This book succeeds Review of Medical Pharmacology , by Meyers, Jawetz, and Goldfien. Edited by B. G. Katzung, some of the important areas covered include drug receptors and pharmacodynamics, pharmacokinetics of absorption and biotransformation of drugs, autonomic pharmacology of cholinergic and adrenergic receptor stimulants and antagonists, antihypertensive agents, cardiac glycosides and other agents used in the treatment of congestive heart failure, therapeutic drugs for cardiac arrhythmias, diuretics, pharmacology of the CNS drugs such as anticonvulsants and anesthetics, antidepressants, narcotic analgesics, nonsteroidal anti-inflammatory agents, endocrine pharmacology, antimicrobial and antimycobacterial drugs, antiprotozoal and antihelmintic drugs, cancer chemotherapy, and drugs and the immune system. Written by several prominent researchers and scientists, each chapter begins with a section on the basic pharmacology, chemistry, pharmacokinetics, and pharmacodynamics of the agents under discussion. This is followed by a section on clinical pharmacology, which deals with relevant information regarding the clinical use of drugs on the various

Basic and Clinical Pharmacology

Recently, it was reported that anesthetizing infant rats for 6 h with a combination of anesthetic drugs (midazolam, nitrous oxide, isoflurane) caused widespread apoptotic neurodegeneration in the developing brain, followed by lifelong cognitive deficits. It has also been reported that ketamine triggers neuroapoptosis in the infant rat brain if administered repeatedly over a period of 9 h. The question arises whether less extreme exposure to anesthetic drugs can also trigger neuroapoptosis in the developing brain. To address this question we administered ketamine, midazolam or ketamine plus midazolam subcutaneously at various doses to infant mice and evaluated the rate of neuroapoptosis in various brain regions following either saline or these various drug treatments. Each drug was administered as a single one-time injection in a dose range that would be considered subanesthetic, and the brains were evaluated by unbiased stereology methods 5 h following drug treatment. Neuroapoptosis was detected by immunohistochemical staining for activated caspase-3. It was found that either ketamine or midazolam caused a dose-dependent, statistically significant increase in the rate of neuroapoptosis, and the two drugs combined caused a greater increase than either drug alone. The apoptotic nature of the neurodegenerative reaction was confirmed by electron microscopy. We conclude that relatively mild exposure to ketamine, midazolam or a combination of these drugs can trigger apoptotic neurodegeneration in the developing mouse brain.

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Potential of ketamine and midazolam, individually or in combination, to induce apoptotic neurodegeneration in the infant mouse brain.

Tissue specimens from 283 principally spontaneously (naturally) desiccated human mummies from coastal and low valley sites in northern Chile and southern Peru were tested with a DNA probe directed at a kinetoplast DNA segment of Trypanosoma cruzi. The time interval spanned by the eleven major cultural groups represented in the sample ranged from ≈9,000 years B.P. (7050 B.C.) to approximately the time of the Spanish conquest, ≈450 B.P. (≈1500 A.D.). Forty-one percent of the tissue extracts, amplified by the PCR reacted positively (i.e., hybridized) with the probe. Prevalence patterns demonstrated no statistically significant differences among the individual cultural groups, nor among subgroups compared on the basis of age, sex, or weight of specimen tested. These results suggest that the sylvatic (animal-infected) cycle of Chagas' disease was probably well established at the time that the earliest humans (members of the Chinchorro culture) first peopled this segment of the Andean coast and inadvertently joined the many other mammal species acting as hosts for this parasite.

https://www.pnas.org/content/pnas/101/7/2034.full.pdf

A 9,000-year record of Chagas' disease

There is increasing evidence that lack of facilities, equipment, and expertise in district hospitals across many low- and middle-income countries constitutes a major barrier to accessing surgical care. However, what is less clear, is the extent to which people perceive barriers when trying to access surgical care. PubMed and EMBASE were searched using key words (“access” and “surgery,” “barrier” and “surgery,” “barrier” and “access”), MeSH headings (“health services availability,” “developing countries,” “rural population”), and the subject heading “health care access.” Articles were included if they were qualitative and applied to illnesses where the treatment is primarily surgical. Key barriers included difficulty accessing surgical services due to distance, poor roads, and lack of suitable transport; lack of local resources and expertise; direct and indirect costs related to surgical care; and fear of undergoing surgery and anesthesia. The significance of cultural, financial, and structural barriers pertinent to surgery and their role in wider health care issues are discussed. Immediate action to improve financial and geographic accessibility along with investment in district hospitals is likely to make a significant impact on overcoming access and barrier issues. Further research is needed to identify issues that need to be addressed to close the gap between the care needed and that provided.

