4. TABLE OF CONTENTS
From the Editor
Clinical
Intrauterine insemination versus Fallopian
tube sperm perfusion in non-tubal infertility
A case report: treatment of a medial
condylar humeral fracture in an adult with
osteopetrosis
Review / Commentary
Stress-only nuclear myocardial perfusion
imaging
5. Can we skip the autopsy?
The fundamentals of courage
Omega-3 fatty acids, red yeast rice, and
sudden cardiac death
New Android Applications
Android Apps from the Internet Medical
Association
6. FROM THE EDITOR
What is the price of a medical education?
Whether at the start of our career, or near
the end, we all must pay a constant price in
order to stay up-to-date and well educated.
It takes time, energy, and focus to become
an expert.
With the goal of helping our readers become
experts in their chosen field, the Internet
Medical Association is producing a series of
mobile apps. The apps contain the latest
news, research, and publications in the
specialty. A suggested plan to become and
expert, and to maintain expert status is this:
7. 1. Daily read the news in your specialty.
2. Weekly read the latest research.
3. Monthly read one best selling or new
publication in your chosen specialty.
This system of constant nourishing of the
mind with important information in your
chosen specialty ultimately will allow the
novice to become an expert, and the expert
to continue to be a leader in the field.
This month features two clinical articles
from India, one on intrauterine insemination
and the other on orthopaedic surgery. This is
followed by three review articles and an
essay on courage. Finally, there is a listing
8. of new Android Apps that the Internet
Medical Association has recently published.
We are pleased to welcome Dr. Gulab Singh
Shekhawat as a contributing editor this
month.
Please send us your article submisstions,
comments, or suggestions. We look forward
to hearing from you.
Tom Heston, MD, Editor
9. INTRAUTERINE INSEMINATION
VERSUS FALLOPIAN TUBE SPERM
PERFUSION IN NON-TUBAL
INFERTILITY
AUTHORS: Dr. Col (Retd) G S
Shekhawat, MD(Obst & Gyn) *
(Corresponding. Author), Dr Priyanka S,
MBBS+
PLACE OF RESEARCH WORK:
Assisted Reproductive Technology center,
Armed Forces Medical College/ Command
Hospital (Southern Command), Pune-
411040 and 92 Base Hospital PIN -901218
C/O 56 APO
ADDRESS OF THE AUTHORS:
10. * Associate professor, Dept of Obstetrics &
Gynecology, Smt Kashibai Navale Medical
College, Narhe, Pune-411041, Maharashtra.
Email: gsshekhawata@yahoo.co.in, Tel :
( M) 9372897090,
+Medical Officer, Smt Kashibai Navale
Medical College, Narhe, Pune-411041,
Maharashtra.
INTELLECTUAL CONTRIBUTIONS:
Study concept: Dr G S Shekhawat
Drafting and Manuscript revision: Dr
Priyanka S
11. Statistical analysis: Dr Priyanka S
Study supervision: Dr G S Shekhawat
ABSTRACT:
Background: Controlled ovarian hyper
stimulation (COH) combined with
intrauterine insemination (IUI), using a
volume of 0.5 mail of inseminate is
commonly offered to couples with non tubal
infertility. Another method is Fallopian tube
sperm perfusion (FSP) which is based on a
pressure injection of 4 ml of sperm
suspension while attempting to seal the
cervix to prevent semen reflux. This
technique ensures the presence of higher
12. sperm density in the fallopian tubes at the
time of ovulation than standard IUI. The
aim of this study was to compare the
efficiency of IUI and FSP in the treatment
of infertility.
Methods: 200 consecutive patients with
infertility in 404 stimulated cycles were
included in the study. Those randomized to
standard IUI included 100 patients in 184
cycles [158 Clomiphene citrate/human
menopausal gonadotrophin cycles and 26
Letrozole/FSH cycles exclusively for
polycystic ovarian disease patients] (group
A). Patients subjected to FSP included 100
patients in 220 cycles (193 Clomiphene
citrate/human menopausal gonadotrophin
cycles and 27 Letrozole/FSH cycles
13. exclusively for polycystic ovarian disease
patients] (group B). Swim up semen
preparation technique was used in all cases.
Insemination was performed in both groups
34-37 hours after hCG administration.
Standard IUI was performed using 0.5 ml of
inseminate. In FSP 4ml inseminate was
used.
Results: In group A (184 IUI cycles in 100
patients), 22 clinical pregnancies (presence
of gestational sac with fetal cardiac activity)
occurred (11.95% per cycle over four
cycles). In group B, (220 cycles of FSP in
100 patients), 48 clinical pregnancies
occurred (21.81%per cycle over four cycles)
and this difference was statistically
significant (p<0.05).
14. Conclusions: For non-tubal sub fertility, the
results indicate clear benefit for FSP
(Fallopian tube sperm perfusion) over IUI
(Intrauterine insemination).
Key Words: Intrauterine insemination,
Fallopian tube sperm perfusion, Non-tubal
infertility.
