Serum and urine N-acetyl-beta-D-glucosaminidase in diabetics on diagnosis and subsequent treatment, and stable insulin dependent diabetics.

N-Acetyl-beta-D-glucosaminidase (NAG) activity has been measured in the serum and urine of diabetics. Results have shown significantly higher levels of serum NAG in newly diagnosed diabetics (945 +/- 372 units/ml) compared to non-diabetic controll (668 +/- 225, p less than 0.005) and the levels were reduced by treatment (778 +/- 218, p less than 0.05). Changes occurred in the same direction when urinary NAG was measured falling from a mean of 572 +/- 298 units/mg urinary creatinine, on diagnosis to 291 +/- 176 after treatment (p less than 0.005), as compared with 177 +/- 86 in non-diabetic controls. Established insulin-treated diabetics had a urinary NAG activity of 461 +/- 440 and a serum NAG activity of 790 +/- 245. No correlation was found between urine NAG activity and urine glucose (r = 0.315), or serum NAG and serum glucose (r = 0.273). An assessment of this enzyme is made in relation to early microangiopathy.


An automated amidolytic assay of thrombin generation: an alternative for the prothrombin-time test.

An automated method is presented for the determination of thrombin generation in plasma during activation by thromboplastin. The thrombin generated is allowed to split the chromogenic substrate Tol-Gly-Pro-Arg-pNA yielding p-nitroaniline. The increase in absorbance at 410 nm is recorded. This assay may serve as a specific, precise and fast alternative for the conventional clotting tests: "Prothrombin time" and "Thrombotest".


Leucocyte and erythrocyte magnesium levels after jejuno-ileal bypass surgery.

Leucocyte magnesium concentration was measured in 25 hypomagnesaemic patients following a jejuno-ilean bypass operation for gross obesity. The mean plasma magnesium concentration in the bypass group was 0.67 mmol/l compared with that of 0.90 mmol/l in a group of 17 healthy volunteers, but the leucocyte magnesium concentration in the two groups was not significantly different. The plasma potassium was found to be significantly lower in the bypass group but there was no significant difference in the leucocyte potassium concentration in the two groups. Simultaneous measurements of erythrocyte magnesium, sodium and potassium were made. There was no evidence of intracellular magnesium depletion on the basis of the tissues studied.


A fluorescent artefact resembling BB-creatine kinase in sera of patients with prostatic disease.

A fluorescent zone with mobility towards the anode almost equal to that of human BB-creatine kinase has been detected after electrophoresis on cellulose acetate of sera from each of 28 patients with prostatic carcinoma. The zone is not due to the BB isoenzyme and its appearance does not depend on the presence of substrates of creatine kinase. It therefore appears to be a further example of a fluorescent artefact resembling a creatine kinase ieoenzyme. These observations indicate a need for caution in assessing the possible value of BB-creatine kinase in patients with prostatic disease.


A deletion mutation in glucosephosphate isomerase (GPI Denton).

A new genetic variant form of glucosephosphate isomerase has been found in a family heterozygous for the mutant allele. The mutant enzyme, unlike other phenotypic variants, does not appear to be the result of a single amino acid replacement. The allozyme exhibits an isoelectric point of 5.7 and is thus much more acidic than the normal enzyme (pI = 9.3). The allozyme has been isolated from placenta and separated from the normal homodimer and heterodimer by isoelectric focusing. The enzyme exhibits normal Km and Ki values for the substrates and competitive inhibitors. The allozyme exhibits a normal pH optimum and thermal stability. However, the molecular specific activity of the variant enzyme as quantitated by radioimmunoassay is significantly lower than normal. Analytical gel filtration revealed that the molecular weight of the weight of the enzyme is significantly lower than the normal enzyme. These data thus suggest that the phenotype is unlike any previously reported and is due to a deletion mutation.


Determination of total 3 alpha-hydroxy bile acids in serum.

The usual techniques for determination to total 3 alpha-hydroxy bile acids in serum involving liquid-solid extraction of the bile acids with the adsorbent XAD-2 and fluorimetric measurement of NADH generated from the reaction with a NAD-linked 3 alpha-hydroxysteroid dehydrogenase are evaluated and improved. The influence of different types of enzyme preparations on the results is examined. The results with the improved technique are compared to the results obtained with another method, avoiding extraction of the bile acids before the enzymatic reaction which is followed by fluorimetric measurement of resorufin, produced by transfer of the hydrogen of the generated NADH by diaphorase to resazurin. No significant difference between the results with the two types of methods was found. The concentration of total 3 alpha-hydroxy bile acids in serum of 46 fasting 'healthy' individuals aged 17 to 82 years is estimated. 30 were females, of whom 10 were taking estrogen-containing oral contraceptives, and 16 were males. Mean +/- standard deviation in all the females was 3.0 +/- 1.1 micromol/l, and in the males 4.0 +/- 1.9 micromol/l. There was no significant difference between any of the groups.


Placental type of membrane-bound arylamidase (Shiba isoenzyme) found in human cancerous lung.

A placental type of membrane-bound arylamidase (Shiba isoenzyme) was found in the tissue of adenocarcinoma of the lung. Cancerous lung membrane-bound arylamidase had the same electrophoretic mobility, isoelectric point (pH 4.2), and susceptibility to SDS inactivation as placental membrane-bound arylamidase. Cancerous lung membrane-bound arylamidase had molecular weight and kinetic properties similar to normal lung membrane-bound arylamidase, but differed from the normal lung membrane-bound arylamidase with respect to electrophoretic mobility, isoelectric point, heat stability and inactivation by SDS.


Changes in type of collagen during the development of human post-burn hypertrophic scars.

Neutral-salt soluble collagen was relatively abundant in young post-burn hypertrophic scars. The content of insoluble collagen was fairly low in granulation tissues, whereas it gradually increased over 2 years and reached a significantly higher value than that in normal skins. Interrupted gel electrophoresis was carried out to estimate the relative proportions of type III and type I collagens in the pepsin digests of human normal skins and post-burn scars. Granulation tissues showed an abnormally higher ratio of type III to type I (0.37--0.72) than the mean value of normal skins (0.17 +/- 0.04 (S.D.)). The ratio gradually decreased to the normal range after 2 years or so.


The preparation of 125I-labelled bile acid ligands for use in the radioimmunoassay of bile acids.

A general method for the preparation of 125I-labelled bile acid-histamine or 125I-labelled bile acid-tyramine conjugates is presented. The method is simple, quick and produces ligands in good yield (30%). The characteristics of a radioimmunoassay for conjugated chenodeoxycholic acid, based on an 125I-labelled ligand prepared by the method, are also described. The assay produced values for fasting serum concentrations of conjugated chenodeoxycholic acid that agree well with previous data.


Decreased cerebrospinal fluid concentration of free phenylacetic acid in depressive illness.

Cerebrospinal fluid free phenylacetic acid concentration in a series of depressive patients was significantly lower than values in control subjects. This acid derives from phenylethylamine and the findings may reflect a decrease in its brain formation. Such a deficit may be related to other recent observations of a decrease in urinary output of the major metabolites of the "trace amines", octopamine and tyramine: phenylethylamine is thought to be the precursor of these "trace amines".


Distribution of serum concentrations of creatine kinase MM and BB isoenzymes measured by radioimmunoassay.

Because of the recent interest in measuring serum enzyme concentration as opposed to catalytic activity, we measured the serum concentration of creatine kinase isoenzymes BB and MM by radioimmunoassay and the total creatine kinase enzymatic activity in healthy adults. For sex-race subgroups we report mean values and the 2.5, 5, 25, 50, 75, 90, 95 and 97.5 percentiles. Differences among average values of the subgroups were highly significant. Results within subgroups frequently departed from a gaussian distribution.


Increased CK-BB concentrations in serum following cardiac surgery.

We measured the BB isoenzyme of creatine kinase by a specific radioimmunoassay in the serum of 47 patients following cardiac surgery. A sharp increase in CK-BB occurred immediately after surgery, with rapid return to baseline by the fourth post-operative day. This data, along with other reports in the literature, suggest that CK-BB is released into the circulation following myocardial insult.


[Determination of lysozyme in biological fluids by a semi-automatic kinetic technique. Discussion of the method (author's transl)].

A rapid and semi-automatic determination of lysozyme in biological fluids using kinetic analysis and turbidimetry is described and compared to other commonly used techniques. The specificity of the method is satisfactory while that of clarification of a gel medium is apparently not. Normal values and standard errors for plasma, urine, and leucocytes are given. A standardised expression of lysozyme activity is proposed and discussed. The importance of the means by which the blood sample is collected and prepared is underlined: plasma, decanted soon after collection, is preferable to serum.


Significance of the electrophoretic modifications of defective pyruvate kinase variants. Study of six new observations.

Six new defective pyruvate kinase variants have been characterized in patients suffering from chronic hemolysis. Partially purified enzyme variants exhibited various anomalies from immunological, kinetic, stability and electrophoretic points of view. The significance of the electrophoretic anomalies has been interpreted in view of the normal post-synthetic maturation of the precursor enzyme L'4 into L2L'2 and L4, and the ability of trypsin to induce in vitro the transition L'4 leads to L4 has been tested. One defective enzyme existed in a single L'4 form and could not be transformed by trypsin into L4. In three cases slow-moving L'4 and L2L'2 forms were transformed by trypsin into an abnormal slow-moving L4 form. In the last two observations the L'4 and L2L'2 forms exhibited normal mobility and were normally transformed by trypsin into L4. The relevance of these data to the functional anomalies of the defective variants and to the nature of the primary genetic anomaly giving rise to the congenital defects in erythrocyte pyruvate kinase is discussed.


Acetylcholinesterase activity and its molecular forms in rectal tissue in the diagnosis of Hirsprung's disease.

Acetylcholinesterase (AChE) activity and its molecular forms in the rectal tissue in Hirsprung's disease were studied. Total AChE activity was increased in Hirsprung's disease; the activity was separated by polyacrylamide gel electrophoresis into two molecular forms. The AChE form with higher electrophoretic mobility was not observed in healthy children, and it might be of diagnostic importance in this disease.


L-thyroxine treatment of diffuse non-toxic goitre evaluated by ultrasonic determination of thyroid volume.

