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[Patent medicines and its advertising in Serbia during the second half of the 19th and first half of the 20th century].

The emergence of patent medicines and so called "domestic medicines" could be traced trough different advertisements that appeared in Serbia during the second half of the 19th century. Most of those drugs were imported from abroad without any official control. The new patent medicines explosions, which began with the rising of domestic chemical and pharmaceutical laboratories for industrial compounding and selling medicines, rushed an urgent need to introduce some statutory provisions regulating the matter. Due to enormous advertising in the papers the patent medicines were very popular and widely spread.

Advertising↗

Cyclic variation in ultrasonic myocardial integrated backscatter is due to phasic changes in the number of patent myocardial microvessels.

OBJECTIVE: We tested the hypothesis that the cyclic variation in ultrasonic myocardial integrated backscatter (IBS) is due to cardiac contraction-induced changes in the number of patent myocardial microvessels. METHODS: We performed experiments in open-chest dogs in which we increased the number of patent myocardial microvessels without changing cardiac contraction. We achieved this either by direct intracoronary administration of adenosine (group 1; n = 10) or by producing a noncritical coronary stenosis (group 2; n = 7). RESULTS: At baseline, IBS was lowest in systole and highest in diastole. This cyclic variation in IBS was closely associated with the phasic changes in myocardial blood volume that were measured with myocardial contrast echocardiography. During adenosine administration, the diastolic IBS increased from -18.8 +/- 6.5 to -17.5 +/- 6.1 dB (P = .002), with an associated increase in the difference between the systolic and diastolic IBS from 3.8 +/- 1.1 to 4.6 +/- 1.0 dB (P = .009). After a noncritical stenosis was produced, diastolic IBS also increased from -26.6 +/- 8.3 to -25.2 +/- 7.3 dB (P = .001), with an associated increase in the difference between the systolic and diastolic IBS from 3.7 +/- 1.2 to 5.0 +/- 1.0 dB (P = .02). No change in IBS was noted in the bed that did not receive adenosine or the bed that had a stenosis. CONCLUSIONS: The variation in IBS during the cardiac cycle is closely associated with the phasic changes in myocardial blood volume seen during cardiac contraction. When the number of patent myocardial arterioles is increased via adenosine or placement of a noncritical stenosis, diastolic IBS increases with a concomitant increase in IBS cyclic variation. These results may have important clinical applications for the noninvasive diagnosis of noncritical coronary stenosis at rest.

Adenosine↗

[Re-coronary artery bypass grafting using a MIDCAB technique in a patient with a patent RITA-LAD graft].

In a patient with a patent RITA-LAD (right internal thoracic artery-left anterior descending artery) graft, re-CABG (re-coronary artery bypass grafting) with re-median sternotomy has been a high risk procedure. A 56-year-old male underwent 4-CABG (RITA-LAD, LITA-Dx, SVG-PL, and SVG-RCA) nine years ago. Coronary angiography showed that the RITA-LAD graft was well patent, but there was 95% stenosis distal to RITA-LAD anastomosis site. We performed re-CABG (right gastroepiploic artery-LAD; RGEA-LAD), using MIDCAB (minimally invasive direct coronary artery bypass) technique with neither re-median sternotomy nor cardiopulmonary bypass. The right gastroepiploic artery was harvested through a small upper median laparotomy and anastomosed to LAD through a small left anterior thoracotomy. The postoperative course was uneventful. This technique seems to be useful for re-revascularization of the LAD in a patient with a patent RITA-LAD graft.

Coronary Artery Bypass↗

[Patent blue-induced false-methemoglobinemia].

We experienced an anesthetic case, in which interference in oxygen saturation values by patent blue was mistaken for nitroglycerin-induced methemoglobinemia. A 40-year-old woman underwent mastectomy for breast cancer under general anesthesia. Nitroglycerin was infused to produce hypotensive anesthesia. Patent blue was locally injected around the cancer by a surgeon and surgery was started. A few minutes later, oxygen saturation by finger pulse oximeter suddenly decreased from 100% to 90%. And then, blood gas analysis was performed to confirm this change. The decrease of oxygen saturation and the increase of methemoglobin were also observed in the finding of blood gas analysis. At first, we judged these changes as methemoglobinemia by nitroglycerin infusion. Finally, however, we concluded that all these changes were attributable to the interference by patent blue on oxygen saturation value because we found that there had been some inconsistent findings as methemoglobinemia. The fact seems that nothing happened to the patient during the episode. This case showed us that anesthesiologists should understand the principle of hematological monitors and the meaning of the data obtained by monitors.

