Quantitation of antibiotics by high-pressure liquid chromatography: cephalothin.

A technique for quantitative determination of cephalothin and desacetylcephalothin in serum using a method based on high-pressure liquid chromatography is described. Both compounds were quantitatively extracted from serum by using dimethylformamide. After separation of the drugs by reverse-phase chromatography and detection by ultraviolet light absorption at 254 nm, serum concentrations of cephalothin and desacetylcephalothin as low as 1.0 mug/ml were measured. No interfering absorption was found in extracts of serum samples from normal humans or patients receiving a variety of other drugs, including other antimicrobial agents. Serum specimens obtained after an intravenous infusion of cephalothin to two human subjects and three dogs were assayed by the chemical and microbiological assays. When values, as determined by the chemical method and the microbiological assay in samples from human subjects, were compared, the correlation coefficient (r) was 0.96, whereas, in the dogs, the r value was 0.79. The chemical procedure described in this report for determination of cephalothin and desacetylcephalothin permits future pharmacokinetic investigations of these compounds. This assay is sensitive, specific, accurate, and rapid (approximately 30 min), and appears suitable for routine clinical use.


Diffusion disk susceptibility testing with cefaclor.

The reliability of the standardized 30-mug cephalothin disk and that of an experimental 30-mug cefaclor disk in predicting probable clinical susceptibility to cefaclor were compared. Quantitative determinations of cefaclor susceptibility were measured by the World Health Organization International Collaborative Study agar dilution procedure; diffusion disk tests were performed by the standardized U.S. Food and Drug Administration disk test. The cephalothin disk erred in predicting probable susceptibility in 52% of isolates of Enterococcus spp. resistant to 16 mug or less of cefaclor per ml; the cefaclor disk did not. The cephalothin disk erred in correctly predicting susceptibility in only 20% of cefaclor-susceptible isolates of Enterobacter spp.; the cefaclor disk correctly predicted susceptibility for 70%. These results indicate the need for further evaluation of a separate cefaclor disk for use in susceptibility testing with this new cephalosporin.


In vitro response to chloramphenicol, tetracycline, ampicillin, gentamicin, and beta-lactamase production by halophilic Vibrios from human and environmental sources.

Isolates of Vibrio parahaemolyticus and V. alginolyticus from human and environmental sources were examined for antibiotic susceptibility by the methods of minimal inhibitory concentration (MIC) in broth and agar diffusion. These strains were found to be almost uniformly susceptible to chloramphenicol and tetracycline within attainable serum levels. The relationships of zone sizes to MICs for these two antimicrobial agents and ampicillin conformed essentially to those obtained by standard methods with gram-negative rods. Most strains were resistant to ampicillin and exhibited beta-lactamase activity, which accounted for this resistance. Nine of 30 V. alginolyticus strains from environmental sources were ampicillin resistant but did not produce measurable amounts of beta-lactamase. Three strains exhibited multiresistance to high concentrations of chloramphenicol, tetracycline, and ampicillin, which suggests the presence of plasmids. Although the great majority of vibrios appeared to be susceptible to gentamicin by agar diffusion, susceptibility could not be measured by MIC because the added NaCl, required for growth by the halophilic vibrios, diminished gentamicin activity.


Turbidimetric studies of growth inhibition of yeasts with three drugs: inquiry into inoculum-dependent susceptibility testing, time of onset of drug effect, and implications for current and newer methods.

Susceptibility testing with the broth-dilution visual end-point method is inoculum dependent with miconazole and 5-fluorocystosine, but not with amphotericin B. Turbidimetric measurements of yeast growth in the presence of antifungal drugs were therefore performed. With miconazole and 5-fluorocytosine, over the range of concentrations studied, growth occurred until a plateau phase was reached. With drug present prior to log phase growth, a delayed onset of effect was noted which was proportional to the generation time of the organism. With amphotericin B, in contrast, there was sharp transition with increasing drug concentration from no inhibition to complete arrest of growth, and no relation of onset of effect to generation time. These findings provide a possible explanation of inoculum dependence; i.e., at higher inocula, partially inhibited but growing yeasts become visible at higher drug concentrations. Supporting evidence derives from observations with different starting inocula, varying time of reading end points, and other methods of studying growth inhibition. The delay in miconazole and 5-fluorocytosine effect described suggests that rapid methods of susceptibility testing should be utilized with cultures already in log phase.


Amphotericin B pharmacokinetics in humans.

The pharmacokinetics of amphotericin B were studied in two patients at the conclusion of long-term therapy for disseminated histoplasmosis. The distribution kinetics of this drug were adequately described by a three-compartment mamillary model with a total distribution volume averaging 4 liters/kg. The elimination phase half-life of amphotericin B was approximately 15 days, reflecting slow release of amphotericin B from a peripheral compartment. In accordance with previous reports, renal excretion accounted for only 3% of total amphotericin B elimination. The pharmacokinetic model for one of the patients also was used to compare the simulated amphotericin B serum levels that would be expected if initial therapy followed two recommended regimens.


Isolation of beta-lactamase from a penicillin-susceptible strain of Staphylococcus aureus.

It is generally accepted that strains of Staphylococcus aureus which are susceptible to penicillin G do not produce beta-lactamase. However, we have found that such a strain susceptible to 0.06 mug of penicillin per ml and 0.56 mug of methicillin per ml produces beta-lactamase(s) which hydrolyzes penicillin G, methicillin, 6-aminopenicillanic acid, and probably cephaloridine. The enzyme which is found only during very early log phase of the growth cycle is not inducible either by penicillin or methicillin and is cell bound and liberated only by disruption of the cell. The rate of enzymatic hydrolysis of methicillin was 60% that of benzylpenicillin. This finding suggests that the elaboration per se of beta-lactamase does not necessarily afford resistance to penicillin in this gram-positive-producing cell.


Evaluation of miconazole therapy in experimental disseminated candidiasis in laboratory rats.

Miconazole, a broad-spectrum antimycotic agent with some antibacterial activity, has recently become available for experimental parenteral use in the United States. Its efficacy as an anticandidal drug was tested in adult Wistar rats. A previously established infectious dose of 5 x 10(6)Candida albicans was intravenously injected into 250- to 300-g animals. This dose was fatal to 95% (20/21) of placebo-treated control animals within the 2-week postinfection observation period. Only 4% (2/53) of rats receiving intramuscular miconazole treatment died. Miconazole therapy in Candida-infected rats at a dosage of 50 mg/kg per day resulted in 85% survival, and, although 100 mg/kg per day was 100% efficacious, it was a relatively large volume to give intramuscularly to a rat. Therefore, 75 mg/kg per day was used as a therapeutic dose, and it gave favorable results in this study. Histological examination of all placebo-treated animals revealed C. albicans and a marked inflammatory response in the kidney, brain, and heart. C. albicans organisms were observed to be very prominent in these tissues by using the Gomori methenamine silver stain, and were cultured from these organs. Miconazole-treated rats that were killed after surviving the 2-week observation period had minimal histopathological changes, and the organisms present did not exhibit the same staining characteristics, nor were they isolated like those in the placebo-treated group. Miconazole appears to be an efficacious drug for parenteral therapy, as demonstrated in this reproducible model of disseminated candidiasis in laboratory rats, and more extensive experimental studies are indicated.


Mechanism of transferable resistance to chloramphenicol in Haemophilus parainfluenzae.

A clinical isolate of Haemophilus parainfluenzae resistant to chloramphenicol and tetracycline transferred both cam and tet determinants to Escherichia coli K-12 during mixed cultivation on solid media irrespective of the selection employed. The doubly resistant transconjugant was found to contain levels of the enzyme chloramphenicol acetyltransferase (CAT) comparable to those found in R plasmid-bearing chloramphenicol-resistant enteric bacteria. Purification of CAT from the transconjugant was achieved by affinity chromatography, and the electrophoretically homogeneous protein was compared with previously characterized CAT variants specified by R plasmids. Although the CAT associated with cam from H. parainfluenzae was found to be distinct from the three types described previously, its N-terminal peptide amino acid sequence was identical with that determined for a type II CAT. Attempts to demonstrate covalently closed circular deoxyribonucleic acid in the H. parainfluenzae donor and the E. coli transconjugant were unsuccessful. The cam and tet determinants were nontransmissible from E. coli but could be cotransferred following the introduction of a suitable conjugative plasmid.


Acute toxicity of 12,13-epoxytrichothecenes in one-day-old broiler chicks.

Acute toxic effects of several 12,13-epoxytrichothecenes were investigated in 1-day-old broiler chicks by single oral doses. The 7-day median lethal dose values of purified 8-acetylneosolaniol, diacetoxyscirpenol, T-2 toxin, HT-2 toxin, neosolaniol, deacetyl-HT-2 toxin, and T-2 tetraol were 3.22 +/- 0.26, 3.82 +/- 0.40, 4.97 +/- 0.44, 7.22 +/- 0.39, 24.87 +/- 2.64, 30.18 +/- 7.53 (incomplete value), and 33.79 +/- 5.39 mg/kg of body weight, respectively. Deaths occurred during the 8- to 60-h period after dosing with the tested trichothecenes. Within 4 to 10 h after dosing, inappetence, asthenia, diarrhea, and coma generally developed. Sublethal doses of each toxin decreased feed consumption and weight gain proportionally with the amounts of toxins administered. These results demonstrate that the toxic potency of 12,13-epoxytrichothecenes varies depending on the modification of side chains in the molecule.


Molds on vegetables at the time of harvest.

The mean numbers of colony-forming units of molds present on vegetables at the time of harvest were in the range of 4.2 X 10(3) to 6.7 X 10(3)/g for all vegetables except cucurbits and asparagus. The numbers were not influenced by cultivars within species, duration of the growing season, distant separation of the growing fields, or elevation above ground. Numbers increased with rainfall during either of 3 days before harvest and decreased when the mean daily temperature exceeded 24 degrees C. The most frequently isolated fungi were Aureobasidium pullulans, Fusarium species, Alternaria tenuis, Epicoccum nigrum, Mucor species, Chaetomium fimeti, Rhizopus nigricans, and Phoma species, in decreasing order. All other molds comprised less than 2% of the isolates. Aspergilli and penicillia occurred sporadically and in low numbers. Fusarium species were dominant on cucurbits.


Nonsporing, anaerobic, gram-positive rods in saliva and the gingival crevice of humans.