The effect of a daily dose of 150 micrograms l-thyroxine for one year was studied in forty-five patients with diffuse non-toxic goitre. Thyroid volume was evaluated by ultrasonic scanning. A decrease in the median value of the thyroid volume of about 20% was found after 3 months of therapy and no further change in the median value was observed in the following 9 months of treatment. About 50% of the patients showed a response to therapy and about 30% obtained normal size of the thyroid gland. Median value of the thyroid volume returned to pretreatment value 3 months after thyroxine therapy was stopped. A considerable increase in serum T4 and free T4 index was noted after 3 months of therapy and these elevated values persisted unaltered during the following 9 months of treatment. Serum T3 was studied before and after 3 months of thyroxine therapy in eleven of the patients. A small and insignificant increase in serum T3 and free T3 index was observed.


Serum thyroglobulin in the diagnosis and management of thyroid carcinoma.

Serum thyroglobulin (Tg) was measured by radioimmunoassay in sixty-two control subjects, 163 euthyroid patients with nodular goitre and eighty-one patients with previously treated differentiated thyroid carcinoma. Tg was elevated in 65% of nodular goitres and failed to fall with thyroxine treatment in ten/fifteen patients treated. A diagnosis of differentiated carcinoma was confirmed in fourteen/sixty-four of these patients and Tg was elevated in twelve. Of sixty-five treated thyroid carcinoma patients without evidence of residual tumour, serum Tg was undetectable in thirty-nine, normal in twenty-four and elevated in two. There was evidence of residual tissue in the thyroid in seventeen of the patients with detectable Tg. Of the sixteen patients with residual tumour or metastases Tg was elevated in fifteen. There was a positive correlation between goitre size and Tg levels in multinodular goitre, and thyroid carcinomas of large bulk were associated with higher Tg levels. Serum Tg was normal in medullary carcinoma and in two patients with thyroid metastases from extra-thyroidal malignancies. High Tg levels in patients with residual metastases from thyroid carcinoma following thyroid ablation indicates Tg production by tumour tissue. Measurement of serum Tg of limited value in the differential diagnosis of nodular thyroid disease. It is particularly useful following surgery and 131I therapy for differentiated thyroid carcinoma. In these patients it gives confirmation of thyroid albation and may provide evidence of residual tumour tissue when the other tests are negative.


Plasma levels of norethindrone after single oral dose administration of norethindrone and lynestrenol.

Single oral doses of 0.3 mg, 0.5 mg and 5 mg Norethindrone (NET) and 0.5 mg and 5 mg Lynestrenol (lyn) were given to five women. Lynestrenol is probably metabolized through NET and exerts its main biological activity as NET. Plasma concentrations of NET were determined by a radioimmunoassay at different intervals after administration of the tablets. Peak concentrations of NET were found within two hours after intake of each table. The plasma half life of Net after NET and lyn administration for the period 8-24 h was 8-11 h. No significant difference was found between the half life of NET and the NET tablets and after the lyn tablets. When 5 mg NET was given the plasma half life of NET for the period 24-72 h was around 10 h and this was significantly shorter than the half-life of NET after 5 mg lyn, which was 16 1/2 h. The systemic availability of the drugs was estimated by calculating and comparing the areas under the plasma concentration versus time curve (AUC). 0-24 H. The AUC 0.24 after 0.3 MG NET was almost identical to the AUC 0.24 after 0.5 mg lyn. The AUC 0-24 after 0.5 mg NET was significantly larger than after 0.5 lyn. No difference was found between the AUC 0-24 after 5 mg lyn and 5 mg NET. This study supports the concept of a conversion from lyn to NET. It also shows that there were only minor pharmacokinetic differences between the drugs when all samples were measured as NET.


The effect of sulpiride induced hyperprolactinaemia on glucose tolerance and insulin secretion in normal subjects.

Blood glucose concentration and insulin secretion expressed by peripheral plasma insulin (IRI) and C-peptide levels were measured during saline and sulpiride infusion in five normal men. In another experiment the same variables were analysed in six normal males before and during oral sulpiride treatment for 5 days. The i.v. and oral administration of sulpiride resulted in a significant rise in serum prolactin levels. The stimulated serum prolactin concentrations were equivalent to those seen during stress. The sulpiride induced hyperprolactinaemia did not change blood-glucose, plasma IRI levels, hepatic insulin removal and glucose utilization during basal conditions or after i.v. glucose administration.


Standard dose 131I therapy for hyperthyroidism caused by autonomously functioning thyroid nodules.

Thirty-one patients with hyperthyroidism shown on scintigram to have autonomously functioning thyroid nodules were treated with a standard dose of 15 milliocuries (mCi) of 131I. Of thirty patients who have been followed up for a least 6 months to over 3 years, all but one patient were euthyroid after a single dose. Repeat scintigram and Thyrotropin Releasing Hormone (TRH) test after therapy confirmed that twenty-five patients were cured of the disease. Only one patient developed hypothyroidism. This simplified standard dose regimen of radioiodine is effective in the treatment of hyperthyroidism caused by autonomously functioning nodules and is not complicated by the high incidence of hypothyroidism that is observed following radioiodine therapy of Graves' disease.


Dopamine is a physiological regulator of thyrotrophin (TSH) secretion in normal man.

Using a sensitive and precise radioimmunoassay for human TSH we have demonstrated significant elevations in serum TSH levels in euthyroid volunteers following administration of the dopamine receptor blocking drug metoclopramide when compared with placebo. The degree of TSH response is significantly greater in females than in males and is sustained over a 3-hour period after a single oral 10 mg dose of metoclopramide. The degree of TSH release after metoclopramide is inversely related to the basal TSH level suggesting that dopamine is a determinant of low daytime TSH levels and is thus implicated in the circadian rhythm of TSH secretion. Pretreatment with 10 mg of metoclopramide orally, one hour before TRH administration leads to significant enhancement of the TSH response to TRH. Our findings provide further evidence for the physiological inhibitory role of dopamine in the contol of TSH secretion in normal man. The possible mode of action of dopamine and the clinical implications of this neuroregulatory pathway are discussed.


Inhibition of cimetidine-induced hyperprolactinaemia by pretreatment with levodopa or bromocriptine.

A single i.v. administration of cimetidine, an histamine receptor antagonist, produced a significant increase in serum prolactin (PRL) levels in fifteen normal men. This effect was suppressed by pretreatment with levodopa or bromocriptine.


Platelet monoamine oxidase in a pedigree with schizophrenia: an interlaboratory project.

Conflicting reports on the association between platelet MAO activity and schizophrenia prompted a critical review and determinations on identical samples at one laboratory in Sweden and one in the U.S.A. Samples originated from eight schizophrenics and 27 relatives belonging to a large pedigree, thus ensuring biological homogeneity. In the USA laboratory, a significantly lower MAO activity was found in the schizophrenics when benzylamine or beta-phenylethylamine was used as substrate (but not with tryptamine), while a similar result was obtained in the Swedish laboratory when tryptamine was used (but not with benzylamine or beta-phenylethylamine). Comparisons between materials examined in different laboratories do not seem meaningful until differences in methodologies have been clarified. At present there is neither proof nor disproof of MAO being a "genetic marker" for vulnerability to the schizophrenic disorder.


Analysis of family resemblance for lipids and lipoproteins.

A path analysis of published reports on family resemblance reveals an important role for genetic factors in all lipids and lipoproteins, with no evidence of a discrepancy between twins and other relatives (which might be due to dominance or epistasis) nor between studies which used environmental indices and those which did not. Family environment within population is less important and is significantly greater for twins than for other relatives.


Benign sickle cell disease in Saudi Arabia: survival estimate and population dynamics.

A survey of 8,084 adult Saudi male employment applicants yielded 872 with the sickle cell trait (AS) and 51 with sickle cell disease. Based on the known distribution of hemoglobin S genes between oasis and non-oasis populations in Saudi Arabia, and on calculation of the expected number of abnormal homozygotes within the non-oasis and oasis subgroups as well as the entire employment applicant group, it appears that virtually 100% of Saudis with SS disease survive to adult life. Saudi Arabs and other Caucasian populations in the Middle East exhibit a benign type of SS disease as compared with Blacks in Africa and the Americas. In the Middle East, gene contributions from SS individuals will shift equilibrium frequencies to higher levels than encountered in Black populations under sustained selective pressures, and the polymorphism will tend to be stable with decline in selective pressure. There are some indications that the hemoglobin S gene may have been a recent import into the Middle East.


Hereditary hypoceruloplasminemia.

Serum ceruloplasmin values of less than 21.0 mg/100 ml in males or less than 23.0 mg/100 ml in females were observed in 14 out of 156 otherwise healthy members of a pedigree. The hypoceruloplasminemia segregated in a fashion suggesting that the affected individuals are heterozygous for a mutant gene that results in hypoceruloplasminemia. This mutant gene could be a Wilson's disease gene, but excessive copper loading was absent. It is suggested that hereditary hypoceruloplasminemia may be a benign entity distinct from Wilson's disease.


Partial triplication and deletion of 13q: study of a family presenting with bilateral retinoblastomas.

This report compares the pathogenetic influences of selective deletion and triplicaton of chromosome 13 derived from a familial 12;13 insertional translocation. In the proband a heritable chromosomal basis for his bilateral retinoblastomas is established [46,XY,del (13) (pter leads to q12.5: :q22.1 leads to qter)mat], and in his sister the relatively modest effects of triplication of the mid-portions of 13q are demonstrated [46,XX,ins(12;13) (12pter leads to 12p11.2: :13q22.1 leads to 13q12.5: :12p11.2 leads to 12qter)mat]. Qualitative and quantitative gene marker studies and chromosomal staining techniques to differentiate timing of DNA replication failed to indicate functional gene changes about the breakpoints.


Genetic studies in a family with inverted nipples (mammillae invertita).

A Jewish Sephardi family is reported in which 16 members are affected (15 females and 1 male) with inverted nipples. The one affected male and his brother also have gynecomastia. Under the assumption that this trait is transmitted as an autosomal dominant, linkage studies were done but were not revealing. Further family and investigative studies are needed in this disorder to understand better its pathogenesis and precise mode of genetic transmission.


Autosomal recessive spastic paraplegia: evidence for demyelination.

Neurological evaluation of a family living in rural Louisiana showed that six living members have splasticity, hyperactive stretch reflexes, and pathological reflexes. Ten deceased family members had been similarly affected. All affected persons were offspring of consanguineous marriages, and sex distribution was equal, indicating that inheritance was autosomal recessive. Although undetected clinically, conduction abnormalities suggestive of demyelination in the visual pathways were revealed by special tests.


Bloom's syndrome. VII. Progress report for 1978.

