Plasma progestins, estradiol, and luteinizing hormone following prostaglandin F2 alpha injection

Dairy animals, ranging from days 8 to 13 of the estrous cycle, were fitted with indwelling jugular catheters 1 day prior to either intramuscular injection of prostaglandin F2alpha free acid (30 mg, n=4) or intrauterine deposition of prostaglandin F2alpha free acid (10 mg, n = 3). Blood samples were collected at 6, 4, 2, and 0 h prior to administration of prostaglandin F2alpha and at 1, 3, and every 2 h thereafter until ovulation. Progestins, estradiol, and luteinizing hormone in plasma were measured by radioimmunoassay. Hormonal changes and interrelationships within animals were evaluated by least squares analyses. Decreases in progestins of plasma within 24 h indicated prostaglandin F2alpha induced luteolysis in six of the seven animals. Estradiol increased linearly from time of injection to 52 h postinjection. Intervals from administration of prostaglandin to onset of estrus, peak of luteinizing hormone, and ovulation were 74.9 +/- 21, 78.8 +/- 21, and 99.5 +/- 19 h.     

Plasma levels of clonidine following epidural bolus injection in children

PURPOSE: To describe dense vitritis as the primary manifestation of ocular syphilis in three human immunodeficiency virus (HIV)-positive patients and to determine the response of these patients to the established regimen for neurosyphilis. METHODS: Anti-Toxoplasma gondii IgM and IgG antibody titers, tuberculin skin test, chest radiograph, and serum angiotensin-converting enzyme level were obtained because tuberculosis, sarcoidosis, and toxoplasmosis were in the differential diagnosis. Two of the three patients were not known to have HIV infection at the time of initial examination and consented to HIV testing. Treponemal and nontreponemal tests were performed on serum and cerebrospinal fluid to establish a definitive diagnosis. Treatment for neurosyphilis was initiated, and daily ophthalmic examinations were performed, with careful attention to signs commonly associated with syphilitic eye disease. RESULTS: All three patients exhibited improvement in visual acuity and resolution of vitreous haze. There was no evidence of other signs of posterior uveitis. The one patient for whom there has been a 6-month follow-up showed no sequelae of his eye disease. CONCLUSIONS: Human immunodeficiency virus-positive patients with syphilis may present atypically dense vitritis. In these patients, vitritis may be the first manifestation of syphilis. The regimen for neurosyphilis provides effective therapy. Moreover, in some patients, syphilitic vitritis may be the initial manifestation of HIV disease.     

Long-term erythropoietin expression in rodents and non-human primates following intramuscular injection of a replication-defective adenoviral vector

Erythropoietin (Epo)-responsive anemia is a debilitating complication of chronic renal failure and human immunodeficiency virus (HIV) infection that effects more than 150,000 Americans. Patients with Epo-responsive anemias are currently treated with repeated injections of recombinant human Epo. In the studies described in this report, we have examined the safety and efficacy of using a single intramuscular (i.m.) injection of replication-defective adenoviral vectors (RDAd) encoding Epo for the treatment of Epo-responsive anemias in both mice and non-human primates. Our results demonstrate that there is a threshold dose of virus (2.5-8 x 10(7) pfu/gram of body weight) which is required to obtain long-term Epo expression and polycythemia in both species. A single i.m. injection of mice with 10(9) pfu of an RDAd encoding murine Epo (AdmEpo) resulted in elevations in hematocrits from control values of 49 +/- 0.9% to treated values of 81 +/- 3%, which were stable for more than 1 year. Similarly, a single i.m. injection of a monkey with 4 x 10(11) pfu of an RDAd-encoding simian Epo (AdsEpo) resulted in elevations of hematocrits from control levels of 40% to treated levels of > or =70%, which were stable for 84 days. Intramuscular injection of monkeys with AdsEpo appeared to be safe in that we did not detect abnormalities in chest X-rays, serum chemistries, hematologic, or clotting profiles (apart from elevated hematocrits) or organ histologies during the 84-day time course of the experiment. Taken together, these results suggest the feasibility of using i.m. injection of RDAd for the treatment of Epo-responsive anemias in humans.     

