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The effect of 24-hr water deprivation and subsequent drinking on systemic fluid balance was determined in rhesus monkeys prepared with indwelling cardiac catheters. Significant intracellular and extracellular depletions, as indicated by increased plasma sodium concentrations, osmolality, and plasma protein concentrations, resulted from the deprivation. An early attenuation in rehydrational drinking rate (2--4 min) was not associated with changes in systemic fluid balance, which suggests presystemic influences on behavior at this time. When drinking terminated (10 min), however, plasma dilution was significant. In experiments in which monkeys were sham drinking (open gastric cannula), water but not isotonic saline infusions, given through an intestinal cannula, reduced drinking rate and produced significant plasma dilution. Intravenous water infusions reduced drinking to only a comparable extent despite more rapid and substantial plasma dilution. Thus, systemic absorption does not account entirely for the effect of intestinal water infusions on drinking. It is concluded that stimulation of mechanisms both presystemically (within the intestine or the hepatic portal circulation) and systemically is important in the control and termination of rehydrational drinking in this species.

Angiotensin is a potent dipsogenic substance and causes elevated water intake in some pathological conditions but as yet no physiological role for angiotensin in normal thirst has been proven. If angiotensin is important in normal drinking, then it should contribute to the drinking which follows water deprivation. The rehydration of bilaterally nephrectomized rats, rats with bilateral ureteric ligation and control rats was compared after 21 hours of water deprivation. The total intake during the 6 hour rehydration was the same in the 3 groups despite the differences in the level of circulating angiotensin. Thus the renal renin-angiotensin system is not essential for deprivation-induced drinking. Another way to test any contribution to drinking by angiotensin is the administration of the competitive angiotensin inhibitor, saralasin acetate. In a control experiment saralasin acetate was found to block the dipsogenic effect of intravenous angiotensin. The infusion of saralasin acetate in a wide range of doses did not, however, affect the drinking following ligation of the inferior vena cava. Thus angiotensin is not essential for drinking following caval ligation. Two possible explanations for these results are that angiotensin is not normally involved in these types of thirst or that there is redundancy in the control of drinking with compensation for blocked mechanisms.

Single radial diffusion (SRD) tests for antibodies to influenza type A hemagglutinin, neuraminidase, nucleoprotein, and matrix protein antigens were compared with conventional hemagglutination inhibition, neuraminidase inhibition, and complement fixation tests. Sera used in this study were obtained in 1968-1969 from volunteers before and after vaccination and before and after an ensuing epidemic of Hong Kong influenza. The SRD test compared favorably with conventional tests for assessment of vaccine- or infection-induced rises in antibody titers to influenza type A viruses. Little linear relationshiip was seen between zone areas with SRD and titers with conventional tests, suggesting that the SRD test may detect antibody of different quality or specificity. The SRD seemed equal to the hemagglutination inhibition test for predicting susceptibility to influenza. SRD is a simple test for the recognition of antibody to various antigenic components of the influenza virus and could prove to be a valuable epidemiological tool.

A system for the exchange of specimens between two independent laboratories ("A" and "B") was designed to enable them to review a consecutive series of one another's gynecologic smears. Another cytopathologist "refereed" diagnoses differing beyond agreed limits and examined all smears called carcinoma in situ or a more severe lesion by either laboratory. A ten-numeral gradient nomenclature scale was developed to code all cytodiagnoses for data processing. This analysis of the reproducibility of the experimental diagnostic system is based on all participants' examination of 100 selected specimens, half contributed by reviewing laboratory A and half by reviewing laboratory B, with the target value of each specimen established by the contributor. Intralaboratory reproducibility, expressed by a correlation coefficient (r), ranged from 0.78 to 0.93. After adjusting for straightforward squamous-cell lesions, r ranged from 0.88 to 0.91. Intralaboratory agreement +/- 1 scalar category, defined as a "working consensus," ranged from 77% to 84%. Interlaboratory correlation ranged from r = 0.74 to 0.94. Adjustment for squamous-cell lesions exerted less effect than it had on intralaboratory reproducibility. Interlaboratory agreement within one category ranged from 58% (laboratory B reviewing specimens contributed by laboratory A) to 92% (referee examining specimens contributed by laboratory B). Initially, laboratory A tended to classify a given specimen higher on the scale than did laboratory B and the referee, but as the study progressed, both laboratories tended to converge toward a more congruent diagnostic position, with referee greater than A greater than B. The level of discrimination attained by all participants validates use of this system to compare a larger series of diagnoses.