The Bloom's Syndrome Registry was published in this journal in 1977. Now, in the first in a series of progress reports, recent accessions to the Registry are recorded, new instances of neoplasia are listed, and recent clinical observations and experimental results of general interest are cited.


Abnormal lymphocyte responses in residents of a town with a cluster of Hodgkin's disease.

A time-space aggregate of Hodgkin's disease was observed in a small town. A large elevator for the storage of navy beans was located in the residential area of the town. Lymphocytes of town residents compared to those of non-residents showed increased levels of transformations when challenged with extracts of navy beans. A phytohaemagglutinin from navy beans with the ability to stimulate lymphocytes was isolated and characterized. A hypothesis concerning a connection between this cluster of Hodgkin's disease and the abnormal lymphocyte responses to navy-bean phytohaemagglutinin is discussed.


Heterogeneous neurocytotoxic antibodies in systemic lupus erythematosus.

Sera from eighteen patients with systemic lupus erythematosus (SLE) were tested for cytotoxic antibody to three neuronal and two glial continuous cell lines of human origin. Eighty per cent (fifteen out of eighteen) of the sera were cytotoxic to at least one of the cell lines, but only seven sera were active against all five lines. Three sera had anti-neuronal but not anti-glial reactivity. No sera were gliocytotoxic without neurocytotoxicity. Three SLE sera with relatively strong cytotoxicity to all five cell lines were abosrbed with each of the cell lines separately and the absorbed sera were then tested for residual cytotoxicity to each of the cell lines. The absorptions uncovered at least six different antibody specificities directed at antigens expressed on some but not all of the neuronal and glial cell lines. Each patient's serum had its own profile of antibody specificities reactive with membrane antigens on nervous tissue-derived cells.


IgG synthesis within the brain in multiple sclerosis and subacute sclerosing panencephalitis.

Intracerebral IgG synthesis was measured in patients with multiple sclerosis (MS), subacute sclerosing panencephalitis (SSPE) and in two control groups--patients with other neurological disorders and patients with non-neurological diseases. Significantly increased synthesis was found at all times in SSPE (P less than 0.001). Significantly elevated values were also found in MS (P less than 0.001), but in this group increased values were found mainly during relapse. These findings emphasize the immunological component in SSPE where there is known to be persistent measles virus infection in the brain, and in MS where the aetiology is unknown. Intracerebral IgG synthesis appears to be of diagnostic value in MS. The cerebrospinal fluid (CSF) IgG/total protein ratio was also measured in MS, and correlated only moderately well with the calculated IgG synthesis, indicating that the ratio provides a cruder estimate of intracerebral IgG synthesis.


Relationships between the haemolytic activities of the human complement system and complement components.

The relationships between the haemolytic activities of complement and its components were studied. The activities studied included CH50 (classical pathway), AP50 (alternative pathway), CV50 (early part of alternative pathway) and C(3--9)H50 ((the late part of both pathways). The components included C3, C4, C5, C9, B and D. There was a good correlation between CH50 and AP50. AP50 had a good correlation with B and CV50. There was no correlation between AP50 and C(3--9)H50, and none between C(3--9)H50 and C5 or C9. AP50 may primarily represent changes in the early part of the alternative pathway. C(3--9)H50 is not influenced by respective changes in the amounts of C5 or C9. Since cell lesion is now considered to be caused by a unit of C5b to C9, a change in each component of C5 to C9 may not influence haemolytic activity.


Peritoneal clearance and total body elimination of vancomycin during chronic intermittent peritoneal dialysis.

Vancomycin is a useful antimicrobial agent in patients undergoing chronic hemodialysis treatment; its efficacy in chronic peritoneal dialysis (CPD) has not been established. Serum (VS) and peritoneal fluid (VPF) vancomycin concentrations were measured in two CPD patients with staphylococcal peritonitis. Half-life of VS agreed with the half-life of VPF in each patient, and the VS/VPF ratio was 1.27 in both patients. Distribution volumes were 37.2 and 58.7 l, values approximating total body water in these patients. VS and VPF persisted in the therapeutic range (greater than 5 microgram/ml) for more than 16 days. In one patient, mean peritoneal clearacne was 9.8 ml/min, and overall drug clearance averaged 2.3 ml/min; in the other patient, overall clearance was 2.1 ml/min. These results indicate that therapeutic vancomycin levels can be maintained for more than 16 days with a single 1 g intravenous dose in patients receiving intermittent CPD, as is the case for hemodialysis patients. Because of this, parenteral vancomycin is useful in the treatment of staphylococcal peritonitis in CPD patients.


Persistent anemia associated with reduced serum vitamin B12 levels in patients undergoing regular hemodialysis therapy.

Four patients on regular hemodialysis therapy with a persistent anemia and reduced serum vitamin B12 levels are discribed. In each case a significant improvement occurred with B12 therapy and it is suggested that the vitamin B12 content of a 70 g protein/day diet may not be adequate to maintain stores of the vitamin.


Bilateral cortical necrosis and calcification of the kidneys following snakebite: a case report.

A 16 year-old-boy was admitted to the ICU of university hospital with acute renal failure following snakebite. The clinical evolution of the patient associated with radiological findings of renal calcification suggested bilateral cortical necrosis of the kidneys. The biopsy findings were compatible with this diagnosis. The patient was discharged 86 days after his admission, with chronic renal failure, since a kidney transplantation was not possible.


Urinary fibrinogen degradation products and differential protein clearances in renal disease.

The close correlation observed between urine concentration of fibrinogen degradation products and differential protein clearances in the proteinuria of renal disease has been confirmed. Heavy proteinuria in excess of 5 g/l however leads to raised FDP levels, irrespective of the selectivity of the protein clearance. A correction factor for proteinuria enables an accurate estimate of protein clearance from a single measurement of urine FDP.


Judgments of trained observers on adverse drug reactions.

Patients (672) admitted to a department of medicine during five consecutive months were followed by an investigator who identified 110 clinical manifestations which could have been considered adverse drug reactions. From these, 42 were excluded because they did not correspond to the definition of adverse reaction or they were inadequately documented. The remaining 68 cases were submitted to three independent observers who had to reply to a series of questions; from these replies five degrees of probability for the reaction itself were deduced. Reactions (54; 49% of the manifestations reported) were considered as certain or probable by at least two observers, but only 27 rections of these (25%) were attributed to the same drug by all three observers. There was a low level of agreement between any two observers (paired agreement ratio: 0.6 to 0.7) and little difference of agreement between any one observer and each of the others (personal agreement ratio: 0.6 to 0.7).


Biotransformation and elimination of digoxin with normal and minimal renal function.

Six subjects with normal renal function (NRF) and 6 patients with minimal renal function (MRF) on 3 times weekly hemodialysis received 150 muCi3H-digoxin-12 alpha orally. Serial urine collections were made for five days or more. Digoxin and metabolites were separated using diethylaminoethyl Sephadex LH-20 column chromatography. Mean cumulative percentages of the ingested radioactivity excreted over five days in NRF and MRF groups were: digoin, 54.5% and 14.7%; bis-digitoxoside of digoxigenin, 2.0% and 0.59%; mono-digitoxoside, 0.8% and 0.19%; digoxigenin, 0.25% and 0.03%; and dihydrodigoxin, 0.3% and 0.03%. Half-lives based on the mean rates of disappearance from urine comparing NRF and MRF groups were: for digoxin 40 hr and 120 hr; for bis-digitoxoside, 11.5 hr and 46 hr; for mono-digitoxoside, 8.5 hr and 12 hr; for digoxigenin, 2 hr and 7.5 hr; and for dihydrodigoxin, 1.2 hr and 7.0 hr. Considering the relationships of the five-day cumulative excretion and half-lives of digoxin and metabolites in the NRF and MRF groups, it appears unlikely that there is a major alteration in the biotransformation of digoxin in advanced renal failure when there appears to be a shift from renal to slower biliary excretion.


Cefadroxil kinetics in patients with renal insufficiency.

Kinetic parameters and bioavailability of cefadroxil were studied in 20 subjects with differing renal function as measured by endogenous creatinine clearance (CCr). Two subjects were on hemodialysis. After an overnight fast, each subject ingested two 500-mg capsules of cefadroxil. The peak serum concentration was variable (12 to 57 mg/L) and correlated inversely with the CCr. All but one patient had maximum absorption within 4 hr of ingestion and in most patients the peak was reached within the 2-hr sample. Urinary recovery within 48 hr was 45% to 106% when CCr greater than 8 ml/min. Even in patients with the most severe renal failure (CCr less than 10 ml/min), urine concentrations of cefadroxil were adequate to treat susceptible bacteria. The rate of oral absorption ka, was not affected by the state of renal function and was 0.76 +/- 0.50 hr-1. The apparent distribution volume (V d ext) was 0.28 +/- 0.09 L/kg. The plasma elimination rate was dependent on CCr wih a small fraction of drug being removed by nonrenal routes. Except in advanced renal failure, tubular secretion was present since renal clearance of cefadroxil exceeded CCr. The data suggest that little drug accumulation will occur with the usual 8- to 12-hr dosing schedule except when the CCr is less than 25 ml/min.


Site of renal action of xipamide.

Xipamide, hydrochlorothiazide, and furosemide were given to normal volunteers on a double-blind basis. During maximal water diuresis, there was a reduction in free water clearance and an increase in osmolar clearance after administration of xipamide and hydrochlorothiazide, but not in the case of furosemide. During maximal hydropenia, both xipamide and hydrochlorothiazide increased free water reabosorption in a linear relationship to osmolar clearance, while furosemide increased osmolar clearance with little change in free water reabsorption. It was concluded, therefore, that, as with hydrochlorothiazide, the site of action of xipamide was on the distal convoluted tubule, and that of furosemide on the loop of Henle.


Single and divided doses of penbutolol.

Penbutolol, a nonselective beta-adrenoreceptor antagonist, induced reduction of exercise-induced heartbeats for at least 24 hr after a single 40-mg oral dose, and was equipotent with respect to a 2 X 20-mg regimen over the same period. Ingestion for 7 days did not influence the pharmacodynamics or pharmacokinetics of penbutolol, and there was no cumulation of drug in serum. A relationship was found between the logarithms of measurable serum concentrations of penbutolol and the percentage reduction of total heartbeats. Absorption of oral penbutolol appeared to be reduced when administered in the evening. Since beta-adrenoceptor activity was relatively unchanged between 13 and 24 hr after a single 40-mg dose of penbutolol, there is a possibility that an active metabolite or metabolites may contribute to prolonged duration of action.


