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Report of program activities : National Institute of General Medical Sciences (Volume 1972) online

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number of awards since 1970, the NIGMS proportion of all NIH awardees remained
constant from FY 67 to FY 71. During these years, the NIGMS supported 80 per-
cent of all NIH awards to anesthesiologists. Since that time, all Development
Award applications received from anesthesiologists have been assigned to the
NHLI, and for the first time in five years the number of Awardees supported
by the NHLI will exceed the number supported by the NIGMS.

Clinical Anesthesiology : On June 30, 1972, the 29 clinical anesthesi-
ology training grants supported by the NIGMS were phased out. It was felt that



36



if the Institute is to have a future role in clinical training, its emphasis
should be on the improvement of quality rather than simply adding to the
number of practicing physicians in anesthesiology or any other specialty.

Radiology : The radiology research training program of the Institute
is relatively new and has only recently begun to provide trained manpower for
academic radiology. Unfortunately, enough trained competent investigators
simply do not exist in radiology to support the large expansion of research
efforts needed, and a large infusion of research funds without associated
training support would not solve the problem. At this time, there is a need
to provide small grants for the initial funding of the research of trainees
who have just recently completed their training. Another problem is the lack
of breadth of research by radiologists, who tend to limit their efforts to
the investigative modalities which are available to practicing clinical
radiologists. Closer liaison with basic science disciplines and more oppor-
tunity and encouragement to take course work in research methodology, statis-
tics, experimental design, advanced mathematics, and in the basic sciences
should help to overcome this difficulty.

Important research progress has been made in developing accurate
methods for computer processing of radiological data and has led to more
rapid retrieval of information by clinicians. Basic research on radiological
imaging systems has also resulted in improvements in equipment and technique
and has greatly reduced the hazards of overexposure of patients to radiation.

The funds awarded have been relatively constant at approximately
$1.8 million, increasing by $47,000 during the current year. No new grants
were awarded during the past year. Twenty-three grants (14 in diagnostic
radiology and nine in nuclear medicine) were active, supporting 124 post-
doctoral trainees and two predoctoral physics students. Three diagnostic
radiology training grants terminated June 30, 1972.

Through June 30, 1971, a total of 221 trainees had been appointed
for periods longer than six months, of whom 64 are now in academic positions,
35 are in non-academic work, 24 are in the military, two are unknown, one is
deceased, and 95 are still in training.

Within the fellowships program seven postdoctoral and special fellow-
ship awards and one research developmental award were made. This is an in-
crease of five over last year. Dr. David Shames, Department of Radiology,
University of California, San Francisco Medical Center, represents the first
diagnostic radiologist recipient of an NIGMS Research Career Development Award.

Surgery : From the surgery research training program there is emerging
a cadre of well-educated clinical scientists with an effective combination of
basic science and clinical competence. The goal of the training is develop-
ment of a surgeon, who not only delivers excellent patient care but also is
sufficiently curious to seek and recognize through laboratory and clinical
investigation the solution to problems in human biology as related to surgery.
Surgical scientists have made significant contributions in gastrointestinal
physiology, coagulation, biochemistry, and immunology. A significant portion
of the trainee's program involves study in basic science with opportunity

37



provided for research during the clinical training years.

In the funding of surgery training grants, there has been a decline
from the maximum of 32 programs supported in 1969-1970, to 30 programs active
in 1971-1972. Five additional training programs will terminate June 30, 1972.
Of the 30 programs, nine programs were reviewed for continued support begin-
ning July 1, 1973. One of these was disapproved. Unless additional awards
are made, the number of active programs will total 24 by the end of June 1973.

From the beginning of this program to June 30, 1971, 294 trainees
have been supported for a period of six months or more. Of these, 79 are now
in academic positions, 32 are in non-academic work, 30 are in the military,
the positions of six are unknown, one is deceased, and 146 are still in train-
ing. Although this is a postdoctoral program, trainees may earn advanced
degrees. To date, 12 Ph.D. degrees have been awarded in physiology, micro-
biology, biophysics, biomedical engineering, immunology, and surgery. One M.S<
degree has been awarded in surgery and physiological chemistry. One hundred
and thirty postdoctoral trainees were appointed during the past year.

