Familial clustering and immune response in family contacts of patients with HBsAg-positive liver cirrhosis. Families of 11 patients with hepatitis B surface antigen (HBsAg)-positive cirrhosis were studied to evaluate the immunologic correlates and extent of intrafamilial HBsAg clustering. Of 76 family contacts, 12 were identified to be asymptomatic carriers of HBsAg and two were diagnosed to have HSsAg-positive cirrhosis. The over-all HBsAg prevalence for the 76 contacts was 18% and that for all 87 members studied 29.0%. Serologic evidence of hepatitis B virus (HBV) infection (either HBsAg, anti-HBs, or both) was detected in 59% of all family members. HBsAg was more prevalent in males (47%) compared with females (16%), and anti-HBs was more prevalent in females (42%) compared with males (18%). Evidence of an immunologic response in clinically unaffected HBsAg-negative family contacts consisted of elevated serum IgG levels (mean 1660 mg/100 ml) and increased prevalence of anti-smooth muscle and antimitochondrial antibodies (16% and 6%, respectively). The prevalence of one or more autoantibodies in all HBsAg-negative family contacts was 20%, and it was higher in females (25%) than in males (13%). The present study demonstrates that HBsAg clustering occurs in families of patients with cirrhosis in the Jerusalem area and indicates that HBsAg-negative family contacts may have increased B-cell activity.


Histology of the intestinal peritoneum in patients with cirrhosis of the liver and ascites. Portal hypertension and hypoalbuminemia are usually incriminated in the development of ascites in liver cirrhosis, and altered peritoneal permeability is considered only as a hypothetical possibility. Jejunal postmortem specimens were studied in 15 control patients and 16 patients dying with cirrhosis of the liver and ascites. In decompensated cirrhosis a fibrous thickening of the peritoneum was found, 159.0 +/- 96.4 micrometer (mean +/- SD) compared to 24.5 +/- 10.6 micrometer in controls (P less than 0.001). An increase in the size and number of blood vessels, lymphangiectasiae, and mononuclear cell infiltration were invariably present. These histological changes are consistent with a nonspecific chronic peritonitis. The findings indicate there is increased blood perfusion and lymph flow within the intestinal peritoneum in patients with decompensated cirrhosis of the liver and support the existence of an intestinal peritoneal factor in the pathogenesis of cirrhotic ascites.


Secretory pattern and pathological study of the pancreas of steroid-treated rats. Rat were given 2.5 mg/kg/day prednisolone in drinking water during 1.5 to 12.5 months and an equal group of matched controls received only water. A pathological study of the pancreas and a physiological study of exocrine pancreatic secretion have been done. The most significant pathological effects at 1.5-12.5 months of steroids are dilatation of acini, flattening of duct epithelium, and the presence of protein plugs in the ducts. The most significant functional modifications at 9-11 months of treatment are increased concentrations and output of proteins both in basal and stimulated pancreatic secretion of steroid-treated rats. This is very similar to the results observed by our group in alcohol-induced pancreatitis. It is assumed that the hyperconcentration could be at least partly responsible for precipitation of proteins and the precipitate formation for the lesions. For the large group of acute or chronic pancreatic lesions characterized by the formation of protein plugs in the ducts, the term catarrhal pancreatitis is proposed.


Effect of ethanol on canine gastric epithelial ultrastructure and transmucosal potential difference. We correlated changes in the gastric transmucosal potential difference (PD), as an indicator of the integrity of the gastric mucosal barrier, with morphological evidence of injury in dogs which had received either intragastric saline or 5, 10, 15, or 30% ethanol. Increasing degrees of morphological damage were accompanied by greater, more rapid changes in PD. Furthermore, ultrastructural changes occurred within surface epithelial cells, not in the deeper parietal or zymogen cells, and initially did not involve disruption of the apical cell membrane. Typically, the tight junctions also were not affected, although in a minority of dogs small bleblike separations of the tight junctions were seen. We consider the gastric mucosal barrier to be represented morphologically by the interconnecting sheet of gastric epithelial cells and that ethanol breaks the barrier by first causing intracellular injury.


Effects of E prostaglandins on canine gastric potential difference. Measurement of the gastric transmucosal potential difference (PD) was used to study the effect of gastric antisecretory prostaglandins on the integrity of the gastric mucosa of the Heidenhain pouch dog. Intragastric administration of SC-29333 [(+/-)-15-deoxy-16-alpha,beta-hydroxy-16-methyl PGE1 methyl ester] slightly but significantly increased the transmucosal PD when compared to vehicle control. In addition, SC-29333 administered either intravenously or intragastrically, significantly inhibited the PD fall induced by aspirin, a well-established barrier breaker. In contrast, the intragastric administration of 16,16-dimethyl PGE2 methyl ester (Me-PGE2) significantly lowered the transmucosal PD and failed to modify the actions of aspirin on the integrity of the gastric mucosa. However, the intravenous administration of either prostaglandin did not affect the basal transmucosal PD values. These studies suggest that SC-29333 may strengthen the integrity of the gastric mucosal barrier against aspirin, and this could have important therapeutic potential.


Esophageal ganglia and smooth muscle in the elderly. Esophageal motor dysfunction is a common finding in elderly persons, but its etiology remains unknown. We examined the histology of Auerbach's plexus and esophageal smooth muscle in autopsy material from young and old subjects. There was a significant decrease in ganglion cells per square centimeter (1685 +/- 115.9) in old subjects when compared to young controls (2253 +/- 216.9) (P less than 0.05). Lymphocytic infiltration of Auerbach's plexus was commonly observed in both groups of patients, but heavy lymphocytic infiltration was slightly more common in elderly subjects. No difference was found in thickness of esophageal smooth muscle between young and old subjects. It is concluded that diminution of ganglion cells rather than smooth muscle atrophy may explain the frequent occurrence of esophageal motor dysfunction in elderly persons.


A scanning electron microscopic study of normal human oxyntic mucosa using blunt dissection and freeze fracture. Biopsies from the fundic mucosa of healthy volunteers were examined by scanning electron microscopy following blunt dissection and freeze fracture. The mucosal surface exhibited a cobblestone appearance. With increased magnification, microvilli could be demonstrated on the luminal surface of individual surface cells. Blunt dissection of the gastric mucosa revealed tubular gastric pits descending from the surface until they opened into branched tubular gastric glands. The gastric glands are irregular in outline due to the knoblike projections of individual parietal cells. The internal structure of the component cells also was examined with the scanning electron microscope following freeze fracture. Mucous granules were observed in the apical portion of surface epithelial cells. Lumina of parietal cell canaliculi were found to be continuous with the lumen of the gastric glands. Pepsinogen granules could be seen throughout the cytoplasm of chief cells. The blunt dissection-freeze fracture technique utilizing the scanning electron microscope allows, for the first time, a three-dimensional view of human gastric mucosa, including the gastric pits and glands as well as some of the internal architecture of component cells.


Colon polyps, sebaceous cysts, gastric polyps, and malignant brain tumor in a family. A unique family with a distinct syndrome of adenomatous colonic polyps and sebaceous cysts without osseous or soft tissue abnormalities is presented. One member had benign gastric polyps limited to the upper half of the stomach and another had a medulloblastoma of the cerebellum. A histologic feature in the colon of the propositus was the presence of atypical epithelium in flat mucosa as well as in the colonic polyps.


A simple assay technique for pancreatic lipase. A simple and inexpensive procedure is described to include pancreatic lipase in the protocol for evaluation of pancreatic function by duodenal aspiration. The method involves dilution with an albumin solution, a 2-hr incubation with a commercially available substrate mixture, and manual titration with a burette. Results comparable to assay with a pH-stat were obtained. Assay for pancreatic lipase is recommended as a part of the diagnostic procedure of duodenal aspiration.


Pancreatic, gallbladder, and intestinal responses to intraluminal magnesium salts in man. To assess the effects of magnesium chloride or magnesium sulfate on the release of cholecystokinin from the duodenum, outputs of trypsin and bilirubin were quantified during perfusion of the duodenum with isotonic solutions of these salts. Net intestinal water transport was also quantified. The results suggest that magnesium ion in the duodenum is a relatively weak stimulus to the pancreas and gallbladder, an action not augmented by the concomitant presence of the sulfate ion. As determined by this human bioassay method, magnesium is a weak stimulant to cholecystokinin release. Furthermore, magnesium chloride inhibits net jejunal water absorption and magnesium sulfate is even more potent, promoting net water secretion, effects which cannot be entirely attributed to cholecystokinin release.


Enterocyte turnover and content in fat-fed hamsters. Cryptal lecithin-synthesizing enzyme specific activities have been previously demonstrated to be increased by feeding a fat-supplemented diet to hamsters. To determine if a physiological basis exists for such changes [3H]thymidine incorporation, cellular migration rate, and mucosal concentration of DNA, protein, and lecithin were measured. Radioautographic studies showed that the labeling index and cell migration rate throughout the intestine in the fat-fed hamsters and in the proximal three-quarters of the intestine of the control group were the same. Both parameters were reduced in the distal quarter of the control intestine. The protein/DNA ratio was significantly increased in the proximal three-quarters and modestly in the distal quarter of the intestine of the fat-fed group as compared to controls, suggesting cellular hypertrophy. The lecithin content of the proximal three-quarters of intestine was the same in both groups but reduced in the distal quarter of the gut of the fat-fed group. These studies suggest that lipid feeding in the hamster can have profound effects on intestinal cellular content and turnover.


Mechanism of stress ulcer. Influence of alpha-adrenergic blockade on stress ulceration and gastric mucosal energy metabolism. In previous reports from this laboratory, it has been proposed that stress ulceration results from a severe gastric mucosal energy deficit due to shock-induced mucosal ischemia. In the experiments described in this report, the hypothesis was further tested by studying stress ulceration and gastric mucosal energy metabolism in rabbits subjected to hemorrhagic shock with or without the concomitant administration of an alpha-adrenergic blocking agent. Our data show that stress ulceration and gastric mucosal energy deficits are significantly less severe when shock is combined with alpha-adrenergic blockade.