Introduction
Intrauterine insemination (IUI) with mild
ovarian stimulation has been used for many
years in the treatment of non tubal
infertility. During IUI, pretreated semen is
concentrated in a small volume of 0.5 ml
and deposited by a catheter into the uterine
15. cavity. The overall pregnancy rates reported
in the literature ranged from 5.7% to 17.7%
per cycle [1]. Although the number of
available oocytes can be increased by
ovarian stimulation, the pregnancy rates in
IUI are still not promising, mainly because
of suboptimal spermatozoa at the site of
fertilization [2]. An alternative procedure,
termed Fallopian tube sperm perfusion
(FSP), has been reported with improved
pregnancy rates in comparison with IUI [3,
4, and 5]. In FSP, sperm preparation is
identical to that used in IUI, but the
spermatozoa are diluted in a larger volume
of medium up to 4 ml [6]. This volume has
been considered sufficient for bilateral
passage of the spermatozoa through the
fallopian tubes. Theoretically, this would
16. increase the density of capacitated
spermatozoa near the oocytes and result in
higher pregnancy rates. A prospective
randomized study was designed to
determine whether FSP resulted in higher
pregnancy rates than IUI.
Material & Methods
Two hundred infertile patients, aged 17 to
39 years, undergoing 404 consecutive cycles
of ovarian stimulation were studied from
June 2007 to Jan 2009. Institutional board
approval was obtained. These patients
underwent a basic infertility workup
including confirmation of tubal status by
hysterosalpingogram or laparoscopy and
hormone profile including serum follicle
17. stimulating hormone (FSH), luteinizing
hormone (LH), prolactin and thyroid
hormone tests. Menstrual cycle day 3 basal
transvaginal ultrasonography was done in
all cases to rule out ovarian cysts prior to
ovulation stimulation. Exclusion criteria
were age > 39 years, obstructed fallopian
tubes and cases with marked oligospermia
sperm count<10X106per ml).
The patients were classified for purpose of
etiology of infertility as having mild and
moderate endometriosis; ovulatory disorders
(hormonal profile and transvaginal
sonography characteristic of polycystic
ovarian syndrome); cervical hostility (poor
properly timed post-coital test); male sub
fertility (as per WHO criteria) [7];
18. unexplained infertility (where no infertility
causes were found).
These patients underwent ovulation
induction with either Clomiphene citrate
and Human menopausal gonadotrophin (351
cycles in 174 patients) or Letrozole and
FSH used exclusively for polycystic ovarian
disease patients (53 cycles in 26 patients).
The ovarian stimulation protocol of
clomiphene and hMG (Human menopausal
gonadotrophin) was used in 170 patients. It
consisted of clomiphene citrate 100 mg
daily on days 3-7 of the cycle, and 75 IU
daily of hMG (Human menopausal
gonadotrophin) on days 6-9 of the cycle.
For some of the women, hMG was
increased to 150 IU in subsequent cycles,
19. depending on the previous ovarian response.
Rotterdam ESHRE consensus workshop
criteria (2003) was used for diagnosis of
PCOS. In all PCOS patients (26 patients),
who had been on Metformin 500 mg t.i.d ,
Letrozole was given orally in a dose of
2.5mg/day for 5 days starting from day 3 of
a spontaneous or progesterone induced
menstrual bleeding . Inj purified FSH 75 IU
administered on 6-9 day of menstrual cycle.
Cycles were monitored from day 9 onwards
by transvaginal ultrasound measurement of
the number and diameter of the growing
follicles along with the thickness and
morphology of the endometrium. A dose of
10,000 IU human chorionic gonadotrophin
(hCG) was administered when at least one
20. leading follicle had reached a diameter of 18
mm and at least 8 mm endometrial thickness
with tri laminar ‘halo’ appearance seen.
Patients were called 34 to 36 hours later,
and either standard IUI (group A: 184 cycles
in 100 patients) or FSP (group B: 220 cycles
in the 100 patients) was performed. The
patients were counseled about the two
alternative procedures and informed
consents were obtained before
randomization. Patients were allocated
randomly to standard IUI or FSP on the day
of insemination in the first cycle itself,
according to even or odd serial number in
the register. Maximum of four cycle
treatments of IUI or FSP were considered
for those patients who could not conceive in
previous attempts. However those who
21. failed to conceive with IUI were offered IUI
only and vice versa.
132 male partners were normozoospermic
with count > 20X106 sperm per ml, >50%
motile with forward progression (categories
a and b) within 60 min of ejaculation and >
60% morphologically normal spermatozoa
(WHO criteria) [7]. Male partners with
sperm count ranging from 10X106 to
20X106 were asked to produce a second
semen sample within 2 hours of the first
sample on the day of insemination. Sixty-
eight males having sub fertility as per WHO
criteria did consent to the study. However
04 could not produce a second sample at the
time of IUI, and 1 patient had total sperm
immotility and was excluded from the study.
22. A fresh ejaculate was delivered in a sterile
60 ml jar by masturbation on the day of
insemination. Neat semen was left at room
temperature for liquefaction for 30
minutes.The liquefied semen samples were
analyzed for density and motility using a
fixed-depth counting chamber (Makler).
The liquefied ejaculate was transferred to a
labeled sterile 14 ml round-bottomed
disposable centrifuge tube (Falcon No.2095)
and 4 ml flushing media (Medicult) added
to it. After thorough mixing the sample was
centrifuged at 5000 rpm for 10 minutes.
