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Biomedical subjects

J D Frank

Publications and source records attributed to J D Frank.

At least 19 recordsLinked to original sources
PubMed1992

Immunocytochemical localization of platelets in baboon hepatic sinusoids using monoclonal mouse anti-human platelet glycoprotein IIIa following induction of thrombocytopenia.

A commercially available mouse monoclonal antibody to human platelet glycoprotein IIIa was used to demonstrate sequestration of platelets in hepatic biopsies obtained from baboons following intravenous infusion of echistatin, a novel fibrinogen receptor antagonist derived from the venom of the snake Echis carinatus. Biopsies of liver and spleen were taken prior to administration of echistatin. The hepatic biopsies were either snap-frozen in Freon-22/liquid nitrogen or fixed in 10% neutral buffered formalin. Biopsies of spleen were snap-frozen. During infusion of echistatin (2.3 micrograms/kg/min), circulating platelet counts decreased from 331,000/mm3 to 167,000/mm3. Selective sequestration within the liver was confirmed using whole body gamma camera imaging to demonstrate 111Indium-oxine labeled platelet accumulation within the liver during the thrombocytopenic episode. Hepatic biopsies were again taken and either snap-frozen in Freon-22/liquid nitrogen or fixed in 10% neutral buffered formalin. Biopsies of spleen and inguinal lymph node were also snap-frozen. Platelet rich plasma smears, included as positive controls, dewaxed paraffin sections, and cryosections of liver, spleen, and lymph node were stained with monoclonal mouse anti-human platelet glycoprotein IIIa using an avidin biotinylated peroxidase complex (ABC) technique. Prior to infusion of echistatin, platelet staining within the liver was minimal. After echistatin infusion, hepatic cryosections showed prominent platelet staining within hepatic sinusoids. No localization was shown in lymph node, however, the spleen showed prominent platelet staining both before and after echistatin infusion. Platelet rich plasma smears were intensely positive. No prominent platelet staining was observed in formalin-fixed, paraffin-embedded material. Thus, this immunocytochemical technique may help localize platelets in cryosections of tissues from baboons and other primate species.

Animals↗
PubMed1992

Studies of early hepatocellular proliferation and peroxisomal proliferation in Sprague-Dawley rats treated with tumorigenic doses of clofibrate.

Clofibrate, a peroxisome proliferator, is hepatocarcinogenic in rats in a dose-dependent fashion. While there is a relationship between peroxisome proliferation and rodent liver carcinogenesis, recent evidence also suggests an association between the tumorigenicity of peroxisome proliferators and sustained cell proliferation. To investigate the role of early cell proliferation in clofibrate-induced carcinogenesis and the predictive potential of this endpoint, in a 3-month study, rats were fed clofibrate doses equivalent to those used in the chronic bioassay, and cell proliferation was determined after 1 week and 3 months, using a 1-week continuous bromodeoxyuridine (BrdU)-labeling technique. Adult Sprague-Dawley rats were fed clofibrate at 1500, 4500, or 9000 ppm. Six rats/sex/group were killed after 1 or 13 weeks of treatment. Osmotic minipumps containing BrdU were implanted into rats 7 days prior to necropsy to determine the cumulative 7-day hepatocyte labeling index immunohistochemically. A dose-related increase in hepatocyte labeling index was seen after 1 week of treatment. However, at 13 weeks, sustained increases in hepatocyte proliferation were not seen; but a dose-related decrease in the hepatocyte labeling index was observed. Liver stereology at 13 weeks demonstrated a dose-related increase in liver weight and volume, but a decrease in hepatocyte nuclei per unit volume, a minimal increase or no change in the total number of hepatocyte nuclei per liver, and an absolute decline in the total number of BrdU-labeled hepatocyte nuclei per liver. These data suggest that in rats, clofibrate may influence hepatocarcinogenicity by decreases in normal hepatocyte proliferation over time and this effect may influence the pathogenesis of tumors at time points beyond 13 weeks of treatment.

Administration, Oral↗
PubMed1992

Extracorporeal shock wave lithotripsy for renal calculi in children.

Fifteen children (8 male and 7 female) with an age range of 18 months to 15 years were treated with extracorporeal shock wave lithotripsy (ESWL) using the Siemens Lithostar. Two children had a history of metabolic stone disease and 1 child had previously undergone open stone surgery. Four children were treated with a ureteric stent in place and 1 nephrostomy was inserted before treatment. All children were treated under general anaesthesia and all of the stones treated were confined to the kidney and ranged in size from 5 mm to a complete staghorn. The number of treatments ranged from 1 to 6 and generator voltage ranged from 16 to 19 kV with a maximum number of 30,000 shocks to a complete staghorn. Complications were minimal, with 3 children presenting with colic, 1 child requiring a stent and none requiring a nephrostomy after treatment. The overall stone clearance rate at 3 months was 65%. ESWL provides an effective treatment for selected calculi in children. In the short term, complications are minimal but the long-term effects on children need to be monitored.