Effect of N-methyl-N'-nitro-N-nitrosoguanidine on the gastric mucosal barrier in rats. The gastric mucosal barrier to hydrogen ion (H+) after the administration of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) on the rat stomach was studied. Increased H+ back-diffusion was observed 3 hr after oral doses of 1 mg of MNNG over a 3-day period. MNNG in concentrations of 250 microgram/ml, 167 microgram/ml, 86 microgram/ml, and 50 microgram/ml in the presence of acid caused increased H+ back-diffusion across the gastric mucosa within 1 hr. Gastric mucosal barrier disruption by MNNG may play a pathogenic role in gastric carcinogenesis.


A unique distribution of laxative-induced spike potentials from the small intestine of the dog. The effects of castor oil and ricinoleic acid on small bowel electrical activity were studied in the fasted conscious dog and were compared to the effects elicited by two nonlaxative oils (triolein and oleic acid). Spike potential activity was monitored at two jejunal sites using unipolar recording electrodes. Castor oil, ricinoleic acid, and triolein produced an increased incidence of basic electrical rhythm (BER) with associated spike potentials when compared to a fasted control; however, the total electrical spiking activity produced by these oils was not statistically different from that induced by feeding. No treatment altered any of the characteristics of BER. A novel pattern of electrical spiking activity was observed in response to the laxatives. This pattern consisted of short repetitive bursts of spike potentials which migrated the length of the recording site. The laxative-induced electrical pattern persisted for several days after treatment with ricinoleic acid or castor oil, and interdigestive patterns were occasionally interrupted for as long as 72 hr. Electrical activity following feeding or the nonlaxative oils consisted of random spike potentials, and normal interdigestive electrical activity resumed within 24 hr. The laxative-induced electrical pattern was shown to be quantitatively distinct from those produced by feeding, fasting, or nonlaxative oils. This pattern may reflect an action of these laxatives on intestinal motility during a diarrheal state.


The role of aspirin in gastric ulceration . Some factors involved in the development of gastric mucosal damage induced by aspirin in rats exposed to various stress conditions. The gastric irritant effects of aspirin were studied in rats treated with a variety of physical and "disease" (inflammatory) stress conditions (which may mimic responses to some stress states encountered clinically) with the object of establishing whether these stress states increase the susceptibility of the gastric mucosa to the potentially ulcerogenic actions of aspirin. While exposure to physical (eg, cold) stress conditions markedly increased the sensitivity of the gastric mucosa to aspirin, exposure to various disease stressors (eg, adjuvant arthritis, acute pain, or paw inflammation) did not appreciably affect the mucosal sensitivity to this drug. Attempts were made to determine the mechanisms of the physical stress plus aspirin interaction by use of pharmacological agents. The results suggest a major involvement of the parasympathetic-vagal, sympathetic, and histamine-producing systems, but not the adrenocortical axis, in this model of gastric ulcerogenesis. No differences were observed in the mucosal uptake of [14C]aspirin, showing that accelerated uptake of the drug is not a factor in the development of gastric ulceration.


Effects of dietary protein on body weight, mucosal growth, and calcium absorption in the rat. Previous studies of dietary protein intake and calcium balance demonstrate decreased fecal calcium excretion with high-protein diets. To determine whether a duodenal or ileal calcium transport response could account for these findings, we examined calcium transport by these two segments directly by in situ perfusion. Weight-matched growing rats were pair-fed isocaloric diets for 6-8 days containing 89% protein (casein), 39% and 0% protein. Sucrose was substituted for the decreased casein in the 39% and 0% protein diets. Each diet also contained 5% fat, a mineral mix, and vitamins. Calcium content of all diets was 0.5%. Body weight was maintained by the 39% protein group; weight loss was 5% for the 89% protein group and 18% for the 0% protein group. Small-intestinal weight as a percentage of body weight was the same for the three groups. For both the duodenum and the ileum, mucosal dry weight per centimeter was greater in the 39% protein group than either the 89% protein or 0% protein group. Calcium absorption per gram dry weight of mucosa (absorptive specific activity) was the same for all diet groups, but because of the greater mucosal weight per unit length in the 39% protein group, absorption per centimeter was increased in this group. In conclusion, although we found no direct relation between dietary protein and mucosal absorptive specific activity for calcium, calcium absorption was determined by the amount of mucosa which was dependent on protein intake and reflected the nutritional status of the body.


The logical analysis of the electroenterogram. Simple--and inexpensive--logic circuitry is described which will discriminate three types of spike activity in the canine electroenterogram. Used during high-speed replay of tape-recorded myoelectric activity, it provides a numerical analysis of the duration and spike content of the three types of activity, without the need for sophisticated (and costly) computer analysis. The ability of the analyzer to detect types of activity is illustrated by the analysis of the effects of a peptide hormone infusion on the canine electroenterogram. The device might also serve as the prototype for other applications in which simple digital logic could be used to detect different patterns in continous analog signals.


Fulminant hepatic failure secondary to amebic abscesses. A patient presented with fulminant hepatic failure which rapidly led to his death. At postmortem examination, he had several amebic abscesses secondarily infected with bacteria, one of which had ruptured intraperitoneally, and another of which had occluded major hepatic veins of the right lobe of the liver. In addition, pylephlebitis and occlusion of several right portal venous radicles were noted. Microscopic examination of the right lobe revealed marked sinusoidal congestion and large areas of infarction with severe panlobular necrosis. Fulminant hepatic failure secondary to complications of amebic abscess has been reported infrequently but should be considered in patients with this presentation who have visited or inhabited areas endemic for amebiasis.


Chewing gum diarrhea.

Chewing gum diarrhea. A 66-year-old woman was found to have intractable diarrhea related to excessive consumption of sugarless chewing gum. The effect of sorbitol on the intestinal tract was felt to be the etiology. Upon cessation of gum utilization, the diarrhea ceased. It is suggested that chewing gum usage be included in medical histories!


Increased granulocytic, erythrocytic, and megakaryocytic progenitors in myelofibrosis with myeloid metaplasia. Nucleated cells obtained from blood and/or bone marrow of patients with myelofibrosis with myeloid metaplasia (MMM) were cultured in diffusion chambers (DC) implanted into the peritoneal cavities of irradiated mice. A total of five blood studies and two bone marrow studies were performed using cells obtained from five patients. The DC were harvested at intervals from the host mice and the total and differential cellularity of DC contents were evaluated. The results obtained from MMM cultures were compared with those from similar cultures of blood cells and marrow cells of four and six normal individuals respectively. The proliferation and maturation of the granulocytic, erythrocytic, and megakaryocytic lines in MMM cultures occurred in an orderly fashion as they occur in vivo. The patterns of proliferation and maturation of the three cell lines in cultures after day 7 suggest that they primarily originate from progenitor cells. The numbers of granulocytes in the multiplicative pool, recognizable red cell precursors, and megakaryocytes recovered were significantly greater from the MMM cultures than those from the normal blood or marrow cultures. These results suggest that the blood and marrow cells of MMM patients have increased numbers of progenitors for granulocytes, erythrocytes, and megakaryocytes.


Platelet satellitism--an ultrastructural study. Ultrastructural studies by scanning and transmission electron microscopy were carried out on one of four cases of platelet satellitism. Adherence to the neutrophils was mainly by focal contact between small surface projections of the platelets and neutrophils. Phagocytosis was not seen with the neutrophils but was evident in the monocytes. The degree of satellitism noted increased with the time the blood anticoagulated with EDTA was left at room temperature. Mixing experiments with a patient's plasma and control cells and the patient's cells and control plasma were inconclusive but suggested that the abnormality may reside in the plasma.


beta-Thalassemia arising as a new mutation in an American child. A 6-year-old child of northern European ancestry was found to have microcytic, hypochromic anemia with an elevated level of hemoglobin A2 and an unbalanced pattern of globin chain synthesis characteristic of beta-thalassemia trait. Hematologic and globin synthesis studies of both parents yielded entirely normal results. Identification of the mother and father as the biological parents was established with a high order of reliability by determination of erythrocyte, serum, and HLA genetic markers. These findings suggest that the picture of beta-thalassemia observed in this child represents a new mutation.


Hemorrhagic death associated with a high titer factor V inhibitor. An acquired bleeding diathesis was first noted in a 51-year-old patient 11 days following an exploratory laparotomy. Laboratory studies indicated the cause of bleeding to be the development of a circulating anticoagulant which inhibited factor V activity. The inhibitor, an immunoglobulin of the IgG class, was separated by use of Sephadex G-200 filtration, disc electrophoresis, and isoelectric focusing. Despite vigorous immunosuppressive, antifibrinolytic, and replacement therapy, including the use of a "prothrombin complex" and plasmaphoresis, the bleeding diathesis could not be reversed and the patient died of hemorrhage. Although inhibitors to factor V are not usually associated with major life-threatening hemorrhage, this case demonstrates that the development of such an inhibitor can be an ominous finding. The use of an aminoglycoside antibiotic in this and other patients so reported may be one of the contributing causes to the development of such an inhibitor.


Elevated frequency of Tay-Sachs disease among Ashkenazic Jews unlikely by genetic drift alone. Using the steady-state distribution of recessive lethal gene the probability of finding the elevated frequency of Tay-Sachs (TSD) gene among Ashkenazic Jews is computed. For various estimated values of mutation rate and population size, this probability is found to be statistically significant. This probabiltiy, in fact, becomes even smaller if a steady influx of foreign genes into the Ashkenazic Jewish populations is considered. It is suggested that heterozygote advantage together with random genetic drift should be considered as the most probable mechansim for the elevation of TSD gene frequency among the Ashkenazic Jews.


Ethnic variation of genetic disease: roles of drift for recessive lethal genes. Using Wright's distribution of gene frequencies for a recessive lethal gene, a method is given to analyze the probability that any particular gene frequency is greater than a given threshold gene frequency. The method is introduced to analyze the plausibility of drift for explaining observed data.


