Treatment of postbiopsy pneumothorax with a self-contained pneumothorax treatment device.

PURPOSE: To evaluate the usefulness of a self-contained pneumothorax treatment device, in which a catheter and a one-way valve compose a single unit, in cases of postbiopsy pneumothorax. MATERIALS AND METHODS: Twenty-one patients underwent placement of the device to drain a postbiopsy pneumothorax. Treatment was considered successful when no therapy other than the device was needed. RESULTS: Treatment was successful in 16 (76%) of the 21 patients. Causes of treatment failure were dislodgment of the device (n = 3), malfunction of the device (n = 1), and a persistent air leak that led to pneumothorax recurrence after removal of the device (n = 1). Eight patients (38%) experienced problems after insertion of the device: The device dislodged in seven patients and malfunctioned in one patient. These problems led to treatment failure in four patients (see above). In the remaining four, further treatment after device dislodgment was not required. CONCLUSION: Treatment with the self-contained pneumothorax treatment device shows promise. Modifications to the device may alleviate technical problems and insertion difficulties.

In vivo carcinogenesis assay of L-alpha-acetylmethadol.HCl in rodents.

With increasing clinical use of L-alpha-acetylmethadol.HCl (LAAM), findings of a carcinogenic bioassay could be useful in risk assessment. Initial studies provided a sex-related oral LD50 in B6C3F1 mice, 126 mg/kg for males and 71 mg/kg for females, and changes after treatment with mean doses of 8, 18, and 33 mg/kg for 90 days which included hyperactivity and unchanged growth rate, food intake, and morphology. Twenty-four-month oral doses were 7.6 and 30.1 mg/kg for mice, 3.1 and 9.7 mg/kg for male rats, and 5.7 and 16.6 mg/kg for female rats. LAAM was lethal in high-dose male mice (40% survival) whereas survival rates of 74-78% were similar in other treated and control groups. An 80-90% survival rate was seen for rats. Deaths related to aging and concomitant morphologic changes occurred randomly in all groups. The causes of LAAM-induced deaths were not established. Central nervous system stimulation and fighting were more common to male rodents. A dose-related inhibition of growth was also common but food intake was stimulated in male mice and both sexes of rats. An increase in liver neoplastic nodules was dose related and drug related in rats. Some nonneoplastic lesions may have been drug related. Terminal plasma LAAM and metabolite levels were generally dose related.

In vivo carcinogenesis assay of DL-methadone.HCl in rodents.

The extensive clinical use of methadone encouraged the performance of a carcinogenesis bioassay to support risk assessment in man. An oral LD50 of 178 mg/kg was obtained in B6C3F1 mice. Physiologic changes induced by mean oral doses of 15, 30, and 60 mg/kg for 90 days included dose-related central nervous system (CNS) stimulation, fighting, tolerance development, sex-related alteration of food consumption, and no drug-related pathology. In the chronic study dosages were 15 and 60 mg/kg for mice, 16 and 28 mg/kg for male rats, and 46 and 88 mg/kg for female rats. Survival incidences for treated and control rodents were 72-86% for mice and 80-90% for rats. Deaths related to morphologic changes of aging occurred in all groups. CNS stimulation and fighting were more common to male rodents. Growth rates were unchanged for mice but a dose-related inhibition occurred for rats. Higher doses stimulated food intake in both species. Neither the type nor incidence of neoplasia was drug related but a few nonneoplastic lesions may have been. Preliminary plasma methadone levels at necropsy were dose related in the rat.

Immune response of hospital workers to hepatitis B vaccine.

Hepatitis B vaccine (Heptavax-B vaccine, Merck Sharp and Dohme) was given by injection into the buttock of 109 healthy workers in a community hospital according to the schedule of the U.S.A. Centers for Disease Control. In only 26% of those between 41 and 65 years of age was antibody to hepatitis B surface antigen found after the full course of vaccination whereas 74% of those aged 18-40 years had detectable antibody. We did not find any significant difference between the responses of males and females in either age group. The unusually poor response may be related to injections being given into the buttock rather than the deltoid region of the arm. We, therefore, recommend that injections of hepatitis B vaccine should be given into the deltoid muscle and that vaccinees should be tested after vaccination for evidence of immunity.

Marihuana-induced embryotoxicity in the rabbit.

