[Experimental study of the action of olivomycin on a melanoblastoma of the vascular tract of the eye]. A total of 66 experiments were performed with a purpose of studying the effect of olivomycin on the melanoblastoma cells of the human eye vascular tract. Heterotransplants of the human eye vascular tract melanoblastoma in the anterior chamber of the rabbit eye served the objects of the studies. Olivomycin was used in 34 out of 66 experiments and 32 experiments were control. Separate tumor cells together with pronounced signs of necrosis were detected on histological examination only in 1 out of 34 transplants treated with olivomycin. The transplants in the other 33 experiments resolved. The transplant in the control experiments consisted of viable cells at the same period. On the basis of the experiments it was concluded that olivomycin had a pronounced destroying effect on melanoblastoma cells under conditions of heterotransplantation and may be recommended for clinical use for prophylaxis of metastasis in post-operative periods.


[Pharmacokinetics of ampicillin in peritonitis in children]. Ampicillin levels in the blood serum and abdominal cavity biosubstrates of children with appendicular peritonitis were studied. The antibiotic was administered as intravenous jet infusion in single doses of 12--15 and 25--30 mg/kg and drop infusion continuously for 24 hour in doses of 150 and 250--300 mg/kg. Administration of the drug as intravenous jet infusion provided therapeutical ampicillin levels in the appendix tissue and abdominal cavity exudate. Administration of increased doses of the drug resulted in its higher biosubstrate levels. It was found that the level of the appendix destruction had a significant effect on the antibiotic level in this organ. In cases with gangrenous appendititis the ampicillin levels were 1.5--2.2 times lower than those in cases with catarrhal appendititis. The studies on the effect of the infusion therapy on ampicillin pharmacokinetics showed that the volume of the liquids administered intravenously had no significant influence on the antibiotic circulation in the blood. A continuous drop infusion provided high and stable ampicillin levels in the blood serum which significantly exceeded the antibiotic MIC. During the post-operative period the antibiotic levels in the blood serum after intraperitoneal administration were determined. The data showed that ampicillin administered intravenously 2--3 days after the operation was absorbed into the blood in insignificant amounts.


In vitro activity and beta-lactamase stability of BL-S786 compared with those of other cephalosporins. In vitro activity of BL-S786, a new parenterally semisynthetic cephalosporin, was investigated against 570 bacterial isolates. BL-S786 inhibited most Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Salmonella. It inhibited some Enterobacter and indole-positive Proteus, but it was less active against these later species than was cefamandole, cefuroxime, or cefoxitin. It was not active against Serratia marcescens, Pseudomonas aeruginosa, or Bacteroides fragilis. BL-S786 was the least active new cephalosporin tested against staphylococci and was less active than cephalothin against streptococcal species. The activity of BL-S786 was not altered by the type of assay medium nor by 50% serum. The size of the test inoculum altered the minimal inhibitory and bactericidal concentrations for inhibition of some organisms, particularly those with Richmond type I beta-lactamases. BL-S786 was not hydrolyzed by the R-factor-mediated, Richmond type III beta-lactamase, but it was hydrolyzed by type I beta-lactamases.


Dihydrofolate reductases in some folate-requiring bacteria with low trimethoprim susceptibility. Dihydrofolate reductases from the folate-requiring strains Streptococcus faecalis ATCC 8043, Lactobacillus casei ATCC 7496, and Pediococcus cerevisiae ATCC 8081, as well as from Lactobacillus arabinosus, which is not dependent on exogenous folate, were isolated, and their properties were compared to reductases of Escherichia coli B, Staphylococcus aureus, and rat liver reductase. An inhibition profile with six different inhibitors revealed significant differences among all enzymes. All lactobacilli reductases are less sensitive to trimethoprim than the enzymes of E. coli and S. aureus, the reductase of P. cerevisiae requiring a concentration at least 1,000 times higher for 50% inhibition. Inhibition of growth of S. faecalis by pyrimethamine and 2,4-diamino-6,7-diisopropyl-pteridine was seen to be much stronger than was predicted from the enzymatic data.


Effect of leaf extracts of Aloe arborescens Mill subsp. natalensis Berger on growth of Trichophyton mentagrophytes. The antifungal activity of a lyophilized powder containing aloe leaf homogenate (whole-leaf powder) against Trichophyton mentagrophytes was investigated. The minimal inhibitory concentration was 25 mg/ml by the agar dilution method, using Sabouraud glucose agar medium. At subinhibitory concentrations, the powder exerted its main effect on colony growth by prolongation of the lag phase and inhibition of growth rate. Homogenates of fresh whole leaf were filtered through Whatman GF/A paper, and the filtrate was dialyzed and concentrated by molecular filtration using an Amicon hollow-fiber dialyzer concentrator DC-2, and a powder containing components with molecular weights higher than 10,000 (high-molecular-weight component powder) was prepared by lyophilization. The minimal inhibitory concentrations against three strains of T. mentagrophytes were all 10 mg/ml. The inhibitory activity was fungicidal and was lost by heating at 100 degrees C for 30 min. Both the whole-leaf powder and the high-molecular-weight component powder induced various morphological abnormalities in spores and hyphae by the inhibition of spore germination and development of hyphae.


Metabolic fate of SCE-129, a new antipseudomonal cephalosporin, after parenteral administration in rats and dogs. Disposition of [(14)C]SCE-129 was studied in rats and dogs after intramuscular (i.m.) or intravenous (i.v.) injection. In rats, the plasma level of i.m. [(14)C]SCE-129 attained a peak at 15 min after dosing and then declined with a half-life of 35 min, whereas the half-life after an i.v. dose was 26 min. The area under the plasma level curve within 2 h after the i.m. dose was 85% of that after the i.v. dose. Intramuscular injection of [(14)C]SCE-129 into dogs gave a peak plasma level at 30 min and a half-life of 60 min. In both rats and dogs, the plasma levels of (14)C were closely similar to those of the unchanged antibiotic, which was weakly bound to plasma protein. The rat tissue level of i.m. [(14)C]SCE-129 was maximum at 15 min, with the highest concentration in the kidney, followed by plasma, adrenal, lung, heart, thymus, gastrointestinal wall, and liver, and the lowest in the brain. The antibiotic barely entered erythrocytes of rats and dogs. Whole-body autora-diographic studies showed that i.m. [(14)C]SCE-129 scarcely crossed the rat placenta. (14)C was detected in the milk of rats given i.m. [(14)C]SCE-129. In both rats and dogs, almost all of the dosed (14)C was excreted in urine within 24 h as the unaltered antibiotic, with only small amounts appearing in feces via bile. Thus, these findings evidenced a rapid absorption and wide distribution of i.m. SCE-129, followed by extensive renal elimination as the unaltered antibiotic.


Mode of action of a structurally novel beta-lactam. CP-35,587 {6-[d-2-amino-2-(p-hydroxyphenyl)acetamido]-2,2-dimethyl-3- (5-tetrazolyl)-penam} is a member of a new family of beta-lactam antibacterial agents. Because the biospectrum of CP-35,587 has features similar to both penicillins and cephalosporins, experiments were carried out to explore its mode of action. CP-35,587 did not inhibit peptidoglycan transpeptidase from Escherichia coli, but it did inhibit dd-carboxypeptidase. Similar results were obtained with cephalexin. When these antibiotics were compared for effects on growth and morphology of E. coli, it was observed that filaments formed after exposure to either antibacterial agent for 30 to 60 min. The filaments enlarged, and fragmentation occurred until very few viable cells remained after exposure to CP-35,587. After 180 min in the presence of cephalexin, the cells began to divide, and the filaments formed cross-walls reaching control values in 24 h. CP-35,587 and cephalexin had similar effects on the morphology of the Klebsiella cell: the cells became enlarged within 30 min; with increasing exposure, the filaments became longer, with evidence of cytoplasmic emptying and ghost cell formation. These ghostlike tubules eventually broke apart, leaving fragments. These data indicate differences in the mode of action of CP-35,587 from those of most other beta-lactam antibiotics.


Method for qualitative determination of 2-deoxystreptamine. We have developed a qualitative method to assay for the presence of 2-deoxystreptamine in hydrolysates of crude aminoglycoside preparations using a 2-deoxystreptamine-requiring idiotrophic mutant. The assay involves (i) incubation of a 2-deoxystreptamine-requiring mutant with 1 mg of a hydrolyzed preparation from a crude unknown antibiotic mixture per ml, and (ii) examination of the resultant incubation mixture for production of antibiotic(s) by disk assay.


Antiviral activity of extracts from marine algae. Extracts of two species of marine algae, Constantinea simplex and Farlowia mollis, were tested for antiviral activity in tissue culture and in experimental infections of mice. Treatment of confluent mouse embryo fibroblast cell monolayers with either compound before viral inoculation was effective in inhibiting the replication of herpes simplex virus type 1 and type 2, vaccinia virus, and vesicular stomatitis virus, but not encephalomyocarditis virus, Semliki Forest virus, or murine cytomegalovirus. Prophylactic administration of these extracts was effective in reducing final mortality or prolonging the mean day of death of animals inoculated by the intraperitoneal, intracerebral, or intranasal routes with herpes simplex virus type 2. When therapy was initiated after viral inoculation or at a site other than that of viral inoculation, no significant effect on mortality or on mean day of death was observed. Neither preparation was effective in mice inoculated intraperitoneally with encephalomyocarditis virus, Semliki Forest virus, or murine cytomegalovirus or in animals infected intravaginally with herpes simplex virus type 2. The prophylactic but not therapeutic antiviral activity of these preparations seriously limits their potential use in human herpes simplex virus infections.


Pharmacokinetics of netilmicin in the presence of normal or impaired renal function. A pharmacokinetic study of netilmicin was conducted in 12 healthy subjects and 24 subjects with chronic renal failure. After intramuscular administrations of 2 and 3 mg of netilmicin per kg in normal subjects, the mean peak serum concentrations were 5.46 and 8.83 mug/ml, respectively. After intravenous infusions of identical doses, the mean maximum serum levels, occurring at the end of the infusion, were 11.79 and 15.75 mug/ml, respectively. The pharmacokinetic data were very similar via the two routes of administration and for the two doses. The elimination half-life was 2.20 h, and 80 to 90% of the injected dose was recovered in urine during the first 24 h. After intramuscular administration of 2 mg/kg in subjects with chronic renal impairment, the elimination half-life increased to 29.48 h, and urinary elimination was inversely related to the degree of impairment. A study was conducted throughout hemodialysis sessions: serum concentrations decreased by 63.3%. The linear relationships between the elimination rate constant and creatinine clearance and the elimination half-life and serum creatinine allowed us to establish dosage schedules according to the degree of renal failure.