Adult↗

[A case of patent urachus in an adult male].

A 31-year-old man was referred to our hospital for evaluation of urachal rest. The history of his present illness dated back to birth, when the umbilicus was projected and urinary discharge was noted. At that time, the symptom of discharge had spontaneously subsided. At the age of 22, however, the patient again experienced discharge from the umbilicus. Although he did not seek treatment, after six years this symptom disappeared. Around this time, however, pyuria was revealed during medical examination, and abdominal ultrasonography (US) suggested the presence of urachal rest. At the time of hospitalization, physical examination revealed that the patient's right testis was not palpable. He was diagnosed with patent urachus with hemilateral aplasia and monorchism by US, computed tomography, magnetic resonance imaging and cystoscopy. The patient subsequently underwent radical operation. Patent urachus in adults is very rare, and only a few cases have been reported. To our knowledge, only one previously reported case involved a recurrence after spontaneous healing. Further, this is the first report of a patient with patent urachus with hemilateral aplasia and monorchism. Radical operation is generally recommended, based on the fact that very few cases heal conservatively.

Adult↗

Patent Ductus Arteriosus Diagnosed in Old Age.

Patent ductus arteriosus is a relatively common congenital heart disorder occurring in 0.5 percent of births and accounting for up to 10% of all congenital cardiac anomalies. Due to its early closure during infancy, however, patent ductus arteriosus is rare in the adult. A 76 year old woman was previously reported to be the oldest patient with a new diagnosis of patent ductus arteriosus. We present a woman first diagnosed at age 86.

Journal Article↗

[Advertisements in newspapers and magazines about patent medicines in the Meiji era (the first dissertation) (Part 3)].

After the conclusion of the trial was carried out on december 25th in the 18th year of the Meiji era, write-ups decreased graduallly. Under these circumstances, the traders of medicine began their own publication at their convenience and they put advertisements in them. "Eisei-tebako" by "Kishida ginko" and "Houtan-keikenroku" by "Morita Jihei" were the typical of them. While patent medicines were extremely popular, pharmacists at that time never denied the necessity of patent medicines. Junichiro Shimoyama and Keizo Tanba, who were representatives of pharmacists in Japan, suggested that pharmacists had ought to manage patent medicines and pointed out that excessive write-ups exacerbated the situation.

Advertising↗

Ibuprofen pharmacokinetics in preterm infants with patent ductus arteriosus.

OBJECTIVE: Our objective was to study the pharmacokinetics of ibuprofen in premature infants with patent ductus arteriosus on day 3 and day 5 after birth. METHODS: Ibuprofen was administered on days 3, 4, and 5 by a 15-minute intravenous infusion of 10, 5, and 5 mg/kg, respectively, with the aim of closing the ductus arteriosus. Blood samples were drawn at time zero and at 0.5, 1, 2, 4, 12, and 24 hours after the first and third doses. Ibuprofen plasma concentrations were assayed by HPLC. RESULTS: A total of 27 premature infants were included (gestational age, 28.6 +/- 1.9 weeks; birth weight, 1250 +/- 460 g; values are mean +/- standard deviation). Ibuprofen pharmacokinetics followed a 2-compartment open model. Between the first and third doses (day 3 and day 5) there was a significant decrease of the volume of distribution of the central compartment (Vd(c)) (0.244 versus 0.171 L/kg; P =.03) and area under the plasma concentration-time curve (524 versus 447 mg. h/L; P =.01). The decrease in Vd(c) was most pronounced in patients with a closing ductus. Total body clearance and plasma half-life did not change significantly. No significant differences were observed in ibuprofen peak plasma concentrations after the first and third doses in relation to ductal status after treatment. CONCLUSION: Ibuprofen pharmacokinetics showed a large interindividual variation in premature infants during treatment for patent ductus arteriosus, and significant changes may occur between day 3 and day 5 after birth in those infants with a closing ductus. These findings may have implications for the treatment schedule with ibuprofen in patients with patent ductus arteriosus.