Few teratogenic studies in animals have been performed simulating marihuana smoking in man. An inhalation marihuana teratology study was conducted in albino rabbits utilizing a modified automatic smoking machine originally developed for rats and mice. Appropriate numbers of dams were exposed to 4 puffs (0.14 mg/kg), 8 puffs (0.72 mg/kg), or 16 puffs (1.44 mg/kg) once daily during gestation Days 6 to 18, and sacrificed on Day 28. Control dams were exposed to 12 puffs of placebo cigarettes or sham-treated for a similar duration in the absence of any smoke. Consistency of smoke was monitored by cigarette weights, total particulate matter, concentrations of carbon monoxide (CO), and tetrahydrocannibinol (THC) in smoke, carboxyhemoglobin levels, and plasma THC levels. Except for a transient decrease in dam respiration rates, other gross toxic signs were absent. Reproductive parameters of mothers were generally normal except for a dose-related embryotoxicity predominantly associated with early resorptions. Despite twice the number of embryo/fetal deaths, there were no marihuana soft tissue or skeletal defects. A correlation between dam demises and CO levels among placebo-exposed animals was related to greater quantities of CO being generated during placebo combustion. It has been shown in the rabbit that marihuana is embryotoxic and not a teratogen at plasma THC levels found in human females.

Esters and lactones of phenolic amino carboxylic acids: prodrugs for iron chelation.

The new iron chelator N,N'-bis(2-hydroxyphenyl)ethylenediamine-N,N'-diacetic acid (1), its dilactone 2, N,N'-bis(2-hydroxybenzyl)-2-hydroxypropylene-1,3-diamine-N,N'- diacetic acid (3), and its methyl ester lactone 4 and a series of esters of N,N'-bis(2-hydroxybenzyl)ethylenediamine-N,N'-diacetic acid (5) were prepared and their iron chelating efficacy and toxicity determined by using the hypertransfused mouse model of iron overload. The biological activities were compared with results obtained with use of the hypertransfused rat. Esterification enhanced the oral iron chelating activity but also increased toxicity. The diisopropyl ester of 5 exhibited the highest therapeutic index. In vitro measurements showed that the rate of ester hydrolysis at pH 7.5 increased by a factor of 10(4) in the presence of 5 X 10(-4) M ferric ion, which may account for the utility of esters and lactones as prodrugs. Seventeen other chelating agents were screened but showed no intraperitoneal or oral activity.

Preliminary toxicity findings in dogs and rodents given the iron chelator ethylenediamine-N,N'-bis(2-hydroxyphenylacetic acid) (EDHPA).

Because of a projected pilot study with EDHPA in Cooley's anemia patients, animal studies with emphasis on reversibility of potential toxic signs were performed. Young dogs were treated iv with 6-18 mg/kg or orally with 30-240 mg/kg for 14 days followed by a 16-day recovery period. Drug-induced emesis, elevated BUN changes in kidney, spleen, and thymus weights diminished during recovery. One deceased dog exhibited nephrotoxicity consisting of tubular necrosis and deposition of the iron-EDHPA complex. The latter was observed in the excreta of survivors but kidney damage was not evident. Atrophy of the spleen and thymus in the deceased dog was consistent with less intense organ weight changes in recovered survivors. In the absence of morphologic changes after recovery, the precise effect on the immune system is unknown. The iv LD50 was 53 mg/kg for rats and mice. No rodent deaths occurred at an oral dose of 6000 mg/kg. An elevated BUN and changes in kidney, spleen, and thymus weights were confirmed in rodents given iv doses of 5-20 mg/kg or oral doses of 150-600 mg/kg for 5 days. It is cautioned that during the use of EDHPA derivatives that the functions of the renal and immune systems be monitored.

Staphage lysate: an immunomodulator of the primary immune response in mice.

The immunological enhancing activity of staphage lysate on the primary immune response of mice as reflected by specific heteroantibody production to a single antigenic stimulus and on immunoglobulin synthesis was determined. Staphage lysate was administered at different periods in relation to time of sheep erythrocyte injection so that both the inductive and the productive phase of the immune response could be evaluated. Treatment with staphage lysate induced pronounced enhancement of the hemagglutinin response by day 14 regardless of the dose or the time of its administration. Significantly higher antibody levels in the test groups were observed when compared with the control animals, peak antibody titers being 21 days following antigenic challenge. Furthermore, staphage lysate administered without an accompanying antigen evoked a heightened serum immunoglobulin level in mice for a period of more than 14 days after injection. IgG1, IgG2a and IgG2b were significantly elevated as a direct result of this treatment. This increased output of immunoglobulin synthesis and heightened hemagglutinin titers demonstrate that staphage lysate is not only an immunomodulator of cell-mediated immunity, as previously reported, but also an effective immunoadjuvant of the humoral antibody response capability in the host.

Comparative usefulness of cytology and peroxidase activity in conjunction with carcinoembryonic antigen levels for the diagnosis of mammary cancer.

Diagnosis of cancer via measurement of carcinoembryonic antigen (CEA) levels has been unreliable in early neoplastic stages. In order to improve diagnostic reliability, other cytological parameters were examined with CEA. Fifty specimens of effusion fluid were obtained from 40 hospitalized patients and the levels of CEA determined by radioimmunoassay in conjunction with application of an immunoperoxidase procedure. Simultaneous morphologic assessment was performed without knowledge of the immunoassay findings. In 8 documented cases of mammary cancer, all effusion fluid specimens had CEA levels of 16-1074 ng/ml, 7 cases had morphologically positive cells, but only 3 had a peroxidase positive reaction. Except for one case of ovarian papillary adenocarcinoma, the remaining patients were cancer free, had CEA levels of less than 15 ng/ml and only 2 cases (including the ovarian tumor patient) gave positive peroxidase responses. The presence of mammary metastatic duct carcinoma correlated 88% with CEA measurements but peroxidase response was not diagnostically helpful.