Dichloroallyl lawsone.

Dichloroallyl lawsone (DCL, NSC-126771), a synthetic analogue of the antimalarial lapachol, is potentially useful in cancer chemotherapy. Unlike most anticancer agents, DCL is not significantly myelosuppressive in animals but it induces acute cardiac toxicity in the rhesus monkey. This cardiac toxicity seems to be correlated with the maximal plasma DCL concentration, about 130 mg/L in the monkey. We have studied DCL pharmacokinetics in patients in an attempt to define safe dose limits for the Phase I clinical trial. After the rapid intravenous infusion of 10 mg/m2 of radioactive [1- or 4-14C]DCL, 250 muCi per patient, the mean peak plasma concentration of unchanged DCL in four patients was 2.9 +/- 0.3 mg/L. The drug had a mean initial plasma half-life of 48.9 +/- 19 min and a terminal half-life of 20.3 +/- 1.8 hr, with a C X t of 50.1 +/- 12 mg/L/hr, and a clearance rate of 0.08 ml/kg/min. These data suggest that in clinical trials the DCL dose given by rapid intravenous infusion should not exceed 450 mg/m2 so that the maximal plasma drug concentration remains below 130 mg/L.


Prediction of steady-state imipramine and desmethylimipramine plasma concentrations from single-dose data.

Tricyclic antidepressant plasma levels were measured in patients and healthy subjects after a single dise of desmethylimipramine (DMI) or imipramine (IMI) and after chronic dosing to steady states. Tricyclic plasma levels measured 24 hr after the single oral dose correlated with steady-state plasma levels. In patients receiving DMI there was a correlation (r = 0.97, n = 10) between 24-hr and steady-state DMI levels, while in normal subjects receiving IMI the correlation was r = 0.92 (n = 20) between 24-hr and steady-state total tricyclic levels (IMI plus its metabolite, DMI). These results suggest the possibility that after a test dose of tricyclic antidepressant, a patient may be put on a "therapeutic" dosage regimen without delay.


Treatment of alkalosis with ammonium chloride: a case report.

Coma due to ammonium chloride used in the treatment of severe metabolic alkalosis is reported in a patient with normal hepatic and renal function. All symptoms resolved following discontinuance. Ammonium chloride should be abandoned as a treatment for metabolic alkalosis.


Hodgkin's disease: the pendulum swings. Knox lecture, Royal College of Radiologists, 1977.

There has been a profound change in the attitude of the medical profession towards patients with Hodgkin's disease. Until recently the disease was regarded, quite incorrectly, as inevitably fatal. Nowadays it is frequently assumed that it is constantly curable, which also a totally erroneous view. However, there has been an enormous improvement in the management of patients with all stages of the disease, so much so that further improvements without the production of excessive complications are becoming increasingly difficult to achieve. The author reviews the background to the present situation including some of the studies organised by the British National Lymphoma Group, which may be producing results which could be of benefit for patients. Some measures are discussed which may offer hope of improving even further the situation for the patient, without increasing risks from treatment.


The instant enema in inflammatory disease of the colon.

The instant, or unprepared, double contrast barium enema has been used routinely at St Mark's Hospital in the investigation of active inflammatory disease of the colon since 1963. The use of air contrast is preferred to show the fine detail of the mucosal changes and to detect early involvement. With the instant enema technique the diagnostic results are satisfactory and patients are minimally disturbed by the procedure. The majority of examinations consist of a total of four films, which includes a plain film of the abdomen prior to the administration of contrast. For short-term follow-up a repeat enema with a single film is usually adequate.


Chronic pancreatitis and inflammatory bowel disease.

A consecutive series of 59 patients with abnormal pancreatograms indicative of chronic pancreatitis included five patients who also had inflammatory bowel disease. This is greater number than would be expected by chance. The cases are presented, and possible explanations are discussed.


Rapid duodenal and jejunal intubation.

A size 12 French radiopaque catheter, 135 cm long, suitable for rapid duodenal and jejunal intubation, is described. Its size and flexibility enable it to be passed with ease through the nose, stomach and duodenum. A guide wire is used to act as a stiffener as the catheter is passed through the stomach. The catheter is suitable for infusing barium directly into the small intestine and for performing hypotonic duodenography. The technique for duodenal and jejunal intubation is discussed.


Radiological changes of reflux oesophagitis.

Early changes in reflux oesophagitis are difficult to assess on radiological criteria (Torrance, 1973). The later manifestations, particularly with stricture formation, are best assessed by barium swallow. Apart from stricture formation, marked reflux oesophagitis with coarsened folds may lead to a mistaken diagnosis of varices or carcinoma. The various radiological appearances that have been encountered are described.


Peritoneal cannulography.

Peritoneal dialysis is a simple effective treatment for patients with some forms of renal failure, poisoning and fluid and electrolyte imbalance. There are several well-recognised complications. Common amongst these are malinsertion and positioning of the cannulae, perforation of visci and partial blockage of the cannula by debris. A simple technique of cannulography is described whereby the diagnosis of some of these conditions can be readily achieved.


Computer-assisted tomography in the assessment of cervical spine trauma.

Four patients with cervical spine trauma were examined by computerised tomography in addition to standard radiography and additional useful information was thereby gained. The axial projection is particularly useful in studying the cervical spinal canal and neural arch. The examination may be performed rapidly without moving the patient, an important consideration after severe trauma.


Computed tomography in pulmonary asbestosis.

Attention is drawn to the signs of asbestosis on computed axial tomography and comparison made with findings in conventional radiology in 36 patients. CT was found to be significantly more sensitive in the detection of both pleural and parenchymal disease apart from thickened fissures. A possible sign of early mesothelioma is mentioned and an encasing variety of pleural thickening described. Perfusion changes which may represent a 'pre-radiological' interstitial fibrosis are discussed.


Percutaneous needle biopsy of thoracic lesions--an evaluation of 300 biopsies.

The results of 300 consecutive thoracic needle biopsies have been evaluated. It is concluded that this is a safe procedure for the investigation of peripheral intrathoracic masses. It should not be performed unless excellent facilities for cytopathology are available. Under these conditions there is a high degree of accuracy in differentiating between malignant and non-malignant lesions, particularly if repeated biopsies are performed when the initial results are unrewarding, equivocal or at variance with the radiographic appearances. In this series there was an imperfect correlation between the cytological and subsequent histological cell type except with squamous carcinomas. The indications are changing with the advent of flexible bronchoscopy and the increasing use of chemotherapeutic regimes. Misleading results may be obtained from biopsy of cavitating lesions and necrotic tumours.


A simplified approach to the reporting of intensive therapy unit chest radiographs.

The rationale for a simplified approach to the reporting of intensive therapy unit chest radiographs is presented. Pulmonary shadowing should be reported simply as pulmonary shadowing; histological predictions are unreliable and potentially misleading. One should concentrate on the detection of pneumothorax and the differentiation between pulmonary shadowing, pleural effusion and pulmonary collapse.


CT scanning in two cases of lipoma of the spinal cord.

Two cases of lipoma of the spinal cord are presented. CT gives a specific diagnosis in this condition without any contrast being given. It is important to make a preoperative diagnosis, as in lipoma of the spinal cord biopsy is dangerous and frequently makes the patient worse. CT is also valuable as the length of the required decompression laminectomy can be assessed.


Initial experiences with a formalised teaching programme in diagnostic radiology during the clinical undergraduate course.

The initial experiences of a four-week clinical undergraduate attachment in diagnostic radiology are described. The course is divided into (1) a series of prepared lecture programmes which cover aspects of diagnostic radiology in a systematic manner, (2) experience in hospital X-ray departments, observing special investigations and routine reporting, attending clinicoradiological conferences and receiving informal and formal tuition from radiologists, and (3) visits to specialised radiological and other imaging departments, namely ultrasound, nuclear medicine, neuroradiology and paediatrics. The aims of the courses are: (i) to provide a means of teaching clinical subjects and pathology in a dimension which crosses the tightly compartmentalised undergraduate curriculum; (ii) to instil basic principles of radiological interpretation, (iii) to teach undergraduates how to use the facilities of diagnostic imaging departments effectively and efficiently when they have qualified; (iv) to increase interest in the specialty, and insight into student opinion. There are difficulties involved in this large teaching commitment, for instance, understaffing, and the development of the course has been geared to counteracting these problems.


The Massachusetts Poison Control System.

State and federal law provided the impetus to develop a coordinated statewide poison system in Massachusetts. To achieve this objective the Commissioner of the Department of Public Health established a Statewide Poison Committee, composed of poison control representatives, physicians, nurses, and pharmacists. After a year of regular meetings, a structure for a statewide poison system was developed, meetings, a structure for a statewide poison system was developed, and as January 1978 this System has been operational in Massachusetts. The structure is based on the Department of Public Health contracting with an incorporated institution to implement the Statewide System, which consists of one information center available to the public and professionals as well as a network of all 112 acute care hospitals in the State as "member institutions." Educational institutions" are further designated with a responsibility of professional and public education in various geographic areas throughout the State. The System is responsible for providing comprehensive poison information, treatment, public education, professional education, data collection, and research. A senior Advisory Board representing institutions with major contributions to the System as well as a Coordinating Committee representing diverse geographic and professional interests serve in an advisory capacity to the System. Funding is broad-based and includes federal, state, and private institutional support.


Acute dapsone intoxication: a case with prolonged symptoms.

A 45-year-old man ate about 10 gm of dapsone (DDS). After initial vomiting marked methemoglobinemia with cyanosis, headache, and confusion developed. Methemoglobinemia subsided 7 days after ingestion when the concentrations of DDS and monoacetyldapsone (MADDS) were at the therapeutic level. Signs of hemolysis appeared on the third day after DDS ingestion, the hemolysis being maximal more than one week after ingestion. The initial disappearance of DDS and MADDS was slow, the apparent half-lives being 88 and 67 hr, respectively. Peroral activated charcoal seemed to shorten the half-lives of DDS and MADDS markedly. This result supports the concept of the enterohepatic cycle of dapsone and recommends the use of activated charcoal for several days in acute poisonings caused by DDS.


Acute delirious state after epsilon-amino caproic acid administration.

Prior to intravenous pyelography, a patient known to have iodine hypersensitivity was injected intravenously with a bolus of 2 gm epsilon-amino caproic acid (EACA). Immediately following the injection the patient developed an acute episode manifested by a delirious state, with auditory, visual, and kinesthetic hallucinations. The entire episode lasted 8 min, and no residual psychiatric or neurologic symptoms were observed. To the best of our knowledge no such side effect of EACA has been reported so far.