Detection of antibiotic-producing Streptomyces inhabiting forest soils. A modified agar overlay technique was developed for detecting antibiotic production by Streptomyces isolates and compared with two routinely used overlay procedures and the shake flask-disk assay method. Two types of inhibitory patterns could be discerned in the modified overlay method, and one of these was always exhibited by Streptomyces isolates which produced extractable antimicrobial substances. In a preliminary screening of 600 isolates, higher numbers of antibiotic-producing streptomyces were detected with the modified overlay procedure than with the streak or pour overlay method and the shake flask assay. The modified overlay distinguished between antibiotic production and other antagonistic effects. The inhibitory agents extracted after 6 days of culture growth on the modified overlay agar were of a higher concentration and more stable over longer periods of time than those recovered from shake flasks. It was observed that acidoduric streptomyces produced a greater proportion of antibiotics against gram-negative bacteria than did neutrophilic cultures, and this effect was greatest with the isolates from the most acidic soils. The neutrophiles were more active against gram-positive bacteria and, upon antibiotic classification, it appeared that the neutrophilic and acidoduric cultures from various soils produced different antimicrobial compounds.


Antibiotic biosynthesis by cofermentation of blocked mutants of two Micromonospora species. Two aminocyclitol-negative Micromonospora mutants representing two different species, M. purpurea and M. inyoensis, and blocked at different steps in the biosynthetic pathway were paired and cofermented for the synthesis of antibiotics. The two blocked mutants were incapable of producing antibiotics alone except when 2-deoxystreptamine was added. When combined they produced gentamicins A, X(2), C(1a), and C(2b), which all have an amino group at the 2' position, and gentamicin B, which has a hydroxyl group at this position instead.


In vivo studies with ambruticin in murine histoplasmosis. Ambruticin (W7783) was evaluated in vivo in mice subacutely or nonlethally infected with Histoplasma capsulatum. Results were compared with those obtained with amphotericin B, the drug of choice in human histoplasmosis. In one experiment, ambruticin was shown to be capable of curing infected animals as evidenced by totally negative liver and spleen cultures obtained when mice were sacrificed after 4 weeks of oral treatment with 150 mg of drug per kg per day. The 50% cure dose for ambruticin was between 75 and 150 mg/kg per day; the 50% cure dose for oral amphotericin B in this experiment was between 1.56 and 6.25 mg/kg per day. In a second experiment, both oral ambruticin (150 mg/kg per day) and oral amphotericin B (25 mg/kg per day) were again curative, but to a lesser degree than in the first experiment. Biological cures were obtained with both drugs after 3 and 4 weeks of treatment but not after 2 weeks.


In vitro studies with ambruticin, a new antifungal antibiotic. The in vitro antifungal inhibitory activities of ambruticin and of various antifungal drugs of choice against 190 fungal pathogens representative of the major human mycoses were compared using a modification of the ICS agar dilution technique. Ambruticin compared favorably with amphotericin B and miconazole when tested against the dimorphic pathogens Coccidioides immitis, Histoplasma capsulatum, and Blastomyces dermatitidis and against Aspergillus fumigatus. Miconazole was the most active compound against Sporothrix schenckii, Allescheria (Petriellidium) boydii, and selected dematiaceous fungi, with ambruticin giving minimal inhibitory, concentrations from 3- to 74-fold higher. Ambruticin compared unfavorably with amphotericin B and 5-fluorocytosine when tested against Candida and Torulopsis species. Ambruticin was not as active in vitro as tolnaftate when tested against the three genera of dermatophytic fungi, but compared favorably with miconazole.


Ankylosis of the temporomandibular joint. With the aid of 22 cases of mandibular ankylosis, the classification, aetiology, radiography, clinical symptoms and the operative procedures are discussed. By means of condylectomy (four patients), or a condylotomy (14 patients) or a horizontal ostectomy in the ascending ramus (performed in two patients with a relapse of condylotomy) in which a triangular bone fragment is removed in the dorsocaudal region, bone contact is prevented during mouth-opening. Considering the number of relapses (three of the 18 operated patients) the results as compared with those in the literature may be described as satisfactory.


Stomal dysfunction following partial gastrectomy. The case is reported of a man aged 57 years in whom after partial gastrectomy, gastric emptying remained impaired for a long period of time. The disorder was caused by stomal dyfunction. After 74 days' conservative therapy, mostly on an outpatient basis, passage through the stomach recurred spontaneously. Successful conservative therapy of such a long duration has not previously been reported in the literature. Protracted obstruction of the stoma after partial gastrectomy is rare. On the basis of data in the literature and of personal experience the author advocates prolonged conservation therapy, unless there exists definite proof of a mechanical obstruction.


Resection of the rectum with preservation of continence by means of a transanal anastomosis. Resection of the rectum with restoration of continuity via a transanal side-to-side anastomosis is a relatively simple and safe surgical technique for the treatment of tumours localized 9 cm or more from the anus. Even a temporary artificial anus is superfluous. In none of the six patients thus treated was any complication observed, all are normally continent. The technique used is described in detail.


Tendency of fluorouracil to conceal deep foci of invasive basal cell carcinoma. Topical fluorouracil treatment of invasive basal cell carcinomas (BCC) is not recommended because it often produces the appearance of control with superficial inhibition of the tumor as the deeper extensions continue to grow, which results in a needless delay in obtaining effective treatment. These conclusions are based on data obtained during the microscopically controlled excision of 103 invasive BCCs of the face that had recurred after topical fluorouracil treatment.


Lucio's phenomenon and diffuse nonnodular lepromatous leprosy. The records of ten patients with Lucio's phenomenon showed clinical and histopathological changes similar to those described by others. Lucio's phenomenon is a syndrome distinct from erythema nodosum leprosum as indicated by an absence of fever, leukocytosis and tenderness, a failure to respond to thalidomide, and a restriction to patients with diffuse nonnodular lepromatous leprosy. Lymphopenia associated with splenomegaly in three patients and glomerulonephritis in one patient were unexpected findings of unknown relevance.


Percutaneous absorption in experimental epidermal proliferation. Essential fatty acid deficiency (EFAD) results in epidermal hyperproliferation with acanthosis and hyperkeratosis. The EFAD hairless mouse has been used to study the percutaneous absorption of a 0.1% solution of 4-(14)C-hydrocortisone. In vitro absorption was increased significantly through EFAD compared with normal hairless mouse skin. This is further evidence for a defective skin barrier function in epidermal hyperproliferation.


Histopathology of oral lesions of discoid lupus erythematosus. A review of 25 cases. In a study of 25 oral biopsy specimens of lesions of chronic discoid lupus erythematosus, a characteristic and diagnostic histopathological pattern was confirmed, which consisted of parakeratosis, hydropic degeneration of stratum germinativum, collagen degeneration and a lymphocytic infiltration in a perivascular orientation. It is suggested that more oral biopsies be used in the diagnosis of discoid lupus erythematosus because of the ease of oral mucosal biopsy technique and the absence of scarring and discomfort from oral biopsy lesions.


Lichen planus and discoid lupud erythematosus. Overlap syndrome associated with cryoglobulinemia and hypocomplementemia. A patient with the discoid lupus erythematosus and lichen planus overlap syndrome has profound depression of serum C4 concentration associated with substantial mixed cryoblobulinemia. A family study failed to disclose evidence of a familial hypocomplementemia, cryoglobulinemia, or a dermatologic condition. Immunologlobulin, but no complement, was detected at the site of the skin abnormality. This case illustrates an immune-complex disorder with a mixed cryoglobulinemia that is related to immunoglobulin deposition in the skin.


Eosinophilic fasciitis.

Eosinophilic fasciitis. Localized areas of indurated skin, which were adherent to the underlying tissues of the upper extremities, suddenly developed in 55-year-old woman. Histologic examination of these bound-down areas disclosed a thickening and inflammation of the deep fascia. There was an associated eosinophilia and a marked clinical improvement after 18 months of oral steroid therapy. These gross and microscopic findings, as well as the peripheral eosinophilia and clinical response while oral steroids were administered, are all characteristics of the recently described entity called eosinophilic fasciitis. Its recognition is important since it may be steroid responsive.


Hearing aid dermatitis.

Hearing aid dermatitis. Allergic eczematous contact dermatitis developed in the external auditory canals and external ears of a woman who wore bilateral "in-the-ear" hearing aids. Patch tests demonstrated that methyl methacrylate monomer was the offending chemical. Heat curling the resin increased polymerization and reduced the amount of residual acrylic monomer, thus alleviating the problem.


Lymphomatoid granulomatosis after immunosuppression for pemphigus. Lymphomatoid granulomatosis developed in a patient with pemphigus vulgaris who had been undergoing immunosuppressive therapy for three years. At autopsy, typical angiodestructive and angiocentric lesions with large lymphoid cells (immunoblasts) were found in the lungs and mediastinal nodes. Although a direct causal relationship between immunosuppression and lymphomatoid granulomatosis is lacking, the association of the two has been described. Immunoblastic sarcoma is also seen in immunosuppressed patients, and the role of the immunoblast in both of these disorders indicates that they may be related. This report suggests that, like immunoblastic sarcoma, lymphomatoid granulomatosis may develop under conditions of diminished immunologic surveillance, whether iatrogenic or naturally occurring.


Superior vena caval syndrome.

Superior vena caval syndrome. The two cases of the superior vena caval syndrome described illustrate the problem of making a diagnosis and of determining the etiology of this syndrome. The cutaneous manifestations were typical of the syndrome and included the sudden onset of facial and upper extremity edema, erythema, and telangiectasia. The causes of the syndrome cannot be recognized from the clinical presentation. In one of our cases, the cause was only determined at autopsy and proved to be an unusual benign cause, idiopathic thrombosis, masquerading as a malignant tumor; the other case was caused by an actual malignancy. The manifestations of the syndrome should alert the physician to determine its cause in order that appropriate therapy may be instituted as rapidly as possible.


Ichthyosis hystrix.

Ichthyosis hystrix. According to a popular system of classification, the term ichthyosis hystrix denotes an organoid epidermal nevus composed of hyperkeratotic papules with a bilateral distribution. Our patient had dramatic disfiguring epidermal changes of this type covering nearly all of her body. Although this abnormality began at the age of 2, she does not exhibit any of the various neurological or skeletal derangements that have been reported to be associated with the condition.