Delayed hypersensitivity and systemic arthralgia following transurethral collagen injection for stress urinary incontinence

PURPOSE: During a prospective cohort study to determine the effectiveness of and adverse effects associated with transurethral collagen injection for treatment of stress urinary incontinence in women, we observed 3 cases of delayed allergic reaction at the skin test site associated with arthralgia. MATERIALS AND METHODS: A total of 337 women with at least a 1-year history, physical findings and urodynamic abnormalities consistent with stress urinary incontinence, who required pads or protective clothing and who had no or only grade 1 cystocele were enrolled in this prospective cohort study. Adverse effects were documented by a third party at each followup. RESULTS: Delayed reaction at the skin test site occurred in 3 patients (0.9%), and was associated with arthralgias in 2. CONCLUSIONS: The incidence and systemic nature of this type of reaction suggest that gluteraldehyde cross-linked collagen injection is not as innocuous as previously believed. Patients should be counseled regarding the unknown long-term outcome of this complication. Before treatment clinicians should consider double skin testing.     

Serum and plasma concentrations of clindamycin following a single intramuscular injection of clindamycin phosphate in maintenance haemodialysis patients and normal subjects

Serum levels of clindamycin bioactivity and total clindamycin were studied after single intramuscular injections of 300 mg of clindamycin phosphate in a group of 6 normal subjects and a group of 6 maintenance haemodialysis patients. The patients were studied during a non-dialysis period and then again during haemodialysis. Peak levels tended to be higher and elimination half-lives shorter in the patients than in the normal subjects. Possible reasons for these differences are discussed. There was no evidence that haemodialysis per se influenced the pharmacokinetics of clindamycin phosphate. The proportion of unhydrolysed clindamycin phosphate tended to be higher in the renal failure patients and the reason for this is not apparent. Little, if any, dosage modification is necessary in severe renal fialure although there is probably little point in exceeding a dose of 300 mg intramuscularly every 5 h even in severe infections in patients with severe renal failure. The higher peak levels in patients with advanced renal failure indicate the need for further studies with repeated doses.     

Fibrous contracture of muscles following intramuscular injections in adults

Periarticular fibrous muscle contractures in adults from repeated injections in the same site is predictable. The causes of joint contracture in children are many and complex, but in adults it seems certain that this phenomenon is the result of repeated injections of analgesics or other agents into 1 muscle area. Any drug if repeatedly injected locally may cause fibrosis of the muscle and subsequent joint contracture. Five cases of bilateral abduction contracture of the shoulder in adults including the first case of bilateral abduction contractures of shoulder and hip plus bilateral flexion contracture of elbow and extension contracture of a knee are reported. No underlying disease which might predispose to this fibrosis of muscles was noted. The frequency and period of injections were variable over several years. In all patients the interference in activtities of daily living were serious, but the deformities were corrected by release of the fibrous band with relief of discomfort and restoration of joint motion without recurrence. Noting the potential complication of repeated intramuscular injections in one area, this practice should be avoided whenever possible in adults, as well as in children.     

Plasma levels and urinary elimination of aminosidine in infants]

The course of treatment with polychemotherapy for the progressed and metastasized breast-carcinoma is discussed. The therapy with cytostatics must be continued for the patients entire life. A sample of 27 patients from the Chir; Univ.-Klinik Innsbruck with a course of treatment lasting from 15 to 29 months (October 1973 resp; December 1974 to February 1976) showed a success rate of 81%.     

Iatrogenic compressive lumbar myelopathy and radiculopathy in adult cattle following injection of an adjuvanted bacterin into loin muscle: histopathology and ultrastructure

Compressive lumbar myelopathy is a recognized iatrogenic complication of injecting water-in-oil vaccines into paravertebral sites of laboratory animals and chickens. Herein, we report the histologic and ultrastructural features of a similar complication in a herd of cattle. Iatrogenic posterior paresis developed over 34 days in 56 of 610 cows (9.2%) following injection of a commercial bacterin 11-34 days earlier into M. longissimus lumborum. The bacterin was composed of inactivated Escherichia coli and Campylobacter fetus ssp. venerealis in a proprietary adjuvant. Tissues were collected for histopathology from 9 affected cattle that died or were euthanized after clinical signs lasting 6-38 days. A range of tissues, including the injection site lesion and lumbar spinal nerve roots, was obtained for ultrastructural examination from a cow with paresis of 31 days duration. There was locally extensive pyogranulomatous myositis with fibrosis and necrosis in right M. longissimus lumborum. Extension of the lesion into the vertebral canal via spinal nerve foramina resulted in focal pyogranulomatous inflammation in epidural fat and in adjacent dura mater. There was axonal degeneration in dorsal, lateral, and ventral columns and chromatolysis of spinal motor neurons in lumbar spinal cord, secondary to compression. A distinctive histologic and ultrastructural feature of pyogranulomata was the presence of osmiophilic material at the center of inflammatory foci, surrounded by macrophages and giant cells that contained intracytoplasmic lipid droplets. Ultrastructural examination of entrapped spinal nerves revealed axonal degeneration and loss of myelinated and unmyelinated fibers, segmental demyelination with remyelination, axonal spheroid formation, and early axonal regeneration.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetics, bioavailability and tissue residues of [14C]isometamidium in non-infected and Trypanosoma congolense-infected Boran cattle

