[Carminomycin induction of single-stranded DNA breaks in Micrococcus luteus cells].

The effect of carminomycin, an amtitumor antibiotic from the anthracycline group on DNA of M. luteus cells was studied. It was shown that carminomycin induced one-thread breaks in DNA. The antibiotic effect was proportional to its concentration and depended on the time of the cell exposure. When the incubation time with carminomycin was longer, there was observed disappearance of a significant part of the breaks. The lower was the antibiotic concentration, the rapider was the process, especially after removal of the antibiotic from the medium. Induction of the one-thread breaks by carminomycin in DNA of the cells of the mutant strain DB-7 of M. luteus was more difficult than in that of the cells of the wild type strain which was indicative of the enzymatic character of most of the breaks and of a special role of UV-endonuclease of M. luteus in this process. On the basis of carminomycin hypersensitivity of the mutant it was concluded that the above enzyme was probably involved in reparation of the DNA damages induced by carminomycin. No two-thread breaks induced by the antibiotic were detected.


[Pharmacokinetic indices of penicillin and semicillin (ampicillin) in kidney diseases in children].

The kinetics of penicillin and semicillin was studied in 80 children at the age of 5 to 14 suffering from glomerulonephritis and pyelonephrities. The Bertolotti penicillin test revealed an isolated or associated (with lowered glomerular filtration and function of the osmotic concentration) decrease in the secretory function of the proxymal nephron in the patients without the signs of chronic renal insufficiency. The results of the study on the pharmacokinetics of simicillin indicated definite regularities in its excretion with urine as dependent on the period of its use and the state of the renal function. When semicillin was used in therapeutic doses, its concentration in urine exceeded the MIC with respect to all bacteria isolated from the urine specimens of the patients with pyelonephritis. Control of the antibiotic blood levels in children with kidney diseases at the stage of chronic renal insufficiency is necessary for choosing the optimal dose and intervals between the drug injections.


Sanguicin, a bacteriocin of oral Streptococcus sanguis.

Streptococcus sanguis strain N-2 was found to produce a bacteriocin (sanguicin) which accumulates intracellularly. It was purified by sequential procedures about 98-fold with a recovery of 37% and appeared to be homogeneous on gel electrophoresis. Sanguicin was heat labile and was destroyed by digestion with pronase. The growth of several species of oral indigenous microorganisms was inhibited by sanguicin, of which Bacteriodes melaninogenicus was most susceptible. Sanguicin acted on susceptible cells as a bacteriostatic agent.


Latent infections of sensory ganglia as influenced by phosphonoformate treatment of herpes simplex virus-induced skin infections in hairless mice.

Topical treatment with 3% phosphonoformate of herpes simplex virus type 1 (HSV)-induced skin infections of hairless mice reduced the severity of skin lesions when the treatment was initiated 3 h after virus inoculation in the lumbosacral area or 3 and 24 h after inoculation in the orofacial area. The mortality was significantly reduced in lumbosacral-infected mice and was completely prevented in orofacial-infected mice when the treatment was initiated with a delay of 24 h after virus inoculation. However, phosphonoformate did not prevent the establishment of latent herpes simplex virus type 1 infections in the spinal and trigeminal ganglia, even when treatment was initiated as early as 3 h after infection.


In vitro activity of LY127935.

The activity of LY127935, a beta-lactam antibiotic of novel structure, was studied in vitro against facultative gram-negative bacilli, Staphylococcus aureus, and Bacteroides fragilis. The strains were recent clinical isolates, many of which were relatively resistant to other antibiotics. LY127935 exhibited striking activity against Escherichia coli, Klebsiella pneumoniae, Enterobacter sp., Proteus sp., Serratia marcescens, and B. fragilis with median minimum inhibitory concentrations of less than or equal to 1.0 micrograms/ml. It was somewhat less active against Pseudomonas aeruginosa and S. aureus. Cefotaxime (HR 756) showed very similar activity except that it was substantially weaker against B. fragilis. LY127935 was more active than cefamandole, cefoxitin, or piperacillin; it was also as potent as tobramycin or amikacin against all species except for P. aeruginosa.


Purification and characterization of agrocin 84.

A procedure for the rapid purification of milligram quantities of agrocin 84, a bacteriocin-like compound produced by Agrobacterium radiobacter strain K-84, has been developed. This procedure, which employs charcoal adsorption, ion-exchange, sieving chromatography, and continuous-flow electrophoresis, can yield agrocin 84 which is 65% pure on a dry weight basis. The purest preparations were strongly ultraviolet absorbing, with a maximum at 264 nm (epsilon 7.0/264 = 22,675 cm2 - M-1) and a minimum at 227 nm (ratio of 264 to 227 nm, 6.00). As has been reported, agrocin 84 contains an unusual phosphoramidate or 6-N-acyl linkage to adenine. Adenine, glucose, and phosphate are present in a 1:1:2 molar ratio. The molecular weight was estimated to be 1,350.


Antibiotic susceptibilities of human isolates of Pasteurella multocida.

Seventeen human strains of Pasteurella multocida, biochemically similar to, if not identical with, isolates of animal origins, were tested for susceptibility to 16 antimicrobial agents utilizing a microtiter broth dilution technique. Ten of these isolates were also tested against 11 antibiotics by disk diffusion. The most active drugs with respect to the median minimal inhibitory concentration (micrograms per milliliter) were tetracycline (0.09), penicillin G (0.78), ampicillin (0.78), carbenicillin (1.56), cephalothin (1.56), and chloramphenicol (1.56). With the exception of tetracycline, the median minimal inhibitory concentration and minimal bactericidal concentration values were equal or differed by no more than a factor of two. The semisynthetic penicillins clindamycin, erythromycin, and aminoglycosides had relatively low activities, suggesting that these agents would be poor choices for the treatment of P. multocida infections.


LY127935, a novel oxa-beta-lactam: an in vitro comparison with other beta-lactam antibiotics.

The in vitro activities of LY127935 (LY) were compared with those of other beta-lactam antibiotics. LY was highly active (minimal inhibitory concentration [MIC] range 0.06 to 0.25 micrograms/ml) against the common Enterobacteriaceae (including Providencia stuartiia, Enterobacter, and Serrati marcescens), 8 to 16 times more active than cefoxitin, cefuroxime, or cefazolin, and from one-half to one-eighth as active as cefotaxime (HR756). The activity of LY against Pseudomonas aeruginosa (with MICs of 4 and 64 micrograms/ml for 50 and 90% of test strains, respectively) was essentially similar to that of cefotaxime, but was only one-half as active as CGP 7174/E. LY, cefoxitin, and cefotaxime were essentially equally active against Bacteroides fragilis--each was more active than cefuroxime and cefazolin. Against Staphylococcus aureus, LY (50% MIC and 90% MIC of 4 and 16 micrograms/ml, respectively) was less active than cefotaxime, cefoxitin, or cefuroxime and one-eighth as active as cefazolin. The composition and pH of the culture medium had little effect on the activity of LY, although 7.2 appeared to be the optimum pH.


Clinicopharmacological evaluation of amoxicillin and probenecid against bacterial meningitis.

Forty-three infants and children with bacterial meningitis were treated intravenously with 200 mg of amoxicillin sodium per kg per day for 10 days. (Patients were initially treated with ampicillin and chloramphenicol until the bacterial etiology was defined.) Patients were randomly treated with amoxicillin only or with amoxicillin and four doses of probenecid (10 mg/kg per dose) orally every 6 h for 24 h before the lumbar puncture at day 10. Serum and cerebrospinal fluid (CSF) were obtained on days 1, 5, and 10 of therapy for antibiotic assay. The mean peak serum concentration of amoxicillin of 49.2 micrograms/ml was increased to 61.4 micrograms/ml in patients who received probenecid. The half-life in serum (1.5 h) and area under the curve with probenecid (112.5 micrograms/ml-h) were increased compared with those of amoxicillin alone (1.3 h and 82.2 micrograms/ml-h). The mean peak CSF concentrations on days 1 and 5 were similar, but day 1 concentrations remained between 2.0 micrograms/ml and 5.0 micrograms/ml throughout the 4 h after a dose, whereas the day 5 values decreased at the same decay rate as that in serum. All CSF concentrations were lower on day 10, but patients receiving probenecid had peak values occurring at 1 hr rather than at 0.5 h, and levels were significantly greater at 1 and 2 h after a dose. There were no deaths and patients responded well to treatment.


Correlation of aminoglycoside dosages with serum concentrations during therapy of serious gram-negative bacillary disease.

We prospectively evaluated serum aminoglycoside (AMG) concentrations in 120 patients who received gentamicin or tobramycin for serious gram-negative bacillary disease. AMG serum concentrations were assayed by microbiological and radioimmunoassay techniques. Correlation between the two assay methods was good. When AMG doses were based on total body weight, there was no significant correlation between AMG dosage administered and serum concentrations in patients with either normal or abnormal renal function. The use of ideal body weight for calculation of AMG dosage improved this correlation significantly except in hemodialysis patients. AMG-induced nephrotoxicity occurred in 13 patients. No significant association was noted between the occurrence of toxicity and the specific AMG given or with other commonly recognized risk factors. Among study groups, peak AMG serum concentrations failed to exceed the minimal inhibitory concentration of the infecting organism in 17 to 33% of the cases. Serum inhibitory levels of greater than or equal to 1:8 were not associated with improved survival. There was no significant difference in mortality between the gentamicin- and tobramycin-treated groups. We advise base-line serum AMG levels in seriously ill patients with gram-negative bacillary disease and additional bacteriological studies in selected situations.


Cochlear toxicity of butikacin (UK-18,892), a new semisynthetic aminoglycoside antibiotic, in guinea pigs.

The cochleotoxic potential of butikacin (UK-18,892), a new semisynthetic aminoglycoside, has been evaluated in neonatal guinea pigs in comparison with amikacin, gentamicin, and kanamycin A. All compounds produced a dose-related increase of the mean threshold sound intensity required to elicit Preyer's reflex. Butikacin produced a similar level of cochlear toxicity to that of kanamycin A, but tended to be less cochleotoxic than amikacin. Gentamicin was the least cochleotoxic.


Anaerobic infection in cancer patients: comparative evaluation of clindamycin and cefoxitin.

Clindamycin and cefoxitin with or without gentamicin were administered to cancer patients having localized infections presumably caused by anaerobic pathogens. The rates of favorable response were 89% in patients receiving clindamycine alone and 78% in patients receiving cefoxitin alone. When the total experience is considered (clindamycin or cefoxitin with and without gentamicin), 20 of 24 patients (83%) responded to clindamycin and 18 of 22 (82%) responded to cefoxitin. Both therapies were well tolerated. Clindamycin was found to be more effective than cefoxitin in eradicating the offending anaerobic pathogens from the site of infection. Aerobic pathogens were frequently isolated along with anaerobes from the infectious sites in this series; their susceptibility or resistance to clindamycin or cefoxitin did not influence the therapeutic response.