A diffuse pustular eruption associated with ulcerative colitis. Two patients each with a two-year history of chronic ulcerative colitis developed, over a 24- to 48-hour period, painful pustules involving the skin and oral mucosa. The pustular eruption was associated with a severe exacerbation of the colitis. Culture of the lesions and of the blood failed to reveal an infectious cause for the eruption. Histologic study of a pustule in case 2 revealed suppurative folliculitis. The lesions subsided rapidly in case 1 when intravenous hydrocortisone and intravenous and intramuscular antibiotics were administered, and further resolution occurred after colectomy. A similar rapid resoultion of the pustules occurred in case 2 after initiation of treatment with intramuscular cortisone acetate and antibiotics and with colectomy. This pustular eruption may represent a variant of pyoderma gangrenosum.


Spindle cell lipoma. An unusual dermatologic presentation. A 30-year-old woman had nontender subcutaneous mass over the left temple that histologically demonstrated a mixed pattern of mature lipocytes and spindle cells, many in a palisading and fascicular pattern, separated by fibrous trabeculations. No cellular atypia or increased mitotic activity was seen, and a predominance of mast cells was noted. This case illustrates the spindle cell lipoma, a benign variant of lipoma that has been confused in the past with both malignant spindle cell and lipocytic tumors. Our case, although atypical in sex, age, and location, serves to identify this entity in the dermatologic literature.


Langerhans cells in contact dermatitis of the guinea pig. In the guinea pig, the epidermal Langerhans cells studied by adenosine triphosphatase and electron microscopic techniques in dinitrochlorobenzene-induced contact dermatitis showed early cellular vacuolar and granular changes and intraepidermal contact with mononuclear cells. At later periods of up to 48 hours, the Langerhans cells migrated to the surface of a thickened epidermis and were lost in the parakeratotic horny layer that was shed. Thus, the Langerhans cell probably has a macrophage-type role in the epidermal reaction of contact dermatitis, and as the sponglosis and the inflammatory reaction develop, these cells are shed with the degenerating keratinocytes.


Scleroderma, eosinophilia, and diffuse fasciitis. Skin induration without internal organ involvement, blood and tissue eosinophilla, and fascilitis are features of diffuse fascilitis. However, cellular infiltrates (lymphocytes, plasma cells, and eosinophils) may also be present in the dermis, fat, and muscle. Blood eosinophilia (mild and transient) and skin eosinophilia were observed in about 20% of patients with systemic and localized scleroderma.


Subcutaneous mycosis fungoides.

Subcutaneous mycosis fungoides. In five cases of mycosis fungoides, previously treated with electron-beam therapy, subcutaneous nodules developed. Clinically, these lesions were thought to be epidermoid cysts or lipomas, but on biopsy were discovered to be subcutaneous infiltrates, three of which were diagnosed as mycosis fungoides. The other two specimens showed only a nonspecific subcutaneous infiltrate. There is no ready explanation for the appearance of these lesions, but it is speculated that they may be the result of inadequate penetration of the electron beam to the depth at which some atypical cells may originally have been located. Patients with mycosis fungoides who develop unusual subcutaneous nodules should be fully investigated so that appropriate and adequate therapy may be initiated.


Dermatitis from purified sea algae toxin (debromoaplysiatoxin). Cutaneous inflammation was induced by debromoaplysiatoxin, a purified toxin extracted from Lyngbya majuscula Gomont. This alga causes a seaweed dermatitis that occurs in persons who have swum off the coast of Oahu in Hawaii. By topical application, the toxin was found to produce an irritant pustular folliculitis in humans and to cause a severe cutaneous inflammatory reaction in the rabbit and in hairless mice.


Cutaneous leishmaniasis: surgical management of a case with unusual clinical and histological features. Our case of cutaneous leishmaniasis clinically resembles the atypical form "infiltrees en nappes" that was described by Photinos in 1930. A subsequent biopsy of the lesion was performed more than one year after its onset and after a full course of stibogluconate sodium and the specimen showed multiple organisms in multinucleated giant cells as well as in histiocytes. Electrodesiccation and curettage of the lesion resulted in complete healing with minimal scarring.


Basal cell nevus syndrome in a black patient: report of a case and review of the literature. An 80-year-old black man had multiple basal cell epitheliomas (BCEs), palmar pits, and mandibular cysts. This patient is unusual, not only because of multiple BCEs, but also becuase they developed when the patient was at age 77. Only three other black patients with multiple BCEs in association with basal cell nevus syndrome have been reported previously.


Retroperitoneal liposarcoma metastatic to scalp. Metastasis of liposarcoma to the scalp occurred in a 50-year-old-man. Review of the literature disclosed no documented reports. Although cutaneous metastases from internal malignancies are of relative infrequent occurrence, such metastases may be limited to the scalp and a diagnosis can be established by a biopsy.


Pilomatricomas associated with myotonic dystrophy. A report of the ninth and tenth cases of myotonic dystrophy associated with pilomatricomas and a review of the previously reported eight cases showed that seven of the ten patients had multiple pilomatricomas. Six of ten patients had another relative with both myotonic dystrophy and pilomatricomas. Patients with both myotonic dystrophy and pilomatricomas are more likely to have multiple tumors and to have a familial occurrence. The prevalence of pilomatricomas in patients with myotonic dystrophy is higher than in the general population. Pilomatricomas may be a cutaneous manifestation of the myotonic syndrome.


Vitiligo, chronic thrombocytopenia, and autoimmune hemolytic anemia. A 12-year-old boy with vitiligo, chronic thrombocytopenia, and a Coombs's positive autoimmune hemolytic anemia was treated with oral psoralens and exposure to ultraviolet light. An acute hemolytic crisis developed and he died. The association of autoimmune hemolytic anemia and vitilligo should be looked for in other cases. Until more information is available, patients with vitiligo and thrombocytopenia should not be treated with psoralens and exposure to ultraviolet light.


An unusual case of North American blastomycosis. A patient with a laryngeal tumor first diagnosed as squamous cell carcinoma was subsequently found to have North American blastomycosis. Diagnosis of this condition eventuated in eradication of the lesion as well as removal of a tracheostomy, which was thought to be permanent.


Defective leukocytotaxia and recurrent staphylococcal infecion: deficiency of leukocytotaxia and abnormal granulocytes associated with increase serum IgE levels in an adult with recurrent staphylococcal infection. A man who was suffering from recurrent staphylococcal infection had antecedent symptoms of severe pruritus. Laboratory investigations showed leukocytosis with eosinophilia, hyperimmunoglobulinemia of all fractions, but particularly of IgE, and a deficiency of cell-mediated immunity on in vivo testing. Phagocytosis and bactericidal activity of polymorphonuclear leukocytes were normal, but a cellular and serum-associated defect in leukocytotaxia was present. Ultrastructural changes were observed in polymorphonuclear leukocytes. Association of impaired leukocytotaxia and elevated levels of IgE is not uncommon. Recurrent bacterial infections in the patient described are probably related to defective chemotaxis.


Gluten challenge in treated coeliac disease. Thirty-two children with a past diagnosis of coeliac disease were reinvestigated by means of gluten challenge. They had received a gluten-free diet for a mean period of 6-5 years (range 0-25-11-0) before gluten challenge, and had a mean age of 9-9 years (range 3-0-15-3) at the onset of challenge. Small intestinal biopsies were performed before and after the gluten challenge (at least 10 g natural gluten per day for 3 months in the majority) and, as judged by light microscopy and morphometric techniques, coeliac disease was confirmed in 25 (78%) of the 32 patients; challenge was continued in the remaining 7 for a total period of 2 years when biopsies were repeated in 6 children and all were normal. Serum and RBC folate, serum iron, Hb level, and clinical symptoms were unpredictable variables in identifying children who developed gluten-induced enteropathies. The social and emotional effects of gluten challenge are discussed. The results highlight the importance of gluten challenge and intestinal biopsy in the diagnosis of coeliac disease and strongly suggest that a normal biopsy after a 3-month gluten challenge (as described above) excludes coeliac disease.


Renin and aldosterone response in human newborns to acute change in blood volume. Increased activity of the renin/aldosterone system in the neonatal period is now well established in both animals and man but the control mechanisms are poorly understood. We have monitored the plasma renin activity (PRA) and plasma aldosterone concentration (PAldo) in 14 infants undergoing 21 exchange transfusions. PRA and PAldo were measured before and at 5, 10, 15, 30, 45, and 60 minutes after the injection, and 5, 10, 15, and 30 minutes after the withdrawal of 7 ml blood/kg birthweight immediately before exchange transfusions. PRA increased to a maximum of 53% and decreased to a maximum of 39% of the resting values after withdrawal or injection of blood respectively. PAldo values did not change significantly during the same period. Thus the renin-angiotensin system in the newborn infant is responsive to changes in blood volume.


Recurrent wheezing in the preschool child. The bronchoconstrictor response to exercise was measured in 29 healthy children and in 23 children with recurrent wheezing attacks, using the Wright low-range peak flow meter and a modification of the forced oscillation technique. None of the healthy children showed significant change in airflow obstruction after a 6-minute run, whereas 20 of the 23 wheezy children showed a mean rise in total respiratory resistance of 65-5%. All 23 children showed a fall in airflow obstruction after inhaling salbutamol solution.


Reduction of bile acid loss in cystic fibrosis by dietary means. On a 'normal' diet increased faecal bile acid excretion was found in 14 of 16 children with cystic fibrosis who had steatorrhoea, but excretion was normal in 2 such children without steatorrhoea. The 16 children with steatorrhoea took 3 regimens of diet and therapy: a 'normal' diet with pancreatic enzyme supplements, a diet of reduced long-chain triglycerides with added medium-chain triglycerides, and the same diet with added pancreatic enzyme supplements. On each of these three regimens steatorrhoea and faecal bile acid loss were significantly less than on no treatment, with the lowest excretions occurring on the diet of reduced long-chain triglycerides with added medium-chain triglycerides and pancreatic enzyme supplements. Although a reduction in steatorrhoea was nearly always accompanied by a decrease in bile acid excretion, the initial bile acid loss was very variable and could not be predicted for any given degree of steatorrhoea. This suggests that at least one other factor, possibly liver disease or bile acid pool size, influences bile acid loss in the faeces.


Sweat testing for cystic fibrosis. Diagnostic screening with a combination chloride ion-selective electrode. Screening of sweat chloride in newborn infants with the Orion Skin Chloride Measuring System and incorporating some procedural innovations is described. The results indicate that while diagnostic screening for cystic fibrosis can be readily undertaken, the test with the chloride ion-selective electrode is best left at least to the second day of life or later because of insufficient sweating in very young babies. Measurements on 2 babies with cystic fibrosis are also discussed.