Quantitative and qualitative examination of anaerobically isolated flora of the gingival crevice and saliva was carried out. It was found that half the organisms were anaerobes and that there were twice as many gram-positive organisms as there were gram-negative ones. Rods were predominant in the gingival crevice (60.5%) and cocci in saliva (69.1%). Of the total organisms, nonsporing, gram-positive anaerobic rods accounted for 24% in the gingival crevice and 9.7% in saliva. These organisms were characterized on the basis of the type of fatty acids produced from glucose and various biochemical reactions. They belonged to the following genera: Actinomyces, Propionibacterium, Arachnia, Lactobacillus, Eubacterium, and Bifidobacterium. Bifidobacteria were present only in saliva. Although members of the other genera were present both in the gingival crevice and saliva, there were considerable differences in the proportion of any particular organism (in relation to the total anaerobic viable count) between the two sites. The result of this study also indicates a greater than previously appreciated level of Propionibacterium and Arachnia in the human mouth.


Bacterial oxidation of polyethylene glycol.

The metabolism of polyethylene glycol (PEG) was investigated with a synergistic, mixed culture of Flavobacterium and Pseudomonas species, which are individually unable to utilize PEGs. The PEG dehydrogenase linked with 2,6-dichlorophenolindophenol was found in the particulate fraction of sonic extracts and catalyzed the formation of a 2,4-dinitrophenylhydrazine-positive compound, possibly an an aldehyde. The enzyme has a wide substrate specificity towards PEGs: from diethylene glycol to PEG 20,000 Km values for tetraethylene glycol (TEG), PEG 400, and PEG 6,000 were 11, 1.7, and 15 mM, respectively. The metabolic products formed from TEG by intact cells were isolated and identified by combined gas chromatography-mass spectrometry as triethylene glycol and TEG-monocarboxylic acid plus small amounts of TEG-dicarboxylic acid, diethylene glycol, and ethylene glycol. From these enzymatic and analytical data, the following metabolic pathway was proposed for PEG: HO(CH2CH2O)nCH2CH2OH leads to HO(CH2CH2O)nCH2CHO leads to HO(CH2CH2O)nCH2COOH leads to HO(CH2CH2O)n-1CH2CH2OH.


Biocidal properties of anti-icing additives for aircraft fuels.

The biocidal and biostatic activities of seven glycol monoalkyl ether compounds were evaluated as part of an effort to find an improved anti-icing additive for jet aircraft fuel. Typical fuel contaminants, Cladosporium resinae, Gliomastix sp., Candida sp., Pseudomonas aeruginosa, and a mixed culture containing sulfate-reducing bacteria were used as assay organisms. Studies were carried out over 3 to 4 months in two-phase systems containing jet fuel and aqueous media. Diethylene glycol monomethyl ether, triethylene glycol monomethyl ether, triethylene glycol monoethyl ether, and 2-methoxyethanol were generally biocidal in aqueous concentrations of 10 to 17% for all organisms except Gliomastix, which required 25% or more. 2-Ethoxyethanol, 2-propoxyethanol, and 2-butoxyethanol were biocidal at progressively lower concentrations down to 1 to 2% for 2-butoxyethanol. The enhanced antimicrobial activity of these three compounds was attributed to cytoplasmic membrane damage because of the correlation between surface tension measurements and lytic activity with P. aeruginosa cells. The mechanism of action of the less active compounds appeared to be due to osmotic (dehydrating) effects. When all requirements are taken into account, diethylene glycol monomethyl ether appears to be the most promising replacement for the currently used additive, 2-methoxyethanol.


Effects of low concentrations of bisulfite-sulfite and nitrite on microorganisms.

A wide range of microorganisms was tested to determine their sensitivity to low concentrations of bisulfite-sulfite and nitrite, solubility products of SO2 and NO2, respectively. Photosynthesis by blue-green algae (cyanobacteria) was more strongly inhibited by 0.1 mM bisulfite-sulfite and 1 mM nitrite at pH 6.0 than photosynthesis by eucaryotic algae and respiration of bacteria, fungi, and protozoa. At pH 7.7, blue-green algae were still more sensitive to bisulfite-sulfite and nitrite than eucaryotic algae, but the toxicity of bisulfite-sulfite and nitrite decreased as the pH increased. Photosynthesis by Anabaena flos-aquae at pH 6.0 was inhibited 25% by a bisulfite-sulfite concentration of 10 micrometer and 15% by a nitrite concentration of 50 micrometer. Photosynthesis by the blue-green alga, Lyngbya sp., was not exceptionally sensitive to chlorate and thiosulfate. Acetylene-reducing activity of Beijerinckia indica was completely inhibited by 0.1 mM bisulfite-sulfite at pH 4.0, the suppression being decreased with increasing pH.


Response of terrestrial microorganisms to a simulated Martian environment.

Soil samples from Cape Canaveral were subjected to a simulated Martian environment and assayed periodically over 45 days to determine the effect of various environmental parameters on bacterial populations. The simulated environment was based on the most recent available data, prior to the Viking spacecraft, describing Martian conditions and consisted of a pressure of 7 millibars, an atmosphere of 99.9% CO2 and 0.1% O2, a freeze-thaw cycle of -65 degrees C for 16 h and 24 degrees C for 8 h, and variable moisture and nutrients. Reduced pressure had a significant effect, reducing growth under these conditions. Slight variations in gaseous composition of the simulated atmosphere had negligible effect on growth. The freeze-thaw cycle did not inhibit growth but did result in a slower rate of decline after growth had occurred. Dry samples exhibited no change during the 45-day experiment, indicating that the simulated Martian environment was not toxic to bacterial populations. Psychotrophic organisms responded more favorably to this environment than mesophiles, although both types exhibited increases of approximately 3 logs in 7 to 14 days when moisture and nutrients were available.


Bacteria isolated from the duodenum, ileum, and cecum of young chicks.

Facultatively anaerobic and strictly anaerobic bacteria colonizing the intestinal tracts of 14-day-old chicks fed a corn-based diet were enumerated, isolated, and identified. Colony counts from anaerobic roll tubes (rumen fluid medium) or aerobic plates (brain heart infusion agar) recovered from homogenates of the duodenum, upper and lower ileum, and cecum varied appreciably among samples from individual birds. Anaerobic and aerobic counts from the duodenum and ileum were similar. Anaerobic counts were highest from the cecum (0.7 X 10(11) to 1.6 X 10(11)/g of dry tissue) and exceeded aerobic plate counts by a factor of at least 10(2). Facultatively anaerobic groups (Streptococcus, Staphylococcus, Lactobacillus, and Escherichia coli) comprised the predominant flora of the duodenum and ileum, although large numbers of anaerobes (9 to 39% of the small intestine isolates), represented by species of Eubacterium, Propionibacterium, Clostridium, Gemmiger, and Fusobacterium, were also recovered. Strict anaerobes (anaerobic gram-positive cocci, Eubacterium, Clostridium Gemmiger, Fusobacterium, and Bacteriodes) made up nearly the entire microbial population of the cecum. Scanning electron microscopy of the intestinal epithelia of chicks revealed populations of microbes on the duodenal, ileal, and cecal mucosal surfaces.


Interactions between the diatom Thallasiosira pseudonanna and an associated pseudomonad in a mariculture system.

The marine diatom Thallasiosira pseudonanna (3H) and several bacteria associated with it were isolated from batch cultures at the University of Delaware mariculture facility. The interaction between the algae and each of the bacteria was investigated. One of the isolates, T827/2B (Pseudomonas sp.), was incapable of surviving in f/2 culture medium unless the algae were present. When the algae and T827/2B were grown together in the f/2 medium, the bacterial growth was stimulated and the algal growth was inhibited. Bacterial filtrate had a similar effect on the algae, indicating that the bacterial effect is an indirect one most likely resulting from the excretion of a harmful compound into the medium. Preliminary characterization of the material excreted by the bacteria indicates that it s proteinaceous in nature. The interactions observed does not fit into any single category of interactions but can be explained as a combination of competition and indirect parasitism.


Catabolism of 2,4,5-trimethyoxybenzoic acid and 3-methoxycrotonic acid.

4-Methoxygentisic acid was an intermediate formed when Arthrobacter degraded, 2,4,5-trimethoxybenzoic acid. Isolates of Pseudomonas and Arthrobacter from soil grew at the expense of 3-methoxycrotonic acid. Evidence is presented that enzymatic hydration, with elimination of methanol, accounted for replacement of the methoxyl group of 3-methoxycrotonic acid and also of one methoxyl group of 2,4,5-trimethoxybenzoic acid.


Dermatologic manifestations of the hypereosinophilic syndrome.

We report the histopathologic and dermatologic manifestations of eight patients with hypereosinophilic syndrome (HES). Skin lesions occurred in eight patients (53%) in a group of 15 patients with HES, and were generally of two types: (1) erythematous pruritic papules and nodules, or (2) urticaria and angioedema. As HES was treated with appropriate therapy, the skin lesions improved. Skin eruption may be the only manifestation of disease in otherwise asymptomatic patients with HES.


Experimental cutaneous candidiasis in rodents; II. Role of the stratum corneum barrier and serum complement as a mediator of a protective infalmmatory response.

Of six species of Candida applied epicutaneously to rodents, only C albicans and C stellatoidea penetrate the stratum corneum and produce inflammation. The role of the stratum corneum and produce inflammation. The role of the stratum corneum in experimental murine Candida infections was studied, therefore, by intraepidermal injection of blastospores in mice that received a prior injection of staphylococcal epidermolysin. All six species caused accumulation of neutrophils if placed within an intraepidermal cleft in contact with viable epidermis. The role of serum complement in cutaneous candidiasis was also studied in vivo in rodents depleted of complement with cobra venom factor or deficient in the fifth component of complement. These animals failed to develop neutrophilic inflammatory responses to the six Candida species tested in contrast to control animals. Candida albicans, C stellatoidea, and C tropicalis developed extensive hyphal proliferation with invasion of the entire cutis and subcutis in these animals. The stratum corneum provides an effective barrier to some, but not all Candida species. When this barrier is penetrated, complement mediates an acute neutrophilic pustular response that resticts Candida proliferation and prevents deep invasion of tissue.


Neutrophil chemotaxis in patients with atopic dermatitis without infection.

Atopic dermatitis has been associated with recurrent infection and impaired neutrophil chemotaxis in some patients. In order to determine if dermatitis per se could decrease polymorphonuclear leukocyte (PMN) chemotaxis, we investigated chemotaxis in 13 patients with atopic dermatitis and no clinical or historical evidence of recurrent or severe infections. Most patients had extensive, but mild, disease. Leukocyte chemotaxis was measured by the Boyden chamber and agarose techniques; There was no difference between patient and control neutrophil chemoatactic activity. These findings suggest that atopic dermatitis is not ordinarily associated with impaired PMN chemotaxis in the absence of generalized erythroderma or increased susceptibility to infection.