High-pressure liquid chromatography analysis of antibiotic susceptibility disks.

The analysis of antibiotic susceptibility disks by high-pressure liquid chromatography (HPLC) was investigated. Methods are presented for the potency determination of mecillinam, ampicillin, carbenicillin, and cephalothin alone and in various combinations. Good agreement between HPLC and microbiological data is observed for potency determinations with recoveries of greater than 95%. Relative standard deviations of lower than 2% are recorded for each HPLC method. HPLC methods offer improved accuracy and greater precision when compared to the standard microbiological methods of analysis for susceptibility disks.


Piperacillin susceptibility tests by the single-disk agar diffusion technique.

Piperacillin is a new semisynthetic penicillin with a spectrum of activity broader than that of carbenicillin or ticarcillin. Studies were performed to establish standards for agar diffusion susceptibility tests with piperacillin disks. Tests with 100-, 150-, and 200-micrograms piperacillin disks and with 100-micrograms carbenicillin disks were evaluated. With both penicillins, 100-micrograms disks were satisfactory, in spite of the fact that piperacillin is a larger molecule and diffuses at a slower rate. With both carbenicillin and piperacillin disks, resistant strains of Staphylococcus aureus produced zones less than or equal to 28 mm and susceptible strains gave zones greater than or equal to 29 mm in diameter. When testing other microorganisms, zone standards of less than or equal to 13 mm for resistant (minimal inhibitory concentration, greater than or equal to 256 micrograms/ml) and greater than or equal to 17 mm for susceptible (minimal inhibitory concentration, less than or equal to 64 micrograms/ml) are recommended for tests with 100-micrograms piperacillin disks. Similar zone standards are currently recommended for carbenicillin and ticarcillin disk tests.


Ceforanide: in vitro and clinical evaluation.

Ceforanide, a new cephalosporin antibiotic with a long half-life (3 h), can be administered twice daily. We evaluated its antimicrobial activity, pharmacology, and clinical efficacy. Twenty-seven patients with infections due to susceptible organisms received ceforanide, 0.5, 1, or 2 g, intramuscularly or intravenously every 12 h for 6 to 28 days. In vitro studies with the clinical isolates from 27 patients treated plus 263 additional isolates showed that ceforanide was active against cephalothin-susceptible gram-positive and gram-negative microorganisms. In addition, ceforanide inhibited 65% of cephalothin-resistant Escherichia coli and 65% of Enterobacter spp. at </=12.5 mug/ml. After a single 1-g intramuscular dose, the mean peak plasma concentration at 1 h was 48.9 mug/ml and that at 12 h was 4.7 mug/ml. Plasma accumulation occurred in some patients. The infections included 10 pneumonias, 3 with bacteremia and 1 with empyema; 11 soft tissue infections, 4 with abscesses and 3 with sepsis; and 3 urinary tract infections. One case each of endocarditis, osteomyelitis, and septic thrombophlebitis, all due to Staphylococcus aureus, were treated. Clinical response was satisfactory in all patients; bacteriological response was satisfactory in 26 of 27 patients. Ceforanide was well tolerated. Three patients developed mild increases in liver enzymes, and one developed slight eosinophilia. In another case, the antibiotic was discontinued because of a fivefold rise in serum glutamic-oxalacetic transaminase (aspartate aminotransferase) and serum glutamic-pyruvic transaminase (alanine aminotransferase) and a twofold rise in lactic acid dehydrogenase and alkaline phosphatase.


Use of covalently closed circular deoxyribonucleic acid for prescreening for antitumor compounds.

The interactions of PM-2 deoxyribonucleic acid (DNA) with 20 known antineoplastic agents were studied using agarose gel electrophoresis and fluorescence assay systems. Actinomycin D and adriamycin (and all other anthracyclines studied) induced superhelical conformational changes in PM-2 DNA. Bleomycin A2, tallysomycin, neocarzinostatin, macromomycin, and hedamycin degraded PM-2 DNA under various conditions. The potential utility of PM-2 DNA as an antitumor antibiotic prescreening tool was further studied by examining the effects of 200 broths on PM-2 DNA employing both fluorescence and agarose gel electrophorectic assays. The assays were shown to be sensitive and rapid and to provide information not provided by other prescreens with which the PM-2 DNA assays were compared.


Cinoxacin: pharmacokinetics and tolerance in patients with normal and impaired renal function.

The pharmacokinetics of cinoxacin, a new antibacterial compound related to nalidixic acid and oxolinic acid, were investigated in 22 patients with varying degrees of renal impairment. After oral administration of cinoxacin at 500 mg every 12 h for 7 days to all patients, the drug was found to be well tolerated. The urine concentrations of cinoxacin in all patients far exceeded the minimal inhibitory concentrations for susceptible organisms commonly found in urinary tract infections. The serum half-life of cinoxacin in patients with normal renal function was approximately 2.7 h but increased to approximately 8.5 h in patients with creatinine clearance less than 30 ml/min. No undue drug accumulation was demonstrated in any patient group during the treatment. Highly significant correlations were found between the elimination rate constant and creatinine clearance and also between the elimination half-life and serum creatinine. The bioavailability of cinoxacin was independent of renal function.


Lithium compound treatment and psoriasis.

Observations were made of 12 cases of psoriasis that developed and three cases of psoriasis that became exacerbated during treatment with lithium compounds. Only two patients had a family history of psoriasis, and results of a search for increased frequencies of the histocompatibility antigens seen in psoriasis vulgaris were negative. The clinical features were identical to severe psoriasis vulgaris and the diagnosis was confirmed by histologic examination performed in six cases. However, the skin changes disappeared or returned to pretreatment level after withdrawal of lithium compounds. A positive provocation test result was obtained in two cases, the secondary latency time being shorter than the primary. We suggest that the psoriasis was induced or exacerbated by lithium compounds.


Effects of emollients on ultraviolet-radiation-induced erythema of the skin.

Several commonly used emollients were studied as to their effectiveness in absorbing and filtering erythema-causing ultraviolet radiation in the 280 to 315 nm range (UVB). Planter's Peanut Oil (Standard Brands) and Mazola Corn Oil (Best Foods Inc) had no effect; Alpha Keri Bath Oil (Westwood Pharmaceuticals), mineral oil, and Johnson's Baby Oil (Johnson & Johnson Co) had minimal effects. Vaseline Petroleum Jelly (Chesebrough-Ponds Inc), petrolatum, and hydrophilic ointment substantially reduced the erythema that was induced by exposure to low doses of UVB radiation. Therefore, these emollients may interfere with the therapeutic effects of the ultraviolet radiation component of the Goeckerman treatment when it is administered in low doses to patients with psoriasis.


Ungual lichen planus. Lichen planus of the nail.

Although reports in the literature are sparse, a definite relationship exists between nail anomalies and lichen planus. Ungual lichen planus may occur without any mucocutaneous signs, as has been documented by histologic studies. It may be the initial and most important clinical manifestation of the disease process, and permanent anonychia may result unless corticosteroid therapy is initiated promptly. Increased awareness of nail involvement will result in a more frequent diagnosis and better understanding of the disorder.


Amyloid deposition after psoriasis therapy with psoralen and long-wave ultraviolet light.

Histologic examination of skin from 52 patients under continued treatment with methoxsalen and long-wave ultraviolet irradiation (PUVA) disclosed small superficial dermal deposits in six subjects who had completed one year of therapy and in six subjects who had completed two years of therapy. These deposits, by light and electron microscopic criteria, are similar to those of lichen amyloidosus. Amyloid deposition should be regarded as a possible complication of PUVA therapy.


Skin cancer and arsenical intoxication from well water.

A case of acute arsenical intoxication arising from ingested well water containing only 1.2 ppm of arsenic is reported. After a latent period of 14 years, multiple cutaneous basal cell carcinomas developed. The water was analyzed for a variety of other trace elements and compounds and no evidence for the existence of other carcinogens was found. This study strengthens the concept that arsenic is a carcinogen. The role of a possible selenium deficiency is also discussed.


Inflammatory linear verrucous epidermal nevus. Association with epidermal nevus syndrome.

A female infant was noted at birth to have severe skeletal anomalies of the right upper and lowere extremities. These anomalies were associated with an inflammatory linear verrucous epidermal nevus (ILVEN). Like the noninflammatory type of epidermal nevus, ILVEN may be a component of the epidermal nevus syndrome.


Erythematous generalized granuloma annulare.

Two elderly patients had a distinctive generalized, erythematous form of granuloma annulare. The granulomatous changes were shown to be located superficially in the dermis. One patient had diabetes mellitus and carcinoma of the breast. Both patients had pulmonary emphysema.


Disseminated granuloma annulare treated with low-dose chlorambucil.

Disseminated granuloma annulare (DGA) is a frequently severe chronic and disfiguring disease that is resistant to conventional methods of therapy. In a patient with DGA, low-dose chlorambucil therapy (2 mg three times daily, orally administered) resulted in dramatic and rapid clearing of all lesions in a short period of time. To my knowledge, this is the fourth case reported in which this therapeutic modality was used.


Metastatic squamous cell carcinoma of the lip. Occurrence in blacks with discoid lupus erythematosus.

In two black patients, squamous cell carcinoma of the lip developed within lesions of discoid lupus erythematosus (DLE). The association of DLE and squamous cell carcinoma is unusual in blacks, as is the anatomical site involved in these cases. Enhanced metastatic potential may be present when squamous cell carcinoma arises in DLE of the lips.


Generalized pustular psoriasis.

In a patient with a long history of classical psoriasis, a widespread pustular eruption suddenly developed. The precipitating factor appeared to be a high-dose, progesterone-containing hormone preparation. The clinical appearance and manifestations in this patient were typical of pustular psoriasis.


Ultrastructure of eccrine cystadenoma. A case report.

A case of eccrine cystadenoma was studied by electron microscopy. The tumor showed two types of cells, luminal and basal cells. The cells lacked the characteristics of the secretory segment of the sweat glands. The features of the luminal cells are similar to those of the intradermal portion of the eccrine sweat duct. In some areas, the lesion showed features characteristic of apocrine gland structure. Nuclear bodies were very frequent. The ultrastructural findings of eccrine cystadenoma support an origin from the ductal portion of eccrine sweat glands.


Bilateral verrucous carcinoma of the feet.

A 51-year-old woman had had bilateral verrucous carcinoma of the feet for ten years. The tumors had been treated many times as extensive verruca vulgaris before a biopsy was performed and the true neoplastic nature of the lesion recognized. This case illustrates the necessity of performing biopsies on atypical or frequently unresponsive verrucous tumors.


