Estimating the surgical backlog from the COVID-19 lockdown in South Africa: A retrospective analysis of six government hospitals.

BACKGROUND: The COVID-19 pandemic reached South Africa (SA) in March 2020. A national lockdown began on 27 March 2020, and health facilities reduced non-essential activity, including many surgical services. PRIMARY OBJECTIVE: to estimate the COVID-19 surgical backlog in Western Cape Province, SA, by comparing 2019 and 2020 general surgery operative volume and proportion at six district and regional hospitals. SECONDARY OBJECTIVE: to compare the operative volume of appendicectomy, laparoscopic cholecystectomy, cancer and trauma between the 2 years. METHODS: This was a retrospective study of general surgery operations from six SA government hospitals in the Western Cape. Data were obtained from electronic operative databases or operative theatre logbooks from 1 April to 31 July 2019 and 1 April to 31 July 2020. RESULTS: Total general surgery operations decreased by 44% between 2019 (n=3 247) and 2020 (n=1 810) (p<0.001). Elective operations decreased by 74% (n=1 379 v. n=362; p<0.001), and one common elective procedure, laparoscopic cholecystectomy, decreased by 68% (p<0.001). Emergency operations decreased by 22% (n=1 868 v. n=1 448; p<0.001) and trauma operations by 42% (n=325 v. n=190; p<0.001). However, non-trauma emergency operations such as appendicectomy and cancer did not decrease. The surgical backlog for elective operations after 4 months from these six hospitals is 1 017 cases, which will take between 4 and 14 months to address if each hospital can do one additional operation per weekday. CONCLUSIONS: The COVID-19 pandemic has created large backlogs of elective operations that will need to be addressed urgently. Clear and structured guidelines need to be developed in order to streamline the reintroduction of full surgical healthcare services as SA slowly recovers from this unprecedented pandemic.

To what extent does urbanisation affect fragmented grassland functioning?

Urbanisation creates altered environments characterised by increased human habitation, impermeable surfaces, artificial structures, landscape fragmentation, habitat loss, resulting in different resource loss pathways. The vulnerable Rand Highveld Grassland vegetation unit in the Tlokwe Municipal area, South Africa, has been extensively affected and transformed by urbanisation, agriculture, and mining. Grassland fragments in urban areas are often considered to be less species rich and less functional than in the more untransformed or "natural" exurban environments, and are therefore seldom a priority for conservation. Furthermore, urban grassland fragments are often being more intensely managed than exurban areas, such as consistent mowing in open urban areas. Four urbanisation measures acting as indicators for patterns and processes associated with urban areas were calculated for matrix areas surrounding each selected grassland fragment to quantify the position of each grassland remnant along an urbanisation gradient. The grassland fragments were objectively classified into two classes of urbanisation, namely "exurban" and "urban" based on the urbanisation measure values. Grazing was recorded in some exurban grasslands and mowing in some urban grassland fragments. Unmanaged grassland fragments were present in both urban and exurban areas. Fine-scale biophysical landscape function was determined by executing the Landscape Function Analysis (LFA) method. LFA assesses fine-scale landscape patchiness (entailing resource conserving potential and erosion resistance) and 11 soil surface indicators to produce three main LFA parameters (stability, infiltration, and nutrient cycling), which indicates how well a system is functioning in terms of fine-scale biophysical soil processes and characteristics. The aim of this study was to determine the effects of urbanisation and associated management practices on fine-scale biophysical landscape function of urban and exurban grassland fragments, as well as to determine the potential for the use of LFA in decision-making involving the conservation of grassland fragments. The results indicated that the occurrence, size and characteristics of vegetated patches, and especially the presence of litter abundances, were the main factors determining differences in the LFA indices. Furthermore, mowing resulted in the overall fine-scale biophysical indices being higher for some of the urban grassland fragments. This implied that it is not necessarily the influence of urbanisation entailing high or low resource conserving patchiness and patch quality, but rather the management practices associated with urban and exurban areas. Therefore, from a conservation point of view, the grassland fragments in the City of Potchefstroom are just as conservable (on a biophysical function level involving soil processes) than the more "natural" exurban grassland fragments.

