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Data from individual interviews, four questionnaires, and two analogue situations for 12 married couples were examined by six clinical judges and evaluated with regard to various aspects of interpersonal functioning. Orders of presentation were counterbalanced in a Latin square design. Ratings were made after each kind of data had been reviewed, after a case conference, and following discussion leading to consensus. Reliabilities were computed for the sets of variables and for each data mode. The convergent and discriminant validities of judgments based on the three data modes were examined by means of a multitrait-multimethod matrix. The utilities of the data modes and of increasing amounts of information were gauged by correlating partial estimates with average judgments of all judges based on all data following case conference. Among the findings were reasonably high levels of reliability for some aspects of interpersonal functioning but very low agreement regarding recommended treatment, quite high convergent validity across the three data modes, and modest but significantly superiority of the interview over the other procedures for assessing marital relationships.

Less than Glu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2, the luteinizing hormone-releasing hormone, LHRH, is degraded in renal proximal tubules (PT) in vivo (rat) and in vitro (rabbit) to less than Glu-His (2), less than Glu-His-Trp (3), and less than Glu-His-Trp-Ser (4). LHRH may be cleaved by endopeptidases simultaneously at multiple bonds, or initially at Ser4-Tyr5 followed by carboxypeptidase hydrolysis of 4 to 3 and then 2. To distinguish between these mechanisms, [3H]LHRH analogues were incubated with rabbit renal brush-border membranes (BBM), microinfused into PT in vivo or in vitro, and products were analyzed by HPLC. [D-Ser4]LHRH was not cleaved at D Ser4-Tyr5 but yielded less than Glu-His-Trp-D-Ser-Tyr-Gly as the major metabolite plus 2 and 3. [D-Trp6]LHRH was cleaved by BBM and PT to 2 and 3, but not to 4. [D-Ser4, D-Trp6]LHRH was not cleaved by BBM, but was degraded to 2 by PT in vivo. Thus, D-amino acid substituents altered the expected cleavage pattern of these analogues. [3H]LHRH was cleaved by BBM or by endopeptidase-24.11 from porcine PT to metabolites 2, 4, small amounts of 3, and less than Glu-His-Trp-Ser-Tyr-Gly, but cleavage was strongly inhibited by the specific inhibitor phosphoramidon. Thus, normally LHRH may be cleaved in PT by endopeptidase-24.11 to 2 and 4, and by angiotensin I-converting enzyme to 3, its known cleavage site.

The hypothesis, advanced by Asch (Mt Sinai J Med NY 35:214-220, 1968), that a majority of sudden infant death syndrome (SIDS) cases are actually infanticides, is addressed by examination of age comparable infant homicide rates (United States, 1950-1974) and consideration of current theory regarding SIDS pathogenesis. The analysis provides no support for the hypothesis.

Renal structural changes were studied sequentially between 1 hour and 6 days in rats treated with D-serine. Extensive necrosis of proximal straight tubules was rapid in onset and was followed by complete tubular regeneration 6 days post-treatment. The apparent progression of cellular changes was initial shrinkage, followed either by swelling and loss of apical cytoplasm or immediate lysis of cytoplasmic and nuclear contents. Tubular damage left only the basement membrane as a barrier between interstitial and luminal fluids. In similarly treated rats, proteinuria and glucosuria developed at the onset of tubular necrosis and disappeared when the tubules were completely relined by epithelium suggesting that they are due to diffusion of protein and glucose from interstitium into tubular fluid across the denuded basement membranes and that epithelial cells, under normal conditions, act as a barrier to diffusion of certain substances between the interstitium and tubular fluid.

Optimum tissue levels of magnesium and potassium ions are essential to the structure and function of the myocardium. We hypothesized that an inapparent deficiency of one or both of these elements might contribute to sudden cardiac death in a susceptible person, and in this study investigated levels of these elements in the myocardium of men experiencing sudden death to determine if there was such an association. Subjects dying suddenly with ischemic heart disease had significantly lower levels of myocardial tissue magnesium and potassium than the controls (men dying of acute trauma). The four lowest potassium values were obtained for the only men in the group with a history of angina (P less than 0.0005). Three of the men with angina also had the lowest tissue magnesium levels (P less than 0.005). The intriguing finding gives support to the hypothesis.