Thermal keratoses and squamous cell carcinoma in situ associated with erythema ab igne.

A 60-year-old black woman had a large hyperkeratotic lesion and multiple smaller hyperkeratotic papules and plaques on the lower part of her legs in areas of erythema ab igne. Histologic examination of the largest lesion showed hyperplastic carcinoma in situ and the multiple smaller lesions showed varying degrees of squamous cell atypia and dermal elastosis. Histologically, these lesions were identical to solar-induced atypia, indicating that squamous cell carcinoma arising in erythema ab igne may be biologically similar to actinic carcinoma. Discussed here are clinical and histologic features of the thermal-induced lesions and other types of thermal-induced carcinomas.


Auricular sporotrichosis in a brick mason.

A case of cutaneous sporotrichosis involving the auricle of a brick mason is reported. Despite the infrequency of such an infection, sporotrichosis must be considered in the differential diagnosis of perichondritis. The occupational associations with Sporothrix schenckii are reviewed and the relationship with bricks is emphasized.


Linear melorheostotic scleroderma with hypertrichosis.

On the basis of clinical features and histological findings, cutaneous manifestations of linear melorheostotic scleroderma are apparently derived from a localized proliferative disorder and are not secondary to bone changes. If the hypertrichosis has the same origin as the osteocutaneous changes, melorheostosis may represent a congenital disorder with both ectodermic and mesodermic components.


Management of necrotizing vasculitis with colchicine. Improvement in patients with cutaneous lesions and Behcet's syndrome.

Six patients with necrotizing vasculitis were treated with oral colchicine as part of an open study. Four patients with cutaneous vasculitis and normal levels of serum complement and one patient with vasculitis associated with Behcet's syndrome demonstrated clinical improvement while receiving colchicine. One patient with cryoglobulinemia, hypocomplementemia, and cutaneous vasculitis showed no response to colchicine therapy. In three patients, clinical improvement persisted after its withdrawal. Colchicine may be effective in controlling cutaneous necrotizing vasculitis and Behcet's syndrome through its effect on polymorphnuclear leukocyte function.


Wound healing. The effects of topical antimicrobial agents.

The effect of four commonly used topical antimicrobial agents on the rate of reepithelialization of clean wounds was evaluated in white domestic pigs. Neosporin Ointment was found to significantly increase the rate of reepithelialization by 25%, while Furacin significantly retarded the healing rate by 24%. Pharmadine, a preparation containing povidone-iodine, did not affect the rate of healing. Both Silvadene and its vehicle significantly increased the rate of reepithelialization by 28% and 21%, respectively. The effects of these agents cannot be explained on the basis of their antimicrobial activity.


A simple technique for managing digital mucous cysts.

Digital mucous cysts can be effectively managed by multiple needlings and expression of contents. This simple technique cures about two thirds of the lesions. Most of those remaining are reduced to small asymptomatic nodules.


Congenital herpes simplex virus infections. Report of three cases and review of the literature.

Three infants with congenital herpes simplex virus infection were examined and treated. One demonstrated findings of individual vesicles on an erythematous base; another had pustules. The children were treated with vidarabine intravenously. Two of the three survived. The literature suggests a potential increase in the occurrence of this infection in neonates. Since the dermatologist is often asked to aid in the diagnosis of this entity and early recognition is vital, it is important to be familiar with the possible causes of vesicopustular lesions, as well as the epidemiology, clinical manifestations, pathogenesis, and current forms of treatment of congenital herpes simplex virus infections.


Fluoroderma.

Papulonodular eruptions from certain bromide and iodide preparations are widely recognized entities, but skin lesions following fluoride ingestion are rare. Modern prophylaxis for postirradiation dental caries includes the use of fluoride gel preparations applied to the teeth. In two patients receiving such therapy a papulonodular eruption developed, similar to the recognized halogenodermas. These cases may help to increase awareness of this entity.


Sarcoidosis appearing initially as polymyositis.

Polymyositis is an idiopathic progressive muscle disease. Occasionally, sarcoidosis can be associated with a polymyositis-like picture, both clinically and on laboratory investigation. However, serial sections of muscle biopsies will usually demonstrate sarcoid granulomas. A case of sarcoidosis that began as polymyositis with diffuse interstitial pneumonitis is presented.


Squamous cell carcinoma. Occurrence in mycosis fungoides treated with psoralens plus long-wave ultraviolet radiation.

In two patients with mycosis fungoides, a squamous cell carcinoma developed during therapy with psoralens plus long-wave ultraviolet radiation (PUVA). In both patients the carcinoma developed on areas not usually exposed to sunlight. Before receiving PUVA therapy one patient had been treated with topically applied thiotepa and x-ray irradiation, while in the other patient PUVA was the only treatment received except for topical corticosteroids. The carcinomas developed after a total UVA dose of 2,042 and 1,296 joules/sq cm, respectively.


Reticular erythematous mucinosis syndrome. Report of two cases.

Two female patients had eruptions with the morphologic and histologic features of reticular erythematous mucinosis syndrome. However, both cases had features that differed from previous descriptions. In one case the eruption developed three to four weeks after a single erythemogenic sun exposure and faded after two to three weeks. The rash could be reproduced by exposure to ultraviolet B (UVB) or UVC radiation. In the other patient, the eruption involved the arms and face and spared the trunk, which is a more characteristic site of involvement; it was associated with a history of exacerbation following sun exposure, but the rash could not be reproduced on phototesting.


Some gerontologic considerations in the practice of dermatology.

Gerontology and geriatrics are areas of increasing importance in medicine today. Although changes in the appearance and behavior of human skin have long been noted to accompany aging, physicians have only recently begun to consider the impact of such an age-associated change on the manifestations of dermatologic disease and on the dermatologic management of elderly patients. Gerontologic studies in such fields as immunology, epidermal cell kinetics, DNA damage and repair, and therapeutics are potentially of great relevance to the practicing dermatologist and deserve increased emphasis within our specialty.


Congenital fibre type disproportion myopathy. A histological diagnosis with an uncertain clinical outlook.

Nine children with congenital fibre type disproportion (CFTD) are described. Their muscle biopsies contained type 1 fibres which were smaller than the largest type 2 fibres by at least 13.5%. Attention is drawn to the variable natural history of this disorder which generally carries a good prognosis but may sometimes be associated with fatal respiratory problems. For important therapeutic, genetic, and prognostic reasons CFTD must be distinguished from other conditions with similar histochemical or clinical features.


Echocardiographic findings of large patent ductus arteriosus in the very low birthweight infant before and after treatment with indomethacin.

17 very low birthweight infants (mean birthweight 850 g) with large patent ductus arteriosus (PDA) were studied by echocardiography before and after treatment with indomethacin. Before treatment left heart dimensions were increased suggesting large left-to-right shunt. Echographic measurements of augmented left ventricular (LV) contraction could be attributed to increase in preload, and reduction in afterload in PDA. After indomethacin, in infants showing clinical response, left heart dimensions returned rapidly to normal and LV contraction became normal or reduced. Two infants had reduced LV contraction with persistent pulmonary oedema suggesting LV failure. In contrast, infants showing no clinical response to the drug also had no significant changes in echographic measurements. Right ventricular systolic time intervals (RPEP/RVET) did not alter after indomethacin treatment in either group, suggesting that the drug does not increase pulmonary vascular resistance.


Lost to follow up: a study of nonattendance at a general paediatric outpatient clinic.

50 children defined as persistent outpatient nonattenders were compared with 50 children who regularly attended the same clinics. Several factors were often found in the group of nonattenders: (a) initial referral via casualty without a letter from the family doctor, (b) hospital admission before the first outpatient appointment, (c) recognition of multiple medical problems, and (d) evidence of diffuse social problems affecting the family. 34 of the nonattenders had at least 2 of these factors, compared with only 9 children in the other group. Many of these problems can be identified at the initial consultation, and perhaps other methods of continuing health care should be provided for these children.


Oral fat loading test: a reliable procedure for the study of fat malabsorption in children.

Oral triglyceride (TG) loading tests were performed in four groups of children: normal controls, patients with chronic nonspecific diarrhoea (CND), biopsy-proved mucosal pathology (MP), and disturbed intraluminal fat malabsorption (IFM). The rise of plasma TG levels greater than or equal to 55 mg/100 ml (greater than or equal to 0.6 mmol/l) can discriminate between patients with gastrointestinal disease and normal controls or patients with functional disturbances. The postmeal plasma TG rise correlates well with the coefficient of fat absorption (CFA) in normal subjects, patients with CND, and patients with IFM, but not in patients with MP who showed a disproportionally low plasma TG rise compared with their CFA. This test can serve as a useful tool in diagnosis and clinical evaluation for children with gastrointestinal disorders.


Serum cholecystokinin, basal acid secretion, and infantile pyloric stenosis.

The fasting serum cholecystokinin-like activity was measured in 21 infants with pyloric stenosis and in 13 normal controls. No significant difference was found between the two groups. The basal acid secretion was measured by continuously aspirating the previously emptied stomach for one hour. The basal gastric volume and the total and the free acidity were all greater in the pyloric group.


Prolonged QT interval and cardiac arrhythmias in two neonates: sudden infant death syndrome in one case.

Two neonates with arrhythmias and the long QT syndrome are described. The arrhythmias were detected in utero and both infants were apparently well after birth. The first infant, although well, had a bradycardia for the first 9 days of life. A normal heart rate was documented at 10 days but a prolonged QT interval was not appreciated on the ECG. He was discharged from hospital but died suddenly and unexpectedly 3 days later. A post-mortem examination failed to find a cause for his death which therefore fell into the category of the sudden infant death syndrome (SIDS). A retrospective analysis of the perinatal electrocardiogram showed a probable junctional rhythm with 2:1 conduction to the ventricle; the QT interval was prolonged at 0.52 seconds (QTC = 0.63). The second infant had a QT interval of 0.52 seconds (QTC = 0.54) and frequent ventricular premature beats on a 24-hour electrocardiogram. She was treated with propranolol and remains well 2 years later. Sudden infant death has often been described in the siblings of children with the long QT syndrome and one other report described a case of SIDS which was said to have had a prolonged QT interval on the perinatal ECG. This report, however, provides unquestionable evidence, in one case, of an association between the long QT syndrome and SIDS.


The diagnosis of coeliac disease. A commentary on the current practices of members of the European Society for Paediatric Gastroenterology and Nutrition (ESPGAN).