Then, the supernatants were discarded and
the pellet was resuspended and mixed in 3
ml of fresh flushing media (Medicult) and
centrifuged for second wash again at 5000
rpm for 10 minutes. Once again the
23. supernatants were discarded. Each pellet
was now gently layered with 0.5 ml for IUI
and 4 ml for FSP of universal IVF media
(Medicult), and incubated at 37oC in a
humidified incubator with 5% Carbon
dioxide for 1 hour. Post wash semen
analysis was done in all cases using
Makler’s counting chamber before
insemination.
Intrauterine insemination was performed
with conventional catheter using 0.5 ml of
inseminate. To eliminate dead space
problem, IUI catheter was first attached to
syringe and then inseminate was aspirated.
In FSP 4ml inseminate was used and
backflow of inseminate was occluded at the
cervical opening by the long size Allis
24. clamp (Figure-1), which was suitably
modified by attaching cervical occluding
prongs with rubber cushions to avoid
trauma to the cervix and was kept in place
for about 3 to 4 minutes after insemination.
In both groups, the patient rested for 30
minutes after insemination and received oral
micronized progesterone 100 mg, two
tablets per day for luteal-phase support.
Values were recorded as mean ± SD using
Microsoft Excel version 4. Statistical
analysis were performed using student’s t-
test for testing significance of difference
between the means and the X2test to
compute p-values for testing the agreement
between proportions. MedCalc statistical
software (Meriakerke, Belgium) version
25. 9.5.0.0 was used for all statistical analysis.
The significance was defined as p < 0.05.
Results
The patient characteristics for group A and
B were not significantly different
concerning patient’s age (28.42 ± 2.78 years
and 28.19 ± 2.80 years), type of sterility
(primary infertility 74% versus 72%
respectively) and duration of infertility (5.6
± 2.1 and 5.3 ± 1.9 years respectively). The
clinical indications for IUI or FSP were also
not significantly different for the two groups
(endometriosis 12% versus 12%, polycystic
ovarian syndrome 34% versus 36%, cervical
4% versus 4%, unexplained 18% versus
12% and male factor sub fertility 32%
26. versus 36% respectively). The ovarian
stimulation protocol for group A and B were
not significantly different (clomiphene
citrate/hMG 85% versus 87% and
Letrozole/FSH 15% versus 13%
respectively). The parameters of cycle
monitoring for group A and B including
number of follicles=18 mm
diameter(3.93±1.37 versus 3.90±1.17),
endometrial thickness on the day of hCG
administration (9.19±0.58mm versus
9.14±2.1mm) and the number of
spermatozoa(38.83±16.57X106 versus
36.68±13.44X106) inseminated were not
significantly different. However the day of
hCG administration (12.8±3.4 versus
11.1±2.1) was significantly different
between the two groups as shown in table-1
27. and 2.
Clinical pregnancy was defined by the
presence of fetal cardiac activity, detected
by ultrasound examination. Pregnancy rates
were similar when compared for the
etiology of infertility: for ovarian (PCOS)
cause (17.7% versus 21.8%), endometriosis
cause (8.4% versus 10.1%), male infertility
(12.8% versus 16.4%) and unexplained
infertility (14.4% versus 24%) for the two
groups, respectively as shown in table-3.
There was statistically significant difference
(p<0.05) in the overall pregnancy rate per
cycle over four treated cycles (11.95% per
cycle for IUI versus 21.81% per cycle for
FSP over four cycles) as shown in table-4.
Two missed abortions and one twin
28. pregnancy occurred among the patients in
group A (IUI). Three missed abortions and
two twin pregnancies occurred among the
patients in group B (FSP). However, this
limited number of abortions and multiple
pregnancies are too low to allow testing for
statistical significance. Three cases of mild
ovarian hyper stimulation syndrome
(OHSS) occurred in both groups.
Discussion
The purpose of this prospective, randomized
study was to study pregnancy rates in
couples with nontubal infertility when
treated with FSP (inseminate volume 4 ml),
in comparison with standard IUI
(inseminate volume 0.5 ml). Pregnancy
29. rates were 21.81 and 11.95% respectively
over four treatment cycles. The same
protocols for ovarian stimulation were used
in both groups. There was no statistically
significant difference regarding the age of
the patients treated, mean number of
follicles, endometrial thickness on the day
of hCG administration and the total number
of motile spermatozoa inseminated.
However the day of hCG(12.8±3.4 for FSP
versus 11.1±2.1 for IUI) administration was
statistically different between the two
groups (p value <0.05).
Kahn et al. reported the first clinical
experience with FSP. In their study, they
used a Frydman catheter for FSP and
reported a pregnancy rate per cycle of
30. 26.9% in patients with unexplained
infertility and of 2.7% to 7.7% in patients
with other etiologies. These excellent
results, particularly in patients with
unexplained infertility, were confirmed by
other studies [8]. Some investigators used a
paediatric Foley catheter or cervical clamp
double-nut bivalve speculum and very
encouraging results were reported by
Fanchin et al, in which FSP using an auto
blocking device (FAST system) doubled
their pregnancy rates from 20% to 40%
[1].The different types of catheters used for
IUI have been compared but no study
reports a significantly higher rate of
pregnancy with any one type of catheter [9,
10].
