholanthrene-treated C3H/10T1/2 cells.

The uptake of 3H-thymidine in post-confluent cultures of methylcholanthrene-transformed C3H/10T1/I mouse embryo cells was markedly higher than in their non-transformed counterparts. In a reconstruction experiment as few as 2% transformed cells could be detected by increased thymidine uptake. Measurements made at various times up to 110 days in multi-chambered plates revealed that after 25 days methylcholanthrene-treated cultures incorporated significantly more thymidine than the acetone-treated controls. This increased uptake correlated with the appearance of Type III transformed foci.


A case/control study of the association between primary liver cancer and hepatitis B infection in Senegal.

A case/control study has been carried out to determine by radioimmunoassay and passive hemagglutination techniques the prevalence of hepatitis B surface antigen (HBsAg) and antibody (anti-HBs) in patients with primary liver cancer (PLC) and age/sex-matched hospital controls with cancers of other sites (OCC) and similarly matched controls without cancer (NCC). HBsAg was found in 61.2% of 165 cases of PLC as compared to 11.7% of 328 NCC. The frequency of HBsAg in PLC patients was significantly higher (72.2%) in those with detectable alpha fetoprotein as compared to those without (40.3%). There was no difference in the frequency of HBsAg in PLC patients with and without accompanying cirrhosis. No significant difference in potential hepatitis exposure history was found in the three study groups.


Inhibition of in vitro lymphoproliferative responses to tumor-associated antigens by suppressor cells from rats bearing progressively growing Gross leukemia virus-induced tumors.

W/Fu rats were injected subcutaneously with low numbers of cells from the Gross leukemia virus-induced lymphoma, (C58NT)D, which induced transient tumor growth and regression (regressors), or with high numbers of tumor cells resulting in progressive tumor growth (progressors). Spleen cells from regressors had a significant reactivity in the mixed leukocyte tumor cell interation (MLTI), while spleen cells from progressors were unresponsive. Similarly, the responses to the non-specific mitogens, phytohemagglutinin and concanavalin A, were suppressed in spleen-cell cultures of progressors. Passage of spleen cells from progressors over rayon adherence columns or pretreatment with an iron/magnet technique resulted in almost complete restoration of MLTI and mitogen responses. Addition of spleen cells from progressors depressed the MLTI of spleen cells from regressors and the mitogen reactivity of normal spleen cells. Serum from progressors also suppressed MLTI and mitogen reactivity. These data indicate that, in spleens of rats bearing progressively growing tumors, suppressor cells can be demonstrated which inhibit specific reactivity to tumor-associated antigens and non-specific reactivity to mitogens. The presence of suppressor cells or of inhibitory factors in the serum may contribute to the immunosuppression frequently observed in tumor-bearing hosts.


Tumour metastasis in mice with reduced immune reactivity. III. Studies with three weakly antigenic tumours in thymectomized and/or sub-lethally irradiated mice.

A previous observation that increased spontaneous metastasis formation from the highly antigenic MCA-induced sarcoma MCG101 occurred in immunosuppressed C57BL/6J mice prompted the present study to establish whether or not tumours capable of inducing only weak transplantation resistance would behave similarly. One MCA-induced sarcoma, MCG12, one epidermoid carcinoma, EpCa1 in CBA mice and a spontaneous mammary carcinoma, MaCa1 in C3H mice, were transplanted into adult thymectomized and/or sub-lethally irradiated mice at different intervals after irradiation. The effects of the treatments on the immunoreactivity were monitored in separate groups by determining the primary and secondary responses to SRBC and the survival of first set allogeneic skin grafts. The treatment resulted in a significantly increased incidence of mainly the lymph-node metastases with MCG12 and of only the lung metastases with EpCa1. No increase in metastases was noted with MaCa1. Thymectomy potentiated the increase in metastases from MCG12 in irradiated mice but unexpectedly so only for a limited time after irradiation. Local growth of MCG12 and MaCa1 at the transplantation site was more rapid in females than in males. The changes in tumour growth and spread induced by the treatments varied with tumour-host system, sex and time of transplantation after irradiation and did not conform well with any of the tested parameters of immunoreactivity. There was no close parallel between the effects of the treatments on growth and spread of the tumours.


Cellular immunity to transitional cell carcinoma of the urinary bladder. III. Effects of hydrostatic pressure therapy.

The effects of hydrostatic pressure therapy on in vitro cellular cytotoxicity responses have been studied in 19 patients with transitional cell carcinoma of the bladder (TCC). Cytotoxicity was quantitated against allogeneic targets in a microplate assay or by 51chromium isotope release. Two types of reactivity were detected, the most common being a differential cytotoxicity for targets derived from TCC, in either short-term or long-term tissue culture. This reaction is operationally termed "tumor-specific". Less frequently, a general cytotoxicity for targets of diverse histogenic origins was observed. For the present, this is termed "non-specific". Nine patients were tested before pressure therapy and of these only two gave a specific reaction and one a non-specific reaction, while six were non-reactive. Eighteen patients were tested at varying intervals after treatment and of these 11 gave a specific reaction and one a non-specific effect, while six were non-reactive. Three individuals who were non-reactive prior to therapy had a specific reaction post therapy. Two who reacted specifically before therapy became non-reactive post therapy. The results of serial in vitro testing for cytotoxicity are presented with individual case histories, tumor staging and grading and the clinical outcome of hydrostatic pressure therapy.


Evidence that blocking factors in the sera of multiparous mice are associated with immunoglobulins.

Previous work has shown that lymph-node cells from pregnant BALB/c mice can kill syngeneic tumor cells in a microcytotoxicity assay, and that sera from pregnant BALB/c mice can block (inhibit) that effect. The present study shows that passage of such sera through immunoadsorbents charged with anti-mouse IgG2a or IgG2b removed the blocking activity, and that this could be recovered in the eluates; passage through an anti-IgG1 immunoadsorbent was less effective in decreasing blocking serum activity and adsorption to immunoadsorbent charged with anti-IgM or anti-IgA did not remove it at all. Passage of blocking serum through an immunoadsorbent coupled with antibodies from a rabbit anti-mouse embryo antiserum removed all of its blocking activity, and this could be recovered in the eluates. The findings are compatible with the hypothesis that the blocking factors operating in this system are largely complexes between embryonic antigens and IgG2a and IgG2b.


Ultrastructural alterations and modifications of nuclear RNA of rat liver by the combined action of thioacetamide and aflatoxin.

When aflatoxin is administered to thioacetamide-treated rats, the synthesis of nuclear RNA not only stops but the RNA that had accumulated in the nuclei by thioacetamide action disappears, probably by degradation "in situ" as none appears in the cytoplasm. Morphologically, the lesions provoked by aflatoxin add to those caused by thioacetamide. In the gigantic nucleoli that develop upon exposure to thioacetamide, aflatoxin provokes atypical segregations that result in the formation of larger and larger spaces in the nucleoli.


Therapeutic effect of intratumoral injection of bcg and other substances in rats and mice.

The experimental treatment of a rat sarcoma (McFiFi 2) by intratumoral injection of BCG2 is described. Tumors which have a mean diameter of less than 10 mm at the beginning of treatment are fully susceptible to BCG, although spontaneous regression is not observed at this stage. The effective dose of living BCG ranges from two injections of 0.1 mg to two injections of 1 mg, given IT at an interval of 7 days. The permanent cure of a proporation of the tumors may also be induced by IT injection of a similar dose of heat-killed BCG or of MER, or of 10(9) heat-killed C. parvum, according to the same schedule. Preimmunization of the rats with living BCG does not improve the efficiency of heat-killed BCG. Direct contact between the therapeutic material and the tumor cells is critical. If rats are grafted with two pieces of the same tumor in widely separated sites, the intratumoral treatment of only one of these tumors with living BCG is sufficient to induce regression of both tumors in 50% of the animals. The effect of BCG is counteracted by injection of silica or by ingestion of polaramine. The same intratumoral treatment with living BCG was applied to different rat and mouse tumors. Only McFiFi 2 tumors were cured by intralesional BCG. C3H mouse plasmocytoma 5563 was not cured by intratumoral BCG but its growth could be prevented by mixing BCG and tumor cells at the time of grafting; this tumor was considered to be of medium susceptibility. However, until there is definite proof that the two mechanisms are identical, one should consider the regression and cure of a growing tumor, and the prevention of tumor growth, as two different phenomena. The clinical treatment of human tumors resembles the first experimental procedure more closely than the second.


Production of epithelial and mesenchymal tumours with rat liver cells transformed in vitro.

Epithelial-like cells originating from the livers of 10-day and 8-week-old BD rats were established in culture. The cells were treated in vitro for 1 or 4 weeks with dimethylnitrosamine (DMN) or N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Although some structural changes were observed in treated cells, it was not possible to score for morphological transformation in vitro. Newborn syngeneic rats were injected with 1.5-2 times 10(6) treated or 1.5-5 times 10(6) control cells at various times up to 38 weeks from the beginning of treatment with the carcinogen. Following the injection of DMN-treated cells, a total of 32 of the 42 injected rat developed tumours, of which 17 were epithelial, 10 carcinosarcomas and 5 fibrosarcomas. Following the injection of the MNNG-treated cells into 61 rats, a total of 30 tumours were observed, including 8 carcinomas, 9 carcinosarcomas and 13 fibroscarcomas. Tumours, mainly of the mesenchymal type, were also observed in rats inoculated with control cells but at a lower frequency. The observation observed in rats inoculated with control cells but at a lower frequency. The observation of mesenchymal tumours is attributed to the presence of a mixed population of epithelial and mesenchymal cells in the orginal culture.


Human endometrial carcinomas serially transplanted in nude mice and established in continuous cell lines.