In 1977, 53 members of ESPGAN completed a questionnaire on their current practice in diagnosing coeliac disease. The usefulness of the 'Interlaken' criteria enumerated 9 years previously was reassessed. Details were obtained about the initial diagnostic approach, the acceptable histological criteria of the initial jejunal biopsy, and the timing, technique, response, and interpretation of early and late rechallenges with gluten. Answers indicated that, although the initial mucosal lesion is usually 'flat' at the time of diagnosis, a few infants may present at a time when the mucosal lesion is less completely damaged. Furthermore, the degree of histological change after gluten challenge that is acceptable as a positive response may vary according to the state of the mucosa before challenge. It was noted that there are still no generally agreed criteria by which the histological lesions may be described, so that (after further discussions at the Third International Coeliac Conference in Galway) a European panel has been set up to make recommendations. In the experience of ESPGAN members, most coeliac children will have a histological relapse within 2 years of reintroduction of gluten. But a small number of unorthodox cases were reported that suggest that (a) histological relapse may take longer than 2 years to appear, or (b) the degree of sensitivity to gluten may vary at different ages. Very long-term follow-up will be needed to explain these anomalies. Meanwhile the search continues for 'the basic defect'.


Caffeine secretion into breast milk.

Serum and milk concentrations of caffeine were measured in 5 breast-feeding mothers after a standardised oral dose of caffeine. Peak concentrations of caffeine in serum and milk were attained 60 minutes later. Binding of caffeine by constituents of serum and breast milk was low (25 and 3.2% respectively). In breast milk, caffeine binding is associated with the cream layer, and correlates with the butter fat content. Caffeine does not diffuse freely into breast milk and concentrations in milk are lower than in maternal serum.


Recurrent osteolytic lesions and subcutaneous fat necrosis in association with a developmental pancreatic cyst.

A girl had repeated episodes of widespread osteolysis, subcutaneous fat necrosis, and periarticular fat necrosis mimicking arthritis. Her symptoms persisted for 4 years, after in initial episode of severe abdominal pain, and were accompanied by only minor abdominal symptoms. She was found to have a developmental pancreatic cyst (which was excised).


Lumbar punctures, meningitis, and persisting pleocytosis.

A retrospective survey of children with haemophilus and pneumococcal meningitis was carried out to assess the significance of persistent CSF pleocytosis and the need for repeat lumbar punctures after adequate treatment. Persistent pleocytosis was noted in 9 of 27 patients with haemophilus meningitis; this tended to be present in those with higher initial CSF white blood counts and lower initial CSF glucose contents. No sequelae were noted in those with persistent pleocytosis. Repeat lumbar punctures were not of clinical benefit and tended to result in longer treatment which was not warranted.


Confirmation of gestational age by external physical characteristics (total maturity score).

The use of the total maturity score (TMS) as a means of estimating gestational age was assessed in a population of 76 low birthweight infants (less than or equal to 2500 g) and 80 matched controls (greater than 2500 g) all of certain gestational ages. The gestational ages, derived from the last menstrual period and from the TMS, were similar except in preterm low birthweight infants. The discrepancy in this group was attributed to the structure of the scoring system. It is concluded that the TMS is a convenient and accurate method of assessing gestational age in term babies.


Role of viruses and bacteria in acute wheezy bronchitis in childhood: a study of sputum.

Sputum, nasal swabs, and throat swabs were obtained from 22 children aged between 5 and 15 years during 72 attacks of wheezy bronchitis. A virus, most commonly a rhinovirus, was isolated in 49% of all episodes and in 64% of 22 severe episodes requiring treatment with corticosteroids; the isolation rate was higher early in the illness than later. Virus was recovered more often from sputum than from the nose or throat, suggesting that viral replication occurs freely in the lower respiratory tract: the cytological findings in sputum were compatible with an inflammatory response to viral infection. Pathogenic bacteria appeared to play a minor role compared with viruses, and routine antibiotic treatment was probably of little value in moost cases. The significance of the results is discussed in relation to the pathogenesis of childhood wheezy bronchitis.


Changing incidence of neonatal hypermethioninaemia: implications for the detection of homocystinuria.

The Guthrie test was used to measure blood methionine concentrations in 670 764 neonates during the period from May 1970 to December 1977. Raised values (greater than 4 mg/100 ml; 268 mumol/l) were found in 147 babies (6--14 days old) and 55 of these still had raised values when retested 2--6 weeks later. 48 infants had transient hypermethioninaemia of at least 3 weeks' duration, one had a more persistent form associated with abnormal liver function tests, 3 had different forms of homocystinuria, and one infant, who was asymptomatic at the time of detection, had hypermethioninaemia associated with a rapidly fatal form of tyrosinamiea (tyrosinosis). Two infants could not be followed up. Transient hypermethioninaemia has not been detected in this laboratory since 1975. There was a greatly reduced incidence of transient hypermethioninaemia in girls after 1972 and in boys after 1975; this may have been due to recent changes in infant practices in the UK. Homocystinuria was last detected in this laboratory in 1972; the apparent change in incidence is significant (P less than 0.05) and suggests that the diagnostic value of this screening procedure should be reassessed.


Critical assessment of small bowel biopsy in children.

176 biopsies of small bowel mucosa taken during a 5-year period from 162 children were reviewed, and 92 of them were subjected to quantitative measurement using surface/volume ratio and intraepithelial lymphocyte counting. There was good general agreement between stereomicroscopical appearance of fresh tissue, routine pathology reporting, and our independent histological assessment. Most of those in which there was divergence of opinion (11--15%) had intermediate mucosal changes. There was a significant difference between the surface/volume ratio for each of the three grades of histology (P less than 0.001, less than 0.001, less than 0.01), indicating a relationship between qualitative and quantitative methods of assessment. The range of measurements in intermediate biopsies overlapped those of the other two grades. In the 92 biopsies there was a correlation between surface/volume ratio and intraepithelial lymphocyte count (r = -0.56; P less than 0.001) which may reflect our clinical experience, in that 88% of the biopsies were graded as either normal or flat (probable coeliac disease). Very short children had shorter villi than those with nonspecific diarrhoea and a more normal height.


Use of growth hormone-gel.

We evaluated the efficacy of a depot preparation of growth hormone (GH) in a 15% gelatin solution (GH-gel) in the treatment of 15 growth hormone-deficient children. The studies were designed to see if prolonging absorption of GH to achieve lower more physiological concentrations of GH in plasma would decrease the frequency of injection, reduce the amount of GH needed for effective therapeutic response, and improve the response to long-term treatment. We found that after a single dose of GH-gel the plasma concentrations of GH were lower than those achieved after the standard aqueous preparation. The preparation was efficacious in promoting growth and our 1st study of 6 patients suggested that GH-gel given twice a week had a growth response equal to that of the three-times a week aqueous schedule. However both schedules resulted in the frequently observed decreased growth rate during the second treatment year. Our 2nd study, attempting to ameliorate this waning effect by using the GH-gel preparation twice a week in a weight-adjusted dose during the entire second year did not resolve the problem. Thus, GH in depot gel results in more physiological plasma concentrations of GH and may be beneficial in reducing the quantity of hormone needed and the injection frequency but it does not offer a solution to the waning response to the long-term administration of GH.


Pulmonary hypoplasia: lung weight and radial alveolar count as criteria of diagnosis.

A working definition of pulmonary hypoplasia (PH) was established by retrospective assessment of lung growth both in recognised and hypothetical PH-associated conditions. Lung weight: body weight ratios (LW:BW) were calculated, and morphometry was determined by the radial alveolar count (RAC) (Emery and Mithal, 1960). Both parameters were reduced compared with those of normal controls in diaphragmatic hernia, anencephalus, anuric renal anomalies, chondrodystrophies, and osteogenesis inperfecta. Comparison of LW:BW ratio and RAC indicated that the RAC was the more reliable criterion of PH, LW:BW ratio of less than or equal to 0.012 (67%) of mean normal ratio) and/or RAC of less than or equal to 4.1 (75% of mean normal count) are suggested as diagnostic criteria of PH. Evidence of PH was incidentally discovered in a number of clinically unsuspected cases and retrospectively clarified the clinical and radiological findings. Routine assessment of lung growth should be an essential part of the neonatal necropsy.


Neonatal small left colon syndrome.

Five patients with neonatal small left colon syndrome are described together with some early investigative studies on rectal biopsy material. Current reports on this condition are reviewed. The precise aetiology remains unknown, but vigilance and early referral are recommended in view of the several reports of colonic perforation.


Subacute sclerosing panencephalitis after drug-induced immunosuppression.

A girl developed subacute sclerosing panencephalitis (SSPE). Eight years earlier she had had measles infection contracted shortly after cytotoxic treatment and radiotherapy for a spinal neuroblastoma. The case illustrates that typical SSPE, like immunosuppressive measles encephalopathy, can arise after drug-induced immunosuppression, and supports the view that these diseases probably represent opposite ends of a spectrum induced by measles virus infection in an individual with some form of immunological deficiency.


Response of neonatal hypocalcaemia to 1 alpha-hydroxyvitamin D3.

Administration of 1 alpha-OH-D3 to hypocalcaemic neonates (mean +/- SD, serum calcium 1.50 +/- 0.13 mmol/l) significantly increased serum calcium in all 24 infants within 48 hours after starting therapy (mean +/- SD 1.83 +/- 0.23 mmol/1). The time required to correct hypocalcaemia was significantly shorter (2.04 +/- 0.56 days) in infants treated with 1 alpha-OH-D3, than in 24 infants treated with calcium gluconate infusions (4.12 +/- 1.0 days). Treatment with 1 alpha-OH-D3 was effective, easy to maintain, and produced no side effects.


Munchausen syndrome by proxy in twins.

A family is described in which twin infants had repeated admissions for apparent haemoptysis. It was proved that the mother was simulating these episodes and she eventually injured one of the children with a pin. The mother has subsequently shown some evidence of a Munchausen tendency in herself.


Decreased DNA repair activity in sunburn cells. A possible pathogenetic factor of the epidermal sunburn reaction.

The pathogenesis of the formation of sunburn cells is unknown. Based on autoradiographic methods the unscheduled DNA repair synthesis of UV-induced thymin dimers was investigated in vivo in sunburn cells and in irradiated but histologically normal stratum spinosum cells. The results show a significant lower number of sparsly labeled cells in the sunburn cell-population (13.2 +/- 2.5; mean) when compared to the population of normal stratum spinosum cells (57.8 +/- 7.5; mean). These data indicate that the population of those epidermal cells, which become manifest as sunburn cells 24 h after UV exposure exhibit a reduced DNA repair of UV induced thymine dimers immediately after UV irradiation. Nuclear factors thus seem to play at least some role in the origin of sunburn cells.


The measurement of coenzyme A and a coenzyme A-dependent enzyme. In microdissected epidermal material using coupled enzyme and bioluminescent reactions.