Growth hormone release during sleep in growth-retarded children with normal response to pharmacological tests. Twenty-one prepubertal children of small stature, 10 boys and 11 girls, aged from 4-3 to 12-8 years, were studied. Their height was less than 3rd centile, and during the preceding year all had a growth rate less than 4-5 cm/year. Arginine and L-dopa tests were given, and the release of growth hormone (GH) during monitored sleep was investigated. On the basis of the electroencephalogram and horizontal electro-oculogram, sleep was divided into stages 1-2-3-4 and rapid-eye-movement. All the children had a GH response greater than 8 ng/ml in at least one of the two pharmacological tests, and were therefore accepted as not suffering from GH deficiency. In all 21 children during sleep there was at least one secretory peak with GH greater than 8 ng/ml. Of a total of 46 secretory peaks recorded, 22 (48%) took place during deep, slow sleep (stages 3-4), 10 (22%) during light sleep (stage 2), 10 (22%) during REM sleep, and 4 (8%) during wakening. In 4 patients (19%) no secretory peak was observed during stages 3-4, even though there were peaks at other times. The data (a) show that it is essential to monitor GH throughout the night to ascertain with certainty the presence or absence of physiological secretory peaks of GH; (b) emphasise the rare disagreement between pharmacological and physiological tests; (c) suggest the use of this physiological test for GH secretion in those cases where the insulin test may be hazardous.


Growth impairment in children treated for brain tumours. Growth and growth hormone (GH) secretion were studied in 14 children with brain tumours before radiation and chemotherapy and at various time intervals afterwards. The peak GH response to hypoglycaemia was normal in all patients before radiation. In 6 patients the peak GH response was impaired 1 year after radiation, and in a seventh it was normal at 1 year but impaired 2 years after radiation. In 12 of 13 patients the growth velocity during the first year of chemotherapy was below the 3rd centile, although none of these had an initial standing height below the 3rd centile. Thus it appears that poor growth in such children occurs irrespective of whether radiation-induced GH deficiency develops. The cause of this impaired growth is unknown.


Goitre and hypothyroidism in the newborn after cutaneous absorption of iodine. Iodine goitre and hypothyroidism in 5 newborn infants in an intensive care unit were induced by cutaneous absorption of iodine, after numerous skin applications of iodine alcohol. The infant's skin permeability allows severe iodine overloading of the thyroid, resulting in goitre and hypothyroidism. Ioduria should always be sought in a newborn infant showing hypothyroidism. Iodine should not be used as a skin disinfectant in young infants.


Clinical study of prolonged jaundice in breast- and bottle-fed babies. A study of 893 births was undertaken to determine the incidence of prolonged neonatal jaundice. 55% of these babies were breast feeding on discharge from the maternity hospital. Jaundice lasting for 3 weeks or more was found in 12 breast-fed term babies (2-4% of all breast-fed babies), and in no bottle-fed infant. 3 of the jaundiced babies gained weight poorly in the first 3 weeks of life, but after that age failure to thrive was not associated with the prolonged jaundice. The hyperbilirubinaemia, which persisted in 11 infants from between 21 to 80 days (mean 39 days), was due to elevations in both conjugated and unconjugated fractions.


Respiratory depression due to unsuspected narcotic ingestion treated with naloxone. Two patients are presented with respiratory depression for which no cause was apparent. Both had ingested narcotics without the parents' knowledge. Narcotic ingestion should be suspected if signs of respiratory failure with constricted pupils are present, and a diagnostic test with naloxone should be performed.


Estimation of gestational age at birth. Comparison of two methods. Seventy-three low birthweight babies were independently assessed for gestational age using the scoring system of Dubowitz et al. (1970) and 5 neurological reflexes described by Robinson (1966). The results obtained by the 5 reflexes were compared with those obtained by the scoring system and were found to be accurate estimations of gestational age. The 5 reflexes may be used for babies of gestational ages 29 to 37 weeks, but above 37 weeks the scoring system must be used.


Increased urinary catecholamines in an infant with the diencephalic syndrome. In an infant of 15 months with the diencephalic syndrome, urinary excretion of norepinephrine was moderately raised and epinephrine greatly so. It is suggested that catecholamine secretion may be due to sympathetic stimulation at the level of the diencephalon, by a space-occupying lesion pressing on the thalamohypothalamic pathway. Some of the symptoms of the diencephalic syndrome such as euphoria, irritability, skin pallor, and hypertension may be the result of catecholamine secretion.


Use of the diving reflex to treat supraventricular tachycardia in an infant. A simple method for treating supraventricular tachycardias is described--ice cubes are applied to the nose and upper lip. It should be particularly useful in younger children and depends on a sound physiological principle.


At what age do bronchodilator drugs work? Using a modification of the forced oscillation technique we have measured respiratory resistance before and after nebulised salbutamol therapy in 32 wheezing children aged 7 months to 3 years 7 monts. 12 of the children were also studied in a total body plethysmograph. No child under 18 months of aged showed a greater than 5% fall in resistance or any fall in thoracic gas volume. In contrast, 18 of 20 children over 20 months of age showed a fall in resistance greater than 20%.


Effects of delivery by caesarean section on lung mechanics and lung volume in the human neonate. Lung function tests were carried out in the first 6 hours of life on 26 babies born by vaginal delivery and 10 born by caesarean section. The babies born by caesarean section had a mean thoracic gas volume of only 19.7 ml/kg body weight compared with 32.7 ml/kg for the babies born vaginally. We conclude that this is owing to an excess of lung fluid in the babies born by caesarean section.


Percutaneous catheterisation of the radial artery in newborn babies using transillumination. A technique for inserting radial artery catheters percutaneously in newborn babies using transillumination is described. Catheterisation was successful in 69% of the 107 babies in whom it was attempted. In the last 30 attempts there was an 85% success rate with an average useful life of 100 hours. The average weight of these babies was 1405 g, with a range of 620--4250 g. The method has several advantages over previous methods.


Neurological sequelae in newborn babies after perinatal asphyxia. A total of 53 babies, 37 to 44 weeks' gestational age with a history of fetal distress in labour, and severe neurological abnormalities in the early newborn period, were followed up for between 2 and 5 years. Their progress was compared with an equal number of normal babies matched for gestational age, birthweight, sex, and social class, but without a history of fetal distress or delay in establishing spontaneous respiration at birth. In the set of babies with a history of fetal distress no perinatal condition was identified that could predict with certainty the type of neurological status in the newborn period, or the occurrence of neurological abnormality in later childhood. Follow-up disclosed a considerable improvement in function in most of the apparently brain-injured babies. It is suggested that such babies exhibiting apathy initially but subsequently hyperexcitability and extensor hypertonia carry the worst prognosis.


Value of screening for deafness in the first year of life. Despite efforts to screen all babies for deafness within their first year, the handicap is still being detected later than is desirable. This study designed to evaluate the effectiveness of current audiometric screening programmes. Hearing tests were carried out on 535 infants between the ages of 6 months and one year using conventional tests, which depend on the infants' response to familiar sounds, and pure-tone audiometry. The results reveal inadequacies in both sets of tests which, coupled with a high default rate, may well account for the very small contribution that routine audiometric screening is making to the early diagnosis of deafness.


Behavioural treatment of hyperactive children. This study reports the value of behavioural treatment of hyperactive children. Twelve children with multiple behavioural problems, including concentration difficulties, were identified and treated during a 3-month period. Six of the children began treatment immediately; the other 6 children received similar treatment but after a delay of between 4 and 6 weeks. Children were seen at the clinic or in the home, depending upon the individual difficulties and geographical distances. Initially the families were seen weekly, but the frequency later was determined by the severity of the problems and the response to treatment. There was a significant improvement in the children's behaviour as reported by the parents, the home visitor, and videotaped recordings. During the initial period of beteen 4 and 6 weeks the treated children improved significantly, whereas the others, as yet untreated, showed no change. As soon as the treatment was introduced to the second group these children's behaviour also improved and to about same extent in 6 weeks as the treated children had in up to 12 weeks' treatment. This interesting observation suggests that a short period of treatment, only 6 weeks, may be sufficient for most children with hyperactivity. This is more feasible with the present-day resources of many departments.


Successful restoration of immunity in the DiGeorge syndrome with fetal thymic epithelial transplant. A 13-month-old girl presented with right upper lobe pneumonia and hypocalcaemic seizures: investigations showed hypoparathyroidism and impaired cell-mediated immune responses. Other features of the DiGeorge syndrome included hypertelorism, short philtrum of the lip, right-sided aortic arch, and aberrant origin of the left subclavian artery. Successful restoration of the immunodeficiency was achieved by transplantation of fetal thymic epithelium.


Position of the apex beat in childhood.

Position of the apex beat in childhood. The position of the apex beat in relation to the midclavicular and nipples lines and the intercostal spaces was studied in 353 healthy Jamaican children from birth to 10 years. The traditional use of the midclavicular line as a reference point in relation to the apex beat is not an accurate index of normal heart size at all ages. For this purpose actual measurement of the apex beat, which ranges between 2.8 and and 5.4 cm from the midline, should be made. However, for a rough estimate of normal cardiac size the midclavicular line may be used. In contrast, the nipple line lies outside the apex beat at all ages; it should not be used in the clinical evaluation of normal cardiac size. From birth to age 3 years the apex beat is located in the 4th intercostal space and with increasing age gradually moves into the 5th space in most children.


Repeat lumbar puncture in the diagnosis of meningitis. Meningitis may be difficult to diagnose. If it is suspected clinically and a first lumbar puncture is normal, a second cerebrospinal fluid (CSF) sample may be required within a few hours to confirm the diagnosis. A child is presented in whom CSF was normal 14 hours after the onset of illness, but who 14 hours later showed the characteristic changes of purulent meningitis. This case differs from those previously cited in the literature, in that the blood cultures taken at the time of the first lumbar puncture were also negative.


Significance of intracranial bruits in neonates, infants, and young children. In a control group an intracranial bruit (ICB) was heard in 4 of 13 children aged between 4 months and 3 years, but in none of 43 younger infants between the ages of one day and 4 months. In a group of 70 infants with cardiac murmurs of intensity grade III/VI or more, 19 of 30 aged between 4 months and 3 years had an ICB, compared with 4 of 40 younger infants aged between one day and 4 months (P less than 0.0005). It is concluded that in infants under the age of 4 months, even in the presence of a loud cardiac murmur, an ICB is rarely heard. The presence of an ICB, with or without signs of cardiac failure, strongly suggests an intracranial arteriovenous fistula.