Use of IUDs was examined among 962 women whose pregnancy was terminated at the University Hospital of Trondheim, Norway during 1983. Ectopic pregnancy was significantly more often diagnosed among women with an IUD in place at conception compared to non-users (7.8% vs 1.3%, p less than 0.01). Despite removal of the IUD during the first trimester, women who became pregnant with an IUD in situ had spontaneous abortion more often than non-users (15.6% vs 7.0%, p less than 0.05). The causal significance of these findings will require further investigation. The small number of ectopic pregnancies subsequent to an IUD contraceptive failure in relation to the number of all pregnancies within the same time frame may explain the lack of a demonstrable link between increasing IUD use and increasing rates of ectopic pregnancy.

Regeneration of the ray kidney was observed for six days after inducing acute tubular necrosis of the proximal pars recta with d-serine (80 mg/100 g body weight. Regenerating cells appear by two days post-treatment, and re-epithelialization of the nephron is completed within six days, with the most mature cells approaching normal morphology. Regeneration originates from viable cells adjacent to the necrotic zone which divide and follow a template provided by the intact basement membrane. Transient, cytoplasmic regenerative activity among developing tubular cells is characterized by the presence of large, irregularly shaped nuclei, prominent nucleoli, abundant ribosomes and lysosomes, and abnormal mitochondrial configurations. Microfilaments appear to be involved in the formation of apical microvilli and the basal labyrinth of plasmalemmal convolutions. These data suggest that d-serine induced acute tubular necrosis of the proximal pars recta may be followed by rapid, patterned regeneration along an intact basement membrane, and that microfilaments are involved in differentiation of cellular morphology.

To explore the relationship between vigorous physical activity and primary cardiac arrest (PCA), we identified, through emergency service incident reports, 163 cases of PCA aged 25 to 75 years. Control subjects matched for age, sex, residence, and the absence of prior clinical heart disease or major comorbidity were identified from the community. Spouses of subjects were interviewed to quantify leisure-time activity (LTA) during the prior year. Energy expended in high-intensity LTA, requiring 60% of maximum oxygen intake, was determined. The risk of PCA was 55% to 65% lower in persons in the two upper quartiles of high-intensity LTA than in persons without high-intensity LTA (95% confidence interval of relative risk, 0.22 to 0.85). Because this association was demonstrated in a clinically healthy population without prior morbidity, our data support the hypothesis that high-intensity LTA protects against PCA.

This is a study of the epidemiology of dental emergencies based on information abstracted from the microfilmed dental claim forms of a large American insurance program in 1981-82. Overall, about 4% of all dental visits were classifiable as emergencies. There were significant seasonal and age variations in dental emergencies. There was no variation with respect to geographic regions in the State of Washington (USA) or sex. Paradoxically, residents in regions having fluoridated water supplies were at equal risk of developing dental emergencies due to dental caries, relative to those residing in non-fluoridated regions. There was also no difference in risk associated with insurance deductibles, although generally deductibles are thought to deter first-contact visits.

A unique opportunity to study proven infant apnoea (PIA) and Sudden Infant Death Syndrome (SIDS) occurrences epidemiologically in 12 Counties in north-western Washington State during the same time period during which 180,017 live births were recorded revealed markedly dissimilar distribution patterns. The overall incidence of SIDS exceeded that of PIA by a factor of 3. Five PIA babies subsequently succumbed to SIDS. Statistical analysis reveals that these five events cannot be explained as random coincidences; they represent 3% of 163 PIA cases but only 1% of 503 SIDS occurrences. Infant apnoea is an infrequent precursor of SIDS. These results do not support the view that SIDS and infant apnoea are related conditions caused by a common underlying disorder. Aetiological models other than infant apnoea must be devised if the momentum of SIDS research is to be sustained.