Three out of five human endometrial carcinomas were successfully grafted into nude mice (BALB/c/nu/nu). Two of these tumors could be maintained by serial transplantation. The morphological characteristics displayed by the grafted tumors were comparable to those of the original carcinomas. Permanent cell lines were established from these two tumors. Reinjection of cells grown in vitro into nude mice produced nodules of identical histology as compared to original solid transplants. The influence of medroxyprogesterone acetate on tumor growth in vivo and cell proliferation in vitro was studied. This hormonal treatment did not produce any significant effect on tumor cells, either in vitro or in vivo, for the two endometrial carcinomas. After medroxyprogesterone administration, a slight but non-significant growth inhibition of the tumor cells in vitro was observed and the tumor transplants in vivo did not appear to be influenced. The experiments illustrate the possible use of this model for testing potential anti-cancer agents.


Early onset of serum blocking in a murine melanoma model.

The early onset of serum blocking of host cell-mediated immunity was investigated in a transplantable murine melanoma employing two in vitro assays. One of these was based on the Takasugi and Klein cytotoxicity test; the other was a new test based on the inhibition of adherence of leukocytes to a plastic surface in the presence of tumor antigen. Both tests yielded similar results, and the adherence inhibition test was more sensitive. Blocking could be detected as early as 1 h after the inoculation of 1 times 10(7) melanoma cells. Early onset of serum blocking was also demonstrable if homogenized of tissue-cultured tumor cells were inoculated. Serum blocking under these circumstances was initially transient, declining at 24 to 48 h, but reappearing by the 4th day after inoculation. Furthermore, a functional immune system was not required for blocking factor development in this system, as evidenced by the onset of a similar pattern of blocking activity in heavily irradiated animals.


Activation of "eclipsed" lymphoid cells from advanced tumor-bearing mice through adoptive transfer to sublethally irradiated syngeneic hosts.

Immunologically inactive or "eclipsed" lymphoid cells from advanced tumor-bearing mice were investigated following their adoptive transfer to irradiated syngeneic hosts. Experiments were performed with two syngeneic tumor-host system: the T5-BALB/c tumor line chronically infected with a low-leukemogenic Rauscher virus variant and the TM1-C3H tumor line developed from a spontaneous C3H/He mouse mammary tumor. In confirmation of our previous data, peritoneal cells (PC) from advanced tumor-bearing mice (EPC) appeared to have lost any capacity to inhibit specifically the growth of corresponding tumor target cells in vitro colony inhibition (CI) tests, whereas PC from immunized mice (IPC) were perfectly active. When these EPC were adoptively transferred by intraperitoneal inoculation into sublethally irradiated (450 R) syngeneic mice in association with respective tumor extracts (TE), the PC from such recipient mice, taken 5 to 13 days later, were nearly as active in in vitro CI tests as were PC from parallel IPC-recipient mice. For this recovery of specific immunological activity following the adoptive transfer of EPC the adjunction of the TE and irradiation of the recipient animals seem important and may be necessary. On the other hand, no specific immunological activity was seen in PC from irradiated mice to which PC from normal mice had been transferred with TE. In addition to the in vitro results, an effect of adoptive transfer of EPC (retardation of tumor growth) was also observed in vivo. It is concluded that the "eclipsed" immunologically inactive state of the EPC in mice bearing advanced tumor is not irreversible and that activation of these cells can occur in vivo under certain conditions helped by the presence of tumor-specific antigenic stimulus.


Mutation induction in Chinese hamster V79 cells by two vinyl chloride metabolites, chloroethylene oxide and 2-chloroacetaldehyde.

Chloroethylene oxide and 2-chloroacetaldehyde, two possibly carcinogenic metabolities of vinyl chloride in mammals, caused a dose-dependent induction of 8-azaguanine- and ouabain-resistant mutants in Chinese hamster V79 cells in vitro. Up to one-hundred-fold higher concentrations of 2-chloroethanol or monochloroacetic acid, a urinary vinyl chloride metabolite in rats and man, were inactive.


Retention of tritium during the binding of tritiated benz(a)pyrene to DNA.

Chemical conversion of generally tritiated benzo(a)pyrene to 6 and 1,6-substituted derivatives resulted in 30% and 48% loss of tritium respectively. Metabolism of [3H], [14C]-benzo(a)pyrene by rat liver microsomes yielded 3-hydroxybenzo(a)pyrene with 30% loss of tritium, a mixture of quinones with 50% loss of tritium and three dihydrodiol metabolites which had retained all the tritium of the parent hydrocarbon. DNA isolated from mouse embryo cells which had been exposed to [3H], [14C]-benzo(a)pyrene, and DNA with this hydrocarbon bound following in vitro rat liver microsomal incubation were degraded enzymically and the hydrocarbon-deoxyribonucleoside products isolated. The tritium contents of the products obtained from both DNA samples were very close to those of the original double labelled benzo(a)pyrene. These results are inconsistent with a phenol or quinone intermediate being responsible for the reaction with DNA, but fully consistent with a diol epoxide intermediate as proposed by Sims et al. (1974).


A long-term 51chromium assay for in vitro cell-mediated tumor immunity. Correlation with simultaneously performed microplate assays.

In vitro assays of cell-mediated tumor immunity utilizing 51Chromium (51Cr) labelling of cultured adherent solid tumor cells were designed which allowed an effector cell/target cell incubation time of 48 h without overriding spontaneous 51Cr release. In a series of 16 consecutive experiments, blood lymphocytes from healthy human donors, from patients with tumors unrelated to the cultural tumor target cells, and from colon carcinoma and melanoma patients were tested for their cytotoxic effects on various target cell pairs, human colon carcinoma, melanoma, or skin fibroblasts. The same reagents were used in simultaneously performed microplate and 51Cr assays. Results obtained by visual counting of microplate tests and by 24-h assays of 51Cr release or 51Cr retention correlated in 20/25 effector-cell/target-cell combinations. In a series of six consecutive experiments, lymph-node cells from untreated Wistar/Furth rats, and rats bearing either chemically-induced colon carcinoma NG-W1 or polyoma virus-induced sarcoma P-W13 were tested for their cytotoxicity on syngeneic rat colon carcinoma and sarcoma target cells. Criss-cross type experiments were performed by microplate and 15Cr techniques done in parallel. Results obtained by visual counting of microplate tests and by 48 h assays of 51Cr release or 51Cr retention correlated in 15/18 effector-cell/target-cell combinations.


Problems of adjustment reported among a group of heroin addicts.

Many reports in the literature concerning the heroin addict and his addiction have been related to psychological tests and the personality and behavior among addicts. However, studies have not cited his adjustment problems. Forty-seven narcotic addicts were surveyed to determine their adjustment difficulties by an administration of the Mooney Problem Checklist. The results indicate that the most difficult areas of adjustment were related to personality, self-improvement, the home and family, and occupation. It was concluded that among these participating narcotic addicts, four areas were noted as frequent problems while five additional areas were reported as less of an adjustment difficulty.


Variables related to cannabis use.

A sample of 4,564 self-admitted cannabis users was compared with a sample of airmen who had no known record of drug abuse. This study indicates that there is a very strong likelihood for cannabis users to abuse other drugs. There are relationships between cannabis use and geographic area of enlistment, religious preference, aptitude scores, race, educational level, and age at enlistment. Cannabis use is also related to the likelihood of getting an undesirable discharge, to Airman Performance Report, and to promotion rate.


An examination of patterns of drug use in six suburban groups.

An investigation into the patterns of drug use of drug users was conducted across six specific groups in a northeatern suburb and at a state university. Information was obtained concerning past and present frequency of use, location of use and procurement, and availability and source of procurement. Relative similarities and differences in patterns of drug use an understood through the resulting group and drug matrix is discussed.


Some correlates of drug use among high school youth in a Midwestern rural community.

A study of the correlates of drug use (marijuana, LSD, mescaline, speed) among high school youth in a rural, Midwestern community indicated that peer group factors were the most influential in such behavior. Also, youth from less intact families and whose parents were perceived to use various legal drugs were more prone to drug use. Drug education was seen as not having as significant an impact in differentiating between users and nonusers nor in deterring users from further involvement. In support of previous research, we conclude that drug use is a form of behavior learned through peer and family socialization.


The effects of videotaped modeling and self-confrontation on the drinking behavior of alcoholics.

Alcoholics were exposed to behavior counseling alone (N =10), or behavior counseling with either videotape self-confrontation (N = 10) or role-modeling (N = 10), and compared to alcoholics receiving standard inpatient treatment (N =10). Immediate alternation of drinking topographies and posttreatment follow-up drinking dispositions served as dependent variables. Subjects receiving videotape self-confrontation achieved greater positive changes in posttreatment drinking analysis sessions than did other treatment groups. Follow-up probes suggested superiority of the experimental treatments in general, and particularly videotape self-confrontation. Performance in the posttreatment analysis sessions was predictive of follow-up drinking status (p less thann .05).


Instances of treatment for opiate and nonopiate drugs in one urban community.

Study was made to learn the extent of drug abuse coming to the attention of treatment personnel in private and public facilities within one urban community during a 1-month period. Reports from 105 facilities indicated alcohol was the major drug of abuse with heroin and nonopiate drugs running a distant second and third, respectively. Of 8,784 requests for treatment in which the use of drugs was seen as a factor, 83% involved alcohol, 9% opiates, 6% nonopiate, nonalcoholic drugs, and 2% unknown drugs.


Double-blind detoxification of methadone maintenance patients.