Landscape functionality of plant communities in the Impala Platinum mining area, Rustenburg.

The tremendous growth of the platinum mining industry in South Africa has affected the natural environment adversely. The waste produced by platinum mineral processing is alkaline, biologically sterile and has a low water-holding capacity. These properties in the environment may constitute dysfunctional areas that will create 'leaky' and dysfunctional landscapes, limiting biological development. Landscape Function Analysis (LFA) is a monitoring procedure that assesses the degradation of landscapes, as brought about by human, animal and natural activities, through rapidly assessing certain soil surface indicators which indicate the biophysical functionality of the system. The "Trigger-Transfer-Reserve-Pulse" (TTRP) conceptual framework forms the foundation for assessing landscape function when using LFA. The two main aspects of this framework are the loss of resources from the system and the utilisation of resources by the system. After a survey of landscape heterogeneity to reflect the spatial organisation of the landscape, soil surface indicators are assessed within different patch types (identifiable units that retains resources that pass through the system) and interpatches (units between patches where vital resources are not retained, but lost) to assess the capacity of patches with various physical properties in regulating the effectiveness of resource control in the landscape. Indices describing landscape organisation are computed by a spreadsheet analysis, as well as soil surface quality indices. When assembled in different combinations, three indices emerge that reflect soil productive potential, namely: the (1) surface stability, (2) infiltration capacity, and (3) the nutrient cycling potential of the landscape. In this study we compared the landscape functionality of natural thornveld areas, rehabilitated opencast mines and rehabilitated slopes of tailings dams in the area leased for mining in the Rustenburg area. Our results show that the rehabilitated areas had a higher total SSA functionality due to higher infiltration and nutrient cycling indices than the natural thornveld landscapes. The length of interpatches and the width of patches greatly influenced the landscape function of the studied areas. The natural thornveld areas had a marginally higher total patch area than the rehabilitated areas. Vegetated patches (grass-, sparse grass-, grassy forb-, and grassy shrub-patches) generally scored the highest functionality indices, whilst bare soil interpatches contributed to the landscape functionality of the various plant communities the least.

PTEN mutations in uterine sarcomas.

OBJECTIVE: Uterinesarcomas comprise three main types: carcinosarcomas, leiomyosarcomas, and endometrial stromal sarcomas. Carcinosarcomas are highly aggressive neoplasms with a biphasic histology of carcinomatous and sarcomatous elements. It is now generally accepted that carcinosarcomas are biphasic tumors that have to be regarded as endometrial carcinomas where metaplasia occurs. Mutations of the PTEN tumor suppressor gene, located on 10q23, play a significant role in the pathogenesis of the endometrioid type of endometrial carcinoma. Loss of heterozygosity of chromosome 10q has been reported in uterine leiomyosarcoma. Since little is known about the molecular pathobiology, our goal was to investigate the potential role of the PTEN gene in the carcinogenesis of uterine sarcomas. METHODS: We examined 21 carcinosarcomas, 21 leiomyosarcomas, and 5 endometrial stromal sarcomas using exon-by-exon polymerase chain reaction-single-strand conformation polymorphism analysis. RESULTS: Overall 8.5% (4/47) of uterine sarcomas were found to harbor somatic PTEN mutations. Of these, approximately 17% (3/18) were carcinosarcomas with endometrioid-type carcinoma components and approximately 5% (1/21) were leiomyosarcomas. No mutations were detected in carcinosarcomas with nonendometrioid carcinoma components (0/3) and in endometrial stromal sarcomas (0/5). CONCLUSIONS: These data suggest that intragenic PTEN mutations are involved in the genesis of uterine carcinosarcomas with endometrioid-type carcinoma components but rarely contribute to the pathobiology of uterine leiomyosarcomas.

Dose-dependent effects of exogenous gonadotrophins on the endometrium of the rat.