Prenatal diagnosis of hypophosphatasia; genetic, biochemical, and clinical studies. This report has considered three approaches to the prenatal diagnosis of the severe, early onset form of hypophosphatasia. Two of these approaches, ultrasonography and the determination of the bone/liver isozymes of alkaline phosphatase (ALP) in cultured amniotic fluid cells, have proven useful diagnostically. The third method, assay of the bone/liver isozyme activity or total activity in supernatant amniotic fluid, was not informative for the affected fetus we studies. Failure to visualize a well-defined fetal skull after 16 weeks of pregnancy when the level of alpha-fetoprotein in the amniotic fluid is normal should arouse the suspicion of hypophosphatasia. Because the disease is known to manifest clinical variabiltiy, studies to detect both the biochemical defect as well as the structural manifestations should be considered. The combined use of ultrasonography, analysis of amniotic fluid alpha-fetoprotein, and the measurement of the bone/liver ALP in cultured amniotic fluid cells would appear to be the best approach to the prenatal diagnosis.


A note on the essential parameters of the two-allele autosomal locus model. A resolution of the parameter problem for the two-allele autosomal locus (TAAL) model has been presented. It was shown that three are four essential parameters which describe the model, by examination of the joint probability for sibs with specified parental phenotypes. This equation together with previously derived prevalence relationships uniquely specifices all parameters of the model except for the singular case VA = 0.


Phenylketonuria heterozygote detection in families with affected children. Improved approaches to the problem of heterozygote detection for phenylketonuria (PKU) were developed in this study. The discrimination was based on 85 obligate heterozygotes and 45 controls who were neither pregnant nor on birth control medication. The best separation between hetrozygotes and normals was achieved with a linear discriminant function involving the logarithms of the serum concentrations of phenylalanine, tyrosine, and tryptophan. The theoretical overlap area between the distributions of heterozygotes and controls based on the above function, was 3.75%. In the 19 obligate hetrozygotes and 13 controls who were either pregnant or on birth control medication, the best separation was achieved with a linear discriminant function involving the logarithms of the serum concentrations of phenylalanine and tyrosine. The theoretical overlap area was 8.23%. The genetic accuracy of the discriminant function was confirmed by testing the results with parental-child exclusions, segregation analysis, and the frequency of heterozygosity in nonrelated collateral spouses. Finally, there was evidence suggesting that the antihypertensive agent, aldomet, alters serum tyrosine and tryptophan levels.


Structural difference at the active site of dibucaine resistant variant of human plasma cholinesterase. Human plasma cholinesterase from five different genotypes -- E1U E1U, E1U E1A, E1A E1A, E1U E1S, E1A E1S, and E1U E1U C5+ -- was purified 8,000 fold from serum by a two-step procedure involving chromatography on DEAE-cellulose and preparative disc electrophoresis. The esterases were labeled with diisopropyl-1, 3-C14-fluorophosphate (DFP) aminoethylated, and digested by trypsin. The trytic digests were subjected to high voltage electrophoresis, and the radioactive peptides were detected by radioautography. Comparison of the peptides revealed different electrophoretic mobilities of the usual and atypical (dibucaine resistant) plasma cholinesterase peptides. The results are consistent with a structural abnormality of the active center in the variant enzyme. No difference was observed an the esteratic site of the enzyme with C5 component.


A robust method for the detection of linkage in familial disease. A nonparametric method for the detection of critical genes associated with familial disease was presented. The method involves the detection of deviations from expected identity by descent distributions at polymorphic marker loci for affected sib pairs. The method thus avoids the difficulties arising from incomplete penetrance, variable age of onset and other complications present in other forms of linkage analysis. The theoretical properties of method were worked out in detail for two important cases -- that of an incompletely penetrant recessive or incompletely penetrant dominant critical autosomal gene linked to a codominant marker locus. An easily implementable decision rule for the detection of linkage was proposed, and its operating characteristics for a variety of alternative hypothesis were obtained.


Community, hospital and clinical pharmacists and drug information centers as physician drug information sources. The use of drug information centers and clinical, hospital and community pharmacists by university and community practice physicians in North Carolina was examined. Questionnaires were sent to 674 nonfederal physicians with a response rate of 203 (35.5%). Approximately half of the sample were staff members of a university hospital. The questionnaire covered eight types of drug information. Significant results were reported at the p = 0.05 level. Physicians sought specific drug information approximately one to four times a month. University hospital-affiliated physicians rated clinical and hospital pharmacists significantly higher than community pharmacists for six subject areas, and they also ranked clinical pharmacists over hospital pharmacists on four subject areas and considered them more reliable than other pharmacy drug information sources. Physicians associated with community hospitals ranked hospital pharmacists over community pharmacists as sources of information for four areas and rated them more reliable than other pharmacy drug information sources; this group preferred to use community pharmacists for information on product availability. It appears that clinical pharmacists are used by university-associated physicians as drug information sources. Use in community hospitals of the hospital pharmacist as a drug information source is better than the literature might suggest.


Basic skills for hospital pharmacy technicians: development of a programmed training manual. The development of a programmed training manual to teach basic skills to hospital pharmacy technicians is described. Steps in the development of the manual included reviewing pertinent literature, writing a job description for a pharmacy technician position, performing a task analysis, writing learning objectives and sequencing course content into a programmed format. Five units of the manual cover dosage forms and routes of administration, drug nomenclature, abbreviations, calculations and medication orders. The programmed format should help to provide quality, economic and efficient training for technicians.


Food and Drug Administration's adverse drug reaction monitoring program. The adverse drug reaction monitoring program of the Division of Drug Experience within the FDA is described. Historical information on the development and activities of the current drug reaction monitoring program, and goals and objectives of the current program are discussed. Also presented are a brief description of the Voluntary Reporting System, intensive drug monitoring studies and special epidemiologic studies, and a workable definition of alert reports and examples of their previous role within the FDA. Pharmacists should participate actively in adverse drug reaction monitoring.


Cephalosporins: use review and cost analysis. The prescribing patterns for the cephalosporins and the cost-savings following restriction of cephalothin sodium and approval of cefazolin sodium were studied over a three-year period at a university hospital. The prescribing patterns for cefazolin relative to dose, frequency, duration of therapy and clinical indications were studied for 64 patients during a one-month period. Parenteral cephalosporin use for three years was analyzed to determine comparative use rates and costs. For the most part, cefazolin was used properly during the one-month study. The greatest misuse was as prophylactic therapy in postsurgical patients. The switch from cephalothin to cefazolin resulted in a projected annual savings of $5,500, equal to more than 10% of the hospital's expenditures for parenteral cephalosporins. The prescribed daily dose of cephalosporin dropped by one-third following the formulary change. The decision to use cefazolin as the major parenteral cephalosporin resulted in substantial cost savings.


Multidisciplinary audit of digoxin.

Multidisciplinary audit of digoxin. Use review of digoxin as part of a medical care evaluation study in a hospital is described. This drug audit within the hospital's quality assurance program used a multidisciplinary approach. The study was designed to measure the incidence of digoxin toxicity, evaluate monitoring practices for digoxin use and evaluate the adequacy of digoxin dosing patterns. Forty-eight patients were involved. Results indicated that some patients were not adequately assessed in regard to renal function and digoxin serum level. Further, there was a 17% incidence of digoxin toxicity. Studies such as this give pharmacists an opportunity to use their knowledge of proper drug use through a structured hospital program.


Survey of clinical pharmaceutical services in Florida hospitals. A survey of clinical pharmaceutical services in Florida hospitals is described. Questionnaires were mailed to the pharmacy departments of 210 hospitals containing 50 or more beds; 172 (82%) responded. Data were collected concerning the extent and types of clinical services provided; the reasons for not implementing the services were also obtained. Twenty (12%) hospitals employed a full-time clinical pharmacist. Inservice drug education, formalized drug information, cardiopulmonary resuscitation and patient medication histories were provided by 78%, 47%, 19% and 6% of the hospitals, respectively. Hospitals with a total or partial unit dose drug distribution system seemed more likely to provide clinical services than those with other types of distribution systems. Hospitals employing a clinical pharmacist were engaged in a wider range of clinical services and provided these services to a larger portion of their patient population. The reason most frequently cited for not implementing clinical services was inadequate staff.


Medication delivery time requirements in centralized and decentralized unit dose drug distribution systems. Medication delivery time requirements in centralized and decentralized unit dose drug distribution systems were compared. Four stages in the receipt of medication orders and the delivery of doses were identified, and the time required to perform each stage was recorded by pharmacist observers for seven days in each system. In the centralized system, it required 138--220 minutes to deliver doses after orders were ready to be collected at the nursing station, with the time varying according to order type. The same cycle required 1--40 minutes in the decentralized system. Delays in medication delivery were shorter in the decentralized system.


Estimation of serum digoxin levels in geriatric patients. The correlation in geriatric patients between estimated serum digoxin levels based on pharmacokinetic calculations and serum digoxin levels measured by radioimmunoassay was studied. Serum digoxin levels were estimated for 17 geriatric patients recieving digoxin using the "total body stores" concept. A statistically significant correlation between calculated and measured digoxin levels was shown (p less than 0.05, r = 0.51); however, 95% confidence limits were so large (+/- 1.75 ng/ml) that the results were clinically unacceptable. Until data describing specific causes of variance are available and calculations modified to account for specific variations, pharmacokinetic models should not be relied upon for accurate estimates of digoxin levels in geriatric patients.


Interpretation of digoxin blood levels by programmable calculator. The usefulness of a computer algorithm, for a hand-held calculator, in the calculation of steady-state blood levels of digoxin was studied. The calculator was programmed using the Wagner-Northam steady-state equation. The program was tested on data obtained from the charts of 14 patients recieving digoxin. Blood levels of digoxin were determined by radioimmunoassay. In nine patients, the calculated values correlated well with measured values. In five patients, calculated values did not correlate with measured values; half-life was underestimated in two patients, a charting error was made with one patient and digoxin disappearance was suggested to be unusual in two patients. This study suggests that a measure of scientific precision in planning and monitoring of drug therapy regimens is possible using a programmable calculator.