Twenty-four methadone maintenance patients were assigned to (1) decreasing dose (N = 12) or (2) continued methadone maintenance (N = 12), matching for dose, initial complaint levels, and counselor. After 14 weeks most patients in both groups had terminated from the study. Detoxifying patients usually terminated by obtaining a dose increase or dropping out; maintenance patients usually terminated for external reasons. Prior to terminating, detoxifying patients reported increased withdrawal complaints but no awareness doses had decreased. Termination was not directly related to dose level or percentage decrease. In both groups, terminators were likely to have been high in complaints during the baseline period.


A client-developed methadone maintenance program.

A realistic methadone maintenance program is a continuum of four related areas: intake, rehabilitation with on-going evaluation, detoxification, and postdetoxification followup, each jointly administered by client volunteers and professional staff. In the early stages of client treatment, pharmacists have more frequent contact with program participants than do other staff professionals. At the Minneapolis Pilot City Health Center, 31 of 69 participants in the methadone maintenance program were interviewed by their pharmacist to determine client understanding of program objectives, interpretation of program effectiveness, and suggestions for program improvement. Client understanding of the objectives or program elements ranged from 30 to 97 %. Client evaluation of the effectiveness of program elements ranged from 0 to 65%. The client-developed program included intake procedures to establish for each client the program objectives, rules, evaluation, guidelines, client goals, dismissal guidelines, and a review of supportive services. Rehabilitation would be continuous with consistent on-going evaluation to measure goal attainment, a decline in disruptive behavior, and freedom from illicit drug use. Detoxification should be undertaken after the client's behavior has stabilized and he has developed a marketable skill. Monitoring of the client to assure a drug-free state would be an important element of the postdetoxification follow-up.


Misuse and abuse of diazepam: an increasingly common medical problem.

Misuse and abuse of diazepam among addiction-prone individuals is reported. The most common pattern of abuse appears to be periodic ingestion of 30 to 80 mg of diazepam in one dose, either alone or in conjunction with methadone or other narcotics. Two cases of physical dependency to diazepam have been observed. Many addict patients using diazepam are buying it on "the streets". All physicians should know that diazepam abuse and misuse is occurring, and careful attention should be given to prescribing, transporting and storing this drug.


Personality correlates of drug preference among college undergraduates.

Three groups of college drug users--those expressing a preference for marijuana, amphetamines, or barbiturates--reported on experiences resulting from their drugs, and these groups, together with a group of nondrug-users, completed the Omnibus Personality Inventory (OPI). On the OPI the nonusers appeared more conventional and conforming than each drug group. Those preferring marijuana were less anxious than any other group, but the most distinctive group was that preferring barbiturates, which appeared the least intellectually inclined and the most emotionally distressed. This group's personality dispositions also seemed generally concordant with the experiences they reported from the drug.


Alcoholism treatment and evaluation: in search of methods. II. Collation of two-year follow-up studies.

This study collated 23 articles reporting outcome of alcoholism treatment efforts over a 2-year follow-up period. Broad conclusions reached by Costello (1975) in a similar collation of studies reporting on a 1-year follow-up interval found general support. Similar consistencies were noted across studies within groups described as having good outcome profiles as was noted by the previous collation. Good outcome results from matching relatively better prognostic cases wtih programs with broad treatment resources. Multiple baselines were offered as guidelines for program evaluation. Baselines were generated in the process of collation by hierachal grouping of outcome profiles. Different baseline to measure effectiveness of performance should prove appropriate for different measuring tasks. No one baseline is appropriate for all measuring tasks.


Drunkenness, a "special circumstance" in crimes of violence: sometimes.

A preliminary investigation into belief systems of the public about interactions between drunkenness and crime is reported. Fifty respondents, randomly selected, were interviewed first about their beliefs regarding the "effects of alcohol" along three dimensions--control, responsibility, and accountability. Second, they were asked to consider whether being legally drunk when committing a violent crime constitutes a "special circumstance" deserving other than the usual penalty. Three other possible contributing factors were also examined to determine their relationship to drunkenness as a "special circumstance"--premeditation, alcoholism, and recidivism. Two preliminary conclusions are suggested: (1) it appears that many members of the public still view alcohol abuse as an associated criminal offense, and (2) respondnets' beliefs about the "effects of alcohol" do not demonstrate a rational consistency as relates to penalty judgments concerning violent crimes committed by drunken individuals. This finding is, in part, consistent wtih Linsky's earlier work.


The effect of therapeutic intervention on the assessment scores of narcotic addicts.

The findings presented tend to support already established trends reported in the literature concerning the performance of opiate users on standard psychological tests. Evidence which suggests that addicts are not functioning at full intellectual capacity was presented for the first time. Moreover, the use of psychological tests as outcome measures for drug treatment was indicated.


Dose-response relations in drug-induced inappropriate secretion of ADH: effects of clofibrate and carbamazepine.

The effect of different doses of clofibrate and carbamazepine on water metabolism was compared in a patient with psychogenic polydipsia. A definite relationship was found between the doses of both drugs and the antidiuretic effect. Daily 2--4 g clofibrate was ineffective, but 6--8 g induced the syndrome of inappropriate secretion of ADH. 600 mg carbamazepine a day induced a marked antidiuretic response which could be further augmented by administering daily 1200--1800 mg. The discrepancy between the effective "hypolipidemic" and "antidiuretic" dose of clofibrate may perhaps explain the lack of reports on water intoxication induced by this agent, despite of its entensive use in clinical practice.


[Plethysmographic and in vitro studies of the vasodilator effect of furosemide (Lasix)].

The beneficial effect of furosemide in treatment of chronic and particularly of acute congestive heart failure has been attributed to its potent diuretic action. In recent studies [16], it has been postulated that the effect of this diuretic agent is primarily vascular in origin. The results of venous occlusion plethysmographic experiments (modificated Whitney-gauge technique) carried out in this study on the forearm of 6 healthy men, show that furosemide (40 mg. i.v.) does not influence arterial blood flow (4-5 ml/100 ml tissue - min). In contrast furosemide induces a prompt significant (p less than 0.001) and sustained (about 45 min) increase in venous capacitance (deltaV/100 ml tissue = 15%) and a corresponding decrease in E'. The direct effect of furosemide on vascular muscle tone was studied in vitro on portal vein and aortic strip preparations from 76 male rats. In 18 experiments mechanical and electrical activity (using three pressure electrodes) were simultaneously recorded. The results of the in vitro experiments show: 1. Only extremely high furosemide concentrations (greater than 500 mg/l) induce slight relaxation of aortic strips. 2. Furosemide causes in contrast a marked dose-dependent per cent decrease of the integrated isometric tension in portal vein preparations: 14 mg/l reduce the initial tension (= 100%) to 80%; 35 mg/l to 65%; 70 mg/l to 50% and 100 mg/l to 35%. 3. The venodilating furosemide effect is significantly (p less than 0.001) increased by reduction in external Na+-concentration [Na+]0 to 120 mM though further reduction in the [Na+]0 to 90 mM does not cause additional changes in the relaxation slope. 4. The simultaneous records of electrical activity demonstrate that the relaxing effect of furosemide is based on decreased spike frequency in shortened bursts as well as on pronounced impairment of conduction velocity without relevant changes in pacemaker frequency. These in vitro results are discussed from the point of view that a furosemide induced decrease in Na+-permeability may determine the changes obtained in electrical and mechanical behaviour of portal veins of the rat.


The gingival hyperplasia resulting from diphenylhydantoin in children and adults.

The incidence of gingival hyperplasia resulting diphenylhydantoin was studied in two hundred and nineteen patients of epilepsy from children to adults. The children group below puberty showed unexpectedly low incidence of gingival hyperplasia among the side effects of it comparing with other age groups.


Ultrastructural changes induced by vinblastine in cutaneous lesions of histiocytosis X.

The ultrastructural examination of the skin lesions of 2 typical patients with subacute disseminated histiocytosis X 12, 24, 36, 48 and 72 hours after the intravenous administration of vinblastine enabled us to observe that, after 12-24 hours, there were numerous Langerhans cells undergoing mitosis which had no spindle microtubules but showed fragments of newly forming nuclear membrane, thus demonstrating that mitosis was arrested in anaphase. Later on, in the Langerhans cells mainly, we observed degenerative phenomena (mitochondrial swelling, perinuclear edema and rupture of the plasma membrane) and, finally, a marked reduction in the number of this type of cells were observed.


Primary cutaneous cryptococcosis in Egypt.

Neither systemic nor primary cutaneous cryptococcosis has ever been reported in Egypt. The case of a 14-year-old girl with a solitary primary cutaneous cryptococcosis lesion is presented. A surgical specimen proved the diagnosis, although the lesion resembled a rapidly growing epithelioma. Follow-up for 4 months did not reveal evidence of systemic involvement.


Some comments on the narcissistic aspects of self-righteousness: defensive and structural considerations.

An analysis of the structural and defensive aspects of the self-righteous personality has been presented. Some genetic factors leading to the development of such a personality were considered. Analysis indicated that introjection of the idealized, righteous parent and identification with this introject was motivated by the need for narcissistic supplies. Fusion with this introject occurs during outbursts of self-righteous indignation directed towards an object cathected to a great extent with narcissistic libido. For the unconscious of the patient such an object represents in large measure the repressed aspects of his devalued self-representation. Some dynamic constellations encountered during treatment have been described.


Some further observations and comments on the earliest role of the father.