Phototoxicity to a sunscreen ingredient. Padimate A.

Para-aminobenzoic acid and certain of its esters are widely used in sunscreens. We found that one of these, amyl paradimethylaminobenzoate (padimate A) was capable of provoking phototoxic reactions; With ultraviolet A (UV-A) dosages of about 30 joules/sq cm, a reaction grossly resembling sunburn developed in most subjects. The dominant histological feature was vacuolar degeneration of the epidermis without sunburn cells. Proprietary sunscreens containing padimate A were also shown to produce a similar reaction. Our explanation for the paradox of a sunscreen that promotes "sunburn" is that, as affected users have concluded, the product was ineffective. The similarity between sunburn and a phototoxic response has delayed recognition of this adverse effect until now.


Migraine and systemic scleroderma.

Scleroderma with typical migraine headaches occurred in 16 well-documented cases observed over a 25-year period. Although the number of cases is within the expected range of coincidence of both diseases, in 13 of the 16 patients the scleroderma developed after 15 years or more of therapy with ergot or methysergide preparations. Eleven of the 13 patients had Raynaud's vasospastic phenomenon as part of their systemic scleroderma. The vascular pathology of scleroderma, Raynaud's phenomenon, and ergotism is similar enough to suggest caution in the administration of these drugs to patients with migraine and extra caution in observing for signs of Raynaud's phenomenon or early vascular scleroderma.


The Shulman syndrome.

The Shulman syndrome is a symptom complex recently described in the rheumatology literature that is characterized by eosinophilia, hypergammaglobulinemia, and a diffuse scleroderma-like process of the extremities. The onset of illness has been associated with a period of unusual physical exertion. The condition seems to respond to corticosteroid therapy for systemic effect.


Primary inoculation tuberculosis of the skin. Prosector's paronychia,.

Subsequent to an autopsy of a tuberculotic cadaver, a pathology resident presented with a painless paronychia and axillary adenopathy after surgical incision and broad-spectrum antibiotics had failed to improve his condition. Demonstration by culture of Mycobacterium tuberculosis var hominis, positive smears, and findings of acid-fast organisms in a skin biopsy specimen proved the diagnosis of tuberculosis. Conversion of a previously negative skin test permitted the diagnosis of primary inoculation tuberculosis of the skin. The disease responded well to treatment with isoniazid, rifampin, and pyridoxine hydrochloride.


Carcinoid in an umbilical nodule.

An umbilical nodule may be an early or late sign of metastasis from an internal location. To our knowledge, we are reporting the first case of carcinoid occuring as an umbilical mass. The occurrence in our patient of idiopathic hyperparathyroidism, diabetes mellitus, and carcinoid suggests the diagnosis of multiple endocrine adenomatosis, type I, which may result from a developmental defect in the amine and amine precursor uptake and decarboxylation cell system.


Atypical purpura fulminans with benign monoclonal gammopathy.

A 67-year-old woman with a history of thrombophlebitis had been taking warfarin sodium for 1 1/2 years when she developed multiple skin lesions resembling warfarin-induced skin necrosis or purpura fulminans. Despite discontinuing the warfarin and administering prednisone, the lesions increased in size. Disseminated intravascular coagulation (DIC) was found and resolved with heparin sodium therapy, and her skin lesions healed. This patient was believed to have an atypical form of purpura fulminans rather than warfarin-induced skin necrosis because of the duration of warfarin therapy and the dramatic resolution with heparin. A monoclonal (IgG) gammopathy was found, which stabilized as the skin lesions resolved, and fulfilled the criteria for a benign (asymptomatic) monoclonal gammopathy.


Necrotizing fasciitis.

Two patients had limited necrotizing fascilitis. The morbidity and mortality from this infectious necrotizing process of the superficial fascia have not changed significantly since its initial description in 1924. The characteristic clinical findings of necrotizing fascilitis makes early recognition possible. Within 24 to 48 hours, redness, pain, and edema rapidly progress to central patches of dusky blue discoloration, with or without serosanguineous blisters. By the fourth or fifth day, these purple areas become gangrenous. Although necrotizing fascilities originally was associated exclusively with beta-hemolytic Streptococcus, recent cases have shown a variety of bacteria. The essential treatment remains wide local surgical débridement.


Multiple cutaneous metastases of a scapular chondrosarcoma.

The onset of metastatic chondrosarcoma in a young woman was heralded by the appearance of multiple firm, tender, cutaneous nodules two years after the primary tumor in the left scapula had been resected. Chondrosarcoma rarely metastasizes to the skin, but when it does, it may have an identical histological appearance to a cartilaginous tumor of the skin, an entity that is generally considered clinically benign. Although it is very unlikely that an occult chondrosarcoma will be first manifested clinically by a solitary cutaneous metastasis, the abrupt appearance of multiple cutaneous cartilaginous lesions would seem to warrant an investigation for primary chondrosarcoma.


Aneurysm of the superficial temporal artery.

An aneurysm of the superficial temporal artery is a rare lesion, which should be suspected after blunt trauma to the forehead that is followed by the appearance of a pulsatile cystic lesion in the region of the superficial temporal artery. Treatment by excision of the aneurysm with ligation of the afferent and efferent arteries is curative. As this lesion may be mistaken clinically for an epidermal inclusion cyst, aneurysm should be included in the differential diagnosis prior to therapy.


Aspiration metastases from basal cell carcinoma: the 92nd known case.

Was aspiration a cause of lung metastases from basal cell carcinoma? We compared our case to prior reported cases with metastases to the lung attributable to aspiration and considered a prior experimental model. We are convinced we have another case of aspiration metastases from basal cell carcinoma, and hereby report "the 92nd known case."


Hereditary painful callosities.

An autosomal dominant genodermatosis that is characterized by painful callosities develops over pressure points. Histologically, these lesions are similar to epidermal nevi.


Human infection with Dirofilaria.

Human infection with Dirofilaria is rare. Fewer than 100 cases have been reported in the world's literature. Among the cases reported in the United States, most of the patients have been from Florida and Louisiana. The majority of the patients had a single lesion that involved either the skin or the lung. The case presented here is unusual because the patient had two skin lesions, and because the condition occurred in a patient who lived in the North-Central portion of the United States (Upper Michigan).


Histoplasmosis due to Histoplasma capsulatum var duboisii in a Canadian immigrant.

Histoplasmosis due to Histoplasma capsulatum var duboisii developed in a Canadian immigrant one year after his entry into Canada. He had lived in Guinea for two years prior to immigration. Lymphatic infection characterized the course of his illness. The clinical and pathologic features of this disease's distinctive skin and bone manifestations are outlined. The causal agent's mycologic features are compared with those of H capsulatum var capsulatum. Treatment with amphotericin B was successful.


Dermatofibrosarcoma protuberans with lymph node and pulmonary metastases.

Dermatofibrosarcoma protuberans is a locally aggressive histiocytic tumor that, on rare occasions, may metastasize to regional lymph nodes or even to distant sites. We report a dermatofibrosarcoma protuberans with lymph node involvement in a 27-year-old woman. This tumor recurred repeatedly after local excisions, and ten years after the first resection, widespread pulmonary metastases developed in the patient and she died four years later. More than 400 patients with dermatofibrosarcoma protuberans have been reported in the literature; including the present case, five of these patients had lymph node metastases, 17 patients had hematogenous spread, and three had both lymphatic and blood-borne metastases.


Nasopharyngeal cardcinoma associated with long-term arsenic ingestion.

A nasopharyngeal carcinoma occurred in a 41-year-old white woman who had received Fowler's solution (potassium arsenite) almost yearly for more than 20 years for the treatment of psoriasis. Palmar and plantar keratoses were present. Because of the rarity of this malignant neoplasm in white people, a relationship with arsenic ingestion is suggested.


Psoralen-UVA-treated psoriatic lesions. Ultrastructural changes.

Psoralen-ultraviolet light (PUVA)-treated psoriatic lesions were studied for ultrastructural changes. In early stages of treatment, sunburn cells in the epidermis and bizarre giant cells in the dermis were more frequently observed. When clinical improvement was apparent, these changes had subsided. Dermal abnormality in long-term therapy consisted of a thick perivascular coat of amorphous substance. No abnormality was found in the epidermal keratinocytes in long-term therapy, except a clustering and giant cell formation of melanocytes, a heavy melanization of keratinocytes, and hyperkeratosis. Low-dose initiation and slow increment of both 8-methoxypsoralen and UVA is probably a reasonable regimen for benign dermatoses such as psoriasis because it will allow enough time for the skin to become more protected, while the therapeutic results are as satisfactory as in a high-dose schedule.


Variably occlusive tape systems and the mitotic activity of stripped human epidermis. Effects with and without hydrocortisone.

This study elaborates on the effect of occlusive, partially occlusive, and nonocclusive tape systems containing hydrocoritsone on human epidermal mitotic activity that has been increased by tape stripping. The experimental variables included tape delivery systems affording total, partial (50%), or no occlusion to normal human skin. The test corticosteroid was hydrocortisone at a dose range of 1, 4, and 20 microgram/sq cm. Utilizing demecolcine cream, biopsy specimens, were taken and mitotic figures determined. Results suggest that potent antimitotic effects occur equally with semiocclusive and nonocclusive tapes containing hydrocortisone as with total occlusive tapes. Verification of the practicality of this in clinical use will depend on appropriate clinical trials in diseased states.


Origin of familial malignant melanomas from heritable melanocytic lesions. 'The B-K mole syndrome'.

Distinctive melanocytic moles are described in 37 patients from six melanoma families. Among the family members examined by the authors, 15 of 17 patients with melanoma and 22 of 41 nonmelanoma relatives had the unique moles. The clinical and histological features of these moles have been designated the "B-K mole syndrome." The clinical features of the syndrome include the presence of less than 10 to greater than 100 moles prominent of the upper trunk and extremities, and variability of mole size (5 mm to 15 mm), outline, and color combination. Histologically, B-K moles show atypical melanocytic hyperplasia, lymphocytic infiltration, delicate fibroplasia, and new blood vessels that occur within a compound nevus or de novo. The transformation of two B-K moles into malignant melanomas was documented photographically.