Using pharmacokinetics in drug therapy III: Estimating dosage regimens and blood levels using the fraction-lost method. The "fraction of drug lost during dosage interval" method, which yields rapid estimates for drug dosage regimens and blood levels, is described. Estimation of the fraction lost during a dosage interval allows further calculation of dosage regimens and steady-state blood levels. The estimates derived from this method are valid only when the pharmacokinetics of the drug are linear and elimination from the body occurs according to first-order kinetics. Other limitations of the method are discussed.


Acetaminophen poisoning: a case report of the use of acetylcysteine. Acetylcysteine treatment of acetaminophen overdose (24--30 g) in a 31-year-old female is reported. Acetylcysteine was used to prevent acetaminophen-induced hepatotoxicity. An oral loading dose of 7 g of acetylcysteine was followed with oral administraton of 3.6 g every four hours for 17 doses. Liver enzymes were elevated on the fourth day after overdose. Phytonadione was administered on days four through six for elevated prothrombin time ratios. Only mild elevations of liver enzymes still were present on day seven. Previous case reports and studies of acetaminophen-induced hepatotoxicity and acetylcysteine therapy are reviewed. The use of acetylcysteine in this case appeared to be beneficial.


Credentialing in the clinical laboratory sciences. There are essentially two types of credentialing. One recognizes the competence of educational programs to prepare personnel and is generally referred to as accreditation. The second recognizes the competence of individuals to deliver services and includes the processes of certification, licensure, and registration.


Development of competency-based, career-entry examination for clinical laboratory personnel. The process of developing a competency-based credentialing examination for career-entry practitioners is described, including a review of pertinent literature. A modified Delphi technique was used to achieve consensus among a panel of experts with respect to Career-Entry Statements of Competence. Items were written which were referenced specifically to one or more of the statements. The resulting genralist examination for the technologist and technician personnel levels is the first such examination to be reported in the field of clinical laboratory sciences which utilized a formal process involving such large numbers of practicing professionals.


Laboratory detection of thalassemia.

Laboratory detection of thalassemia. The thalassemias are a heterogeneous group of genetically determined disorders of hemoglobin synthesis and can be divided into alpha-thalassemias and beta-thalassemias. The genes for these disorders are carried as relatively harmless traits which can be detected in the laboratory by a series of tests. As there are several variant genes in each group, heterozygotes for two slightly different genes occur, and interaction of these thalassemia genes with the hemoglobinopathies is quite common. Severe clinical disease usually only occurs in homozygotes, as in Cooley's anemia. The problem for the laboratory is to distinguish thalassemia trait from other causes of microcytosis and hypochromia in an economical and efficient way. The various proposed schemes are discussed, and it is suggested that detection of these traits should be part of a comprehensive screening program for hemoglobinopathies and thalassemias.


The role of the interview in student selection. Four types of data are commonly considered in selecting applicants for academic programs: 1) test scores; 2) grade-point averages; 3) personal data; and 4) interview results. Limitations and advantages of using interview data in the selection decision are discussed. Fifteen suggestions are offered for improving the validity and reliability of interview data. Strategies for data collection and analysis are suggested for validation studies of selection interviews.


Michaelis-Menten constant of serum aspartate amino transferase (AST) in heart and liver diseases. The activity and the Km (Michaelis-Menten constant) of serum aspartate amino transferase (AST) were investigated in normal subjects, in patients with recent myocardial infarction, and in patients with infectious hepatitis. AST activity was elevated in both groups of patients. While the Km value of serum AST was not affected in myocardial infarction, it was increased in infectious hepatitis when the total serum bilirubin was higher than 13 mg/dl. Thus, while an investigation of activity of AST in serum did not help in differential diagnosis of heart and liver diseases, determination of Km value was helpful in the diagnosis of infectious hepatitis.


Task analysis of medical technology administration and supervision. The purpose of this study was to develop a hierarchical set of administrative and supervisory competencies that a medical technology student should acquire before graduation from a medical technology program. The information that formed the basis for this research project was derived from responses to the Clinical Laboratory Supervision Survey completed by medical technologists, laboratory supervisors, administrative technologists, and education coordinators who are members of the American Society for Medical Technology. This paper presents the competencies that were identified as desirable from this task analysis study.


Duplication 2q33 leads to 2q37 due to paternal ins (12;2) translocation. An 18 month-old boy with partial duplication of the long arm of chromosome 2, based on a paternal balanced translocation, 46,XY,ins (12,2)( q23;q33q37), is described and compared with five previously reported cases. These children have in common a short nose with broad flat bridge and small anteverted nostrils, long upper lip, low-set ears, and minor digital anomalies.


An unusual dysplasia-malformation-cancer syndrome in two patients. We report two patients with a similar syndrome of gross malformation of a lower limb and contiguous structures due to involvement with dysplastic, teratomatous tissue. This dysplasia seems to have arisen in a paramedian position in the embryonic hindquarter at the time of lower limb-bud differentiation. Malignant degeneration at 5--7 months led to metastases and death in both cases around 1 year of age. The behavior of the dysplastic/oncoplastic tissue suggests a 2-"mutational" causal model. This is an apparently previously undescribed formal genesis syndrome.


Severe mental retardation, cataracts, short stature, and primary hypogonadism in two brothers. Two severely mentally retarded brothers are described who had a similar facial appearance, cataracts, short stature, minor digital abnormalities, and primary hypogonadism. Their parents were first cousins. Numerous laboratory investigations failed to elucidate a basic metabolic cause for their disorder.


Minor chromosome variants in child psychiatric patients. The frequency of minor chromosome variants, as detected by conventional chromosome analysis, was examined among 1,289 child psychiatric patients, of whom one-fourth had only behavioral problems and three-fourths had congenital abnormalities and more severe mental disorders. There was no more than random association between prominent satellites, prominent secondary constrictions or a long Y chromosome, and congenital abnormalities or more severe mental disorders. The frequencies of these chromosome variants were affected by race as has been shown in previous studies. These findings do not support the evidence for a developmental effect of minor variants in man.


X-inactivation pattern in three cases of X/autosome translocation. We describe an X/15 translocation which was balanced in a phenotypically normal mother [46,X,t(X;15)(p22;q15)] and unbalanced in her phenotypically abnormal daughter [46,X,der(X),t(X;15)(p22;q15)mat]. A third case involves a balanced X/21 translocation in a girl with a multiple congenital anomaly-retardation syndrome [46,X,t(X;21)(p11;p11?)]. 5-BrdU acridine orange banding on lymphocytes revealed late replication of the normal X chromosome in the mother and of the normal or abnormal X chromosome in the two other cases. Our findings are only partially consistent with previous observations. All X-inactivation patterns can be explained by random inactivation and subsequent selection against specific cell lines. Furthermore, the findings in our patient with X/21 translocation support the hypothesis of the existence of one inactivation center on Xq.


Autosomal dominant inheritance of annular pancreas. This report describes a family with apparent autosomal dominant transmission of congenital annular pancreas. Four individuals in two generations were affected; all developed duodenal obstruction. The implications for genetic counseling are discussed.


National crisis in mental retardation research. The incidence of mental retardation will be significantly reduced only when we have a greater understanding of the nonorganic form of mental retardation, the type that afflicts approximately 75 percent of persons labeled mentally retarded. Such an understanding requires an interdisciplinary research effort that includes a major contribution from the behavior sciences. The current level of support of mental retardation and behavior science research by the National Institute of Child Health and Human Development limits the nation's capability of achieving the goals of preventing and ameliorating mental retardation.


Taking the role of retarded children: effects of familiarity and similarity. As a first step in improving social relations between nonhandicapped and retarded children, this study was designed to investigate children's ability to take a retarded child's role and the effects of two variables on this ability: (a) familiarity with the characteristics of retarded children and (b) similarity of experiences to those of retarded youngsters. Findings were interpreted as indicating that children's ability to take the perspective of retarded children may be a productive area for further research.


Social interactions and communication patterns in mentally retarded children. An observational approach and videorecordings were used to investigate a group of four mentally retarded kindergarten children with minimal language development. Results showed that when a facilitator (teacher) was present, there were more social interactions and vocalizations, but there was no significant increase in meaningful verbal content. Nonverbal communication rose sharply in the presence of the facilitator. The findings indicate that an observational analysis of patterns of interaction is useful in planning intervention programs in the area of social and communication development.


Porteus Maze Test performance of retarded young adults and nonretarded children. Performances of retarded young adults on the Porteus Maze Test were compared with those of first- through fourth-grade nonretarded children. The retarded subjects, approximately matched on MA with the fourth-grade group, performed at the level of the first graders and were reliably poorer than the third and fourth graders. This MA lag of at least 2 years is consistent with the MA lag previously found on strategic games and puzzles. The retarded and first-grade groups spent more time completing mazes than did the other groups.


Comparability of naturalistic and controlled observation assessment of adaptive behavior. The comparability of retrospective naturalistic and controlled observation assessment of adaptive behavior was evaluated. The number, degree, and direction of discrepancies were evaluated with respect to level of retardation of the client, rater differences, behavior domain sampled, and prior observational base for the ratings. Generally poor comparability between the procedures was found and questions were raised concerning the types of generalizability that can be made from adaptive behavior assessment obtained under the two procedures.


Stability of direct and transfer effects of number-conservation training with mentally retarded adults. Twenty nonconserving retarded adults were assigned to equated training and control groups (n = 10 in each group). Training-group subjects were given multiple-strategy training for number conservation consisting of: demonstrating effects of addition-subtraction; negation of addition-subtraction by inverse operations; and addition-subtraction combined with perceptually induced cognitive conflict, reversibility, and verbal-rule instruction. Analyses of variance and critical difference multiple comparisons showed significant direct-training effects immediately after training and after 8 monhts. Significant short-term transfer was obtained on other types of conservation (discontinuous quantity, substance, liquid quantity, length, and weight), but long-term transfer was much weaker and less consistent. Transfer resulted primarily from gains in correct conservation judgements, with a majority of trained subjects failing to give any acceptable conservation explanations.


Effects of clustering instructions and category size on free recall of nonretarded and retarded children. The effects of category size and instructions to cluster on the free-recall learning of 112 nonretarded and retarded children were assessed. Simultaneously presented lists of 12 pictures composed of 2, 3, or 6 categories were shown for three study-test trials. Instructions to cluster significantly increased recall and cluster scores on a new list for both nonretarded and retarded children. The category-size effect was weak, although it was related to the magnitude of the correlations between organization and recall scores.