Adolescent↗
PubMed1992

Fixation of a single testis: always, sometimes or never.

If it is necessary to perform an orchiectomy for an intravaginal testicular torsion it is the usual practice of surgeons to fix the contralateral testis. When faced with a child with only one testis for another reason it is our practice to fix this single testis to eliminate the small but disastrous risk of a torsion. We were interested to see whether this practice was usual and therefore sent out a questionnaire to the 67 consultant paediatric surgeons and urologists in Great Britain. Sixty-six surgeons replied. Seven surgeons (11%) always fix the single testis, 28 (42%) sometimes and 31 (47%) never fix a single testis. Five surgeons had looked after 6 patients who had a torsion of a second unfixed testis after losing the first for a reason other than intravaginal torsion. Four of these patients had initially had a neonatal supravaginal torsion, 1 had a torsion of an undescended testis and the sixth had severe testicular atrophy following an inguinal herniotomy. In our opinion the devastating loss of these solitary testes makes contralateral testicular fixation after an orchiectomy for whatever reason mandatory.

Attitude of Health Personnel↗
PubMed1992

Pharmacological assessment of the antithrombotic activity of the peptide thrombin inhibitor, D-methyl-phenylalanyl-prolyl-arginal (GYKI-14766), in a canine model of coronary artery thrombosis.

The antithrombotic activity of the tripeptide thrombin inhibitor, D-methyl-phenylalanyl-prolyl-arginal (GYKI-14766), was compared to heparin in a model of canine coronary artery thrombosis. Thrombogenesis was initiated by electrolytic injury of the intimal surface of the left circumflex coronary artery. Drug administration was started 15 min before initiation of intimal injury. Clotting times and ex vivo platelet aggregation were determined on citrated blood samples. Gingival template bleeding times were determined. Clotting times (thrombin time; activated partial thromboplastin time, APTT; prothrombin time, PT) increased in a dose-dependent manner with both anticoagulants. The two anticoagulants selectively inhibited thrombin-induced platelet aggregation. GYKI-14766 and heparin were found to delay thrombosis significantly when compared to vehicle-treated animals; minimum effective antithrombotic doses were 0.25 mg/kg/h and 80 U/kg + 30 U/kg/h, respectively. GYKI-14766 (0.25 mg/kg/h) had no effect on template bleeding time, APTT or PT. Heparin (80 U/kg + 30 U/kg/h), however, was associated with a 2.5- to 3.0-min increase in template bleeding time, a 1.8-fold and 1.7-fold increase in APTT and PT, respectively. Antithrombotic efficacy was achieved at doses of GYKI-14766 that did not affect APTT, PT or template bleeding time, whereas antithrombotic efficacy observed with heparin was associated with significant increases in APTT, PT and template bleeding time. These data demonstrate that the tripeptide thrombin inhibitor, GYKI-14766, could potentially prove to be a safer and more effective antithrombotic agent than heparin.

Animals↗
PubMed1992

Inappropriate circumcision referrals by GPs.

One hundred and twenty boys were referred by GPs over a 12-month period to a paediatric urologist for circumcision. The reasons for referral were: ballooning in 36, non-retraction in 28, balanoposthitis in 36 or a combination in 15. On examination 53% had a retractile, 21% a partially retractile and 21% a non-retractile foreskin. Six patients had obvious balanitis xerotica obliterans. Only one quarter of the patients required a circumcision. The penis was not examined by the referring doctor in 15 patients. The implications of this survey are that a large proportion of general practitioners have difficulty in discriminating between a true phimosis and a developmentally non-retractile foreskin. This diagnostic inaccuracy was greatest when the referring doctor did not examine the patient.

Adolescent↗
PubMed1992

Comparison of the thrombolytic activity of the novel plasminogen activator, LY210825, to anisoylated plasminogen-streptokinase activator complex in a canine model of coronary artery thrombolysis.