Scalpel excision of basal cell carcinomas.

A total of 468 coded, histologically proved basal cell carcinomas were excised from 446 patients in the Skin and Cancer Unit of New York University Medical Center from 1955 to 1967. The five-year cumulative recurrence rate was 6.8%. The highest recurrence rates, in areas in which sufficient data were available, were for the periocular regions, the scalp, and the nose and paranasal areas. Following re-treatment of recurrences, 464 of the 468 lesions (99.1%) were cured at the time of the most recent examination. After the second postoperative year, at least 70% of results were recorded as cosmetically good or excellent at the time of last follow-up. The most common complication was hypertrophic scars. There was a tendency for increasing incidence of such scars with increasing diameters of the lesions.


Multiple hamartoma syndrome (Cowden's disease).

The four male patients with multiple hamartoma syndrome (Cowden's disease) in this report, have most of the previously reported findings associated with this syndrome and several important unreported findings that include multiple cutaneous trichilemmomas, cafe-au-lait spots, cutaneous squamous cell carcinoma, pathologic fracture, craniomegaly, probable malignant lung tumor, retinal glioma, drusens of the optic disk and retina, pseudotumor cerebri, mediastinal mass, and multiple small papillomatous lesions of the esophagus, stomach, and duodenum.


The epidemiology of scabies in Denmark, 1900 to 1975.

Denmark is the only country in which scabies has been reported for many decades. The present study is based on 850,629 cases reported between 1900 and 1975. The incidence of scabies showed pronounced peaks around 1918 and 1945. Since the end of the 1960s, a new increase in incidence has been observed. The rates were high and rather uniform among infants, children, and young adults. Before puberty, the rate for girls was on an average 1.4 times higher than for boys. Scabies showed the same incidence in the capital as in the provinces, and marked seasonal variations occurred, with a winter maximum and a summer minimum. No single factor could be identified to explain the cyclic occurrence in time, the sex and age pattern, and the seasonal variation. These patterns probably have a multifactorial genesis!


Tumbleweed dermatitis.

Russian thistle (Salsola kali), the most common plant referred to as "tumbleweed" in the western United States, can cause a dermatitis in persons who come into direct contract with it. Tests were conducted to determine the mechanism of this dermatitis. Mechanical contact with plant branches, as well as scratch, patch, and photopatch tests with Russian thistle extract and scratch tests with 1.5% potassium nitrate, a plant constituent, were employed. These tests, along with transparent adhesive tape preparations and a skin biopsy, showed that in nonsensitized persons, dermatitis was due only to mechanical irritation of plant floral bracts. In sensitized individuals, Russian thistle floral bracts pierced the skin and stimulated an urticarial reaction.


Keratosis follicularis spinulosa decalvans. An infant with failure to thrive, deafness, and recurrent infections.

A 10-month-old male infant had keratosis follicularis spinulosa decalvans, an X-linked dominant disorder. His cutaneous abnormalities consisted of generalized hyperkeratosis, spiny follicular papular lesions, universal alopecia, and hypoplastic nails. Ocular changes characteristic of the disease were also present. Unusual findings included deafness, failure to thrive, predisposition to bacterial infections without demonstrable immune defect, and transient hepatomegaly with abnormal liver function studies.


Hyperimmunoglobulin E syndrome.

A 24-year old woman had the major features of the hyperimmunoglobulin E syndrome: recurrent staphylococcal skin infections (from the age of 6 months), an extremely elevated serum immunoglobulin E level (25,000 units/ml), and defective neutrophil chemotaxis. This patient also had peripheral blood eosinophilia and cutaneous candidiasis. There was a family history of asthma, but the patient herself did not have a history of asthma or hay fever, and, on examination, had no evidence of atopic dermatitis. The patient has not had any systemic infections. Results of the skin biopsy showed dermal edema and a perivascular infiltrate with eosinophils and an increased number of mast cells. The clinical spectrum of the hyperimmunoglobulin E syndrome may include atopic dermatitis, mucocutaneous candidiasis, systemic infections, and/or the features of Job's syndrome.


Unilateral segmental hyperhidrosis. Response to 20% aluminum chloride solution and plastic wrap.

A young woman had unilateral dermatomal hyperhidrosis documented by a starch-iodine technique. Evaluation failed to reveal any associated causative conditions. She was treated with 20% aluminum chloride hexahydrate solution in absolute alcohol (Drysol) with a favorable response. With recurrent use, however, she developed miliaria following exertion. Aluminum chloride hexahydrate was shown to be an effective agent to treat this unusual condition, but miliaria with exertion secondary to its use may be a limiting factor.


Universal acquired melanosis. The carbon baby.

A Mexican child was born white and progressively became black. At the age of 21 months, the whole integument was deep black in the absence of other alterations. Electron microscopy showed a Negroid pattern in the epidermal melanosomes. Among the different forms of progressive mucocutaneous pigmentations previously described in the literature, we were unable to find a similar case.


Aggressive basal cell carcinoma of the scalp.

Three examples of an unusually aggressive form of basal cell carcinoma in the skin of the scalp were treated surgically. The extent of each tumor was verified with gross and microscopic examination. The tumors invaded fat, muscle, fascia, and bone. Dural involvement was seen in one case. Light microscopy showed a marked variation in growth patterns and cytologic types from one portion of the tumor to another. Characteristics included a diffusely infiltrating pattern with a fibrotic stromal response, rare intraepidermal tumor nests, formation of occasional duct-like structures, poor cellular cohesion with single-life invasion through dermal collagen, perineural invasion, and pleomorphism with varying nuclear cytoplasmic ratios. Basaloid populations with peripheral palisading were seen in each tumor. These malignancies may be representative of an unusual basal cell carcinoma variant unique to the scalp.


Essential IgG cryoglobulinemia with purpura and cold urticaria.

An 80-year-old woman with essential cryoglobulinemia developed recurrent, widespread, purpuric lesions with superficial skin ulcers and cold urticaria. No disorders of other organ systems were recognized. Attempts to transfer the cold sensitivity passively by serum and isolated cryoprecipitate of the patient were successful. Immunochemical studies showed that the cryoglobulin was composed of IgG only. It was suggested that the cryoprecipitate might not be due to immune complex formation in this case.


Effect of children's and parents' smoking on respiratory symptoms.

It has been suggested that the apparent relationship between children's cigarette smoking and their respiratory symptoms could be explained by the effect of parents' smoking upon both child's smoking and symptoms. This was investigated in a study of 6000 Derbyshire schoolchildren. Children who smoked regularly were more likely than nonsmokers to report cough first thing in the morning, cough at other times during the day or at night, and breathlessness. Children whose parents smoked were also more likely to report these symptoms than were the children of nonsmokers. Both the child's and parents' smoking were independently related to the child's respiratory symptoms. Morning cough was less prevalent than cough at other times during the day or at night, but the relationship between the child's smoking and morning cough was much closer than its relationship to cough at other times. The relationship between parents' smoking and the child's symptoms was similar for each symptom.


Computed tomography in diagnosis of abdominal masses in infancy and childhood. Comparison with excretory urography.

Computed tomography (CT) of the abdomen and pelvis was performed in 26 instances of suspected mass in 24 infants and children. The information obtained was compared to that of standard abdominal radiography and excretory urography (IVP). Results were analyzed prospectively. CT was able to detect and define masses more precisely than abdominal radiography and IVP. The information obtained by CT, in a single noninvasive examination emitting minimal ionising radiation, seems comparable to that offered by a combination of multiple radiological and other imaging procedures. It is conceivable that with accumulating experience and further technological improvement CT may become an excellent screening procedure in the investigation of abdominal and pelvic masses. The high cost of CT scanning may be offset by the benefits cited.


Management of congenital adrenal hyperplasia. Urinary steroid estimations--review of their value.

A retrospective study was made of 16 children with 21-hydroxylase-deficient congenital adrenal hyperplasia of the salt-losing variety, who were treated with fludrocortisone and prednisone and were in good health during the period under review. The height velocity of the children was subnormal, height achievement was poor, and their bone ages retarded. Urinary 17-oxosteroid and pregnanetriol excretion were used to monitor the therapy of the children and these data have been related to growth velocities. In spite of urinary steroid figures in excess of those published as desirable for monitoring therapy, the children failed to grow properly, probably as a result of glucocorticoid overdosage. Published urinary steroid criteria are considered too strict and in order to achieve them one would need to give unnecessarily high doses of steroid. Regular measurement of height velocity and skeletal maturation rate are better indicators of therapeutic control and should lead to more satisfactory growth and ultimate height.


Serial determinations of oxygen profiles in infants with respiratory distress.

Serial oxygen profiles were determined for 20 newborn infants by measuring arterial tensions at low (20--40%), intermediate (60--80%), and high (95--100%) levels of inspired oxygen. These points were plotted on a graph which estimated the percentage of venous admixture at any particular level of inspired oxygen. The infants' oxygen profiles were then determined. As much as 25% of venous admixture could be attributed to the presence of diffusion and distribution abnormalities in infants with hyaline membrane disease. A substantial number of infants showed increased shunting at high levels of oxygen, even in the presence of continuous distending airway pressure. It is hypothesised that a rising shunt is due to complete absorption of gas in poorly ventilated alveoli at high concentrations of inspired oxygen, resulting in the presence of atelectasis and redistribution of blood to poorly ventilated areas.


Occurrence of circulating immune complexes in beta-thalassaemia major.

The presence of circulating soluble immune complexes and the level of complement were investigated in sera from 21 patients with beta-thalassaemia major, including both splenectomised and nonsplenectomised patients. A high level of immune complexes was found in half of these cases. Reduced complement levels were seen less frequently. There was no correlation between the presence of circulating immune complexes, decreased complement levels, and thpresence or absence of the spleen. The level of immune complexes increased with the age ofthe individual, i.e. with the duration of the disease.


Cows' milk protein-sensitive enteropathy. An important factor in prolonging diarrhoea of acute infective enteritis in early infancy.

The possible role of cows' milk protein in prolonging diarrhoea in very young infants with acute infective enteritis was studied in 14 infants, 9 under the age of 2 months and 5 older than 6 months. Bacterial pathogens were isolated from the stools of 4 infants from the younger age group. After appropriate initial treatment the infants were maintained on a cows' milk protein-free formula. 6 weeks later jejunal biopsies were performed before and 24 hours after challenge with a low lactose cows' milk protein formula. The immunoglobulin and complement levels in the serum and duodenal juice were also estimated at these times. Attempts to isolate bacterial and viral pathogens in stools were again made in all patients. The 5 older infants clinically tolerated cows' milk protein and their pre- and postchallenge jejunal biopsies were within normal limits. However, significant histological changes were observed in the postchallenge jejunal biopsies of all 9 infants under 2 months of age. In addition, 5 of these infants developed diarrhoea. This suggests that the jejunal mucosa of very young infants previously fed a cows' milk protein-based formula and who contract infective enteritis suffers damage when rechallenged with cows' milk protein.