Systematic review of barriers to surgical care in low-income and middle-income countries.

Aim: To investigate the aspects of spectacle correction of vision-impairing refractive error and presbyopia in those aged ⩾40 years in Timor-Leste. Method: A population-based cross-sectional survey with cluster random sampling was used to select 50 clusters of 30 people. Those who had uncorrected or undercorrected refractive error (presenting acuity worse than 6/18, but at least 6/18 with pinhole), uncorrected or undercorrected presbyopia (near vision worse than N8), and/or who were using or had used spectacles were identified. Dispensing history, willingness to wear and willingness to pay for spectacles were elicited. Results: Of 1470 people enumerated, 1414 were examined (96.2%). The “met refractive error need” in the sample was 2.2%, and the “unmet refractive error need” was 11.7%. The “refractive error correction coverage” was 15.7%. The “met presbyopic need” was 11.5%, and the “unmet presbyopic need” was 32.3%. The “presbyopia correction coverage” was 26.2%. Lower correction coverage was associated with rural domicile, illiteracy and farming. Of the sample, 96.0% were willing to wear spectacles correcting impaired vision. Of these, 17.0% were willing to pay US$3 (£1.52, €2.24) for spectacles, whereas 50.2% were unwilling to pay US$1 (£0.51, €0.75). Women and rural dwellers were less likely to be willing to pay at least US$1 for spectacles. Conclusion: Refractive error and presbyopia correction coverage rates are low in Timor-Leste. There is a large need for spectacles, especially for elderly and illiterate people, farmers and rural dwellers: those least able to pay for them. An equitable cross-subsidisation spectacle system should be possible.

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Correction of refractive error and presbyopia in Timor-Leste

Purpose: To describe the first pediatric cataract surgery case series report from Nepal. Setting: Tilganga Eye Center, Kathmandu, Nepal. Methods: This study comprised a consecutive series of 112 eyes of 85 children having cataract surgery with intraocular lens (IOL) implantation. General anesthesia of ketamine combined with peribulbar block was used in all patients. Patients' demographics, cataract type and presenting symptoms, surgical intervention, preoperative and postoperative visual acuities, and follow-up clinical examinations were recorded. Results: Seventy-three eyes (65.2%) of 53 patients had extracapsular cataract extraction with posterior capsulotomy, anterior vitrectomy, and posterior chamber IOL implantation (ECCE+PCAP+AV+PCIOL), and 39 eyes (34.8%) of 32 patients had cataract extraction and IOL implantation with an intact posterior capsule (ECCE+PCIOL). Of all patients, the mean age at surgery was 6.2 years ± 4.3 (SD). The median age in the ECCE+PCAP+AV+PCIOL group was 4.7 years and in the ECCE+PCIOL group, 11.0 years. The mean follow-up was 5.4 ± 5.3 months. The most common postoperative complication in the ECCE+PCIOL group was visual axis/posterior capsule opacification, which was seen in 18 eyes (46.2%) compared to 4 eyes (5.5%) in the ECCE+PCAP+AV+PCIOL group. Visual acuity improved with surgery in both groups. The leading cause of poor outcomes was deprivation amblyopia. There were no anesthesia-related complications. Conclusions: Implantation of an IOL at the time of cataract extraction under combined systemic ketamine and peribulbar lidocaine anesthesia appeared to be well tolerated and produced significant visual improvement in pediatric patients in Nepal. Primary posterior capsulotomy and AV helped prevent visual axis opacification without a significant increase in complications.

Pediatric cataract surgery in Nepal.

Aim: A cross sectional study was carried out on 78 screened cataract patients of two screening camps in Kathmandu valley, Nepal, to assess the willingness to pay for cataract surgery.

Methods: A non-probability sampling technique with open ended and close ended questionnaires was used.