We compared the serum levels of oestrogen and progesterone and the endometrial morphology of normal pregnant rats at 5,5 days' gestation with those of pregnant rats given either low (10 IU) or high (20 IU) doses of two gonadotrophins: follicle-stimulating hormone (FSH) and human chorionic gonadotrophin (HCG). Evidence of ovarian hyperstimulation was observed in the high- but not the low-dose group; both treatment regimens caused significant changes in the endometrial surface, epithelial height, the microvillous border, the glycocalyx, the subepithelial stromal cells and the mitotic activity of the surface epithelial and stromal connective tissue cells. The effects of the high-dose treatment were more severe than those of the low-dose treatment. The serum oestradiol and progesterone levels of the treated groups were not significantly different from those of the control group. The changes in the endometrium after both treatment regimens may interfere with normal trophoblastic-endometrial interactions and could influence the maintenance of pregnancy. This investigation demonstrated that even low doses of gonadotrophins, which do not cause obvious ovarian stimulation, affect uterine morphology. The findings have important implications for in vitro fertilisation and embryo transfer programmes.

Gastric acid secretion and gastrin release in the baboon.

Significant species differences have been demonstrated in gastric physiology, a factor that limits extrapolation of animal data to man. Primate physiology is thought to be similar to that of man; however, gastric function has not been adequately documented in the primate. In the present study six baboons (body weight 25.5 +/- 1.8 kg) were trained to sit in a chair and gastric acid secretion and gastrin release was studied in conscious animals. Mean basal acid secretion was 1.3 +/- 0.1 mmol (H+)/hr. Maximum output after pentagastrin (12 micrograms/kg/hr) was 9.5 +/- 0.9 mmol (H+)/hr and 11.0 +/- 0.4 mmol (H+)/hr after histamine (40 micrograms/kg/hr). A statistically significant (by cosinor analysis) circadian rhythm was demonstrated for intragastric pH over 24 hr in fasted baboons (P less than 0.001). Mean basal serum gastrin level was 37.7 +/- 8.3 pg/ml. The integrated gastrin response after administration of a protein rich meal was 2.52 +/- 0.07 ng x min/ml and this increased to 5.17 +/- 0.18 ng x min/ml (P less than 0.05) following simultaneous administration of a meal with atropine (0.2 mg/kg) (P less than 0.05). Our results suggest that there is significant basal and stimulated acid secretion in the baboon; the amount of acid secreted is similar to that reported in man. Gastric pH demonstrated a circadian rhythm. Postprandial gastrin release was significantly enhanced by cotreatment with atropine. As the present findings are similar to those previously reported in man, the baboon may be a useful model for further studies in gastric physiology and experimental peptic ulceration.

Characterization of human progesterone receptor by high performance hydrophobic interaction chromatography.

High performance hydrophobic interaction chromatography has been used to separate progestin receptors (PRs) from human uterus and from the T47D human breast cancer cell line. Reproducible separations of high resolution were achieved using a TSK Phenyl-5PW column and a reverse salt gradient of 400 mM to 0 mM sodium sulfate in phosphate buffer, pH 7.4. Peaks of radioactivity exhibiting hydrophobic behaviour were isolated, as well as a smaller proportion of specific bound receptors located in the void volume fraction. No differences in retention times were observed between uterine and breast cell line samples. When the technique was used in conjunction with rapid vertical tube sucrose density gradient centrifugation, the 8S sedimenting PR from fresh, low-salt cytosol always eluted with a retention time of 24 min. The natural 4S receptor chromatographed as a single peak at 29 min while the 4S receptor species from high-salt cytosol appeared as two distinct peaks of radioactivity with retention times of 29 and 33 min. While specific binding was shown to occur in the void volume of the column, the origin of these receptors were indeterminate. These results would suggest that under these conditions the 8S receptor occurs as a single hydrophobic class of protein, whereas the data provides evidence that transformed 4S receptor may be proportioned into two unequal entities as a function of exposure to salt.