Glucose stimulates calcium transport in vitro in rat duodenal tissue and isolated enterocytes. Under short-circuited conditions, glucose increased mucosal to serosal calcium flux (JCa(m----s)) without altering serosal to mucosal calcium flux (JCa(s----m)) in the duodenum, the primary site of active calcium absorption in the rat small intestine. The half-maximal dose (ED50) of the glucose stimulatory effect was less than 1 mM, and an increase in JCa(m----s) of 80% over control was seen at a glucose concentration of 50 mM. Glucose did not increase calcium flux in the ileum where active calcium absorption is minimal. Glucose stimulated net calcium uptake by 35% in isolated duodenal enterocytes. Glucose did not alter calcium efflux from preloaded enterocytes suspended in calcium-free buffer. Glucose enhancement of net calcium uptake in enterocytes was not caused by altered cell membrane integrity or functional viability. The nonmetabolizable glucose analogue alpha-methylglucoside did not stimulate calcium transport. Our findings suggest that glucose can stimulate intestinal calcium absorption, at least partially, by enhancing transcellular calcium transport and that cellular glucose metabolism is necessary for stimulation of this route of calcium transport.

The present study investigated the effect of glucose polymer on jejunal calcium, magnesium, and zinc absorption in eight normal subjects, using the triple-lumen intestinal perfusion technique. For each subject, a 30-cm segment of jejunum was perfused for 60 min each with two different test solutions. When 4 mM glucose polymer was perfused net calcium absorption increased by fourfold (95 vs 488 mumol/30 cm/h), and net jejunal uptake of magnesium (393 mumol/30 cm/h) was observed, as compared to net magnesium secretion in the absence of glucose polymer. In addition, coadministration of glucose polymer doubled net zinc absorption (13 vs 29 mumol/30 cm/h). The rate of water absorption increased from 49 to 111 ml/30 cm/h. No further change in jejunal water and mineral absorption was observed when glucose polymer in the perfusate was increased from 4 to 8 mM. These results suggest that glucose polymer may have potential as an agent to significantly enhance mineral absorption.

Glucose polymers have been shown to enhance intestinal calcium absorption in normal subjects as well as in patients with gastrointestinal disease. Glucose polymers are widely used as an energy source in enteral nutritional supplements and infant formulas. In this study, eight normal subjects underwent 47Ca absorption tests to compare the effect on calcium absorption of carbohydrate given orally as a simple carbohydrate (glucose) or a more complex carbohydrate (glucose polymers). Oral coadministration of glucose with calcium increased the efficiency of intestinal calcium absorption by 20% and coadministration of glucose with glucose polymers increased calcium absorption by 27%. This suggests that glucose, derived from glucose polymers by hydrolysis, may be responsible for the positive effect of polymers on calcium absorption. The potential positive effect of coadministration of carbohydrate on calcium bioavailability deserves considerations in the design of calcium supplementation strategies.

Split-thickness skin graft donor sites are often areas of significant morbidity in the elderly, in immunocompromised patients, and in steroid-dependent patients. We found that managing these donor sites with split-thickness skin and transparent dressings greatly increases the rate of healing and diminishes morbidity.

Evidence is presented which confirms the influence of linkage group II on adult DDT-resistance in one strain of Aedes aegypti (Bangkok-MR) but not in another strain (Bangkok-HR).

An autosomal recessive gene bw (probably closely linked to y on chromosome 2) gives a brown eye colour. When this gene and the sex-linked gene re (red-eye) are both homozygous, a colourless-eye results. Brown-eye shows good viability and penetrance, and it has been maintained as a pure stock. Colourless-eye shows 87% penetrance in both sexes, and the females are low in viability and fertility. A colourless-eye stock has been maintained by crossing colourless-eyed males to their heterozygous red-eyed sibs. Crosses indicated no allelism between bw and ru (rust-eye), nor with w (white-eye). However some complementation between bw and w was indicated.

Glucose polymer derived from corn starch is widely used in infant formula and nutritional supplements as a readily digestible, low osmolarity source of calories. We have previously observed that glucose polymer causes a marked increase in intestinal calcium absorption in patients with intestinal malabsorption and in normal subjects. The present study investigates the effect of concurrently administered glucose polymer on intestinal 45calcium absorption in rats. The effect of glucose polymer on calcium absorption was compared to that of equivalent doses of dextrose or lactose. Femur radioactivity was determined as an index of calcium absorption. Carbohydrates were prepared at doses of 0.5, 2.0 and 4.0 mg/g body weight and administered with 45Ca by stomach gavage. Control rats received 45Ca in water alone. Coadministration of glucose polymer resulted in a dose-dependent increase in calcium absorption. At the highest dose of polymer studied calcium absorption was 75% greater than in control animals. Administration of lactose and dextrose also resulted in a dose-dependent increase in calcium absorption. Calcium absorption was 122 and 67% greater than controls when 4 mg/g BW lactose and dextrose were given with the 45Ca. We conclude that glucose polymer stimulates calcium absorption in rats similar to lactose and glucose. These results suggest that glucose polymer may be a useful therapeutic adjunct in patient groups in which there is a desire to increase intestinal calcium absorption.