31. The FSP increases the intrauterine
pressure(70-200 mmHg) necessary for a
flush influx of spermatozoa directly into the
fallopian tubes. The high pregnancy rate
per cycle for FSP as compared with standard
IUI can be due to several causes as
follows: firstly, the pressure injection of
inseminate can either remove and/or
circumvent transitory or partial obstruction
of fallopian tubes, such as that created by
thick mucus or tubal polyps; secondly, the
concentration of motile spermatozoa around
the oocytes after FSP is higher than that
obtained after standard IUI; and thirdly, FSP
leads to inseminate overflowing into the
pouch of Douglas. The more accepted
hypothesis is the existence of a similar
mechanical effect created following a
32. hysterosalpingography [10].
In this study, we tried to evaluate FSP not
only in patients with unexplained infertility
but also in patients with other causes of
infertility including male causes. Two
different stimulation regimes were used;
however, the distribution of the two types of
stimulation protocols (clomiphene
citrate/hMG and Letrozole/FSH) appeared
homogenous in both studies groups.
Clinical pregnancy was defined by the
presence of fetal cardiac activity, detected
by ultrasound. When comparing the
pregnancy rates in both IUI and FSP in
relation to the etiology of infertility, it is
found to be statistically similar as shown in
33. table-3. Though the pregnancy rates of FSP
in PCOS and unexplained infertility group
of patients is superior to IUI, this finding is
statistically not significant. This analysis
revealed that couples suffering from any
specific etiological sub fertility did not
benefit from FSP over IUI.
However, there was statistically significant
difference in the overall pregnancy rate per
cycle over four cycles of treatment (11.95%
per cycle over four cycles for IUI versus
21.81% per cycle for FSP over four cycles)
as shown in table-4(p value<0.009).
Pregnancy rates improved in subsequent
attempts with FSP in comparison to IUI.
The cumulative pregnancy rates even after
the second attempt, over two cycle
34. treatment, were statistically significant (p
value <0.03), however there was no
statistical difference when each attempt of
treatment cycles was compared between the
two groups (p value >0.05).
Four studies [2, 4, 6, and 11] mentioned a
maximum of three cycles per couple; one
study [12] reported a maximum of four
cycles. We also allowed maximum of four
cycles treatment of IUI or FSP before
considering them for In vitro fertilization
and embryo transfer (IVF-ET).
The type of catheter has no impact on the
pregnancy rate after intrauterine
insemination [13]. We suitably modified the
long size allis clamp, by attaching cervical
35. occluding prongs with rubber cushions,
which was kept in place for about 3 to 4
minutes after insemination to prevent any
significant reflux. Mild reflux does not seem
to influence the results of the FSP but the
significant reflux (> 0.4 ml) may reduce the
pregnancy [14]. If more than 1 ml comes
back in the catheter, the operator needs to
wait for a few minutes and re-inseminate
again. All the authors agreed that women
tolerated the FSP technique very well. In
our study some patients complained of post
insemination pelvic transient pain, more so
in FSP than in IUI. Other interesting domain
of FSP application is the immunological
infertility in the presence of anti-sperm
antibodies [15, 16].This aspect could not be
studied in this study because pre and post
36. FSP anti-sperm antibody assay was not
done.
In this study by comparing the overall
results, we conclude that FSP over four
cycles of treatment offers an advantage over
the standard IUI, and can replace the IUI for
all its indications because of its better
pregnancy rates. However FSP is more
expensive than IUI due to the increased
media usages. It could be used as an
alternative for couples with non tubal
infertility before embarking on IVF-ET
treatment.
References
1. Fanchin R, Oliveness F. A new system for
37. fallopian tube sperm perfusion leads to
pregnancy rates twice as high as standard
intrauterine insemination. Fertility and
Sterility 1995; 64(3):505–10.
2. Kahn JA, Sunde A, Von During V, et al.
Treatment of unexplained infertility. Acta
Obstetrica Gynaecologica de Scandinavia
1993; 72(3):193–9.
3. Trout SW. Fallopian tube sperm perfusion
versus intrauterine insemination: a
randomized controlled trial and meta-
analysis of the literature. Fertility and
Sterility 1999; 71(5):881–5.
4. Ng EHY, Makkar G. A randomized
comparison of three insemination methods
38. in an artificial insemination program using
husbands’ semen. The Journal of
Reproductive Medicine 2003; 48(7):542–6.
5. Nuojou-Huttunen S, Tuomivaara L,
Juntunen K. Comparison of fallopian tube
sperm perfusion with intrauterine
insemination in the treatment of infertility.
Fertility and Sterility 1997; 67(5):939–42.
6. Gregoriou O, Pyrrgiotis E, Konidaris S.
Fallopian tube sperm perfusion has no
advantage over intra-uterine insemination
when used in combination with ovarian
stimulation for the treatment of unexplained
infertility. Gynecologic and Obstetric
Investigations 1995; 39: 226-8.