Exogenous gonadotropins--serum oestrogen and progesterone and the effect on endometrial morphology in the rat.

The serum levels of oestrogen and progesterone in hyperstimulated, pregnant rats were compared with those of normal pregnant animals. The endometrial morphology was studied before (4.5 days), at the time of (5.5 days) and after (6.5 days) implantation. In the hyperstimulated group serum oestradiol levels were significantly higher than in the controls at 2.5 and 4.5 days, while progesterone levels were similar in the two groups. Consequently the progesterone:oestradiol ratio was significantly lower in the experimental groups prior to implantation. Significant changes in the endometrium caused by the raised oestradiol levels, included an early increase in gland epithelial height, increased surface epithelial height, increased number and length of microvilli, deficiencies in the glycocalyx and decreased mitotic activity in the surface epithelium and stromal cells. In addition, epithelial cell degeneration and failure of decidualisation of stromal cells was observed. These morphological changes adversely affect embryo attachment and implantation. Similar pathological changes in the endometrium may occur in human in vitro fertilisation utilising superovulation and may be an important factor in the low success rate of these programmes.

Endocrine profile associated with estrogen and progesterone receptors in leiomyoma and normal myometrium.

In leiomyoma and normal myometrium estrogen receptors act independently at low or high levels of the normal serum steroid range in the menstrual cycle. It might be an inherent characteristic of leiomyomas, which results in their progressive growth in the absence of any abnormal stimulation. In the secretory phase of the menstrual cycle, serum progesterone suppresses estrogen receptor concentrations in leiomyoma. In the present study serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) showed direct as well as inverse correlations with estrogen and progesterone receptors in different phases of the menstrual cycle.

Plasma lactoferrin content in pregnancy.

Plasma lactoferrin concentration, leucocyte count, serum prolactin concentration and storage iron status were studied in 313 women at various stages of pregnancy. The mean serum iron value, percentage saturation of transferrin and geometric mean serum ferritin concentrations decreased as pregnancy progressed. In contrast, the total iron-binding capacity showed a highly significant increase with advancing gestation. Plasma lactoferrin concentration showed a mild progressive increase during pregnancy (peaking 29-32 weeks). The increase in lactoferrin concentration was, however, disproportionately small when compared with the concomitant pregnancy-related elevation in leucocyte count. The ratio of plasma lactoferrin concentration to leucocyte count therefore appeared to be abnormally low during pregnancy suggesting an acquired defect of lactoferrin release by leucocytes of pregnant women. It is unlikely that prolactin was the factor responsible for the reduced leucocyte release of lactoferrin. The lactoferrin:leucocyte ratio was already significantly reduced early in pregnancy at a time when prolactin concentration was relatively low. Furthermore, the correlation between prolactin concentration and both lactoferrin concentration and lactoferrin:leucocyte ratio was positive. Pregnancy appears to be associated with an acquired abnormality of leucocyte degranulation, the cause of which is not clear at present.

Multidimensional chromatographic separation of estrogen receptors.

Analyses of estrogen and progesterone receptors in biopsies of breast carcinoma play a vital role in the selection of patients likely to respond to hormone manipulation. Sucrose density gradient centrifugation has been the reference method in the determination of estrogen receptors in human breast carcinoma cytosols. To reduce assay time and circumvent prolonged manipulation of labile receptor preparations, high performance liquid chromatography techniques in the size-exclusion and ion-exchange modes were compared as potential alternate methods for the rapid separation of receptor isoforms. Multidimensional analyses were performed by reapplying estrogen receptor isoforms obtained from high performance size-exclusion and ion-exchange chromatography to sucrose density gradients and vice versa. This confirmed that the estrogen-binding components identified by high performance liquid chromatography appear to correspond to estrogen receptor species from sucrose density gradients.

Oestrogen receptor assay by ER-D5 immunocytochemistry fails to correlate with ligand-binding assay in breast cancer.