Future directions for this program include an increasing emphasis on
the multifaceted problem of trauma. We hope to direct this interest not only
to a basic understanding of the mechanisms of injury and repair, but also to
improved methods of care for the trauma victim including initial treatment
and prompt evacuation, definitive therapy at appropriate centers, and adequate
rehabilitation. To this end, closer liaison between trauma research centers
and surgery training grants is being encouraged and increasing emphasis will
be placed on programs offering significant improvements in the care of the
critically ill.

The following five schools which have Trauma Research Centers funded
by NIGMS , also have surgery research training grants in the academic surgery
training program:

*Columbia Presbyterian Medical Center
New York, New York

Focus: Studies of human energy exchange and changes
in body metabolism following severe trauma

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania

Focus: Shock at the cellular level

*University of Texas Southwestern Medical School
Dallas, Texas

Focus: Comprehensive baseline studies on the
traumatized patient

^^University Hospital, Boston University Medical Center
Boston, Massachusetts

Focus: Correlation of pulmonary function with hormone
metabolism and intracellular chemistry in
trauma and shock



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San Francisco General Hospital

University of California, San Francisco

San Francisco, California

Focus: A multidisciplinary approach to trauma

combining clinical and animal studies in
the areas of wound healing, coagulation
and microcirculation changes, and pulmonary
changes following positive pressure ventilation •

*It is noteworthy that three of the principal investigators' of trauma centers
are program directors of academic surgery training grants as well. In 1971-
1972, approximately 30 trainees were appointed to training grants in these
five schools.

Special fellowships in the area of trauma dropped from 14 awards
last year to only five in FY 72, and of these two were new awards. Eleven
fellows presumably completed their training in FY 71. RCDA support was
continued for Dr. Leena Mela, Department of Surgery, at the University of
Pennsylvania, whose work in trauma was first supported by this Institute in
FY 71. The small number of NIGMS Awardees in diagnostic radiology and trauma
reflects a virtual absence of applications in these areas up to the present
time. However, applications for RCDA's in both areas are scheduled for
review during FY 73. Thus, it is anticipated that the number of Av/ardees in
diagnostic radiology and trauma may double during the coming year.

Staff has been active in stimulating an assessment of the continued
needs for research-trained manpower. On September 10, 1971, a meeting of the
surgery training program directors was held in Bethesda, Maryland, to review
the future status of surgery training grants and the appropriate role they
play in the training of academic manpower. The participants identified the
need for small research grants, available to recent graduates of the training
program, before they have had time to establish themselves and apply for
support through the usual channels. It was noted that while there was no
shortage nationally of physicians doing surgery, board qualified surgeons
were still in short supply and academic surgeons especially so. A factor
which tends to increase the demand for academic surgeons is the relatively
short period that a surgeon scientist remains creative and productive in the
laboratory. After 10-15 years, the majority become laden with administrative
responsibilities. The academic needs for surgical manpower and research will
be further evaluated by a comprehensive study ("SOSSUS Evaluation of Surgical
Research" contract) initiated at the end of FY 72.

As an outgrowth of the Program Directors' meeting, the Surgery
Training Committee and the NAGMS Council recommended minor revisions in the
Guidelines, initially written in February 1966, to conform to policy and
program changes which have taken place since that time.

A meeting of the Program Directors of the diagnostic radiology
training grants program was held January 17-18, 1972. The evaluations were
made of the existing programs as to accomplishments, trends and future needs.
It was recommended that the program be not only continued but expanded to



39



achieve the goal of adequate staffing for all departments of radiology in the
nation's medical schools.

"Research Training in Radiology," a report written by the Radiology
Training Committee in June 1971, was published by the Government Printing
Office during the current year. Approximately 2,000 copies were distributed
to interested persons. It is believed that this is a reflection of the
current interest in manpower in this discipline.