Structure of periadrenal brown fat in childhood in both expected and cot deaths.

A quantitative study was carried out of the fat cells of the hilar pannicle of the adrenal in 150 infants comprising 60 hospital deaths, 2 accidental deaths, and 88 cot deaths. The cells were rated in categories of fat vacuolation. For a period of up to 8 weeks after birth there is an apparent depletion in the number and size of overt fat vacuoles in the cell and from this time on there is a progressive change to monolocular fat cells. The postnatal discharge of fat from the cell in the pannicle seems to be reduced in some children presenting as unexpectec death in infancy.


Aortic thrombosis in the newborn period.

Three cases are reported in which thrombi were found in the aorta at postmortem. In each case the thrombus had originated within the ductus arteriosus. We believe that in recent years the attention paid to the presence of indwelling cannulae as a cause of embolic phenomena in the newborn period has led to a reduction in emphasis on the importance of the ductus in this field. We think that the ductus should still be regarded as an important source of some emboli.


Effect of practical timing of dosage on theophylline blood levels in asthmatic children treated with choline theophyllinate.

Two dosage schedules, 8 mg/kg per dose daily and 10 mg/kg per dose tds of choline theophyllinate were evaluated in asthmatic children. The times of the doses were considered the most practical for use outside hospital. Theophylline levels were measured 2 hours after each dose and were satisfactory in both schedules. The levels before the first dose of the day were, however, unsatisfactory. We emphasis the desirability of measuring blood levels in any patient receiving a theophylline compound.


Computer system for recording and display of data from newborn infants with respiratory illnesses.

A computer system has been used for the recording and display of data from 277 infants with respiratory illnesses consecutively admitted to a neonatal intensive care unit during a period of 25 months. Improved efficiency of data handling was demonstrated, and the system proved valuable for teaching and research.


Effect of phototherapy on thermal environment of the newborn.

Oxygen consumption was studied in 40 newborn babies undergoing phototherapy for hyperbilirubinaemia, both when enclosed within an incubator or nursed in an open cot. Exposure to phototherapy caused a rise in temperature at the mattress surface. This could result in overheating a baby nursed in an incubator, but by contrast is likely only partially to compensate for the loss of insulation of an unclothed baby in an open cot.


Tubular duplication of the bowel. Use of technetium 99m pertechnetate in diagnosis.

Preoperative identification of tubular duplication of the bowel is possible by the use of technetium 99m pertechnetate if gastric mucosa is present within the duplicated bowel. A case of a 4-year-old boy with abdominal pain is described. The scan showed diffuse activity which increased in step with gastric activity.


Acute neonatal and benign citrullinaemia in one sibship.

Citrullinaemia was diagnosed in an infant who died at age 8 days. The clinical picture was of the disease in its acute neonatal form. A sib has a blood citrulline of 100 times normal and about 10% of normal argininosuccinic acid synthetase activity in cultured fibroblasts. Clinically he is normal with an IQ of 94 on the Wechsler Intelligence Scale for Children.


Fundamental voice frequence during normal and abnormal growth, and after androgen treatment.

A simple treatment was shown to be suitable for clinical measurement of fundamental voice frequency. Basal frequency (SFF) and lowest frequency (LF) were determined in 374 normal subjects aged 6 years to adulthood. SFF fell between ages 8 and 10 years in boys (from 259 to 247 Hz), but not in girls (253 Hz). LF fell between ages 6 and 10 years in boys (from 234 to 203 Hz) and girls (from 230 to 218 Hz), and a sex difference appeared. In puberty, parallel to pubic hair (PH) development, a gradual fall of SFF and LF occurred in both boys (to 100 and 90 Hz, respectively) and girls (to 213 and 180 Hz). As a group, young hypopituitary children and girls with Turner's syndrome had a high SFF, and prepubertal boys with delayed maturation a low SFF. In some children with prenatal growth failure, SFF was abnormally high. The girls with Turner's syndrome exhibited a high, though individually variable, sensitivity of voice to androgen; their voices became lower before the appearance of any other masculinising effects. The instrument is useful for characterisation of growth failure syndromes and stages of puberty. It is particularly recommended for monitoring an undesirable effect on the voice during androgen treatment.


Renal scarring and vesicoureteric reflux.

A review of 105 children with urinary tract infection showed an increasing prevalence of grades II-III vesicoureteric reflux with diminishing age. During infancy reflux was almost always severe, and affected boys as often as girls. Radiologically scarred kidneys were drained by refluxing ureters in 98% of cases. The prevalence of scars also rose significantly with increasinglyly severe reflux. Deterioration of existing scars or new scar formation was seen in 15 children; 18 out of 20 affected kidneys (90%) were associated with grade III vesicoureteric reflux. 2 out of 5 children who developed new scars did so after 5 years of age. Because severe reflux may occasionally be seen in the presence of a normal intravenous urogram, and since the finding of grades II-III vesicoureteric reflux is an indication for chemoprophylaxis, we consider cystourethrography essential in children of all ages with recurrent urinary tract infection. In children under 5 years the increased prevalence of both severe reflux and renal scarring are arguments for regarding cystourethrography as a necessary initial investigation.


Tests of skeletal muscle function in children.

The contractile properties of a large proximal muscle (quadriceps femoris) and a small distal muscle (adductor pollicis) have been measured in normal children and children with neuromuscular disorders. The method of stimulating the quadriceps femoris to contract, previously evaluated in adults, was found to be acceptable to children. In normal children a number of indices of muscle function were found to be similar to those in adults. A small study of the function of the adductor pollicis using supramaximal stimulation of the ulnar nerve was carried out in boys with Duchenne dystrophy. Decreased contractile force and prolonged relaxation times from a tetanic stimulation were noted in both the proximal and distal muscles of the boys with Duchenne dystrophy.


Homocystinuria in New South Wales.

Homocystinuria was studied in 27 patients from 15 families in New South Wales. All 2 had biochemical findings consistent with cystathionine synthetase deficiency. One patient was ascertained by newborn screening, but the remaining index cases were detected because of symptoms: poor eyesight 6, mental retardation 3, thromboses 2, skeletal abnormalities 2, and urinary infection1. 9 patients, one-third of all cases, were mildly affected: either they had no features of the disease, or these did not occur until the late teens. Pyridoxine responsiveness was found in 8 sibships, and clinically there were two distinct kinds of response. For patients born in the decade 1960-69 the ascertainment rate for the total population was 1:58 000. The true incidence must be much higher. Our series indicates that homocystinuria occurs more frequently than has heretofore been thought, and that mild cases are common. It is likely that cases are often missed in current newborn screening programmes.


Tracheal compression as a cause of respiratory symptoms after repair of oesophageal atresia.

A case of tracheal compression in an infant after repair of a tracheo-oesophageal fistula and oesophageal atresia is reported. Tracheopexy completely relieved the symptoms of apnoeic attacks, cyanosis, and convulsions. We suggest that tracheal compression in infants and children with repaired oesophgeal atresia can not only cause life-threatening attacks but also be responsible for recurrent chest infections. All infants and children with signs and symptoms of tracheal compression as shown by the presence of a barking type of cough, recurrent chest infections, or persistent mild respiratory symptoms should be referred for thorough investigation of the tracheobronchial tree.


Preventable death in oesophageal atresia.

We report on experience gained in the treatment of 158 cases of oesophageal atresia presenting during a period of 10 years. The factors influencing mortality were analysed. During the period studied there was a slight improvement in survival, and this was probably due mainly to improved preoperative preparation of those babies undergoing primary repair. At best, 'staging' was thought to have had little influence on the survival of poor risk cases. Midwives, obstetricians, paediatricians, surgeons, and general practitioners did not do all that they could have done to prevent morbidity and mortality in these babies. At least one-third of the 79 deaths could have been prevented, and several deaths were caused solely by lack of awareness of the possible complications and associated abnormalities.


Nutrition, sex, gestational age, and hair growth in babies.

Hair growth measurements are a sensitive indicator of nutrition and we have assessed their value in the perinatal period. The proportion of growing roots and their diameter were studied at birth in 114 babies and repeated 3 weeks later in 29 low birthweight babies. Intrauterine malnutrition resulted in thinner roots but the changes after birth were not related to nutrition and these measurements will not be useful in feeding studies in this period. At birth, gestational age and sex affected the hair root, and it may be important to recognise these differences if the hair root is used in biochemical screening tests. We have used a new simple technique for measuring the root diameter using an image-splitting eye-piece.


Increase in hospitalisation for childhood asthma.

Asthma admissions among children under 15 years of age have increased nearly three-fold over the period 1959-73. The possible reasons for this increase have been examined using available data supplemented by the results of a special study of hospital disease indexes and case notes. Changes in diagnostic coding and trends in diagnostic fashion do not appear to be important. Part of the increase may be due to an increase in readmission rates. Changes in admission criteria resulting from changes in therapy, organisation of care, and illness behaviour have been considered. However, on present evidence an increase in morbidity cannot be excluded, and this could be investigated by repeat prevalence surveys of schoolchildren. If morbidity remains unchanged, admission policies for children with asthma should be reviewed.


Normocalcaemic pseudohypoparathyroidism with unusual phenotype.

We describe a boy who presented at 4 years of age with radiological hyperparathyroidism, osteosclerosis, and necrosis of the femoral heads. Plasma biochemistry was normal but the parathyroid hormone (PTH) level was very high. He was deaf and had an unusual facies but did not have the phenotype of Albright's hereditary osteodystrophy. Plasma and urine cyclic AMP reponses to bovine PTH were markedly subnormal. Vitamin D produced sustained hypercalcaemia and a fall in plasma phosphorus. After four hyperplastic parathyroid glands were removed he became hypocalcaemic and plasma phosphorus rose. After operation he remained unresponsive to exogenous PTH; We suggest that he had a form of pseudohypoparathyroidism without the phenotype of Albright's hereditary osteodystrophy and with some residual skeletal and renal responsiveness to PTH.


Value of serum ferritin estimation in sickle cell anaemia.