Fenfluramine poisoning.

In a series of 53 fenfluramine intoxications (15 taken from the literature), 10 were lethal after doses of 28.7--70 mg/kg of body weight. Cardiac arrest occurred 1--4 hr after ingestion in 9 cases; all these 9 patients died. Two out of 3 patients with more than 15 mg/kg had coma and convulsions. Other frequent signs were mydriasis, tachycardia, and rubor of the face. The additional signs of nystagmus, hypertonia, trismus, hyperreflexia, clonus, excitation, hyperthermia, and sweating define the clinical syndrome of fenfluramine intoxication. Symptoms begin 30--60 min after ingestion and can persist during several days. Early gastric lavage, instillation of activated charcoal, diazepam in case of seizures, chlorpromazine for malignant hyperthermia, propranolol for extreme tachycardia, and lidocaine in the event of ventricular extrasystoles are recommended. If trismus is a prominent sign, muscle relaxants must be given before gastric lavage can be done. The relatively benign course after survival of the first 4 hr suggests supportive therapy only in the later phase of intoxication.


California Association of Toxicologists proficiency testing program.

A proficiency testing program that has been conducted by the California Association of Toxicologists for 10 years is described. The purpose of the program is to allow each participant the opportunity to evaluate their methodology and efficiency on a qualitative as well as quantitative basis with other laboratories in the organization. The program is conducted entirely on a volunteer basis with the sample prepared by a different member each time. The selection of drugs for inclusion in the sample, the preparation and distribution, and the collation and dissemination of the results are discussed. An evaluation of all aspects of the program is presented.


A program for maximum likelihood estimation and likelihood ratio tests in one-locus ABO-like systems based upon population phenotype data.

Phenotypes in an ABO-like system of a number of genetically-independent persons from a number of populations are supposed to be observed. The program which is written in FORTRAN calculates maximum likelihood estimates of gene frequencies and their standard errors in each population and in the populations taken together. Furthermore the program calculates expected values and likelihood ratio and goodness of fit chi-square tests of Hardy-Weinberg equilibrium. If several subpopulations are pooled together a likelihood ratio test of homogeneity is performed.


A computer program for testing average partial association in three-way contingency tables (PARCAT).

PARCAT is a computer program which implements alternative tests for average partial association in three-way contingency tables within the framework of the product multiple hypergeometric probability model. Primary attention is directed at the relationship between two of the variables, controlling for the effects of a covariable. This approach is essentially a multivariate extension of the Cochran/Mantel-Haenszel test to sets of (s x r) tables. A set of scores such as uniform, ridits, or probits can be assigned to categories which are ordinally scaled. In particular, if ridit scores with midranks assigned for ties are utilized, this procedure is equivalent to a partial Kruskal-Wallis test when one variable is ordinally scaled, and is equivalent to a partial Spearman rank correlation test when both variables are ordinally scaled.


A method of correction for curvature and inhomogeneities in computer aided calculation of external beam radiation dose distributions.

This paper deals with the problem of finding the effective pathlength along a ray passing through a patient's outline and internal structure. The pathlength contributes to the correction applied for curvature and inhomogeneities in the computer-aided calculation of external beam radiation dose distributions. The pathlength is found by first determining the intersections of the ray with the contours defining the patient's body and the interior inhomogeneities. From these intersections the geometric length within each contour is obtained. This information is then employed in a treatment planning program for high energy gamma and X-rays and electrons, in which the radiation dose distribution is computed taking into account the actual inhomogeneous tissue structures. Other applications of the techniques described to problems in the field of radiation therapy are briefly discussed.


Two-dimensional fast transforms applied to memory limited disk operating computers.

Two-dimensional transform algorithms are usually impractical to small machines which cannot handle N2 real (or complex) data points in core when N is large. Storing the input data in N disk records and computing two sequential one-dimensional transforms requires N(N + 3) disk access and 2 N applications of the one-dimensional procedure. Expanding the fast one-dimensional algorithm it is suggested that only 2 N log2N disk accesses are needed whereas the one-dimensional procedure is activated only N times.


Interactive computer supported tumor registry in the state of Rhode Island.

A new interactive computerized tumor registry has been established for the state of Rhode Island. The registry is implemented with new data base software which features a pagination scheme with rapid retrieval of non-coded variable data. The types of data stored are discussed as well as the computer system and methods of data entry storage and retrieval.


A new interactive computerized data base and retrieval system.

A new computerized data base and retrieval system for a minicomputer has been devised for storing and retrieving clinical data. It features interactive terminal input and output using a pagination scheme as well as a subset mapping scheme for interactive retrieval. The pagination system, file structuring and retrieval system are discussed.


Compact digital storage of ECG's.

The technique of predictive coding is applied to the problem of reversible compression of digitized electrocardiograms. Integer-based predictors and MMSE predictors are studied as regards performance at varying sampling rates and digital resolutions for both long-term ECGs and ECGs recorded at rest. It is concluded that MMSE predictors are to be preferred only in the case when the ECG is oversampled (i.e., the sampling rate is much higher than twice the cut-off frequency of the presampling filter). In other cases the integer predictor which yields the so-called 2nd differences is superior. The problem of encoding the resulting residuals with a variable-length code is studied for long-term ECGs digitized at 100 Hz and using 8 bits digital resolution. The code has a simple struture leading to speed of execution while the efficiency loss is small.


Pulmonary capillary pressure and permeability.

An appreciation of the "state of the art" of pulmonary capillary pressure and permeability must necessarily form an important part of the basis of a rational choice of fluid therapy. The present state of the understanding of pulmonary transcapillary fluid exchange is developed. Laboratory data are used in conjunction with clinical evidence to construct and support the physiological concepts set forth.


Gene dosage effect: intraband mapping of human soluble glutamic oxaloacetic transaminase.

Quantitative assays of soluble GOT were performed on fibroblasts (from two individuals) with duplications of the long arm of chromosome 10 (10q24 leads to qter). Improved karyologic technique demonstrated that the duplications differ by half a band. Correlation of GOTS activity with the karyologic data indicates that the structural locus for GOTS maps within band 10q24. This study demonstrates the utility of this approach to fine structural mapping of the human genome.


The chromosomes of the southern elephant seal, Mirounga leonina (Phocidae: Mammalia).

Chromosome analyses were carried out on bone marrow cells from three elephant seal pups (Mirounga leonina), a species characterized by a 2n = 34 chromosome number. Arm ratios for the different chromosomes were calculated to facilitate the classification of chromosomes into groups. The karyotype of the southern elephant seal differs from other reported 34-chromosome phocids in the morphology of the Y chromosome and in that of one of the autosomal chromosome pairs.


Meiotic studies of translocations causing male sterility in the mouse. II. Double heterozygotes for Robertsonian translocations.

Unusual meiotic behavior of the XY chromosome pair was observed in sterile male mice doubly heterozygous for two Robertsonian translocations, Rb(16.17)7Bnr and Rb(8.17)1Iem. Nonrandom association between the X chromosome and the translocation configuration, ascertained from the frequencies of relevant C-band contacts, was found in 9 of 10 sterile males. Besides the nonrandom association, the XY chromosomes showed signs of impaired condensation, as judged by measurement of their lengths at diakinesis/MI of the first meiotic division. In contrast, neither nonrandom contact nor decondensation of the XY chromosomes pair was found in fertile males heterozygous for a single Robertsonian translocation, Rb1Iem or Rb7Bnr. The present observations lend indirect support to the working hypothesis advanced previously, the assumption that interference with X-chromosome inactivation is a possible cause of spermatogenic breakdown in carriers of various male-sterile chromosomal transloations. Alternative explanations of the available data, which cannot be ruled out, are briefly discussed.


Genetic studies in NZB mice. II. Hyperdiploidy in the spleen of NZB mice and their hybrids.

The presence of hyperdiploidy was studied in New Zealand black (NZB) mice and the progeny of NZB X DBA/2 crosses and backcrosses. Hyperdiploidy was observed in the spleens of a majority of NZB mice but not in DBA/2 mice at 1 year of age. In crosses of NZB with the DBA/2 strain, hyperploidy was observed only in backcrosses to NZB. Hyperdiploidy appeared to be determined by a recessivley inherited trait and was not related to the presence of other immunological abnormalities, including splenomegaly, hypergammaglobulinemia, and spontaneous antibodies cytotoxic for T cells and reactive with single-stranded DNA. Abnormal cells were not present in Concanavalin A-stimulated 48-h spleen cultures. There was no difference in the in vitro sister chromatid exchange rate between the autoimmune NZB strain and the non-autoimmune DBA/2 strain. Identification of NZB chromosomes by banding analysis showed that chromosomes 15 and 17 were frequently present in more than two copies in hyperdiploid spleen cells. NZB chromsomes also had reduced C-banding in an autosomal pair. These studies indicate that chromosomal abnormalities which occur in NZB mice may be useful as genetic and cytogenetic markers.


Emergency room intubations--complications and survival.

Forty-three consecutive patients requiring endotracheal intubation in an emergency room were studied prospectively to define the complications associated with intubation and the survival of these patients, and to evaluate emergency room policies. The indications for intubation were acute respiratory failure (ARF) in 22 patients and cardiopulmonary arrest (CPA) in 21 patients. Thirty-eight complications occurred in 24 of the 43 patients. The department or level of training of the intubator did not affect the rate of complications. Furthermore, specific complications did not influence survival. Seventeen patients survived, all in the ARF group. Age less than 40 years and admission PaO2 greater than 40 mm Hg also were associated with increased survival. We conclude that the complication rate of emergency room intubations is high and would not appear to be lowered by limiting intubations to physicians from specific departments or with certain levels of training. The underlying diagnosis and condition on admission to the emergency room appear to be more important factors relating to survival than complications during intubation.


Airway response to hair spray in normal subjects and subjects with hyperreactive airways.

Short-term 20-second exposure to hair sprays A and B failed to show significant decreases in maximum expiratory flow rates at low pulmonary volumes in normal subjects; however, significant decreases were observed with hair spray B in eight subjects with hyperractive airways (abnormal response to inhalation of methacholine). On the partial flow-volume curves, flows at 40 percent and 25 percent of forced vital capacity decreased 8.9 to 10.3 percent and 14 to 18.7 percent, respectively. The hair sprays differed in their content of perfume and plasticizer, and since the latter is generally considered nontoxic at room temperature, the perfume may be the responsible agent. It would appear from this study that normal healthy individuals are at little risk, at least from brief exposure to hair spray; however, in the presence of hyperreactive airways, as seen in asthmatic subjects and in some people with allergic rhinitis and viral respiratory infections, an immediate response of the airways may result from exposure to some hair sprays.