Propranolol as an antihypertensive agent in children. The antihypertensive effect of oral propranolol was studied in 9 children with hypertension. After treatment with propranolol, systolic blood pressure fell by an average of 26 mmHg (P less than 0.01). Diastolic pressure decreased by 20 mmHg on average (P less than 0.01). The mean propranolol dose was 2.5 mg/kg per day. Side effects included bradycardia and anorexia. There was no correlation between pretreatment plasma renin activity and fall in blood pressure. Propranolol is an effective and well tolerated antihypertensive agent in children.


Heights and weights of West Indian children with the sickle cell trait. No consistent differences were found in mean heights and weights of 170 schoolchildren aged 6--12 years with the sickle cell trait and 1247 schoolchildren with normal haemoglobin living in Dominica and Jamaica.


Weaning very low birthweight infants from mechanical ventilation using intermittent mandatory ventilation and theophylline. Two very low birthweight infants with severe clinical hyaline membrane disease requiring mechanical ventilation were dependent on slow-rate intermittent mandatory ventilation, without which they developed apnoea or hypopnoea and hypercarbia. Their ventilator dependence was apparently owing to inadequate ventilatory effort, and treatment with oral theophylline allowed easy weaning to continuous-positive airway pressure and extubation. PaCO2 was significantly lower during theophylline treatment, suggesting that the drug may have improved alveolar ventilation.


Right-sided congenital diaphragmatic herniae presenting as pleural effusions in the newborn: dangers and pitfalls. Congenital diaphragmatic hernia presented with right-sided pleural effusion in two newborn infants.


The relation of nervous elements to intradermal nevi. As electron microscopic study. Intratumoral nerves of dermal nevi were investigated by electron microscopy in order to elucidate the role of neural elements in the development of these tumors. The following results were obtained: 1. Intratumoral nerves exhibit an increased cellularity, but the number of myelinated fibers is reduced. 2. Nevus cells type B and C are frequently present within nerve fascicles. 3. Unmyelinated axons were found in close relationship to nevus cells. 4. Schwann cells may show proliferations similar to early stages of neurofibroma and can be differentiated from unpigmented tumor cells by their relation to axons only. These findings indicate that identical cell populations are present within the intratumoral nerves and the tumor itself. Therefore, the theory of a neural component in the histogenesis of intradermal nevi is supported.


Plasminogen activators of psoriatic scale extracts. Separation of two plasminogen activators by isoelectric focusing. Psoriatic scale extracts were fractioned by using polyacrylamide gel isoelectric focusing (PAGIF) and preparative electrofocusing in granulated gel (PEGG). The largest protein fraction was found with Ip at pH 4.8--5.0, and the main protein bands within pH values 4.0--7.5. PEGG separated three main fractions with plasminogen activator or trypsin-like esterase activity with isoelectric points at pH 6.5--6.6, 5.4--6.2 and 4.9. The enzyme with Ip at pH 6.5--6.6 hydrolyzed trypsin substrates but lacked plasminogen activator capacity. The enzyme with Ip at pH 5.4--6.2 showed both activities but the third enzyme with plasminogen activator capacity with Ip at pH 4.9 was without detectable esterolytic activity towards substituted basic amino acid esters. The third enzyme was prominent in KCl-extract and the second in KSCN-extract. The first was equal in both extracts. The enzyme with Ip at pH 4.9 is possibly of bacterial origin while the plasminogen activator with Ip at pH 5.4--6.2 extracted in KSCN probably represents tissue activator of psoriatic scales.


Dark effect of 8-methoxypsoralen (8-MOP) on lymphocytes. In order to find, whether 8-MOP has an inhibiting effect on the proliferation of lymphocytes in the dark, we studied in vitro the lymphocyte proliferation by a mitogen (HgCl2) and by an antigen (tuberculin) from 16 psoriatic patients during the first oral PUVA treatment immediately before 8-MOP intake (03.--0.5 mg/kg body weight), 2 h later (time of maximal serum concentration) and after 24 h. The percentages of B- and T-lymphocytes were measured from 15 other psoriatic patients at equal times. There was a significant decrease (P less than 0.05) of the lymphocyte proliferation after stimulation with HgCl2 in culture, 2 h after 8-MOP, returning completely to the starting range after 24 h. On the contrary, neither the proliferation capacity of lymphocytes after stimulation with tuberculin nor the percentages of B- and T-lymphocytes were significantly changed. Obviously, 8-MOP, even without UVA irradiation, has a direct inhibiting effect on lymphocyte proliferation in concentrations therapeutically used. However, this effect is seen only with stimulation by a mitogen, not by an antigen. It cannot be explained by a change in the ratio between B- and T-lymphocytes.


Synergistical effects of ficoll and phytohemagglutinin on human lymphocytes. The influence of increasing concentration of the highly polymerized dectran Ficoll on cultured peripheral human blood lymphocytes stimulated or not stimulated by PHA was studied. The incorporation of 14C-thymidine into acid-insoluble material of unstimulated lymphocytes has not been influenced in the presence of increasing concentrations of Ficoll either pretreated with chelating resin or not pretreated. Ficoll not pretreated with chelating resin potentiates the PHA-induced stimulation by the factor 4.3 at 0.1 mg Ficoll/ml culture medium, and by the factor 3.2 at 1.0 mg/ml when PHA stimulated HPBL were used. Ficoll after pretreatment with chelating resin does not influence the DNA-synthesis at 0.1 mg Ficoll/ml medium, but causes a drop of the incorporation of 14C-thymidine by the factor 2.0 at 1.0 mg/ml. Using 10.0 mg per ml, both Ficoll preparation cause a decrease of the DNA-synthesis by the factor 2.5--3.0--probably a cytotoxic effect. The results obtained with emission spectrographic analysis and conductivity measurements show, that Ficoll after treatment with chelating resin contains about 10 times more ions (Mg, Ca, Na, Si) and has a 3.2-fold higher conductivity then Ficoll without pretreatment. It is possible that phenomena like electrochemical changes on the surface of the lymphocytes and osmotic alterations in the culture medium are responsible for these effects.


Psoralen/UVA treatment and chromosomes. II. Analyses of psoriasis patients. Five psoriasis patients treated with 8-methoxypsoralen and UVA (PUVA) were studied by lymphocyte cultures at the 1st, 5th, 10th and 20th treatment and at a maintenance treatment 6 months later. Abnormal amounts of chromosome aberrations were not found, and the frequency of sister chromatid exchange (examined at the last treatment) was not increased. In vitro experiments with nanogram doses of psoralen (similar to plasma levels in patients) showed no increase in chromosome aberration or SCE freqency. The results indicate that therapeutic doses of PUVA have no clastogenic effect.


Staphylococci of the normal human skin flora. Variety of biotypes and antibiograms without direct correlations. 352 strains of Staphylococci of the normal human skin flora were sampled from one volunteer by single scrabbing in a ca. 3 cm2 measuring area. They were biotyped by the scheme of Pelzer et al.(1973)--a modified Baird-Parker-Scheme (1963)--and the resistance to antibiotics was investigated by the method of Bauer et al. (1966). All the nine biotypes of Staphylococci were found in variable quantities. It seems problematic to call one biotype as the main type. Morphologically identical colonies of Staphylococci from the indigenous flora of the human skin were not identical in their biotypes as previously described by Pelzer (1976). Only the investigation of all Staphylococci colonies from the culture plate can evaluate all biotypes of Staphylococci of the normal human skin flora, and can give the right quantitative correlation. Staphylococci were found to be sensitive and resistant up to four antibiotics, and one biotype did not show one type of antibiogram.


On the occurrence of the contact allergen primin and other quinoid compounds in species of the family of primulaceae. 82 different species of the Primulacea family have been investigated by a screening test. In 16 Primula species and 4 species of other genera the strong contact allergen primin could be detected by the Craven-test. Extracts of only 12 plants gave no color reaction. In the remaining species other quinoid components were detectable. From 4 species new quinoid substances were isolated. Primin itself was obtained from Primula elatior and from the petals (corollas) of Primula obconica. The results indicate that the presence of primin and other quinones is determined by their origin and seasonal variations. It is supposed that some of the detected quinones may function as allergens and therefore may be responsible for the contact dermatitis described in the literature due to several Primula species and some other species of the same family. Some indications point to the suspicion that primin occurs in the plant as a glycoside which is separated by extraction treatment to give its quinole and an unknown substance. The quinole oxidizes then to the quinhydrone and finally to primin itself.


Erythrocyte glucose-6-phosphate dehydrogenase in lichen planus. Cotton et al [1] comparing glucose-6-phosphate dehydrogenase (G-6-PD) activity in biopsies from patients with lichen planus (LP) with that in normal skin suggested that LP might be associated with a congenital abnormality of the enzyme in the skin. Ryan et al. [7] were unable to confirm these results. It is known that individuals with erythrocyte G-6-PD deficiency show a similar decrease of the enzyme in the skin [2] and that skin biopsies can be used to diagnose favizm [3]. The increased incidence of LP in the tropics [6, 8] coincides with the prevalence of erythrocyte G-6-PD deficiency in the same geographical region. The semi-quantitative method of Motulsky did not reveal any difference of erythrocyte G-6-PD activity between patients with LP and control subjects [5]. The present study reports the results obtained with a more sensitive method of erythrocyte G-6-PD determination in a group of Africans with LP. Thirty Nigerian patients with typical clinical picture of LP (23 men and 7 women), aged 15--45 were studied. Control 30 subjects were matched for age, sex and tribe and included persons suffering from scabies and mild pyogenic and superficial mycotic infections. The activity of the erythrocyte G-6-PD was determined at 37 degrees C using the WHO method [9]. Normal values for Northern Nigerians are 1200 +/- 234 mu/1010 red cells. The results (Fig. 1) show a decrease of the erythrocyte G-6-PD activity in patients with lichen planus (P less than 0.01). No relationship between erythrocyte G-6-PD activity and extensiveness, activity or age of onset of the skin lesions was found. The finding of decreased erythrocyte G-6-PD activities in patients with LP in an area where an increased incidence of this skin disease coincides with higher frequency of favizm might suggest a biochemical overlap between these two conditions. Holzmann et al [4] have suggested that the reverse situation of mutual exclusiveness exists between G-6-PD deficiency and psoriasis. In regions with high frequency of G-6-PD defiency psoriasis is uncommon.


Serum levels of 8-methoxypsoralen in psoriasis patients using a new fluorodensitometric method. A method is described for the determination of 8-methoxypsoralen in human serum using a fluorodensitometric method. The fluorescence densitometry was carried out directly on the thin layer plate. The developing fluid consisted of chloroform/methanol. In patients with psoriasis after oral application of 8-methoxypsoralen the peak serum levels are mostly found between 2 and 3 h. One milliliter serum is sufficient to determine 8-methoxypsoralen levels. The results are in accordance with those obtained with gas chromatographic methods.