The longitudinal observation in the family setting of a boy (Michael) during his first two years is used to explore further the earliest role of the father, and to refine my 'early triangulation' model. This model was meant to account for some basic phenomena of Mahler's rapprochement subphase, and was partly based on Piaget's framework. The data are presented along three developmental lines. (1) The specific relationship with father as a different person: the concepts of 'specific refuelling' and of object-specific libido are introduced; and it is suggested that during the subphase of differentiation, all of Michael's specific objects (in particular, the father) shared some 'symbiotic' quality with the mother. (2) On the other hand, qualitative differences of the father relationship were also noted; they confirmed my earlier findings and Mahler's view. (3) Very early, Michael began to acknowledge the relationship with the parents as a couple. After a fleeting indication of rivalry (with mother!), a ritual game of 'getting his parents together' developed at the onset of the rapprochement subphase. This is discussed as one of many possible compromise solutions to avoid the full achievement of the anxiety-provoking 'early triangulation' process. This process, if completed, would involve 'identification with the rival parent', formation of a mental image of the self, and the positive cathexis of neutralized intragroup relationships (which presupposes symbolization). The ubiquitous observation of 'identification with the rival baby' may represent another such compromise solution, and thus a precursor of early triangulation. It might also be a parellel process, leading to 'generational identification' as distinguished from 'gender identification'. The isomorphism of these processes with Piaget's outline of cognitive development is pointed out.


A fresh look at perverse behaviour.

A review of psychoanalytic thinking on perversions is offered and brought up to date with an outline of Kohut's concept of perversions representing sexualization of narcissistic configurations. An emphasis is made on the sexualization of the affects to underscore the structural defect in perverse behaviour. Broad constructions directed to the disavowal of feelings are considered most meaningful in analytic treatment of individuals suffering from sexual perversions.


A search for predictive factors in institute supervised cases: a retrospective study of 183 cases from 1959-1966 at the Boston Psychoanalytic Society and Institute.

The purpose of this project was to determine if it is possible to predict from the information contained in the write-ups of the preliminary evaluations of patients accepted for Institute supervised analyses those patients who would successfully complete their analyses and those who would not. Three raters independently studied the write-ups of 183 cases treated at the Boston Institute during the period 1959-1966. Each rater filled out a questionnaire of 105 items which were thought to be of possible predictive value. Outcomes were sought from the analysts who treated the patients. 130 outcomes were obtained and revealed that the patients fell into 4 distinctly different outcome groups: (Group 1) those who completed analysis by mutual agreement between the analyst and patient; (Group 2) those who prematurely terminated their analyses against the advice of their analysts; (Group 3) those whose analyses were prematurely interrupted by their analysts; (Group 4) those whose analyses became interminable. Statistical analyses were done to see which of the 105 predictor items distinguished these four distinct outcome groups. Many of the predictor items were not useful because they either showed no variation among patients, or were too often left blank, or were rated with very low interrater agreement. Of the remaining items, we found ten items which did show a highly significant difference between Group 1 patients and those patients in at least one of the other three outcome groups. We found five other predictor items which showed large, although not quite statistically significant, differences between Group 1 and at least one of the other three groups. Of these 15 items, 7 dealt with family history. The others concerned the patient's past history (2), object relationships (2), patient's sex (1), symptomatic state (1), field of endeavour (1), and history of previous psychotherapy (1). We found it made no difference in terms of these 4 outcome groups what the patient's diagnosis was or whether he was a 1st, 2nd, 3rd or 4th supervised case. Among the other negative findings were patient's age and the ability to experience and tolerate felt anxiety. These did not distinguish any of the outcome groups. These findings show that additional predictively useful information is present in the preliminary evaluations of patients already screened and accepted for Institute analysis by trained evaluators. These results suggest that one particularly important area on which to focus future attention is family history.


A repeater type biotelemetry system for use on wild big game animals.

A repeater type telemetry system was developed and field tested on a wild elk near laramie, Wyoming, in the summer of 1973. The telemetry system consisted of the following: (a) a heat flow rate sensing implanted transmitter, (b) a repeater type neck collar and (c) a portable receiving station consisting of a receiver, decoding circuitry and analog chart recorder. The transmitter in (a) produced relatively low frequency rf pulses whose repetition rate was directly proportional to heat flow rate through the hide of the animal. In (b), the pulses from the implant are sensed and retransmitted using a relatively high power, high frequency transmitter. A second rf pulse was generated whose pulse spacing was related to animal activity. Details of circuit design and performance are given. Field experience has shown that this method is extremely useful for the monitoring of biological data from secretive big game animals such as elk.


The effect of radar on cardiac pacemakers.

The susceptibility of 16 noncompetitive cardiac pacemakers to radiation from a powerful radar system was investigated in the laboratory and in the vicinity of its prototype. From comparative in vitro tests in air, fat, water, and saline it was concluded that only tests in fat or air represent the worst case condition after implantation. In air all pacemakers showed signs of interference at pulse power densities between 0.025 mW/cm2 and 62.5 mW/CM2. Three of six implanted pacemakers were triggered or inhibited depending on their mode of operation when tested at a location 1.2 km away from the radar station by the radar beam occurring every 5.5 sec. Because interfering radiation can enter the pacemaker circuitry directly along the electrode, acting as an antenna, metal encapsulation of the pulse generator does not provide sufficient shielding against microwave radiation. However, pacemakers modified by metal encapsulation and a low-pass filter at the electrode remained undistrubed at pulse power densities of greater than 10 W/cm2 when tested under worst case condition in air.


Dangerous-electricity annunciator and detector.

Investigations into electrical accidents in hospitals have shown that the hazards are usually associated with the simultaneous use of two or more instruments. Recognizing this, several groups have written safety standards which limit the allowable potential difference between any two conductors near or connected to the patient. Implementing such a standard may be difficult since there may be a large number of such conductors and they must be tested using all combinations of two conductors. A simple scanning circuit using programmable operational amplifiers (PRAMs) and MOS digital circuitry makes the series of safety checks quickly and efficiently. The design includes both the ability to detect dangerous conditions and a digital annunciator to indicate which of the many leads being checked simultaneously is at fault. The scanning rate is rapid enough to allow the detection of dangerous transients. Preliminary results indicate that this portable, battery operated device is useful in providing an electrically safe environment for patients.


Instrument safety in explosive atmospheres.

The current "Energy Crisis" has dramatically increased our potential need for coal, the worlds most abundant fossil fuel. This will probably lead to a greater use of automation and instrumentation in the coal mining industry. The presence of methane in coal mines and in the coal itself plus the presence of coal dust, both of which can form an explosive atmosphere in air, means that the possibility of a gas or coal dust ignition must be considered when designing, purchasing and installing new equipment in this industry. In addition, many metallurgical processes involve the use of potentially explosive substances against which similar safety precautions must be taken. This paper outlines the various methods of protection currently in use and proposed for electrical instruments in explosive atmospheres, with particular emphasis on the work of the International Electrotechnical Commission.


The flammability limits of lean fuel-air mixtures: thermochemical and kinetic criteria for explosion hazards.

The present state of knowledge is reviewed concisely in terms of the experimental methods used, the effect of apparatus size, accuracy of data, methods of data presentation, and the sensitivity of the limits to initial temperature and pressure. The heat of combustion per mole of gas mixture at the lean limit is a reliable thermochemical criterion for the flammability of organic fuels with comparable reactivities. The limit calorific value for the heavy paraffins is 11.5 +/- 0.1 kcal mole -1. However, kinetic effects strongly influence this value. Highly reactive fuels (hydrogen, acetylene) require lower energy contents, whereas less reactive fuels (ammonia) require higher values. Hydrogen-starved fuels (carbon monoxide, cyanogen) show marked anomalies and are sensitive to impurities that can provide H-atom chain carriers. These kinetic effects are reflected in the experimentally measurable burning velocity of the fuel. This parameter is a key ingredient in the theory of flammable limits, which is briefly sketched. Five competing processes dissipate power from the combustion wave and quench it at some characteristic limit velocity. The prevalent consensus that the limits are controlled by natural convection is clearly demonstrated, and the complex interplay of kinetics and thermochemistry follows logically therefrom.


Design philosophy of air quality surveillance systems.

This paper discusses the design philosophy of the air quality surveillance systems which Kennecott is installing in the vicinity of its copper smelters in Arizona, Nevada, New Mexico, and Utah. These monitoring systems are part of supplementary control systems (SCS) that are utilized to ensure that short-term ambient air quality standards are met. These systems utilize minicomputers as remote terminals. The interface between a terminal and the primary sensors is via specially designed input/output circuitry. The system is controlled by a centralized host minicomputer, which is connected to each of the remote stations via a telephone line communication network. Real time data is displayed on cathode ray tubes located at strategic locations in the plants. This paper will discuss the system design philosophy from both a hardware and software point of view. The actual experience in design, development, and installation of the system will also be discussed.


Application of microwave spectroscopy to chemical analysis.

Traditional analytical techniques have been sucessfully employed on a great variety of systems for identifying stable reaction products as well as for purity analysis and reaction efficiency. However, most analytical techniques generally can only be applied to "well-behaved" chemical systems. Since gas phase reaction products do not always follow the "well-behaved" guideline, an alternate analytical tool, such as microwave spectroscopy, could prove beneficial for analyzing such systems and may well provide some new routes to synthetic chemistry. A general review of the present state-of-the-art for applications of microwave techniques to analytical studies will be presented. An attempt will be made to describe the limitations and advantages of microwave spectroscopy for probing chemical systems for product identification and for optimization of the efficiency of gas phase chemical reactions. As an illustration, some recent results obtained in our laboratory on the complex pyrolytic decomposition reactions of ethylamine will be described. Further examples of possible applications will be taken from typical industrial processes that employ vapor phase chemical synthesis techniques.


Ambient ground level monitoring: a sensible control system for the industry.

Sulfur emission rules are being changed. This action and a proposed EPA Supplementary Control strategy that would allow industrial facilities to continue their operations based on emission measurements and weather conditions is a logical step. Nevertheless, other EPA requirements and limitations are not acceptable to the electric power generating industry. Effective sulfur removal processes and equipment are yet beyond the "state of the art" and thus are not cost effective capital investments while the technology is in development. Field proven ambient monitoring networks are available now to implement fuel switching which is the preferred method of the power industry. This permits remaining within ambient limits, thus fulfilling the basic requirements of the primary SQX stand"... to protect the public health.".