The following chart shows training and fellowships awards for FY 72
that directly relate to the existing research centers and program projects.

Research Research
P.P & Centers Training Career
Area Grants Grants Fellowships Awards

Anesthesiology 7 7 2 3

Diagnostic P^.adiology 5 4 11

Trauma 10 5 4 1

C. Research Highlights

J. Bunker, Stanford University School of Medicine ,
Stanford, California, GM 12527

"Teratogenicity of Anesthetics "

Demonstration that inhalation anesthetics produce teratogenetic
responses in both avian and mammalian species has raised concern as to their
effects in an estimated 50,000 women in the United States who annually under-
go surgery and anesthesia during gestation. Dr. Bunker and his team of in-
vestigators have recognized that a second group of women are also exposed to
the effects of inhalation anesthetics. These are the nurses and anesthetists
who work daily in operating rooms, contaminated with trace concentrations of
these gases. Studies recently completed at Stanford University confirm a
contamination of the operating rooms with waste anesthetic gases, and indicate
an increased spontaneous miscarriage rate in operating room nurses and female
anesthetists which is 2.9 and 3.7 times the control group. Also, it was
shown that an 85-90 percent reduction in the concentration of waste anesthetic
gases found in the operating room atmosphere can be achieved through the use
of appropriate scavenging devices. Such devices attached to the exhaust valve
of the anesthesia machine can readily be installed in most operating rooms at
nominal cost. These devices are being used in many of the hospital operating
rooms and delivery suites throughout the country.



40



i J. Bonica, University of Washington Medical Center^ Seattle,

Washington, GM 15991

"Pain; Where Does It Hurt?"

"Pain: Where Does It Hurt?" is an NBC hour long documentary pre-
sented to TV audiences in 1972„ It received the greatest public response of
any documentary in the history of NBC. On the basis of the NIGMS brochure,
I Pain , and the Institute's film. Threshold , the documentary was developed
'around Dr„ Bonica 's pain center. The research involving the patients in this
center is supported under the anesthesiology research center grant. This
research involves (1) developing more precise measurements of the pain ex-
perience in both the clinical context and the laboratory and (2) evaluating
the effects of morphine, aspirin, placebos, and hypnosis on pain. This group
of investigators is currently studying the effects of diazepam on the tolerance
of tourniquet pain and state of anxiety during pain. The drug and a matching
placebo are administered in two separate experimental sessions. State of
anxiety during time in pain increases over time when subjects have taken the
placebo but decreases substantially over time in pain when subjects have taken
diazepam. Diazepam leads to significantly greater pain tolerance times than
does the placebo.

W. K. Hamilton, University of California, San Francisco, California,
GM 15771



"Evaluation of New Anesthetic Agent, Forane"

I

Dr„ Eger, one of the investigators in this program-project on
anesthesiology, has been evaluating the new agent, Forane,



Currently used anesthetic agents have a remarkable record of safety
when the degree of drug depression necessary to produce general anesthesia
for surgical procedures is considered. However, there are inherent and
seemingly unavoidable side effects which cause a continuing search for new and
better agents with which to provide anesthesia. A series of seven articles in
the July 1971 issue of Anesthesiology report several of the initial studies of
this team with the proposed new agent. The investigations have been carried
out in laboratory animals and man and have now progressed to the stage of
clinical trials. The new drug boasts several potential advantages, e.g.,
cardiac output is maintained at control levels, and the heart does not appear
to be sensitized to epinephrine. Further, the drug does not appear to undergo
metabolism in the body. Evaluation of this new agent is greatly enhanced by
critical comparison with currently used anesthetic agents using techniques
kjorked out by Dr. Eger under previous support by this grant. A good deal of
"further information must be gathered before the drug is declared available for
regular operating room usage.