39. 7. World Health Organization. WHO
laboratory manual for the examination of
human semen and sperm cervical mucus
interaction. WHO laboratory manual.
Cambridge: Cambridge University Press,
1992.
8. Mamas L. Comparison of fallopian tube
sperm perfusion and intrauterine
tuboperitoneal insemination: a prospective
randomized study. Fertility and Sterility
2006; 85(3):735–40.
9. SmithKL, GrowDR, WiczykHP, et al.
Does catheter type effect pregnancy rate in
intrauterine insemination cycles? Journal of
Assisted Reproduction and Genetics 2002;
19(2):49–52.
40. 10. Noci I, Dabizzi S, Evangelisti P, et al.
Evaluation of clinical efficacy of three
different insemination Techniques in couple
infertility. Minerva Ginecologica 2007;
59(1):11–8.
11. Ricci G, Nucera G, Pozzob et al. A
simple method for fallopian tube sperm
perfusion using a blocking device in the
treatment of unexplained infertility. Fertility
and Sterility 2001; 7 Suppl 1:1242–8.
12. Biacchiardi CP, Revelli A, Gennarelli G,
et al. Fallopian tube sperm perfusion versus
intrauterine insemination in unexplained
infertility: a randomized, prospective,
crossover trial. Fertility and Sterility 2004;
81(2):448–51.
41. 13. Vermeylen AM, D’Hooghe T, Debrock
S, et al. The type of catheter has no impact
on the pregnancy rate after intrauterine
insemination: a randomized study. Human
Reproduction 2006; 21(9):2364–7.
14. Kahn JA, von During V, Sunde A, et al.
Fallopian tube sperm perfusion. First
clinical experience. Hum. Reprod. 1992; 7:
19-24.
15. El Sadek MM, Amer MK, Abdel-Malak
G. Questioning the efficacy of fallopian
tube sperm perfusion. Human Reproduction
1998; 13 (11):3053–6.
16. Elhelw B, Matar H, Soliman EM. A
randomized prospective comparison
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Middle East Fertility Society Journal 2000;
5(1):83–4.
48. A CASE REPORT: TREATMENT OF A
MEDIAL CONDYLAR HUMERAL
FRACTURE IN AN ADULT WITH
OSTEOPETROSIS
Authors: Dr Calvin CHIEN, MBBS. Dr
Rajesh BEDI, DNB (Ortho). Dr Richard D.
LAWSON, FRACS (Ortho)
Abstract
Patients with osteopetrosis often present
with orthopaedic problems such as frequent
fractures. Management of fractures with
open reduction and internal fixation is
difficult but possible. We report on a 22 year
old patient with a medial humeral condyle
fracture treated successfully with internal
49. fixation using a pre-contoured plate.
Introduction
In 1904 Albers-Schoenberg described a
condition characterised by marked
radiographic density of the bones (1).
Despite the sclerotic radiographic
appearance of the thickened cortices and its
material hardness, osteopetrotic bone is
weak, brittle and prone to fracture after
minor trauma (1). Most literature regarding
treatment of osteopetrotic patients with
fractures concentrates on paediatric patients
or on the difficulty of operative intervention
in adults (2). We report the case of an adult
patient with osteopetrosis and a low medial
column fracture (Milch Type I (1)) of the
50. distal humerus after minor trauma. The
fracture was treated operatively utilising
internal fixation with a pre-contoured peri-
articular plate.
Case
A 22 year old female with known
osteopetrosis presented with an elbow injury
after bracing herself with the right arm after
a fall. The mechanism described suggested a
valgus injury to the right elbow resulting in
a Milch Type I (3) low medial column
fracture of the distal humerus (Fig. 1). There
were no neurological deficits. As an
adolescent she had previous injuries
including one to the radius of the same side
limiting elbow extension by twenty degrees.
51. She was also partially blind and was
receiving psychiatric treatment for
depression.
Two days later, open reduction of the right
distal humerus was performed with internal
fixation using a pre-contoured medial
condylar locking plate (Fig 2). This was
done through a posterior approach after
identifying the ulnar nerve. Anterior
transposition of the ulnar nerve was done
before closure. The patient was discharged
two days later in a plaster-of-paris back slab
with outpatient follow-up. After two weeks
the arm was placed in a range of movement
elbow brace with unrestricted range of
motion. Serial radiographs were performed
at four-weekly intervals and complete bony
52. union with disappearance of the fracture
line was evident on the radiographs taken at
fourteen weeks (Fig 3). Outpatient as well
as a home-based physiotherapy program
was arranged and full pre-injury range of
motion was achieved by ten weeks.
Discussion
Osteopetrosis is a rare hereditary disease of
the osteoclasts first described by Albers-
Schönberg, a German radiologist, in 1904.
Defective osteoclastic activity or a reduced
number of osteoclasts results in a failure of
bone remodelling (4). This is manifested on
radiographs as an increase in bone mass and
osteosclerotic changes (4).
