The effect of inhaled nitric oxide on shunt fraction in mechanically ventilated patients with COVID-19 pneumonia.

Background: Studies in patients with severe acute respiratory distress syndrome (ARDS) with refractory hypoxaemia suggest that inhaled nitric oxide (iNO) can be added to ventilatory strategies as a potential bridge to clinical improvement. However, the potential role of iNO as a management strategy in severe COVID-19 pneumonia remains unclear. The authors describe their clinical findings of using iNO for severe COVID-19 pneumonia in 10 patients with refractory hypoxaemia in a tertiary respiratory intensive care unit. The results showed an improvement in shunt fraction, P/F ratio, PaO2 and arterial oxygen saturation but the improvements did not translate into a mortality benefit. This report adds to the current body of literature indicating that the correct indications, timing, dose and duration of iNO therapy and how to harness its pleiotropic effects still remain to be elucidated. What the study adds: This brief report adds to the body of literature exploring the potential use of inhaled nitric oxide as a management strategy in patients with severe COVID-19 pneumonia with refractory hypoxaemia. What are the implications of the findings: The findings of the report shows that there is a beneficial role of using inhaled nitric oxide to improve respiratory parameters, but that it does not translate to a mortality benefit. It adds to the investigation of establishing which patients, the duration and at what dose, inhaled nitric oxide should be used to gain maximum benefit for this subgroup of patients.

Comparison of patients with severe COVID-19 admitted to an intensive care unit in South Africa during the first and second wave of the COVID-19 pandemic.

Background: The second wave of coronavirus disease 2019 (COVID-19), dominated by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Beta variant, has been reported to be associated with increased severity in South Africa (SA). Objectives: To describe and compare clinical characteristics, management and outcomes of COVID-19 patients admitted to an intensive care unit (ICU) in SA during the first and second waves. Methods: In a prospective, single-centre, descriptive study, we compared all patients with severe COVID-19 admitted to ICU during the first and second waves. The primary outcomes assessed were ICU mortality and ICU length of stay (LOS). Results: In 490 patients with comparable ages and comorbidities, no difference in mortality was demonstrated during the second compared with the first wave (65.9% v. 62.5%, p=0.57). ICU LOS was longer in the second wave (10 v. 6 days, p<0.001). More female admissions (67.1% v. 44.6%, p<0.001) and a greater proportion of patients were managed with invasive mechanical ventilation than with non-invasive respiratory support (39.0% v. 14%, p<0.001) in the second wave. Conclusion: While clinical characteristics were comparable between the two waves, a higher proportion of patients was invasively ventilated and ICU stay was longer in the second. ICU mortality was unchanged.

Mesopotamian medicine.

Although the Mesopotamian civilisation is as old as that of Egypt and might even have predated it, we know much less about Mesopotamian medicine, mainly because the cuneiform source material is less well researched. Medical healers existed from the middle of the 3rd millennium. In line with the strong theocratic state culture, healers were closely integrated with the powerful priestly fraternity, and were essentially of three main kinds: barû (seers) who were experts in divination, âshipu (exorcists), and asû (healing priests) who tended directly to the sick. All illness was accepted as sent by gods, demons and other evil spirits, either as retribution for sins or as malevolent visitations. Treatment revolved around identification of the offending supernatural power, appeasement of the angry gods, for example by offering amulets or incantations, exorcism of evil spirits, as well as a measure of empirical therapy aimed against certain recognised symptom complexes. Medical practice was rigidly codified, starting with Hammurabi's Code in the 18th century BC and persisting to the late 1st millennium BC. Works like the so-called Diagnostic Handbook, the Assyrian Herbal and Prescription Texts describe the rationale of Mesopotamian medicine, based predominantly on supernatural concepts, although rudimentary traces of empirical medicine are discernible. There is evidence that Egyptian medicine might have been influenced by Mesopotamian practices, but Greek rational medicine as it evolved in the 5th/4th centuries BC almost certainly had no significant Mesopotamian roots.

Medical practice in Graeco-roman antiquity.

The roots of modern medicine can be traced back to the 5th century BC when Hippocratic rational medicine originated on the Greek islands of Cos and Cnidos. In this study we examine the way in which practitioners conducted their profession in Graeco-Roman times, as well as their training. Medical training was by way of apprenticeship with recognized doctors, but no qualifying examinations existed and the standard of practice thus varied enormously. Even in the Roman era the vast majority of medical doctors were Greek and in private practice as itinerant physicians. Civic doctors in the paid service of local communities appeared in Greek society from the 5th century BC onwards, but much later in Rome - probably as late as the 4th century AD. Rome's unique contributions to medicine lay in public health measures (e.g. their aqueducts, public baths and sewages systems) and an excellent medical service for their armies and navy. Hospitals (valetudinaria) were established for military purposes and for slaves on large Roman estates from the 1st century BC, but civic hospitals for the general public originated as late as the 4th century AD. The Greek medical schools of Cos and Cnidos were eventually superseded by the school of Alexandria in Egypt and towards the end of the Roman Empire by that of Carthage in northern Africa. Its gradual demise in the Christian era lowered the curtain on original medical endeavours during antiquity.