[The Goltz-Gorlin syndrome. Review and case reports].

A case of Goltz-Gorlin-Syndrom (GGS) is reported with ectodermal and mesodermal defects. Differential diagnoses were: congenital poikilodermias, naevus lipomatodes cutaneous superficialis (Hoffmann-Zurhelle) and incontinentia pigmenti. Clinical aspects, histopathology, pathogenesis, genetics, and chromosomal patterns are compiled and the cases reviewed which were reported until 1974.


[Zinc therapy in acrodermatitis enteropathica].

Report of two patients with acrodermatitis enteropathica, one of them 20 years old and with very severe symptoms of the disease. Oral therapy with zinc resulted in complete cure within two months. The theory about chelating of dietary zinc in patients with acrodermatitis enteropathica is discussed.


[Demonstration of pathogens in lymphogranuloma inguinale. An electron microscopy study].

A case of lymphogranulomatosis inguinalis is reported, in which the definite diagnosis was made by the electronmicroscopical demonstration of Chlamydia lymphogranulomatosis in the lymphnode. The value of this diagnostical method is discussed in regard to verifying the diagnosis and in comparison with other methods. The lifecycle of the Chlamydia lymphogranulomatosis could be demonstrated electronmicroscopically. Its exceptional position in microbiological classification is discussed.


[Pediatric psychotherapy within the scope of dermatology].

The possibilities of psychotherapy of children with psychosomatic skin diseases on an outpatient basis are reported. Twenty children in their pre-school and school years were treated over a period of one to two years using conversational therapy and the Sceno test (from G. v. Staabs). The results underline the necessity of identification and working up of conflicts in order to prevent recurrences or shifting of the disease.


[Initial results in the treatment of male fertility disorders with kallikrein: asthenozoospermia].

30 patients with asthenozoospermia were treated with kallikrein a kinin-liberating proteinase over a period of seven weeks. During parenteral and oral application of kalikrein and after medication within an observation period of 3 months a significant increase of the quantitative and qualitative sperm motility was found. Parenteral application of kallikrein led to a significant increase of the number of spermatozoa 3 months after beginning of the kallikrein therapy. Other semen parameters were not influenced. No side-effects were observed.


[Functional, conservative treatment of tibial schaft fractures].

This paper presents the functional conservative treatment of tibial shaft fractures following the principles of DEHNE and SARMIENTO. The disadvantages associated with classical conservative treatment (fracture disease, stiff joints, atrophy and dystrophy) are diminished by early mobilization, early weight bearing, and free mobility of the knee joint. Shaft fractures which give optimal results are those with minimal displacement and which are easily reducible. It is suggested that intraarticular fractures, fractures which have a marked tendency to slip, and those which are a part of multiple trauma, are more successfully treated applying rigid fixation according to ASIF principles.


Localization of casein-rich, fat-rich and DNA-synthesizing cells in monolayer cultures of mid-pregnant mouse mammary epithelium.

Monolayers of 16-day pregnant BALB/cfC3H/Crl mouse mammary epithelial cells were examined for the occurrence and distribution of cells which contain large amounts of casein and fat and those which synthesize DNA. Cells within the central portions of epithelial cells appeared rich in casein and fat, whereas cells on the peripheral edges of the colonies synthesized DNA almost exclusively. Casein deposits and DNA synthesis were mutually exclusive phenomena, since only 2% of the cells synthesizing DNA also stained for casein. Of the casein-rich cells, 74% were also rich in fat, suggesting that cells wich contain large deposits of casein almost always contain large amounts of fat. These results indicate that a specialization of function exists between cells on the growing edge and those centrally located within a single colony of mammary epithelial cells.


A quantitative microspectrophotometric study of the lead precipitation reaction for the histochemical demonstration of acid phosphatase.

The possibility of quantitating microspectrophotometrically the lead precipitation reaction for the histochemical demonstration of acid phosphatase was studied using the following models: sections of rat kidney and human prostate gland, and polyacrylamide films with incorporated prostate gland homogenate. The activity of the polyacrylamide models was previously evaluated by a biochemical method and the specificity of the reaction was controlled with specific inhibitors. Linear relations between cytophotometric reading and enzymatic activity, and between optical densities and different incubation periods, were demonstrated. The results obtained indicate the validity of the microspectrophotometric quantitation for this reaction with direct readings over a wide range of the visible light spectrum.


The in situ localization of folic acid.

A histochemical azo-coupling method for localizing folic acid in situ is described. Cat and rat liver, kidney, bone marrow and brain were found to be rich in folic acid; stomach, intestine, salivary glands, and blood contained less. Folic acid was localized in the cytoplasm of tissues having a very active metabolism, but in the nucleus of highly specialized cells such as neurons.


Biochemical aspects of aldehyde fixation and a new formaldehyde fixative.

In this paper, it is assumed that tissue fixation is a process in which the proteins become less soluble and catabolic reactions stop. With this definition in mind, 2.5 and 5% glutaraldehhde and 4% formaldehyde in 0.1 M potassium phosphate buffer, pH 7.4, were compared with a new fixative, bicarbonate-formaldehyde. The following results were obtained. (I) With 2.5 and 5% glutaraldehyde, the solubility of tissue proteins were not decreased unifromly, and tissue glycogen was poorly preserved. (2) 4% formaldehyde in potassium phosphate buffer gave relatively good results. (3) Bicarbonate-formaldehyde decreased the solubility of tissue proteins reliably and preserved tissue glycogen perfectly. Histologically, it yielded excellent results. Since glutaraldehyde alters the properties of proteins substantially (Hopwood, 1972; Habeeb & Hiramoto, 1968), and since the natural appearance of tissues depends on native tissue proteins, formaldehyde-containing fixatives, in particular bicarbonate-formaldehyde, are preferable to glutaraldehyde-containing fixatives for all tissue preparative techniques. However, it is important that the fixation time in formaldehyde is kept short.


Calcium oxalate and the von Kossa method with reference to the influence of citric acid.

Crystals of calcium oxalate in pathological material and artificially precipitated in the absence or presence of citric acid in gelatin models were examined by polarized light and treated with silver nitrate under a variety of conditions. It was found that the intensity of the staining reaction was largely proportional to the strength of the silver solution, and was enhanced in in vitro studies by the presence of citric acid. Staining was also influenced by the crystal form, which was itself related to the absence or presence of citric acid.


Dermatophilosis in Australian bearded lizards.

Dermatophilosis (Dermatophilus congolensis) was diagnosed in 3 Australian bearded lizards. Each lizard died of causes associated with stress and poor adaptability, although the lesions appeared to be regressing at the time of death.


Dermatophilosis in two polar bears.

Dermatophilosis was diagnosed in 2 of 13 captive polar bears (Thalarctos maritimus), causing generalized dermatitis of 3 years' and 6 months' duration, respectively. Progressive clinical signs included yellowing and darkening of the hair, pruritus, encrustation of skin, and reluctance to bathe. Dramatic resolution of lesions occurred during 8 weeks of twice-weekly intramuscular treatment with long-acting penicillin.


A survey for Toxoplasma gondii antibodies in deer and other wildlife on a sheep range.

Blood samples were obtained from native mammals and birds on a sheep range (Hopland Field Station) in northern California. Serums were tested for antibodies to Toxoplasma gondii by the indirect hemagglutination test. Of 382 deer that were tested from 1964 to 1973, 77 (20%) were seropositive for T gondii. Among 36 serums representing 6 species of wild carnivores (badgers, bobcats, coyotes, foxes, raccoons, and skunks), 18 (50%) were seropositive. All of the 5 bobcats tested were seropositive, with antibody titers ranging from 1:65,536. The testing of 175 serums from small wild mammals indicated antibody prevalence of 8% among jackrabbits, 6% among brush rabbits, and 2% among squirrels. None of the native mice tested was seropositive for T gondii. Of 120 native birds tested, 6 (5%) were seropositive. Of the resident domestic species of animals tested, antibodies were found in 1 of 7 domestic cats, 1 of 5 feral cats, 1 of 2 dogs, and 54 (13%) of 405 sheep.


Nasal carcinoma in a captive Eld's deer.

A 7-year-old Eld's deer (Cervus eldii) developed a swelling rostromedial to the left eye in association with signs of weakness, blindness, and discomfort. By means of radiography and biopsy, the swelling was found to be a carcinoma of lining epithelium of the caudal nasal cavity and left frontal sinus. Within 2 weeks of initial observation, signs of neurologic involvement developed and the deer was euthanatized. Necropsy revealed metastasis to lungs, liver, kidneys, and abdominal lymph nodes.


Xylazine as an immobilizing agent for captive white-tailed deer.

Xylazine, at dosages of 0.89 to 8.00 mg/kg of body weight, was injected intramuscularly by manual or projectile syringe into 68 captive white-tailed deer (Odocoileus virginianus) to facilitate handling. Of 63 deer given the intended dose, 59 were moderately to deeply sedated and immobilized. Deer began to react visibly within 0.75 to 4.25 minutes after injection. Mean induction time (+/- SD) was 5.15 +/- 4.08 minutes and mean duration of immobilization was 197.90 +/- 101.13 minutes. Other than the prolongation of immobilization at dosages larger than or equal to 3 mg/kg, these times were not significantly affected by dosage or sex of the deer. Induction times were shorter in fawns than in older deer and much shorter in freshly trapped deer than in deer that had been trapped but kept undisturbed in semidarkened pens for 6 to 48 hours or in deer that were semitame captives. Dosages as low as 0.89 mg/kg were effective, and the safety margin appeared to be at least 8 times the minimal effective dose; however, immobilized deer were frequently unable to maintain sternal recumbency and required attention throughout the period of immobilization.