We have compared the thrombolytic efficacy of a novel single-chain, recombinant tissue-type plasminogen activator variant, LY210825, containing the second kringle and serine protease domains of native tissue-type plasminogen activator, with anisoylated plasminogen-streptokinase activator complex (APSAC). Male hounds (16-22 kg) were anesthetized, the left circumflex coronary artery was isolated and an electromagnetic flow probe was placed around the artery proximal to the first main branch for the measurement of coronary blood flow. An occlusive thrombus was formed after electrolytic injury of the intima of the coronary artery. After an occlusion period of 1 hr, either LY210825 (n = 8) or APSAC (n = 6) was administered as a single i.v. injection of 0.45 mg/kg. Blood was drawn (3.8% citrate) for determination of plasma fibrinogen, plasminogen and alpha-2 antiplasmin. Time to reperfusion was significantly faster with LY210825 than with APSAC, 20 +/- 2 vs. 54 +/- 8 min, respectively. The incidence of reocclusion was similar for both agents. APSAC produced significant depletion of alpha-2 antiplasmin, plasminogen and circulating fibrinogen, whereas LY210825 caused only slight consumption of plasminogen and only small decreases in fibrinogen. After a single injection of LY210825, thrombolytic concentrations of plasminogen activator were available immediately, whereas there was a significant delay in lytic concentrations of active streptokinase-plasmin complex. Consequently, LY210825 reperfused the coronary artery faster than did APSAC. In addition, LY210825 spared plasma fibrinogen, plasminogen and alpha-2 antiplasmin and therefore, could potentially minimize the risk of bleeding complications.

Animals↗
PubMed1991

Angiotensin II receptor subtypes in renal cortex of rats and rhesus monkeys.

The angiotensin II (ANG II) receptor has recently been shown to exhibit subtypes with respect to antagonist binding. Of particular interest are the potent nonpeptide antagonists, DUP 753 and PD 121981, which exhibit selectivity for the subtype 1 (AT1) and subtype 2 (AT2) receptors, respectively. We used these high-affinity antagonists in competition with 125I-[Sar1,Ile8]ANG II to determine autoradiographically the distribution of these ANG II-receptor subtypes in the renal cortex of rats and rhesus monkeys. Binding of the radioligand to receptor in sections of rat renal cortex was inhibited by DUP 753; inhibition by PD 121981 was not detected. By contrast, AT1 and AT2 receptors are present in the renal cortex of rhesus monkeys in regionally distinct structures. DUP 753 inhibited binding to the ANG II receptor in glomeruli. PD 121981 inhibited binding to arterial smooth muscle and the juxtaglomerular (JG) apparatus. The JG apparatus also exhibits radioligand binding, which is inhibited by DUP 753. The effect of DUP 753 and PD 123177 (a more water-soluble analogue of PD 121981) on changes in plasma renin activity was examined to determine if one or both of these subtypes participate in the ANG II-mediated negative feedback of control of renin release. Although DUP 753 increased plasma renin activity to the same extent as the angiotensin-converting enzyme inhibitor, enalaprilat, in rats and rhesus monkeys, the AT2 antagonists did not affect renin release in either species. Thus both subtypes of ANG II receptor are present in rhesus monkey cortex, but a function for only the AT1 subtype was demonstrated.

Aldosterone↗
PubMed1989

Anterior abdominal wall defects.

A total of 48 infants with abdominal wall defects referred to the South West Regional Neonatal Surgical Centre over a period of six years were reviewed. There were 27 (56%) infants with gastroschisis and 21 (44%) infants with exomphalos. At the regional centre, four pregnancies with gastroschisis were terminated following a prenatal diagnosis, one child was stillborn, and one with exomphalos and trisomy 13 died soon after birth. Of the remaining 42 live births, the one year survival for babies born with a gastroschisis was 95% (21/22) and with an exomphalos was 81% (17/20). All deaths, except one, were due to factors other than the abdominal defect. The effect on outcome of prenatal diagnosis, parental counselling, in utero transfer, mode of delivery, and methods of surgical closure was reviewed.

Abdominal Muscles↗
PubMed1989

The drive for power and conceptual inertia.

This presentation has considered only two of many psychological factors that contribute to the nuclear predicament. These are the power drive and conceptual inertia and how they encourage the propensity to violence. Psychotherapists can make an indirect but significant contribution toward human survival by calling attention particularly to the pernicious psychological effects of the misuse of language, either deliberate or resulting from conceptual inertia. We should seek to inform and educate the public, including political leaders, about this phenomenon. Those of us who have young children or grandchildren should seek to introduce into school and college curricula issues created by the splitting of the atom, since the young are best able to achieve the massive psychological changes necessary for coping with a new and unprecedented predicament.

Competitive Behavior↗
PubMed1988

Correlation of the in vivo anticoagulant, antithrombotic, and antimetastatic efficacy of warfarin in the rat.