Did Adolf Hitler have syphilis?

The evidence that Adolf Hitler might have suffered from incapacitating syphilis is reviewed. Rumors that he acquired syphilis from a prostitute at the age of 20 years, with possible re-infection during World War I, can no longer be verified. Evidence is that he was sexually rather inactive throughout his life. Suggestions that Hitler's cardiac lesion and complaints such as transitory blindness, tremor of his left arm and leg, recurring abdominal pain and a skin lesion of the leg were of syphilitic aetiology cannot be supported. Hitler's progressive mental and physical deterioration after 1942, his growing paranoia, fits of rage, grandiosity and symptoms of possible dementia would fit in neurosyphilis. There are, however, also other explanations for his terminal syndrome, and evidence that repeated clinical examinations did not show the characteristic signs of dementia paralytica or tabes dorsalis, swings the balance of probability away from tertiary syphilis.

Congenital eunuchism and Favorinus.

Ancient Hebrew literature as well as the New Testament differentiate between castrated eunuchs and congenital eunuchs. Congenital eunuchism is very rare today, and assuming that this was also the case in classical times, we investigated possible reasons why congenital eunuchs feature prominently. We discuss the probability that the concept 'congenital eunuchism' might in ancient times have included effeminate men who, according to cultural views on 'maleness' and androgyny, were almost equated with eunuchs. The causes of congenital hypogonadism are reviewed in order to attempt clarification of the condition of Favorinus, a congenital eunuch in the second century AD. We suggest that although he might have been a true hermaphrodite, as suggested by some authors, it is more likely that he had one of the following conditions: functional prepubertal castrate syndrome, testicular gonadotrophin insensitivity, selective gonadotrophin deficiency or Reifenstein's syndrome.

The history and pathology of crucifixion.

In antiquity crucifixion was considered one of the most brutal and shameful modes of death. Probably originating with the Assyrians and Babylonians, it was used systematically by the Persians in the 6th century BC. Alexander the Great brought it from there to the eastern Mediterranean countries in the 4th century BC, and the Phoenicians introduced it to Rome in the 3rd century BC. It was virtually never used in pre-Hellenic Greece. The Romans perfected crucifion for 500 years until it was abolished by Constantine I in the 4th century AD. Crucifixion in Roman times was applied mostly to slaves, disgraced soldiers, Christians and foreigners--only very rarely to Roman citizens. Death, usually after 6 hours--4 days, was due to multifactorial pathology: after-effects of compulsory scourging and maiming, haemorrhage and dehydration causing hypovolaemic shock and pain, but the most important factor was progressive asphyxia caused by impairment of respiratory movement. Resultant anoxaemia exaggerated hypovolaemic shock. Death was probably commonly precipitated by cardiac arrest, caused by vasovagal reflexes, initiated inter alia by severe anoxaemia, severe pain, body blows and breaking of the large bones. The attending Roman guards could only leave the site after the victim had died, and were known to precipitate death by means of deliberate fracturing of the tibia and/or fibula, spear stab wounds into the heart, sharp blows to the front of the chest, or a smoking fire built at the foot of the cross to asphyxiate the victim.

Snake and staff symbolism, and healing.

Since time immemorial the snake has been venerated as an enigmatic creature with supernatural powers. As a snake and staff symbol it is also traditionally associated with the healing arts, either as the single-snake emblem of Asklepios, or as the double-snake emblem (caduceus) of Hermes. The mythological basis for this symbolism is reviewed. The Asklepian emblem has been associated with health care since the 5th century BC, when Asklepios became accepted by the Greeks as the god of healing. Whether he was also an historical figure as healer in earlier ages is less certain. The origin of the double-snake emblem is shrouded in the mists of antiquity. In classical times it became the herald's wand of Hermes, messenger of the gods who guided departed souls to the underworld, and was seen as protector of travellers, shepherds and merchants. In the latter capacity Hermes also conveyed a negative connotation as protector of thieves. During the Middle Ages the caduceus became a symbol of the healing sciences (pharmacy and alchemy in particular), and today, although mythologically incorrect, it is in common usage in the health care field.

The evolution of the hospital from antiquity to the end of the middle ages.