The use of diazepam and methocarbamol in the treatment of toxaphene poisoning in a Bangal tiger.

A 12-year-old female Bengal tiger was presented with clinical signs of acute chlorinated hydrocarbon poisoning and a history of recent consumption of food contaminated with toxaphene. Hyperreflexia and periodic convulsions were controlled by initial intramuscular injections of 30 mg diazepam and 2 g methocarbamol, followed at 6-hour intervals with intramuscular injections of 30 mg diazepam each, for 2 additional treatments. Following the initial treatment, hyperreflexia and convulsions did not recur.


Leptospirosis in selected wild mammals of the Florida panhandle and southwestern Georgia.

A group of 144 wild mammals, including white-tailed deer, cottontail rabbits, fox squirrels, gray squirrels, raccoons, opossums, a bobcat, and various small rodents was examined for cultural or serologic evidence of leptospiral infection. Leptospires were isolated from 1 of 25 rabbits, 1 of 27 fox squirrels, 1 of 26 gray squirrels, 4 of 18 mice and rats, 8 of 21 raccoons, 7 of 17 opossums, and a bobcat. Isolations were not made from 6 deer examined. Serotypes isolated were Leptospira interrogans, serotype grippotyphosa and L interrogans, serotype ballum. New host-serotype relationships were noticed in the following instances: bobcat: grippotyphosa, and gray squirrel: ballum. These studies further confirm the occurrence of grippotyphosa in the fox squirrel. Serologic response in these animals did not necessarily correlate with isolations, although some relationship was noticed in raccoons and opossums.


Opossums as a reservoir for Salmonellae.

Approximately 200 opossums, trapped during the fall of 1973 in the vicinity of Raleigh, NC, were maintained in the Institute's breeding colony in individual cages until the breeding season. Clinically normal, dead, and moribund opossums were examined for Salmonella. Six serotypes of Salmonella were identified in both clinically normal and diseased opossums. Positive culture results were obtained on 39 of 56 (70%) rectal swab specimens collected in the fall from incoming opossums, and on 30 of 50 (60%) rectal swab specimens collected during midwinter from an additional group of clinically normal opossums, which were maintained in isolation for approximately 3 months before testing. At necropsy, 87 of 108 (81%) diseased opossums were culture positive for Salmonella. Salmonellae in serogroups B and R were isolated from the spleen, liver, kidneys, or heart blood as well as the ileum of 57 diseased opossums. In 23 cases, S typhimurium or S bern was isolated in pure culture from the visceral organs. These findings indicated bacterial septicemia. In contrast, salmonellae in serogroups C1, E1, and F were routinely isolated from the feces of clinically normal and diseased opossums, suggesting a habitat restricted to the intestinal tract and probably the mesenteric lymph nodes. It was concluded that the opossum serves as a reservoir for a number of serotypes of Salmonella and may have an important role in the epizootiology of wildlife salmonellosis.


An epizootic of cerebrospinal nematodiasis in cottontail rabbits.

A progressively debilitating neurologic syndrome characterized by torticollis, ataxia, circling, and abnormal posture was observed in 16 of approximately 60 cottontail rabbits (Sylvilagus floridanus) captured in a 12-hectare portion of a woodlot in southwestern Virginia. Inflammatory and degenerative alterations in cerebellum and midbrain regions were characterized principally by malacia, perivascular cuffing, and gliosis. Single Ascaris columnaris larvae were found in the cerebellum of 2 rabbits and the spinal cord of 1 rabbit.


A microbiologic study of the urban gray squirrel.

Bacteriologic, virologic, and serologic examinations were conducted on 180 urban gray squirrels (Sciurus carolinensis) during a 1-year period in a metropolitan area. Evidence was not found of infections with leptospires, enteric or other bacteria, rickettsial agents, Francisella tularensis, or arthropod-borne viruses. The squirrels were remarkably free of evidence of bacterial or viral infections of importance to man and lower animals.


The role of indigenous wild, semidomestic, and exotic birds in the epizootiology of velogenic viscerotropic Newcastle disease in southern California, 1972-1973.

During an epornitic of velogenic viscerotropic Newcastle disease (VVND) in southern California, free-flying wild birds, captive and free-ranging semidomestic birds, and exotic birds were collected from the quarantine area to determine their role in the epizootiology of the disease. The VVND virus was isolated from 0.04% of 9,446 free-flying wild birds, 0.76% of 4,367 semidomestic birds, and 1.01% of 3,780 exotic birds examined. Three house sparrows and 1 crow directly associated with infected poultry flocks were the only free-flying wild birds from which VVND virus was isolated. Among semidomestic species, ducks, quail, chukars, pheasants, peafowl, pigeons, and doves were found to be infected. Psttacines, pittas, and toucans accounted for 92% of the VVND virus isolations from exotic birds. In addition, domestic Newcastle disease virus (NDV) was isolated from 0.29% of the free-flying wild birds, from 1.65% of the semidomestic birds, and from 0.19% of the exotic birds collected. Hemagglutination-inhibition against domestic NDV was demonstrated in 0.24% of 3,796 wild bird serums, 8.28% of 2,004 semidomestic bird serums, and 3.90% of 231 exotic bird serums tested. Although few free-flying wild birds were infected with VVND virus in this epornitic, the isolation of domestic NDV strains from free-flying wild ducks and mourning doves suggests the potential for transportation of NDV over long distances by migratory birds.


Anatrichosoma infection in two white-handed gibbons.

Multiple nodular lesions of the nematode Anatrichosoma were observed on the ears, lips, nares, and eyelids of 2 adult gibbons (Hylobates lar). The lesions were 4 to 7 mm in diameter, gray to pink, and firm on palpation. Microscopically, the nodules consisted of thickened epidermis having intraepidermal cysts containing the nematode and eggs. Live female nematodes were recovered from fresh biopsy specimens. Because male specimens were not obtained, the species could not be identified.


Autonomic nervous system and adaptation to cold in man.

The responses to cold hand test (blood pressure increase and tachycardia) and to a cold face test (blood pressure increase and bradycardia) were used to study the role of the autonomic nevrous system in cold adaptation in humans. The Eskimos (men, women, children) were shown to have a very weak sympathetic response to cold but the vagal response (bradycardia) was identical to that of white people. A group of mailmen from Quebec city living outdoors approximately 30 h/wk throughout the year was also studied. A significant decline in the cold pressor response and an enhanced bradycardia (cold face test) were observed at the end of the winter. Similarly the fall in skin temperature of the cheek was not as pronounced when the measurements were made in May compared to those made in October. A group of soldiers was also studied before and after an Arctic expedition. It was found that the bradycardia of the cold face test was also more pronounced after sojourning in the cold. These results indicate that repeated exposures to severe cold in men activate some adaptive mechanisms characterized by a diminution of the sympathetic response and a concomitant enhancement of the vagal activation normally observed when the extremities and the face are exposed to cold.


Simulation of regional lung emptying during slow and forced expirations.

Regional lung emptying was simulated by means of a bialveolar lung model. The influence of bronchial asymmetry and the vertical pleural pressure gradient was evaluated. The model suggests that 1) in vivo the influence of the pleural pressure gradient prevails over that of the bronchial asymmetry; 2) in the presence of this gradient, the shape of phases III and IV of the single-breath washout curves obtained following inspiration of a tracer gas bolus at residual volume is determined by the recoil pressure-volume curve of the lung, by the vertical displacements of the alveoli, and,, at higher flow rates, by the elastic characteristics of the airways; 3) if the pleural pressure gradient is independent of lung volume and of flow rate, the factors mentioned in 2 suffice to produce single-breath washout curves (phases III and IV) and regional vs. overall lung volume relationships corresponding to those observed in vivo; 4) the configuration of the maximal expiratory flow-volume curve is relatively insensitive to pulmonary and bronchial asymmetry, at least in healthy individuals.


Experimental cardiac necrosis in hypobaric and anemic hypoxia.

Resistance to isoproterenol-induced cardiac necrosis (IPRO) was compared in rats exposed to two types of hypoxia (i.e., hypobaric and anemic). IPRO was induced by two consecutive, subcutaneous injections of isoproterenol (80 mg/kg) at 24-h intervals. The animals were killed on the third day and the severity of the lesion was evaluated on a 0 (no damage) to 4 (severely damaged) scale. White male rats (HA) were exposed in a barometric chamber to a simulated altitude of 7,000 m (307 mmHg) for 4 h/day for 24 days. Two groups of control rats were kept at sea level; one group (SLA) was the same age and one group (SLW) was the same weight as the altitude-exposed rats. The HA rats were significantly more resistant to IPRO with a mean necrogenic rating of 1.8 compared to 3.3 for the SLA and SLW rats. Infant rats (AA) were made anemic by feeding full-cream milk and glucose for 100 days after weaning. Two groups of control animals were fed a standard laboratory diet; one group (AC) was the same age and one group (AW) was the same weight as the AA rats. There was no significant difference in the necrogenic ratings of the AA (3.3), AC (3.5), or WC (3.7) hearts. Thus, hypobaric hypoxia affords some protection against IPRO which is not afforded by anemic hypoxia. Similarities and differences in the two hypoxias are discussed.


Integration of chemoreceptor stimuli by rostral brainstem respiratory areas.