Prediction of retarded adults' work performance through components of general ability. A factor analysis was performed on a set of variables used to predict work performance, or industrial rate, for 127 mentally retarded adults. The results indicated that there is a general ability factor that can be partitioned into three components: cognitive, visual-motor, and work sample/sorting abilities. The latter two components were more closely related to industrial rate than was the former. Variables included subject characteristics, standardized tests, ratings, and work samples. As a group, the work samples were the best predictors of industrial rate; the subject characteristics were the poorest.


Attention to compounds by retarded adults. Severely retarded adults were presented with a matching task in which each of the alternatives to the stimulus that was identical to the target stimulus differed from it on one dimension only. Matching performance was found to be good both when the target stimulus had two relevant dimensions and when it had three relevant dimensions. The findings were consistent with those of Tighe and Tighe (1972) and other (Cole, 1973; Tighe, 1973) that the salience of compounds is higher than that of components for persons of lower developmental level.


Comparison of the performance of first-grade and mentally retarded students on the Peabody Mathematics Readiness Test. The Peabody Mathematics Readiness Test was developed to assess mathematics readiness and identify children who would encounter difficulty in first-grade mathematics. In the present study, we compared performances of mentally retarded subjects and first-grade subjects on this test. Retarded subjects' mean scores were significantly lower than those of the nonretarded subjects on the drawing test; however, there were no significant differences between the mean scores of the groups on the other five subscales.


Self-regulation in retarded persons: acquisition of standards for performance. Twenty-four TMR children (mean IQ = 40.1, mean MA = 46.4 months) were divided into three groups equated by stratified assignment on IQ, MA, and CA. One group was then randomly assigned to each treatment condition: (a) Training 1 (live/film), (b) Training 2 (film/live), and (c) control. In the first phase of the study, both training groups watched five clown models set their standard at 6 on a bowling game. Subsequent standards set by the training and control groups indicated that these retarded children did base their standards on the models' standards (i.e., social referent). A training program including both live and filmed demonstrations was developed in order to teach the children a concept (i.e., "between") that would allow them to set their standards based on their own past performance. We found that both training groups acquired, retained, and generalized the concept as evidenced by the standards they set.


Perceptual and intellectual factors affecting number concept development in retarded and nonretarded children. The role of MA and visual-perceptual ability in number concept development was examined with nonretarded and retarded children from regular school settings. Both groups were matched on MA and divided into high and low perceptual-ability levels. Using the Dodwell Number Concept Test, we tested each subject on various Piagetian tasks. Although retarded and nonretarded groups differed in IQ and CA, equivalence in MA resulted in equivalent number concept performance. For both groups, regardless of variation in IQ and CA, perceptual ability exerted a significant influence on number concept, with high perceptual ability resulting in superior number concept performance.


Screening for fetal and neonatal risk in the postdate pregnancy. One hundred four postdate pregnancies were managed according to a well-defined protocol calling for weekly oxytocin challenge tests and urinary estriols three times per week. Although the perinatal mortality rate in these patients was not increased there was a significant increase in the incidence of neonatal morbidity and complications. The clinical syndrome of dysmaturity was seen in 20 per cent of the neonates. When meconium was present in the amniotic fluid the incidence of neonatal and fetal complications was higher. The cesarean section rate was twice the normal rate, with nonprogression of labor being the commonest indication. It is recommended that: (1) pregnancies carried beyond 42 weeks do not require termination simply because they are post dates; (2) all postdate patients should be monitored during labor; (3) trained personnel to initiate neonatal resuscitation should be present at each postdate delivery.


Pregnancy in the massively obese: course, outcome, and obesity prognosis of the infant. The obstetric performance and pregnancy outcome in 208 massively obese patients who were delivered over an eight-year period were compared with those of nonobese control subjects. The incidence of obesity in their infants was also compared. No significant increase in the incidence of urinary tract infection, diabetes, breech presentation, cesarean section, forceps delivery, or maternal and infant morbidity was noted in the obese women. Significantly increased incidences of hypertensive disorders of pregnancy (p less than 0.01), gestational diabetes (p less than 0.01), inadequate weight gain (p less than 0.001), and wound or episiotomy infection (p less than 0.05) were observed in the study group. The mean birth weight of the infants of obese women was 209 grams greater than that of the control subjects. A significantly increased number of the obese patients were delivered of excessive-sized infants. Despite this, the incidence of obesity in infants of obese women was not significantly increased at birth or six months of age. By 12 months of age, however, these infants were significantly more obese than the control infants.


Plasma prostaglandin metabolites in human labor. To elucidate the role of prostaglandins in initiating uterine contractions we studied the concentrations of 13,14-dihydro-15-keto-PGE2 (PGE2-M) and 13,14-dihydro-15-keto-PGF2alpha (PGF2alpha-M) in peripheral plasma of pregnant patients. The concentrations of PGE2-M and PGF2alpha-M in pregnant patients at term not in labor were not significantly different from those at midpregnancy. Induction of labor at term pregnancy caused a significant rise of both PGE2-M and PGF2alpha-M. During spontaneous labor there were no significant minute-to-minute fluctuations of plasma PGE2-M and PGF2alpha-M and their concentrations were not different from those at oxytocin-induced labor. Initiation of uterine contractions and abortion at midpregnancy by the intra-amniotic infusion of hypertonic saline was not associated with any change in PGE2-M concentration and a rise in PGF2alpha-M was noted in only one of five patients. The vaginal administration of PGE2 and the intra-amniotic infusion of PGF2alpha were associated in each case with a significant rise of both prostaglandin metabolites. It is concluded that the rise of prostaglandin metabolites in peripheral plasma is secondary to the initiation of uterine contractions at term pregnancy. Such a rise is not usually observed after the initiation of uterine contractions by hypertonic saline at midpregnancy.


Free amino acids in plasma throughout pregnancy. Plasma amino acid analyses on 27 amino acids in serial samples from 15 pregnancies in 14 patients are reported. Variations of amino acid levels with gestational age are reported both for absolute amino acid levels and for levels normalized to total amino acids, with a t test used to determine which amino acids vary significantly. The extent to which individual results differ from the means is indicated. Correlation and regression analyses were done for each amino acid vs. every other amino acid and for each amino acid vs. gestational age. Significant differences were found in amino acid results for plasma from an individual in whom pregnancy resulted in spontaneous abortion.


Steroid concentrations in human myometrial and placental tissues at week 39 of pregnancy. Endogenous levels of P, E1, and E2 were determined by radioimmunoassay in human myometrium and placenta at week 39 of pregnancy. In the myometrium, P and estrogens were higher in the inner layer near the placenta than in other zones. Higher E2/P ratios were found in placental sites. A large difference in the E2/P ratios was observed between placenta and corresponding adjacent myometrial area, indicating an easier diffusion of E2 from the site of its production.


The relationship between premature rupture of the membranes and the respiratory distress syndrome. An update and plan of management. The records of 340 infants of 36 weeks' gestational age or less were reviewed to study the relationship between premature rupture of the membranes (PRM) and the development of the respiratory distress syndrome (RDS). Twins and infants of diabetic mothers were excluded from the data analysis. PRM of 16 hours or more was associated with statistically significant reduction in the incidence of RDS in infants of 31 weeks' gestational age and older. The association between PRM in excess of 16 hours and survival, however, was only statistically significant for infants of 33 weeks' gestational age and older. The implications of these results and a proposed plan of management for premature infants with PRM are discussed.


Meconium passage: a new classification for risk assessment during labor. The significance of MSAL as a sign of fetal distress is controversial. To better assess this condition, we present a classification of MSAL based on the timing and quantity of meconium passed and divided into early light, early heavy, and late passage of MSAL. By means of this classification with a problem-oriented risk assessment system, 2,933 pregnancies were prospectively evaluated during labor. The incidence of meconium passage was 22 per cent, of which early light constituted 53.6 per cent, early heavy 25.2 per cent, and late passage 21.2 per cent. Early heavy MSAL is associated with increased fetal and neonatal morbidity and death, and with a number of antecedent obstetric problems. Late passage of MSAL encountered no perinatal losses, but is associated with increased neonatal morbidity occurring late in labor. Early light MSAL, constituting over half of all our meconium group of patients, is not associated with any increased intrapartum or neonatal morbidity or death. This classification of MSAL is an effective tool for risk assessment during labor.


The effect of fetal age, birth weight, and sex on cord blood immunoglobulin values. In order to determine the role played by fetal "factors" in fetal immunoglobulin levels, cord blood samples from 176 normal infants were analyzed for the relationship between immunoglobulin concentration and the gestational age, birth weight, and the sex of the fetus. Cord blood IgM and IgG both increased with gestational age until term, while IgA, its subclasses IgA, and IgA2, and IgD were unaffected by gestational age. IgM and IgG were higher in fetuses weighing 2,000 grams or more, while IgA, IgA, and IgA2 were not influenced by birth weight. Cord blood immunoglobulin values were the same in male and female infants. The interrelationship between cord blood immunoglobulin class and subclass concentrations was examined in two ways: (1) The correlation coefficient r for paired samples was calculated between immunoglobulin concentrations in individual cord sera. (2) Student's test for the mean was used to compare subgroups of the entire sample populations, divided into high, intermediate, and low immunoglobulin values. IgM and IgG, and IgM and IgD were correlated. The data obtained indicate the need to consider the gestational age and birth weight of a neonate in the use of cord blood immunoglobulin values to evaluate the possibility of fetal infection.


An assessment of continuous fetal heart rate monitoring in labor. A randomized trial. Intrapartum continuous fetal heart rate monitoring has been routinely performed at the Jessop Hospital for Women for some years. However, no controlled trials had ever been performed to show its advantages over intermittent auscultation in low-risk patients. A prospective randomized study of 504 patients compared continuous fetal heart rate monitoring with intermittent auscultation. There was no significant difference between the two groups in neonatal deaths, Apgar scores, maternal and neonatal morbidity, and cord blood gases. The cesarean section rate was significantly increased (p less than 0.05) in the monitored patients but this did not seem attributable to fetal monitoring. No beneficial or deleterious effects of continuous fetal heart rate monitoring in labor were shown.