The evolution of the hospital is traced from its onset in ancient Mesopotamia towards the end of the 2nd millennium to the end of the Middle Ages. Reference is made to institutionalised health care facilities in India as early as the 5th century BC, and with the spread of Buddhism to the east, to nursing facilities, the nature and function of which are not known to us, in Sri Lanka, China and South East Asia. Special attention is paid to the situation in the Graeco-Roman era: one would expect to find the origin of the hospital in the modern sense of the word in Greece, the birthplace of rational medicine in the 4th century BC, but the Hippocratic doctors paid house-calls, and the temples of Asclepius were visited for incubation sleep and magico-religious treatment. In Roman times the military and slave hospitals which existed since the 1st century AD, were built for a specialized group and not for the public, and were therefore also not precursors of the modern hospital. It is to the Christians that one must turn for the origin of the modern hospital. Hospices, initially built to shelter pilgrims and messengers between various bishops, were under Christian control developed into hospitals in the modern sense of the word. In Rome itself, the first hospital was built in the 4th century AD by a wealthy penitent widow, Fabiola. In the early Middle Ages (6th to 10th century), under the influence of the Benedictine Order, an infirmary became an established part of every monastery. During the late Middle Ages (beyond the 10th century) monastic infirmaries continued to expand, but public hospitals were also opened, financed by city authorities, the church and private sources. Specialized institutions, like leper houses, also originated at this time. During the Golden Age of Islam the Muslim world was clearly more advanced than its Christian counterpart with magnificent hospitals in various countries.

Tumours and cancers in Graeco-Roman times.

In Graeco-Roman times all tumours (Greek: onkoi, abnormal swellings) were considered to be of inflammatory origin, the result of unfavourable humoural fluxes, and caused by an extravascular outpouring of fluid into tissue spaces. The neoplastic nature of tumours is a more recent concept, barely two centuries old. In Hippocratic literature tumours were mainly classified as karkinômata, phumata, and oidêmata. Phumata included a large variety of tumours, inflammatory and neoplastic in origin, and mostly benign (in modern terms), while oidêmata were soft, painless tumours and even included generalised oedema (dropsy). Although all categories possibly included occasional cancers, the vast majority of what appears to have been malignant tumours were called karkinoi karkinômata (Latin: cancrum/carcinoma). There was, however, no recognition of benign and malignant, primary and secondary tumours, in the modern sense.

Efficacy and tolerability of 20 mg pantoprazole versus 300 mg ranitidine in patients with mild reflux-oesophagitis: a randomized, double-blind, parallel, and multicentre study.

BACKGROUND AND AIM: The aim of this study was to compare the efficacy and tolerability of low dose pantoprazole (20 mg) (a gastric proton pump inhibitor) with standard dose ranitidine (300 mg) (a histamine-receptor antagonist), in their ability to relieve symptoms and heal oesophageal lesions associated with gastrooesophageal reflux disease (GORD). METHODS: Patients with endoscopically established mild GORD (stage I, modified Savary-Miller classification) were enrolled into a multicentre, randomized, double-blind, parallel-group comparison study (intention-to-treat population, n = 201; age range, 18-82 years). Patients took either oral pantoprazole 20 mg in the morning (n = 101) or ranitidine 300 mg in the evening (n = 100) once daily for 4 weeks or, if the healing was not complete, 8 weeks. Relief from key symptoms (heartburn, acid regurgitation, pain on swallowing) was assessed after 2, 4, and if applicable, 8 weeks. Healing of lesions was confirmed endoscopically after 4 and, if applicable, 8 weeks. RESULTS: Complete relief from key symptoms was noted after 2 weeks in 70/88 (80%) patients treated with pantoprazole vs 45/89 (51%) patients treated with ranitidine ('per-protocol and key-point available' populations, P < 0.001); the corresponding results after 4 weeks were 77/88 (88%) vs 51/88 (58%) (P < 0.001). Complete healing of lesions after 4 weeks of treatment was seen in 74/88 (84%) vs 49/89 (55%) in the pantoprazole and ranitidine group, respectively (P < 0.001, per-protocol); by week 8 the cumulative healing rates were 84/88 (95%) vs 69/89 (78%) in the pantoprazole and ranitidine group, respectively (P < 0.001). For the intention-to-treat populations, the corresponding values for healing after 4 and 8 weeks were 73% vs 49% (P < 0.001) and 83% vs 69% (P < 0.05), respectively. Both study medications were well tolerated. CONCLUSION: Compared to ranitidine 300 mg, the regimen with pantoprazole 20 mg provides faster relief from symptoms and is significantly more effective in healing of oesophageal lesions in patients with mild reflux-oesophagitis. Thus, the low dose of pantoprazole offers a treatment approach which minimizes drug exposure and costs while retaining high efficacy.

The epidemic of Athens, 430-426 BC.