A sensitive micromethod for the determination of Coenzyme A and its esters down to about 0.2 pmol in a volume of 10 microliters and of the activity of citrate synthase is outlined. Epidermal material from healthy and psoriatic skin was utilized in microgram quantity as tissue source. The assay utilizes the ketoglutarate dehydrogenase reaction to yield NADH on addition of free Coenzyme A and the subsequent measurement of NADH by a bioluminescent reaction with Acromobacter fischerii. The total Coenzyme A content in six healthy subjects measured in stratum Malpighii was 1.58 +/- 0.19 mmol per kg dry weight. In six psoriatic patients non-involved and involved epidermis contained 1.51 +/- 0.27 and 1.50 +/- 0.25 mmol/kg, respectively. Long-chain acyl-Coenzyme A comprised about 20% in lesion-free skin and 60% of total content in the involved psoriatic epidermis. The activity of citrate synthase in basal layers of healthy epidermis was 0.30 +/- 0.04 mkat/kg dry weight.


Studies on fibronectin in the skin. II. Indirect immunofluorescence studies in psoriasis vulgaris.

Affected and unaffected skin from patients with vulgar psoriasis and normal skin from a control group were investigated for the presence of fibronectin with an indirect immunofluorescence technique. In the control group, fibronectin is missing in the epidermis, but is found in the basement membrane zone of the dermo-epidermal junction area, in the papillary and the reticular dermis, and in the vascular and neural systems of the skin. The same distribution is also found in unaffected psoriatic skin, whereas in affected skin a change in the distribution of fibronectin is found in the dermis and in the basement membranes, together with the presence of fibronectin in the epidermis, mainly in the cornified layers.


Tactile corpuscle-like structures in a case of plexiform neurofibromatosis.

Tactile corpuscle-like structures were identified in a plexiform neurofibroma, which was localized on the right cranial hemisphere os a 16-year-old boy and had necessitated repeated surgery. These structures were studied by light and electron microscopy. The origin of their component cells is, however, still controversial. We believe to have accumulated sufficient evidence for a Schwann cell origin of these cells.


In vitro examination of cell proliferation in dermatofibroma and in the overlying epidermis.

In nine typical cases of dermatofibroma autoradiographic methods were used to examine the proliferative activity in the tumor and in the overlying epidermis. The number of DNA-synthesizing cells in the dermal nodular lesions was extremely low (0 -- 0.1%). In seven of nine skin lesions acanthosis was to be seen in the overlying epidermis. The quantity of DNA-synthesizing cells in the epidermis overlying the dermatofibroma was not related to the thickness of the epidermis and remained independent, whether the predominant element in the tumor is fibrillar or cellular. In this study we were able to demonstrate the existence of a direct relation between the degree of epidermal proliferation and the distance between the tumor and the epidermis. The duration of DNA-synthesis was constant.


Dopamine effects on the microcirculation and veins of the skin after local application and their changes by antagonistic drugs.

Dopamine causes reflex erythema, central blanching, and piloerection depending on the dose and the type of application wheal reaction. Intracutaneous application shows from 1.5 gamma/0.1 ml wheal formation, erythema, piloerection, and blanching combined with increased heat radiation from the skin surface (AGA thermovision). Epicutaneous application from 500 ml (occlusive patch test) following horny layer stripping, causes marked blanching with weak piloerection. Iontophoretic application of dopamine 1/1,000 (60 s, 0.5 mA) causes only blanching and weak surrounding erythema; application of dopamine 1/100 additionally causes piloerection. This application shows no changing of infrared radiation. Iontophoretic application of dopamine 1/100 or 50 gamma/0.1 ml i.c. in a blanched area after locally applied corticosteroids (McKenzie test) shows diminution of infrared radiation proved by AGA thermovision thermography. Antihistaminics, applied externally, decrease reddening, wheal development as well as blanching by dopamine. Guanethedine (1% in eucerin) increases the blanching phenomenon (false transmitter effect of dopamine). Phentolamine 1% in W/O emulsion is without effect on dopamine reaction. Caffeine ointment (4%) reduces erythema and accentuates the degree of blanching. Oral haloperidol has no influence on the dopamine skin reaction, but increases the blanching in areas of antihistamine treatment. Skin veins and varices show marked vasoconstriction within 10 min after iontophoretic (1 : 100, 3.5 mA, 60 s) or i.c. application (50 gamma/0.2 ml).


Effects of glucocorticosteroids on cultured human skin fibroblasts. V. Influence of anabolic steroids on the inhibitory effects of clobetasol-17-propionate on cell proliferation and collagen synthesis.

As previously found, the glucocorticosteroid clobetasol-17-propionate inhibits cell proliferation during the early growth stage of normal baby foreskin fibroblasts and collagen synthesis in confluent cultures of these cells. The degree of inhibition of cell proliferation decreases with increasing cell density and, moreover, is transient. The anabolic steroids nandrolone and nandrolone-phenyl-propionate have similar effects on these cells. Likewise the magnitude of the inhibition is dose-dependent. When present together the two types of drug do not act in an additive manner. Even at low concentrations the anabolic steroids abolish the inhibitory effect of the glucocorticosteroid on cell proliferation. Furthermore, in this case only the inhibitory effect of the glucocorticosteroid on collagen synthesis is found and there is no further increase in this effect due to the presence of the anabolic steroids. Our results imply that the use of low concentrations of anabolic steroids combined with glucocorticosteroids in topical application to the skin may abolish some of the undesirable side effects of the glucocorticosteroids.


[The BCG as coadjuvant in the treatment of bladder carcinoma].

Thirty one patients with bladder carcinoma of different grades and stages were treated by endoscopic surgery and oral administration of bacillus Calmette-Guerin (BCG). They were randomly separated in two groups: one was treated surgically and the other was treated surgically and with the BCG. According to the ability to develop an immune response to the antigens, patients were divided into three groups. The group who had been treated by endoscopic surgery only had 7 patients with recurrent bladder cancer during a median interval of 30 months. The group treated surgically and with BCG had only one patient with bladder cancer recurrence within a median follow-up period of 30 months. The results obtained with the use of BCG inducing tumor regression seem to indicate a favorable response.


[Vesico-ureteral reflex. Medical treatment].

We have reviewed the problem of vesico-ureteral reflux in children and comment upon the selection guidelines followed for indicating medical treatment, on the basis of the clinical picture and the radiographic and analytical findings. We assess the results obtained (58.06% of cures) as a result of which we stress the need for conservative treatment in cases of moderate refluxes.


[Diagnostic value of computerized axial tomography in urology].

A study is made of the diagnostic value of computerized axial tomographies in 57 patients suffering from urogenital pathology. Only three mistakes which may be attributed to a wrong assessment of the sections support its high degree of reliability. The CAT does not replace the intravenous urography. With regard to other more aggressive means (angiography, endoscopy) or less determining ones (isotopes, ultrasounds), it establishes some stricter indications for the same. The main indications of the CAT in Urology are the study of non-cystic, kidney masses as well as non-functioning kidneys, retroperitoneum and suprarenal glands and finally the establishment of the tumoural stage of prostate, bladder and testicle neoformations. The future of the CAT offers great possibilities as certain technical problems are solved and at the same time as greater experience is gained and its price reduced, all of which constitute factors which currently limit its clinical use.


[Structure of secondary or exogenous prostatic calculi].

Out of a series of 70 prostatic stones, we found 8 considered to be "secondary" or "exogenous" (i.e. originated inside the acinis, following the initial crystallization of the components of the orine introduced into the acini) which underwent crystallographic analysis, using basically the "fine plate" to determine their structure. There were found to be two types of stones: one kin essentially uric (5 in all) and others essentially oxalic (3). We observed that these may be formed by pure substances as in the case of two uric stones but generally the nucleus is made up of uric or oxalic components with a tendency in the periphery to form concentric layers of apatite or whitlockite, similar to those observed in primary or endogenous prostatic stones, accompanied by other oxalic or uric components or not. We found that both the uric acid (anhydrous) as well as the oxalates may adopt the same strucutre presented by the urinary stones (renal, vesical) but the anhydrous, uric acid may also present in the nucleus of a stone, an association of 3 structures (granuloporous + fibrosoradiated + palisaded) which does not occur in urinary stones and it may also form a structure which we call "concretioning" which has not previously been described.


[Priapism: analysis and results of surgical treatment in 9 cases].

A review is made of nine cases of priapism, seven of which were idiopathic and two secondary. The different etiological and clinical aspects are analyzed. All the patients underwent surgical treatment, with 42.8% of good, long-term results and the authors always recommend aggressive and early, surgical treatment.


Neutrophil function in anergic surgical patients: neutrophil adherence and chemotaxis.

Skin test anergy (A) to recall antigens identifies surgical patients at high risk for sepsis. We studied neutrophil function in such patients to assess any alteration in their host defense mechanisms. Neutrophil adherence was measured with a modified adherence assay capable of measuring the adherence of neutrophils in whole blood or purified neutrophil suspensions, and neutrophil chemotaxis was assessed by the Boyeden technique. Twenty-one laboratory controls had a neutrophil adherence of 71.5 +/- 3.8% (mean +/-SD) and chemotaxis of 128.1 +/- 2.4,micro (mean +/-SD). Fifty-four hospitalized patients with normal skin tests had neutrophil adherence of 72.5 +/- 13.1% (p ~ 0.5 relative to control) and chemotaxis of 123.3 +/- 3.1 micro (p ~ 0.5). Twenty three relatively anergic patients had values of 84.3 +/- 7.9% (p < 0.001) and 103.7 +/- 2.0 micro (p < 0.001). Forty five A patients had adherence of 85.0 +/- 7.0% (p < 0.001) and chemotaxis of 90.4 +/- 2.9 micro (p < 0.001). The correlation coefficient between increased neutrophil adherence and decreased chemotaxis r = 0.81 has p < 0.0005. A factor which increased the adherence of normal control neutrophils was found in the plasma but not the serum of anergic patients. Inhibitors of control neutrophil chemotaxis have been shown in both serum and plasma of patients with decreased autologous neutrophil chemotaxis. We propose that this altered neutrophil function (possibly with other defects) in anergic patients may compromise their host defenses and render them susceptible to infection.


Mass in the head of the pancreas in cholestatic jaundice: carcinoma or pancreatitis?

The clinical, biochemical and radiological findings in 16 patients with carcinoma of the head of the pancreas were compared with that of 13 with cholestatic jaundice due to chronic pancreatitis. Patients presenting with malignancy had more severe hyperbilirubinemia (18.5 +/- 2.1 vs 5.6 +/- 1.6 p to ten days of hospital admission was the single most accurate test distinguishing carcinoma from pancreatitis. The mean bilirubin rose in carcinoma but fell in pancreatitis (mean net change 15.1 +/- 2.9 vs 3.9 +/- 0.6, p less than 0.001). Calcification in the pancreatic region was identified on a flat plate of the abdomen in 8/13 with pancreatitis but 0/16 with malignancy. Preoperative percutaneous transhepatic cholangiography was helpful in defining the site of biliary obstruction but the radiologist was unable to clearly predict the definitive diagnosis in five of the 29 patients. A point score based upon the major significant differences noted, predicted the presence or absence of malignancy in all patients (16/16 vs 0/13, p less than 0.01).