Anti-Inflammatory Agents, Non-Steroidal↗

[Anaphylactic shock after injection of patent blue for sentinel lymph node biopsy].

After being diagnosed with a melanoma, an 18-year-old woman developed anaphylactic shock following an intracutaneous injection of patent blue during a sentinel lymph node biopsy procedure. Intracutaneous allergy tests revealed positive reactions with patent blue (Bleu patenté V 'Guerbet') as well as with several anaesthetics and morphine. It was concluded that patent blue was the most probable causative agent for the anaphylactic reaction and that the possibility of such a reaction should be taken into consideration during sentinel node procedures. After a few days the operation was completed under epidural anaesthesia with technetium Tc 99m sulphur colloid being used to detect the sentinel node.

Adolescent↗

[Redo coronary artery bypass operation under beating heart via the left thoracotomy reusing patent grafts].

We report three cases of successful redo coronary artery bypass grafting (CABG) under beating heart via left thoracotomy with recycling of patent grafts previously implanted. Case 1 and 2: Anginal attack relapsed due to occlusion of the proximal portions of saphenous vein grafts (SVG) that had been sequentially anastomosed to the left coronary artery branches. In each case, the distal portion of the SVG was patent and functioned as coronary-coronary bypass. The left internal thoracic artery graft (ITAG) anastomosed to the left anterior descending coronary artery (LAD) was patent. Each patient underwent off-pump CABG through a left posterolateral thoracotomy. CABG was performed with the radial artery to the circumflex coronary artery (case 1) or the circumflex coronary artery and previous SVG (case 2). The proximal ends of radial artery grafts were anastomosed to the descending aorta. Case 3: Simultaneous reoperative CABG and the operation for the pseudoaneurysm that developed after the abdominal aortic graft replacement were performed. Bypass grafting between ITAG and LAD was performed with SVG via a left anterolateral thoracotomy because of severe anastomotic stricture of ITAG-LAD. The postoperative courses was uneventful for all patients.

Aged↗

Antagonists at the neurokinin receptors--recent patent literature.

This review describes the patent applications and relevant scientific literature published during 2002 in the field of novel neurokinin receptor antagonists, with an emphasis on the medicinal chemistry of recent patent publications. A brief update on the development status of compounds including: the neurokinin-1 receptor antagonists aprepitant (Merck & Co Inc), vofopitant, ezlopitant (Pfizer Inc), R-673 (F Hoffmann-La Roche Ltd); the neurokinin-2 receptor antagonists nepadutant (Menarini Ricerche SpA), saredutant (Sanofi-Synthelabo), SR-144190 (Sanofi-Synthelabo) and UK-290795 (Pfizer Inc); and the neurokinin-3 receptor antagonists osanetant (Sanofi-Synthelabo) and talnetant (GlaxoSmithKline plc) will be given. The review also reports the recent published patent literature in the area of novel therapeutic uses and novel formulations and combinations claimed for neurokinin receptor antagonists.

Animals↗

[False decrease in pulse oximetry readings due to patent blue in a patient with breast cancer].

A 61-year-old woman with breast cancer was scheduled for breast preserving therapy under general anesthesia. After the tracheal intubation, 4 ml of 2% patent blue was injected into the skin to determine sentinel lymph node. Thirty seconds after injection, the pulse oximetry reading (SpO2) decreased from 100% to 60% and recovered to 90% over the next 5 minutes. At the time when SpO2 was 88%, arterial blood gas analysis showed PaO2 184.4 mmHg (FIO2 0.45) and all other vital signs were normal. About 120 minutes later, SpO2 rose to 99%. The operation was completed uneventfully and the patient recovered from anesthesia smoothly. After extubation, arterial blood gas analysis was performed again and it showed PaO2 of 82.5 mmHg (FIO2 0.21). We conclude that patent blue injection caused this decrease in SpO2 and recommend to evaluate the oxygen status not only by pulse oximetry but also by blood gas analysis when patent blue is used.