53. Osteopetrosis can be classified into three
main forms: a malignant autosomal
recessive, intermediate autosomal recessive
and benign autosomal dominant form; the
vast majority of these cases are the benign
autosomal dominant form. The malignant
autosomal recessive type, also known as
infantile, is characterised by growth
retardation, failure to thrive and cranial
nerve palsies manifesting as proptosis,
deafness and blindness. In addition,
pancytopenia and thrombocytopenia may
result from bone marrow failure. Many
features of the intermediate form of
osteopetrosis are similar to those of the
malignant form but the intermediate form is
less severe and later in onset. It is often
diagnosed after a fracture, usually occurring
54. in the first decade. Benign osteopetrosis has
been further subdivided into types I and II.
However, recent genetic studies have shown
that autosomal-dominant osteopetrosis type
I is caused by an increase in osteoblastic
activity rather than osteoclastic dysfunction.
In this case osteoblasts deposit excessive
amounts of bone matrix (4). Type II
autosomal dominant osteopetrosis is the
form Albers-Schönberg first described and
so is often named after him. The onset is in
later childhood and is usually diagnosed
incidentally during a radiographic
examination (4). It is also associated with
increased fracture frequency. Other
manifestations include coxa vara,
osteoarthritis, spondylolysis, back pain,
osteomyelitis and cranial nerve palsies.
55. Radiographic features include skull-base
thickening, vertebral end-plate thickening
and endobone appearance (4).
Isolated medial condylar fractures of the
humerus in adults are uncommon and we
have not discovered a report of this fracture
in an osteopetrotic patient. Medial condylar
fractures are intra-articular and like lateral
condylar fractures are prone to non-union
(1). Usually, the mechanism for this fracture
is through a valgus force on an extended
elbow where the force is transmitted via the
olecranon or coronoid process into the
medial condyle (3). The fracture can also
arise from an avulsion injury of the condyle
through forceful contraction of the forearm
flexors. With minimally displaced fractures
56. of the medial humeral condyle, good
fracture healing and functional outcomes
can be expected with non-surgical treatment
consisting of immobilisation in a splint and
a gradually increasing permissible range of
motion (7). On the other hand, studies
specifically examining displaced medial
humeral condylar fractures treated by open
reduction internal fixation reported good or
excellent outcome in 86% of patients (2). As
mentioned earlier, patients with
osteopetrosis are prone to infections and the
reported incidence of post-operative
infection is 12% (2). Furthermore, some
authors have reported delayed and non-
union following fractures in osteopetrotic
patients (2). A study has shown fracture
healing time in osteopetrotic mice to be
57. more than twice as long (2).
Despite the difficulties of surgery, the risk
of infection, and the higher incidence of
delayed and non-union, the patient achieved
an excellent functional outcome with no
surgical complications. Open reduction and
internal fixation to a fractured medial
humeral condyle in a young osteopetrotic
patient is certainly an option.
References
1. Albers-Schönberg H. Roentgenbilder
einer seltenen Knochennerkrankung. Munch
Med Wochenschr 1904;51:365.
2. Armstrong DG, Newfield JT, Gillespie R.
58. Orthopedic management of osteopetrosis:
results of a survey and review of the
literature. J Pediatr Orthop 1999;19:122–
132.
3. Milch H. Fractures and fracture
dislocations of the humeral condyles. J
Trauma 1964;15:592-607.
4. Tolar J, Teitelbaum SL, Orchard PJ.
Osteopetrosis. N Engl J Med 2004;
351:2839-2849.
5. Abe S, Watanabe H, Hirayama A,
Shibuya E, Hashimoto M, Ide Y.
Morphological study of the femur in
osteopetrotic (op/op) mice using
microcomputed tomography. Br J Radiol
59. 2000;73:1078-82.
6. Bollerslev J, Mosekilde L. Autosomal
dominant osteopetrosis. Clin Orthop Relat
Res. 1993;294:45-51.
7. El Ghawabi MH. Fracture of the medial
condyle of the humerus. J Bone Joint Surg
Am 1975;57:677-80.
8. Jupiter JB, Neff U, Regazzoni P,
Allgower M. Unicondylar fractures of the
distal humerus: an operative approach. J
Orthop Trauma 1988;2:102-109.
9. Shapiro F. Osteopetrosis: Current clinical
considerations. Clin Orthop Relat Res
1993;294:34-44.
60. 10. Marks SC Jr, Schmidt CJ. Bone
Remodeling as an Expression of Altered
Phenotype: Studies of Fracture Healing in
Untreated and Cured Osteopetrotic Rats.
Clin Orthop Relat Res 1970;137:259-264.
61.
62.
63.
64. STRESS-ONLY NUCLEAR
MYOCARDIAL PERFUSION
IMAGING
Author: Tom Heston, MD
Inducible myocardial ischemia from
coronary artery disease is diagnosed when
blood flow to the heart at stress is
significantly less than blood flow at rest.
The identification of inducible ischemia is
important in people with chest pain, because
with proper treatment the risk of a major
adverse cardiac event is greatly reduced.
Many different conditions can cause chest
pain, most of which are benign and non-life
threatening. However, inducible ischemia
can be life threatening, and when left
65. untreated the consequences are severe.