A prospective study of mitral valvular prolapse in young men.

A cardiac history, a physical examination, an electrocardiogram, phonocardiograms in the supine and standing positions, and an M-mode echocardiogram were obtained in 100 randomly selected, presumably healthy, male medical students (mean age, 26 years). Four percent met standard echocardiographic criteria for mitral valvular prolapse. No midsystolic clicks or late systolic murmurs were appreciated in this group, and none complained of chest pain or palpitations. To elucidate further the clinical implication of the echocardiographic pattern of mitral valvular prolapse, 24-hour ambulatory ECGs, multistage exercise tests, and scintiscans of myocardial perfusion at rest and after exercise (using radioactive 13nitrogen-labelled ammonium) were obtained, with normal results. The absence of life-threatening arrhythmias and exercise-induced abnormalities in these four asymptomatic subjects without abnormal physical findings suggests that the echocardiographic pattern of mitral valvular prolapse in such individuals may represent a variant of normal which does not require extensive evaluation.


Irradiation-induced pericarditis.

Three patients with pericarditis following therapeutic irradiation for malignant tumors were studied at autopsy. In one subject, death occurred five days after the last dose of radiation. The pericardial involvement was characterized by fibrinous exudation. This was more marked in degree over the right side of the heart than the left and corresponded with the field of irradiation. In the remaining two patients, two and four courses of radiation had been applied, the interval between the last dose and death being seven weeks in one patiet and 1 1/2 years in the other. The lesions were those of organizing pericarditis.


Occurrence of frequent complex arrhythmias detected by ambulatory monitoring: findings in an apparently healthy asymptomatic elderly population.

In order to delineate the frequency of arrhythmias and conduction abnormalities in a group of apparently healthy elderly people, 24-hour ambulatory ECG recordings were obtained on subjects recruited from the Veterans Administration Voluntary Service. Their ages ranged from 60--84 (average 69). It is concluded from this preliminary study that complex supraventricular and ventricular arrhythmias occur in an apparently healthy elderly population. These findings must be taken into account in assessing the clinical significance of arrhythmias in an elderly population.


Antimicrobial activity of antituberculosis agents against anaerobic bacteria.

Anaerobic infections may coexist with tuberculosis, and can be mistaken for one another. The effect of therapy with antituberculosis chemotherapeutic agents against anaerobic bacteria (with the exception of rifampin) is unknown. We therefore examined the in vitro efficacy of certain commonly used antituberculosis agents (rifampin, isoniazid, and ethambutol) against 370 strains of anaerobic bacteria, including 86 isolates of Bacteroides fragilis. Rifampin at a concentration of 2 microgram/ml inhibited 91 percent of all anaerobic isolates. Both ethambutol and isoniazid were totally ineffective against any of the anaerobes tested, even at 64 microgram/ml. Therapy with rifampin in an unsuspected anaerobic infection can be misdiagnosed for tuberculosis. Therefore, when tuberculosis is suspected, isoniazid and ethambutol can be used and rifampin withheld until the acid-fast bacilli are demonstrated by additional diagnostic procedures, such as transtracheal aspiration.


Evaluation of criteria for diagnosis of myocardial infarction: study of 256 patients with intermittent left bundle branch block.

In an attempt to elucidate the specificity and sensitivity of atypical findings during left bundle branch block (LBBB) with respect to myocardial infarction (MI), we analyzed ECGs from patients with intermittent LBBB obtained by mail solicitation of cardiologists. The group consisted of 256 patient files fulfilling the following criteria: 1) complete LBBB present on one or more 12-lead ECGs, and 2) at leat one 12-lead ECG taken subsequent to a LBBB tracing exhibiting absence of LBBB (non-LBBB). The sensitivity of atypical LBBB for predicting presence of MI was 0.41, the specificity 0.64, and the accuracy 0.59. No specific atypical finding was significantly better than any other in predicting MI. We conclude that atypical findings present during LBBB are of little value in predicting the presence of MI (as diagnosed by significant Q waves present during non-LBBB conduction).


Cardiac anatomy viewed systematically with two dimensional echocardiography.

The details of three-dimensional cardiac anatomy are complex, and structure recognition is difficult in tomograms produced with recently developed two-dimensional ultrasonic sector scanners. This article presents a method we have found useful for systematic inclusion of most cardiac structures during such echocardiographic examinations. Orthogonal planes, aligned parallel and perpendicular to the long or major left ventricular axis, are obtained from each of three transducer positions on the body surface. Moving this X-Y image plane through the heart perpendicular to the plane (z axis) allows the viewer to integrate the images into a mental picture of the whole structure. The illustrations are oriented as they are displayed by ultrasonic sector scanners so they aid rapid recognition of cardiac structures.


Electrophysiologic study of the left ventricle: indications and safety.

Eighty patients (69 with documented or suspected recurrent ventricular tachycardia or fibrillation, ten with left bundle-branch block, and one with the Wolff-Parkinson-White syndrome) underwent both right ventricular and left ventricular programmed electrical stimulation, including ventricular pacing and the introduction of one or two ventricular extrastimuli or electrode catheter mapping of the left ventricle (or both). Left ventricular catheters were introduced precutaneously via the femoral artery (of 61 patients, one required secondary repair) or via brachial arteriotomy (of 19 patients, two required secondary repair). All patients received an intravenously administered bolus of hep arin (5,000 units) following the insertion of the left ventricular catheter and then 1,000 units/hr after the first hour of study. No patients had cerebrovascular, systemic thromboembolic, or cardiac sequelae. In four (12 percent) of 34 patients with inductible ventricular tachycardia, programmed electrical stimulation of the left ventricle was required for initiation. Extensive left ventricular endocardial mapping was performed in 45 patients. Our experience suggests that (1) electrophysiologic study of the left ventricle can be performed safely, (2) programmed electrical stimulation of the left ventricle is indicated when a suspected ventricular tachyarrhythmia cannot be induced from the right ventricle, and (3) endocardial mapping of the left ventricle is indicated when surgery is being considered to abolish recurrent sustained ventricular tachycardia.


Chronotropic and dromotropic effects of histamine on the canine heart.

The actions of 2-methylhistamine (H1 agonists), 4-methylhistamine (H2 agonist), and histamine were studied by selective perfusion of the sinus node artery and atrioventricular node artery in 75 dogs anesthetized with pentobarbital sodium. 2-Methylhistamine and histamine had variable and inconsistent effects on the sinus rate. 4-Methylhistamine (100 microgram/ml) produced acceleration of the sinus rate from 158 +/- 4 to 173 +/- 5 beats per minute (P less than 0.05) when perfused via the sinus node artery. The effects of the histamine agonists on atrioventricular junctional rhythms were similar to the effects on sinus rhythm. The response of the sinus node to vagal stimulation was attenuated by selective perfusion with histamine; however, the direct negatively chronotropic action of acetylcholine was not affected by histamine. Neither 2-methylhistamine nor 4-methylhistamine affected the response of the sinus node to vagal stimulations. Both 4-methylhistamine and histamine (but not 2-methylhistamine) attenuated (P less than 0.05) the response of the sinus node to stimulation of the right stellate ganglion. The positively chronotropic effects of directly perfused norepinephrine were unaffected by histamine or 4-methylhistamine. These results suggest a neural depressing action of histamine on autonomic efferent fibers. In the atrioventricular junction, both histamine and 2-methylhistamine (but not 4-methylhistamine) had negatively dromotropic effects. Cimetidine (an H2 antagonist) had no significant direct effects on the sinus rate or atrioventricular conduction and failed to prevent the acceleration of the sinus rate produced by local perfusion with 4-methylhistamine.


False aneurysm of the right atrium.

A false aneurysm of the right atrium is described. The false aneurysm appeared after open-heart surgery and was probably related to loosening of a right atrial suture. Because of the low pressure in the right atrium, the danger of rupture seemed to be low, and conservative therapy was chosen.


Acute miliary blastomycosis presenting as fluminating respiratory failure.

A patient with miliary blastomycosis had acute fulminating respiratory failure requiring prolonged external ventilatory support. Treatment consisted of antifungal chemotherapy with two drugs and administration of corticosteroids. Restrictive ventilatory impairment and exercise-induced hypoxemia persist at one year after completion of therapy.


Spontaneous resolution of mediastinal pancreatic pseudocyst.

We report the findings in a 39-year-old man with alcoholic pancreatitis and a lower posterior mediastinal mass. Endoscopic retrograde pancreatographic and ultrasonographic studies permitted an unequivocal diagnosis of mediastinal pancreatic pseudocyst. The pseudocyst resolved spontaneously five weeks after diagnosis, without specific therapy.


Effect of postural changes on pulsus alternans: an echocardiographic study.

We describe a patient who had severe left ventricular dysfunction and pulsus alternans following an episode of severe viral myocarditis. Pulsus alternans was mild with the patient in the supine and squatting positions but increased dramatically on standing. Echocardiograms were used to study changes in left ventricular dimension and function with changes in posture. On standing, there was a decrease in the left ventricular diameter and an increase in the absolute and relative shortening fraction and the velocity of shortening on the strong beats, and there was a decrease in end-diastolic dimension and the measurements of ventricular contractility on the weak beats. The marked increase in pulsus alternans during standing may have been induced by increased sympathetic stimulation following the decrease in ventricular loading conditions, while the great beat-to-beat differences in end-diastolic dimension suggest, in addition, the importance of Starling's mechanism.


Psoriasis, sacroiliitis, and aortitis: an echocardiographic mimic of aortic root dissection.

A patient with psoriasis, HLA-B27-positive sacroiliitis, and aortitis presented with clinical features suggesting acute aortic dissecting aneurysm. Although M-mode and two dimensional echocardiography supported the diagnosis, dissection was excluded by angiography and by direct observation at surgery. Asymmetric thickening of the right coronary cusp secondary to psoriatic aortitis was found to be etiologic of both the regurgitation and the false-positive echo for dissection. It is emphasized that in the setting of any fibrocalcific or inflammatory disease of the aorta, the echo diagnosis of dissection is fraught with hazard.


Endobronchial polyposis secondary to thermal inhalational injury.