Diagnostic and therapeutic hysteroscopy for traumatic intrauterine adhesions. During diagnostic hysteroscopy, I found intrauterine adhesions in 192 patients; central adhesions appeared as a bridgelike tissue connecting the anterior and posterior walls of the uterus, and marginal adhesions appeared as a partial ledgelike tissue projected from a part of the uterine side wall. All of the central adhesions and most of the marginal adhesions were removed by pushing with the tip of the outer sleeve of the hysteroscope under visual control. Moreover, hysteroscopy made rough estimates of the histology of the adhesions from the surface appearance of the adhesions before removal, the force needed for separation, and the appearance of the stumps of adhesions removed. The effects of adhesionolysis were evaluated by recovery of endometrial function, that is, increase of menstrual blood flow and achievement of a viable pregnancy. Among the 192 patients, 143 recovered previous menstrual flow, the others remained hypomenorrheic. In 79 pregnant patients, 45 were delivered of viable infants. Improvement of endometrial malfunction in advanced cases of intrauterine adhesions is a problem awaiting a solution.


Catechol-O-methyltransferase activity in erythrocytes of pregnant women. Catechol-O-methyltransferase (COMT) is the enzyme that converts catechols, e.g., catecholamines and catechol estrogens, to their methyl ethers. COMT activity measured in erythrocytes (RBC's) of healthy men (No. = 47) and healthy nonpregnant women (No. = 53) was 8.2 +4- 0.17 nmoles X ml.-1 (mean and standard error). The COMT activity in RBC's of healthy pregnant women (No. = 100) was 10.7 +/- 0.29 nmoles X ml.-1 RBC X hr.-1, a value which is significantly higher than that found in RBC's of men and nonpregnant women (p less than 0.001).


The essential iris atrophies.

The essential iris atrophies. We studied 82 cases of essential iris atrophy. The findings support some traditional concepts of this complex spectrum of disorders, but conflict with others. Corneal abnormality appeared early and may be the primary disorder. A corneal endothelial disturbance was present in 55% of cases and corneal edema was present in 50%. Peripheral anterior synechiae occurred in all but one of the cases studied by gonioscopy. The pupil was distorted in 71% of the cases and was usually pulled in the direction of the most prominent synechia. The iris was stretched with stromal atrophy in 71%. Iris holes occurred in 33%. The degree of corneal and iris changes occurred as a spectrum of disorders. The prognosis for most patients with essential iris atrophy is slow progression with eventual involvement of vision because of corneal edema, secondary glaucoma, or both. Treatment of increased IOP was required in 77% of our cases, and 44% required surgical intervention.


Pulsating metastatic tumor of the orbit. A 47-year-old white man in apparent good health had diplopia and swelling of the right upper eyelid. Ocular examination showed proptosis of the right eye, together with a large, pulsatile, collapsible mass simulating a vascular neoplasm and involving the right temple as well as the right upper outer quadrant of the orbit. Biopsy of the orbital tumor disclosed a clear-cell carcinoma compatible with a renal primary tumor; subsequent laboratory examination revealed the offending tumor in the left kidney. Renal carcinomas may metastasize to the globe or to the orbit before the primary tumor is recognized. Pulsatile exophthalmos acquired in middle life associated with significant bone destruction represents a constellation of findings most consistent with a metastatic tumor, probably renal carcinoma, caused by the exceedingly rich vascularization of these metastatic deposits.


Clinical manifestations of brawny scleritis. We studied four patients with posterior brawny scleritis. Two underwent enucleation for suspected melanoma, and in the other two, the correct diagnosis was made and effective therapy begun. Of seven other eyes with brawny scleritis from other sources, five were enucleated after diagnosis of choroidal melanoma and one for suspected intraocular tumor. This experience and other previous reports indicate the high incidence of diagnostic confusion regarding brawny scleritis. We therefore emphasized clinical symptoms and signs of brawny scleritis: inflammation, tenderness or pain of the globe, history of collagen vascular disease, proptosis, bilaterality, and retinal and choroidal detachment. A preserved normal choroidal vascular pattern over an elevated subretinal mass may be indicative of posterior brawny scleritis. Scleral biopsy is useful for tissue diagnosis. Radioactive phosphorus uptake tests and ultrasonography may erroneously indicate choroidal melanoma and lead to enucleation of a potentially salvageable globe.


A modified silicone frontalis sling for the correction of blepharoptosis. We devised a frontalis sling by using two No. 40 silicone bands. Each free end was sutured to the tarsus and joined in the central brow area. We used pulley sutures in the medial and lateral brow incisions to prevent migration of the bands. With this method, adjustment of the eyelid level can be made anytime postoperatively through the central eyebrow incision because of the ease in finding the overlapped ends of the silicone bands. This is particularly useful for patients with chronic progressive ophthalmoplegia where poor closure and exposure keratopathy are potential postoperative problems.


Ophthalmic sequelae of infantile hemangiomas of the eyelids and orbit. The major findings in a study of 51 infants and children with infantile hemangioma of the eyelid were as follows: Visual complications occurred in 27 patients. The most common complications were amblyopia (in 22) and strabismus (in 17). Amblyopia of 6/60 (20/200) or less was probably caused by stimulus-deprivation, but amblyopia in the range of 6/30 (20/100) to 6/12 (20/40) was likely caused by anisometropia or strabismus. Eyelid occlusion of six months or more invariably resulted in amblyopia of 6/60 (20/200) or less. Occlusion for even one month carried a risk of amblyopia. Each child must be considered individually for therapy, which must be started as early as possible. Patients should receive careful follow-up from the beginning to prevent severe amblyopia. For difficult cases, we need more efficacious, safe methods to induce regression of these tumors.


Ectropion of the lower eyelid secondary to Müller's muscle-capsulopalpebral fascia detachment. A patient developed severe lower eyelid ectropion after a bilateral levator aponeurosis and Müller's muscle advancement-and-truck blepharoptosis procedure and bilateral attachment of the lateral canthi to the lateral canthal tendons. The cause of this ectropion was detachment of Müller's muscle and capsulopalpebral fascia from the inferior tarsus and recession of these tissues into the orbit. This left the inferior tarsal border with only redundant conjunctiva attached to it, which could not maintain it in a downward direction; thus, an ectropion occurred. Müller's muscle and capsulopalpebral fascia were detached from the inferior tarsus and recessed 15 mm into the orbit. Reattaching Müller's muscle and capsulopalpebral fascia to the inferior tarsus relieved the ectropion.


Intralesional corticosteroid therapy of chalazia. Twelve adult patients with 17 chalazia underwent trial intralesional injection of triamcinolone acetonide. Seven chalazia resolved within two weeks after only one injection, and another six after two injections. Two lesions failed to respond to two injections, and two lesions responded to one injection, but either recurred or another lesion developed. Patients were satisfied with the procedure, which appears to be a safe, convenient, and effective altefnative to chalazion surgery.


Generalized fibrosis of the extraocular muscles. We studied four patients with the general fibrosis syndrome. One patient had bilateral inguinal hernias and unilateral cryptorchism; the other patients had no other congenital abnormalities. The patients developed normally both neurologically and metally. We successfully treated amblyopia and achieved good functional and cosmetic results with strabismus and blepharoptosis surgery. Histopathologic study revealed fibrous infiltration of extrinsic eye muscle and Tenon's capsule without inflammatory changes.


Efficacy of bifocals in the treatment of accommodative esotropia. We treated 84 patients with a partially refractive accommodative esotropia with bifocals. Twelve patients were able to fuse without bifocals at the end of therapy; in 19, the bifocal power could be reduced and further improvement can be expected in the future. Thirty-nine remained dependent on bifocals; and in 14, fusion had deteriorated in spite of therapy. Patients with a high AC/A ratio and those receiving supportive orthoptic treatment seemed to fare best with bifocals. In those with a low AC/A ratio, fusion tended to deteriorate because of a slowly increasing esodeviation at near fixation.


Secondary diabetic retinopathy in chronic pancreatitis. We found abnormal glucose tolerance curves in 45 of 47 patients with chronic pancreatitis and observed secondary diabetic retinopathy in eight of 45 cases showing slight changes in the fundus. Abnormal glucose tolerance curves were somewhat related to the exocrine dysfunction of the pancreas. Slightly abnormal glucose tolerance curves were observed frequently in patients with chronic pancreatitis, and both insulin and glucagon responses were decreased. We could not explain the cause of the low frequency of secondary diabetic retinopathy in pancreatic diabetes from the results of insulin and glucagon response tests.


Teratoid intraocular medulloepithelioma. The right eye of a 1-year-old black infant with a painful blind eye was studied histologically. It contained a tumor at an advanced stage of growth. The tumor consisted of moderately large, round, and elongated undifferentiated cells and anaplastic cells with mitotic figures combined with multilayered, poorly differentiated epithelial cells that resembled the medullary epithelium of embryonic retina. Strap cells with cross striation typical of striated muscle were also present, together with islands of hyaline cartilage and areas of calcification.


Association of presumed ocular histoplasmosis with HLA-B7. Thirty-one white patients who fulfilled the clinical criteria of the syndrome recognized as presumed ocular higtoplasmosis were typed for common histocompatibility antigens. These clinical criteria included the presence of multiple peripheral punched out choroidal atrophic scars, compatible macular disciform lesion in at least one eye, and clear vitreous. Seventeen out of 31 patients were found to have HLA-B7, which is statistically significant at the P less than .005 level when compared to a normal population. More patients should be tested to establish this correlation more firmly. Though this is statistically significant, other factors must be involved as there still remain many patients who fulfill the clinical criteria but do not demonstrate a common histocompatibility antigen.


The prevalence of HLA-B7 in presumed ocular histoplasmosis. Eighteen patients with the presumed ocular histoplasmosis syndrome were typed for HLA histocompatability antigens and 78% were found to have the B7 antigen. This data implies an underlying immunogenic predisposition to the development of the clinical eye findings and active posterior pole lesions in the presumed ocular histoplasmosis syndrome. It is likely that some feature of the immune system of these patients renders them more susceptible either to the initial infection or to a later activation of posterior pole lesions mediated through immunologic mechanisms.