One of the best and most thoroughly
validated method of testing for inducible
ischemia is stress-rest myocardial perfusion
gated SPECT imaging. This involves
injecting a patient with a radiotracer at rest
and during peak stress. The radiotracer is
primarily designed to map blood flow to the
heart. However, using a gated SPECT
protocol also allows determination of left
ventricular size, wall motion, and ejection
fraction. Inducible ischemia is suggested by
abnormalities in any of these imaging
variables at stress, that are not present at
rest. Because the objective is to identify
abnormalities at stress that are not present at
rest, current utilization guidelines for
66. myocardial perfusion gated SPECT
recommend imaging both at rest and
immediately post-stress.
Newer research in myocardial perfusion
imaging has looked at the possibility of
imaging patients only post-stress, and
omitting the rest scan. The reasoning for this
is that if the stress scan is normal, then the
rest scan is medically unnecessary,
financially costly, and exposes patients to
excess radiation. Although not yet widely
validated, stress-only imaging may be
reasonable in low-risk patients as long as
any abnormal stress study is followed-up
with a rest scan. Nevertheless, at the current
time, clinical practice guidelines have not
fully addressed or endorsed stress-only
67. imaging, and nearly all nuclear cardiology
clinics continue to perform stress-rest
imaging.
There are several reasons for continuing the
practice of stress-rest imaging until more
research is done. One reason is that
myocardial perfusion imaging is not
indicated in low-risk patients, so the
research doesn't apply to clinical medicine.
The research protocols for stress-only
imaging typically involved attenuation
correction SPECT, a technique that has not
been widely accepted due to a relative lack
of solid evidence supporting its use. Another
reason is that risk stratification prior to
imaging is often inexact, so it is medically
safer to assume at least an intermediate risk
68. and perform a stress-rest study. Finally, the
goal of myocardial perfusion imaging is to
maximize sensitivity, since the
consequences of failing to identify inducible
ischemia can be severe. Stress-only imaging
is not thought to be as sensitive as stress-
rest imaging.
The current prevailing medical practice to
perform stress-rest imaging as a routine
appears to be clinically appropriate, with a
recent clinical update (2009) from the
American Society of Nuclear Cardiology
concluding that a stress-only strategy "does
not yet have sufficient data to support a
widespread utilization." Nevertheless, the
research supporting stress-only imaging
continues to grow, with one recent paper
69. finding its use even in high-risk patients to
be appropriate in some circumstances.
REFERENCES
Heller G, Hendel R. Nuclear Cardiology:
Practical Applications, Second Edition
[2010].
70. CAN WE SKIP THE AUTOPSY?
AUTHOR: Tom Heston, MD
The postmortem autopsy is considered the
gold standard in the determination of the
cause of death. Newer imaging
technologies, however, including high
resolution computed tomography (CT) and
magnetic resonance imaging (MRI), may
allow in some cases a virtual autopsy
instead, that utilizes medical imaging alone.
The benefits of a virtual, imaging autopsy
include the potential for conducting more
autopsies which could lead to more accurate
mortality statistics, and reduced costs. The
virtual autopsy may also be more widely
accepted by families and religions.
71. A study published in the January 14th, 2012
issue of the Lancet compared traditional
autopsy results with virtual autopsy by both
CT and MRI. They randomly enrolled 182
cases that underwent both virtual and full
conventional autopsy. The CT and MRI
scans were independently interpreted for
cause of death, then a combined report was
created from both imaging modalities. The
radiologists also indicated how confident
they were in their diagnosis, which was
based entirely upon the scan images. The
cases were then dividing into two groups:
those with a definite imaging diagnosis, and
those without a definite imaging diagnosis.
The researchers found that overall, about 1
72. in 3 virtual autopsies contained a major
discrepancy when compared with the full,
traditional autopsy. Radiologists considered
the imaging diagnosis for cause of death to
be definite in about half of the cases. In
these cases where the imaging results were
considered definite, the major discrepancy
rate with full autopsy was about 1 in 6. The
researchers also found that CT was more
accurate than MRI when using a
conventional autopsy as the gold standard.
Major common sources of error were when
the cause of death was coronary heart
disease, pulmonary embolism,
bronchopneumonia, and intestinal
infarction. As the study progressed, the
radiologists improved their interpretation
73. accuracy, however, major discrepancies
continued to exist.
The researchers concluded that when
conducting a virtual autopsy, CT imaging
was better than MRI scanning in providing
an accurate cause of death. When the
findings on virtual autopsy were considered
definite, the major discrepancy rate with full
autopsy was 16%.
COMMENT: This is a new, emerging
application of medical imaging that has
tremendous potential. The authors note that
when the imaging diagnosis was considered
definite, the error rate was comparable to
the error rate of a conventional, full autopsy.
As physician experience with this relatively
74. new application of medical imaging
improves, it is likely that the accuracy will
significantly rise. Because of the relatively
low cost and ease of conducting a virtual
autopsy, it is likely to become fully
integrated into and a routine part of
postmortem investigation.