Decrease in neutrophils observed in vivo in psoriatics after PUVA therapy. In 56 patients leucocyte and differential counts were done before and at weekly intervals during PUVA treatment of chronic recalcitrant psoriasis. A statistical significant (P less than 0.01) decrease in the percentage of neutrophils was observed during the first week of the PUVA therapy. This observation could be closely related to the clinical clearing of psoriasis (P = 0.02). The effect of PUVA therapy in psoriasis may be due to a decrease in the number of immunocompetent neutrophils demonstrated in psoriatic lesions.


Effect of repeated ultraviolet irradiation on skin of hairless mice. The effect of repeated UV-irradiation on mechanical and biochemical parameters was studied in skin of hairless mice. UV-A irradiation for a period of 1 h daily over 8 weeks caused only a slight increase in skin thickness and a decrease in ultimate strain. The changes induced by UV-B and C, however, were quite remarkable. Skin thickness was increased depending on the daily dose exposure time (15--90 s at an irradiation rate of 20 mW/cm2 UV-B and A and of 14 mW/cm2 UV-C) and the duration of treatment (1--6 weeks). Ultimate load, tensile strength and modulus of elasticity showed an increase following medium dosages after 1 and 2 weeks, however, a decrease after high dosages and longterm treatment. Ultimate strain was found to be the most sensitive parameter being decreased depending on exposure time and duration of treatment. Insoluble collagen and total collagen were decreased after long-term treatment thus being correlated with the mechanical parameters. The elastin content was only barely influenced and not correlated with the mechanical data, e.g. the modulus of elasticity. Thus, a favourable effect of short-term treatment with low doses of UV-irradiation of mechanical parameters of skin could be demonstrated. Long-term treatment with relatively high doses of UV-B, however, resulted in unfavourable effects, whereby first ultimate strain, then ultimate load, modulus of elasticity and tensile strength were decreased.


DNA-repair after UV-irradiation in skin fibroblasts from patients with actinic keratosis. Autoradiographic counting technique was utilized to measure the ultraviolet-induced unscheduled DNA synthesis of skin fibroblasts from 12 patients with chronic actinic keratosis and from 12 healthy donors of about the same age. In order to reveal a possible regional difference of DNA repair between the parts of the body ordinarily exposed and those parts unexposed to sunlight, two cell strains were used for each examined subject; one developed from the forehead skin and the other from the abdominal or axillary skin. Unscheduled DNA synthesis appeared depressed in actinic keratosis patients, as compared with controls. In all examined subjects however cell strains from exposed skin showed a DNA repair more active than cell strains from unexposed skin. These findings show that skin cancer may be promoted in actinic keratosis patients by a defect of DNA repair. The exalted DNA repair of chronically sun exposed skin is probably the consequence of a defensive process caused by enzymatic induction.


[Skincycle of a new spontaneous mutant (Nackig) with abnormal hair keratinization in the mouse (author's transl)]. The pathomorphological and pathophysiological reactions of the first skincycle of the mutant (Ng) were histologically investigated. 1. During the hair growth disturbances as the result of imperfect keratinisation changes of the morphology and function of different skin areas could be observed. 2. The developments of abnormal thinner hair growth were correlated to hyperorthokeratotic, inter-respectively intrafollicular hyperplasia of the epidermis and to infraseboglandular hypoplasia of the follicles. 3. The hyper- and hypoplasia of the epidermis corresponded with a functional pseudohypo- and pseudohypertrophy of the cutis. 4. During the skincycle the perifollicular epithelium ranged from the inter- to intrafollicular skin areas. The inter- and intrafollicular epidermal sections varied simultaneously. 5. These results are important for the understanding of some pathomorphological and pathophysiological reactions of skin compartments of man.


Actinic elastosis in black skin. A light- and electronmicroscopic study. In 9 otherwise dermatologically normal South African Balck volunteers (1--72 years old), sunlight-exposed and non-exposed skin has been examined by light- and electronmicroscopy with special references to age-dependent and actinic alteration of dermal structures. Two 72 year old Blacks exhibited typical dermal elastosis: in 1 case to a marked extent and already detectable by lightmicroscopy, in the other case only to a mild degree. In contrast, only age-related elastic fibers were revealed in the lower dermis of sunlight-exposed skin and in all dermal layers of unexposed skin. These observations are contradictory to the general view that actinic elastosis does not occur in Blacks. The elastotic material is obviously a de-novo synthesized and secreted pathological product of chronically UV-altered fibroblasts.


Ultrastructural studies of epidermis in acute radiation dermatitis. Basal lamina thickening and coated vesicles. Fine structural changes of keratinocytes by X-ray were examined in normal skin area around a lesion of Bowen's disease. The area was exposed to about 6000 r over 28 days. The findings were: a decreased number of desmosomes and microvilli, formation of cytoplasmic vaculoes with or without membrane, perinuclear aggregation of tonofibrils, intracytoplasmic desmosomes and gap junction, cytoplasmic occurrence of dense bodies, lipid droplet and glycogen particles, changes in mitochondria, endoplasmic reticulum and Golgi complex, and deep invagination of the nuclear membrane. Besides these, conspicuous in the present study were, changes in the basal lamina which consisted of multiplication, thickening and occasional detachment from basal cells, and frequent occurrence of coated vesicles along with the basal lamina alteration. Possible exocytotic nature of coated vesicles in X-ray irradiated keratinocytes is discussed.


[Maturation and aging of elastic fibers (authors transl)]. The non-sunexposed skin of 12 healthy individuals was investigated under the electron microscope and the fine structure of normal elastic fibers was compared by different methods in 3 groups of age: 1--10 years, 30--50 years, and 60 years. 1. The elastic fibers of human skin may be semiselectively stained with silver tetraphenylporphyrine sulfate (Ag-TPPS), uranyl acetate, lead citrate and tannic uranyl acetate. They are composed of an amorphous matrix which is interwoven and surrounded by microfilaments. Elastic fibers are fully developed in early periods of age, first showing numerous microfilaments as structural glycoproteins, and then the deposition of the amorphous proelastin to be transformed into elastin. 2. The period of maturation is followed continuously by processes of physiological aging: a) decreasing number of microfilaments, b) appearing of electron-dense inclusions into the elastin matrix and c) fragmentation and disintegration of the fiber. 3. These changes indicate that aging of the fiber includes diminished synthesis of structural glycoproteins (microfilaments) and increasing content of osmiophilic groups, such as polar aminoacids, fatty acids and calcium salts. The fiber becomes thus more susceptible to the activity of elastase, and may totally disintegrate in older age.


Pseudolymphoma of skin induced by oriental hornet (Vespa orientalis) venom ultrastructural study. A single subcutaneous injection of Oriental hornet venom into black mice led to the development of a subcutaneous nodule which showed no change during the period of 1 year. Study of the ultrastructure revealed an accumulation of lymphocytes and lymphoblasts and a few plasma cells with formation of Russel bodies. In addition, a few melanin-containing macrophages and macrophages filled with cellular debris were found. This reaction is compared to other pseudolymphomatous reactions in the dermis.


Impairement of thymus derived rosette forming cells during photochemotherapy (psoralen--U.V.A.). Lymphocyte subpopulations were studied in 45 PUVA treated patients and in 45 controls matched for sex and age. The results demonstrate that, in vivo PUVA induces a decrease in the capacity of the E-Rosette formation by lymphocytes separated from the peripheral blood. However, the circulating lymphocytes count remains unchanged. Mitogen induced blastogenesis is not affected. No correlation is found between the decrease in the level of E-rosettes, the disease which motivated PUVA therapy, the energy in UVA and the number of irradiation. Electrical and/or chemical modifications on the cell surface of the lymphocytes during PUVA therapy are postulated to explain this phenomenon.


Plasma kinin activation in tranexamic acid treated patients with hereditary angioneurotic edema. Plasma kinin formation after in vitro activation of factor XII in the coagulation system was examined in 4 patients with hereditary angioneurotic edema. Compared to controls activationcurves showed a steeper increase and higher maximum levels. Administration of tranexamic acid to the patients resulted in partial normalisation of plasma kinin activation.


[Oxygen consumption of the spontaneous and artificially induced skincycle at different times of day (author's transl)]. In the "clean" rat skin purified from the panniculus carnosus the oxygen consumption of the spontaneous and artificially induced skincycle was measured at different times of day. The level of oxygen consumption correlated to diurnal and nocturnal periods. During the skincycle the oxygen consumption showed fluctuations. There were indications that the value of oxygen consumption of the early anagen is influenced by that phase of the cycle at which the new cycle is artificially induced. Furthermore, it was found that a certain decrease of oxygen consumption stimulates the quiescent hair follicles to spontaneous proliferation. During the katagen the peak value of the oxygen consumption seemed to be correlated with specially morphofunctional perifollicular changes. The application of these findings to the pathophysiology of human hair growth disturbances is discussed.


[Qualitative and quantitative investigations of the skin nerves of patients with psoriasis light- and electronmicroscopical study (author's transl)]. This study was aimed at investigating the role of the nerves in the pathomechanism of psoriasis. The structure of skin nerves of 10 patients with active psoriasis and of 6 healthy control persons has been studied by means of the microscope and the electron-microscope. Eight of the patients were subjected to punch biopsies of psoritatic plaques as well as clinically normal skin. No qualitative difference could be detected between the skin nerves from psoriatic patients and from healthy persons. Quantitative investigations showed that the density of myelinated and unmyelinated axons in psoriatic skin nerves did not differ from that in normal skin nerves in a statistically significant degree. This means that the ratio of myelinated to unmyelinated axons was alike in both normal and psoriatic skin nerves. Also the diameter distribution of myelinated and unmyelinated axons was similar. The difference in the degree of myelinisation and in the myelinperiodicity between psoriatic and control skin was not statistically significant. Neither qualitative nor quantitative morphologic alterations in the skin nerves of psoriatic persons could be detected.


[Bone findings in psoriasis].

[Bone findings in psoriasis]. Three female patients out of 40 psoriatics examined with scintigraphical methods (Tc-diphosphonate) were found to have a diffuse and circumscribed pathological increase of nuclide at the skull. These abarticular signes of proliferation at the bone-area indicate an early affection of skeleton of patients with psoriasis which is similar to the joint-scan that is mostly obtained in positive bone-scan.