Novel electrochemical methods have been developed for determination of total hemoglobin, hematocrit, and detection of hemolysis in whole blood. Hemoglobin is measured through its peroxidase activity, a fluoride ion-selective electrode being used to monitor the rate of fluoride ion production from the oxidation of an organofluorine compound. Results agree well with those obtained with the cyanmethemoglobin method (r = 0.970). Hematocrit is determined from the ratio of the sodium ion concentrations measured with an ion-selective electrode before and after lysis of the erythrocytes. Results by this and the microhematocrit method correlated well (r = 0.987). Hemolysis in a whole-blood sample is detected by using an oxygen electrode to measure the oxygen released when hemoglobin in plasma is oxidized.

Reabsorption and/or degradation of proteins or peptides are functions of the proximal tubule. Large polypeptides or proteins are reabsorbed by luminal endocytosis and hydrolyzed by lysosomal enzymes. Our recent studies indicate that small linear peptides are hydrolyzed at the luminal membrane, with reabsorption of metabolites. The renal transport and hydrolysis of radiolabeled Al, All, BKN, oxytocin, glucagon, insulin, and LHRH were studied. Techniques for in vivo microinfusion of surface tubules in rats, arterial infusion in filtering and nonfiltering rat kidneys in vivo, and in vitro microperfusion of isolated rabbit nephron segments were used. Reabsorption of radiolabeled material was measured and the intact peptide or its metabolites were identified and quantified in urine, renal venous blood, bathing medium, and/or collection fluid. In addition, peptides were incubated in the presence of isolated renal membrane preparations to identify a probably cellular site of hydrolysis. The findings indicate that in proximal, but not distal tubules, radiolabeled Al, All, BKN, glucagon, and LHRH are hydrolyzed by brush border enzymes at the luminal membrane, followed by reabsorption of metabolites. In addition, it was found that, similar to the small intestine, the proximal tubule reabsorbed small peptide fragments, which were further degraded intracellurarly, In vivo inhibition studies with excess peptides revealed that hydrolysis is a more specific process than studies with excess peptides revealed that hydrolysis is a more specific process than reabsorption of metabolites. Large or small, complex peptides like insulin, oxytocin, or vasopressin that contain disulfide bridges are not hydrolyzed at the luminal brush border of the proximal tubule. In vivo sequestration and slow degradation of insulin by rat tubules suggest that this peptide is reabsorbed by endocytosis and degraded in lysosomes. Thus, as the molecular complexity or weight of a peptide increases, the mechanism for renal tubular degradation, instead of depending on luminal membrane hydrolysis, may primarily involve endocytosis and lysosomal digestion. This recently described mechanism for hydrolysis and transport of small linear peptides in the proximal nephron is characterized by having a high capacity and is analogous to membrane hydrolysis described for intestinal microvilli. The process may be biologically important to (1) conserve amino acids, (2) inactivate toxic peptides, and (3) help regulate circulating levels of peptide hormones.

Libraries in thirteen chiropractic colleges in the United States and Canada were surveyed in 1981/82. Data include operating expenditures, library resources, staffing levels and salaries, and size of physical plant. The survey identified wide differences among the population in all variables measured.

This study provides evidence that: 1) LHRH is degraded by renal brush border hydrolases, followed by reabsorption of oligopeptide metabolites in the proximal kidney tubule. 2) Peptide carriers are present in the luminal membrane of the proximal nephron, which apparently function to reabsorb oligopeptide metabolites resulting from hydrolysis of filtered peptides, including LHRH. 3) Renal brush border hydrolysis of LHRH involves cleavage at multiple sites by endopeptidases like angiotensin I-converting enzyme and endopeptidase 24.11; D-amino acid substituents at these sites may alter the expected cleavage pattern of the analogs. 4) A transcytotic pathway is present in the proximal nephron which is facilitated by endocytosis of cationic macromolecules; such a pathway may function to reabsorb hydrolytically resistant peptides, but the issue of potential toxicity must be clarified.