REFERENCE
Roberts IS, Benamore RE, Benbow EW et
al. Post-mortem imaging as an alternative to
autopsy in the diagnosis of adult deaths: a
validation study. Lancet. 2012 Jan
14;379(9811):136-42
75. THE FUNDAMENTALS OF COURAGE
AUTHOR: Tom Heston, MD
"You gain strength, courage, and confidence
by every experience in which you really stop
to look fear in the face. You must do the
thing which you think you cannot do." -
Eleanor Roosevelt
Eleanor Roosevelt faced many challenges
during her life. She married Franklin Delano
Roosevelt at age 20, then around age 30 she
discovered that FDR was having an affair
with her own secretary. Shortly thereafter,
FDR became paralyzed, and her
campaigning on his behalf played a huge
role in him winning election to the
76. Presidency of the U.S. Through her fearless
and direct actions, she was able to make the
most of things, and ultimately became one
of the ten most widely admired people of
the 20th century according a poll of the
American people. She knew that positive
thinking was not courage. Talking to her
friends about plans for the future is not
courage. Courage is an action.
It takes action to overcome a fear, and only
through taking action does one become
more bold and courageous.Through action
directed at fear, the fear is overcome and
courage is strengthened. So, in order to
become more courageous, it is necessary to
embrace the first fundamental element of
courage- action.
77. "Conscience is the root of all true courage;
if a man would be brave let him obey his
conscience." - James Freeman Clarke
James Clarke was an early 19th century
theologian and author. A graduate of
Harvard College in 1829, he then became a
minister for the Unitarian church in
Louisville, Kentucky. At the time, Kentucky
was a slave state, but James Clark stood up
against his state's government and
advocated strongly for the abolition of
slavery. This strength of conviction, coupled
with action, made Clarke a courageous
person others could follow and respect.
Courage comes from this strength to follow
one's conscience, even if it goes against
popular opinion or as in the case of Clarke,
78. the government. This is the second
fundamental principle of courage. When
actions become aligned with the conscience,
courage grows and is strengthened.
Taking positive action that is in alignment
with the conscience is a simple concept. To
strengthen courage, one must act upon the
things known to be true, just, and right.
Is there something the community needs to
be improved? What can be done to help? Is
there something in the family that can
improve? What are some simple actions that
will help make things better? Is there
something that should be confronted, but
fear is getting in the way of acting?
79. REFERENCES
Gallup News Service. Mother Teresa Voted
by American People as Most Admired
Person of the Century. 31-Dec-1999.
Retrieved 24-Feb-2012.Eleanor Roosevelt
was #9 on this list.
Heston T (ed). Courage Builder. Internet
Medical Association, Las Vegas, 2011.
80. OMEGA-3 FATTY ACIDS, RED YEAST
RICE, AND SUDDEN CARDIAC
DEATH
For people with high cholesterol, or at an
increased risk of cardiovascular disease,
there are a couple of concentrated
nutritional supplements that may be helpful
to aid in lowering the risk of a fatal heart
attack or disabling heart disease.
The first is the unique and natural native
product from China - red yeast rice. It has
been used in customary medical systems
from about 800 A.D. This rice is produced
when white rice is fermented with
(monascus purpureus) red yeast. It is said to
be used first in China (more than 2800 years
81. in the past) as food coloring agent and food
preservative. The first assumed use of the
recipe for making red yeast rice was in
1368-1644 - the Ming Dynasty. It was
reported even at that time to boost blood
circulation. There is careful production of
the red yeast rice extract to prevent any
citrinin presence, a by-product of the
process of fermentation which is sometimes
toxic. When CoQ10 is added, there appears
to be further enhancement of the product to
support the immune system as well as
healthy cardiovascular functions.
Chinese cuisine has used red yeast rice as
cardiac supplements for centuries - that is,
to encourage blood circulation and reduce
clotting. Asian countries use red yeast rice
82. as a staple for diets, used in making rice
wine, flavour agent, as well as to maintain
the colour and flavour of meat and fish. The
red yeast rice develops inhibitors referred to
as monacolins. These inhibitors
(hydroxymethylglutaryl-CoA reductase
(HMG-CoA reductase)) occur naturally. The
healing properties of the red yeast rice
positively affect the lipid reports of patients
who are hypercholesterolemic.
The second concentrated nutritient that may
be of benefit to your heart is omega-3 fatty
acid. This appears to be helpful for people
that are at risk of heart disease, or are
currently experiencing the negative effects
of heart disease. Omega-3 fatty acids appear
to have an anti-arrhythmic effect, and have
83. been shown in some research to reduce the
risk of sudden death by about a half, and
reduce the risk of cardiac death by a third.
Modest doses are recommended because of
the possible interaction with other
supplements or medications a person may
be taking, such as aspirin and other blood-
thinning medications.
The primary side effects of red yeast rice
appear to be primarily due to contaminants
during production. Selecting a product from
a reputable manufacturer is especially
important for this supplement. The primary
side effects of omega-3 fatty acids likely
come from interactions with
pharmaceuticals. It is important to let your
physician and pharmacist know about what
84. you are taking, so they can help you
minimize any side-effects. Also, keep in
mind that supplementation does not replace
a healthy diet full of plant foods. Balance
supplementation with a moderate and
balanced diet.
REFERENCE
Ong HT, Cheah JS. Statin alternatives or
just placebo: an objective review of omega-
3, red yeast rice and garlic in cardiovascular
therapeutics. Chin Med J (Engl). 2008 Aug
20;121(16):1588-94.