Results: The average age of patients was 68.8 years. The ratio of men and women was 0.9:1. 42.3% (33) of patients were willing to pay for cataract surgery. Among them 48.5% (16) of people were willing to pay less than $13 and 51.5% (17) were willing to pay more than $13. The mean was $2.3 (SD $15.5) per case. Patients with bilateral cataract were more willing to pay than unilateral cases. Poverty (44.4%, 20) was the main barrier for unwillingness to pay for cataract surgery. Other reasons were the lack of family support (28.9%, 13), lack of knowledge of surgery and belief that it was an unnecessary procedure (15.6%, seven), and waiting for a free surgical service (11.1%, five).

Conclusion: This study clearly indicates that although there was awareness of the availability of treatment and services provided within the reach, people are not willing to pay for the surgery and use the facility primarily because of poverty. Hence, to change patients’ attitudes, a more holistic approach is needed, keeping in view the cultural, social, and economic background of the society.

https://bjo.bmj.com/content/bjophthalmol/88/3/319.full.pdf

Willingness to pay for cataract surgery in Kathmandu valley.

Aims: Children with treatable, vision impairing conditions may not have access to surgical care when they live in regions where anaesthesia is unavailable. The use of ketamine anaesthesia in a developing region was studied to determine its safety and effectiveness.

Methods: This is a consecutive series of 679 children who had a variety of paediatric eye disorders necessitating a short general anaesthesia. Ketamine was administered intravenously by a paediatrician with training in paediatric resuscitation procedures. Both intraocular and extraocular procedures were performed. The location of treatment was the Tilganga Eye Hospital in Kathmandu, Nepal, a developing region of the world. The study took place over a 5 year period.

Results: All procedures were performed without any anaesthetic complications. No child required unanticipated resuscitation or laryngeal intubation. Postoperative dysphoria occurred occasionally and was difficult to measure quantitatively. This side effect of ketamine resolved by the first postoperative day.

Conclusion: Ketamine is an effective agent for both intraocular and extraocular surgery in the paediatric age group. None of the children in this series needed resuscitation or intubations, and the ophthalmic surgery was carried out safely. Ketamine can be used safely in any ophthalmic procedure of short duration by a person having some training in anaesthetic resuscitation procedures. Because of its simplicity and safety, ketamine may be useful in a simple ophthalmic setup in the developing word.

https://bjo.bmj.com/content/bjophthalmol/87/5/535.full.pdf

Ketamine anaesthesia for paediatric ophthalmology surgery

To determine the clinical profile of retinoblastoma and to provide baseline data for further studies on this subject. Prospective evaluation of 30 consecutive patients with retinoblastoma admitted at the B. P. Koirala Lions Center for Ophthalmic Studies, Kathmandu, Nepal, between October 1998 and July 2000 was carried out. Age, sex, laterality and time from onset of symptoms to diagnosis (lag time) were noted. Ancillary tests were undertaken to rule out metastasis. Male to female ratio was 1.1:1 and the median age of presentation was 3.1 years. Of 30 cases, 23 (76.6%) had unilateral involvement. Leukocoria was the presenting sign in 13 cases (43.3%) and fungating mass in 10 cases (33.3%). In 11 (36.7%), the latency period from onset of symptoms to diagnosis was 6-12 months. In bilateral cases, advanced disease was treated surgically and the fellow eye was treated with cryotherapy, photocoagulation and chemotherapy. Histopathological examination of 21 (70.0%) enucleated/exenterated cases revealed a poorly differentiated type of retinoblastoma. This is the first study of retinoblastoma from Nepal. Early diagnosis of this disease when it is localized to the eye is important to salvage the life of the child. An informational program directed toward the public in general, as well as careful screening of any white pupillary reflex by the pediatrician and/or primary health worker will encourage and support early diagnosis.

Retinoblastoma in Nepal: a clinical profile of 30 cases.

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Jaya Thakur

Papers

Pediatric cataract surgery in Nepal.

Willingness to pay for cataract surgery in Kathmandu valley.

Ketamine anaesthesia for paediatric ophthalmology surgery

Retinoblastoma in Nepal: a clinical profile of 30 cases.

Ketamine Anaesthesia for Paediatric Ophthalmology Surgery