[pyroglutamyl-3,4-3H]Luteinizing hormone-releasing hormone (LHRH) was microperfused through isolated segments of rabbit proximal straight tubules and incubated with isolated brush border microvilli from rabbit renal tubules. About 4.8% of perfused 3H label was reabsorbed into the bathing medium per millimeter of tubule length per minute, and 1% or less of perfused label was sequestered per millimeter of nephron segment. The 3H label content of the bathing medium varied linearly with perfusion time (30 min), suggesting a constant rate of reabsorption. Analysis by high performance liquid chromatography showed that the collection fluid and brush border incubation medium contained significant amounts of labeled pGlu-His, pGlu-His-Trp, and pGlu-His-Trp-Ser, as well as LHRH, while the bathing medium contained pGlu, pGlu-His, pGlu-His-Trp-Ser, a very small amount of pGlu-His-Trp, and no LHRH. These data suggest that the partial hydrolysis of [3H]LHRH to these peptide metabolites takes place in proximal tubules through contact digestion by brush border enzymes. The metabolites and/or hormone are probably reabsorbed and broken down further within the cell to produce pGlu, which becomes an additional metabolite found in the bathing medium.

The subcellular sites of insulin degradation as measured by trichloroacetic acid precipitation were defined for rabbit renal proximal tubule cells. Fractionation in linear sucrose gradients of the postnuclear supernates prepared from isolated proximal tubule segments revealed three pools of insulin hydrolytic activity. Insulin hydrolytic activity assayed at pH 3.5 distributed in the gradients in a manner nearly identical to the activity of the lysosomal enzymes, N-acetyl-beta-glucosaminidase and alpha-mannosidase. At pH 7.4 the insulin-degrading activity distributed in a bimodal fashion with the major component following the cytosolic enzyme, phosphoglucomutase, and the minor component nearly identically overlapping with the activity of the inner mitochondrial enzyme, cytochrome oxidase. Upon microperfusion of 125I-insulin through proximal straight nephron segments, metabolites of the hormone were not observed in the collected perfusates for six of eight experiments. Average values for percent intact insulin in the original and collected perfusates showed no significant difference. These data suggest that three potential sites for insulin hydrolysis are present in proximal tubule cells, including lysosomes, the cytosol, and mitochondria. The results do not support the concept of degradation occurring at the brush border or contraluminal membranes.

Rabbit proximal nephron segments were microperfused in vitro to determine whether active contraluminal uptake of serine occurs in the renal proximal tubule during bath-to-lumen transport (influx) of the L- and D-isomers in the convoluted (pars convoluta) and straight (pars recta) segments. It is known that several amino acids are actively reabsorbed in the proximal nephron by a mechanism involving co-transport with sodium at the luminal membrane. There is some evidence that certain amino acids may also be accumulated across the contraluminal membrane by an energy-dependent mechanism, indicating that net reabsorption is the result of two oppositely directed active transport processes. During in vitro microperfusion of rabbit proximal nephron segments in this study, inward movement of L- and D-serine occurred in a bath-to-cell direction against a concentration gradient in the range 305-2735:1, indicating active uptake at the contraluminal membrane. The concentration gradients were maintained during influx of both isomers of serine in the proximal tubule. L-Serine accumulation by tubular cells was similar in the pars convoluta and recta, and significantly greater than that of D-serine, which was the same in both regions of the proximal tubule. The data support the conclusion that renal handling of serine involves active contraluminal uptake of the L- and D-isomers in both regions of the proximal tubule, and suggest that contraluminal events play an important role in renal handling of amino acids.

Renal processing of glucagon and insulin was compared. Iodinated glucagon (mol wt 3,674, linear molecule) or insulin (mol wt 6,000, two chains with disulfide bonds) was microinfused into surface nephrons of the rat kidney, and the radiolabel recovered in the urine was quantified and characterized. Proximal but not distal reabsorption of both peptides was observed, and uptake varied similarly as a function of tubular length. After proximal microinfusion, [125I]glucagon was largely degraded to [125I]tyrosine in the urine, but remained intact after distal infusion. [125I]Insulin was recovered as intact peptide following both proximal and distal microinfusion. Prolonged tubular sequestration of 125I label was observed following proximal microinfusion of [125I]insulin, with efflux requiring longer than 1 h for completion. No measurable cellular sequestration of [125I]glucagon was observed. Incubation of both peptides with rabbit renal microvilli membranes resulted in enzymatic hydrolysis of [125I]glucagon but relatively little or no degradation of [125I]insulin. It is concluded that glucagon and insulin are reabsorbed in the proximal tubule by predominantly different mechanisms.