Hypertensive reactions to phenylephrine eyedrops in patients with sympathetic denervation. We studied the effects of topical phenylephrine eyedrops on systemic blood pressure in 298 patients about to undergo ocular surgical procedures by comparing their blood pressure on admission to the hospital with that measured immediately before surgery. The patients were divided into three groups. Group 1 consisted of 230 patients who had neither history of insulin-dependent diabetes nor prior teatment with reserpine or guanethidine. Group 2 included 41 insulin-dependent diabetic patients. Group 3 contained 27 hypertensive patients who had been taking reserpine or guanethidine. Patients in each group were divided into two subgroups (A and B). The 202 patients in the three A subgroups received preoperative phenylephrine eyedrops, whereas the 96 patients in the three B subgroups did not. All three B subgroups and Group 1A (176 patients) did not show significant increases in blood pressure. There was a statistically significant increase in both systolic and diastolic pressures in Group 2A (14 patients) and in Group 3A (12 patients). From this study, we concluded that administration of preoperative phenylephrine eyedrops can be hazardous in patients with long-standing insulin-dependent diabetes or in hypertensive patients receiving reserpine or guanethidine.


A simple device to improve blinking.

A simple device to improve blinking. A blink beeper was devised to remind patients with incomplete or infrequent blinking to blink completely and at normal intervals; the beeper worked by transmitting an audible tone every ten seconds through an earphone. In three postkeratoplasty patients, this simplistic approach not only resulted in a complete blink at regular intervals, but seemed to condition this response to continue when  the blink beeper was taken away; this resulted in healing of large chronic epithelial defects. The blink beeper has also proved valuable in patients with either punctate epithelial erosions or those who wore hard contact lenses unsuccessfully because of infrequent or incomplete blinking.


Retail cost of antiglaucoma drugs in two cities. Volunteer shoppers purchased antiglaucoma medications dispensed from prescriptions written according to generic and brand-name products in Manhattan and in the St. Louis area. All drugs obtained were more expensive in Manhattan than in St. Louis. No significant cost difference was found between generic and brand-name items in either city, but only in a few instances were generic drugs actually dispensed. No difference in overall price was found between pharmacies located in better and poorer neighborhoods in Manhattan or between pharmacies located in urban, suburban, or rural areas in St. Louis. A white shopper paid significatnly lower retail prices than did a Hispanic shopper in Manhattan, particularly in better neighborhoods. The range of prices in each city for all drugs studied was greater than twofold. Pharmacies offering more patient services tended to charge higher prices, but frequently, pharmacies did not actually offer the services they advertised.


Serum obstruction of aqueous outflow in enucleated eyes. We perfused enucleated human eyes via the anterior chamber by the constant pressure technique. Infusion of human serum into the anterior chamber of enucleated human eyes for 30 minutes at 23 mm Hg pressure induced a 42% decrease in facility of outflow, which was not relieved by irrigation of the anterior chamber with balanced salt solution or alpha-chymotrypsin. Diluted serum also reduced the facility of outflow. Measured in a glass viscometer, diluted serum had less viscosity than undiluted, but interfered with outflow from the eye more than anticipated on the basis of viscosity alone. When we used lens depression to induce tension on the iridocorneal angle to simulate the effects of contraction of the ciliary muscle, outflow facility increased in control eyes that had not been exposed to serum and in serum-perfused eyes. However, the partial obstruction to outflow that had been induced by serum persisted. Normal serum components may become adsorbed or entrapped in the aqueous outflow system so as to obstruct outflow, and this may result in secondary glaucoma in eyes with chronic uveitis.


Subacute sclerosing panencephalitis.

Subacute sclerosing panencephalitis. A 17-year-old white woman had an acute left maculopathy of unknown etiology. She was in excellent health and had only had rubeola at 3 years of age. Hruby lens examination of the left eye, visual acuity of 6/60 (20/200), revealed a normal vitreous, macular edema, intraretinal hemorrhage, and cotton-wool exudates. Xenon photo-coagulation was performed on the left eye. The visual acuity remained 6/60 (20/200) with drying of the retina. The patient remained in excellent health until 22 months after the initial ocular problem when she developed a left homonymous hemianopia. Then her mind deteriorated, and she became demented. We diagnosed subacute sclerosing panencephalitis after finding an increased spinal fluid gamma globulin, raised serum and spinal fluid titers of measles antibodies, and an electroencephalogram pathognomonic for this condition.


Horner's syndrome with ipsilateral accommodative paresis. In a 12-year-old girl with Horner's syndrome and an ipsilateral accommodative paresis, intravenous administration of edrophonium chloride improved the accommodative defect on several occasions, which suggested a possible relationship to myasthenia gravis. Additional testing of the accommodative paresis revealed some of the characteristics of Adie's syndrome and suggested a relationship to pupil-sparing Adie's syndrome.


Persistent pupillary membrane associated with aniridia. Familial aniridia is an autosomal dominant condition in which only a small iris remnant is present. A controversy exists as to whether the pathogenetic, embryologic origin of this condition is neuroectodermal or mesodermal. We examined a male infant with bilateral congenital aniridia associated with persistent pupillary membranes. This child had a prominent arcade of vessels extending onto the anterior lens surface for 360 degrees from small iris remnants in both eyes. The presence of a mesodermal pupillary membrane despite absence of the iris suggested a primary neuroectodermal defect as the pathogenetic factor in this case of aniridia.


Rapid access fluorescein angiography.

Rapid access fluorescein angiography. The time interval usually required for processing fluorescein angiography films has been dramatically shortened to 90 seconds by using Kodak Linagraph Shellburst Film 2474 processed in the automatic Kodak RP X-omat processing machine, with attendant increases in image clarity and contrast.


Nonfatal methazolamide-induced aplastic anemia. An 83-year-old man developed nonfatal aplastic anemia after taking methazolamide for three months. We made a diagnosis of methazolamide-induced aplastic anemia, discontinued all medication, gave the patient platelet and red blood cell transfusions, and treated him with oxymetholone. Approximately four months after initiation of treatment, the patient felt well, and he is currently receiving packed red blood cell transfusions every three weeks.


Cyclocryotherapy in neovascular glaucoma. To determine the long-term effects of cyclocryotherapy, we conducted a follow-up with a mean of 24.9 +/- 13.9 months in 50 eyes of 46 patients with neovascular glaucoma. On final examination, intraocular pressure in 16 (32%) of the eyes was greater than 26 mm Hg and in 17 (34%), less than or equal to 25 mm Hg; 17 (34%) developed phthisis bulbi. Enucleation was performed in three of the eyes. Anterior segment necrosis occurred immediately postoperatively in four eyes. Twenty-four of 41 eyes (58.5%) with vision lost light perception during our study. All patients were comfortable except the three who required enucleation.


Retinal surgery complicated by a spontaneously acquired factor VIII inhibitor. We studied a factor VIII inhibitor spontaneously occurring in an otherwise healthy patient who underwent retinal reattachment. The clotting defect first manifested itself as a delayed hemorrhagic choroidal detachment. His bleeding diathesis was successfully managed by infusion of factor VIII concentrate, prednisone, and cyclophosphamide. Surgical procedures in patients with severe bleeding disorders present a difficult therapeutic problem which can be effectively managed by the close cooperation of the surgeon, hematologist, coagulation laboratory, and blood bank.


Dilated episcleral vessels and open-angle glaucoma. We studied four patients with idiopathic dilated episcleral vessels. Three of these patients had asymmetric or unilateral open-angle glaucoma in the eye with the greater degree of episcleral vascular anomaly. The fourth patient showed dilated episcleral vessels, but the intraocular pressure (IOP) was not increased. In the three patients with increased IOP, the facility of outflow was decreased. The episcleral venous pressure was not measured, but in one eye Schlemm's canal was engorged with blood despite an IOP of 35 mm Hg. We explored the possibility of a congenital vascular anomaly in the four cases.


Oculodentodigital dysplasia syndrome with angle-closure glaucoma. A 14-year-old girl with typical oculodentodigital syndrome had been treated for chronic glaucoma for seven years. She had corneas measuring R.E.: 10 mm; L.E.: 9 mm, with narrow angles open on the right, but almost entirely closed on the left. Gonioscopic examination of the right iris revealed that the root was attached forward on the trabecular meshwork, which suggested a congenital anomaly. Peripheral iridectomies were ineffective. In a case previously studied, a 20-year-old woman with typical oculodentodigital syndrome developed typical acute angle-closure glaucoma seven years after the original examination.


Retinal depression sign indicating a small retinal infarct. Retinal depression, a newly observed sign, has been observed as an abnormality in the reflection from the internal limiting lamina produced by depression of the inner surface of the retina after a small retinal infarct. These depressions were first observed in 16 patients with sickling hemoglobinopathies. Additionally, I examined a patient with systemic hypertension, a patient with retinal arteriolitis, and a patient with juvenile onset diabetes mellitus who also had retinal depression.


Pigmented macular pucker.

Pigmented macular pucker. A 66-year-old woman developed a darkly pigmented preretinal membrane. In the fundus periphery there was a round retinal hole about one disk diameter with pigmentation in its immediate vicinity. Pigmented, preretinal membranes arise from retinal pigment epithelium cells that exit through a retinal tear and settle on the inner retinal surface where they proliferate and form a membrane. Some preretinal membranes arise from unpigmented cells such as glial cells and become colored with iron pigment because of the accumulation of pigmented macrophages and free pigment debris. A retinal hole is not necessary for the occurrence of a glial membrane.


Ocular perforation following retrobulbar anesthesia for retinal detachment surgery. We encountered three examples of the perforation of the globe by the retrobulbar needle in a series of 4,000 patients who had undergone retinal reattachment surgery with local anesthesia. The presence of significant myopia was a contributing factor in all three cases. We managed the perforation site through the detached retina with cryopexy and external tamponade, and we treated perforations through the attached retinas either with cryopexy at surgery or photocoagulation postoperatively.