In a group of 35 children with sickle cell anaemia serum ferritin concentration ranged from 70 to 2460 microgram/l (mean 367, median 180 microgram/l). This was significantly higher than the ferritin levels (range 8-101, mean 34, median 30 microgram/l) in a group of 63 normal control children of the same age group. 30 (86%) of the sickle cell children showed serum ferritin levels greater than 101 microgram/l, and 2 (6%) levels greater than 1000 microgram/l. 7 of the patients had not been transfused before this study. Their serum ferritin levels were all raised and showed a significant correlation with age but not with haemoglobin level. In the remainder of the patients the serum ferritin bore no significant correlation with age, haemoglobin level, or number of units of blood transfused. 2 children with HbSC disease had levels within the control range. Since patients with sickle cell anaemia have an increasing chance of long survival, we suggest that serial estimations of their iron status be made by means of serum ferritin assay in order to determine which patients are accumulating excessive iron.


Clinical applications of serum theophylline measurement by high pressure liquid chromatography.

Serum theophylline concentration was measured in children both during treatment of status asthmaticus with intravenous aminophylline, and as outpatients while they were taking oral theophylline compounds for long-term management of asthma. The clinical value of the measurements was assessed. Measurement using high-pressure liquid chromatography is simple and requires only a small volume of blood. Knowledge of serum theophylline concentration facilitates careful control of dosage of both intravenous aminophylline during treatment of status asthmaticus, and of oral theophylline in outpatients. It is useful in the evaluation of symptoms which may be due to toxic side effects of treatment. It also makes possible an assessment of patient compliance with prescribed treatment among those whose symptoms have not improved.


Deafness and biochemical imbalance after burns treatment with topical antibiotics in young children. Report of 6 cases.

Six children are described in whom deafness followed treatment of full thickness burns with topical antibiotic spray containing neomycin. 3 children developed hypocalcaemic tetany, and were shown to have a metabolic disorder involving hypocalcaemia, hypomagnesaemia, and hypokalaemia. The dangers of treating burns with topical ototoxic and nephrotoxic antibiotics are emphasised.


Simple and versatile method for measuring oxygen consumption in infants.

A simple, rapid, and accurate method for measuring oxygen consumption in infants is described. Expired gas is entrained in a stream of air drawn through a gently applied face mask. Oxygen consumption is derived from (1) gas flow rate, measured with a flowmeter, and (2) the fall in oxygen concentration of the gas mixture, measured with a paramagnetic analyser. A measurement can be made at the bedside within 2 minutes without disturbing the infant. In 17 mature 2-day-old neonates mean oxygen consumption was 6.52 ml/kg per min, SD 0.90, similar to that previously reported using less simple methods,


Dosage schedule of gentamicin for chronic renal insufficiency in children.

Gentamicin was given to paediatric patients with chronic renal disease complicated by infections by Gram-negative organisms, in which renal function varied from normal to severely insufficient. Peak serum levels after an intramuscular dose of 1 mg/kg body weight ranged from 3.1 to 9.4 microgram/ml, which appeared adequate for therapy. The peak value was not related to the renal function of the individual patients. The serum half-life of gentamicin correlated inversely with the value for endogenous creatinine clearance. A diagram for the estimation of the serum half-life of gentamicin using the creatinine clearance value is presented. As a practical guide, it is recommended that the dose of gentamicin in children with renal function impairment be 1 mg/kg given intramuscularly and that the interval between doses be almost three times as long as the serum half-life, which can be estimated by means of the diagram for individual patients. The accuracy and safety of this method were confirmed by treating children with this adjusted dosage schedule.


Late functioning adrenocortical carcinoma in a 5-year-old girl.

A 5-year-old with adrenocortical carcinoma presented with acute paraplegia. The tumour was initially nonfunctioning but finally showed rapid dissemination and the patient then developed Cushingoid features and virilisation.


Unusual case of adrenal cortical carcinoma in a female infant.

Adrenal cortical carcinoma in a 4 1/4-month-old girl was treated by surgery in combination with actinomycin D, cyclophosphamide, and 5-fluorouracil given daily for 5 days every third week for 13 1/2 months. Postoperative hypertension and raised 24-hour 17-hydroxy- and 21-oxosteroids suggested residual microscopical tumour activity. These findings resolved during chemotherapy. The patient is alive and well 22 months after completing chemotherapy. Adrenal cortical carcinoma may rarely mimic neuroblastoma or nephroblastoma when the tumour is not clinically secretory.


Systemic lupus erythematosus presenting as chorea.

A child presenting with chorea developed the full clinical and laboratory findings of systemic lupus erythematosus after hospitalisation. He responded dramatically to haloperidol. 6 months after diagnosis he began to manifest renal involvement.


Serum 25-hydroxyvitamin D levels in thalassaemia.

Serum 25-hydroxyvitamin D levels were measured in 36 thalassaemic children and 27 controls aged 5-15 years. Blood specimens were collected from the beginning of April until the end of October 1976. We considered as the winter period the first 3 months and the summer period the last 4 months. We found that (a) thalassaemic children had lower levels of serum 25-hydroxyvitamin D than controls: (b) there was a seasonal variation of serum 25-hydroxyvitamin D in both groups; and (c) the thalassaemic children had malabsorption of vitamin D. We suggest that the bone lesions in thalassaemic children are related to vitamin D deficiency.


Short- and long-term cadmium distribution in rat livers after different routes of administration.

Intracellular hepatic distribution of cadmium in male Wistar rats were determined after various time intervals up to 6 months following a single intraperitoneal injection of cadmium chloride (3.75 mg/kg). After an initial liver accumulation period of approximately 2 weeks, cadmium was slowly eliminated. This decrease occurred primarily in the soluble fraction, but also to a lesser extent in the nuclear and mitochondrial fractions. No detectable decrease of cadmium was observed in the microsomal fraction. There was no apparent redistribution of cadmium within these hepatic fractions during the 6-month period of study. A comparison of the intracellular cadmium distribution following administration by intraperitoneal, oral, and pulmonary routes revealed that in each instance the soluble fraction contained the greatest amount of this element by far with decreasing amounts in the microsomes, mitochondria, and nuclei in that order.


In vitro responsiveness of lymphocytes to phytohemmagglutinin.

Peripheral blood lymphocytes from 20 human subjects exposed to 784 microgram/m3 ozone for 4 hours, and from 11 subjects exposed to clean air for the same length of time were studied for in vitro responsiveness to phytohemagglutinin (PHA). Thymus-derived (T) lymphocyte response to PHA (normal response is proliferation of lymphocytes) was significantly suppressed (P less than .01) in samples obtained immediately after subjects' exposure to ozone. Recovery of response occurred 2 weeks postexposure. Responses were unchanged in subjects exposed to clean air. Existing studies suggest that ozone exposure may generate free radicals or other reactive molecules or both, that could be responsible for immediate changes in metabolic events leading to blockage or inhibition of deoxyribonucleic acid (DNA) synthesis in T lymphocytes as shown in this study. It is possible that some prerequisite to active cell metabolism such as ribonucleic acid (RNA) may be impaired by ozone exposure. The significance of the suppression of T-cell response noted in this study is that: (1) if continuous exposures to ozone are shown to induce an immunosuppressed state for a significant time period, an important factor in carcinogenesis might be elucidated; (2) immunosuppression may cause a progression of an already present tumor; (3) immunosuppression may enable endogenous latent infections such as tuberculosis to reactivate; and (4) immunosuppression may explain in part the relationship between chronic oxidant air pollution and influenza-like illnesses in population.


Systemic lupus erythematosus. A prospective analysis.

The spectrum of organ involvement in 50 patients with systemic lupus erythematosus has been assessed in a prospective study. All patients were admitted to hospital electively for 2 days and a complete clinical and laboratory assessment protocol completed. Subsequent hospital admissions depended on clinical status. The overall mean observation period was 29 months. Widespread multisystem involvement was found in every patient. Subclinical abnormalities of respiratory and cerebral function were common even in patients in clinical remission. A more conservative approach than has been generally recommended was used for the management of systemic lupus erythematosus and is supported by the estimated 5-year survival of 98%.


A tobacco smoke inhalation exposure device for rodents.

A system which utilizes a piston pump to generate cigarette smoke under standard conditions, and expose rodents to the inhalation of diluted smoke for controlled periods of time is described. Variations of the basic system have been employed to exposure groups of ten to twenty hamsters or rats, and should allow exposures of up to forty mice. The system has been in use for approximately 24 months in routine chronic exposures of rats. Data are presented to define the operating characteristics and typical dosimetry. Animal containment peculiar to this apparatus is described.


Electric kettles as a source of human lead exposure.

Five hundred and seventy-four households in Ottawa were surveyed to evaluate water boiled in electric kettles as a source of lead exposure. Samples of boiled water exceeded the World Health Organization mandatory limit for drinking water (50 microgram/l) in 42.5% of the households. Excessive lead concentrations were observed in 62.8% of water samples from kettles more than 5 years old. Multiple regression analysis indicated that age, sex, and cigarette smoking habits, but not lead concentration in boiled water, nor weekly consumption of boiled water were significantly associated with blood-lead concentration. Lead exposure from electric kettles may be a significant problem only in infants receiving formula prepared with boiled water.


Immunological studies in frozen shoulder.

Serum immunoglobulin levels were determined in 25 patients with frozen shoulder and in 25 age- and sex-matched controls. Serum IgA levels were significantly reduced (P less than 0.001) in the patients with frozen shoulder and remained so after clinical recovery. Lymphocyte transformation to phytohaemagglutinin in 21 patients also showed significant depression (P less than 0.01). These results support the suggested immunological pathogenesis of this condition.


Phenol poisoning due to contaminated drinking water.

Accidental spillage of 37,900 1 of 100% phenol (carbolic acid) in July 1974 caused chemical contamination of wells in a rural area of southern Wisconsin. Human illness characterized by diarrhea, mouth sores, dark urine, and burning of the mouth was subsequently reported by seventeen individuals who consumed the contaminated water; their estimated intake of phenol was 10 to 240 mg/person/day. Clustering of the illnesses in time and place, as well as the similarity of these cases to previously documented cases of phenol poisoning, suggest that phenol in water caused the illness. Physical and laboratory examinations 6 months after the exposure revealed no residual abnormality in exposed persons. Water testing and geologic evaluations indicate that contamination of the underground water system may persist for many years.


Synovial pathology in Behcet's syndrome.