Ventilatory regulation by brainstem sites rostral to the midpontile level was assessed in decerebrate cats by comparing the effects of punctate pneumotaxic center lesions with those of midpontile transection. After either procedure, PACO2 was significantly elevated. Moreover an equal suppression of hypercapnia-induced minute volumes and maintenance, at some PACO2 levels, of minute volume responses to hypoxia was observed. Tidal volume elevations accounted for the maintenance of hypoxia-induced minute volumes. Following pneumotaxic center lesions, hypercapnia-induced tidal volumes were higher than those exhibited subsequent to midpontile transection. After carotid sinus nerve section, PACO2 was elevated and hypoxia-induced alterations were abolished. Bilateral vagotomy resulted in apneusis. These data demonstrate that, in the brainstem area examined, only the pneumotaxic center influences the PACO2 level or set point for respiratory activity. A locus of tidal volume generation is ascribed to rostral brainstem sites outside this pneumotaxic center. Data obtained support the hypothesis of a differential brainstem integration of peripheral and central chemoreceptor afferent stimuli.


Prediction of body composition in habitually active middle-aged men.

In 45 physically active men (ages 35-67 yr) who underwent hydrostatic weighing to determine body composition, multiple regression equations were developed for the prediction of body density (D), lean body weight (LBW), fat body weight (FBW), and % fat using selected anthropometric measurements. The prediction accuracy for these parameters using several previously generated anthropometric regression equations was also determined. With equations developed from the present data a substantially higher correlation was obtained between measured and predicted LBW (r = 0.95) than between measured and predicted D (r = 0.85), FBW (r = 0.88), or % fat (r = 0.84). When previously developed equations were applied to the present sample, correlations between measured and predicted values were considerably lower (4-42%) than in the original studies; this reduction was least in the case of LBW. Analysis of previous data indicated that in selected populations total body weight can account for a relatively large fraction of the variance in LBW. LBW may be estimated quite accurately (r greater than or equal to 0.90) in physically active men with one of several regression equations which include total body weight as an independent variable.


Circadian variations in the sweating mechanism.

Sweat rates and body temperatures of human subjects were measured at 0200, 1000, and 1800 h during a heat exposure of 90 min. The latent period of sweating was not significantly altered in the evening but significantly shortened during the night. Mean body temperature corresponding to the onset of sweating was nearer to the basal body temperature during the night, while during the day the difference between these two temperatures became larger. This phenomenon seems related to the circadian cycle of vasomotor adjustment, since during the night body conductance was higher than during the day and corresponded to a state of a vasodilatation similar to that observed at the onset of sweating. During the day, this situation was reversed. During steady state, the following changes were observed: sweating rate, night less than morning less than evening; skin temperatures, night less than morning less than evening; and rectal temperature increase, morning less than evening less than night. It is hypothesized that these changes are due to either different metabolic rates or an imbalance between heat gains and losses which preserve the circadian rhythm of the body temperature, even under thermal loads.


Relationship between turnover rate and blood concentration of lactate in exercising dogs.

Steady-state blood lactate concentrationss and lactate turnover, or entry, rates were determined by use of constant infusion of L(+)-[14C]lactate in seven anesthetized dogs before and during electrically induced exercise. Lactate entry rates increased during exercise in all dogs with or without the infusion of additional exogenous cold lactate. Blood lactate concentrations, on the other hand, rose to levels considerably below those predicted for these entry rates in a previous study of the relationship in normal nonexercising dogs. It is concluded that improved efficiency of lactate removal during exercise allows low blood concentrations despite large increases in entry rates.


"Closing volume" changes in alloxan-induced pulmonary edema in anesthetized dogs.

"Closing volume" (CV) was measured by the single-breath oxygen (SBO2) test in six dogs (alloxan group) before and after alloxan 100-200 mg/kg iv) was injected. CV increased significantly (P less than 0.05) from 32 +/- 3.2% (base line) to 45 +/- 3.5 % in period 1 (0-30 min after alloxan), but vital capacity (VC), respiratory system pressure volume (PV) curves, and alveolar plateau slopes did not change. No radiologic evidence of pulmonary edema was demonstrated in two dogs studied in period 1. CV decreased to 20 +/- 3.9% during period 2 (30-80 min after alloxan) and was associated with tracheal frothing, decreased VC, changes in the PV curve, and alveolar plateau slope, as well as histologic evidence of severe pulmonary edema. CV was 29 +/- 3.0%, and there were no changes in VC, PV curves, or alveolar plateau slopes in 6 other dogs studied for 2 h (control group). CV increased during period 1 before pulmonary edema could be demonstrated by changes in VC, PV curves, or radiography, but in period 2 lung function was so altered that CV by the SBO2 technique gave no useful information.


Effects of dry air and subsequent humidification on tracheal mucous velocity in dogs.

The impairment of mucociliary transport by dry air breathing and the restoration of function with subsequent humidification of inspired air were investigated in anesthetized dogs. Tracheal mucous velocity was measured by a cinebronchofiberscopic technique. The breathing of dry air through an uncuffed endotracheal tube produced almost complete cessation of the flow of tracheal mucus after 3 h. Subsequent breathing of air at 38 degrees C with 100% relative humidity restored tracheal mucous velocity to control values by the end of and additional 3 h. Histologic examination of the trachea at the end of the 3-h dry air breathing period revealed focal areas of sloughing of the ciliated epithelium and submucosal inflammation. Although morphometry was not employed, the inflammatory changes appeared to have progressed during 3 h of breathing fully humidified air subsequent to the dry air breathing period. These findings were consistent with previous reports that the inflammatory response to injury of the tracheobronchial mucosa might be delayed and that the mucociliary transport system has a great deal of functional reserve. We found that an artificial heat and moisture exchanger placed on the proximal end of an endotracheal tube partially protects against the suppression of tracheal mucous velocity caused by dry air breathing.


Turnover of free fatty acids during recovery from exercise.

The turnover of plasma free fatty acid (FFA) was studied during the recovery from exercise with the aid of a continuous infusion of 14C-labeled oleic acid. Arterial FFA reached a maximum of twice the exercise value after 6 min of recovery and was still 75% above the basal level after 20 min. Within 2 min after exercise, plasma radioactivity had increased and the specific activity of plasma oleic acid had fallen. The rate of uptake of FFA from the plasma pool rsoe by 40% during the first minutes after exercise. The rate of release of FFA to the plasma pool showed a peak 2 min after exercise and was thereafter about 40 mumol/min lower than the rate of uptake. The fractional turnover of FFA decreased to resting levels within 5-10 min after exercise. It is concluded that the postexercise peak in arterial FFA is a consequence of augmented release of FFA into the plasma pool above the level during exercise, possibly related to the release of sympathetic vasoconstrictor tone. As a consequence, the rate of removal of FFA rises at the end of exercise and remains augmented above the basal level for as long as the arterial concentration is increased.


Altitude-induced erythrocytic 2,3-DPG and hemoglobin changes in rats of various ages.

Rats of various ages (2, 12, 24, and 40 mo of age) were exposed for 4 wk to either a simulated high altitude of 23,000 ft or to a Peoria, Ill., altitude of 650 ft above sea level. Hematocrit ratios, hemoglobin, and erythrocytic 2,3-diphospho-glycerate (2,3-DPG) concentrations were measured. Hematocrit and hemoglobin determinations revealed a decrease in erythrocytic content with increasing age, and the augmented  erythropoietic response was seen in all age groups of animals as a result of altitude exposure. The maximal erythrocytic content of hemoglobin in the 40-mo-old animals was significantly lower than that of all other age groups. Erythrocytic 2,3-DPG levels were significantly changed by aging alone. In the 40-mo-old group there was a 35% increase over the next highest sea-level value. However, while erythrocytic 2,3-DPG content increased significantly in all other age groups following altitude exposure, it decreased 46% in the 40-mo-old group.


Effects of equivalent sea-level and altitude training on VO2max and running performance.

Twelve middle-distance runners, each having recently completed a competitive track season, were divided into two groups matched for maximal oxygen uptake (VO2max), 2-mile run time and age. Group 1 trained for 3 wk at Davis, PB = 760 mmHg, running 19.3 km/day at 75% of sea-level (SL) VO2max, while group 2 trained an equivalent distance at the same relative intensity at the US Air Force Academy (AFA), PB = 586 mmHg. The groups then exchanged sites and followed a training program of similar intensity to the group preceding it for an additional 3 wk. Periodic near exhaustive VO2max treadmill tests and 2-mile competitive time trials were completed. Initial 2-mile times at the AFA were 7.2% slower than SL control. Both groups demonstrated improved performance in the second trial at the AFA (chi = 2.0%), but mean postaltitude performance was unchanged from SL control. VO2max at the AFA was reduced initially 17.4% from SL control, but increased 2.6% after 20 days. However, postaltitude VO2max was 2.8% below SL control. It is concluded that there is no potentiating effect of hard endurance training at 2,300-m over equivalently severe SL training on SL VO2max or 2-mile performance time in already well conditioned middle-distance runners.


Effects of hyperoxic gas mixtures on energy metabolism during prolonged work.

These experiments were designed to study selected respiratory and metabolic responses to exercise in hyperoxia. Four subjects were examined during 30-min bicycle ergometer rides at both 40% and 80% of their aerobic maximum. The VO2 was significantly increased at both work levels breathing 60% O2 versus 21% O2, while VCO2 showed no significant change during the 40% exercise tests but was significantly decreased during the 80% intensity rides. The average increase in the volume of O2 taken up during 30 min of hyperoxic exercise, compared with normoxia, was 3.3 liters at the 40% exercise level and 5.6 liters at the 80% level. Neither the magnitude of the O2 nor the CO2 storage calculated for the exercise bouts could explain these increases. Steady-state criteria for the gas stores were established by the stable values of PETCO2, VO2, VCO2, and VI from minute 6 through 30 at both work levels. R values decreased during the hyperoxic tests suggesting the possibility of a shift toward increased fatty acid metabolism.