Cockade-like vitiligo and linear vitiligo a variant of fitzpatrick's trichrome vitiligo. The authors report 2 cases of atypical vitiligo in which they observed 1) "cockade-like" lesions resembling those of "trichrome" vitiligo (from the centre to the periphery, achromic area, hypochromic ring, normal or hyperchromic border), 2) numerous linear achromic lesions corresponding to former excoriations (Koebner's phenomenon, isomorphic phenomenon). Related affections are discussed with reference to these cases; the trichrome vitiligo described by Lerner and Fitzpatrick, and the primary leukomelanodermas described in black patients by Basset and by Sarrat and Nouhouayi.


The ultrastructure of mycobacterium marinum granuloma in man. 3 biopsies of 3-5 week-old nodular lesions in 2 patients with so-called swimming-pool (aquarium-) granuloma have been examined by electron microscopy. The cytohistological spectrum simultaneously comprises acute exudative as well as chronic proliferative phenomena. Epithelioid cells and collagen producing fibroblasts are already conspicious in 3 week-old granuloma. According to the cytological composition the Mycobacterium marinum granuloma represents a high-turnover granuloma with immunogenic origin. It is comparable to mycobacterial diseases in the presence of well developed cell mediated immunity (Lupus vulgaris, tuberculoid leprosy). Degrading mycobacteria have been rarely detected in phagocytes and are compared with viable bacilli in macrophages of experimentally infected mice. Curved and annular parallel membranes ("worm-like structures") in the cytoplasm of transformed macrophages and in fibroblasts presumably originate from the membranes of endoplasmic reticulum. Cord-like structures with transverse bands (periodicity 170-180 A) in the lumen of RER of some fibroblasts are interpreted as intracellularly aggregated collagen precursors.


Specific Y chromosome fluorescence in interphase nuclei of epithelial cells in human buccal smears. A simplified method is described to demonstrate Y chromosome fluorescence in interphase nuclei of epithelial cells in human buccal smears using Quinacrine Mustard. This technique turned out to be efficient in our hands and would be of value in determining the sex chromosomes in the epithelial cells of the skin in cases of allogeneic transplantations from females to males and vice versa to determine the peroid during which the grafts survived.


Radioactive mercury distribution in biological fluids and excretion in human subjects after inhalation of mercury vapor. The distribution of mercury in red blood cells (RBCs) and plasma, and its excretion in urine and feces are described in five human subjects during the first 7 days following inhalation of radioactive mercury vapor. A major portion (98%) of radioactive mercury in whole blood is initially accumulated in the RBCs and is transferred partly to the plasma compartment until the ratio of mercury in RBCs to plasma is about 2 within 20 hr. The cumulative urinary and fecal excretion of mercury for 7 days is about 11.6% of the retained dose, and is closely related to the percent decline in body burden of mercury. There is little correlation between either the urinary excretion and plasma radioactivity of mercury, or the specific activities of urine and plasma mercury, suggesting a mechanism other than a direct glomercular filtration involved in the urinary excretion of recently exposed mercury. These studies suggest that blood mercury levels can be used as an index of recent exposure, while urinary levels may be an index of renal concentration of mercury. Howver, there is no reliable index for mercury concentration in the brain.


Arc Welders' pneumoconiosis: application of advanced scanning electron microscopy. Study of lung tissue from necropsy of a 58-year-old arc welder with arc welders' pneumoconiosis, confirmed by history, chest radiography, and pathology, demonstrates the versatility and usefulness of new techniques in scanning electron microscopy (SEM). Secondary electron imaging, the most familiar SEM mode, showed heavy cellular infiltrates in alveoli, the interstitium, and within the interstices of loose whorled fibrotic nodules. Backscattered electron imaging, in which contrast is proportional to elemental atomic number, revealed intracellular metal particles not otherwise visible. Microprobe analysis, energy-dispersive x-ray spectrometry, mapped elemeental iron over the particle image and identified traces of silicon in the whorled nodules. Arc welders' pneumoconiosis appears to be more than a benign siderosis resulting from particulate iron deposition. Simultaneous exposure to other components of welding fumes may alter the pathologic picture, inducing a more complicated fibrotic reaction. The more recently developed advanced techniques of SEM are well suited to the study of pneumoconioses and other problems of heterogenous tissue and mixed chemical systems.


Relationship between respiratory cancer and wetlands residency in Louisiana. Cancer mortality is high among white men residing in southern Louisiana parishes (counties). In an effort to elucidate this phenomenon, we studied three environmental correlates of cancer-namely, smoking, residence in urban communities, and residence in the wetlands. Multiple regression analysis was applied to cancer mortalities adjusted for age and urban residency, and specific for race, sex, amount of standing water area in the parish, and cancer site. Cancer sites were grouped according to their correlation with smoking: strong, moderate, and no correlation. For men, the smoking-related cancer mortality not only showed an association with residence in wetlands but also was higher in the Louisiana wetlands than in the remainder of the United States.


Effect of vitamin E and ozone on pentane and ethane expired by rats. Pentane and ethane, which arise during lipid peroxidation in vivo, were measured by gas chromatography in breath samples of rats fed for 8 weeks a vitamin E-deficient diet to which had been added 0, 11, or 40 IU vitamin E acetate per kg. Further lipid peroxidation was induced by exposure of individual rats to 1 ppm ozone for 60 min. Nonparametric statistical analysis of the data for pentane expired before exposure of rats to ozone gave alpha values (alpha = 2P) of 0.006 when the O vitamin E group was compared with either of the vitamin E-supplemented groups. For ethane, comparison of the O vitamin E group with the groups supplemented with 11 and 40 IU vitamin E/kg of diet were 0.0294 and 0.0080, respectively. Alpha values less than .05 were considered significant. After a 60-min exposure of rats to 1 ppm ozone, the paired t-test showed pentane to be significantly (P less than .005) increased in only the rats fed the vitamin E-deficient diet.


In vitro toxicity of tobacco smoke solutions to rabbit alveolar macrophages. The biological activity of various cigarette smokes has been assessed by treating cell cultures of rabbit alveolar macrophages with salt solutions of "whole smoke," smoke "vapor phase," and smoke "particulate phase." The results of these tests revealed degrees of toxicity that varied in accordance with the smoke treatment used. Further, these differences in toxicity were statistically significant at the 95% confidence limit. Observations of changes in cell morphology on exposure to the smoke solutions indicated smoke toxicity to be caused, in part, interference with cell membrane activity.


Abdominal pain in lead workers.

Abdominal pain in lead workers. Thirty-four lead smelter workers with excessive lead absorption were evaluated and followed. Abdominal pain was present in 27 patients. Fifteen patients who had left the site of lead exposure experienced persisting abdominal pain for as long as 29 months; some of these demonstrated acceptable levels of lead in blood. There is no correlation between lead levels and persisting pain. Twenty-three patients developed abdominal pain with blood lead lower than 80 microgram/100 ml while working. Four out of 15 patients with persisting abdominal pain had blood lead between 40 and 60 microgram/100 ml while working. Typical lead-induced abdominal pain is a sensitive symptom of intoxication and may be a criterion for removal from exposure regardless of blood lead levels.


Lead in deciduous teeth of Norwegian children. Two thousand two-hundred and thirty-three deciduous teeth were collected from cities, industrialized areas, and rural and fishing communities in several Norwegian counties. Teeth from Medieval Bergen were also included. Lead analysis of whole teeth revelant that in Norway there are many communities where lead absorption is minimal and comparable to background absorption in ancient societies. Such conditions are reflected in a lead level of 2.92 microgram/g in deciduous teeth. However, the analysis also revealed that urbaization and industrialization increased lead absorption, although the mean level recorded in Norway of 3.73 microgram/g was far lower than normal levels found in other countries. Automobile exhaust was rejected as an important source of undue lead absorption. This study indicated that 0.18% of Norwegian children from the ages of 7 to 12 yr may have been victims of undue absorption, reflected in a tooth lead level of about 70 microgram/g.


Subjective annoyance from noise compared with some directly measurable effects. In epidemiological investigations of annoyance it is important to search for directly measurable effects that are associated with reports of annoyance. The relationship between reported experiences of annoyance, performance on an arithmetic test, and hormonal stress reactions was studied on 100 male students during acute exposure to 85 dB (A) of traffic noise in a laboratory setting. An association was demonstrated between reported feelings of annoyance, performance efficiency, and the subjects' experience of the influence of noise on their performance. The exposure to noise was found to affect performance more negatively in the more annoyed individuals. The results indicate that the annoyance-inclined individuals in a community may constitute a special risk group that will suffer more from the adverse effects of community noise.


Brake reaction time--effects of age, sex, and carbon monoxide. Simulated braking responses have been tested in relation to blood carboxyhemoglobin (HbCO) levels. The main determinants of percentage of HbCO in 352 subjects attending a fall fair were daily cigarette consumption and minutes since the last cigarette. In women the brake response time deteriorated from age 16 yr, but in the men there was an improvement from age 16 to the early 20s. Times at all ages were better for men than for women. Average response times and the rate of aging of the braking response were very similar in smokers and in nonsmokers. In the nonsmokers, however, response time with step function CO increments of as much as 7% HbCO. There was a suggestion of a small increase of reaction time, with an opposing decrease of leg movement time, during the first few minutes after CO exposure; nevertheless, these trends were statistically insignificant.


Experimental studies on human health effects of air pollutants. IV. Short-term physiological and clinical effects of nitrogen dioxide exposure. Adult male volunteers were exposed to nitrogen dioxide (NO2) at 1.0 ppm in purified air under conditions simulating ambient photochemical smog exposures (2-hr exposure with intermittent light exercise at 31 degrees C and 35% relative humidity). Sham exposures to purified air alone served as controls. Exposure effects were assessed by pulmonary physiological tests and by a standardized clinical evaluation. No statistically physiological changes attributable to NO2 exposure were found except for a marginal loss in forced vital capacity after exposure on two successive days (1.5% mean decrease, P less than .05). Reported respiratory and other symptoms were slightly increased with exposure as compared to control, but the change was not significant. Short-term toxicity of NO2 at peak ambient concentrations appears to be substantially less than that of ozone in healthy people, but adverse NO2 effects in diseased people or in long-term exposures cannot be ruled out at present.