The Athenian epidemic of 430-426 BC, at the outbreak of the Peloponnesian War, caused the death of the great statesman, Pericles, decimated the population and contributed significantly to the decline and fall of classical Greece. In his remarkable documentation of the epidemic, Thucydides (who survived the disease) not only left us a clear clinical picture of the pestilence but also identified its infectious nature and the fact that it conferred at least partial immunity on survivors. As confirmed by a large number of scholars who studied the subject, Thucydides' description does not accurately fit any existing disease, but we suggest that analysis of the signs and symptoms, considered in conjunction with significant epidemiological evidence, narrows down the many possibilities to epidemic typhus, plague, arboviral disease (e.g. Rift Valley fever) and smallpox. Typhus and smallpox fit best, but we favour the latter for reasons given. Unless further primary sources of information become available (and this seems most unlikely), productive speculation as to the cause of Thucydides' epidemic has probably reached the end of the road.

[Strife between the dispensing physician and the pharmacist--a historical overview. II. 1840-1928]. / Broedertwis tussen die resepterende geneesheer en die apteker--'n historiese oorsig. Deel II. 1840-1928.

The professional interaction between physicians and the pharmaceutical profession in South Africa in the years 1840-1928 is reviewed. The years 1840-1880 were characterised by relatively peaceful coexistence in metropolitan areas, but rather unorthodox developments in outlying rural areas. Here physicians found it difficult to make a living due to fierce competition from medicine-selling traders, self-medicating farming communities and apothecaries allowed to practise as clinicians (even appointed as district surgeons). The establishment of professional and statutory organisations and the promulgation of appropriate health legislation brought stability to the health scene but failed to remove friction between dispensing doctors and pharmacists. After the unification of South Africa in 1910, the two professions co-operated in fits and starts towards the ultimate formulation of the Medical Dental and Pharmacy Act of 1928. The rise of the pharmaceutical manufacturing industry brought a new perspective to the retail pharmacist's professional role.

[Strife between the dispensing physician and the pharmacist--a historical overview. I. To 1840]. / Broedertwis tussen die resepterende geneesheer en die apteker--'n historiese oorsig. Deel I. Tot 1840.

The historic origins of the medical and pharmaceutical professions, since the dawn of civilization, are briefly reviewed. The development of these professions in Great Britain as a prototype of the European situation over the past 3 centuries is traced, with emphasis on the developing strife between apothecaries and physicians. The corresponding situation in South Africa over the period 1652-1840 is then reviewed. The first Commission of Inquiry into health matters at the Cape, appointed by the British after their occupation of the region in 1806, was precipitated by complaints regarding unsatisfactory services rendered by apothecaries and medical practitioners. Health services were subsequently regulated by way of two Medical Proclamations in 1807, one Medical Proclamation in 1823 and a Medical Ordinance in 1830. According to this legislation apothecaries in Cape Town were not allowed to treat patients, and doctors were not allowed to sell medicines--but due to a shortage of rural practitioners, apothecaries and doctors were allowed to supplement each other in the country districts.

[Strife between the dispensing physician and the pharmacist--a historical overview. III. 1930-1979]. / Broedertwis tussen die resepterende geneesheer en die apteker--'n historiese oorsig. Deel III. 1930-1979.

The uneasy relationship between pharmacists and dispensing doctors during the years 1930-1979 is reviewed. The relatively easy association of the 1930s and the early 1940s ended abruptly in the post-war era when the impact of the manufacturing industry rang the death knell of the old-fashioned dispenser and at the same time made dispensing by doctors easier and safer. The retail pharmacist attempted unsuccessfully to define an acceptable new professional role, and the two professions failed to formulate an amicable working relationship. The promulgation of the Medicines Control Act (1964), the Pharmacy Act (1974) and the Medical, Dental and Supplementary Health Professions Act (1974) brought new dimensions to the strained relationship.

[Strife between the dispensing physician and the pharmacist--a historical overview IV. 1979-1987]. / Broedertwis tussen die resepterende geneesheer en die apteker--'n historiese oorsig. Deel IV. 1979-1987.

In 1981 a liaison committee established between the Medical Association of South Africa (MASA) and the Pharmaceutical Society of South Africa (PSSA) to probe the dispensing-doctor issue, published a joint declaration of co-operation. After a brief truce, however, relationships deteriorated again. Pharmacists claimed that the numbers of dispensing doctors were rapidly increasing and each profession accused the other of breaking the agreement. According to the PSSA many doctors were transgressing the MASA's guidelines and the Medical Council's ethical rule 28 by trading in medicines. Subsequent legislation approved by the Council and designed to obviate this problem brought unexpected complications, and led to a joint effort by the Medical Council and the Pharmacy Council to reach an acceptable compromise. In 1984 a tentative agreement was reached but not endorsed by the full Medical Council, largely because of pending recommendations from the Competition Board which would profoundly affect dispensing by pharmacists and doctors. These recommendations were made public in November 1986, and the Government's response to them is still being awaited. The author finally summarises the status quo of the age-old feud as he perceives it.