Evaluation of polymeric hydroxamic acid iron chelators for treatment of iron overload.

A series of polymers bearing hydroxamic acid-terminated side chains were prepared for the purpose of developing new iron chelators for treating iron overload in beta-thalassemia (Cooley's anemia) and other iron diseases. The polymers are for the most part amino acid amide derivatives of acrylic and methacrylic acid with the terminal carboxyl group converted to the hydroxamic acid. The polymers are generally water soluble and sequester iron(III) avidly. The polymeric iron chelators were assayed via a mouse screen for activity in removing iron. Iron overloaded mice were administered i.p. the iron chelator over a 7-day period. Urine and feces were collected and the iron content measured by atomic absorption. At the end of the treatment period the mice were sacrificed and the livers and spleens were homogenized and examined for iron content. The results were compared with similar data obtained for the iron chelator drug desferrioxamine as a standard. Four of the polymers prepared exhibited strong activity, as good or better than desferrioxamine in iron removal capability. The four polymers are the polyacroloyl and polymethacryloyl derivatives of beta-alanine with the side chain carboxyls converted to the N'--H or N'--CH3 hydroxamic acids. Of these four the polyacryloyl N'--CH3 derivative exhibited superior behavior, being 3 to 5 times as effective as desferrioxamine at the lower dose level. None of the four polymers produced toxic signs and the administration was accompanied by little or no pain response.

Physiologic and morphologic changes and incidence of neoplasms in mice and rats fed naltrexone HCl for 24 months.

Short-term (acute oral LD50 and 90-day oral subchronic) studies in mice and long-term (24 months) carcinogenesis bioassays were performed in B6C3F1 mice and Fischer 344 rats given naltrexone. The oral LD50 was approximately 1500 mg/kg; convulsions, hypopnea, and cardiac failure were dose-related. Naltrexone mixed with feed over 90 days did not evoke definitive signs of gross toxicity, and histopathology was unrelated to drug treatment. Similar drug/feed admixtures given for 24 months to mice or rats did not disturb behavior. In mice, naltrexone reduced growth rates 5-10% and food intake 9-19%, but survival rates were 70-82% for treated mice and controls. The frequency and location of predominant tumors were similar in treated and untreated mice. In the rat, the same dosages had little effect on growth or food intake. The majority of all sacrificed rats had neoplasms. Neither neoplasms nor nonneoplastic lesions in mice or rats were associated with drug treatment. It is concluded that naltrexone is not a carcinogen.

Renal devitalization using 95 per cent ethyl alcohol.

Preoperative embolization of renal arteries with solid material before nephrectomy is a standard procedure for the treatment of renal cell carcinoma. However, it often is difficult to use these materials and sometimes special equipment is required. We have used 95 per cent ethyl alcohol in 3 patients to devitalize kidneys with tumors. Our results show 95 per cent ethyl alcohol to be safe, effective and easy to use. When combined with epidural anesthesia alcohol embolization is well tolerated by the patient, and its destructive effect is complete and limited to the selected organ.

Computed tomography in congenital hip dislocation. The role of acetabular anteversion.

Computed tomography usually can provide accurate documentation of the adequacy of a reduction in congenital dislocation of the hip. It should supplement other radiographic examinations when the status of a reduction is in question because the patient is wearing a plaster cast. The computed tomography scan provides a clear image of the reduction in the transverse plane, so that anterior or posterior subluxation of the femoral head can be easily detected. In addition it allows direct measurement of acetabular anteversion which previously had not been possible with non-invasive studies in the living patient. Radiation exposure is less than that for conventional tomography. We used computed tomography in five patients with congenital dislocation of the hip and our study provided new evidence concerning the role of acetabular anteversion in this condition. Acetabular anteversion was increased on the dislocated side in each patient, and returned to normal as treatment progressed.

Postembolic colonic infarction.

From a total of 23 cases from five hospitals, acute colonic mucosal necrosis developed in three patients following transcatheter embolotherapy for colonic hemorrhage. Although embolic therapy for lower gastrointestinal bleeding is associated with appreciable risk, these risks are less than those of emergency operation for hemorrhage. The alternative transcatheter therapeutic modality, vasopressin infusion, is often associated with continued or recurrent hemorrhage, is relatively contraindicated in patients with coronary disease, and produces numerous complications. Transcatheter embolotherapy is recommended for patients with colonic bleeding who have a contraindication to vasopressin administration, who are refractory to vasopressin, or who rebleed following treatment with vasopressin.