In this paper, pharmacokinetics, bioavailability and tissue residues are reported in non-infected and Trypanosoma congolense-infected Boran steers following either intravenous or intramuscular injection of [14C]isometamidium at a dose rate of 1 mg kg-1 body weight. Two differently labelled compounds of isometamidium were used; 6-14C (ISMM-1) and ring-U-14C (ISMM-2). The cattle were divided into 5 groups: group 1 consisted of 3 non-infected cattle treated with ISMM-1 by intravenous injection; group 2 consisted of 2 non-infected cattle treated with ISMM-1 by intramuscular injection; group 3 consisted of 2 Trypanosoma congolense-infected cattle given similar treatment as group 2 cattle; group 4 consisted of 3 non-infected and group 5 of 2 infected cattle treated with ISMM-2 by intramuscular injection. Radioactivity was measured in plasma, urine, faeces and tissues, and drug concentrations were calculated. Data obtained following i.v. treatment were best described by tri-exponential equations with half-lives of 0.13, 1.22 and 120.7 h. Bioavailability of the intramuscular dose was 58% in group 2 cattle. The major route of excretion was in faeces. Approximately 80% of the intravenous dose given was excreted within 21 days out of which only 18% was through urine. Total residues accounted for approximately 15% the total dose given. Drug residues remained high in organs with excretory functions including the liver and kidneys.     

Local anesthetic effect of tramadol, metoclopramide, and lidocaine following intradermal injection

A 30-year-old black man came to the emergency department with gross hematuria, prostatitis, and urethritis 4 months after immigrating to this country from the Sudan in Africa. Urinalysis revealed hematuria and no ova or parasites. An intravenous urogram showed normal kidneys and ureters. The patient had cystoscopy with biopsies of an inflamed and ulcerated bladder mucosa. The nematode Schistosoma haematobium and schistosome eggs were identified without evidence of urothelial malignancy. The patient was treated with praziquantel and is currently asymptomatic. Over 200 million people are infected with schistosomiasis worldwide, yet this disease is rarely encountered in this country. The differential diagnosis and assessment of patients must include exposure to uncommon diseases that are endemic to other geographic regions.     

Collagen injection therapy in the treatment of urinary incontinence

Impairment from depression and its impact on productivity are of profound societal importance. We report the results of an evaluation of depression and academic impairment in university students, using standardized measures. Sixty-three students completed the Beck Depression Inventory and the work role section from the Social Adjustment Scale-Self Report. Academic impairment, manifested as missed time from class, decreased academic productivity, and significant interpersonal problems at school, was seen in 92% of the students. More severe depression was related to a higher level of impairment. At all levels of depression, affective impairment-inadequacy, distress, and disinterest in school-was more prevalent than was academic impairment. The risk of academic impairment became likely at only moderate-to-severe levels of depression. Discussing the implications of depression with students and aggressively pursuing both medication and nonmedication therapies are essential in preventing the high morbidity associated with untreated depression.     

Plasma levels and urinary elimination of diftalone, paracetamol, and their metabolites after single oral administration in man

The plasma levels of diftalone, its metabolite 7-hydroxydiftalone, unconjugated and total paracetamol have been assessed in 6 healthy volunteers after oral administration of diftalone 0.75 g and of paracetamol 1.0 g, given alone and in combination in a cross-over fashion. In the same subject the urinary elimination of 7-hydroxydiftalone, and of unconjugated and total paracetamol has also been estimated. The results provide some indication of a slight increase in the plasma levels of unconjugated and total paracetamol, when the drug is administered in combination with diftalone. The increase, however, does not reach the significance level. As to diftalone and its metabolite, the differences between the plasma levels obtained after administration of the compound alone and those obtained when it was given in combination were negligible. Furthermore, the urinary recoveries of 7-hydroxydiftalone and of unconjugated and total paracetamol were very similar after administration of each compound alone and of their combination. It is concluded that the administration of single doses of diftalone and paracetamol in combination does not produce any pharmacokinetic interaction likely to be of clinical relevance.     