A 28-year-old man who sustained inhalational injury in a house fire developed symptoms of chronic cough and hemoptysis requiring bronchoscopy. Two months after the initial injury, numerous endobronchial polyps were found in the trachea and throughout the bronchial tree. His symptoms have subsequently improved over a six-month period while receiving steroid therapy. To our knowledge, this delayed complication of inhalational burn injury has not been previously reported.


Course of pulmonary hemodynamics in patients with chronic obstructive pulmonary disease.

Eighty-five patients with chronic obstructive pulmonary disease, mainly chronic bronchitis (71 patients), who had arterial hypoxemia and moderate to severe obstruction of the airways underwent at least two right cardiac catheterizations in a clinical steady state, with a delay of three years or more between the first and the last catheterization. The average delay was 60 +/- 19 months (range, 36 to 119 months). Patients were regularly examined (quarterly clinical and functional checkups). The changes in pulmonary hemodynamic data were small. In the group of 53 patients with an initial mean pulmonary arterial pressure of 20 mm Hg or less, this pressure varied from 15.4 +/- 3.1 to 18.3 +/- 6.6 mm Hg (P less than 0.001); in the group of 32 patients with an initial mean pulmonary arterial pressure greater than 20 mm Hg, this pressure varied from 27.7 +/- 6.0 to 31.0 +/- 9.3 mm Hg (P less than 0.05). The mean pulmonary arterial pressure increased by 5 mm Hg or more in only 28 patients. In these patients with hemodynamic "worsening," the final arterial oxygen pressure (PaO2) was lower and the final arterial carbon dioxide tension was higher than in the remaining patients. A significant negative correlation (r = -0.39; P less than 0.001) was observed between changes in PaO2 and mean pulmonary arterial pressure. There was a generally good agreement between the course of pulmonary hemodynamics (mean pulmonary arterial pressure), on the one hand, and the clinical, radiologic (transverse diameter of the heart), and electrocardiographic evolution, on the other hand. In the 33 patients who died, a relatively long survival was observed after the first episode of right-sided heart failure or after ascertaining pulmonary hypertension.


Bronchostenosis due to sarcoidosis: a cause of atelectasis and airway obstruction simulating pulmonary neoplasm and chronic obstructive pulmonary disease.

Ninety-nine patients with clinically and histopathologically established sarcoidosis were studied during the period of January 1971 to October 1977 using the bronchoscope. In 32 patients, biopsy of the bronchial mucosa showed a microscopic picture typical of sarcoidosis. In eight (8 percent) of the 99 patients, severe stenosis of the bronchi was seen. We conclude that bronchial sarcoidosis with multiple segmental or lobar stenosis can closely imitate the clinical picture of chronic obstructive pulmonary disease. Bronchostenosis in sarcoidosis can cause atelectasis visible on the chest x-ray film and thus closely simulate a pulmonary neoplasm.


Historic and angiographic features of young adults surviving myocardial infarction.

Sixty-eight survivors of myocardial infarction occurring before the age of 36 years were studied using selective coronary cinearteriograms, regardless of symptoms. Three groups of patients were delineated; 56 patients (82 percent) had obstructive coronary arterial disease, nine (13 percent) had normal coronary arteries, and three (4 percent) had congenital coronary arterial anomalies. Because the prognosis in these three groups is different, all young patients with myocardial infarction should undergo coronary arteriographic studies after a suitable period of convalescence. Myocardial infarction in the young differs from that in the elderly by virtue of a more heterogeneous underlying coronary anatomy, an overwhelming preponderance of male patients, and a better reported prognosis.


A rational approach to ligation of patent ductus arteriosus in the neonate.

During a 23-month period, 25 premature infants underwent ligation of a patent ductus arteriosus performed in the neonatal intensive care unit utilizing a limited posterolateral muscle-retracting incision. This approach afforded adequate exposure with minimal surgical time and trauma. All infants manifested severe respiratory distress and congestive heart failure. Both standard and contrast echocardiographic studies were used for noninvasive preoperative evaluation. Echocardiographic study proved to be a highly reliable and sensitive indicator of ductal patency. Eight infants (32 percent) died at 8 to 225 days of age. The primary cause of death was progressive pulmonary disease with subsequent failure of multiple organ systems. Seventeen (68 percent) of the 25 infants survived to leave the hospital. Advantages of ligation of a patent ductus arteriosus in the neonatal intensive care unit include the elimination of problems of transportation (thermoregulation, ventilation, and loss of lines) and continuity of ongoing care and monitoring. The standard facilities of the neonatal intensive care unit proved completely satisfactory for ligation of a patent ductus arteriosus. Ligation in the neonatal intensive care unit is suggested to minimize potential complications of care in the operating room and transport of these critically ill infants.


Pulmonary manifestations in patients with malignant melanoma during BCG immunotherapy. A preliminary report.

Ten patients with malignant melanoma who were treated with bacillus Calmette-Guérin (BCG) were studied with chest roentgenograms, scintiscans with radioactive 67gallium citrate, and the single-breath diffusing capacity of carbon monoxide (Dsb). Three patients (stage 1B) with normal findings had no evidence of progression of disease. Seven patients had abnormal findings on at least one test. Two patients (stage 3B and stage 4B) with focal uptake in the lungs on the scintiscan had metastatic melanoma. Three patients (stage 3B) with diffuse uptake on the scintiscan and a reduced Dsb had no evidence of progression of disease. One patient (stage 1B) with an abnormal chest roentgenogram had a benign pleural effusion, and one patient (stage 4B) with a reduced Dsb was free of melanoma. A diffuse increase in the uptake of radioactive 67gallium in the lungs and a low Dsb may not indicate progression of melanoma. On the other hand, a focal uptake of 67gallium in the lungs is highly suggestive of metastatic disease.


Pulmonary reaction to upper mantle radiation therapy for Hodgkin's disease.

To study the effects of upper mantle radiation therapy on pulmonary function, forced expiratory volume in one second (FEV1), vital capacity (VC), inspiratory capacity (IC), diffusing capacity for CO (DLCO) and diffusion per unit of alveolar volume (DL/VA were determined in 28 patients with Hodgkin's disease, stages 1--3, before therapy and at regular intervals thereafter. Within the first year of follow-up there were significant declines in DLCO, VC, and IC, whereas there were no significant changes in FEV1 or DL/VA. DLCO showed the greatest decline in the largest number of subjects (22/28). Eleven of the 22 had 20 to 60 percent decline of DLCO from baseline. The maximum mean decline in DLCO was -12.7 +/- 3 percent at the 87th +/- 3 days from initiation of therapy postradiation sustained through the 150th day and improving to pretreatment value (+/- 5 percent) by the 8th to 12th month. The changes in DLCO seemed to be independent of the radiation dose ranges evaluated, clinically apparent intrathoracic lymphoma, postradiation radiographic abnormalities and respiratory symptoms. We concluded that impairment in diffusing capacity and loss of vital capacity will develop in most patients receiving upper mantle radiation therapy, indicating that pulmonary reaction occurs despite lung shielding. The functional losses were prolonged and occasionally severe, but were transient and subclinical in most but not all cases. A case of fatal radiation pneumonitis affecting the lung beyond the field of irradiation is reported.


Myocardial oxygen supply-demand ratio: a validation of peripherally vs centrally determined values.

We sought to validate that the supply-demand ratio for myocardial oxygen could be accurately measured from tracings of peripheral as well as central arterial pressure. This ratio was the ratio of the diastolic pressure-time-index (DPTI) over the systolic pressure-time index (SPTI). Sixteen patients had the peripheral DPTI/SPTI determined at cardiac catheterization by the following two different methods: (1) P1, using the mean diastolic and systolic peripheral arterial pressure and the ratio of the duration of diastole and systole; and (2) (P2, where the peak systolic and diastolic peripheral arterial pressures are used, eliminating the need for planimetric data. The results of P1 and P2 correlated closely with the central value (r = 0.96 and 0.92, respectively). We conclude that DPTI/SPTI can reliably be measured from a tracing of peripheral arterial pressure, enabling reliable continuous monitoring of this ratio.


Secundum atrial septal defect and significant mitral regurgitation: incidence, management and morphologic basis.

To better understand the association between mitral regurgitation and secundum atrial septal defect and to clarify the evaluation and management of these patients, the records of 235 adult patients with atrial septal defect were reviewed. Ten patients (4 percent) had significant mitral regurgitation defined by clinical, hemodynamic and angiographic criteria. Three patients required mitral valve replacement at the time of closure of the atrial septal defect and four patients had closure alone, one of whom required mitral valve replacement after five years. Three patients did not undergo closure of the atrial septal defect or mitral valve replacement because of severe coexisting medical problems. In six patients, the mitral valves were studied pathologically and all had thick, fibrotic leaflets and short, thick, fibrotic chordae tendineae. Three of these valves also had scattered areas of patchy myxomatous degeneration and three had areas of vascular ingrowth suggestive of rheumatic disease. Although both invasive and noninvasive studies have high-lighted the coincidence between atrial septal defect and mitral regurgitation, particularly the frequent association of mitral valve prolapse, our data indicate that this association rarely has clinical significance. Furthermore, the morphologic basis for mitral regurgitation in patients with atrial septal defect consists of leaflet and chordal thickening fibrosis and deformity rather than attenuation and ballooning as would be expected in mitral valve prolapse.


Alveolar epithelial injury causing respiratory distress in dogs: physiologic and electron-microscopic correlations.

Structural and mechanical changes were correlated in 29 dogs with acute alveolar injury induced by the subcutaneous administration of N-nitroso-N-methylurethane (NNNMU). The injury was characterized by necrosis and repair of alveolar epithelium while the vascular endothelium remained essentially intact. Compliance of the lung (CL) decreased and elastic recoil increased as epithelial necrosis occurred. During recovery, improved elastic recoil coincided with epithelial regeneration, although CL remained abnormal. The late phase was characterized histologically by widespread closure of clusters of alveoli alternating with dilated small air spaces. The process resulted in distortion of lung architecture and resembled interstitial fibrosis. Reduced lung volume and decreased distensibility of dilated small air spaces may have accounted for the persistently abnormal CL. Because of the specific site of anatomic involvement, the predictable evolution of deranged lung mechanics, and the similarity to human lung injury (adult respiratory distress syndrome), the lung injured by administration of N-nitroso-N-methylurethane is a suitable model to study pathophysiology and types of therapy in a controlled setting.