A method for the large-scale production of a (1 yields 3)-beta-D-glucan glucohydrolase (EC 3.2.1.58) from the culture filtrate of Basidiomycete QM806 is described. The final preparation is homogeneous by disc electrophoresis under non-dissociating and denaturing conditions, by ultracentrifugation, and by isoelectric focusing. Various physical and chemical characteristics of the enzyme have been determined, including terminal amino acid residues, extinction coefficient, and stability to pH extremes. The N-terminal amino acids are leucine and serine (Sanger's method) and the C-terminal amino acids are alanine, serine, and glycine (hydrazinolysis). pH profile studies show that no group titrating in the region 2.5-8 is directly involved with substrate binding and that a single group having a pKa of 6.5 is involved in the catalysis. Photooxidation of the enzyme caused rapid inactivation. The pH-dependence of this photooxidation, and amino acid analysis of the photooxidized enzyme, indicate that decomposition of histidine is probably responsible for the loss of activity. Other chemical modifications performed were: treatment with hydrogen peroxide under acidic conditions, esterification with diphenyldiazomethane, and oxidation with N-bromosuccinimide. Oxidation with N-bromosuccinimide indicated that a tryptophan side-chain is involved in, but not necessary for, the catalytic activity.

In summary, we believe that the osmotic difference between the brain cell and the extracellular fluid is the critical parameter in determining therapy. A gradient of 30 mosm/kg or more produces significant shifts of intracellular water and cell damage. Seizure and coma are the neurologic signs associated with acute life-threatening osmotic imbalance between swelling brain cells and the extracellular space. Treatment is designed to decrease this osmotic gradient to less than 30 mosm/kg to prevent this cell swelling. Thus in acute symptomatic hyponatremia, treatment (fluid restriction alone if urine osmolality is less than 100 mosm/kg or 3% saline if needed or both) is needed to decrease this osmotic gradient. If hyponatremia is chronic and brain osmotic adaptations have already taken place, increased extracellular osmolality would cause brain cells to undergo water loss, which may result in cell shrinkage and neurologic damage (for example, central pontine myelinosis). Unfortunately, there is as yet no clinically available tool to rapidly assess intracellular brain osmolality. Clinical judgment is therefore mandatory in trying to estimate the osmotic gradient between the intracellular and extracellular environment. Appropriate treatment must be initiated to prevent excessive changes in cell volume.

Despite many imperfections in the nationwide reporting of toxic shock syndrome, the available data provide some useful information. The crude toxic shock morbidity rate has been estimated as approximately 0.50 per 100 000 United States population per year. This morbidity rate exceeds those for paralytic poliomyelitis, tetanus, tularemia, diphtheria, and typhoid fever, and is about one half of the rate for meningococcal infections and pertussis. The estimate of 8.9 cases of toxic shock syndrome per 100 000 menstruating women is similar to the crude rates for primary and secondary syphilis and mumps. From these comparisons, the incidence of toxic shock syndrome does not appear as low as some might suppose.

Fecal and serum specimens taken from 30 cases of sudden infant death and from eight cases of nonsudden infant death that were diagnosed at a single facility in King County, Wash., were examined for the presence of Clostridium botulinum organisms and toxin. Organisms, but not toxin, were recovered from a fecal specimen in one case of sudden infant death, results that parallel those from studies previously reported by investigators in California. Studies made in our laboratory of a nonfatal case of infant botulism revealed that an estimated 366,000 mouse minimal lethal doses of toxin were excreted in feces collected by purging the infant. Organisms and toxin were excreted for at least 15 days after the infant was hospitalized. Observations made in our laboratory of atypical responses in mice to both fecal and serum extracts, coupled with recently described experiments in which mice were used as an animal model for infant botulism in humans, provide a biologically plausible foundation for the hypothesis that C. botulinum may be implicated etiologically in some sudden infant deaths. Additional microbiologic, physiologic, and toxicologic data are needed to adequately test this hypothesis.