Control of erythropoietin delivery by doxycycline in mice after intramuscular injection of adeno-associated vector

We reported previously that controlled expression of a foreign gene in response to tetracycline derivative can be accomplished in mice by the autologous transplantation of retrovirus-modified muscle cells. Although regulated systemic delivery of therapeutic proteins from engineered tissues has potential clinical application, the transplantation of muscle cells is not currently feasible in humans. Several studies have shown that a single injection of adeno-associated virus (AAV) vectors into mouse muscle results in long-term expression of reporter genes as well as sustained delivery of proteins into the serum. Because this method is potentially applicable clinically, we constructed an AAV vector in which the expression of the mouse erythropoietin (Epo) cDNA is modulated in response to doxycycline. The vector was injected intramuscularly in normal mice. We observed that hematocrit and serum Epo concentrations could be modulated over a 29-week period in response to the presence or absence of doxycycline in the drinking water of these animals. Thus, a regulated gene expression cassette can be incorporated into a single AAV vector, such that intramuscular injection of the vector allows sustained and regulated expression of a desired gene.     

Demonstration of tissue lesions after intramuscular injection by determination of creatine kinase in blood

Local muscle tissue damage by Terramycin-LA (20 mg/kg BM) injected at the neckmuscle was tested with seven pigs prepared with veneous catheters. Four of the pigs were used as the control group and were treated with an intramuscular injection of 0.9% NaCl-solution into the opposite neckmuscle later on. The tissue damage was clinically, pathologically and enzymatically examined. A significant rise of creatinkinase (CK) in bloodplasma up to 48 hours after intramuscular injection of Terramycin-LA proves to be a good indicator of local muscle damage. Based on enzymekinetic calculations it was possible to estimate the amount of muscle laesions after intramuscular injection of Terramycin-LA up to 13 g/100 kg BM and of NaCl-solution up to 0.5 g/100 kg BM respectively. The difference is significant.     

Molt induction in lobsters (Homarus americanus) by intramuscular injection of ecdysterone triacetate

The principal component of the successful, molt-inducing ecdysterone acetate mixture was established as ecdysterone triacetate and shown to have the same activity as the acetate mixture. The triacetate induced ecdysis in male lobsters collected in winter and summer and in female lobsters collected in winter. Intramuscular injections of triacetate in ethanol were as effective as those with oil emulsions.     

The behaviour of healthy awake cats following intravenous and intramuscular administration of midazolam

The onset of action and behavioural effects following intravenous (i.v.) and intramuscular (i.m.) administration of 0.05, 0.5, 1.0, 2.0 and 5.0 mg/kg of midazolam were studied for 2 h in 20 awake, healthy cats. All cats, except one that received 0.05 mg/kg i.m., showed effects of the drug, whereas no effects were observed in cats administered only the vehicle in which midazolam was dissolved. The onset of action was rapid following both i.v. and i.m. administration, some cats became ataxic, while others assumed positions of sternal or lateral recumbency. Even after administration of the highest dose (5.0 mg/kg), anaesthesia was not induced, with swallowing reflexes and conscious perception of a clamp placed on the tail still present in all cats. An abnormal arousal state was observed in many cats after administration of midazolam. During the first hour, restlessness was more commonly observed, while from 1 to 2 h, sedation was more prominent in cats that received the highest dose. Ataxia occurred in all but one cat, was short-lived in cats that received the lower doses, but still present at 2 h in all cats that received 2.0 and 5.0 mg/kg. Midazolam caused some of the cats to behave differently when approached and restrained compared with behavioural patterns identified prior to administration of the drug. The cats were more likely to behave abnormally following i.v. administration rather than i.m. administration and, for the most part, abnormal behaviour was equally distributed between the two extremes; cats being easier to approach and restrain and cats being more difficult to approach and restrain. Food consumption increased significantly, during the 2 h period, following all i.m. doses and all but the highest (5.0 mg/kg) i.v. dose, with most of the food being consumed in the first hour after administration.