41



H. N. Wagner, Johns Hopkins University, Baltimore, Maryland,
GM 10548

"Rapid Antibiotic Sensitivity Testing"

Dr. Wagner and his team of investigators, working in the radiology
research program-project, have developed a new and accurate method for rapid,
automatic radiometric testing of antibiotic sensitivity within three hours
following inoculation of a culture medium. This is compared to the conven-
tional tube dilution technique of antibiotic effects on bacterial growth which
has taken 48-hours to complete in most laboratories. The radiometric method
measures the amount of radioactive COo generated by the bacterial metabolism
of ■'•^C-glucose in the presence of antibiotics. Antibiotic effect on bacterial
growth is standardized by measuring the evolution of ■'-^C02 three hours after
inoculation. The accuracy of the two methods run in parallel and therefore,
the use of the radiometric method would permit early administration of the
proper antibiotic in such life-threatening conditions as septicemia.

K. Rossmann, University of Chicago, Chicago, Illinois, GM 15806

"Improved Angiograms Make Cerebral Pathology More Detectable"

It has been shown from physical measurements and clinical radiographs
that the sharpness of cerebral angiograms can be improved significantly by
using a combination of slow intensifying screens and fast film rather than the
commonly used combination of fast screens and film of normal speed. The
resulting increased visibility of smaller blood vessels makes it feasible to
study their diagnostic significance. No degrading effects due to poor screen-
film contact and motion of the film changer were observed. Other methods of
improved image processing are being continued in the new research center grant
awarded to Dr. Rossmann in June, 1972.

R. H. Egdahl, Boston University Medical Center, Boston,
Massachusetts, GM 17366

"Accurate and Rapid Correction of Hyperglycemia Following Shock"

Hyperglycemia is a common entity of the shock syndrome. Patients
admitted to the hospital with severe burns or in hemorrhagic shock are
routinely given insulin and glucose despite the fact that relatively few
data are available to suggest exactly how this should be done. Dr. Egdahl
and his associates have devised a method for directly measuring insulin se-
cretion rate in man. This is of great importance in understanding the dynamics
of the insulin system. Previous studies have been based on measurements of
insulin concentrations in the peripheral blood. These are not considered true
measurements since pancreatic insulin enters the portal venous system where it
is altered by the liver secretions. The Boston University group has devised a
technique in which cannulas are placed in the umbilical and portal veins per-
mitting measurement of blood flow and insulin secretion. Using a continous
infusion of lipiodol, it is possible to accurately measure portal blood flow;
and this, multiplied by the portal insulin concentration, provides the means
for determining insulin secretory rate. Currently this method is used to
measure effects of epinephrine, corticosteroids, and other critical hormones on

42



insulin secretion during hemorrhagic shock. The investigators conclude that
hyperglycemia results from epinephrine release, which inhibits insulin release
from the pancreas. Another conclusion drawn is that the adrenal medullary se-
cretions inhibit glucose assimilation in shock, irrespective of the effects of
corticosteroids. Findings suggest the use of adrenergic blocking agents might
be a rational approach to increasing glucose assimilation. Continued research
in this area should provide information on which vital decisions regarding treat-
ment can be made .

S. Powers, Albany Medical College, Albany, New York, GM 15426
"Electronics Help Prevent Shock Deaths"

About 70 victims of severe trauma have been saved from possible death
at the Albany research center because of the collaborative efforts of physicians
and computer scientists. They have found through the use of electronic equip-
ment a way to predict the occurrence of post-traumatic pulmonary distress syn-
drome, the most frequent cause of death following physical injury. The electronic
equipment in the one-bed trauma room was developed by biomedical engineers at
nearby Rensselaer Polytechnic Institute and is used to measure a patient's vital
processes. Through the use of high speed computer analysis the results are re-
turned within minutes to the bedside physician, permitting him to apply life-
saving measures. Although the initial cost for developing the trauma room was
high. Dr. Powers feels it can now be duplicated at a fraction of this cost.