Anesthesia, General↗

Meticulously restored lumina of injured veins remain patent.

We report our experience with 38 major venous injury repairs in 37 patients between January 1981 and December 1989. The injuries were caused by gunshot (n = 27), shotgun (n = 3), knife (n = 5), blunt trauma (n = 1), and dog bite (n = 1). These involved 27 femoral, 10 popliteal, and one brachial veins. Thirty patients had associated major arterial injuries and seven had major long bone fractures. Retrospective analysis yielded two groups. Group I consisted of 17 patients who underwent meticulous restoration of venous lumina ensured by intraoperative postreconstruction venography (IPV) in all patients. Two of these required revision on the basis of IPV findings. Late patency of venous repair was confirmed by postoperative venography (n = 10) or duplex scans (n = 7). All 17 venous repairs were patent (100%). In group II none of the 20 patients (21 veins) underwent IPV. Fifteen of the 20 patients underwent venography and five patients (six veins) underwent duplex scanning after surgery. Eight veins were occluded and 13 (62%) were patent. The difference in patency rates of venous repair between groups I and II was significant (p = 0.02). Three (37.5%) of eight patients with occluded venous repair required delayed fasciotomy, but only 1 (3.4%) of 29 limbs (30 veins) with patent lumina required fasciotomy (p = 0.03). We conclude that meticulous restoration to normal-caliber venous lumina, confirmed by IPV, can achieve high patency and low morbidity rates.

Adolescent↗

Transcatheter closure of a patent foramen ovale in an adult with hypoxemia after cardiac transplantation.

We describe a case of refractory hypoxemia secondary to a patent foramen ovale immediately after orthotopic heart transplantation in a 60-year-old woman. The patent foramen ovale was successfully closed with a septal occlusion device, with resolution of the hypoxemia. To our knowledge, transcatheter closure of a patent foramen ovale in an adult patient with refractory hypoxemia during the immediate post-transplant period has not previously been reported.

Aged↗

Intermittent disappearance of a patent ductus arteriosus murmur: report of a case and review of the literature.

A 10-year-old girl with a diagnosis of patent ductus arteriosus from the time of birth was noted to have disappearance of her typical continuous murmur on two separate, well-documented occasions. Cardiac catheterization showed a small patent ductus arteriosus with a pulmonic/systemic flow ratio of 1.3:1. Conservative treatment was advised. Twelve other cases of intermittent disappearance of the murmur of a patent ductus arteriosus were found in the literature.

Journal Article↗

Angiogenesis inhibitors--a review of the recent patent literature.

The development of a general appreciation for the central role of angiogenesis in cancer growth and metastasis and other disease states has led to a wide range of new therapeutic strategies. This paper reviews the patent applications that appeared over the 6-month period between April and September 2000 in the field of angiogenesis inhibition. The review focuses on those approaches that directly target angiogenesis. The majority of the review covers patents in the area of mechanism-based inhibitors in which most of the activity of this field is focused. Later sections will cover the patenting of endogenous inhibitors and small molecules of unknown target, where there is significant effort but less understanding of mechanisms.

Journal Article↗

Patents are pivotal.

This seminar was the first in a series organized by Southern Bioscience, and examined the role of patent agents in protecting inventions. Presentations covered application for patent protection, exploitation of patent rights, and licenses and infringements.

Journal Article↗

Chinese patent medicine as a potential source of mercury poisoning.

This research is an effort to create an awareness of the potential hazards of some Chinese patent medicines which contain mercurial ingredients. This should be of consideration when screening symptomatic patients who are of Asian ethnic background or other users of these medicines. This research discusses reported cases of mercury poisoning related to the use of Chinese patent medicines and the potential toxicity of cinnabar (red mercuric sulfide) and calomel (mercurous chloride), 2 mercurials commonly used in these medicines. A list of mercurial-containing Chinese patent medicines available on the open market in North America has been compiled, together with their traditional uses and mercurial contents and is presented as a quick reference for Specialists in Poison Information. This class of medicine may not pose a problem when used appropriately; however, its misuse, abuse, overdosage and improper storage can lead to serious mercury poisoning.

Adult↗