Splenectomy for Gaucher's disease.

The records of ten patients who underwent splenectomy for Gaucher's disease were reviewed. All patients had the adult type of the disease. The indications for splenectomy were hypersplenism and mechanical problems. The hematological picture returned to normal in all cases and has remained so throughout the follow-up period. The different forms Gaucher's disease and specific diagnostic tests are discussed. Even though splenectomy is indicated when hematological and mechanical problems exist, selective enzymatic replacement therapy seems to be the preferred future mode of treatment.


Thrombotic complications of heparin therapy: including six cases of heparin--induced skin necrosis.

Thrombotic complications of heparin administration were observed in eight patients during a two year period. At sites of subcutaneous heparin injection, six patients developed areas of the skin and subcutaneous necrosis. Systemic thrombotic events and thrombocytopenia were observed in two of these patients when they received intravenous heparin and in two other patients who did not have primary skin necrosis. The complications included peripheral ischemia in three patients (two requiring amputation), myocardial infarction in two, and a cerebral infarction in one. All patients were receiving heparin for at least six days before complications occurred. Seven patients received heparin of bovine origin. Heparin-induced in vitro platelet aggregation was present in all six of the eight patients tested. (It was marked in four of these patients). It is theorized that skin necrosis and the other thrombotic complications observed are the result of heparin-induced in vivo platelet aggregation followed by intravascular thrombosis. Heparin-induced skin necrosis is a rare but serious hazard encountered with prophylactic heparin regimens. If heparin-induced thrombosis is present, the further use of heparin is contraindicated in most instances.


Saphenous neuralgia: a complication of vascular reconstructions below the inguinal ligament.

Although relatively frequent in our experience saphenous neuralgia (SN) is not usually reported as a complication of vascular operations below the inguinal ligament. In 55 patients undergoing extended deep femoral angioplasty (EDFA, n = 28) and femoropopliteal bypass graft (FPBG, n = 27) special attention was paid to incidence and severity of postoperative SN. Severe early postoperative SN was seen in 8/28 patients with EDFA and in 6/27 with FPBG. Milder SN was seen in 10 more patients with EDFA, and 3 other developed SN many months after surgery. The milder forms of SN and late SN were not encountered after FPBG. SN usually improved with the passage of time, and at last follow-up averaging 18 months for EDFA and 33 months for FPBG there remained only 23 patients with mild SN (15 after EDFA and 8 after FPBG). The etiology of SN appears to be trauma to the nerve sustained during operation. Age, sex, diabetes, or the addition of lumbar sympathectomy to the vascular operation did not affect the risk of sustaining early postoperative SN. Increased awareness of this complication may help to understand its pathophysiology better, and possibly to decrease its incidence.


Vascular access grafts for chemotherapy. Use in forty patients at M. D. Anderson Hospital.

Forty-two arteriovenous grafts were placed to provide vascular access in 40 patients with poor or sclerosed superficial veins. Thirty-nine patients had malignant disease and required chemotherapy, while one patient with aplastic anemia needed frequent transfusions. Thirty-two grafts were placed in the arm (27 straight and 5 loop), and ten in the leg (femoral-femoral loop). Thirty-seven shunts consisted of 6 mm polytetrafluoroethylene (PTFE), and five were 6 mm Dacron((R)). The straight brachial artery to axillary vein PTFE graft was preferred, while the PTFE femoral loop graft was a satisfactory alternative. The loop arm graft was associated with a high complication rate and is no longer used. Local anesthesia was employed in all cases except for a 3-year-old child. There was no operative mortality and no severe morbidity, despite subsequent myelosuppression by chemotherapeutic agents injected via these grafts. Thirty patients are alive, while ten died of their malignancy. Twenty-six grafts are functional and have been in place an average 4.4 months (range: 1 to 14 mo.). Acceptance by patients and particularly by personnel in the out-patient chemotherapy unit has been enthusiastic. Vascular access grafts can be inserted safely and provide a convenient route for drawing blood samples, and for administering chemotherapy and intermittent intravenous therapy in selected patients with neoplastic disease.


Intrapulmonary clotting and fibrinolysis during abdominal aortic aneurysm surgery.

Intravascular clotting and fibrinolysis (C and F) are events which often accompany major surgical trauma. Their role in inducing cardiopulmonary failure is debated and prompted this study of 13 patients undergoing elective AAA. Following intubation, anesthesia and pressure breathing fibrinolytic activity (FA) in arterial blood exceeded that in mixed venous blood (p < 0.001) indicating pulmonary secretion of proteolytic activity. Fibrinogen, plasminogen and fibrin degradation products (FDPs) were normal. During surgery, fibrinogen and plasminogen fell (p < 0.001) while nonplasmin mediated FA and FDPs rose (p < .001). Despite heparinization (5000 U IV) aortic clamping (avg 56 min) led to evidence of C and F within the lungs. Arterial fibrinogen was 33.2 mg/ml lower than mixed venous blood (p < 0.01) and plasminogen was 0.47 Sherry units lower (p < 0.001). Soluble fibrin monomer appeared in arterial blood (p < 0.01). At the same time nonplasmin mediated FA was consumed within the lungs (p < 0.01) and FDPs were produced (44.6 microg/ml higher in arterial blood, p < 0.001). Similar changes were noted after aortic declamping. The transient 5.3 ml/cm H(2)0 fall in dynamic compliance was unrelated to C and F. Pulmonary vascular resistance and arterial pressure were unchanged. During wound closure intrapulmonary C and F ceased. Postoperatively (6 h), the physiologic shunt of 15.1% was similar to tbe preoperative value of 13.3%. All C and F factors returned to normal except FDPs which remained elevated. An average of 0.2 U blood was given prior to aortic clamping and 3.1 U during clamping. Neither the volume nor the type of blood (7 patients received washed RBCs) influenced pulmonary C and F. The results show that pressure breathing will alter pulmonary metabolism from clearance to secretion of fibrinolytic activity. Surgery leads to systemic C and F while intrapulmonary C and F is triggered by aortic clamping despite IV heparin. Delayed functional consequences of C and F are possible. Immediate postoperative effects are not apparent.


Venous capacitance and outflow in the postoperative patient.

Venous capacitance and outflow were measured in a series of 50 unselected patients undergoing a variety of general surgical procedures. Studies done prior to operation and the morning after demonstrated a fall in capacitance and outflow that was related to the degree of ambulation. Fully ambulatory patients demonstrated no changes. Males under the age of 40 were unchanged regardless of the type of operation or degree of ambulation. It is likely that the observed changes reflected a reduction in arterial flow but alterations in venous tone cannot be ruled out.


Portal hypertension secondary to choledochal cyst.

Two patients with portal hypertension secondary to choledochal cyst are reported and combined with four others previously reported in the literature. Choledochal cysts may, by extrensic compression, cause partial or complete portal vein obstruction, portal hypertension and esophageal varices. Needle biopsy of the liver is probably not a reliable means of differentiating choledochal cyst from other intrahepatic causes of portal hypertension. Internal drainage of the choledochal cyst has been performed in four patients and in each instance resulted in satisfactory portal decompression.


Thoracic outlet syndrome: current concepts of treatment.

This current concept of treatment of the Thoracic Outlet Syndrome based on a personal experience with 304 patients, resulted in complete (85%) or partial (7%) relief of symptoms in 92% of operated patients. The diagnosis centers upon a thorough history and the exclusion of other causes of arm and shoulder pain utilizing a strict flow pattern of differential diagnosis. Angiography and electromyography are of limited value and are only performed in selected cases. Operation should be reserved for the thoroughly evaluated patient who continues to have pain despite adequate conservative therapy. Transaxillary removal of the first rib, fibromuscular bands and cervical rib, when present, is the operation of choice.


The value of transperineal injection for the diagnosis of imperforate anus.

Imperforate anus is one of the most common causes of intestinal obstruction in the newborn and the exact estimation of the level of the blind rectal pouch is of primary importance. We present 11 cases of imperforate anus and demonstrate the accurate location of the rectal pouch by transperineal injection of contrast media. This method shows an advantage in comparison to the classical plain roentgenogram in the inverted position of the baby. No unnecessary colostomies were performed since intraduction of the transperineal injection. The method is simple and there were no complications due to injection 10-15 cc of 20% Hypaque. Further studies are not in progress to demonstrate the presence or absence of an associated internal fistula in all cases.


Successful management of early stroke after carotid endarterectomy.

This paper concerns the management of stroke coming on in the early postoperative period after successful carotid endarterectomy. Our experience in effectively reversing hemiplegia in three such consecutive patients forms the basis of this report. The value of instant reoperation is emphasized, and several factors that facilitate urgent reoperation have been identified. These include omission of preoperative angiography, immediate reexploration under local anesthesia, and rapid restoration of cerebral flow by insertion of a shunt. Our experience would indicate that reversal of neurological deficit in such patients can be accomplished if reoperation is carried out within one hour of onset of stroke. All three patients managed by these criteria recovered and were neurologically intact eight to twelve months later. These results are in contrast to the failure to reverse stroke noted by us and others when the above measures were not followed.


Aortoplasty compared with resection for coarctation of the aorta in young children.

We repaired coarctation of the aorta in a group of 18 children less than 3 years old, using either resection with end-to-end anastomosis (8 patients, Group 1) or patch graft aortoplasty (10 patients, Group 2). The two groups were similar preoperatively in age, pressure difference between proximal and distal aorta (delta PA0), and severity of aortic arch hypoplasia. Three patients, all less than 2 months old, died early postoperatively. Among the survivors, the right brachial artery systolic pressure was significantly higher in Group 1 (133.1 +/- 7.0 mm Hg) (mean +/- standard error of the mean) than in Group 2 (102.5 +/- 7.2 mm Hg) (p less than 0.05). The delta PA0 was significantly higher in Group 1 (33.0 +/- 7.5 mm Hg) than in Group 2 (5.1 +/- 2.3 mm Hg) (p less than 0.01). Three patients in Group 1 required reoperation and were treated with patch graft aortoplasty; relief of delta PO0 was complete in 2. Patch graft aortoplasty is more effective than resection in reducing proximal aortic systolic pressure and in relieving delta PA0 in infants and small children with coarctation of the aorta.


Surgical treatment of atrial myxomas: early and late results of 11 operations and review of the literature.