Peripapillary pigmentary retinal degeneration. We studied four patients with peripapillary pigmentary retinal degeneration, an asymptomatic disorder that was probably benign and nonprogressive. The ophthalmoscopic appearance showed a segmental, grayish metallic sheen in association with bone spicule pigmentation, which radiated from the disk along the temporal vessel arcades and joined temporal to the macula. The optic disk, retinal vessels, periphery, and macula were normal in all patients. Visual function tests and fluorescein angiography indicated a segmental disease of the retinal pigment epithelium-photoreceptor complex.


Metastatic choroidal melanoma.

Metastatic choroidal melanoma. We studied the metastatic pattern of 41 patients initially referred with a primary choroidal melanoma who later developed widespread disease. In the order of frequency, the most common sites of metastatic involvement were the liver (56%), subcutaneous tissue (36.5%), and bone (7%). Whereas the median interval between enucleation and the onset of metastatic disease was approximately four years, in rare cases, metastases were diagnosed concurrently with a primary choroidal melanoma. Since patients with choroidal melanomas usually survive less than one year after the development of widespread disease, a metastatic examination should be done in all patients with pigmented choroidal tumors both before and after ocular therapy. From the data obtained in this and other studies on metastatic melanoma, a reasonable basic metastatic examination for choroidal melanoma patients should include a serum lactic dehydrogenase, a serum alkaline phosphatase, a routine chest X-ray, and a general physical examination.


Crystalline retinopathy.

Crystalline retinopathy. A 34-year-old woman had crystalline dystrophy of the retina associated with atrophy of the choriocapillaris and pigment epithelium, and pigment clumping in the fundus periphery. Consanguinity of her parents suggested an autosomal recessive inheritance pattern for this type of crystalline retinal dystrophy. The patient did not have corneal crystals. Her electroretinogram was normal, although her electro-oculogram was abnormal.


Stability of back-toric prism-ballast hydrogel contact lenses. We fitted each of 20 eyes with 3 different Hydrocurve contact lenses: (1) spherical with prism ballast, (2) back-toric without prism ballast, and (3) back-toric with prism ballast. We monitored the stability of the lenses. The prism-ballast lenses were generally stable on corneas with zero to 3.5 DK of with-the-rule toricity; the back-toric nonprism lenses were not stable.


Carel C. Koch Memorial Lecture--1977. Optometry-Ophthalmology--the future. In looking to the future of optometry and ophthalmology, the author identifies four interacting components--the public, optometrists, ophthalmologists, and eye-health-care manpower, including opticians--which he evaluates. The interactions are discussed, and specific recommendations are made to improve relations between the two professions,


Evaluation of 225 consecutive intraocular-lens implants. A retrospective study of the first 225 intraocular lens implants (IOL) performed by a single surgeon was conducted for this report. In complication rate and visual acuity assessed 4.5 months postoperatively, these patients (pseudophakes) compared very closely with 2 populations of aphakic patients who had had phacoemulsification surgery without lens implantation by the same surgeon. The majority of pseudophakes were left with moderate to low refractive errors. Patient satisfaction was found to be high. It appears that implantation of iris and capsular fixated intraocular lenses is a comparatively safe and in many cases advantageous procedure.


Water flow conductivity and pore diameter in extended-wear gel lens materials. The water flow conductivity of 3 high-water-content (70 to 85%) gel materials proposed for extended-wear contact lenses was measured. Pore diameter was calculated from these flow conductivities. High-water-content gels were found to have pore diameters in the range of 20 to 30 A compared with about 8 A for the lower-water-content HEMA gel. The larger pore diameter of extended-wear lenses will permit entry of drugs, hormones, and enzymes and thereby may pose new problems for wearers.


Julius F. Neumueller Award Paper--1977. Static fracture resistance of Schott S-1005 lenses as a function of thickness. High-Lite S-1005 lenses (Schott Optical Company) of various center thicknesses were tested for static load fracture resistance. Chemically tempered High-Lite lenses of 1.7-mm center thickness were found to be equivalent in strength to 3.0-mm heat-tempered crown lenses; 1.34-mm chemically tempered High-Lite lenses were equivalent in strength to 2.07-mm heat-tempered crown lenses. These findings agree closely with earlier data on chemically tempered crown glass and therefore illustrate that chemically hardened lenses can be made significantly thinner than Z-80 specifications and still meet FDA strength requirements.


Recording monocular VEPs under binocular conditions. This report describes a technique for recording the visual evoked potential (VEP) arising from 1 eye under conditions of binocular pattern stimulation. The subject views a sinusoidally modulated vectographic checkerboard with orthogonally oriented polarizing filters before the eyes. This technique results in waveforms that contain monocular VEPs distributed in time. The technique is sensitive to interocular suppression and controls for the influence of various extraneous sources of variability. It is useful in clinical VEP testing.


A foot-operated camera trip for the Nikon photo slit lamp. A simple foot-operated shutter cable frees both hands for holding the gonioscope lens and adjusting the Nikon slit lamp during photography of the recess of the anterior-chamber angle.


Dose-response effects of corneal anesthetics. With double-masking procedures, the dose-response curves for 0.1, 0.2, and 0.4% benoxinate and 0.125, 0.25, and 0.50% proparacaine hydrochloride were determined by monitoring changes in corneal touch threshold after applying each anesthetic. The level of corneal anesthesia necessary for applanation tonometry was also determined. The maximum increase in threshold that could be measured following instillation of 50 microliter of the drug was 200 mg/mm2 All 6 anesthetic solutions produced this amount of decreased corneal sensitivity. Recovery from the anesthetic was exponential for all concentrations; however, the lower doses had the shortest duration. For applanation tonometry, the corneal threshold for touch must be 75 mg/mm2 or higher. We conclude that a quarter to a half of the commonly used anesthetic dose is sufficient for routine tonometric evaluation.


Rod and cone contribution to the EOG ratio. The EOG ratio is an established clinical test of retinal function. Since its development by Arden and coworkers in 1962, it has been thought of as simply a rod-medicated response. Using scotopically matched red and blue lights, we found a 24% larger response to the red light than to the blue light, establishing that a cone contribution exists in the EOG ratio of normal subjects.


Corneal temperatures--a study of normal and laser-injured corneas in the Dutch belted rabbit. Air Force laser safety standards are developed from laser-exposure data obtained in studies using experimental  animals and from biomathematical modeling procedures. Interpretation of research data and predictive modeling calculations are enhanced by knowledge of the temperature values of the tissue absorption sites. Corneal temperature values for the normal, the anesthetized, and the laser-injured Dutch belted rabbit are presented and compared with values obtained in other studies. The corneal temperatures were measured by infrared radiometry.


Prevalence of trachoma among Navajo Indian children. Examination of some 6000 Navajo children in their schools in the Shiprock, New Mexico area between 1975 and 1977 yielded an overall prevalence of trachoma of 2.4%. The prevalence was highest for high schoolers (3.8%) and lowest for preschoolers (2.3%). These prevalences are lower than those found (6.0%) for Navajo schoolchildren in the Gallup, New Mexico area 8-9 yr previously.


Changes in tear flow accompanying aging. The tear-turnover rate of 68 normal human subjects (age range 15-63 yr) was determined using a slit lamp modified to serve as a fluorophotometer. Tear volume and tear secretion, computed from tear-turnover rate, had mean values of 8.47 microliter and 1.78 microliter/min, respectively. Analysis of the results shows a decrease in tear production with age. The mean tear-flow rate was 1.55 microliter/min in subjects aged 15-39 and 0.95 microliter/min in subjects aged 40-63. This fluorophotometer is adaptable to a clinical setting and may prove useful in diagnosis and treatment of anomalies of tear production.


Changes in hydrogel contact lens power due to flexure. When a hydrogel lens is placed on the eye, its power may change because of flexing of the lens. The correcting power of the lens when on the eye can be calculated by assuming that the lens flexes to the shape of the underlying cornea. Actual measurements of the correcting power of Hydrocurve lens on the eye were not in agreement with the calculated values. Assuming that the front and back surfaces of the lens flex by the same amount, the presence of a fluid lens between the hydrogel lens and the cornea would account for this discrepancy. For minus lenses of moderate and high power, it was found that the change in power was in the direction of more plus; for low minus and all plus lenses, the change was in the direction of more minus. Under the conditions of the present investigation, correcting power measured with the lens on the eye was in agreement with the calculated value for regular-thickness Hydrocurve lenses of -2.00 D and thin lenses of -0.75 D. This is interpreted to mean that lenses of these powers conform to the shape of the cornea so that the fluid lens is thin and plano. The clinical implications are discussed.


Accommodation as a function of object form. The steady-state, monocular accommodation resposne to sinusoidal grating targets was assessed as a function of the spatial frequency of the grating and its vergence at the eye, using a laser optometer. At all levels of accommodative stimulus, the response was found to be dependent on grating frequency. At very low frequencies, the response was often substantially in error and was closely related to the accommodation exercised by the observer when viewing an empty field. At  higher frequencies, the response became more accurate. Possible models for accommodative strategies underlying the experimental results are discussed. A model involving dynamic evaluation of the changes in retinal-image modulation produced by accommodation fluctuations for  many features of the observations.


Light transmission of hydrogel contact lenses. The visible-light transmission of various Bausch & Lomb Soflens contact lenses and HydrocurveTM contact lenses was measured with a Perkin-Elmer model 202 UV spectrophotometer. The light transmission for both types of lenses ranged from 96-99%, and was almost constant over the visible spectrum. Neither the power, the thickness, nor the posterior apical radius of the lenses had a  significant effect on the amount of light they transmitted.


Thickness of human cornea measured by topographic pachometry. In the hands of trained user, the topographic pachometer proves to be  an instrument of acceptable clinical precision (standard deviation = 0.006mm). An examination of corneal thinning during waking hours revealed a rate of thinning which was greatest upon lid opening and which declined  uniformly throughout the day (p = 0.01). An investigation into menstrually related change in corneal thickness revealed that at least 122 subjects would be required to investigate this change on an acceptable statistical basis (p = 0.05).