Results obtained with a conventional reference ligand-binding assay were compared with those from an immunocytochemical method employing ER-D5 antigen, a supposedly oestrogen-receptor-related protein. In a group of 144 histologically proven breast carcinomas, no direct correlation could be established. Only 52% of cases would have corresponded in diagnosis. The incidence of false-negatives by ER-D5 immunocytochemistry is of the order of 70% while 32% of patients were false-positive by this method. Since both methods are employed to predict therapeutic responses to hormonal manipulation, the discrepancy between the methods is alarming. While the prognostic and predictive index of conventional oestrogen-receptor assays is well documented, correlation of these assays with ER-D5 immunocytochemistry has not been demonstrated. On the basis of these results, and pending further investigation, the replacement of conventional oestrogen-receptor methods by immunocytochemistry using this antibody is not recommended.

The effect of chronic acidification of the canine duodenum on gastrin release from the antrum transplanted into the colon.

Exogenous infusion of acid into the canine duodenum inhibits acid secretion stimulated by endogenously released and exogenously administered gastrin. The importance of this mechanism in normal acid homeostasis and in the inhibition of chronic endogenous acid hypersecretion is not established. In this study the classic Dragstedt model antral colonic transplant (ACT) was used to produce endogenous hypergastrinemia and acid hypersecretion. The effects of the ACT when the duodenum was retained in continuity with the stomach (gastroduodenostomy) were compared with those obtained when the duodenum was no longer in continuity with the stomach (gastrojejunostomy). The duodenum markedly suppressed gastrin release (p = 0.003) and gastric acid secretion (p = 0.005) in each of the four dogs. The dogs remained free of ulcers for 8 months after gastroduodenostomy and ACT. However, after conversion to gastrojejunostomy, large, chronic peptic ulcers developed after a mean of 3.5 months. The inhibitory effect of the duodenum on gastric release and gastric acid secretion protected the dog against ulceration for an extended period. The duodenum may be the major site of inhibitory control of acid secretion and endogenous gastrin release in dogs.

High-resolution separation of molybdate-stabilized progestin receptors using high-performance liquid chromatography.

Molecular heterogeneity of the human uterine progestin receptor was investigated employing sucrose density gradient centrifugation and high-performance liquid chromatography (HPLC) in size-exclusion (HPSEC), ion-exchange (HPIEC) and chromatofocusing (HPCF) modes. Synthetic progestomimetic ligands, [3H]R5020 and [3H]ORG-2058, were used to identify these receptors. Rapid centrifugation with a vertical tube rotor showed both 8-9 S and 4-5 S receptor species in the presence of 10 mM sodium molybdate with a 90-96% recovery. [3H]R5020 displayed greater nonspecific binding than [3H]ORG-2058. When separated receptor preparations were labeled, each with a different ligand, mixed and separated on optimized gradients, at least two receptor isoforms were identified in the components sedimenting at 8-9 S. HPSEC confirmed the presence of receptor isoforms displaying different molecular size and shape dependent upon the progestin ligand used. When the surface charge properties were examined by HPIEC using AX-1000, two distinct species were observed irrespective of the radioactive ligand. The first peak appeared in the void volume similar to the position of free steroid, indicating the possibility of ligand stripping by the column. The second peak bound steroid specifically and eluted with 100 mM phosphate. If either 8-S or 4-S progestin receptors were first separated by gradient centrifugation then by HPIEC, both receptor isoforms eluted with 60 mM phosphate. Re-chromatography of these on HPIEC also gave the isoform eluting at 60 mM phosphate. HPCF of ligand-bound receptors on AX-500 columns also identified one isoform eluting at pH 5.6-6.1. Using a combination of HPLC techniques and sucrose gradient centrifugation, heterogeneity of the progestin receptor has been demonstrated.

Enhanced phosphorylation of progesterone receptor by protein kinase C in human breast cancer cells.