Eleven patients underwent surgical excision of atrial myxomas during a 15-year period, with no hospital deaths. The operation consisted of excision of the tumor with a generous portion of atrial septum or wall. Patch reconstruction of the atrial septum was required in most patients. There were 2 late deaths (14 and 121 months after operation). Late recurrences have been reported in other series but no recurrences were diagnosed in any of the patients in this series reexamined by echocardiography 7 to 156 months (mean, 48 months) after operation. Late functional results were excellent (78%, New York Heart Association Class D. The pertinent literature is reviewed.


Open lung biopsy in diagnosing pulmonary infiltrates in immunosuppressed patients.

From July, 1973, to June, 1977, 25 patients in an immunosuppressed state from underlying reticuloendothelial neoplasm or associated chemotherapy, underwent open biopsy of the lung at the University of Maryland Hospital for diagnosis of unilateral diffuse pulmonary infiltrates. Eight patients were in marked respiratory distress, 13 in moderate distress, and 4 in little or no distress at the time of open lung biopsy. There were 3 postoperative deaths (12%). The operation-related morbidity was 1 out of 25 (4%). Two of the patients who died were found to have irreversible pulmonary fibrosis secondary to bleomycin drug therapy. The subsequent treatment of all 25 patients was influenced by the biopsy findings as follows: upgrading the disease stage or establishing treatment failure in 11 patients; establishing the presence of inflammatory disease in 3 patients; establishing the diagnosis of fibrosis associated with drug treatment without recurrent disease or infection in 11 patients. The preferability of open lung biopsy as opposed to transbronchial or percutaneous techniques is discussed.


Treatment of inoperable lung carcinoma: a combined modality approach.

Twenty-four patients with inoperable lung carcinoma other than of the small cell type who received cis diamminedichloro platinum (II)-based combination chemotherapy were further treated with all available treatment modalities: radiation therapy, lung resection, chemotherapy, and immunotherapy. There were 2 operative deaths, and 2 patients died 6 and 8 months postoperatively of cardiac causes. Postmortem examination on these 4 patients revealed no evidence of residual tumor. The remaining 20 patients are alive 7 to 33 months from the onset of chemotherapy and 4 to 27 months following lung resection. These results, although preliminary, are encouraging, and further study is in progress.


Acquired benign bronchoesophageal fistulas in the adult.

In a twenty-year period we have seen 7 patients with acquired nonmalignant bronchoesophageal fistulas at the Vanderbilt University Affiliated Hospitals. There were 5 men and 2 women ranging from 24 to 82 years old. Six patients were seen initially with a history of pulmonary inflammatory disease with cough and fever or with an abnormal chest roentgenogram. One patient had a traumatic fistula following blunt chest trauma. Six of the patients were treated surgically with no operative mortality. Five were repaired through a right-sided thoracotomy with division of the fistulous tract and closure of the bronchus and esophagus. One patient required esophageal resection and later reconstruction for permanent fistula closure. The remaining patient was diagnosed at bronchoscopy and was not treated surgically because of supervening complications following an extensive abdominal operation. Once the diagnosis was established, operative management resulted in complete closure of the fistulas, with no mortality and no late recurrences in these patients.


Diagnosis and management of major tracheobronchial injuries.

From 1968 to 1978, 14 patients were treated for major tracheal or bronchial injury. Five injuries resulted from blunt trauma and nine from penetrating injury. Of the 5 patients with injury due to blunt trauma, three had avulsions of the right main bronchus from the trachea. In 2 of them, the injury was associated with stellate tears of the distal trachea and bronchus. The simple avulsion was repaired by a primary anastomosis of the right main bronchus to the distal trachea. For the other 2 patients, treatment consisted of right pneumonectomy. The remaining 2 patients in this group had complete transection of the trachea and underwent primary repair. Of the 9 patients with a penetrating injury, 4 had lacerations of the cervical trachea which were treated with neck exploration and tracheostomy. Three patients with partial transections of the cervical or upper mediastinal trachea were treated by primary closure. The other 2 patients had gunshot wounds to the distal right lateral trachea, which were treated by right thoracotomy and primary closure. There were no deaths, and the subsequent course was generally good in all patients.


Ten years' experience with pulmonary autograft replacements for aortic valve disease.

Pulmonary autograft valves have been used to replace isolated, diseased aortic valves for 10 years, with a long-term survival of 73%. The low incidence of degeneration supports the principle that the autograft valve is a potentially permanent valve replacement. Operative mortality is now less than 5%, despite the longer, more complex operation. The current use of fresh homograft valves for the pulmonary replacement has contributed to these excellent long-term results.


A simple technique for tension-free pericardial closure.

Closure of the pericardium after cardiac operations is desirable but is not always possible to achieve. We describe here a simple technique for tension-free, anterior closure of the pericardium.


A new clamp for patch graft angioplasty of coarctation of the aorta.

A new clamp controls the great vessels in the region of aortic coarctation, allowing unhampered access to the aortotomy in patch graft angioplasty.


Sodium-dependence of p-aminohippurate transport by rat kidney cortex slices.

The effect of medium Na+ concentration on p-amino-hippuric acid (PAH) uptake and efflux were investigated in rat kidney cortex slices. The uptake during 10 min incubation was taken as a measure of the initial influx. At a fixed Na+ concentration, the uptake curve (amount of uptake against substrate concentration) consisted of two distinct components; one linear with medium PAH concentration and the other obeying Michaelis-Menten kinetics. Only the latter was dependent on the Na+ concentration. A reduction of medium Na+ concentration resulted in an increase in Kt for PAH, while Vmax for PAH remained unchanged. In the absence of Na+, the component obeying Michaelis-Menten kinetics still existed, and Vmax for PAH was identical with that in the presence of Na+. The reciprocals of Kt were linearly proportional to medium Na+ concentration. Such kinetic properties could be interpreted on the basis of a kinetic model in which PAH was assumed to be transported across the cell membrane by forming both binary (carrier-PAH, SX) and ternary (NaXS) complexes. An elevation or reduction of Na+ concentration in efflux media caused an immediate decrease or increase in the rate constant for PAH efflux, respectively. Addition of a competitive inhibitor (hippurate) to efflux medium also caused an immediate increase in the rate constant. From these observations, it was concluded that PAH transport in rat kidney was mediated through both Na+-dependent and Na+-independent carrier processes at the peritubular membrane.


Cardiovascular and autonomic actions of ciclazindol and tricyclic antidepressants.

The novel antidepressant ciclazindol had no significant effect on blood pressure at doses of up to 25.6 mg/kg i.v. in anaesthetised rats. Desipramine, imipramine, nortriptyline and amitriptyline evoked significant decreases at 0.8-1.6 mg/kg. Ciclazindol had no sustained haemodynamic actions in anaesthetised cats apart from a small rise in dp/dt. The ECG waveform showed only minor voltage changes. Desipramine and nortriptyline elevated haemodynamic variables at low doses but decreases occurred at higher doses. Amitripyline and imipramine decreased blood pressure. ECG changes evoked by the tricyclics included QRS complex distortion, ventricular ectopic beats, nodal rhythm, bundle branch block and ventricular tachycardia. In skin wheal tests ciclazindol was equiactive with the tricyclics as a local anaesthetic. In isolated tissues ciclazindol was not anticholinergic, showed no marked antagonism of 5-HT, potentiated responses to noradrenaline and was weakly antihistaminic. Ciclazindol appears to be pharmacologically different from the tricyclics and may not produce the unwanted side effects associated with these compounds.


Electrophysiological effects of droperidol on sinoatrial nodal fibers.

The influence of 1 and 5 mg/l of droperidol on rabbit sinus node intracellular recordings was evaluated. At 1 mg/l the drug merely prolonged the spontaneous basic cycle by reducing phase 4 slope of the action potential. At the higher concentration, droperidol induced a more pronounced effect of these variables and after 20 min perfusion, it also decreased the upstroke velocity and the threshold potential. Further exposure continued to reduce spontaneous rate, until irregular failure of impulse initiation and subthreshold oscillations appeared. After 45 min exposure to droperidol, only subthreshold oscillations could be recorded. Isoproterenol (0.2 mg/l) rapidly restored normal action potentials, while acetylcholine (0.5 mg/l) caused an immediate arrest leaving a stable level of membrane potential. The activity of droperidol in 1 mg/l concentration could be dependent on a partial blockade of the sodium leakage current, while at higher concentrations of 5 mg/l the drug seems to provoke a total blockade of Na--Ca slow channels. Subthreshold oscillations could be explained by changes in K conductance together with a remanent of the sodium leakage current.


Comparison between the pressor response and the rise in plasma catecholamines induced by acutely elevated intracranial pressure.

The influence of an abrupt elevation of intracranial pressure (ICP) on arterial blood pressure and on plasma catecholamines was studied and compared both in anaesthetized rats and cats. In rats, the elevation of ICP to 160 mm Hg caused an immediate rise in mean arterial blood pressure (MAP) and heart rate. Plasma noradrenaline and adrenaline also increased, though much slower than the circulatory changes. The duration of the pressor response was reduced after either reserpinization or adrenalectomy and virtually abolished after a combination of both pretreatments. The rise in plasma noradrenaline and adrenaline was virtually abolished in rats pretreated with reserpine or subjected to bilateral adrenalectomy. Acute elevation of ICP up to 160 mm Hg also caused pressor and chronotropic responses in cats, which were reduced by preceding reserpinization and adrenalectomy and abolished by a combination of both pretreatments. The rise in plasma noradrenaline was similar to that in rats, also with respect to its development, which proved to be much slower than that of the circulatory changes. The rise in plasma adrenaline was much less pronounced in cats. Pretreatment with reserpine or adrenalectomy virtually abolished the ICP-induced rise in plasma noradrenaline. Reserpine pretreatment had relatively little influence on the rise in plasma adrenaline but bilateral adrenalectomy virtually abolished it. In venous blood directly obtained from the adrenal gland the rise in plasma noradrenaline ICP elevation caused a rapid increase in plasma catecholamines, which could be reduced by pretreatment with reserpine. Our experiments confirm the hypothesis that the elevation of ICP causes an increase in sympathetic tone. The determination of plasma catecholamines, however, is not an adequate method to study rapidly occurring changes in sympathetic tone.


The effects of drugs and electrical field stimulation on the human lower oesophageal sphincter.

Acetylcholine, bethanechol, pentagastrin and dopamine contracted muscle strips cut transversely from the human lower oesophageal sphincter (LOS). In the presence of hyoscine the contraction to acetylcholine was changed to a relaxation; tolerance was observed to the effect of pentagastrin. Metoclopramide and adenosine triphosphate were only partially effective on LOS muscle, some strips were unresponsive, others gave small contractions. Noradrenaline, dimethylphenylpiperazinium and histamine relaxed LOS muscle, relaxations to noradrenaline were blocked by propranolol. In contrast to drug action the response of LOS muscle to electrical field stimulation was dependent on the exact origin of the muscle strip. Muscle cut adjacent to the oesophagogastric junction only relaxed, strips cut progressively more rostral to this point showed a biphasic response with the after contraction becoming more obvious as the distance from the oesophagogastric junction increased. Relaxation of LOS muscle to electrical field stimulation appeared to involve non-adrenergic non-cholinergic nerves. It is suggested that muscle obtained from the terminal oesophagus may be identified as the LOS if it responds to electrical field stimulation with only a relaxation.