Effects of epinephrine on resisitive and compliant properties of the canine vasculature.

The peripheral circulation of 22 anesthetized dogs was separated into three parallel regions, where the outflow from each region could be measured and both outflow and inflow pressures could be controlled. We were thus able to estimate arterial and venous resistance and venous compliance for each region. The pressure dependency of these parameters was determined before and during continuous infusion of epinephrine (3 mug-kg-1 min-1). Epinephrine increased the arterial resistance in all regions but did so in such manner as to increase the fraction of cardiac output perfusing the splanchnic region. The venous resistances were all elevated by epinephrine and showed a greater pressure dependency than during control. Systemic venous complicance was found to be pressure dependent during both control and epinephrine administration, decreasing by nearly 50% from the lowest to the highest venous pressures (4-12 mmHg) investigated. Splanchnic compliance was found to comprise nearly half the total systemic compliance. Results were interpreted using an extension of the parallel compartment model of the peripheral circulation described by Caldini, Permutt, Waddell, and Riley (2).


Shunt dynamics in experimental atrial septal defects.

Inorder to study the hemodynamic variables involving the magnitude, direction, and timing of phasic shunt flow, both the interatrial pressure gradient and blood flow along with other pertinent hemodynamic variables were measured instantaneously across a surgically created atrial septal defect (ASD) in seven awake dogs. Atrial and ventricular pacing and infusion of phenylephrine and isoproterenol were used to alter hemodynamic conditions. The wave form of phasic ASD flow was similar both in configuration and timing to the interatrial pressure gradient. During the cardiac cycle, both left-to-right (L-R) and right-to-left (R-L) shunting occurred: atrial contraction augmented L-R flow; the onset of ventricular contraction was associated with R-L flow; during the latter part of ventricular contraction, flow returned to L-R with the maximum L-R shunting occurring in early diastole. Tachycardia, infusion of phenylephrine and isoproterenol did not alter the phasic flow pattern. Both spontaneous and positive pressure respiration decreased net L-R shunting.


Circadian variations in concentrations of plasma thyroxine and triiodothyronine in man.

The plasma concentrations of thyroxine (T4), triiodothyronine (T3), and total protein (Pr) were measured at 2-h intervals in 8 male subjects during two 24-h periods. Plasma T4 and T3 levels varied significantly during the day. T4 values were highest at 0900 hours and thereafter declined rapidly reaching lowest levels at 1500-1700 hours (mean decrement, 13.2% of 0.00-hour value). Plasma T3 was highest at 0900 hours and lowest at 1700-1900 hours (mean decrement, 16.7% of 0900-hour value). Fluctuations observed in Pr were not significant. Variations in plasma T4 and T3 appeared concordant with respect to time, since no significant variation was detected in T3:T4 plasma concentration ratios. In view of previous studies that have demonstrated circadian variations in the binding of thyroid hormones by plasma proteins, it is suggested that the observed temporal variations in plasma concentrations of T3 and T4 reflect parallel changes in the capacity or affinity of specific plasma binding proteins of these iodothyronines.


In vivo measurement of variations in the oxygen 18 content of water in rat brain.

A method of analysis for oxygen 18 is described, based on the anodic oxidation of specially prepared tantalum wires implanted through cannulas into the tissue of living animals. The thin anodic oxide layer formed on these wires is then analyzed by the 18O(p,alpha)15N reaction. The isotopic oxygen concentration of water in the brain obtained by this method compares very well with the values obtained by conventional analysis using mass spectrometry. This in vivo method of nuclear microanalysis has been used in both metabolic and equilibration experiments involving oxygen 18. The half-life for the turnover of 18O in body water was found to be about 3 days. A simple three-pool model is presented which can account for the experimental results obtained from the dilution by body water of interperitoneally injected water highly enriched in 18O.


A modified measurement of respiratory resistance by forced oscillation during normal breathing.

We have modified the measurements of the resistance of the respiratory system, Rrs, by the forced oscillation technique and we have developed equipment to automatically compute Rrs. Flow rate and mouth pressure are treated by selective averaging filters that remove the interference of the subject's respiratory flow on the imposed oscillations. The filtered mean Rrs represents a weighted ensemble average computer over both inspiration and expiration. This method avoids aberrant Rrs values, decreases the variability, and yields an unbiased mean Rrs. Rrs may be measured during slow or rapid spontaneous breathing, in normals and in obstructive patients, over a range of 3-9 Hz. A good reproducibility of Rrs at several days' interval was demonstrated. Frequency dependence of Rrs was found in patients with obstructive lung disease but not in healthy nonsmokers.


Alternative method for measurement of arterial pressure in the rabbit.

By using an electrical impedance plethysmorgraph and a pressure applicator to a rabbit's earlobe artery, it became possible to monitor the blood pressure for periods of several months. A study of the correlations of the blood pressure from carotid and ear was also made at varied blood pressures under different conditions which showed excellent correlations. This method could effectively replace the encannulation technique for monitoring rabbit's blood pressure in chronic experiments.


Computerized method for analyzing maximum and partial expiratory flow-volume curves.

Computerized instrumentation and software have been developed to obtain maximum expiratory flow-volume (MEFV) and partial expiratory flow-volume (PEFV) curves. The computerized system calculates and prints out the flow at 25% and 40% of control vital capacity (VC), the expiratory volume, peak expiratory flow rate and expiratory volume at one second (FEV1) divided by VC, the latter expressed as a percent. The flow-volume curves can be displayed on an oscilloscope or plotter and stored on magnetic tape. A pilot study was completed to demonstrate the reliability and validity of the data obtained.


A high accuracy linear rate meter.

By implementing analog computer techniques using digital circuits, an instantaneous rate meter was built with approximately 100 times the accuracy of commercially available rate meters. The circuit is accurate to within +/- 0.2 events/min over a range of rates of 0.2-900 epm. Modifications can be made to provide a digital display of rate. The circuit design techniques used in developing the rate meter may be used to generate a wide variety of functions of time with very high accuracy.


Multichannel subcarrier ECG, respiration, and temperature biotelemetry system.

A three-channel biotelemetry system measuring ECG, respiration, and body temperature is described. The transmitter employs a 6-kHz subcarrier oscillator and is small enough for surgical implantation in animals the size of rats or larger. The frequency modulated 6-kHz tone from the reciver can be demodulated directly or recorded on an inexpensive cassette tape recorder for future analysis. The transmitter cost is approximately $35.00 and measures 3 times 1 cm. A battery life of several weeks and transmitter range of 10-100 m is typical. Transmission is on the FM broadcast band (88-108 MHz) and reception from an inexpensive FM portable receiver is possible.


Body surface area in the infant rat.

Body surface area (SA), one index used to minimize size differences in metabolic studies, was estimated by a coating method in rats aged 1, 7, 14, and 21 days (d) (n = 100-107). Body weights (BW) at each age varied about twofold. Regression equations were calculated for SA (cm2) vs. BW (g) (SA = 8.73 + 2.29 BW, 17.79 + 1.71  BW, -4.92 + 2.16 BW, and 53.68 + .82 BW at 1, 7, 14, and 21 days, respectively) and log SA vs. log BW (SA = 6.71 BW0-667, 9.12 BW0-577, 1.73 BW1-042, and 18.97 BW0-412). All the latter differed significantly from SA = 10 BE2/3, frequently used with adult mammals. Correlation coefficients were approximately 0.6-0.9 and did not differ with mode of expressing results. Regressions, whether linear or logarithmic, differed significantly among ages, apparently reflecting appreciable conformational changes in the rapidly growing and maturing preweanling rat.


Reproducibility of dynamic compliance and flow-volume curves in normal man.

To evaluate methods proposed for the early detection of small airways obstruction. we have compared the precision of the forced expiratory flow-volume curve and of measurements of the frequency dependence of lung compliance in normal subjects, in 10 of whom these measurements were made on four occasions, and in 5 on two occasions. The maximal expiratory flow rate was highly reproducible, revealing consistent differences between these normal subjects, particularly when measured at 60% of TLC and corrected for differences in body size. The frequency-dependence measurements, expressed as the slope of the regression line relating dynamic compliance to frequency, showed much greater variation between repeated measurements in the same subject. Comparison with earlier published accounts is difficult in view of lack of quantitative data, but the variability between single measurements on different normal subjects appears to be similar to that which we have found when the results are expressed in a comparable manner. Dynamic compliance at a frequency of 1 Hz lay between 48% and 141% of the value obtained by extrapolation to zero frequency.


Effect of lactate on FFA and glycerol turnover in resting and exercising dogs.

The rates of appearance of FFA (RaFFA) and that of glycerol (RaGLY) were measured simultaneously with [1-14 C]palmitate and [2-3H]-glycerol, in dogs with indwelling arterial and venous catheters. Lipolysis was stimulated by exercise (treadmill run on 10% slope) or by the infusion of norepinephrine (0.5 mug/kg-min). Na-L(+)-lactate (L), Na-pyruvate (Py), or Na-nicotinate (N) were infused. All three components decreased RaFFA. RaGLY was increased by L, unaltered by Py, and decreased by N. There was an inverse correlation (P less than 0.001) between the logarithms of RaFFA and plasma lactate. A linear correlation was obtained between RaGLY and plasma lactate when this latter was increased by the infusion of L. It is suggested that a) lactate in physiological concentrations inhibits the release of FFA stimulated by exercise and b) the increase of the NADH/NAD ratio leads to the formation of alpha-glycerophosphate which in turn yields glycerol. Therefore changes in plasma glycerol do not reflect lipolysis when blood lactate increases. c) The effect of lactate on RaFFA can be explained by an enhanced reesterification, although a direct inhibition on lipase could not be excluded.