A study has been made on the genetic basis of meiotic drive at the Distorter (D) locus which, in coupling with the male-determining gene (or region) M on the Y chromosome, causes production of excess male progeny. Its effect is regulated by the sensitivity/resistance of the X chromosome. This study demonstrates that there are two major loci controlling resistance/sensitivity to MD: (1) the m gene (or region) on the X chromosome (allelic with M) which may be either mR or mS (resistant or sensitive), (2) the t (tolerance) gene (or genes) which recombines with m and, if present, largely counteracts the effect of mS. There is also evidence that MD itself is capable of limited adaptation. The conclusions were derived from using MD males of the T30 or ACCRA strains (from Trinidad and Ghana respectively). The work involved the use of the CHIPEI and RED strains with sensitive X chromosomes, the latter also carrying the t (tolerance) gene which is linked to re (red eye) and m (the sex-determining locus or region) but recombines with both. The implications of these findings for using MD as a method of population control are discussed.

1. After overnight deprivation of water both the cellular and extracellular fluid volumes are significantly reduced in the rat. 2. In the rat with functional kidneys oral, intragastric or intravenous preloads of 10 ml. water reduce the total water intake after 1 hr by 64-69%. These preloads restore plasma osmolality to pre-deprivation levels but have little effect on plasma volume. 3. In the same rats if the plasma volume is restored with an oral, intragastric or intravenous preload of 10 ml. of an isotonic balanced salt solution which has little effect on osmolality, drinking is significantly reduced by 20-26%. The reduction of drinking correlated with the volume of the preload of balanced salt. 4. Plasma analysis shown that 1 hr after an oral preload of 10 ml. isotonic balanced salt solution, the extracellular fluid volume of the deprived rats is restored to pre-deprivation levels but osmolality is unchanged. Three hr after the balanced salt preload, extracellular fluid volume is still at pre-deprivation levels and there has been a slight decrease in osmolality due to excretion of salt. 5. In rats which had been nephrectomized or had the ureters ligated so there could be no renal modification of the preloads, the effects of the preloads of water and balanced salt are the same as in rats with intact kidneys. 6. The results indicate that after water deprivation in the rat, changes in both the cellular and extracellular fluid compartment are stimuli to drinking.

Metabolic bone disease has been reported in patients receiving long-term cyclic administration of total parenteral nutrition (TPN). The exact etiology of this disturbance in mineral homeostasis has not been identified, however many of these patients are markedly hypercalciuric and in negative calcium balance. We have studied the effects of cyclical versus continuous infusion of nutrients on urinary calcium losses in a group of patients beginning a program of long-term home TPN. Cyclic TPN, when administered over either 18 or 12 hours, significantly increased daily urinary calcium excretion compared to continuous 24-h TPN infusion by 19 and 28%, respectively. During cyclic TPN, frank negative calcium balance was observed in 3 of 5 patients studied compared to 2 of 5 patients during continuous TPN. The pattern of urinary calcium loss during cyclic TPN was such that approximately 80% of the daily urinary calcium losses occurred during the 12 hours of TPN infusion. Cyclic administration of TPN increased the urinary calcium losses in all patients suggesting that an intermittent TPN infusion schedule, as typically utilized in home TPN programs, increases the risk of developing negative calcium balance, at least during the early phase of cyclic TPN administration.

A sensitive and practical radioreceptor assay method for pharmaceutical insulin products has been developed with partially purified rat liver plasma membranes and the optimal conditions under which the best overall assay performance is obtainable have been defined. Intra- and inter-assay variations of the method averaged 7.3 and 12.2% of the man, respectively, when expressed as the coefficient of variation. Potency estimates of an insulin product obtained with the proposed method correlated well with those determined by the mouse convulsion bioassay method. Liver membranes prepared according to the method could be stored for up to ten weeks at 4 degrees C and for 6 months or more at - 18 degrees C without losing insulin-binding ability.

Hypercalciuria and negative calcium balance are potential complications of total parenteral nutrition (TPN). Dietary phosphorus has been observed to have an hypocalciuretic effect. The present study evaluates the effects of administration of increasing intravenous phosphorus (P) loads on urinary calcium excretion in TPN patients. Urinary calcium exceeded daily calcium intake by 50 mg/d when 700 mg/d P was administered, was equal to intake at 1000 mg/d P, and was 30 mg/d less than calcium intake when 1300 mg/d P was given. These findings suggest that TPN-induced hypercalciuria can be attenuated in the short-term by intravenous phosphate. Reevaluation of the phosphorus requirement in patients receiving long-term TPN should be considered.