Affinity-isolated progesterone receptor (PR) from human breast cancer cells incubated with [32P]orthophosphate was shown to exist as a phosphoprotein. Exposure of the cells to 10 nM phorbol-12-myristate-13-acetate (PMA) for 10 min increased by 30-40% the amount of label incorporated into the 116-kDa receptor protein. A two-fold increase in the total number of steroid binding sites was also observed in cells receiving PMA treatment. This apparent unmasking of PR binding sites by phosphorylation probably involved conformational changes to existing receptor complexes and affected the eventual state of receptor dissociation or transformation. An increase primarily in the 8 S sedimenting molecular species was observed but PMA treatment also led to the appearance of a smaller, 2-3 S form of receptor (10% of total) that was not present in control samples. When cytosols were partially transformed in vitro by ATP and salt, all molecular species of receptor (8, 4, and 2-3 S) from the PMA-treated samples consistently migrated faster in sucrose gradients. The larger amount of 2-3 S receptor in PMA-treated samples disappeared when ATP, but not salt, was the transforming agent. These results suggest a major role for phosphorylating reactions in the receptor-mediated action of steroids by regulating hormone-binding and influencing receptor transformation. Tumor promoters such as the phorbol esters may act by artificially increasing the level of processing of steroid receptor.

Oestrogen and progesterone receptor concentrations in leiomyoma and normal myometrium.

The content of cytoplasmic 17 beta oestradiol and progesterone receptors in human uterine leiomyoma and normal myometrium in the Negroid population was determined. Eighteen women of reproductive age, at various stages of the menstrual cycle, were included in the study. The serum oestrogen and progesterone concentrations were also measured. This is the first report in the literature in which oestrogen and progesterone receptors in leiomyoma are significantly higher than in normal myometrium (P = 0.0002). The steroid dependence of the growth of leiomyomas may be related to the steroid receptor level. The presence of persistently high concentrations of oestrogen and progesterone receptors in leiomyoma should be helpful in the treatment of this benign tumour.

Circulating thyroid hormones in primates with mild or severe hepatitis following liver transplantation.

In order to study the effects of acute immunologically mediated liver disease on circulating thyroid hormones, serum levels of thyroxine (T4, total and free) and triiodothyronine (T3) were measured in 8 baboons before and for 60 days after allogeneic liver transplantation. In 3 animals early rejection and jaundice developed; T4 levels declined as liver function deteriorated. In the 5 tolerant animals liver function was only temporarily deranged without jaundice and there was a consistent early rise in T4 (P less than 0.01) followed by a later fall. T3 concentrations were relatively normal in both groups. The T3 resin uptake test remained virtually unchanged in all animals. Serum T4 and T3 responses to exogenously administered bovine thyrotropin (TSH) were similar in the jaundiced and anicteric animals. We conclude that the early rise in T4 in the tolerant animals was caused by transient increases in thyroid binding globulin in (TBG) while the fall in thyroid hormones in these and in the jaundiced animals was related to a decline in TBG levels. Thyroid responsiveness to TSH is not disturbed by moderately deranged liver function.

Thyroid hormone and carrier protein interrelationships in children recovering from kwashiorkor.

We have studied 15 infants with severe protein energy malnutrition (PEM) as a model of nutritional nonthyroidal illness. Changes in circulating thyroid hormones, binding proteins, and their interrelationships were assessed before and during recovery. Serum concentrations of total thyroxine and triiodothyronine and of thyroxine-binding proteins were extremely reduced, and increased progressively during 3 wk of refeeding. The T4:TBG molar ratio was initially 0.180 +/- 0.020, and increased progressively, parallel to the increases in TT4, to 0.344 +/- 0.038 after 21 days (p less than 0.025). The changes in free T4 estimates varied according to the methods used--FTI and analogue FT4 increased, dialysis FT4 fraction decreased. Serum TSH levels increased transiently during recovery. It is concluded 1) there is reduced binding of T4 and T3 to TBG in untreated PEM which takes 2-3 wk to recover; 2) there are methodological differences in evaluating free T4 levels in PEM; 3) increased TSH secretion appears to be an integral part of the recovery from PEM.