Eight specimens of synovial membrane from 6 patients with 'definite' Behcet's syndrome were available for histological examination. Only the superficial zones of the synovia were affected, all except one being replaced by dense inflamed granulation tissue composed of lymphocytes mingled with macrophages, vascular elements, fibroblasts, and neutrophils. There was a marked plasma cell infiltrate and lymphoid follicle formation in one synovium only, and there was no evidence of infection. Pannus and erosive change were present in the three specimens which included the articular surface, the erosive change being visualised radiologically in two of these. It is suggested that these appearances are characteristic of Behcet's syndrome and should be added to the list of diagnostic criteria.


Immune response inversion after hyperimmunisation. Possible mechanism in the pathogenesis of HLA-linked diseases.

The crosstolerance hypothesis suggests that animals sharing antigens with some microorganisms will produce low antibody levels in the early part and high levels in the latter part of an infection. Antibody responses have been measured in high responder B10.M and B10.D2 mice and low responder C3H and A.Thy-1.1, as well as F1 hybrids (B10.M X A.Thy-1.1) and (B10.M X C3H/He), after repeated immunisation with the antigen ferritin, involving altogether 483 mice. An inversion in the immune response was found to occur and similar delayed high antibody responses have been described in rheumatic fever. It is suggested a mechanism of immune inversion may operate in the pathogenesis of HLA and blood group-linked diseases.


Detection of immune complexes in serum of patients with ankylosing spondylitis.

Immune complexes were measured in the sera of 18 patients iwth ankylosing spondylitis and 5 normal control subjects by their ability to inhibit antibody-mediated lymphocyte-induced cytotoxicity. 11 of the spondylitis and none of the control sera contained circulating complexes. Fractionation of sera on Sephadex G-200 showed that complexes were of two molecular sizes, one of intermediate and the other of large molecular weight. The presence of immune complexes did not correlate with activity of disease or the presence of peripheral arthritis although the one patient with polyarthritis had the highest level of complexes detected in this study. The nature of the antigen in these antigen-antibody complexes is of great interest since it may provide evidence of the aetiological agent in the disease.


Impairment of lachrymal and salivary secretion and cellular immune responses to salivary antigens in rheumatoid arthritis.

During a systematic investigation of 100 unselected outpatients with rheumatoid arthritis, 58 were found to have reduced lachrymal or salivary secretion. No correlation could be detected between the presence or absence of secretory abnormalities and the age or sex of the patient, the presence of nodules or salivary duct antibody, or the occurrence of vasculitis. However, there was a significant correlation between diminished salivary of lachrymal flow and the occurrence of cellular immune responses to a protein fraction of normal human saliva, sensitisation being found in 94% of those with impairment of salivary and lachrymal secretion as compared with 33% of those without.


Isolation of Mycoplasma pneumoniae from the synovial fluid of a hypogrammaglobulinaemic patient in a survey of patients with inflammatory polyarthritis.

Mycoplasmas were not isolated from synovial fluid or membrane specimens taken from 41 patients suffering from inflammatory polyarthritis. However, Mycoplasma pneumoniae was isolated in two laboratories and on two occasions from the knee joint of a hypogammaglobulinaemic patient with a chronic polyarthritis.


Rheumatoid synovial cells in culture produce a growth inhibitor.

Cultures of synovial cells obtained at surgery from patients with rheumatoid arthritis produced a protein which inhibits the mitosis of normal rabbit and human synovial cells, and of human lung fibroblasts. This mitotic inhibitory effect can be transferred to rabbit synovial cells by intra-articular injection of the animals with rheumatoid synovial cell cultures.


Diagnostic value of sacroiliac joint scintigraphy with 99m technetium pyrophosphate in sacroiliitis.

Using a quantitative method, scintigraphy of SI joints was performed by means of 99m technetium pyrophosphate in 21 patients with definite ankylosing spondylitis, in 17 control patients, and in 26 patients 'at risk', i.e. patients with complaints of back pain of the inflammatory type where on clinical grounds there was a possibility of sacroiliitis developing but with normal x-ray findings of the SI joints. Radioisotope uptake was higher in the ankylosing spondylitis group than in the other two groups, although the difference was not statistically significant with regard to the group 'at risk'. The high variance in the three groups considerably reduces the diagnostic value of the examination. In the ankylosing spondylitis group no correlation was found between radioisotope uptake and age, duration of disease, erythrocyte sedimentation rate, or radiological stage of scaroiliitis. Since the specificity and sensitivity of scintiscanning are lower than that of clinical and radiological diagnosis of the disease, we conclude that scintigraphy is not very helpful in the early diagnosis of sacroiliitis, at least by the techniques used here.


Intra-articular yttrium 90 in rabbits. Comparison of behaviour of various radiocolloids in rabbits and in man.

Comparative studies of the retention of various yttrium 90 radiocolloids and of noncolloidal yttrium 90 chloride were performed in rabbits with arthritis induced in one knee. Two colloids, the citrate and resin forms, showed a statistically significant difference in retention between inflamed and normal knees, isotope being retained better in the normal knee. Marked differences were found in the handling of the various yttrium preparations in rabbits compared with previously reported results in man. These differences suggest that the rabbit with induced arthritis is not a suitable model in which to test retention of different radiocolloids before use in man.


Angiography as an aid in extra-enteric gastrointestinal bleeding due to visceral artery aneurysm.

Three unusual patients with visceral artery aneurysms involving the hepatic artery, inferior pancreaticoduodenal artery, and a mesenteric branch artery are presented. Each of these lesions is unusual and all were diagnosed preoperatively. Surgical intervention was planned on the basis of angiography. In two patients with hypovolemia a simple diagnostic approach employing emergency selective angiography was formulated and successfully used.


Systemic prophylaxis with doxycycline in surgery of the colon and rectum.

A prospective double-blind study on the effects of doxycycline as a prophylactic antimicrobial in elective colonic surgery is presented. One hundred-eighteen patients were evaluated. Fifty-eight were treated and 60 were controls. Two hundred milligrams, doxycycline or placebo (two capsules) were given orally four to six hours prior to surgery and 100 mg or placebo (one capsule) for five days postoperatively. Doxycycline levels in serum and tissues were determined and related to the MICvalues of the contaminants of the operative field. A significantly lower incidence of abdominal wound sepsis, intra-abdominal complications, and septicemia was recorded in the doxycycline group compared to the control group, 12.1 and 45% respectively. The prophylactic effect was most pronounced in patients with a negative wound culture upon closure. Macroscopical peritoneal contamination was associated with less severe consequencies in the doxycycline group. Infections in the perineal field, 3/15 vs 8/17, appeared alone in the doxycycline group, whereas they were combined with abdominal sepsis in 6/8 among the controls. Treatment also reduced the incidence of repeat laparotomy due to septic complications, 0 vs 8. Thus systemic per and postoperative prophylaxis with doxycycline significantly reduced both the incidence and the severity of postoperative sepsis in potentially contaminated elective colorectal surgery without any adverse reactions.


Non-mechanical hemorrhage in severe liver injury.

Coagulopathy, or non-mechanical hemorrhage, complicated the operative course of 17 of 33 (51.5%) patients suffering severe liver trauma. The highest incidence of non-mechanical hemorrhage (66.7%) occurred in patients undergoing anatomic lobectomy. Serial hemostatic parameters were assessed and thrombocytopenia was the most striking abnormality in patients with non-mechanical hemorrhage. The degree of thrombocytopenia was directly correlated with the number of blood transfusions administered. The mean operative blood transfusion requirement was significantly greater in patients with non-mechanical hemorrhage, 25.1 +/- 2.87 (S.E.M.) units, than in those without, 12.2 +/- 1.83 units (p < 0.001). The bulk of this transfusion was given before the onset of clinically overt coagulopathy. Massive transfusion of stored blood was felt to be the most important factor in causing non-mechanical hemorrhage. Convincing evidence for disseminated intravascular coagulation was lacking, and abnormal fibrinolysis was infrequent and mild when observed. Although uneventful in most, in six patients non-mechanical hemorrhage resulted in excessive blood transfusion, unnecessary operation or death. Infusions of platelet concentrate, fresh frozen plasma, and fresh blood were used to successfully treat most cases of non-mechanical hemorrhage. In all cases, these components were not started until non-mechanical hemorrhage was clinically apparent. The value of prophylactic use of blood components is stressed. Because of troublesome side effects associated with the use of prothrombin complex concentrates, these agents are contraindicated in patients with severe liver injury. After receiving concentrates, one patient developed severe hypotension leading to ventricular fibrillation, two developed transient thrombocytopenia and two others demonstrated multiple pulmonary microthrombi at autopsy, a finding not observed in autopsied patients not receiving the concentrates.


Modification of the Longmire procedure.

Two modifications of the Longmire procedure of intrahepatic cholangiojejunostomy are reported. The first involves the preoperative placement under fluoroscopic control of a large Teflon catheter in the distal left hepatic duct to facilitate the identification and isolation of the duct at the time of surgery. The second modification is the use of a transhepatic silastic biliary stent positioned by utilizing the Teflon catheter. These modifications make the Longmire procedure technically much easier, and should help insure long-term success in both benign and malignant strictures. A successful case utilizing these modifications is reported.


Increased rates of whole body protein synthesis and breakdown in children recovering from burns.

The rates of whole body protein synthesis and breakdown were determined, with the aid of a constant administration of [15N]glycine, during recovery in 11 acutely burned children, involving a total of 24 studies. Eleven studies were also conducted in seven healthy children before and after reconstructive surgery. Rates of whole body protein synthesis and breakdown, expressed as g protein/kg body weight/day, were significantly (p less than 0.05) and positiviely correlated with per cent body surface area total burn, per cent third-degree burn, and per cent open wound. These rates (synthesis, 7.1 +/- 2.1 g protein/kg/day; breakdown, 6.3 +/- 1.8 g protein/kg/day) were 80 to 100% greater (p less than 0.05) in patients with total burns greater than or equal to 60%, as compared to patients with less than 25% total burns or to the surgical patients. Because of the high energy cost of protein synthesis, it is proposed that an increased whole body protein turnover is partly responsible for the reported elevations in rates of heat production occurring in patients recovering from thermal injury.


Appendicitis in the elderly.