The Olympus "Quickrate", a photometer built for both kinetic and end point analysis was evaluated in this laboratory. Aspartate transaminase, lactate dehydrogenase, hydroxybutyrate dehydrogenase, creatine kinase, alkaline phosphatase and gamma glutamyl transpeptidase were measured in the kinetic mode and glucose, urea, total protein, albumin, bilirubin, calcium and iron in the end point mode. Overall, good correlation was observed with routine methodologies and the precision of the methods was acceptable. An electrical evaluation was also performed. In our hands, the instrument proved to be simple to use and gave no trouble. It should prove useful for paediatric and emergency work, and as a back up for other analysers.

Urinary C-peptide excretion has been found to be an accurate index of insulin secretion under a variety of physiologic conditions, such as acute starvation and exercise, and after oral and intravenous glucose administration. We investigated urinary C-peptide responses in a group of patients who were receiving all of their nutrient intake by intravenous administration. In these patients receiving total parenteral nutrition (TPN), we were able to monitor changes in insulin secretion when the same nutrients were infused at different rates, for example, during cyclic vs. continuous TPN administration, and to observe changes in the insulin secretory response as the pattern of nutrient delivery was altered in the same individual. We found that increasing the TPN infusion rate by 50% during cyclic TPN caused a 65% increase in serum insulin levels over levels observed during continuous TPN administration (93 vs. 60 microU/ml), whereas a 100% increase in the cyclic TPN infusion rate above the continuous TPN rate increased insulin levels by 147% (147 vs. 60 microU/ml). The molar ratio of insulin to C-peptide was increased by increasing rates of TPN infusion, from 0.116 during fasting periods to 0.151 during maximum rates of TPN administration. An additional finding of this study is that 24-hour insulin secretion, estimated by urinary C-peptide measurements, was equivalent in all treatments regardless of the pattern of insulin response elicited.

Serologists are making increasing use of the term "reproducibility" when referring to the reliability or repeatability of serological tests. The practical use of the concept, however, has been limited by the absence of an appropriate numerical scale on which differing reproducibilities can be quantified and objectively compared. This limitation can be overcome by adopting the proposed quantitative measure of reproducibility. The recommended measure is a natural extension of the common practice of considering a serological test to be acceptably reporducible so long as replicate titers remain within a twofold range. The measure can be readily used in the field of serology, and examples are given of how this can be done.

Sixty-nine-day-old female Wistar rats that had been made diabetic 9 days earlier by an intraperitoneal injection of streptozotocin were studied by a combination radioisotope and balance technique that evaluates calcium absorption, excretion, and bone calcium deposition and resorption rates. Streptozotocin-induced diabetes was associated with a marked drop in calcium absorption and a threefold rise in urinary calcium excretion, changes that greatly exceeded the expected effects from the hyperphagia and increased calcium intake of the experimental animals. Bone calcium deposition was halved in the diabetic rats, with bone resorption unchanged and equal to the deposition rate. As a result, the bone and body calcium balances were zero in the experimental animals. To maintain plasma calcium near normal under these circumstances, the diabetic animals turned over their skeletal calcium in relationship to the central pool much more rapidly than the controls. Although the skeleton in the normal animals serves as both storehouse and regulator of the plasma calcium, in short-term streptozotocin-induced diabetes there is no calcium storage in bone, with the skeleton only playing the role of regulator of calcium homeostasis.

Previous genetical investigations on the Trinidad DDT-resistant strain of Aedes aegypti, involving mass crosses with susceptible strains, had indicated that a single major semi-dominant gene controlled resistance to DDT. The present study, in which single-pair matings were made, indicates that the genetic control of resistance is, in fact, more complex. The considerable variation observed could not be interpreted in terms of normal segregation at a single locus. At least three genetic factors appear to be involved: a major gene conferring low resistance but of variable expression, a chromosomal modifier of the dominance of this first factor, and a sex-dependent factor that may or may not be chromosomal. Whether the major gene for low resistance, variously modified, is also responsible for higher levels of resistance remains uncertain.

Investigating heterogeneity in response to DDT with 2 strains of Aedes aegypti, the author has compared DDT-resistance in the F(1) and F(2) progenies of single-pair matings of resistant with resistant (TRINIDAD) and susceptible with susceptible (QS) strains.Both strains showed heterogeneity; however, there was little overlap between the most tolerant QS progeny and the least resistant TRIN progeny. A substrain of very high resistance was isolated from a single TRIN progeny and one of very low tolerance from a single QS progeny.Between QS progenies there was wide variation in DDT-tolerance, due in part to an environmental component but in part also to a genetic component. Variation between progenies in the already very resistant TRIN strain was marked. However, a genetic component was shown by the fact that it was possible to select an exceptionally resistant TRIN substrain in one step by rearing from the most tolerant TRIN progeny.