A nonoccupational outbreak of inorganic mercury vapor poisoning. An outbreak of inorganic mercury vapor poisoning involving 12 people occurred in a trailer park in Mississippi in 1973-74. For information concerning levels of mercury in hair and blood of humans with short-term exposures, these individuals were observed for as long as 10 months after the end of their exposures, and the amount of mercury in their blood and scalp hair was serially measured. Specimens were also obtained from nonexposed individuals in the trailer park. Inorganic mercury was measured in 1-cm segments of hair samples obtained both 6 and 9 months after termination of exposure. Over a 3-month period, the peak amount of inorganic mercury per gram of hair shifted in position from 7 cm to 13 cm from the scalp. The average mercury concentration in newly formed hair (the 4 cm of hair closest to the scalp) decreased fourfold over the same time period. Surface contamination of exposed hair by exogenous mercury also occurred. Levels of inorganic mercury in blood from exposed individuals ranged from 183 to 620 ng/ml and fell to levels similar to those of controls 4 to 6 months after ending exposure. The source of the outbreak was metallic mercury spilled on rugs. Attempts to remove the mercury failed and actually dispersed the metal over a larger surface area. Air mercury levels as high as 1.0 mg/m3 of air were found in one of the contaminated house trailers. Rugs or carpets contaminated with metallic mercury are a significant health risk.


Human alveolar deposition of 4 micron teflon particles. On two occasions ten healthy men inhaled with maximally deep inhalations at 0.5 1/sec a test aerosol of 4 micron teflon particles tagged with 111In. Radioactivity in the lungs was measured a few min, 24 hr, and 2, 3, and 4 days after inhalation. Retention decreased greatly between the measurements performed a few min and 24 hr after inhalation, but was similar in measurements 1 to 4 days after inhalation. Among individuals, retention varied considerably 1 to 4 days after inhalation (by a factor of 2), but the retention in each individual subject was uniform. Measuring the retention of a radioactively tagged test aerosol 1 day after inhalation, and regarding this retention as alveolar deposition, might be of value in preventive measures against certain toxic dusts.


Physiological effects of acute passive exposure to cigarette smoke. Effects of passive inhalation of cigarette smoke at levels typically encountered in public buildings have been investigated. Twenty normal male and female nonsmokers (18 to 30 years) were each exposed for two hours on alternate days (in random order) to either room air or room air plus machine-produced cigarette smoke. Exposures were conducted in an unventilated chamber (14.6 m3). Subdivisions of lung volume, maximum expiratory flow-volume curves, single-breath nitrogen washout curves, blood carboxyhemoglobin levels, and heart rates were obtained before, during, and after exposure. A submaximal bicycle ergometer test and a symptom questionnaire were also administered after exposure. Statistical analysis revealed several significant differences between test and control days; the magnitude of the changes was small and of questionable biological significance, however, particularly when account was taken of the number of statistical comparisons made. Despite the relatively small physiological changes, subjective complaints were common-cough, and eye irritation, for example. It is concluded that in normal subjects the magnitude of physiological responses to acute exposures is minimal; thus arguments concerning effects rest on symptomatology and such other factors as the unknown risks of chronic exposure.


Effects of exercise on mice exposed to ozone. The effects of exercise on response to ambient levels of ozone exposure were studied by using a sensitive indicator of the pulmonary effect of ozone, viz., the elevation of reduced glutathione levels in the lungs. Mice were exposed to 0.2, 0.5, or 1.0 ppm ozone for 3 hr daily for 4 days. For exercise study, animals were placed in a rotating cage in which they were alternately exercised and rested every 15 min during exposure periods. The susceptibility of mice to the pulmonary effects of ozone was found to be approximately tripled by concurrent exercise. The results indicate the importance of exercise in the evaluation of health hazards from photochemical smog.


Joint hypermobility leading to osteoarthrosis and chondrocalcinosis. We have reviewed 21 adults referred to rheumatology clinic and considered to have generalised joint hypermobility by the criteria of Carter and Wilkinson (1964), modified by Beighton et al. (1973). They fell into two categories. 5 patients had a raised plasma viscosity (PV) and in each case a definite pathology was found to account for this, superimposed on hypermobile joints. The remaining 16 had a normal PV and this group was thought to represent the late natural history of hypermobility. 5 of these (aged 32 to 54 years) had no evidence of osteoarthrosis but the remaining 11 (aged 34 to 80 years) had widespread radiological osteoarthrosis. Synovial histology was obtained at arthroscopy in 6 of these patients and 4 (aged 60 to 75) had chondrocalcinosis. This previously undescribed finding may be the end result of hypermobile joints. Hypermobile patients with joint deformity (lax connective tissue), widespread synovial thickening (traumatic), and hot joint effusions (chondrocalcinosis) may mimic rheumatoid arthritis. They must be distinguished from patients who develop rheumatoid arthritis in hypermobile joints.


Polyneuritis incidence in shoe factory workers: cases report and etiological considerations. This study describes an outbreak of polyneuropathies in an artificial leather shoe factory. Thirty-seven females employed in the factory were examined; clinical findings and hematochemical data suggest a possible role of tricresylphosphate (TCP) in the genesis of these polyneuropathies. A high percentage of subjects evidenced definite signs of upper-motor neuron involvement, which appeared at an early or late stage of the disease. A statistically significant (P less than .001) reduction of red-blood-cell acetylcholinesterase (AChE) was found in the subjects. The ascertained upper-motor neuron involvement suggests a connection with previously described intoxications by TCP- by ingestion or occupational poisoning. The reduction of AChE seems attributable to TCP, and not to n-hexane, whose anti-AChE activity has never been demonstrated.


Precipitating antibodies to cellular antigens in Sjögren's syndrome, rheumatoid arthritis, and other organ and nonorgan-specific autoimmune diseases. The prevalence of three precipitating antibodies, anti-SS-A anti-SS-B, and rheumatoid arthritis precipitin (RAP), reacting with an extract of the human lymphoid cell line Wil2, was studied in the sicca syndrome, Sjögren's syndrome with rheumatoid arthritis, rheumatoid arthritis, various seronegative spondyloarthritides, and organ and nonorgan-specific autoimmune disease. Anti-SS-A and snti-SS-B occurred most frequently in the sera of patients with the sicca syndrome whereas RAP occurred most frequently in seropositive rheumatoid arthritis sera. However, the data did not support previous studies where patients with sicca syndrome had a high incidence of anti-SS-A and/or -SS-B antibodies but had a low frequency of RAP, and patients with Sjögren's syndrome in association with rheumatoid arthritis had a high incidence of RAP but a low incidence of anti-SS-A and/or -SS-B. Instead the three antibodies were present in both forms of Sjögren's syndrome. This suggested a difference in the diseases in the UK compared to the USA, or that these antibodies do not have the more subtle diagnostic specificity that was originally suggested.


Experience with Silastic prostheses in the rheumatoid hand. A 5-year follow-up. Nine patients with rheumatoid arthritis, who had Silastic prostheses (Swanson's) introduced into 34 metacarpophalangeal joints, were reviewed 5 years after surgery. The most important long-term advantage conferred by the introduction of prostheses was pain relief; functional benefit was marginal. The majority of prostheses eventually fractured but this did not necessarily lead to a functional deterioration. Impairment of function was usually the result of loss of flexion at the metacarpophalangeal joints, but it was sometimes due to excessive instability after fracture of the prostheses. It is suggested that Silastic joint replacement may be a worthwhile procedure in rheumatoid patients with moderate destruction or deformity of the metacarpophalangeal joints when pain is a predominant feature. Significant functional improvement can be anticipated only when secondary to pain relief.


Rheumatoid polyarthritis after rubella.

Rheumatoid polyarthritis after rubella. A 21-year-old woman developed persistent polyarthritis indistinguishable from rheumatoid arthritis after rubella. The arthritis persisted for approximately 30 months and was associated with high levels of antibody to rubella virus and with rheumatoid factor. The antibody titres declined pari passu with clinical improvement which progressed to complete resolution. Fractionation of serial serum specimens showed a substantial and persistent IgM antibody response to rubella virus. Rubella antigen was not demonstrated in the synovial exudate.


Juvenile rheumatoid arthritis with cardiac tamponade. A 4-year-old girl with seronegative systemic juvenile rheumatoid arthritis developed acute cardiac tamponade. Pericardiocentesis and systemic corticosteroids resulted in complete recovery of the pericardial involvement. This was followed by complete remission of rheumatoid disease.


Somatomedin activity in synovial fluid from patients with joint diseases. The somatomedin activity in synovial fluids from 50 patients with a variety of joint diseases has been studied and compared with the activity in each of the patient's own serum and a standard reference serum (SRS). The porcine costal cartilage bioassay of Van den Brande and Du Caju (1974a) has been used with the isotopes 3H-thymidine and 35S-sulphate. Synovial fluids from most patients with post-traumatic and post-operative effusions, osteoarthritis and arthritis associated with psoriasis, Reiter's disease, and ankylosing spondylitis stimulated the synthesis of DNA and proteoglycans in cartilage. Synovial fluids from patients with rheumatoid arthritis either had impaired capacity to stimulate DNA synthesis, or they inhibited it; a similar, but less evident pattern was observed for proteoglycan synthesis. Some synovial fluids from patients with miscellaneous synovitides stimulated, while others inhibited cartilage metabolism. It is concluded that the synovial fluid from patients with rheumatoid arthritis and from some patients with miscellaneous synovitides contained an inhibitor(s) to DNA and possibly proteoglycan synthesis. The sera from nearly all the patients stimulated both DNA and proteoglycan synthesis, but the somatomedin potency ratios for serum in terms of SRS were generally less than 1.0. There was a significant inverse correlation between the serum somatomedin potency ratio and the age of the patient.


Prostaglandin production in arthritis.

Prostaglandin production in arthritis. Inflammatory cell populations from synovial effusions or synovial villi in rheumatoid arthritis have been cultured in vitro. Prostaglandin productive capacity, measured by radioimmunoassay, showed the polymorphonuclear leucocyte rich populations from synovial effusions to be poor sources of PGE production whereas the synovial fragments produced substantial amounts of PGE activity. It is suggested that the macrophage is the major source of local prostaglandin formation both in gout and rheumatoid arthritis.


The relationship between uric acid and potassium in normal subjects. The serum uric acid concentration in normal healthy subjects has been studied in relation to sex, height, weight, lean body mass measured from total body potassium and predicted from the Hume-Weyers formula (1971), total body potassium, plasma potassium and urea, and packed cell volume. The strongest correlation was found with sex, but height, weight, total body potassium, lean body mass (measured and predicted) also correlated significantly with serum uric acid concentration. However, when the sex variable was removed, the other factors lost their significant correlation. Finally, total red blood cell and plasma volumes were predicted (Hume and Goldberg, 1964) and from these an estimate of total plasma uric acid, total plasma potassium, and total red blood cell potassium obtained. Measured total body potassium was found to correlate well with total plasma potassium and total red blood cell potassium independent of sex. Total plasma uric acid correlated well with measured total body potassium when both sexes were considered and when separated into male and female groups the males retained a significant correlation as did the female group.