Data from an earlier study on postnatal growth and the sudden infant death syndrome (SIDS) by Peterson et al. (Am J Epidemiol 1974;99:389-94) were reanalyzed in light of new evidence on the effects of maternal smoking on prenatal and postnatal growth and on the relative risk of SIDS. The data set available for reanalysis consisted of weight and length (crown to heel) measurements at birth and autopsy for 155 babies diagnosed with SIDS in King County, Washington, in 1968-1971. The comparison group consisted of 270 contemporary living peers with weight and length data available. This reanalysis reveals that the retarded growth pattern of SIDS victims is remarkably similar to those of babies born to mothers who smoke during pregnancy. Known and suspected effects of maternal smoking on the fetus and neonate can account for increased susceptibility of death from a variety of causes, including SIDS. The association, if confirmed by further studies, could help clarify the pathogenesis of SIDS in victims with postmortem evidence of antemortem hypoxia with or without a history of periodic apnea.

The diagnosis of sudden infant death syndrome (SIDS) is less than 100% certain in any given instance. Approximately 90% of all SIDS have occurred by age 6 months. A visual aid consisting of 1,000 dots helps in communicating numerical information such as 'rates' to parents (and others as well). The annual and seasonal occurrence patterns are independent of so-called SIDS risk factors. A single, major gene defect cannot account for SIDS but the root cause may be genetic (polygenic). Recent estimates of sibling risk to SIDS indicate that earlier estimates were inflated. Use of apnea monitors to prevent SIDS has no basis in fact but may provide emotional support. DTP immunization does not cause SIDS.

Although it is generally accepted that calcium ion homeostasis is performed primarily by bone, the mechanism by which this regulation is accomplished remains unclear. The recent demonstration of a metabolism-related electrical potential difference across bone membrane implies an active transport process within this layer of cells lining bone surfaces. This work presents a determination of the effect of parathyroid hormone on the measured potential difference to demonstrate whether this potential is involved in the homeostatic mechanism. A thermodynamic evaluation is performed based on a measurement of the distribution of charged and uncharged tracers between bone extra-cellular fluid and the bathing medium. For embryonic chick calvaria whose viability was assured by the measurement of oxygen consumption, parathyroid hormone at dosage levels up to pharmacological caused an increase in the measured potential difference and thus in the inferred activity level of ionic transport through the membrane. This result is shown to be consistent with an indirect regulation of Ca++ ion through a variable active transport of K+ ion into the interior of bone and thus provides support for the argument that the membrane potential is part of the calcium homeostatic mechanism.

Data from six geographically dispersed metropolitan areas in the United States in which special sudden infant death syndrome (SIDS) surveillance programs for detection and autopsy diagnosis existed during the period 1965 through 1974 reveal considerable diversity in overall ten-year incidence rates as well as in annual rate distribution patterns. A downward trend in SIDS incidence occurred in some areas but not in others. Non-SIDS postneonatal death rates, which were used for comparison, also decreased in some areas. Rate trends for whites and nonwhites were not consistent. During the same period, the fertility rate in the United States decreased by about a third for both whites and nonwhites. To explain the observed trends we postulate that concomitants of the fertility rate decline may have reduced the number of "high mortality risk babies" to a variable degree in different places and at different times.

Knowledge of the likelihood of a repetition of sudden infant death syndrome within a sibship, particularly in the next sibling, is important to parents. Methodologic considerations with respect to the studies of recurrence risk already published indicate that the rates reported are overestimates. This suspicion is confirmed by our study based on 826,162 infants surviving the first week of life on file in the Medical Birth Registry of Norway. A total of 1062 (1.3 per 1,000) infants died of SIDS; five deaths occurred as the second case in a family. The recurrence risk for the nextborn sibling was 5.6 per 1000, and for all subsequent siblings 4.8 per 1000, which would seem encouragingly low from a counseling point of view.