The action of acetaldehyde on the intracellular electrical activities of the guinea-pig taenia coli.

The effect of acetaldehyde on the membrane potential and the membrane resistance of the guinea-pig taenia coli has been studied with an intracellular recording technique. Application of acetaldehyde in the concentration of between 5 and 20 mM produces reduction or elimination of the spontaneous spike activity and hyperpolarization of the membrane. The amplitude and the rates of rise and fall of the action potential are reduced by the drug. The duration of the spike is slightly prolonged. Acetaldehyde also reduces the amplitude of the evoked action potential produced by externally applied cathodal stimulation in twice hypertonic solution. Electronic potentials induced by anodal current are reduced both in size and time course by acetaldehyde during the stage of hyperpolarization.


Action of S-adenosyl-L-homocysteine on the metabolism of dopamine, norepinephrine and serotonin in rat brain.

S-Adenosylhomocysteine (SAH) (0.1 to 30 mg/kg/i.p.) increased 3H-norepinephrine synthesis from 3H-tyrosine in the rat brain stem and mid brain, but did not alter its tissular level. It decreased both the serotonin level and the formation of 3H-serotonin from 3H-tryptophan and increased the formation of 3H-5hydroxyindolacetic acid. Its effects began 1 hr after administration and was still present 6 hr later. It did not alter dopamine metabolism. A correlation between the hynotic effect of SAH and the modification of the metabolism of cerebral monoamines was pointed out.


Cellular uptake and subcellular distribution of two non-steroidal anti-inflammatory drugs: indomethacin and ketoprofen.

The cellular uptake and intracellular localization of indomethacin and ketoprofen were studied on rat embryo fibroblasts in vitro. The two drugs are taken up by the cells, but to a lesser extent for ketoprofen than for indomethacin. Inside fibroblasts ketoprofen is rapidly metabolized whereas indomethacin seems accumulated as such inside the cells. After different incubation times, ketoprofen is partly associated to the cytosol and partly to another cellular component, probably the endoplasmic reticulum. Indomethacin on the other hand is almost exclusively distributed inside the cytosol. No clear association of the two drugs can be found with the lysosomes.


The respiratory effects of 1-cis-2-(a-dimethylamino-m-hydroxybenzyl) cyclohexanol-HCl and pentazocine in man.

The respiratory effects of 1-cis-2-(a-dimethylamino-m-hydroxybenzyl) cyclohexanol-HCl (WY-15,705) were compared to those of pentazocine when given intramuscularly to man. It was found that WY-15,705 was 2.8 times as potent in terms of its respiratory depressant effects.


Quantitative evaluation of the actions of anticonvulsants against different chemical convulsants.

Anticonvulsants were tested on mice for their effectiveness against different chemical convulsants. Ethosuximide is very effective against pentylenetetrazol (PTZ), but ineffective against 3-mercaptopropionate (3-MP) which is an inhibitor of gamma-aminobutyrate (GABA) synthesis. Trimethadione, chlordiazepoxide and mesuximide are less effective against 3-MP than against PTZ. The same tendency was apparent, though falling short of statistical significance, with phenobarbital, mephenytoin, carbamazepine and valproic acid, whereas aminooxyacetic acid (AOAA) appeared to be somewhat more effective against 3-MP than against PTZ. Several anticonvulsants were tested also against bicuculline (BIC), picrotoxin (PIC) and bemegride (BEM), and profiles depicting their relative capacities to antagonize the convulsants were constructed. These show major differences and few resemblances. Likewise the convulsants show little resemblance to each other in their patterns of sensitivity to different anticonvulsants. The data do not support the concept that PTZ, BEM, BIC or PIC induce seizures primarily by blockading GABA-mediated inhibition, since their patterns are so unlike that of 3-MP. The profiles of clinically used anticonvulsants suggest that none of those tested acts primarily on the GABA system, since all are so unlike that of AOAA.


The effects of methyl-3-O-methyl gallate on isolated nerve activity.

Methyl-3-O-methyl gallate (M30MG), extracted from Crinodendron hookerianum Gay, decreased both sciatic nerve accommodation and the amplitude of the compound action potential and increased the threshold to rectangular and exponential currents applied to the isolated sciatic nerve in a manner similar to that observed when tetrodotoxin is applied to the nerve. M30MG would act mainly on the large nerve fibres by a mechanism probably resembling that of tetrodotoxin.


Effects of nomifensine on the isolated vas deferens of the rat.

The effects of nomifensine on the rat isolated vas deferens was studied. Nomifensine (7.60 X 10(-11) molar--7.60 X 10(-8) molar) enhanced the stimulant effects of dopamine and prevented the inhibitory action of pimozide on dopamine-induced contractions. Higher concentrations of nomifensine blocked the effects of dopamine noncompetitively (pD2' = 7.25 +/- 0.12). Nomifensine (7.60 X 10(-9) molar--3.80 X 10(-6) molar) enhanced noradrenaline-induced contractions and reduced phentolamine-induced antagonism of noradrenaline. Higher concentrations of nomifensine blocked the effects of noradrenaline competitively (pA2 = 5.50 +/- 0.06). Guanethidine induced supersensitivity of the vas to noradrenaline and further enhanced the potentiating effect of nomifensine. The effect of 5-HT was reduced competitively by nomifensine (pA2 = 7.50 +/- 0.10). Desipramine produced a similar preferential enhancement of dopamine-induced contractions and antagonized dopamine at higher concentrations. It is concluded that nomifensine may act prejunctionally by inhibiting uptake of the amines and postjunctionally by blocking the receptors.


Effect of sodium taurocholate on hepatic uptake and biliary excretion of organic anions in rats.

Hepatic uptake and biliary excretion of some exogenous organic anions administered simultaneously with sodium taurocholate (TC) have been investigated in anaesthetized (1.2 g/kg urethane i.p.) rats. TC (100 or 200 mumol/kg i.v.) significantly increased the biliary excretion of indocyanine green (ICG), bromcresol green (BCG), rose bengal (RB) and bromsulphthalein (BSP). The biliary excretion rates of eosine (EO) and bromsulphthalein-glutathione conjugate (BSP-GSH) were not affected by TC. However, simultaneously given TC significantly reduced the biliary excretion of amaranth (AM). The effect of TC on the biliary excretion rates of organic anions seems to depend on the properties of the anions investigated. ICG, BCG, RB and BSP depress bile production, inhibit mitochondrial respiration and are excreted at low rates. Biliary excretion of these anions was enhanced by TC. EO, BSP-GSH and AM had no depressing effect on the function of liver cells and showed higher excretory rates than the above-mentioned substances. The changes in biliary flow measured during excretion of drugs did not parallel the changes in biliary excretion rate. The hepatic uptake of all organic anions studied was depressed by TC. This finding indicates that no correlation exists between the effects of TC on hepatic uptake and biliary excretion of organic anions.


In vitro activities of some synthetic substance P analogs.

Substance P (SP) and several analogs and fragments have been synthesized and evaluated on non-stimulated and stimulated guinea-pig ileum. In the former test system the potency order was as follows: SP(4--11) greater than SP = [Tyr7]-SP = [Eth11]-SP = [Nle11]-SP greater than [Dala9]-SP greater than SP(7--1) = [Tyr7]-SP(7--11) greater than [Eth11]-SP(7--11) greater than [DAla9]-SP(7--11) greater than [Nle11]-SP(7--11) greater than SP(1--7). The spasmogenic activity of SP and analogs was preserved in the same potency order on stimulated guinea-pig ileum; none of these modifications resulted in an analog with narcotic-like activity. These data are discussed in terms of a hypothetical SP receptor in extravascular smooth muscle.


Antagonism of some contractile responses to prostaglandins by cyproheptadine.

In the present study antagonism of the contractile responses to PGE1 and PGF2 alpha, by cyproheptadine on isolated rat stomach strip, rabbit uterus, guinea-pig ileum and rabbit jejunum is documented. Cyproheptadine blocks the responses to PGE1, PGF2 alpha, acetylcholine, 5-hydroxytryptamine in extremely small concentrations varying from 10 ng to 1 microgram/ml. The blockade is persistant, provided the exposure is prolonged. However, it does not antagonise the responses of adrenaline on guinea-pig seminal vesicle. Polyphloretine phosphate was used in the concentration of 2.5 to 100 micrograms/ml on the rat stomach strip, rabbit jejunum and rabbit uterus; it failed to produce any blockade of contractile responses to prostaglandins. It is concluded that cyproheptadine nonspecifically antagonised the responses to acetylcholine, 5-hydroxytryptamine, PGE1 and PGF2 alpha in extremely small concentrations.


Cutaneous vascular histamine H1 and H2 receptors in the guinea-pig: the histamine skin wheal as a cutaneous vascular model.

The roles of histamine H1 and H2 receptors in histamine skin wheals were studied in the guinea-pig. Intradermal injections of histamine, 0.125--2 micrograms/0.1 ml, produced wheals in a dose dependent manner. Pyrilamine maleate (3.2 mg/kg p.o., pretreatment for 1 hour) produced a dose dependent shift of the histamine wheal dose-response curve to the right in a parallel fashion. Metiamide, 3, 10 or 30 mg/kg p.o., had no effect on the histamine dose-response curve. However, a combination of metiamide (10 or 30 mg/kg) and pyrilamine (3.2 mg/kg) further increased the effect of pyrilamine. It is concluded that both H1 and H2 receptors are involved in histamine-induced wheals in the guinea-pig.


Effects of lithium on time to onset of aconitine-induced initial arrhythmia and ventricular tachycardia.

The effects of lithium on the time to onset of aconitine-induced initial arrhythmia and onset of ventricular tachycardia were determined in mice. The mice were pretreated intraperitoneally with 1.73, 3.0, 5.1 and 8.8 mEq lithium chloride/kg/day for 5 days, or 8.8 mEq LiCl/kg/day i.p. for 1, 3, 5, 7 and 10 days. Lithium prolonged the onset-time to ventricular tachycardia, and this effect was both dose and time dependent. Under these conditions, lithium pretreatment had no effect on the time to onset of aconitine-induced initial arrhythmia. The LD50 was 15.3 mEq/kg. The observed prolongation of the onset of ventricular tachycardia can be explained in part by the influence of lithium on myocardial cations and catecholamines, and the pharmacologic effect of lithium on Purkinje fibers.