The charts of 68 patients from 65 to 99 years of age who underwent appendectomy for appendicitis were reviewed between 1964 and 1976. Thirty-three were men and 35 women. All patients underwent appendectomy. Four patients had normal appendices. The remainder had appendicitis; 74% were ruptured. The duration of symptoms varied greatly, and was related to outcome. The mean duration was 58 hours, but both those who died and those who suffered complications had significantly longer mean duration while those who had an uncomplicated course had a shorter mean duration of symptoms. The incidence of rupture rose from 60% in those seen with symptoms less than 48 hours to 90% in those with symptoms longer than 49 hours. Delay was invariably related to delay in seeking medical treatment. In no case was the patient under the care of another physician for an extended period of time. Pain was the chief complaint in 63 patients, and was present in all. Seventy-four per cent had fever and 78% had leukocytosis. Those with normal appendices had normal white blood cell counts. Right lower quadrant tenderness was present in 80%. Thirty-nine per cent had significant additional medical problems. Most (73%) had operation within six hours of their original evaluation, and yet the overall complication rate was 34% including six deaths. Delay during evaluation did not correlate with unsatisfactory outcome as did delay in seeking medical attention. The most common complications were due to infection. In at least three of the deaths wound infection was associated with sepsis and death. Delay in seeking medical care, advanced age, and underlying problems were the most significant factors in those who died.


Infrarenal aortic occlusion.

Twenty-eight patients with total occlusion of the infrarenal aorta have been seen at the UCLA Hospitals in the past 11 years. Claudication was the presenting complaint in all but one patient, with one-third having ischemic rest pain. The average age of these patients was 54 years, and their histories revealed a surprising absence of myocardial infarction, stroke, or diabetes, although 40% had essential hypertension. Heavy tobacco use, however, was characteristic of the entire group. Arteriography proved valuable in identifying and characterizing the vascular abnormalities, but posed problems in technique and interpretation. Significant distal arterial disease was detected radiographically in only 21% of these patients. Operative correction of the aortic occlusion was performed on 26 patients, 18 by aortic bypass grafts and eight by aorto-iliac endarterectomy, with one early postoperative death. Although the thrombus extended to the renal artery origins in 77% of the cases, a well-designed technical approach did not require renal artery occlusion. Using serial creatinine determinations, one case of renal insufficiency was detected which was associated with prolonged postoperative hypotension. Although the extent of distal disease was more severe in those who underwent bypass, symptoms of claudication returned earlier and were more prominent in the endarterectomy group. This recurrence of systems was not favorably altered by sympathectomy performed concomitantly with the initial procedure. Even though this condition seems to pose difficult technical obstacles and has a poor prognosis, infrarenal aortic occlusion can be successfully treated by aortic bypass, with favorable long-term results, if particular attention is paid to elements of the preoperative evaluation and the intraoperative technical requirements peculiar to this relatively uncommon disease entity.


Experimental subcapsular hematoma of the spleen: natural history and radioisotope scan correlation.

An experimental model was developed in dogs to correlate radioisotope scan findings of iatrogenic, in vivo, splenic injury with the natural history of the injury as determined by the clinical course and both gross and microscopic observations. It was found that small subcapsular injuries do not appear as discrete focal defects on scanning as do larger injuries; however, both small and large injuries cause an increased uptake of the radioactive colloid and increased clearing from the blood. In no dog did the subcapsular injury lead to delayed rupture, bleeding, or cyst formation, and all injuries healed by scarring and thickening of the overlying capsule. This study suggests that the entity of delayed rupture of the spleen in humans is, in fact, delayed diagnosis and not delayed bleeding.


A three year experience using modified bovine arterial heterografts for vascular access in patients requiring hemodialysis.

Between January 1974 and December 1976 28 arteriovenous fistulae were created in 25 uremic patients using modified bovine arterial heterografts. Bovine grafts were inserted only if the patient's own vessels were deemed inadequate to permit the development of a useable Brescia fistula. Graft patency by the life-table method was 92% at three months and 75% at one year. Complications leading to graft failure included late thrombosis, inadequate healing of skin flaps, and graft disruption secondary to faulty cannulation. Ten patients died; none of the deaths were graft-related. At the end of the period of observation all patients requiring hemodialysis had functioning bovine grafts. It is felt that for this purpose the modified bovine arterial heterograft is superior to any other currently available vascular conduit. The location of these grafts should be planned so as to make maximal use of distal vasculature and allow multiple sequential access procedures in the same extremity. An idealized approach which encompasses these principles is presented.


Diagnosis and thereapy of necrotizing soft tissue infections of the perineum.

Nine patients with necrotizing soft tissue infection of the perineum and adjacent areas developed following perirectal absecess, retroperitoneal infection, local trauma or apparently spontaneously. Skin changes and crepitus were often present but severe local pain was the only indication of infection in three patients. Repeated surgery or in one case, a necropsy, were required to uncover the extensive, dissecting, purulent and necrotizing subcutaneous process. Myonecrosis had occurred in three cases. Operation was often delayed for several days because of the difficulty in recognizing the presence of infection or because the urgency for treating an already apparent infection was not appreciated. The mortality was high (5/9 cases). The bacterial isolates were predominantly of a mixed aerobic-anaerobic nature. Needle aspiration of suspicious areas, even where classic signs of inflammation are lacking and Gram staining of exudate are valuable procedures for diagnosis and institution of appropriate presumptive antibiotic treatment. Thorough surgical exploration and debridement must be performed promptly to maximize chances for survival.


Rubber band seton in the management of abscess-anal fistula.

An elastic seton has been used in more than 35 patients in the surgical management of anterior abscess-anal fistula and anterolateral anal fistula in women. Elastic setons are applicalbe in the treatment of other complicated abscess-anal fistulas. The advantage of this method is the good functional result, with a minimal deformity of the anus. The treatment can be administered with a minimal number of hospital days or, in some instances, on an outpatient basis.


Cardiac function at rest and during exercise in normals and in patients with coronary heart disease: evaluation by radionuclide angiocardiography.

This study demonstrates that radionuclide angiocardiography provides a simple and noninvasive approach for evaluation of myocardial function. Previous work concerning myocardial performance has been generally conducted with the patient in the supine position. Radionuclide angiocardiograms were performed in the present study at rest and during exercise in 30 normal subjects and in 30 patients with ischemic coronary artery disease. There were 30 normal controls (Group I), ten with single coronary artery disease (Group II), and 20 patients with multiple vessel coronary disease (Group III). All subjects were studied in the erect posture on a bicycle ergometer. In the normal controls, the mean heart rate doubled and the cardiac output tripled during exercise. Intensive training can lead to extraordinary levels of cardiac performance as shown in a world-class athlete who during peak exercise attained a heart rate of 210, an ejection fraction of 97%, and a cardiac output of 56 litres per minute. In the patients with coronary artery disease, both groups, were able to increase cardiac output to approximately twice the resting value. The magnitude of increase in blood pressure during exercise was not significantly different in the three groups. However, definite changes were present in the end-diastolic volume at rest was 116 and rose to 128 ml in Group I, 93 rising to 132 ml in Group II, and 138 increasing to 216 ml in Group III. The stroke volume increased comparably in all three groups, but the ejection fraction from rest to exercise showed a marked contrast in the controls compared to those with multivessel coronary disease. The ejection fraction rose in Group I from 66 to 80% during exercise, while in Group II it fell from 69 to 67%, and in Group III from 60 to 46%. These findings indicate that patients with ischemic myocardial disease respond to the stress of exercise by cardiac dilatation to maintain of increase stroke volume at increased heart rates. Moreover, the magnitude of this response appears to be greatest in patients with left main coronary artery stenosis. This approach for evaluating myocardial function during exercise provides useful data of importance in selecting medical versus surgical management of patients with ischemic coronary artery disease.


Staging laparotomy in Hodgkin's disease.

Staging laparotomy was performed at the University of Virginia Medical Center on 111 patients with Hodgkin's disease. The operation included multiple liver and lymph node biopsies and, excepting three patients, splenectomy. The histopathology was reviewed and the 111 patients were classified as follows: nodular sclerosis, 74; mixed cellularity, 28; lymphocyte predominance, 7; and undetermined, 2. There were no deaths. Wound, pulmonary or urinary tract complications occurred in 11 patients. One case of postoperative thrombophlebitis occurred and in another case small bowel obstruction developed, and resolved without reoperation. The pathologic stage (PS) following laparotomy was unchanged from the clinical stage (CS) in 64%, reduced in 20%, and advanced in 16%. The therapy, however, was altered in 38% of the patients. Lymphangiography in 103 patients was interpreted as showing lymph node involvement in 38, equivocal involvement in 11, and no involvement in 54. Among the 92 examinations reported as either positive or negative, 77% were confirmed histopathologically, 21% were falsely positive, and 2% were falsely negative. The spleen was positive for Hodgkin's disease in 39% of cases, and in these patients with positive spleens there was no reason to suspect intra-abdominal involvement preoperatively in 21%.


Breast reconstruction following mastectomy for cancer.

Breast reconstruction following mastectomy for cancer is a feasible procedure. The selection of the proper type of mastectomy should be the decision of the cancer surgeon. However, with the advent of modified mastectomies, the use of fewer primary skin grafts, and the preservation of all or part of the pectoralis major muscle, breast reconstruction has become more satisfactory. Since many women adjust poorly to mastectomy, the chance for reconstruction offers hope for a fuller life. Reconstruction of the postmastectomy cancer patient can be accomplished in three basic steps: 1) An adequate breast mound can be constructed with a prosthesis. A flap may be used if the skin cover is inadequate. 2) The size and shape of the remaining breast can be adjusted to obtain symmetry. 3) The nipple-areola complex can be reconstructed if the patient desires. Correction of the infraclavicular and axillary defects may be required. The techniques employed in 14 patients are presented.


The prevention of bypass enteritis after jejunoileal bypass for morbid obesity.

The symptoms of bypass enteritis are disabling sequelae in many patients after jejunoileal bypass. This is a preliminary report of efforts to devise a valve to prevent reflux into the bypassed intestine after jejunoileal bypass. Valve I (42 cases) was formed by dividing the ileum, everting the proximal end as one matures an ileostomy, and inserting this into the distal ileum. Only 12 of these valves were competent. Valve II (six cases) was formed by dividing the ileum and merely inserting the proximal bowel into the distal, allowing it to evert spontaneously as with an unmatured ileostomy. In two cases the valve was competent, but four cases became obstructed and this valve is mentioned only to be condemned. Valve III (19 cases) is similar to an isoperistaltic Kock valve, except that the intussuscepted ileum is first divested of its mesentery. All such valves have been competent. All 33 patients with a competent valve have been free of the stigmata of bypass enteritis, whereas 54% of 156 patients showed the symptoms of enteritis after conventional jejunoileal bypass.