Dysfunction of small airways following pulmonary injury due to nitrogen dioxide.

Serial physiologic studies were performed to characterize both the immediate and delayed effects of a single occupational exposure to nitrogen dioxide in a nonsmoker. During the initial acute stage of pulmonary edema, the abnormal static pressure-volume curve and decreased static compliance corresponded to a reduction in pulmonary volume. During the delayed acute stage, elastic recoil and properties of resistance to flow were normal, but dynamic compliance was reduced and dependent on respiratory frequency, and oxygen transport was abnormal during exercise, which is consistent with dysfunction of the small airways.


Precipitation of heart failure following sudden withdrawal of hydralazine.

Sudden withdrawal of oral therapy with hydralazine for reduction of afterload in a patient precipitated severe congestive heart failure. Signs of metabolic encephalopathy evolved due to low cardiac output. Reinstitution of therapy with hydralazine resulted in prompt improvement in cardiac and neurologic status. This case underscores the need for careful follow-up of such patients and argues against sudden withdrawal of vasodilator therapy.


Mixed pneumoconiosis: silicosis, asbestosis, talcosis, and berylliosis.

Mixed pneumoconiosis is pulmonary disease due to two or more inhaled mineral irritants. Chronic disease due to beryllium has not been a component of any described mixed pneumoconiosis. A man with occupational exposure to a combination of dusts developed severe pulmonary disease. Silicosis, talcosis, asbestosis, and berylliosis were all documented by an open biopsy of the lung. The varieties of mixed pneumoconiosis are summarized.


Transient focal septal block.

A 65-year-old woman with an acute myocardial infarction, as judged by serial enzyme changes, developed transitory Q waves in leads V2 to V4 and leads 2, 3, and aVF during an attack of pain in the chest. These Q waves were not present 12 hours later. It is suggested that these changes represent a focal block in the septal fibers of the left bundle-branch system. This defect could underlie the transient right precordial Q waves seen in myocardial infarction or ischemia, as well as the fixed Q waves of many patients without septal infarction at autopsy.


Pulmonary edema following intracranial hemorrhage.

Hemodynamic changes and samples of fluid from pulmonary edema were studied in a 50-year-old woman who developed florid pulmonary edema following intracranial hemorrhage. Marked systemic and pulmonary arterial hypertension were associated with the rapid production of edema fluid that contained red blood cells, but had a lower protein content than plasma. After restoration of pulmonary vascular pressures to a normal range, the production of fluid ceased, and clinical signs of edema resolved. These findings point to the sudden increase in pulmonary microvascular pressure as the cause of pulmonary edema in this patient. Our findings contrast with those of previous reports and with speculations on the extent of a defect in permeability accounting for pulmonary edema following injury to the brain.


Superior vena cava syndrome due to a retained central venous pressure catheter.

A 70-year-old man had the superior vena cava syndrome. At thoracotomy a retained central venous pressure line was found to be the cause of venous thrombosis at the outlet of the superior vena cava into the right atrium. A retained central venous pressure catheter and catheter-induced venous thrombosis should be added to the list of causes of the benign form of the superior vena cava syndrome.


Pathologic findings and long-term sequelae in Legionnaires' disease.

A recently recognized sporadic case of Legionnaires' disease occurring in North Carolina is described. Diagnosis was made by special serologic studies performed at the Center for Disease Control, Atlanta. The light-microscopic and electron-microscopic findings are described. Organisms consistent with the etiologic agents of Legionnaires' disease were seen by electron microscopic examination. An eight-month follow-up in this case still showed the presence of some radiologic abnormalities of the pulmonary parynchema, as well as abnormal data on tests of pulmonary function.


Apical fibrobullous disease with rheumatoid arthritis.

We describe a patient who developed noninfectious apical fibrobullous disease 12 years after the diagnosis of seropositive, nodular, deforming rheumatoid arthritis. Fibrobullous disease of the pulmonary apices is a rare entity that is usually found in association with ankylosing spondylitis. Its appearance with rheumatoid arthritis has not been reported. Speculative factors which may predispose to apical fibrobullous disease, such as a stiff chest wall, impaired esophageal motiligy, and HL-A antigen B27, were not present in our patient.


Interpreting Parents Anonymous as a source of help for those with child abuse problems.

A study of reasons for joining the self-help group offers some considerations and guidelines for child welfare workers recommending this step to clients.


A network of services for severely disturbed adolescents.

A centralized network of facilities offering a comprehensive package of treatment modalities avoids the difficulties involved in the coordination of scattered services.


An estimate of nationwide incidence of sexual offenses against children.

Complete data are lacking for accurately estimating sexual offenses against children on a national scale, but projections from statistics available indicate the magnitude of the social problem.


Preschoolers entering foster care in New York City: the need to stress plans for permanency.

Analysis of data furnished by a computer system makes clear the need for special programs to plan permanency for infants and young children in foster care. A report on New York upstate data is appended to this article.


Obstacles encountered in permanent planning for foster children.

Mandatory periodic review of cases of children in foster care is a promising method of preventing children from languishing in limbo, but achieving permanent planning involves difficult decisions.


Removal of status offenders from the juvenile justice system: the Florida experience.

In 1975 Florida transferred jurisdiction over runaway, truant or ungovernable children from the juvenile justice system to the child welfare system. This paper reports on the results of decriminalization.


Continuity of treatment and the County Department of Social Services.

Restructuring of the service delivery system in county departments of social services is proposed to accommodate the changes that followed separation of those services and public assistance.


Staff conflicts over use of authority in residential settings.

Confusion and controversy over the role of authority in treatment and limit setting can undermine staff morale and weaken a residential program.


A child welfare agency project: therapy for families of status offenders.

A pilot project providing therapy for families of status-offender youths has proved effective in reducing placements and costs.


Spontaneous spinal epidural haematoma in a youngster.

The case of an 8-year-old boy with spontaneous spinal epidural haematoma and complete post-operative recovery is described. A review of the literature with particular emphasis on the paediatric age-group is given. The clinical presentation and aetiology are discussed.


Early surgical intervention in posthemorrhagic hydrocephalus.

10 premature infants were found to have posthemorrhagic hydrocephalus (PHH) over a 4-year period. All weighed less than 2,500 g. The diagnosis was established by ventricular puncture and ventriculogram. Ventriculo-peritoneal (V-P) shunt placement was done in each infant soon after establishing the diagnosis, while the cerebrospinal fluid (CSF) was bloody. The mean age of infants at surgery was 21.4 days (range 16-33 days). Shunt obstruction occurred in 3 infants and infection in 1. No other complication was observed. All infants improved markedly in the immediate postoperative period, especially respirator-dependent infants. All survived; preliminary follow-up revealed that 3 were severely retarded and 2 mildly retarded; 5 infants were normal. Our preliminary experience with early V-P shunt procedure in the treatment of PHH has been favorable and follow-up appears encouraging.


Successful surgical treatment of pontine vascular malformation in a 3-year old. Case report.

A 3-year-old male presented with progressive right hemiparesis. Clinical and radiological studies suggested the diagnosis of brain stem glioma. At surgery, a small vascular malformation of the pons was encountered. Although rare, vascular malformations must be considered in the differential diagnosis of brain stem masses.


Subtemporal decompression for the slit-ventricle syndrome after shunting in hydrocephalic children.

During the past 2 years, we have performed subtemporal decompression to deal with recurrent shunt obstruction in 22 hydrocephalic patients with the slit-ventricle syndrome. 13 patients have been followed-up for more than 1 year and 2 others for more than 2 years. The frequency of hospitalization for shunt-revision has been greatly reduced. These results confirm that subtemporal craniectomy is useful in the treatment of patients in whom this syndrome develops.


Hydrocephalus and elevated intracranial venous pressure. Case report.

An infant with a large arteriovenous malformation and communicating hydrocephalus is described. The author suggests that the hydrocephalus is caused by impaired absorption of cerebrospinal fluid due to increased intracranial venous pressure.


On the pathology of experimental hydrocephalus induced by artificial increase in endoventricular CSF pulse pressure.

In lambs, acute and chronic communicating hydrocephalus has been created by merely increasing the amplitude of the intraventricular cerebrospinal fluid (CSF) pulsations, leaving the mean CSF pressure unchanged. The pathologic changes occurring in this type of hydrocephalus do not differ qualitatively from those observed in obstructive hydrocephalus. Beside demonstrating a direct role of ventricular pulsations in the ventricular dilation, the observed findings indicate that an increase in mean CSF pressure is not a necessary condition for the occurrence of the hydrocephalus. Consequently, the hypothesis of abnormal high intraventricular CSF pressure oscillations at the basis of the ventricular dilation of normal pressure hydrocephalic patients, receives a significant support. Further support is provided is provided by considering the recorded experimental pathological lesions are quite similar to those observed in normal pressure hydrocephalic patients with patent subarachnoid CSF pathways.


Teratocarcinoma of the brain -- a treatable disease?

Teratocarcinoma of the brain is a rare teratoid tumor. Less than 100 cases have been previously reported and only 4 were patients with tumors in the lateral ventricular system. At the Children's Hospital of Philadelphia, 2 patients with teratocarcinoma of the lateral ventricle of the brain have been treated in the past 5 years and both are long-term survivors. A third patient with a recurrence at University Hospital is now receiving chemotherapy. Our experience suggests that a combination of radical surgery, supervoltage radiotherapy and chemotherapy may be successful in controlling these neoplasms. Furthermore, since there is increasing evidence that they have a strong histologic relationship to the embryonal carcinomas that arise in the testes and elsewhere, it appears logical to apply chemotherapeutic strategies to these intracranial neoplasms based on experience with such tumors located in other regions of the body.


[Hypothyroid, iodine-deficient goitre in neonates (author's transl)].

Within one year 1750 mature neonates were examined for congenital hypothyroidism. The region of Göttingen is known to be an iodine-deficient one. Sixteen goitrous, hypothyroid neonates with a low total thyroxine, and raised serum TSH concentration were first diagnosed through this screening programme. As a result of the intra-uterine iodine deficiency, serum triiodothyronine concentration was elevated while urinary iodine excretion was reduced compared with euthyroid neonates. During iodine treatment the size of the thyroid became normal within eight days, TSH after 3.8 days and serum thyroxine after three days. Serum triiodothyronine concentration remained elevated for several weeks, presumably as a result of the persisting iodine deficiency. The results indicate that a neonatal screening programme for hypothyroidism is as essential as adding iodine to table salt for avoiding neonatal and foetal maldevelopment.