F. W. Blaisdell, University of California, San Francisco,
California, (M 18470

"I.V. Phosphate Possibly Eliminates Need for "Fresh" Blood Transfusions"

Recent studies have suggested that fresh blood should be used to
transfuse patients suffering from post -traumatic shock, in which there is an
oxygen deficiency in the tissues. This is because blood stored in usual liquid
preservative for over seven days will increase its capacity to hold onto oxygen,
theoretically diminishing the red cell's ability to deliver oxygen to the
tissues. At this new research center. Dr. Blaisdell and his team have been
successful in restoring the red blood cell's ability to unload oxygen by in-
fusing a simple inorganic phosphate solution. If further studies confirm
these findings, it would permit the use of banked blood which is currently the
only blood readily available for emergencies.

II. Program Administration

During FY 72, the Institute continued to develop high quality programs
! in each of the defined clinical science areas. It was evident that in order
to have strong programs in trauma and anesthesiology the Institute should
support more individual projects with basic research orientation. Although a
larger number of trauma project proposals were received, relatively few of
these were considered of adequately high scientific merit. Also, the cate-
gorical focus of these applications precluded primary assignment to this
Institute. It became obvious that better lines of communication are needed
within the NIH as well as with the scientific community. As a result, a new
f) set of referral guidelines for trauma were prepared in the hope that they will

43



more clearly define trauma and its continued role in the program of the NIGMS.

The status of the anesthesiology program revealed very little change
in the numbers and dollars of grant support from the previous year. No new
applications for anesthesiology research centers or program-projects were
received and individual projects were considered primarily on the basis of
their categorical focus. It therefore appeared that the Institute should con-
centrate on some specific areas of anesthesiology as a discipline. Renewed
interest occurred in the area of pain research, and support was afforded for
a pain symposium. The area of acupuncture research was assigned to the Insti-
tute by the Director, NIH, and plans made for a two-day acupuncture meeting
at NIH July 17-18, 1972. There is continued interest in the pharmacokinetics
of anesthetic agents, in new instrumentation for inducing and monitoring anes-
thesia, in management of respiratory emergencies arising from inhalation
therapy, and in the relationship of projects in anesthesia and diagnostic
radiology with trauma research.

In diagnostic radiology, efforts were concentrated on the development
of a research center which would be worthy of support. The fruits of these
labors were the awards for the two research centers. Activation of new indi-
vidual projects in diagnostic radiology has continued at a steady pace.

This was a year to put the center concept to test. With major support
of large program-projects and centers in the clinical programs and with an
appreciable number of these having renewals at this time, it was felt that an
adequate appraisal could be made. Consequently, a more critical look was
taken of the review mechanism as well as the applications being reviewed.

The General Medical Program-Project Committee devoted its October 1971
meeting to a discussion of research centers. The primary objective was to
formulate opinions and advice which could be used by staff in developing better
guidelines for the Committee and site visitors. It was the opinion of the
Committee that the major shortcoming of centers and program-projects relate to
the inadequate preparation of proposals for such large programs. Although a
careful review compensates in part for this deficiency, poor research may be
more difficult to identify. This problem solving can best be achieved by
more careful scrutiny for scientific excellence plus adequacy of administra-
tive and environmental aspects.

Suggestions to improve quality control included the use of NIH con-
sultants in teams as monitors, the appointment by the center director of an
extramural committee of peers which might or might not submit reports to NIH
stating deficiencies and corrective actions, the use of a review group com-
posed of senior scientists from the applicant's own institution, and desig-
nation of grant funds to support frequent reviews by scientists chosen by the
Director. The notion that centers should be problem oriented (e.g., "Trauma")
rather than discipline oriented (e.g., "Anesthesiology") was mentioned.

It was felt that attempts to coordinate all center research nation-
ally to avoid duplication should be encouraged, and that requirements for
fixed ratios of basic to clinical science projects were not realistic. Rela-
tionships of a center to the university, medical school, and hospital should

44



>



be "excellent" and "subservient," and these relationships, which form an
important aspect of the proposal, should be explored in depth during the site
visit. A center represents a kind of conglomerate of program-projects designed
to study problems of broad scope through a team approach. Both program-projects
and centers were designed to meet national health needs through training and
research, creating high visibility, "forced" cooperation, and core facilities,


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