Fibrin formation has been hypothesized to be an element of the metastatic process in cancer, and pharmacological interference with such fibrin formation has been proposed as a means of antimetastatic therapy. We have tested this hypothesis through an in vivo study of warfarin in two independent rat disease models--a model of chemical-injury-induced arterial thrombosis, and a model of spontaneous metastasis. We found 0.50 mg/kg-day warfarin to be uniformly lethal after two weeks treatment. The chronic dose of 0.25 mg/kg-day was non-toxic and produced effective anticoagulation and marked antithrombotic and antimetastatic activity. The 0.125 mg/kg-day dose produced a reduction in factor IIc (50%) and factor VIIc (70%), and resulted in statistically significant antithrombotic and antimetastatic activity. The 0.0625 mg/kg-day dose failed to reduce the vitamin K-dependent clotting factors, and failed to produce any antithrombotic or antimetastatic effects. The substantial correlation (very similar dose-response effects) among the anticoagulant, antithrombotic and antimetastatic efficacies of warfarin in the rat suggests that anticoagulation provides the pharmacological mechanism underlying both the antithrombotic and the antimetastatic effects. The poor therapeutic index we observed in the rat may be the attribute which limits the efficacy of warfarin in the treatment of human cancer.

Animals↗
PubMed1988

Urethral strictures in childhood.

Thirty-six children have been treated for a non-hypospadiac urethral stricture. Of 12 patients with meatal or submeatal stenosis, 10 had undergone circumcision for balanitis xerotica obliterans. The strictures were successfully treated by meatoplasty or meatal dilatation. Twenty-four children had a more proximal urethral stricture: 16 were caused by urethral catheterisation, 4 were post-traumatic, 2 were congenital and 2 were idiopathic. Sixteen children were treated by visual urethrotomy; this was successful in 12 after a maximum of 2 urethrotomies. Two children required 4 or more urethrotomies and 2 required urethroplasty for restricturing. Seven children were treated by a formal urethroplasty. There were no complications. Two patients died of unrelated medical conditions. Follow-up was for a mean of 2 years.

Child↗
PubMed1987

Morbidity and mortality in small bowel atresia. Jejuno-ileal atresia.

One hundred and one babies were admitted to the Hospital for Sick Children, Great Ormond Street, London, between 1967 and 1981, suffering from small bowel atresia. The overall mortality in this period was 23%, although in the years 1974-81 this fell to 12%. Mortality was considerably higher in jejunal atresia than in ileal atresia. The improved survival in the second half of the series was related to more frequent use of parenteral nutrition. Morbidity and mortality following the Bishop-Koop procedure was high and this operation is inappropriate for the treatment of small bowel atresia.

Humans↗
PubMed1987

The management of obstructive renal candidiasis in the neonate.

Neonatal renal candidiasis is a rare complication of prematurity associated with a mortality rate of 50%. We describe a patient who was treated by nephrostomy drainage together with the removal of the fungal debris and both systemic and local antifungal therapy. The infection was eradicated and the baby survived with minimal renal morbidity. A rational plan of treatment is presented which may help to reduce the mortality rate in future.

Acute Kidney Injury↗
PubMed1986

Morbidity and mortality in duodenal atresia.

98 babies were admitted to the Hospital for Sick Children, Great Ormond Street, London, with duodenal atresia between 1967 and 1981. The overall mortality was 32%, although it fell from 39% in the first half of the series to 26% in the second half. This reflected the better management of babies in risk group C (Watterson et al 1962). However, the high incidence of associated anomalies, involving particularly the alimentary tract, was demonstrated to carry a grave prognosis.

Duodenal Obstruction↗
PubMed1986

Psychotherapy--the transformation of meanings: discussion paper.

This paper presents the hypothesis that psychotherapy seeks to produce changes in attitudes and behaviour through transformation of meanings. Patients come to psychotherapy because they are demoralized by the menacing meanings of their symptoms. The psychotherapist collaborates with the patient in formulating a plausible story that makes the meanings of the symptoms more benign and provides procedures for combating them, thereby enabling the patient to regain his morale. As a result, he feels better and functions more effectively, leading to progressive improvement. Various implications and limitations of this hypothesis are explored.

Behavior↗
PubMed1985

The outcome of antenatally diagnosed urological abnormalities.

Twenty-eight patients undergoing routine antenatal screening by ultrasound were found to have a fetus with a major urological abnormality. In addition, two babies suspected of having an enlarged bladder were found post-natally to be normal. Seven of the 28 pregnancies were terminated before 26 weeks' gestation as a result of the ultrasound findings and all these fetuses had lethal renal abnormalities. Of the remaining 21 babies, four died of renal failure following delivery. Fifteen of the 17 babies who are alive and well had an ultrasound scan before 24 weeks' gestation. Only one of these scans revealed the abnormality. In the remaining patients the abnormality was first detected after 28 weeks. No patient had surgery in utero. Our data suggest that renal abnormalities detected prior to 24 weeks' gestation are associated with severe renal impairment. It appears that the role of antenatal drainage procedures may be of limited value.

Female↗